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Phosphorylation of UVR8 photoreceptor in Arabidopsis: insights into UV-B signalling and responses
No full textAbstract not currently available
Dynamic navigation for endodontic access in calcified maxillary molars
Get PDFRationale.
Endodontic access on teeth with calcified canals is challenging, time consuming and requires significant expertise. Dynamic navigation (DN) is a recent advancement within endodontics that provides real-time guidance during endodontic access. Dynamic navigation may improve the accuracy of canal location in teeth with calcified canals compared to freehand (FH) access.
Aim 1.
To carry out a systematic review of existing literature to assess the accuracy of canal location using DN in teeth with pulp canal obliteration when compared to FH and static navigation (SN) and to inform the design of an in vitro study.
Methods 1.
The systematic review eligibility criteria included 3D-printed or human teeth with pulp canal obliteration (PCO), endodontic access performed using DN and comparison to FH and/or SN. Embase, MEDLINE and CENTRAL and clinical trial registries were last searched on 31 March 2023. Additional searches included leading endodontic journals, conference proceedings and contact with manufacturers. The risk of bias was assessed using a modified Joanna Briggs Institute (JBI) checklist. Study characteristics and outcomes were tabulated and outcomes were explored as a narrative synthesis.
Results 1.
Systematic review identified three eligible articles for inclusion with a total of 172 teeth. All studies were of in vitro design on human and 3D-printed anterior and premolar teeth with varying levels of PCO. No studies included teeth with multiple canals or roots. The overall risk of bias was low in two studies and moderate in one study. Meta-analysis was not performed due to heterogeneity and the results presented as a narrative synthesis. Dynamic navigation improved accuracy of canal location in teeth with PCO in all three studies when compared
to FH access. No studies compared DN to SN.
Aim 2.
To perform an in vitro study to compare the tooth volume loss following DN and FH endodontic access in anatomically accurate 3D-printed maxillary molars with simulated calcified canals, performed by two operators with differing levels of experience.
Methods 2.
The in vitro study utilised a custom 3D-printed, anatomically accurate maxillary molar with four simulated calcified canals. A total of 40 identical teeth were accessed, 20 using the Navident Dynamic Navigation System (ClaroNav, Toronto, Canada) and 20 FH, by two operators with different levels of endodontic experience. The primary outcome measure was total tooth volume loss, while secondary outcome measures included the incidence of successful canal location, incidence of perforation and procedural time. Volume loss was assessed using pre- and post-operative cone-beam computer tomography, automatic segmentation and volume analysis software.
Results 2.
There was no significant difference in tooth volume loss between DN and FH endodontic access in 3D-printed maxillary molars with simulated calcified canals (53.824 vs. 48.144mm3, p=0.085). However, DN significantly reduced the median procedural time (6 minutes 52 seconds vs. 21 minutes 56 seconds, p<0.05)
Conclusions.
The systematic review suggested that DN may increase the accuracy of canal location in teeth with PCO when compared to FH access. However, the findings should be interpreted with caution due to the small number of included studies, all of which were of in vitro design.
The in vitro study was the first to compare endodontic access of multiple canals using DN and FH methods. It demonstrated that while DN does not significantly impact tooth volume loss in 3D-printed maxillary molars with simulated canal calcification, it significantly reduces procedural time and enhances consistency.
Further research should involve a range of multi-rooted teeth to validate the findings of the current in vitro study, as well as clinical studies to evaluate the clinical application of DN and address the inherent limitations of in vitro and ex vivo study designs
Controlled design of human-like agents with context-guided learning for automated video game playing
Get PDFThe video game industry state-of-the-practice ad hoc behaviour authoring techniques produce transparent and highly controllable autonomous agent artificial intelligence (AI) representations, but show limitations in adaptive and human-like behaviour design. Machine learning (ML) methods can cope with such constraints, but the black-box nature, high training costs in terms of data volume and time, as well as incompatibility with iterative workflows, make ML models unsuitable for commercial game development. To address the shortcomings of both these approaches, we investigate a non-disruptive, modular design approach to integrating small-scale learning models featuring performance and execution guarantees, as well as embedded human designer intent, into behaviour tree (BT) architecture for autonomous video game agents.
