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Change and adaptation in the fiction of John Wyndham
No full textThis thesis examines the writings of the British author John Wyndham (1903–1969), whose body of work comprises fiction, including science fiction (SF), crime, horror and fantasy, as well as published and unpublished SF criticism. Wyndham’s career spanned almost half a century, during which he wrote 12 novels and over 70 stories, using nine different pseudonyms. The commercial success of Wyndham’s The Day of the Triffids (1951) prompted critics to firmly divide his career into two periods: the early fiction written predominantly for the emerging American SF pulp magazine market, and his more mature work geared towards the general British audience. The thesis challenges this demarcation, which rests on deliberately overlooking Wyndham’s early fiction, and instead, it argues for continuities in his work. Wyndham’s unwavering fascination with the concepts of change, including biological, evolutionary, environmental, scientific and social change, and adaption to that change, serves as a framing mechanism that enables the discussion of his early and more obscure fiction alongside his later works. Chapter 1 examines critical and archival material to illustrate how Wyndham’s journey as a writer mirrored the evolving nature of SF, and how, at the same time, the subject matter of his fiction remained fundamentally unchanged. Chapters 2 to 5 illustrate these points through analysis of his works. His fiction is grouped thematically, according to the main themes dominant in SF: science and technology (Chapter 2); apocalypse and dystopia (Chapter 3); aliens and space exploration (Chapter 4); and time travel (Chapter 5). Appendix 1 examines the artwork accompanying Wyndham’s publications throughout his career. It illuminates why his early fiction, due to its pulpish associations, was often mistakenly treated as a separate period in his career. Appendix 2 is a detailed and updated chronological bibliography, whose aim is to verify, correct and supplement the existing bibliographical information. Wyndham’s early fiction was published and serialised under different pseudonyms in a variety of magazines in both Europe and America. The aim of Appendix 2 is to further illustrate that this dispersion was the reason Wyndham’s early fiction went unnoticed by critics and became separated from his later career. The thesis contributes to the following fields: American and British SF studies, ecocriticism, feminist studies, and British and American pulp fiction magazine culture
Techno-economic analysis and supply chain optimisation for CCS and bioenergy in hard-to-abate sectors
No full textThis thesis investigates the feasibility of deploying carbon capture and storage (CCS) and bioenergy in hard-to-abate sectors through techno-economic analysis and supply chain optimisation. It focuses on (i) dispatchable fossil fuel power plants serving as backups in power systems with high penetrations of variable renewable electricity (VRE), and (ii) sectors such as cement, steel, and industries that rely on combined heat and power (CHP) systems.
First, a techno-economic model is developed to assess the cost of CCS integration into natural gas combined-cycle gas turbine (CCGT) power plants to account for the kinds of capacity factors expected in high VRE power systems. Results show that as CCGT capacity factors decrease due to VRE expansion, CCS costs per tonne of CO₂ captured rise significantly, strongly affecting the levelised cost of electricity (LCOE) for the CCGT. For example, at 70% CCGT capacity factor and NG price of 40 €/MWh, a CO₂ emission price of around ~170 €/tCO₂ is needed for the LCOE with CCS to remain lower than without CCS. At 30% CCGT capacity factor, this figure is over 300 €/tCO₂. Higher NG prices require even greater CO₂ prices to sustain cost-effectiveness. Sensitivity analysis indicates that reducing the fixed costs of capture systems is more beneficial than enhancing capture efficiency, especially for low capacity factor operations.
Building on these results, the study investigates the broader impact of low capacity factor power plants on the entire CCS supply chain through a case study for the island of Ireland. Techno-economic models are developed for CO₂ capture from cement, metals production, and CHP-dependent industries, along with transportation models (via truck, pipeline and ship) and CO₂ storage. Ten scenarios, with and without fossil fuel power plants and CHP industries, are evaluated. Findings reveal that, for the same quantity of CO₂ processed, building shared infrastructure only for emission sites with long-term CO₂ supply certainty (e.g., process emissions from cement and metal industries) reduces total infrastructure costs by up to 34% compared to initially accommodating all sources and subsequently losing CO₂ supply from fossil fuel based emission sites.
