143174 research outputs found
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Understanding preferences for low-carbon technologies, retrofit and ownership models for domestic heating in the UK
No full textPreprint versio
Reflections on bio-based PET and plastic waste management: a responsible research and innovation approach
No full textPlastics drive twin crises: persistent pollution and greenhouse gas emissions. Bio-based approaches using enzymes and microorganisms to depolymerise plastics and valorise monomers show promise but raise societal, ethical and regulatory questions central to Responsible Research and Innovation (RRI). In this Perspective, we reflect on RRI implications of bio-based plastic degradation, informed by stakeholder discussions across the plastics value chain and public engagement. We identify broad support alongside concerns about scalability, interaction with existing recycling, governance and containment of genetically modified organisms, management of additives and contaminants, and the roles of regulation and economic incentives in enabling adoption
Impartial games: a challenge for reinforcement learning
No full textAlphaZero-style reinforcement learning (RL) algorithms have achieved superhuman performance in many complex board games such as Chess, Shogi, and Go. However, we showcase that these algorithms encounter significant and fundamental challenges when applied to impartial games, a class where players share game pieces and optimal strategy often relies on abstract mathematical principles. Specifically, we utilise the game of Nim as a concrete and illustrative case study to reveal critical limitations of AlphaZero-style and similar self-play RL algorithms. We introduce a novel conceptual framework distinguishing between champion and expert mastery to evaluate RL agent performance. Our findings reveal that while AlphaZero-style agents can achieve champion-level play on very small Nim boards, their learning progression severely degrades as the board size increases. This difficulty stems not merely from complex data distributions or noisy labels, but from a deeper representational bottleneck: the inherent struggle of generic neural networks to implicitly learn abstract, non-associative functions like parity, which are crucial for optimal play in impartial games. This limitation causes a critical breakdown in the positive feedback loop essential for self-play RL, preventing effective learning beyond rote memorisation of frequently observed states. These results align with broader concerns regarding AlphaZero-style algorithms’ vulnerability to adversarial attacks, highlighting their inability to truly master all legal game states. Our work underscores that simple hyperparameter adjustments are insufficient to overcome these challenges, establishing a crucial foundation for the development of fundamentally novel algorithmic approaches, potentially involving neuro-symbolic or meta-learning paradigms, to bridge the gap towards true expert-level AI in combinatorial games
A comprehensive review of global per- and polyfluoroalkyl substances (PFAS) in water and their remediation through degradation and defluorination techniques
No full textPer- and polyfluoroalkyl substances (PFAS) are of growing concern to the environment and human health due to their suspected toxicity, chemical stability and potential for long-term persistence in environmental matrices. The unique characteristics of the carbon-fluorine (Csingle bondF) bond in these substances indicate the need for innovative approaches to achieve effective environmental remediation. This review examines global PFAS contamination across various water sources and evaluates different degradation and defluorination methods. It also includes a bibliometric analysis covering the years 2010 to 2024. The paper thoroughly analyses citations, maps keyword co-occurrences, and assesses trends to identify significant research themes, key articles, and emerging technological conceptual pathways. Several PFAS degradation and defluorination methods, including chemical, biological, and physical technologies, are systematically evaluated for their effectiveness and potential limitations. This review aggregates global data on PFAS occurrence in water sources and employs bibliometric analysis to assess the present status of remediation research. The findings indicate that degradation and defluorination are the most effective approaches for the permanent removal of PFAS, exceeding basic separation procedures. An essential observation is that the efficacy of these destructive processes is significantly contingent upon structural characteristics, particularly the length of the fluoroalkyl chain, which affects the primary degradation pathway. Consequently, the formulation of future remediation techniques must be grounded in a comprehensive understanding of the relationship between structure and reactivity to ensure more efficient and thorough elimination of PFAS
PFAS-driven modulation of algal organic matter enhances dissolved organic matter reactivity and disinfection by-product formation: mechanistic elucidation via multi-spectroscopic analysis, and mitigation by coagulation and nanofiltration
No full textThe quality of drinking water is crucial for public health and sustainable development. This study elucidates the interaction between per- and polyfluoroalkyl substances (PFAS) and algal organic matter (AOM) in freshwater sources, which modifies the composition and reactivity of dissolved organic matter (DOM), enhances the formation potential of disinfection by-products (DBP), and may impact drinking water treatment (DWT) systems. The study employs multi-spectroscopic analysis like excitation emission matrix-parallel factor analysis (EEM-PARAFAC), Fourier-transform infrared spectroscopy (FTIR), and DBP quantification to demonstrate that specific PFAS (hexafluoropropylene oxide dimer acid (GenX), and perfluorobutane sulfonate (PFBS)) with AOM shift DOM to protein-like dominance, reducing the humification index (HIX) by 70 % and disrupting amide I bonds. This transition elevated brominated DBPs (>90 % of total DBPs in algae-PFAS systems). Coagulation (Polyaluminum chloride, PACl, 50–200 mg/L) exhibited concentration-dependent flocculation index (FI) increases, with GenX (1 μg/L) and PFBS (10 μg/L) peaking at 1.1–1.18 % FI, enhancing floc formation within 300 s, though AOM reduced baseline FI to 0.7 %. Nanofiltration (NF-270 membrane) showed flux reductions of 36–43 % for GenX (0.1–10 μg/L) and 39–47 % for PFBS (0.1–10 μg/L) without AOM, intensifying to 46 % (GenX10) and 52 % (PFBS10) with AOM due to biopolymer release and algal stress. Combined coagulation and nanofiltration treatment reduced DBP precursors by 60–85 % and mitigated fouling. These findings reveal that PFAS-AOM complexes elevate DBP formation risks and impair DWT efficiency, emphasizing the need for integrated coagulation, filtration, and nanofiltration processes to manage water quality hazards arising from PFAS-algal-impacted water sources
Physical activity and the risk of aortic dissection: results from the UK Biobank
No full textPurpose: We investigated the association between physical activity and the risk of aortic dissection in the UK Biobank.