We deployed the proposed design in the environment of a published, commercial video game 60 Seconds!, which we instrumented for agent training and evaluation using an off-the-shelf game engine, BT and a learning library. After quantitative analysis of the mass-scale gameplay telemetry dataset of 8,244,111 trajectories from real game users, we clustered the player population with respect to estimated play skill, using a gameplay context-based score metric. Output agent models were then developed and trained in the game’s environment by applying the design, guided by game context-relevant segmentation of logic and behaviour of the top play skill persona model, derived from the trajectory data of the 7% top-scoring player cluster.
The output agent’s gameplay performance was benchmarked against that of a reference agent, and experimentally evaluated in a normalised game scenario against 18,947 human players. It was found to be valid in the context of the game environment, functional, and capable of pursuing gameplay objectives in unseen scenarios with competency. However, it was unable to outperform human players due to the suboptimal performance of its trained learning models. We determined that software stability issues of the learning library used, limited observation space, and egocentric data adversely affected agent training. While further work to improve the training process is necessary, the successful application of the context guided agent design in a commercial video game environment confirmed its potential for industrial applications. By contributing the design, the mass-scale dataset, and the tools used in our research, we enable the context-guided agents to be deployed in alternative contexts
Dramaturgy of exile: an autopoietic exploration
Get PDFThis thesis presents a practice-led, dramaturgical inquiry into autopoiesis in exile. It provides a methodology for the recreation or the autopoiesis, of the (writing) self in exile by presenting the emergence of a new languaging of the exilic condition within the exile but, more importantly, outwith the exile, and within the host.
Through the researching and crafting of three works of theatre and film the thesis examines the poetic self in exile through written language. The subject is vast and much discussed by many, from classical Greek and Roman antiquity to modernity and postmodernity. The innovation this work offers emerges from writing under the condition of existential peril against “authoritarian and fascist threat” (Stanley, 2024). Through dramatisation, it explores what can happen when language is instrumentalised, decontextualised and turned against its former emancipatory function. Within the chronological impetus of less than one hundred years, there is presently a virulent re-emergence of all five conditions of fascism as set out by philosopher Jason Stanley alongside numerous studies by Arendt, Snyder, Klemperer, Bertrand Russell, Ecco and many others. Exposure to this “descent to fascism” (Snyder, 2025) is taking place through traditional but also technological and complex digital means. In that sense, we are all exiles. As the writer in exile, I have thus addressed a gap in the scholarship by foregrounding the method of autopoiesis as an embodied, dramaturgically situated and performative practice of resistance under contemporary conditions of linguistic, ontological and material exclusion.
This work on autopoiesis has been designed as a philosophical pentagon of a Contract of Vulnerability constructed around the wound of exile and its potential for transforming vulnerability into a new language. The first play, LESBOS, examines the term Wound. By exposing the wound, the timing of the wound and the invulnerability of the Antigonian drama, it examines constitutive exclusion and dramatizes the conditions of exilic presence and how these may be regenerated and reimagined. The second play, A Seafarer’s Elegy, is an absurdist piece which examines the condensation of political language. Led by Martin Esslin’s 1960 study on the theatre of the absurd, it considers the sloganification of language and the potential for remaking meaning in a time of depletion of traditional codes of signification. The final piece, A Poetic Constitution for Scotland revisits Scotland as a repository of trauma and contestation and a scene of political resistance. The thesis further examines the function of literature in exile as a precondition of writing and, lastly, problematises translational and extractive poiesis in a moment when the exilic writer is mined for cultural and linguistic capital while simultaneously re-languaging, resisting and producing new dramaturgies in exile
Tuning single-ion magnet properties through primary and secondary coordination sphere modification
No full textAbstract not currently available
How should UK population surveys represent differences in terms of sex and gender?
Get PDFThis research investigated how UK population surveys should represent differences in terms of sex and gender, with some exploration of how sexuality is represented in relation to these concepts. It shows how essentialist ontologies manifest in the production of knowledge, leading to some populations being misrepresented or rendered invisible. Informed by a critical queer feminist lens, this work centres populations overlooked by large-scale surveys, such as those utilised in the UK censuses. Through this research, participants from these populations played an active role in knowledge production, co-producing new survey questions to meet the needs of overlooked populations.