Finally, the work examines bioenergy supply chains, focusing on hydrothermal carbonisation (HTC) of wet biomass residues to produce hydrochar as a coal substitute in steel mills. A Swedish case study covering 21 paper plants and two steel mills is conducted, assuming a configuration with (i) onsite HTC, due to the high moisture content of paper sludge, and (ii) centralised drying and pelletisation. Techno-economic models are developed for all stages. The study emphasises the importance of a non-linear optimisation approach to identify optimal hub locations and sizes without predefined sets, demonstrating a 35% cost reduction compared to decentralised configurations for the case study. The findings also indicate that maintaining lower moisture levels in pressed cakes, which is a HTC intermediate product, is essential not only for minimising transportation costs but also for enabling fewer hubs to fully leverage the cost advantages of economies of scale.
Overall, this thesis makes novel contributions to advancing CCS and bioenergy supply chain research. It examines the feasibility of CCS integration in power plants with low capacity factors and explores other influencing parameters. Additionally, it highlights the need for careful emission site selection before full-scale CCS implementation in hard-to-abate sectors. Finally, it demonstrates the advantages of non-linear optimisation for determining optimal hub locations and sizes in bioenergy supply chains.Sustainable Energy Authority of Ireland (SEAI) Project No. RDD447, European Commission under the F-CUBED Horizon 2020 project (Grant Agreement No. 884226
A function for ATR kinase in the regulation of cytokinetic abscission
No full textAbscission, the final stage of cytokinesis, separates the two daughter cells through cutting of the intercellular bridge. This occurs on either side of a proteinaceous, microtubule-dense structure known as the midbody. Abscission is mediated by the ESCRT proteins that are recruited sequentially to the midbody. These include the ESCRT-III complex which is composed of eight families of ‘CHMP’ proteins that are responsible for a series of membrane remodelling events that ultimately results in abscission. These ESCRT-III filaments in turn interact with a hexameric AAA ATPase VPS4. VPS4 is a ‘remodelling’ complex that continuously remodels ESCRT-III filaments by exchanging CHMP subunits for those with geometries that favour membrane deformation and ultimately constrict the plasma membrane. The ESCRT- III subunit CHMP4B is the main positive regulator of the ESCRT-III filament architecture, required for abscission. An isoform of CHMP4B, termed CHMP4C, negatively regulates abscission by preventing the formation of ESCRT-III filaments of the correct architecture.
Abscission timing is regulated by Aurora B kinase which localises to the cytokinetic midbody to prevent premature abscission in the presence of chromatin between the separating daughter cells, which can result in binucleate cells and/or DNA damage. This so-called ‘abscission checkpoint’ controls abscission timing via the ANCHR protein which ‘anchors’ the VPS4 protein at the midbody thereby preventing VPS4 from catalysing the ESCRT-III remodelling required for abscission at the final ‘cut’ site until chromatin has been removed from the intercellular bridge I have shown that in each cell cycle, irrespective of any chromatin bridges, ATR localises to the cytokinetic midbody specifically during late cytokinesis. Furthermore, ATR at the midbody corresponds to its activated phosphorylated form (ATR-T1989p). Consistent with previous genetic studies using a chicken Atr conditional null DT40 cell line, chemical inhibition of ATR activity results in premature abscission and cytokinetic defects. Interestingly, ATR-T1989p midbody localisation is dependent upon the negative regulator CHMP4C, and ATR kinase activity is required to impede the recruitment of CHMP4B, as well as promoting the recruitment of the abscission checkpoint regulator ANCHR to the midbody. Together, this data supports a role for ATR in regulating the correct timing of abscission which is separate from its canonical role in the replication stress response
Human trafficking for forced labour along the East Africa to the Gulf Cooperation Council labour migration corridor: A case of Kenya, Uganda and Qatar
No full textTemporary labour migration between East Africa and the Gulf Cooperation Council states have increased since the early 2000s. Particularly, Kenya and Uganda have implemented deliberate policies of labour migration to the GCC states in response to growing domestic unemployment and to benefit from a growing migration economy. Similarly, countries in the GCC, such as Qatar rely primarily on labour migration for a functional labour force. Within this burgeoning migration corridor, reports of trafficking of migrant workers dominate United Nations specialised agenices’, media, and civil society reports. Trafficking of migrant workers occurs despite intensified efforts to arrest the issue since the adoption of the 2000 Protocol to Prevent, Suppress, and Punish Trafficking in Persons and the 2014 Protocol to the ILO Forced Labour Convention. This thesis sets out to understand why this is so. It applies a Third World Approaches to International Law (TWAIL) lens to critically analyse the relationship between labour migration and trafficking of migrant workers along the East Africa to the GCC migration corridor.
