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Ionic glass formers show an inverted relation between fragility and non-exponential alpha-relaxation
No full textSupercooled liquids undergo a rapid change in dynamics as they are cooled to their glass transition temperature and turn from a flowing liquid into an amorphous solid. Depending on how steeply the viscosity changes with temperature around the glass transition, glass formers are classified as strong or fragile. An empirical relation exists between the fragility of the liquid and the non-exponentiality of its α-relaxation. However, the microscopic origins of this correlation remain unclear and its generality has been debated. Here, we demonstrate that this relationship is inverted in organic materials with ionic interactions. We introduce a class of materials consisting of highly charged hydrophobic polymers cross-linked via moderated ionic interactions, and show that these combine a strong glass transition with an unusually stretched mechanical relaxation spectrum. By surveying a large variety of ionic liquids, polymerized ionic liquids, and ionomers, we show that all these charged materials follow a trend between fragility and non-exponential relaxation that is opposite to that of non-charged materials. This finding suggests a special role of long-ranged ionic interactions in vitrification and opens up a route toward developing new materials that combine the processability of strong glass formers with the mechanical dissipation of polymers.</p
The feasibility of diol-assisted fractionation for lignin-first biorefinery:An integrated process design and sustainability study
No full textLignin-first biorefinery strategies have emerged as powerful method to prevent undesired recondensation during biomass fractionation, thereby enabling the sustainable valorization of lignin and cellulose. Among these, the diol-assisted fractionation (DAF) operates via stabilization of reactive aldehyde intermediates with simple diols, thus without the need of heterogeneous catalysts or pressured H2. This study presents the first conceptual process design of a specific DAF process, targeting lignin oil production as well as carbohydrates valorization at an industrial scale. We systematically evaluated the economic and environmental performance of this process through integrated process simulation, techno-economic analysis (TEA) and life cycle assessment (LCA). TEA indicates a minimum selling price of refined lignin oil (MSP-RLO) produced via DAF as 853.5/t), primarily due to reduced total capital investment (TCI) associated with milder processing conditions and the absence of hydrogenation. LCA further reveals the strong environmental benefits, with the DAF process achieving a negative carbon footprint (-1.13 kg CO2-eq./kg lignin oil), attributed to the co-production of valuable carbohydrate pulp and the resulting environmental burden allocation. Sensitivity analysis identifies the solvent consumption and feedstock costs as the most influential factors affecting economic performance, while Monte Carlo simulations indicate that increasing the market price of lignin oil to $2,000/t could reduce the investment risk of the production process to below 10%. This work establishes a viable and scalable lignocellulose fractionation platform aligned with the evaluation of both the economic and environmental performance, advancing the lignin-first valorization strategy.</p
Unravelling the Role Played by Non-covalent Interactions in the Action Mechanism of PCDDs within Cells
No full textThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates biological signals and regulates diverse cellular functions. Of particular concern are the effects triggered by dioxins and dioxin-like compounds (DLCs), whose toxicological outcomes arise through both canonical and noncanonical pathways, leading to the designation of AhR as the "dioxin receptor". However, conventional risk assessment approaches based on toxic equivalency factors (TEFs), which primarily reflect the capacity of these compounds to bind and activate AhR, do not fully account for critical aspects such as environmental concentration and bioavailability, potentially underestimating their true impact. In this work, we present a comparative analysis of polychlorinated dibenzo-p-dioxins (PCDDs) with varying degrees of chlorination, focusing on their interactions with the AhR at the ligand-binding domain and on their permeation abilities across a model lipid membrane. To this end, we combine classical molecular dynamics (CMD) simulations with a hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA) framework. This integrated approach enables a molecular-level characterization of receptor binding affinities and membrane permeation efficiencies. Our findings provide novel insights into the mechanisms underlying the relative toxicity of DLCs and highlight the need for integrative assessment strategies that encompass both receptor-ligand interactions and physicochemical behavior in biological environments. It is noteworthy that the toxicity of these compounds, as quantified by the pEC50 index, correlates with the membrane permeation barrier rather than with AhR binding affinity, identifying permeation as the key mechanistic step in the toxicological process of these compounds.</p
The Position of Human Rights in EU Export Controls:Examining the Coherence Between the EU Common Position on Arms Exports and the Dual-Use Goods Regulation