To address the multifaceted issue of survey representation, a three-strand, exploratory, sequential, mixed-methods approach was employed. In Strand 1, the design of 27 UK population surveys were systematically analysed. This produced an understanding of current UK survey practices and identified four overlooked populations: people with variations of sex characteristics (VSC), trans people, non-binary people, and anyone whose relationship to sexuality could not be categorised as only bisexual, gay, heterosexual/straight, or lesbian. In Strand 2, focus groups were employed, engaging with these populations to understand what they thought should be represented by surveys, why, and how. The overlooked populations actively engaged in knowledge production by co-producing survey questions they felt better represented their populations. In Strand 3, these questions were tested using an online survey of 347 LGBTI+ people aged 16 and over across the UK. Alongside testing the co-produced questions, the survey indicated whether the overlooked population’s perspectives on survey representation were shared by a broader sample. Finally, the three strands were integrated to create a comparison between current survey practices and the co-produced perspectives on how surveys should be designed. This comparison enabled direct recommendations on how to improve UK population surveys.
This research enables an understanding of how misrepresentation and invisibility occur in large-scale surveys, and how to challenge this. Centring overlooked populations meant working with them to identify not only what information they were willing to provide and in what contexts, but also what information was in their best interests to share. Through this, I produced question design standards and emphasised key principles for data production to guide survey designers towards approaches that prioritise the participants’ autonomy over their own identities. The overlooked populations engaged with in this research emphasised the importance of having the choice to be represented based on how they see themselves, for both maximising the participant response rate and producing data that can be used to meet their needs
OntolinkX: a context-aware linking approach integrating SapBERT and a cross-encoder reranker with hard negative training scenario for enhancing biomedical entity linking task
Get PDFBiomedical Entity Linking (BEL), a crucial task in natural language processing, involves mapping mentions of biomedical entities in free text to their corresponding concepts in standardized and structured biomedical ontologies such as the Unified Medical Language System (UMLS). The increasing volume of biomedical literature and the complexity of medical terminologies present significant challenges for BEL, including entity ambiguity, dynamic knowledge bases, evolving terminology, and the need to maintain accuracy across diverse biomedical domain texts. Existing BEL systems often struggle with disambiguation, especially in the face of minimal context or sparse ontology descriptions, leading to reduced generalization ability in retrieval performance.
To address these challenges, we propose OntolinkX model, a context-aware linking approach that integrates SapBERT and a cross-encoder reranker using hard negative sampling scenarios. It builds on SapBERT which is a state-of-the-art entity linking approach that mainly focuses on synonym disambiguation and semantic alignment via contrastive learning but does not take full contexts into account. We show that adding a cross-encoder improves on SapBERT’s performance in entity linking tasks. We explored the impact of incorporating additional information into the representation of both mention text and ontology concepts, two essential components in entity linking tasks. We start by taking entity names to represent ontology entries, then progressively augment the representations with semantic types and definitions. On the mention side, we incorporate contextual information from surrounding tokens within a dynamic window size. Furthermore, we examine the combined effect of full contextualized mention representations and enriched ontology representations.
Our two-stage pipeline begins with SapBERT retrieving potential entity candidates for each mention text. In the second stage, a cross-encoder is trained with negative sampling learning approach, starting from randomly generated negative samples and progressing to challenging ”hard negatives”, which are closest incorrect candidates from the retriever. Experiments show that incorporating richer information from both mention context and ontology descriptions improves retrieval performance. These findings suggest that our OntolinkX linking approach, alongside enriched representations from hard negative sampling strategy, can substantially improve BEL in complex biomedical texts
Ethics in extraterrestrial humanity
Get PDFWith the launch of the first satellite into Earth’s orbit, we turned the Archimedean point from our home planet towards the heart of the Universe. By the end of this decade, humans will live and work permanently on the Moon and, at the beginning of the next one, on Mars. Life outside our home planet, in lethal and challenging environments, will propel our civilisation into the extraterrestrial, to embark on an even greater – interstellar – civilisation.
Some predict that there will be new generations of humans born and evolved into extraterrestrial gravities that will eventually lead to a ‘new’ human race. Extraterrestrial humans will no longer consider the Earth to be their home, but rather Mars. For creatures and humans who evolved on Earth to live on objects of our solar system and beyond it will only be possible with the support of technology and nanotechnology. This life will no longer be comparable with life as we know it now, and one of the major challenges we will face will be the ethical implications of that.
There are many questions to be answered. The core one for this research is: are we going to conquer solar system objects as good citizens or as cosmic vandals? What kind of relationship will we establish with these planets we are not made of, in the case that these planets contain life? Are we allowed to contaminate planets we are not made of, even if they do not present any indication of possible life forms? Also – an important question – life as we know it on Earth is based on carbon, but could other objects in the universe evolve life forms based on silicon? Knowing our practices on Earth, how we assess all situations from an anthropocentric point of view, is it at all possible to acknowledge and even give priority to living creatures – if there are any – outside our home planet?