Employing TWAIL lens through comparative international legal research, socio-legal inquiry, critical historical analysis, and doctrinal examination, this thesis critically examines the development of a fragmented approach to anti-trafficking within labour migration contexts. It examines the relationship between this fragmented development and international migration law. Within this context, this thesis contends that the colonial foundations of anti-trafficking, anti-slavery, and anti-forced labour influences contemporary approaches to anti-trafficking on the international and domestic plane. Within the context of Kenya, Uganda, and Qatar, the thesis argues that colonial legacies impact trafficking of migrant workers for forced labour as well as responses. This thesis contends that the colonial influence on anti-trafficking has resulted in manufactured ambiguities that obscure accountability for recruitment violations that lead to trafficking and entrenching legal uncertainty. It introduces the concept of transnational elite solidarity that perpetuates racialised labour hierarchies, externalising risks to migrants while securing capital and developmental benefits for states and intermediaries. Finally, legacies of colonislaisation in anti-trafficing results in a false universalisation that masks racial undertones and neglect legacies of exclusion
Optimizing nickel-based catalysts for sustainable hydrogen production: Insights from structural, electrochemical, and theoretical analysis
No full textThe presented thesis deals with the areas of design, synthesis, and electrochemical evaluation of Ni-based electrocatalysts for oxygen evolution reaction and urea oxidation reaction in hydrogen production. The work presented here is divided into several sections, beginning with an introductory chapter on the main topics involved in the investigational work. The experimental and computational research is divided into four separate chapters
Vascularization of cerebral organoids: Imporving in vitro modelling of the neurovascularity
No full textBrain organoids (BOs) are multicellular, self-organized, stem cell-derived in vitro 3D systems aim to recapitulate morphological and physiological features of the human brain. These emerging models are attractive for developmental biology, disease modelling and drug screening, and represent an alternative to animal experimentation in neuroscience. However, low oxygen and nutrients diffusion due to a missing vascularity limits their growth and survival, hence their translatability to clinical applications. Vascularization of BOs poses several technical challenges, including the simultaneous differentiation of two tissues of different origin, uneven distribution and limited penetration of the vascular networks within the microtissue, and the absence of luminal perfusion. To mitigate these issues, we devised an encapsulation approach in which human brain microvascular endothelial cells (HBMVECs) were delivered to developing cerebral organoids (COs), a self-patterned type of BOs, from a progressively degrading surrounding biomaterial. The composition of the media and the concentration of the hydrogel were tuned to promote both neurodevelopment and endothelial network formation. Using this strategy, we identified a higher density of vascular-like networks that expanded towards the organoid centre. By using pathway inhibitors and fluorescent endothelial cells, the origin of these endothelial networks was revealed to arise from both endogenous differentiation and the exogenously introduced HBMVECs. Endogenous endothelial contributions were enhanced in unguided BO protocols and varied across cell lines. Vascularized COs displayed typical blood–brain barrier (BBB) characteristics, including claudin 5 expression, astrocytes and pericyte-like cells interactions, and laminin and collagen IV depositions. They also showed smaller necrotic cores and increased permeability to an external dye, although intraluminal flow was not demonstrated. Fluorescence-activated cell sorting (FACS), RNA sequencing and immunohistochemistry (IHC) revealed enhanced cortical regionalization with PAX6 expression and expanded radial glia layers, while later neuroglial differentiation remained unaltered upon vascularization, as confirmed by calcium imaging and IHC. Vascularized COs have also been integrated into microfluidic devices to incorporate directional flow within the vessels, but further optimization is required. Overall, these findings establish an accessible model of the human neurovascularity as a platform for disease investigation and drug discovery.This work was supported by Research Ireland 18/EPSRC-CDT/3583 and the Engineering and Physical Sciences Research Council EP/S02347X/1.
