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Nomenclature for Tracking of Genetic Variation of Seasonal Influenza Viruses.
Get PDFBACKGROUND: Genomic surveillance of human seasonal influenza viruses is an essential component of the Global Influenza Surveillance and Response system (GISRS) and informs the recommendations for the seasonal influenza vaccine composition. Phylogenetic analysis of viral genome sequences is used to identify groups of viruses sharing potential antigenic change, and computational models are used to predict which viral variants are likely to circulate at high levels in upcoming seasons. To facilitate discussion and reporting of genetic diversity, as well as to communicate antigen recommendations, up-to-date and sufficiently granular definitions of genetic clades are important. METHODS: We implemented a nomenclature system for Segments 4 (haemagglutinin) and 6 (neuraminidase) of human Influenza A(H3N2), A(H1N1)pdm09, and Influenza B that dynamically adapts to the diversity of circulating viruses. New subclades were proposed by a clade suggestion algorithm based on criteria including (i) the number of sequences in the group, (ii) the distance from the direct parent clade, and (iii) the weighted number of amino acid substitutions on the branch leading to the common ancestor of the subclade. RESULTS: Algorithmic clade proposals were reviewed and assigned a systematic hierarchical label consisting of a leading letter, followed by numbers (e.g., G.1.3). Names are kept short by aliasing that is collapsing prefixes into unique letters. Subclade definitions are shared openly to promote adoption and tool development. Nextclade is supporting this new nomenclature, and it is being used routinely by the GISRS network. CONCLUSIONS: With increasing genomic surveillance, the need for up-to-date classification schemes is growing and we hope that the current dynamic proposal will adapt to growing data volumes and aid in simplifying the interpretation of these data
Advances in Hybrid Icing and Frosting Protection Strategies for Optics, Lens, and Photonics in Cold Environments Using Thin‐Film Acoustic Waves
Get PDFFogging, icing, or frosting on optical lenses, optics/photonics, windshields, vehicle/airplane windows, and solar panel surfaces have often shown serious safety concerns with hazardous conditions and impaired sight. Various active techniques, such as resistive heating, and passive techniques, such as icephobic treatments, are widely employed for their prevention and elimination. However, these methods are not always suitable, effective, or efficient. This review provides a comprehensive overview of the fundamentals and recent advances of transparent thin‐film surface acoustic wave (SAW) technologies on glass substrates for monitoring and prevention/elimination of fogging, frosting, and icing. Key challenges related to fogging and icing on glass substrates are discussed, along with fundamental mechanisms that establish thin‐film SAWs as optimal solution for these issues. Various types of thin‐film acoustic wave technologies are discussed, including recent wearable and flexible SAW devices integrated onto glass substrates for expanding future applications. The focus of this review is on the principles and strategies for hybrid or integrated de‐fogging/de‐icing and sensing/monitoring functions. Finally, critical issues and future outlooks for thin‐film‐based SAW technology on glass substrates in industry applications are presented
Alzheimer's disease and memantine effects on NMDA-receptor blockade: non-invasive in vivo insights from magnetoencephalography.
Get PDFTo accelerate new treatments for Alzheimer's disease, there is the need for human pathophysiological biomarkers that are sensitive to treatment and disease mechanisms. In this proof-of-concept study, we assess new biophysical models of non-invasive human MEG imaging to test the pharmacological and disease modulation of NMDA-receptor inhibition. Magnetoencephalography was recorded during an auditory mismatch negativity paradigm from (1) neurologically-healthy people on memantine or placebo (n = 19, placebo-controlled crossover design); (2) people with Alzheimer's disease at baseline and 16-months (n = 42, amyloid-biomarker positive, longitudinal observational design). Optimised dynamic causal models inferred voltage-dependent NMDA-receptor blockade using Parametric Empirical Bayes to test group effects. The mismatch negativity amplitude was attenuated when Alzheimer's disease was more severe (lower baseline mini-mental state examination) and after follow-up (versus baseline). Memantine increased NMDA-receptor inhibition, compared to placebo. Alzheimer's disease reduced NMDA-receptor inhibition in proportion to severity and over time. In line with preclinical studies, we confirm in humans that memantine and Alzheimer's disease have opposing effects on NMDA-receptor inhibition. The ability to infer such receptor dynamics and pharmacology from non-invasive physiological recordings has wide applications, including the assessment of other neurological disorders and novel drugs intended for symptomatic or disease-modifying treatments
A prospective investigation of early-onset colorectal cancer risk factors-pooled analysis of three large-scale European cohorts.
