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Advancing Tidal Turbine Blade Manufacturing: Exploring Current and Alternative Manufacturing Methods
Get PDFRotor blades are critical components of tidal energy converters, typically manufactured from thermoset fibre-reinforced composite (FRC) materials using vacuum infusion processing. High load demands result in thick-section laminates (10–100 mm), particularly at the blade root, posing manufacturing challenges. While tidal and wind turbine blades appear similar in design, the fundamentally different operational conditions lead to distinct structural differences and, therefore, manufacturing requirements, offering opportunities for the tidal sector to innovate. Advances in materials and manufacturing technologies provide opportunities to rethink current practices for improved design and process efficiency. Additionally, the relative immaturity of tidal technology allows for early integration of circularity principles, minimising waste and optimising resource. This paper serves as a comprehensive resource for the tidal turbine blade sector, reviewing current manufacturing practices and exploring alternative techniques. Combining knowledge from academic literature and industrial reports, it outlines blade design, material selection, and current manufacturing processes. The paper evaluates emerging techniques and potential modifications to established methods. Due to the range of turbine designs in the sector, optimal materials and manufacturing combinations will differ. This study offers manufacturers valuable insights to support informed and strategic choices to improve and advance tidal turbine blade production
Preclinical evaluation of candidate "kill or cure" strategies to treat MFN2-related lipodystrophy
Get PDFBACKGROUND: The mitofusin 2 (MFN2) R707W mutation causes debilitating human lipodystrophy featuring lower body adipose loss, upper body adipose hyperplasia, and dyslipidaemic insulin resistance. Mechanical complications include airway compromise due to head and neck adipose overgrowth. This condition, sometimes called Multiple Symmetrical Lipomatosis (MSL), is also seen in sporadic form strongly associated with excess ethanol consumption. Mitigating the cellular pathology, or, conversely, exacerbating it, inducing selective death of affected adipocytes, are potential therapeutic strategies.METHODS: Candidate exacerbating and mitigating approaches to MFN2-MSL were tested in human MFN2 R707W/R707W fibroblasts, and in Mfn2 R707W/R707W mice and derived preadipocytes. Cell survival, mitochondrial network morphology and integrated stress response markers were assessed in cells, and body composition and metabolic indices in mice. RESULTS: Forcing galactose metabolism in human MFN2 R707W/R707W dermal fibroblasts did not replicate the overt adipose mitochondrial phenotype. 50mmol ethanol had little effect on Mfn2 R707W/R707W white preadipocytes, but increased mitochondrial content and blunted mitolysosome formation in Mfn2 R707W/R707W brown preadipocytes. 20% EtOH consumption increased brown adipose tissue in female Mfn2 R707W/R707W mice, and serum lactate in males. Rapamycin - a candidate mitigating treatment - increased size and mitolysosome content of WT preadipocytes, and to a lesser degree of Mfn2 R707W/R707W preadipocytes. In male Mfn2 R707W/R707W mice, rapamycin reduced weight gain, brown adipose mass, and increased serum Fgf21. Finally, a panel of mitochondrial stressors solicited no selective death or ISR in Mfn2 R707W/R707W preadipocytes. CONCLUSIONS: Ethanol mildly exacerbates murine MFN2-related MSL, while rapamycin is tolerated. MFN2-related MSL may not be solely attributable to compromised oxidative phosphorylation.</p
Fans and AI:Transformations in fandom and fan studies
Get PDFAI, and especially generative AI, has intersected with fandom in specific ways as fans adopt new practices, scholars have access to additional research methods, and AI tech companies challenge existing concepts of open data, privacy, ownership, fairness, and exploitation. We identify potential areas of disruption to contemporary fandom and fan studies arising from the various uses of AI and suggest what the consequences might be for our understanding of ownership, legality, the fannish gift economy, and even creativity itself. These debates form the backdrop to the four articles and two symposium pieces in this special section, which each interrogate one aspect of the potential transformations that AI is bringing about in fandom and fan studies. We finish with an overview of the individual submissions, demonstrating the value of their contributions to fan studies and their relevance to wider discussions around the relationships between humans, technology, and creativity
Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy
Get PDFSpinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of survival motor neuron (SMN) protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated patients with SMA, indicative of alterations in brain development. Here, using a mouse model of severe SMA, we revealed an underlying neurodevelopmental phenotype in SMA where prenatal SMN-dependent defects in translation drove disruptions in nonmotile primary cilia across the central nervous system (CNS). Low levels of SMN caused widespread perturbations in translation at E14.5 targeting genes associated with primary cilia. The density of primary cilia in vivo, as well as cilial length in vitro, was significantly decreased in prenatal SMA mice. Proteomic analysis revealed downstream perturbations in primary cilia-regulated signaling pathways, including Wnt signaling. Cell proliferation was concomitantly reduced in the hippocampus of SMA mice. Prenatal transplacental therapeutic intervention with SMN-restoring risdiplam rescued primary cilia defects in SMA mouse embryos. Thus, SMN protein is required for normal cellular and molecular development of primary cilia in the CNS. Early, systemic treatment with SMN-restoring therapies can successfully target neurodevelopmental comorbidities in SMA.</p
Precarity and second job-holding in the creative economy
