Read-Across of 90-day Rat Oral Repeated-Dose Toxicity: A Case Study for Selected n-Alkanols

n-Alkanols provide an excellent example where a category-approach to read-across may be used to estimate the repeated-dose endpoint for a number of untested derivatives (target chemicals) using experimental data for tested derivatives (source chemicals). n-Alkanols are non-reactive and exhibit the unspecific, reversible simple anaesthesia or non-polar narcosis mode of toxic action in that the metabolic products of the parent alcohols do not contribute to the toxic endpoint evaluated. In this case study, the chemical category is limited to the readily bioavailable (C5 to C13) analogues. The toxicokinetic premise includes rapid absorption via the gastrointestinal tract, distribution in the circulatory system, and first-pass metabolism in the liver resulting in metabolism via oxidation to CO2 and with minor elimination of oxidative intermediate as glucuronides. Two analogues have experimental 90-day oral repeated-dose toxicity data which exhibit qualitative and quantitative consistency. Typical findings include decreased body weight, slightly increased liver weight which, in some cases, is accompanied by clinical chemical and haematological changes but generally without concurrent histopathological effects at the Lowest Observed Effect Level (LOEL). Chemical similarity between the analogues is readily defined by a variety of structure-related properties; data uncertainty associated with toxicokinetic and toxicodynamic similarities is low. Uncertainty associated with mechanistic relevance and completeness of the read-across is reduced by the concordance of in vivo and in vitro results, as well as high throughput and in silico methods data. As shown in detail, the 90-day oral repeated-dose toxicity No Observed Effect Level (NOEL) value of 1000 mg/kg bw/d for 1-pentanol and 1-hexanol based on LOEL of very low systemic toxicity can be read across to fill the data gaps of the untested analogues in this category with acceptable uncertainty

On the difference between type E and A OH/IR stars

The observed SEDs of a sample of 60 OH/IR stars are fitted using a radiative transfer model of a dusty envelope. Among the whole sample, 21 stars have reliable phase-lag distances while the others have less accurate distances. L*-P,Mlr-P and Mlr-L* relations have been plotted for these stars. It is found that type E (with emission feature at 10um and type A (with absorption feature at 10um) OH/IR stars have different L*-P and Mlr-L* relations while both of them follow a single Mlr-P relation. The type E stars are proven to be located in the area without large scale dense interstellar medium while the type A stars are located probably in dense interstellar medium. It is argued here that this may indicate the two types of OH/IR stars have different chemical composition or zero age main sequence mass and so evolve in different ways. This conclusion has reinforced the argument by Chen et al.(2001) who reached a similar conclusion from the galactic distribution of about 1000 OH/IR stars with the IRAS low-resolution spectra (LRS).Comment: 6 pages, 9 figures, 2 table

Meson-Baryon Form Factors in Chiral Colour Dielectric Model

The renormalised form factors for pseudoscalar meson-baryon coupling are computed in chiral colour dielectric model. This has been done by rearranging the Lippmann-Schwinger series for the meson baryon scattering matrix so that it can be expressed as a baryon pole term with renormalized form factors and baryon masses and the rest of the terms which arise from the crossed diagrams. Thus we are able to obtain an integral equation for the renormalized meson-baryon form factors in terms of the bare form factors as well as an expression for the meson self energy. This integral equation is solved and renormalized meson baryon form factors and renormalized baryon masses are computed. The parameters of the model are adjusted to obtain a best fit to the physical baryon masses. The calculations show that the renormalized form factors are energy-dependent and differ from the bare form factors primarily at momentum transfers smaller than 1 GeV. At nucleon mass, the change in the form factors is about 10% at zero momentum transfer. The computed form factors are soft with the equivalent monopole cut-off mass of about 500 MeV. The renormalized coupling constants are obtained by comparing the chiral colour dielectric model interaction Hamiltonian with the standard form of meson-nucleon interaction Hamiltonian. The ratio of $\Delta N\pi$ and $NN\pi$ coupling constants is found to be about 2.15. This value is very close to the experimental value.Comment: 16 pages, 7 postscript figure