Get PDFBACKGROUND: Colorectal cancer (CRC) incidence is rising among adults under 55 years, but its causes remain unclear. Large-scale prospective studies are needed to identify risk factors for early-onset CRC (EOCRC). METHODS: We pooled three large European prospective cohort studies, examining 14 known or suspected risk factors with EOCRC (diagnosed <55 years, N = 1369) and later-onset CRCs (LOCRC) (diagnosed ≥55 years, N = 13,490). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Higher body mass index (BMI, per 5 kg/m2 increase), was strongly associated with EOCRC in men (HR 1.33, 95% CI: 1.18-1.51), particularly for early-onset colon cancer (HR 1.55, 95% CI: 1.32-1.82), compared to later-onset disease (HR 1.25, 95% CI: 1.19-1.31) (Phet = 0.01). Weaker associations with BMI were observed for women and rectal cancers. Similar sex and subsite specific trends were observed for waist circumference and waist-to-hip ratio. Current smoking (HR 1.24, 95% CI: 1.07-1.44) and alcohol use (HR 1.15, 95% CI: 1.06-1.25) increased EOCRC risk, and physical activity (HR 0.71, 95% CI: 0.54-0.95) was protective. DISCUSSION: Adiposity, physical inactivity, smoking, and alcohol consumption are risk factors for EOCRC. Risk factors were largely similar between EOCRC and LOCRC, except for adiposity, with stronger EOCRC association in men
New Route to Battery Grade NaPF6 for Na-Ion Batteries: Expanding the Accessible Concentration
No full textSodium-ion batteries represent a promising alter
native to lithium-ion systems. However, the rapid growth of sodium-ion battery technology requires a sustainable and scalable synthetic route to high-grade sodium hexafluorophosphate. This work demonstrates a new multi-gram scale synthesis of NaPF6 in which the reaction of ammonium hexafluorophosphate with sodium metal in THF solvent generates the electrolyte salt with the absence of the impurities that are common in commercial material. The high purity of the
electrolyte (absence of insoluble NaF) allows for concentrations up to 3 M to be obtained accurately in binary carbonate battery solvent. Electrochemical characterization shows that the degradation dynamics of sodium metal-electrolyte interface
are different for more concentrated (>2 M) electrolytes, suggesting that the higher concentration regime (above the conventional 1 M concentration) may be beneficial to battery performance
Flexibility and modulation of translation initiation in enterovirus genomes.
No full textEnteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. Additionally, we demonstrate regulation of uORF translation in response to stress. These findings reveal the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems
A note on Guillaume Amontons and the laws of friction
No full textAmontons’ widely cited paper of December 1699 on the subject of friction in machines is not the first to contain his statement of the laws of friction. An earlier paper on a novel heat engine, presented to the Académie Royale des Sciences 6 months earlier, describes the measurements of forces in glass polishing and contains a clear statement that the friction force is independent of contact area and proportional to normal load. The comments in Amontons’ paper on the physical origins of the friction force at surface irregularities (asperities) do not appear in the contemporary record of his lecture in December 1699, but were included in the published version after similar ideas had been presented by Philippe de la Hire; credit for these ideas should be given to La Hire rather than to Amontons
Addressing vulnerability in customer experience with AI-agents
No full textPurpose Artificial intelligence (AI) agents have the potential to fundamentally change customer experience (CX) by addressing vulnerability. Advancements in AI offer service accessibility and responsiveness, providing scope for improved customer experience. Any consumer can be vulnerable, depending on context, and as AI-agents proliferate, there is a risk that these agents prioritize interests of more powerful service providers over consumers. Instead, we envision personal AI-agents advocating on behalf of consumers, improving access to services, enhancing CX and shifting power from providers to consumers. Design/methodology/approach This conceptual theory-adaptation paper first synthesizes literature on consumer vulnerability to advance understanding of vulnerability in customer experience (CXV). Agency theory is then applied as a theoretical lens, building on the notion of perceived control applied to design personal AI-agents to act on behalf of consumers experiencing vulnerability. Findings Drawing on vulnerability, CX and AI in service literature, this paper, first, proposes a novel CXV conceptual framework to design personal AI-agents to enhance CX. Our conceptual framework identifies five design attributes