No full textThe European Union (EU) has formally integrated human rights into its external policies, yet tensions continue to exist between these commitments and other objectives within the filed of export controls. The main export control regimes in the EU – the Dual-Use Goods Regulation and the EU Common Position on Arms Exports – both integrate human rights commitments but differ in terms of their legal bases, substantive rules and procedural mechanisms. This article examines whether these instruments ensure coherence, understood not merely as the absence of contradictions but as the mutual reinforcement of human rights considerations. Through legal analysis, this research finds that the fragmentation between the two frameworks, in combination with the wide Member State discretion, undermines a coherent EU approach. Divergences in denial obligations, the lack of common definitions and the absence of EU-level risk assessments show how institutional and procedural disparities can weaken human rights protection in practice. Ultimately, the article provides recommendations for strengthening the coherence between the two frameworks, situating these within the broader challenge of reconciling economic, security and human rights priorities within EU external action.</p
Effect of Positive End-Expiratory Pressure on Cardiac Index and Right Ventricular Performance in Ventilated Children Post-Cardiac Surgery
No full textObjective: – Lower positive end-expiratory pressure (PEEP) is commonly suggested in congenital heart disease (CHD) patients to prevent hemodynamic impairment and right ventricular (RV) dysfunction. We sought to study the effect of different levels of PEEP on cardiac index, lung mechanics, and RV function in subjects after cardiac surgery.Design: – Prospective, single-center physiology study conducted in a tertiary pediatric cardiac ICU between November 2023 and July 2024.Setting: – Operating room (OR) and cardiac ICU (CICU).Patients: – Subjects younger than 5 years post-cardiac surgery for CHD.Interventions: – Four consecutive PEEP levels: baseline (PEEPstart), high PEEP (baseline plus 4 cm H2O; PEEPhigh), low PEEP (baseline minus 4 cm H2O; PEEPlow), and return to baseline (PEEPend).Measurements: – In 58 subjects, cardiac index and RV function, static (Cstat) and dynamic compliance, and transpulmonary pressures were measured at each PEEP level and with constant driving pressure. Of these subjects, 81.0% underwent surgery with cardiopulmonary bypass (CPB). The median age was 4.9 months, and 55% of subjects were male. The mean baseline PEEP was 6.2 cm H₂O (sd 1.4), the mean PEEPhigh was 10.2 cm H₂O (sd 1.4), and the mean PEEPlow was 3.3 cm H₂O (sd 0.7).Main Results: – Overall, cardiac index and RV performance increased significantly with PEEPhigh (p < 0.01). Cardiac index decreased in 7 of 58 patients (12%)with PEEPhigh and in 18 of 58 patients (31%) with PEEPlow. Directional change in measures of RV performance and Cstat over time was generally concordant; with manipulation of PEEP, both improved or worsened together, independent of the underlying lesion. Sensitivity analyses showed that the results remained consistent regardless of the location of the measurement (OR vs. CICU), whether inhaled nitric oxide or milrinone was used, whether RV outflow tract obstruction was present, and whether CPB was used.Conclusions: – In children with CHD who underwent biventricular repair, cardiac index, RV function, and Cstat generally improved with higher PEEP, indicating pulmonary recruitment. Changes in cardiac performance and Cstat were closely related, with both improving or worsening together with manipulation of PEEP. This study supports the use of PEEP to optimize lung volume and cardiopulmonary interactions after cardiac surgery.</p
How do microgrid PV systems help communities respond to energy supply disruption? A review of the socio-economic interrelationships in West Africa
No full textWest Africa, marked by rapid urbanization and socio-economic vulnerabilities, faces persistent energy challenges, including unreliable electricity and climate-induced disruptions to energy supply. This study investigates the socio-economic consequences of microgrid photovoltaic (PV) systems in and on vulnerable West African communities, with a focus on the food-water-energy and health-energy nexus. The latter, interlinked sectors are critical to understanding the broader implications of PV systems on resilience. Using a systematic literature review guided by the PRISMA framework, the research synthesizes existing academic knowledge on microgrid solar PV's role in promoting economic development, energy access, and public health while supporting food and water security. The findings suggest that small-scale PV systems offer climate-resilient alternatives to fossil fuels, improve electrification, foster job creation, and reduce health risks from pollutive fuels. Nonetheless, barriers such as high upfront costs, intermittency, and scalability challenges hinder broader implementation. The study also addresses community responses to energy disruptions, including the use of back-up fossil-fuel generators, alternative renewable energy solutions, and behavioural adaptations. A Causal Loop Mapping (CLM) diagram is used to illustrate the complex feedback dynamics between renewable energy access, food, and water systems in vulnerable contexts. While rooted in the West African region, the findings hold broader relevance for other areas facing similar development-energy dilemmas, offering insights into equitable and context-sensitive energy transitions under conditions of climate vulnerability.</p
Micromechanobiology:A micromechanics approach to mechanobiology
