Global aerosol modeling with MADE3 (v3.0) in EMAC (based on v2.53): model description and evaluation

Recently, the aerosol microphysics submodel MADE3 (Modal Aerosol Dynamics model for Europe, adapted for global applications, third generation) was introduced as a successor to MADE and MADE-in. It includes nine aerosol species and nine lognormal modes to represent aerosol particles of three different mixing states throughout the aerosol size spectrum. Here, we describe the implementation of the most recent version of MADE3 into the ECHAM/MESSy Atmospheric Chemistry (EMAC) general circulation model, including a detailed evaluation of a 10-year aerosol simulation with MADE3 as part of EMAC.We compare simulation output to station network measurements of near-surface aerosol component mass concentrations, to airborne measurements of aerosol mass mixing ratio and number concentration vertical profiles, to ground-based and airborne measurements of particle size distributions, and to station network and satellite measurements of aerosol optical depth. Furthermore, we describe and apply a new evaluation method, which allows a comparison of model output to size-resolved electron microscopy measurements of particle composition. Although there are indications that fine-mode particle deposition may be underestimated by the model, we obtained satisfactory agreement with the observations. Remaining deviations are of similar size to those identified in other global aerosol model studies.Thus, MADE3 can be considered ready for application within EMAC. Due to its detailed representation of aerosol mixing state, it is especially useful for simulating wet and dry removal of aerosol particles, aerosol-induced formation of cloud droplets and ice crystals as well as aerosol–radiation interactions. Besides studies on these fundamental processes, we also plan to use MADE3 for a reassessment of the climate effects of anthropogenic aerosol perturbations.</p

Interactive Visual Labelling versus Active Learning: An Experimental Comparison

Methods from supervised machine learning allow the classification of new data automatically and are tremendously helpful for data analysis. The quality of supervised maching learning depends not only on the type of algorithm used, but also on the quality of the labelled dataset used to train the classifier. Labelling instances in a training dataset is often done manually relying on selections and annotations by expert analysts, and is often a tedious and time-consuming process. Active learning algorithms can automatically determine a subset of data instances for which labels would provide useful input to the learning process. Interactive visual labelling techniques are a promising alternative, providing effective visual overviews from which an analyst can simultaneously explore data records and select items to a label. By putting the analyst in the loop, higher accuracy can be achieved in the resulting classifier. While initial results of interactive visual labelling techniques are promising in the sense that user labelling can improve supervised learning, many aspects of these techniques are still largely unexplored. This paper presents a study conducted using the mVis tool to compare three interactive visualisations, similarity map, scatterplot matrix (SPLOM), and parallel coordinates, with each other and with active learning for the purpose of labelling a multivariate dataset. The results show that all three interactive visual labelling techniques surpass active learning algorithms in terms of classifier accuracy, and that users subjectively prefer the similarity map over SPLOM and parallel coordinates for labelling. Users also employ different labelling strategies depending on the visualisation used

miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449−/− mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449−/− mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis

Emergence of fractal geometries in the evolution of a metabolic enzyme

Fractals are patterns that are self-similar across multiple length-scales. Macroscopic fractals are common in nature; however, so far, molecular assembly into fractals is restricted to synthetic systems. Here we report the discovery of a natural protein, citrate synthase from the cyanobacterium Synechococcus elongatus, which self-assembles into Sierpiński triangles. Using cryo-electron microscopy, we reveal how the fractal assembles from a hexameric building block. Although different stimuli modulate the formation of fractal complexes and these complexes can regulate the enzymatic activity of citrate synthase in vitro, the fractal may not serve a physiological function in vivo. We use ancestral sequence reconstruction to retrace how the citrate synthase fractal evolved from non-fractal precursors, and the results suggest it may have emerged as a harmless evolutionary accident. Our findings expand the space of possible protein complexes and demonstrate that intricate and regulatable assemblies can evolve in a single substitution