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Predictive quality of in-fabrication products in smart manufacturing using graph-based deep learning
No full textGraph neural networks are a very powerful way to learn about relationships between entities in graphs. With the rise of IoT devices in manufacturing, more data is being collected to minimise the waste of both valuable resources and time for fabrication. In this paper, we introduce a methodology for predictive quality of in-fabrication products using graph neural networks. Data is collected from a live-working semiconductor wafer fabrication facility and used to produce heterogeneous graphs that represent the fabrication timeline of a wafer. The model uses the graph attention network architecture to classify whether a timeline is scrap or non-scrap. It uses historical graph-level labelled data and achieves an F1-score of 0.928, compared to baselines models of a LSTM and a Homogeneous Graph Attention Network with scores of 0.424 and 0.786 respectively. It gives a foundational framework for future anomaly detection with semiconductor fabrication, allowing real-world data to be analysed with graph-based deep learning tools to provide interpretation and accessible graph-based results
Democratic consent for the Windsor Framework
No full textThe Windsor Framework establishes a unique status for Northern Ireland in the UK-EU relationship that has proven controversial, particularly for unionists. It also provides members of the Northern Ireland Assembly with regular opportunities to give their ‘democratic consent’ to the continued application of arrangements in the Windsor Framework that place Northern Ireland through regulatory alignment de facto in the EU's customs territory and internal market for goods. A first vote in December 2024 saw a majority in favour of consent, but with all unionist MLAs voting against. The absence of a cross-community majority for consent led to the UK government establishing an independent review of the operation of the Windsor Framework, charged with making practical recommendations that command cross-community support. A closer UK relationship with the EU could address some concerns. The Northern Ireland Assembly has a further opportunity to give its consent in 2028
Open science policy guidelines promoting open data sharing in low and middle-income countries for respiratory health research under NIHR Global RESPIRE project
No full textOpen science drives progress, especially in the low-and-middle-income countries (LMICs), where data security and confidentiality are at risk due to lack of resources and non-compliance with diverse privacy laws. The National Institutes of Health and Care Research (NIHR) Global Health Research Unit on Respiratory Health (RESPIRE 2) project, funded by the UK NIHR, is a global collaboration led by the University of Edinburgh and Universiti Malaya, in partnership with seven LMICs and the UK. The collaboration developed open science policy guidelines to streamline data sharing, while ensuring compliance with privacy laws. They thus enable open data sharing in RESPIRE, furthering knowledge and scientific progress and providing greater research opportunities. This is in alignment with UNESCO, which promotes the open science movement to make scientific research and data more accessible, transparent, and collaborative. Some of the key components of this policy guideline are: Here we outline some of the key components of this policy guideline and provide recommendations. By following ethical data-sharing practices and fostering international collaboration, researchers, research assistants, technicians, and research support services can improve the impact of their research and contribute significantly to resolving global health challenges. Policymakers, research institutions, and funding agencies must support the adoption of open science practices in local contexts for long-term sustainability
Modelling the risk of food-borne transmission of Toxocara spp. to humans
No full textHuman toxocariasis is a worldwide parasitic disease caused by zoonotic roundworms of the genus , which can cause blindness and epilepsy. The aim of this study was to estimate the risk of food-borne transmission of spp. to humans in the UK by developing mathematical models created in a Bayesian framework. Parameter estimation was based on published experimental studies and field data from southern England, with qPCR Cq values used as a measure of eggs in spinach portions and ELISA optical density data as an indirect measure of larvae in meat portions. The average human risk of spp. infection, per portion consumed, was estimated as 0.016% (95% CI: 0.000-0.100%) for unwashed leafy vegetables and 0.172% (95% CI: 0.000-0.400%) for undercooked meat. The average proportion of meat portions estimated positive for spp. larvae was 0.841% (95% CI: 0.300-1.400%), compared to 0.036% (95% CI: 0.000-0.200%) of spinach portions containing larvated spp. eggs. Overall, the models estimated a low risk of infection with spp. by consuming these foods. However, given the potentially severe human health consequences of toxocariasis, intervention strategies to reduce environmental contamination with spp. eggs and correct food preparation are advised
Versatile cell penetrating peptide for multimodal CRISPR gene editing in primary stem cells
No full textCRISPR gene editing offers unprecedented genomic and transcriptomic control for precise regulation of cell function and phenotype. However, delivering the necessary CRISPR components to therapeutically relevant cell types without cytotoxicity or unexpected side effects remains challenging. The RALA cell penetrating peptide is an amphiphilic peptide that self-assembles into nanoparticles through electrostatic interactions with anionic molecules and delivers them across the cell membrane. Given the low cytotoxicity, versatility, and competitive transfection rates of RALA, we aimed to establish this peptide as a new CRISPR delivery system in a wide range of molecular formats across different editing modalities. We report that RALA effectively encapsulated and delivered CRISPR DNAs, RNAs, and ribonucleic proteins (RNPs) to primary mesenchymal stem cells (MSCs), outperforming commercially available reagents. We then used the RALA peptide for the knock-in and knock-out of reporter genes into primary MSCs and the transcriptional activation of therapeutically relevant genes. Finally, we demonstrate in vivo gene editing using RALA to knock-out luciferase and GFP in a reporter mouse model. In summary, we establish RALA as a powerful tool for safer and more effective delivery of CRISPR machinery in multiple cargo formats for a wide range of ex vivo and in vivo gene editing strategies.</p