This work has emanated from research supported in part by a grant from Research Ireland and the European Regional Development Fund (ERDF) under grant number 13/RC/2073_P2
What’s the law got to do with it? Social interpretation patterns of ageism and older adults access to services and goods
No full textIn Western consumer and service-based economies, access to services and goods is an essential part of social participation. For older people, this participation can be undermined by ageism, for example in access to health, financial and transport services. One way to counteract ageism is through anti-discrimination legislation. However, there is no EU-wide prohibition of age discrimination in access to services and goods. Consequently, different or no regulations exist in the various member states. This is also the case in the two countries analysed in this study, namely Austria and Ireland. While there is no national prohibition of age discrimination in access to services and goods in Austria, this form of discrimination is prohibited in Ireland. Such differences in legislation may be reflected in the way individuals experience and talk about discrimination. This thesis therefore examines how the presence or absence of legal prohibitions of age discrimination in access to services and goods shapes older people's experiences and narratives of age discrimination in access to health, finance and transport services.
Drawing on the so-called interpretation pattern analysis, the role of law in the interpretations of ageism was examined based on interviews with 29 older people, 12 expert interviews, two focus groups with a total of 12 representatives of advocacy and interest groups, and the analysis of legal and policy documents. The analysis of this data resulted in the reconstruction of four interpretation patterns of ageism namely: (i) ‘ageism as objectifiable disadvantage’, (ii) ‘ageism as denial of recognition as a person’, (iii) ‘ageism as lack of consideration’, and (iv) ‘ageism as denial of social recognition’.
The discussion of the findings shows that the law assumes a hegemonic role in the constitutive dimension, that is, in its ability to influence how people think and talk about their experiences of ageism. In instrumental terms, however, the data reflected an alienation from the law, as the older people I interviewed did not regard the law as an accessible solution for combating discrimination. Furthermore, the analysis shows that age discrimination is part of the social practices that socially construct aging and older age, as experiences of ageism mediate the transition from the so-called third to the fourth age and undermine related relations of recognition
Harnessing nuclear-organellar genome interactions for seed size heterosis in Arabidopsis thaliana
No full textThe nucleus contains most of the genome, which often leads to the contribution of the cytoplasm to phenotypes being overlooked. However, there was evidence that cybrids (nucleus/cytoplasm-swapped lines), generated through backcrossing or haploid induction, can produce a heterosis-like effect that influences agronomic traits, such as seed size. Heterosis refers to the phenomenon where offspring exhibit superior phenotypes compared to their parents. Despite several hypotheses, the underlying mechanisms remain unclear. Seed size, a critical agronomic trait, is determined by multiple mechanisms. During double fertilization, the embryo and endosperm inherit the nuclear genome from both parents, while all seed structures contain cytoplasm inherited exclusively from the mother. Thus, cytonuclear disequilibrium arises and acts as a regulator for seed development. In this thesis, we generated a series of cybrid lines using the natural variations (accessions) found in Arabidopsis thaliana. By comparing different cybrid line combinations, we provide evidence that cytonuclear interactions significantly influence seed size and that these effects can be transmitted to the F1 generation. Additionally, a GWAS identified a nuclear-encoded gene, RLP15 that may specifically respond to the Col-0 cytoplasm in seed size determining. Our findings also highlight the importance of cytoplasmic inheritance in parental effects. This study underscores that harnessing natural variation in the cytoplasm between accessions can produce a heterosis-like effect that, in certain genetic backgrounds, may be equivalent to or even greater than heterosis out from hybridization. Moreover, the impact of cytoplasm swapping to F1 seed size can be cumulative and interactive with heterosis, suggesting that cytoheterosis is partially independent of traditional heterosis mechanisms. In conclusion, our results indicate a new avenue for improving traits in plant breeding programs by leveraging naturally occurring genome variations
Characterisation of novel preclinical models of wound-related pain: Role of the endocannabinoid system
No full textWound-related pain is a significant unmet clinical need. Up to 80% of individuals with lived experience of chronic wounds experience persistent, debilitating pain. Current wound management therapies typically do not focus on specific management strategies for pain. Current therapeutic approaches for the management of wound-related pain, such as topical morphine, may impede wound healing. Consultation with individuals with lived experience of wounds revealed that wound-related pain management was the area in which they wished to see new research.