Get PDFThere is extensive research on creative occupations, problematising precariousness, pay gaps, unpaid work and other issues. Less research, and little quantitative work, has looked at multiple job-holding. Issues including portfolio careers, moonlighting, “slashies” and side-hustles are emblematic, and core to the discourse surrounding the creative economy. We use the UK's Labour Force Survey to analyse the extent of multiple job-holding in creative work, and identify three types of second job-holding, according to whether the main, second or both jobs are creative. We compare the characteristics of individuals for each type, and use Understanding Society to show how they move between them over time. We find that second-jobholding is twice as common in core creative as other occupations, and that people working outside London are more likely to combine creative with non-creative work. Those with a creative second job are unlikely to move to a single creative job over time.</p
Practitioners’ and researchers’ perspectives on treatment needs and service provision for online child sexual abuse
Get PDFOnline child sexual abuse (OCSA) presents unique and evolving challenges for young people and those supporting them. Although the long-term psychological impacts of OCSA are increasingly recognised, there remains limited guidance for practitioners on how best to assess and respond effectively to its specific features. This study aimed to explore practitioners’ and researchers’ perspectives on current gaps in service provision, assessment practices, and interventions for young people affected by OCSA. An open-ended online questionnaire was emailed to UK-based practitioners (n=10) and researchers with published expertise in OCSA (n = 36), of whom seven also had clinical experience. (i.e., clinical psychologists, psychiatrists). A total of 46 responses were analysed using thematic content analysis. Most participants defined OCSA broadly as ‘any sexually abusive act by an adult or peer with a digital or online component’. Both practitioners and researchers emphasised the need for responses that include psychoeducation, trauma-informed care, and safeguarding measures. Participants also highlighted challenges unique to OCSA, such as the permanence of abuse imagery and the perceived agency of victims in online interactions, factors which were seen to require specialised responses. Despite these needs, both groups highlighted gaps in specialist support, practitioner training, and co-ordinated multi-agency responses. The findings highlight the urgent need for further research to develop consensus-based, evidence-informed approaches to OCSA-specific assessment and intervention, ensuring services are equipped to meet the needs of this vulnerable population
Interacting Particle Langevin Algorithm for Maximum Marginal Likelihood Estimation
Get PDFWe develop a class of interacting particle systems for implementing a maximum marginal likelihood estimation (MMLE) procedure to estimate the parameters of a latent variable model. We achieve this by formulating a continuous-time interacting particle system which can be seen as a Langevin diffusion over an extended state space of parameters and latent variables. In particular, we prove that the parameter marginal of the stationary measure of this diffusion has the form of a Gibbs measure where number of particles acts as the inverse temperature parameter in classical settings for global optimisation. Using a particular rescaling, we then prove geometric ergodicity of this system and bound the discretisation error in a manner that is uniform in time and does not increase with the number of particles. The discretisation results in an algorithm, termed Interacting Particle Langevin Algorithm (IPLA) which can be used for MMLE. We further prove nonasymptotic bounds for the optimisation error of our estimator in terms of key parameters of the problem, and also extend this result to the case of stochastic gradients covering practical scenarios.We provide numerical experiments to illustrate the empirical behaviour of our algorithm in the context of logistic regression with verifiable assumptions. Our setting provides a straightforward way to implement a diffusion-based optimisation routine compared to more classical approaches such as the Expectation Maximisation (EM) algorithm, and allows for especially explicit nonasymptotic bounds.</p
19F NMR-tags for peptidyl prolyl conformation analysis
Get PDFProline cis/trans isomerism plays an important role in protein folding and mediating protein–protein interactions in short linear interacting motifs within intrinsically disordered protein regions. The slow exchange rate between cis and trans prolyl bonds provides distinct signals in 19F NMR analysis of fluorinated peptides, allowing for simple quantification of each population. However, fluorine is not naturally found in proteins but can be introduced using chemical tags. In this study, we evaluate a range of fluorinated cysteine-reactive 19F NMR tags to assess their ability to react with short, linear proline-containing peptides and accurately report on the equilibrium cis/trans-Pro populations. Several fluorinated electrophilic tags, including nitrobenzenes, sulfonylpyrimidines, and acrylamides, were found to react chemoselectively and reliably report on the %cis-Pro in the model peptide Ac-LPAAC. Other 19F NMR tags were found to be poor reporters of local proline conformation. Although pentafluoropyridine was non-chemoselective, it still reliably reported on %cis-Pro when conjugated via cysteine or tyrosine in Ac-LPAAX (X = Cys, Tyr, Lys) peptides. 3,4-Difluoronitrobenzene was found to be compatible with protein tagging, albeit it had modest reactivity and afforded a pair of regioisimeric tagging-products when reacted with a cysteine mutant of α-synuclein. These tools may be valuable for probing cis/trans-Pro populations in proteins
Taming the Interacting Particle Langevin Algorithm - the superlinear case
Get PDFRecent advances in stochastic optimization have yielded the interacting particle Langevin algorithm (IPLA), which leverages the notion of interacting particle systems (IPS) to efficiently sample from approximate posterior densities. This becomes particularly crucial in relation to the framework of Expectation-Maximization (EM), where the E-step is computationally challenging or even intractable. Although prior research has focused on scenarios involving convex cases with gradients of log densities that grow at most linearly, our work extends this framework to include polynomial growth. Taming techniques are employed to produce an explicit discretization scheme that yields a new class of stable, under such non-linearities, algorithms which are called tamed interacting particle Langevin algorithms (tIPLA). We obtain non-asymptotic convergence error estimates in Wasserstein-2 distance for the new class under the best known rate.</p
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