that personal AI-agents should exhibit, underpinned by rebalancing perceived control from service providers, handing agency back to consumers. Second, we provide an actionable design framework comprising four archetypes to guide practice. Third, a compelling research agenda is offered to guide future research on addressing vulnerability in customer experience with personal AI-agents. Practical implications This paper provides practical guidance for agnostic third-party designers to develop personal AI-agents that can rebalance service provider interests with consumer advocacy. To design personal AI-agents, we propose four design archetypes in our 2x2 design framework: (1) service orchestrator, (2) protective sentinel, (3) reliable intermediary and (4) autonomous ally based on the five design attributes, tailored to meet the needs and preferences of consumers experiencing vulnerability. Originality/value This paper summarizes consumer vulnerability literature, developing the definition to provide a foundation for our five design attributes of personal AI-agents depicted in our C×V conceptual framework. This is integrated with practical illustrative vignettes of experiences, bodies, processes and regulations relating to real-world value delivery by AI-agents on behalf of consumers in service settings
Hydrogel-Based Airway-on-Tube With Perfusable Endothelial Lumen and Outward Epithelialization.
No full textChronic lung diseases are a leading cause of mortality worldwide, yet therapeutic options remain limited. A major barrier to pulmonary drug development is the lack of preclinical models that recapitulate lung complexity. While recent airway-on-chip models have advanced by integrating vascular and extracellular matrix (ECM) components, these are largely limited to planar configurations. Only a few tubular designs exist, yet they generally lack a perfusable vascular compartment that supports dynamic endothelial-epithelial interactions. To address this gap, we introduce an airway-on-tube that integrates an engineered ECM (EnECM) hydrogel, tuned to match lung tissue stiffness, with a tubular melt electrowritten (MEW) scaffold. The MEW reinforces the EnECM hydrogel for dynamic culture without affecting cell behavior. The tubular EnECM/MEW construct incorporates patient-derived primary human lung microvascular endothelial cells embedded within the EnECM hydrogel, forming a perfusable endothelial lumen, while primary human bronchial epithelial cells are cultured on the outer (abluminal) surface, establishing an outward-facing epithelium at the air-liquid interface (ALI). Pulsatile perfusion through the endothelial lumen delivers nutrients and mechanical cues (shear stress and cyclic stretch) while maintaining ALI culture. Together, this study establishes a versatile hydrogel-based platform for next-generation airway-on-chip models, opening new opportunities for preclinical lung research and precision therapeutic development
Xyloglucan deficiency leads to a reduction in turgor pressure and changes in cell wall properties, affecting early seedling establishment.
Get PDFXyloglucan is believed to play a significant role in cell wall mechanics of dicot plants. Surprisingly, Arabidopsis plants defective in xyloglucan biosynthesis exhibit nearly normal growth and development. We investigated a mutant line, cslc-Δ5, lacking activity in all five Arabidopsis cellulose synthase like-C (CSLC) genes responsible for xyloglucan backbone biosynthesis. We observed that this xyloglucan-deficient line exhibited reduced cellulose crystallinity and increased pectin levels, suggesting the existence of feedback mechanisms that regulate wall composition to compensate for the absence of xyloglucan. These alterations in cell wall composition in the xyloglucan-absent plants were further linked to a decrease in cell wall elastic modulus and rupture stress, as observed through atomic force microscopy (AFM) and extensometer-based techniques. This raised questions about how plants with such modified cell wall properties can maintain normal growth. Our investigation revealed two key factors contributing to this phenomenon. First, measurements of turgor pressure, a primary driver of plant growth, revealed that cslc-Δ5 plants have reduced turgor, preventing the compromised walls from bursting while still allowing growth to occur. Second, we discovered the conservation of elastic asymmetry (ratio of axial to transverse wall elasticity) in the mutant, suggesting an additional mechanism contributing to the maintenance of normal growth. This novel feedback mechanism between cell wall composition and mechanical properties, coupled with turgor pressure regulation, plays a central role in the control of plant growth and is critical for seedling establishment in a mechanically challenging environment by affecting shoot emergence and root penetration