Interference coloration as an anti-predator defence

Interference coloration, in which the perceived colour varies predictably with the angle of illumination or observation, is extremely widespread across animal groups. However, despite considerable advances in our understanding of the mechanistic basis of interference coloration in animals, we still have a poor understanding of its function. Here, I show, using avian predators hunting dynamic virtual prey, that the presence of interference coloration can significantly reduce a predator's attack success. Predators required more pecks to successfully catch interference-coloured prey compared with otherwise identical prey items that lacked interference coloration, and attacks against prey with interference colours were less accurate, suggesting that changes in colour or brightness caused by prey movement hindered a predator's ability to pinpoint their exact location. The pronounced antipredator benefits of interference coloration may explain why it has evolved independently so many times. © 2015 The Author(s) Published by the Royal Society. All rights reserved

Shot noise-mitigated secondary electron imaging with ion count-aided microscopy

Modern science is dependent on imaging on the nanoscale, often achieved through processes that detect secondary electrons created by a highly focused incident charged particle beam. Scanning electron microscopy is employed in applications such as critical-dimension metrology and inspection for semiconductor devices, materials characterization in geology, and examination of biological samples. With its applicability to non-conducting materials (not requiring sample coating before imaging), helium ion microscopy (HIM) is especially useful in the high-resolution imaging of biological samples such as animal organs, tumor cells, and viruses. However, multiple types of measurement noise limit the ultimate trade-off between image quality and the incident particle dose, which can preclude useful imaging of dose-sensitive samples. Existing methods to improve image quality do not fundamentally mitigate the noise sources. Furthermore, barriers to assigning a physically meaningful scale make these modalities qualitative. Here we introduce ion count-aided microscopy (ICAM), which is a quantitative imaging technique that uses statistically principled estimation of the secondary electron yield. With a readily implemented change in data collection, ICAM nearly eliminates the influence of source shot noise -- the random variation in the number of incident ions in a fixed time duration. In HIM, we demonstrate 3x dose reduction; based on a good match between these empirical results and theoretical performance predictions, the dose reduction factor is larger when the secondary electron yield is higher. ICAM thus facilitates imaging of fragile samples and may make imaging with heavier particles more attractive

O-GlcNAcase:promiscuous hexosaminidase or key regulator of O-GlcNAc signalling?

O-GlcNAc signaling is regulated by an opposing pair of enzymes: O-GlcNAc transferase installs and O-GlcNAcase (OGA) removes the modification from proteins. The dynamics and regulation of this process are only beginning to be understood as the physiological functions of both enzymes are being probed using genetic and pharmacological approaches. This minireview charts the discovery and functional and structural analysis of OGA and summarizes the insights gained from recent studies using OGA inhibition, gene knock-out, and overexpression. We identify several areas of “known unknowns” that would benefit from future research, such as the enigmatic C-terminal domain of OGA

A Fast bipolar H2 outflow from IRAS 16342-3814: an old star reliving its youth

Some evolved stars in the pre-planetary nebula phase produce highly-collimated molecular outflows that resemble the accretion-driven jets and outflows from pre-main sequence stars. We show that IRAS 16342-3814 (the Water Fountain Nebula) is such an object and present K-band integral field spectroscopy revealing a fast (> 150 km/s) bipolar H2 outflow. The H2 emission is shock excited and may arise in fast-moving clumps, accelerated by the previously observed precessing jet. The total luminosity in H2 is 0.37 L$_{\odot}$ which is comparable with that of accretion-powered outflows from Class 0 protostars. We also detect CO overtone bandhead emission in the scattered continuum, indicating hot molecular gas close to the centre, a feature also observed in a number of protostars with active jets. It seems likely that the jet and outflow in IRAS 16342-3814 are powered by accretion onto a binary companion.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Societ

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file