No full textThe thrust of this article is to postulate a possible route along the micro-meso-macro lines of micromechanics to contribute to the vibrant field of mechanobiology. In particular, we focus on mechanotransduction: the machinery by which cells adapt to their environment and how its failure is key to many diseases, including cancer. Starting out from the geometrical similarity with open-cell foams, for which the micro-meso-macro transition is well developed, this paper summarizes the current understanding of the mechanical behavior of biopolymer networks as central entities in mechanotransduction. More specifically, we address the dynamics of molecular networks in the nuclear membrane, filamentous networks in the cytoskeleton, as well as networks making up the extracellular matrix. We emphasize that the enhanced richness in behavior of these networks originates from the relatively large contribution of entropy. We also identify a number of challenges arising from the fact that the materials involved are intrinsically dynamic and active. The development of tools needed to address these challenges has just started and thus offers a bright future for current and new generations of micromechanicians.</p
Generation and characterization of a mouse model for bile salt export pump deficiency with the p.E297G mutation
No full textBACKGROUND & AIMS: Bile Salt Export Pump (BSEP) deficiency is a rare genetic cholestatic liver disease, often necessitating liver transplantation. The p.E297G missense mutation is associated with residual BSEP function in vitro and delayed need for transplantation in patients. We aimed to generate a p.E297G BSEP knock-in (BSEP E297G) mouse model to evaluate interventions to improve residual BSEP function. METHODS: We generated BSEP E297G mice by CRISPR-Cas9 technology. BSEP E297G mice and wild type (WT) littermates were characterized for BSEP expression and liver pathology at 14 weeks of age. Maximal BSEP transport capacity without and after 4-phenylbutyrate (4-PB) treatment were determined in vivo by quantification of biliary bile acid secretion during intravenous infusion of increasing dosages of tauroursodeoxycholic acid (TUDCA) in WT, BSEP E297G and BSEP-/- mice. RESULTS: Western blot analysis showed immature BSEP protein in BSEPE297G livers. Median plasma AST was three-fold higher in BSEP E297G mice (Males: 198 vs. 60 U/L; Females: 188 vs. 50 U/L; each p < 0.001) while plasma bile acid levels were higher in female BSEP E297G mice compared to WT (Females: 36 vs. 6 μM, p < 0.001; Males: 11vs.3 μM, p = 0.07). Histological analysis revealed features of cholestatic liver pathology in BSEP E297G mice. TUDCA infusion strongly increased biliary bile acid secretion in WT but not in BSEP E297G and BSEP-/- mice. 4-PB treatment did not enhance bile acid transport capacity in BSEP E297G mice. CONCLUSIONS: BSEP E297G mice display a BSEP deficiency phenotype with a strongly reduced hepatobiliary bile acid transport capacity. The expression of immature BSEP protein suggests the potential to assess correctors of the BSEP functionality in vivo. </p
NEST:Neural estimation by sequential testing
No full textAdaptive psychophysical procedures aim to increase the efficiency and reliability of measurements. With increasing stimulus and experiment complexity in the last decade, estimating multi-dimensional psychometric functions has become a challenging task for adaptive procedures. If the experimenter has limited information about the underlying psychometric function, it is not possible to use parametric techniques developed for the multi-dimensional stimulus space. Although there are non-parametric approaches that use Gaussian process methods and specific hand-crafted acquisition functions, their performance is sensitive to proper selection of the kernel function, which is not always straightforward. In this work, we use a neural network as the psychometric function estimator and introduce a novel acquisition function for stimulus selection. We thoroughly benchmark our technique both using simulations and by conducting psychovisual experiments under realistic conditions. We show that our method outperforms the state of the art without the need to select a kernel function and significantly reduces the experiment duration
From infant separation distress to preschool behavior problems:The mediating roles of maternal self-efficacy and positive parenting
No full textThis study investigated associations between infant separation distress and preschool behavior problems and examined the mediating effects of parenting self-efficacy and positive parenting on these associations. Participants were 117 young Chinese children and their families. At 14 months, infant separation distress was observed in the Strange Situation Procedure and reported by mothers using the Infant-Toddler Social Emotional Assessment. Mothers reported on their parenting self-efficacy and positive parenting at 38 and 61 months, respectively. The Strengths and Difficulties Questionnaire was used to assess child behavior problems at 61 months. Mediation analyses showed that observed infant separation distress directly predicted emotional symptoms and mother-reported infant separation distress directly predicted hyperactivity/inattention problems. Observed separation distress lowered maternal parenting self-efficacy, which in turn reduced the use of positive parenting, ultimately linking to increases in preschool behavior problems. To conclude, there exist both direct and indirect associations between infant separation distress and preschool behavior problems.</p