This thesis will lead to more questions than answers, and the conclusions will be suggestions based on assumptions of how we could reach the best outcome when we start living our extraterrestrial life. The thesis has two parts. The first part introduces ethical questions and concerns related to the argument that we ought to leave our home planet; the second part will try to predict the possibility of ethics in our extraterrestrial human life, based on the heavy support of technology and nanotechnology and implementation of that on other objects, planets and moons in our solar system. This is a huge scale, so I will concentrate on human extraterrestrial life on Mars for two main reasons: Mars will be the first example of a planet where humans will live and work; and this will happen in the next 10 to 15 years
Engineering a novel bioactive hydrogel for enhanced bone regeneration
No full textAbstract not currently available
Searching novel pharmacological tools for the pharmacology of orphan G protein-coupled receptor GPR84
Get PDFG protein-coupled receptors (GPCRs), a large group of cell-surface receptors, are involved in numerous physiological and pathological processes. Among GPCRs, the pro-inflammatory orphan receptor GPR84, a member of the Class A receptor family, is an attractive drug target for inflammatory diseases and metabolic disorders. However, there remains a significant lack of GPR84 compounds, particularly GPR84 antagonists that can be used in mouse model studies as available GPR84 antagonists display marked species selectivity for human GPR84. The most direct method to overcome this challenge is through the screening and characterization of novel compounds for both human and mouse GPR84 to discover antagonists with similar affinities for both species. Compound 271 was characterized as a competitive orthosteric antagonist for both human and mouse GPR84, and the key residue Arg172ECL2 in the orthosteric binding pocket is not necessary for the binding of compound 271. However, previous studies have shown that the mutation of Arg172ECL2 to alanine or lysine abolished the function of medium-chain fatty acids while having no effect on the potency of the allosteric agonist 3,3’-diindolylmethane in GPR84. Therefore, studying the binding pocket of an antagonist to GPR84 would be essential for understanding the structural determinants of ligand recognition and receptor modulation. In addition to this time consuming method of screening a large number of compounds, generating a novel transgenic mouse strain expressing ‘chimeric’ human orthologue-like GPR84 could be another solution. Similar potencies of agonists at human and mouse orthologues, along with the high similarities between these two orthologues, provide a foundation for this idea. Herein, stable cells expressing each of HA-human GPR84, HA-mouse GPR84 or HA-humanised GPR84 were generated to characterize and compare the pharmacology of these forms using each of cAMP assays, radioligand binding assays and immunoblotting. Encouragingly, the ability of human GPR84 species selective antagonists compound 020, compound 140, compound 837 and GLPG1205 to block the activation of HA-humanised GPR84 was similar to that of HA-human GPR84. The phosphosite-specific antiserum pT263-pT264 recognized the 2-HTP induced phosphorylation of these three forms of receptors, which suggests that this antiserum can be used to detect the phosphorylation of GPR84 in ex vivo studies in the future. However, HA human GPR84 was constitutively phosphorylated at residues Ser221 and Ser224 while HA- humanised GPR84 was phosphorylated in a 2-HTP-dependent manner at these two residues. This result suggests that the differences between HA-human GPR84 and HA-humanised GPR84 still need to be considered carefully in future studies.
In addition to lacking useful compound tools for pre-clinical models, basic research around GPR84 signalling also need to be improved. GPCR phosphorylation plays an important role in GPCR signalling and regulates the downstream signal transduction including desensitization and internalization of receptors. Thus, studying which GRK(s) might be involved in GPR84 phosphorylation is important for further understanding the signalling of the receptor. It was found that both GRK2 and GRK3 are involved in GPR84 phosphorylation, and Gai probably influences the GRK subtypes that phosphorylate GPR84. Moreover, the recruitment and binding of arrestin 3 to GPR84 may not depend on GPR84 phosphorylation. The internalization of GPR84 was also tracked using BRET-based ‘Bystander’ assays and immunocytochemical staining experiments.
In summary, the studies presented herein characterize novel GPR84 antagonists and suggest the development of a ‘chimeric’ human orthologue-like GPR84 mouse model to explore the therapeutic potential of blocking this receptor. Moreover, the understandings on GPR84 phosphorylation and internalization mechanisms are also improved. The results in this thesis may help to better understand the therapeutic potential of GPR84
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