The endocannabinoid system has a role in wound healing, skin homeostasis, and modulation of the pain experience. Several case reports and open-label trials report that administration of cannabis-based therapeutics provides benefit for the management of wound-related pain. However, there is a paucity of preclinical research investigating the potential of the endocannabinoid system for the management of wound-related pain. In fact, to my knowledge, there is no validated, characterised model for the study of wound-related pain in vivo, representing a major barrier to broadening our understanding of the wound-related pain state. The work presented in this thesis tested the hypothesis that current rat models of wound healing, and the aetiologies underlying chronic wound formation, are suitable for the study of wound-related pain, and provide a solid framework for the investigation of endocannabinoid system modulation on wound-related pain. The overarching aims of the work presented herein were to 1) characterise pain-related behaviour, and the endocannabinoid system in a rodent incisional wound model, and a rodent model of ischemia-reperfusion injury, 2) provide evidence for the predictive validity of the incisional wound model as a model for the study of wound-related pain via mu-opioid receptor agonist administration and 3) investigate the effects of endocannabinoid system modulation on pain-related behaviour following incisional wound.
Unilateral hind limb ischemia-reperfusion injury led to robust mechanical hypersensitivity and more transient cold hypersensitivity in male Sprague Dawley rats, with a less pronounced phenotype in females. Investigation into the endocannabinoid system revealed that 30 days following ischemia-reperfusion injury, there were increased levels of N-palmitoylethanolamide (PEA) in the thalamus of female rats vs their female sham counterparts, and vs their male ischemia-reperfusion counterparts.
Following the creation of an incisional wound on the dorsum, there was robust mechanical hypersensitivity at the dorsum for up to 14 days post-incision in male Sprague Dawley rats, and up to 7 days post-incision in females. Secondary mechanical hypersensitivity was observed in the hind paws. There were significantly lower levels of the gene encoding the cannabinoid CB1 receptor in the rostral ventromedial medulla (RVM) of male incision rats vs sham on post-incision day 35.
We sought to pharmacologically validate the phenotype observed post-incision via the administration of a mu-opioid receptor agonist, whilst the pain phenotype was robustly present. Morphine (3 mg/kg s.c.) significantly attenuated mechanical hypersensitivity in the dorsum and hind paws at post-incision day 8. Morphine (3 mg/kg s.c.) significantly increased levels of PEA in the plasma of sham and incision rats, and increased levels of N-oleoylethanolamide (OEA) in the plasma of sham rats.
Finally, an investigation into the effects of inhibiting the endocannabinoid-degrading enzymes, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL) on mechanical hypersensitivity post-incision was completed. Pharmacological inhibition of MGL or FAAH had differential effects on mechanical hypersensitivity post-incision. MGL inhibition attenuated mechanical hypersensitivity at the dorsum and hind paws, whereas FAAH inhibition attenuated mechanical hypersensitivity in the hind paws only. MGL inhibition increased levels of 2-AG in the spinal cord, and key brain regions related to nociception. FAAH inhibition increased levels of AEA, OEA and PEA in the plasma, spinal cord and key brain regions related to nociception.
In conclusion, the data presented in this thesis provides evidence to support the use of the dorsum incision model, and the hind limb ischemia-reperfusion model, as models for the study of wound-related pain. Moreover, there is evidence to suggest that modulation of the endocannabinoid system attenuates wound-related pain behaviour following incisional wound creation
Energy-based versus stress-based material failure criteria: The experimental assessment
No full textPrevious studies have reported fracture localization within the inclusions of 3D-printed staggered composites, despite their significantly higher strength compared to the matrix – a seemingly counterintuitive phenomenon. In this letter, we investigate whether material failure is governed by the volumetric energy of fracture rather than the maximum stress criterion. We perform experiments on the constituent phases of 3D-printed staggered composites to evaluate the validity of energy-based failure criteria. Our findings support the idea that the work of fracture, rather than strength, governs failure. Specifically, at relatively higher strain rates, the ability of the soft matrix to absorb more energy before failure suggests that fracture localization is driven by energy considerations rather than stress thresholds. This aligns with previous observations that inclusions may fail before the matrix despite their higher strength. More broadly, since engineering materials often exhibit a crystalline molecular structure where failure is dictated by the energy required to break atomic and molecular bonds, it naturally follows that the work of fracture – rather than strength – should serve as the primary failure criterion. Our results reinforce this perspective, offering a more physically grounded approach to predicting material failure.The support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (MAGIC –[852281]) is gratefully acknowledged. Also, K. Y. Volokh is supported by the Israel Science Foundation, Israel (ISF-394/20) as well as the Israeli Ministry of Science and Technology (MOST-0005173).peer-reviewe