Facing up to the challenge of behavioural observation in infant hearing assessment

The ability to assess detection and discrimination of speech by infants has proved elusive. Dr Iain Jackson and colleagues discuss how new technologies and fresh approaches might offer valuable insight into young infants’ behavioural responses to sound

Multidirectional In Vivo Characterization of Skin Using Wiener Nonlinear Stochastic System Identification Techniques

A triaxial force-sensitive microrobot was developed to dynamically perturb skin in multiple deformation modes, in vivo. Wiener static nonlinear identification was used to extract the linear dynamics and static nonlinearity of the force–displacement behavior of skin. Stochastic input forces were applied to the volar forearm and thenar eminence of the hand, producing probe tip perturbations in indentation and tangential extension. Wiener static nonlinear approaches reproduced the resulting displacements with variances accounted for (VAF) ranging 94–97%, indicating a good fit to the data. These approaches provided VAF improvements of 0.1–3.4% over linear models. Thenar eminence stiffness measures were approximately twice those measured on the forearm. Damping was shown to be significantly higher on the palm, whereas the perturbed mass typically was lower. Coefficients of variation (CVs) for nonlinear parameters were assessed within and across individuals. Individual CVs ranged from 2% to 11% for indentation and from 2% to 19% for extension. Stochastic perturbations with incrementally increasing mean amplitudes were applied to the same test areas. Differences between full-scale and incremental reduced-scale perturbations were investigated. Different incremental preloading schemes were investigated. However, no significant difference in parameters was found between different incremental preloading schemes. Incremental schemes provided depth-dependent estimates of stiffness and damping, ranging from 300 N/m and 2 Ns/m, respectively, at the surface to 5 kN/m and 50 Ns/m at greater depths. The device and techniques used in this research have potential applications in areas, such as evaluating skincare products, assessing skin hydration, or analyzing wound healing.Foundation for Research, Science & Technology (N.Z.) (Grants UOA21647.001 and NERF 9077/3608892)Tertiary Education Commission of New Zealand (Medical Technologies Centre of Research Excellence (MedTech CoRE)

Delineating the activity of the potent nicotinic acetylcholine receptor agonists (+)-anatoxin-a and (−)-hosieine-A

The affinity and thermodynamic parameters for the interactions of two naturally occurring neurotoxins, (+)-anatoxin-a and (−)-hosieine-A, with acetylcholine-binding protein were investigated using a fluorescence-quenching assay and isothermal titration calorimetry. The crystal structures of their complexes with acetylcholine-binding protein from Aplysia californica (AcAChBP) were determined and reveal details of molecular recognition in the orthosteric binding site. Comparisons treating AcAChBP as a surrogate for human α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) suggest that the molecular features involved in ligand recognition and affinity for the protein targets are conserved. The ligands exploit interactions with similar residues as the archetypal nAChR agonist nicotine, but with greater affinity. (−)-Hosieine-A in particular has a high affinity for AcAChBP driven by a favorable entropic contribution to binding. The ligand affinities help to rationalize the potent biological activity of these alkaloids. The structural data, together with comparisons with related molecules, suggest that there may be opportunities to extend the hosieine-A scaffold to incorporate new interactions with the complementary side of the orthosteric binding site. Such a strategy may guide the design of new entities to target human α4β2 nAChR that may have therapeutic benefit

ISM Properties in Low-Metallicity Environments II. The Dust Spectral Energy Distribution of NGC 1569