Methods: The analytical dataset included 452,994 participants aged mainly between 40-69 years, recruited from 2006 to 2010. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between physical activity and the risk of aortic dissection.
Results: During 12.3 years follow-up, 331 aortic dissection cases were identified. No clear association was observed between the highest vs. lowest quintile of frequency of leisure-time physical activity (HR, 95% CIs: 0.84, 95% CI: 0.59-1.19; ptrend=0.88), moderate physical activity (1.12 (0.77-1.65, ptrend=0.37), or vigorous physical activity (1.11, 0.83-1.50, ptrend=0.51) and risk of aortic dissection. A suggestive inverse U-shaped association was observed for moderate vs. low levels of walking and aortic dissection risk with HRs (95% CIs) of 1.00 (reference), 0.81 (0.54-1.20), 0.65 (0.43-0.99), 0.66 (0.41-1.06) and 0.84 (0.60-1.18) for walking 2, 4, 5, 6, and 7 times/week, respectively. This association was slightly strengthened after exclusion of participants with prevalent CVD, cancer and respiratory disease at baseline. In analyses using MET-hours/week as the metric, a suggestive inverse association was observed for vigorous physical activity (0.66, 0.43-0.99; ptrend=0.09), but not for other physical activity domains.
Conclusion: Overall, we found little evidence of a clear association between physical activity and aortic dissection in the current study. Potential U-shaped inverse associations between frequency of walking and the risk of aortic dissection, and between MET-hours/week of vigorous physical activity and aortic dissection need further study in additional large cohort studies
Identification of missense variants in the C-domains of Von Willebrand Factor that cause gain-of-function-like activity
No full textRecently characterised mutations Phe2561Tyr, Pro2555Arg in the Von Willebrand Factor (VWF) C4 domain and Gly2705Arg in the C6 domain reportedly confer gain-of-function-like activity on the molecule, increasing responsiveness to shear stress, resulting in enhanced platelet capture. This implies that the C-terminal stem, comprised of the D4-C6 domains, plays a crucial role in modulating VWF function. To further investigate this, we used site-directed mutagenesis to generate a panel of uncharacterised C-domain variants. VWF expression and function were analysed under static and shear stress conditions, and the biophysical properties of the variants were characterised by single-molecule optical tweezers (OT), and atomic force microscopy (AFM) imaging. All the expressed variants exhibited normal function in static assays, except the C1 domain Arg2287Trp variant that demonstrated increased binding to GPIbα. Under flow conditions at 1500s-1, all the variants had normal VWF-mediated platelet capture to collagen, however at 5000s-1 Arg2287Trp demonstrated enhanced platelet capture, while Asn2636Tyr (C5 domain), Thr2647Met (C6 domain) and Gly2705Arg showed reduced activity. Further analysis of the formation of rolling VWF-platelet aggregates over a VWF surface demonstrated an enhanced response to shear stress for the Arg2287Trp and Arg2384Trp (C2 domain) variants. OT analysis identified novel extension events exclusive to the C-terminal domains and more frequent unfolding events and longer unfolding extensions for Arg2287Trp and Arg2384Trp, consistent with increased flexibility and stem opening. AFM imaging confirmed that both variants favoured the open stem conformation. Together, we demonstrate that mutations in the C1 and C2 domains alter stem dynamics, rendering VWF more responsive to shear stress
Observation of transition from rate law to Butler–Volmer controlled water oxidation kinetics on hematite photoanodes
No full textDespite its central role in photoelectrochemical (PEC) water splitting, the mechanistic pathway of water oxidation on metal oxides remains unresolved, with population-based and Butler–Volmer (BV) models offering distinct views on how surface valence band holes drive the reaction. Here, we bring together these two perspectives by combining operando photoinduced absorption (PIA) spectroscopy with photocurrent analyses on α-Fe2O3 (hematite) photoanodes as a function of light intensity. We find a crossover from population-controlled, rate law water oxidation at low hole densities to a BV-like, potential driven regime at high densities, triggered by band edge unpinning once surface M–OH species are fully oxidized, and excess holes accumulate without compensation. This mechanistic transition unifies competing models of interfacial charge transfer and reveals design principles for optimizing water oxidation in metal oxide photoelectrodes
Novel biomarkers in antibody mediated rejection of kidney transplants
No full textAntibody-mediated rejection (AMR) is the leading cause of long-term kidney allograft dysfunction and loss. Current diagnosis relies on the Banff Classification, which requires characteristic histopathological features and evidence of antibody–endothelial interaction to diagnose AMR. However, biopsies that have incomplete features of AMR are associated with worse graft outcomes than biopsies with normal histology, highlighting limitations of conventional diagnostics.