Transplantation of mesenchymal stromal cell-derived mitochondria alleviates endothelial dysfunction in pre-clinical models of acute respiratory distress syndrome
No full textBackgroundPulmonary endothelial dysfunction with increased capillary permeability is a key aspect in the pathogenesis of acute respiratory distress syndrome (ARDS). It has been demonstrated that mesenchymal stromal cells (MSC) can modulate host cells through mitochondrial transfer. Although mitochondrial transplantation is a promising treatment strategy for conditions underpinned by mitochondrial dysfunction, its therapeutic potential in ARDS has not been sufficiently investigated. Herein, we tested the potential of MSC mitochondrial transplantation to restore functionality of the pulmonary endothelium in pre-clinical models of ARDS.MethodsMitochondria (mt) derived from human bone-marrow MSC were isolated and immediately used for transplantation to primary human pulmonary microvascular endothelial cells (HPMEC) in the presence of Escherichia coli lipopolysaccharide (LPS) or plasma samples from ARDS patients classified into hypo- and hyper-inflammatory phenotypes. Mitochondrial function, inflammatory status, and barrier integrity of HPMEC were assessed at 24 h. LPS- challenged mice were treated with MSC-mt intravenously, and the severity of lung injury and inflammatory response were evaluated.ResultsExposure to LPS or ARDS plasma induced endothelial hyperpermeability associated with mitochondrial dysfunction. MSC-mt were readily internalized by HPMEC without cytotoxicity or inflammatory response, mitigating mitochondrial dysfunction and restoring barrier integrity. In vivo, administration of MSC-mt alleviated lung injury, reduced inflammatory cell infiltration in the alveoli and increased VE-cadherin mRNA levels in the lung tissue, indicating restoration of the alveolar-capillary barrier integrity.ConclusionThis study demonstrated MSC mitochondrial transplantation as a promising therapeutic approach for treatment of endothelial dysfunction in the context of acute inflammation. Further exploration of mitochondrial transplantation in ARDS is warranted.<br/
Brusselstown Ring: a nucleated settlement agglomeration in prehistoric Ireland
No full textFollowing the identification of more than 600 suspected house platforms on aerial survey data from Brusselstown Ring hillfort, four test excavations revealed evidence of Late Bronze Age and Early Iron Age occupation, positioning the site as the largest nucleated settlement so far identified in prehistoric Ireland and Britain
Noninvasive genotyping and early disease dynamics demonstrate the efficacy of ibrutinib in combination with immunochemotherapy in patients with mantle cell lymphoma treated in the TRIANGLE trial
No full textAdding ibrutinib to first-line immunochemotherapy (Ibru-R-chemo) showed superiority in younger mantle cell lymphoma (MCL) patients in the TRIANGLE trial (NCT02858258). To investigate response mechanisms and kinetics across treatment arms, we genotyped 57 patients from cell-free (cf)DNA using targeted-capture sequencing and investigated measurable residual disease (MRD) in cfDNA and peripheral blood by targeted-sequencing and qPCR. Pre-treatment cfDNA and circulating tumor (ct)DNA levels predicted outcomes, and precisely genotyped all patients. Circulating tumor cell (CTC)-clearance was more frequent and rapid than ctDNA-clearance across arms. At interim staging (IS), 55% of patients were ctDNA-positive while 35% and 41% were CTC-positive by qPCR and immunoglobulin gene (IG)-NGS. At end of induction, 43% were ctDNA-positive, while 15% (qPCR) and 25% (IG-NGS) were CTC-positive. MRD by qPCR was most predictive for outcomes. Ibru-R-chemo seemed to overcome TP53 -mediated risk (hazard ratio 1.9 vs. 10) and induce early MRD response, represented by enhanced CTC (71% vs. 57%) and ctDNA clearance (59% vs. 24%) at IS. Flow-cytometry-based immunomonitoring showed ibrutinib's influence on inhibitory T-cell phenotypes, showing ≥25% reduction in PD1+ and PD1+ KLRG1+ CD4+-T-cells in four patients. Taken together, besides direct anti-B-cell efficacy, ibrutinib improves chemotherapy efficiency by reconstituting an effective immune system and enhancing immune cell control
Semi-submersible hybrid platforms for wind–wave hydrodynamic performance: high-fidelity numerical simulations powered by SPH
No full textHybrid wave–wind energy platforms seem a promising way forward to elevate renewable energy power production by blending in wave energy converters (WEC) and wind turbines. This work proposes an extreme performance estimation through high-fidelity software for a power unitcomprising a 5-MW NREL wind turbine and three WaveStar devices using a numerical framework based on DualSPHysics, which implements the Smoothed Particle Hydrodynamics method to solve the fluid dynamics, powered by state-of-the-art GPU parallelization. First, we validate the response of the power unit by relying on sub-component model validations, specifically, validating an OC4 DeepCwind layout under operational frequencies, and, using their spectral representation, we compare the hybrid platform performance during power production. Using incremental sea-states, we employ the model to evaluate the platform-to-WEC sensitivity for two cases: no power absorption and operational, respectively. This investigation shows that the platform heave and pitch motion increase by about two and three times, respectively, when the devices are operating at their optimal damping. On the other hand, the surge motion only increases by around 50%. It is clear – combined wave and wind energy platforms are more susceptible to wave induced loads when the wave energy process is not interrupted, suggesting how WECs combined to FOWTs do not generally provide a stabilizing effect unless more specific strategies are enforced