We present new 450 and 850 microns SCUBA data of the dwarf galaxy NGC 1569. We construct the mid-infrared to millimeter SED of NGC 1569, using ISOCAM, ISOPHOT, IRAS, KAO, SCUBA and MAMBO data, and model the SED in order to explore the nature of the dust in low metallicity environments. The detailed modeling is performed in a self-consistent way, synthesizing the global ISRF of the galaxy using an evolutionary synthesis model with further constraints provided by the observed MIR ionic lines and a photoionisation model. Our results show that the dust properties are different in this low metallicity galaxy compared to other more metal rich galaxies. The results indicate a paucity of PAHs probably due to the destructive effects of the ISRF penetrating a clumpy environment and a size-segregation of grains where the emission is dominated by small grains of size ~3 nm, consistent with the idea of shocks having a dramatic effect on the dust properties in NGC 1569. A significant millimetre excess is present in the dust SED which can be explained by the presence of ubiquitous very cold dust (T = 5-7 K). This dust component accounts for 40 to 70 % of the total dust mass in the galaxy (1.6 - 3.4 10^5 Msol) and could be distributed in small clumps (size a few pc) throughout the galaxy. We find a gas-to-dust mass ratio of 740 - 1600, larger than that of the Galaxy and a dust-to-metals ratio of 1/4 to 1/7. We generate an extinction curve for NGC 1569, consistent with the modeled dust size distribution. This extinction curve has relatively steep FUV rise and smaller 2175 Angstroms bump, resembling the observed extinction curve of some regions in the Large Magellanic Cloud.Comment: 20 pages, 20 figures, accepted by A&

ReLayer: a free, online tool for extracting retinal thickness from cross-platform OCT images

Purpose: To describe and evaluate a free, online tool for automatically segmenting optical coherence tomography (OCT) images from different devices and computing summary measures such as retinal thickness. Methods: ReLayer (https://relayer.online) is an online platform to which OCT scan images can be uploaded and analyzed. Results can be downloaded as plaintext (.csv) files. The segmentation method includes a novel, 1-dimensional active contour model, designed to locate the inner limiting membrane, inner/outer segmentand retinal pigment epithelium. The method, designed for B-scans from Heidelberg Engineering Spectralis, was adapted for Topcon 3D OCT-2000 and OptoVue AngioVue. The method was applied to scans from healthy and pathological eyes, and was validated against segmentation by the manufacturers, the 39IOWA Reference Algorithms,and manual segmentation. Results: Segmentation of a B-scan took≤ 1 second. In healthy eyes, mean difference in retinal thickness from ReLayer and the reference standard was below the resolution of the Spectralis and 3D OCT-2000, and slightly above the resolution of the AngioVue. In pathological eyes, ReLayer performed similarly to IOWA (p=0.97) and better than Spectralis (p<0.001)

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Probing Interstellar Dust with Infrared Echoes from the Cas A Supernova

We present the analysis of an IRS 5-38 {\mu}m spectrum and MIPS photometric measurements of an infrared echo near the Cassiopeia A supernova remnant observed with the Spitzer Space Telescope. We have modeled the recorded echo accounting for PAHs, quantum-heated carbon and silicate grains, as well as thermal carbon and silicate particles. Using the fact that optical light echo spectroscopy has established that Cas A originated from a type IIb supernova explosion showing an optical spectrum remarkably similar to the prototypical type IIb SN 1993J, we use the latter to construct template data input for our simulations. We are then able to reproduce the recorded infrared echo spectrum by combining the emission of dust heated by the UV burst produced at the shock breakout after the core-collapse and dust heated by optical light emitted near the visual maximum of the supernova light curve, where the UV burst and optical light curve characteristics are based on SN 1993J. We find a mean density of \sim680 H cm^{-3} for the echo region, with a size of a few light years across. We also find evidence of dust processing in the form of a lack of small PAHs with less than \sim300 carbon atoms, consistent with a scenario of PAHs destruction by the UV burst via photodissociation at the estimated distance of the echo region from Cas A. Furthermore, our simulations suggest that the weak 11 {\mu}m features of our recorded infrared echo spectrum are consistent with a strong dehydrogenated state of the PAHs. This exploratory study highlights the potential of investigating dust processing in the interstellar medium through infrared echoes.Comment: 16 pages, 14 figures, accepted for publication in the Astrophysical Journa

A Development Environment for Visual Physics Analysis

The Visual Physics Analysis (VISPA) project integrates different aspects of physics analyses into a graphical development environment. It addresses the typical development cycle of (re-)designing, executing and verifying an analysis. The project provides an extendable plug-in mechanism and includes plug-ins for designing the analysis flow, for running the analysis on batch systems, and for browsing the data content. The corresponding plug-ins are based on an object-oriented toolkit for modular data analysis. We introduce the main concepts of the project, describe the technical realization and demonstrate the functionality in example applications