This study evaluated whether molecular diagnostics using NanoString gene expression profiling with the Banff–Human Organ Transplant (B-HOT) panel could enable earlier and more precise detection of AMR. Our objectives were to identify AMR-associated gene expression signatures; apply these signatures to biopsies with incomplete AMR features; assess molecular profiles in biopsies obtained at the time of donor-specific antibody (DSA) detection; and examine gene expression patterns in biopsies with microvascular inflammation (MVI) in the presence or absence of DSA and in the context of missing inhibitory self-signals (“missing-self”).
We performed an integrated molecular, histological, and serological analysis of kidney transplant biopsies. A 9-gene molecular score was identified that predicted AMR and was associated with increased risk of allograft loss in biopsies with incomplete AMR features. In a separate cohort with MVI, 50% of biopsies lacked detectable DSA, yet their histological and molecular profiles were indistinguishable from DSA-positive cases. Although DSA-negative biopsies more frequently demonstrated missing-self, gene expression patterns were similar, suggesting convergence on a common inflammatory pathway. At the time of DSA detection, only biopsies with histological rejection showed molecular signatures of rejection; however, “normal” biopsies from DSA-positive recipients exhibited distinct molecular profiles compared with DSA-negative controls, consistent with possible accommodation.
In conclusion, integrating molecular diagnostics with histological assessment enhances AMR detection, and may inform early intervention. Future research will focus on multicentre prospective validation and clinical implementation.Open Acces
An improved fully-automated GMP radiosynthesis of [18F]fluoro-pivalic acid with solid-phase extraction purification
No full textBackground: We previously reported the first-in-human evaluation of 3-[18F]-fluoro-2,2 dimethylpropionic acid ([18F]FPIA) for imaging aberrant lipid metabolism and cancer detection.
The first-generation semi-automated radiosynthesis of [18F]FPIA required HPLC purification to provide injection
solution devoid of precursor (methyl 2,2-dimethyl-3-[(4
methylbenzenesulfonyl)oxy]propanoate), radioactive intermediate (methyl-3-([18F]fluoro)-2,2 dimethylpropanoate), and potential chemical impurities (tosic acid, 3-hydroxy-2,2 dimethylpropanoic acid and unlabelled FPIA). In readiness for global use of [18F]FPIA, we report a significant improvement to the GMP production through development of a fully
automated solid-phase extraction (SPE) purification method.
Results: We developed a fully-automated SPE purified radiosynthesis on FASTLab for GMP readiness that was translated to and validated on the Trasis AIO™ platform for routine clinical use. Purification of the radiotracer by SPE on both systems was achieved (>98% radiochemical purity), increasing the radiochemical yield compared to the HPLC-based purification method. Non-decay-corrected radiochemical yields (RCY, n.d.c) were 30.3 ± 2.3 % (n = 8) and 25.8 ± 6.6 % (n = 46) on GE FASTlab™ and Trasis AIO™, respectively. Non-radioactive FPIA and other analytes determined by HPLC were below the limit of detection (<1.0 µg/mL) from GE FASTlab™ and ≤1.2 µg/mL from Trasis AIO™.
Conclusions: The synthesis of [18F]FPIA was validated on the Trasis AIO™ platform for GMP production and is currently used to produce clinical doses for phase II clinical trials. Readiness for GMP validation was also demonstrated on GE FASTlab™ and can be adopted on other automated platforms