Neuropilin-mediated neural crest cell guidance is essential to organise sensory neurons into segmented dorsal root ganglia

The peripheral nervous system (PNS) of higher vertebrates is segmented to align the spinal nerve roots with the vertebrae. This co-patterning is set up during embryogenesis, when vertebrae develop from the sclerotome layer of the metameric somites, and PNS neurons and glia differentiate from neural crest cells (NCCs) that preferentially migrate into the anterior sclerotome halves. Previous analyses of mice deficient in the class 3 semaphorin (SEMA3) receptors neuropilin (NRP) 1 or 2 raised the possibility that each controlled a distinct aspect of trunk NCC migration. We now demonstrate that both pathways act sequentially in distinct NCC subpopulations and thereby cooperate to enforce segmental NCC migration. Specifically, SEMA3A/NRP1 signalling first directs one population of NCCs from the intersomitic path into the sclerotome, and SEMA3F/NRP2 signalling acts subsequently to restrict a second population to the anterior half of the sclerotome. NCC exclusion from either the posterior sclerotome or the intersomitic boundary is sufficient to enforce the separation of neighbouring NCC streams and the segregation of sensory NCC progeny into metameric dorsal root ganglia (DRG). By contrast, the combined loss of both guidance pathways leads to ectopic invasion of the intersomitic furrows and posterior sclerotome halves, disrupting metameric NCC streaming and DRG segmentation

Neuropilin 1 signaling guides neural crest cells to coordinate pathway choice with cell specification

Neural crest cells (NCCs) are highly motile embryonic stem cells that delaminate from the neuroectoderm early during vertebrate embryogenesis and differentiate at defined target sites into various essential cell types. To reach their targets, NCCs follow 1 of 3 sequential pathways that correlate with NCC fate. The firstborn NCCs travel ventrally alongside intersomitic blood vessels to form sympathetic neuronal progenitors near the dorsal aorta, while the lastborn NCCs migrate superficially beneath the epidermis to give rise to melanocytes. Yet, most NCCs enter the somites to form the intermediate wave that gives rise to sympathetic and sensory neurons. Here we show that the repulsive guidance cue SEMA3A and its receptor neuropilin 1 (NRP1) are essential to direct the intermediate wave NCC precursors of peripheral neurons from a default pathway alongside intersomitic blood vessels into the anterior sclerotome. Thus, loss of function for either gene caused excessive intersomitic NCC migration, and this led to ectopic neuronal differentiation along both the anteroposterior and dorsoventral axes of the trunk. The choice of migratory pathway did not affect the specification of NCCs, as they retained their commitment to differentiate into sympathetic or sensory neurons, even when they migrated on an ectopic dorsolateral path that is normally taken by melanocyte precursors. We conclude that NRP1 signaling coordinates pathway choice with NCC fate and therefore confines neuronal differentiation to appropriate locations

Density-PDFs and Lagrangian Statistics of highly compressible Turbulence

We report on probability-density-functions (PDF) of the mass density in numerical simulations of highly compressible hydrodynamic flows and the corresponding structure formation of Lagrangian particles advected by the flows. Numerical simulations were performed with $512^3$ collocation points and 2 million tracer particles integrated over several dynamical times. We propose a connection between the PDF of the Lagrangian tracer particles and the predicted log-normal distribution of the density fluctuations in isothermal systems

Q-Value and Half-Lives for the Double-Beta-Decay Nuclide 110Pd

The 110Pd double-beta decay Q-value was measured with the Penning-trap mass spectrometer ISOLTRAP to be Q = 2017.85(64) keV. This value shifted by 14 keV compared to the literature value and is 17 times more precise, resulting in new phase-space factors for the two-neutrino and neutrinoless decay modes. In addition a new set of the relevant matrix elements has been calculated. The expected half-life of the two-neutrino mode was reevaluated as 1.5(6) E20 yr. With its high natural abundance, the new results reveal 110Pd to be an excellent candidate for double-beta decay studies

L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

On the 3D dynamics and morphology of inner rings

We argue that inner rings in barred spiral galaxies are associated with specific 2D and 3D families of periodic orbits located just beyond the end of the bar. These are families located between the inner radial ultraharmonic 4:1 resonance and corotation. They are found in the upper part of a type-2 gap of the x1 characteristic, and can account for the observed ring morphologies without any help from families of the x1-tree. Due to the evolution of the stability of all these families, the ring shapes that are favored are mainly ovals, as well as polygons with `corners' on the minor axis, on the sides of the bar. On the other hand pentagonal rings, or rings of the NGC 7020 type hexagon, should be less probable. The orbits that make the rings belong in their vast majority to 3D families of periodic orbits and orbits trapped around them.Comment: 11 pages, 12 figures, to appear in MNRA

Penning trap mass measurements on (99-109)$Cd with ISOLTRAP and implications on the rp process

Penning trap mass measurements on neutron-deficient Cd isotopes (99-109)Cd have been performed with the ISOLTRAP mass spectrometer at ISOLDE/CERN, all with relative mass uncertainties below 3*10^8. A new mass evaluation has been performed. The mass of 99Cd has been determined for the first time which extends the region of accurately known mass values towards the doubly magic nucleus 100Sn. The implication of the results on the reaction path of the rp process in stellar X-ray bursts is discussed. In particular, the uncertainty of the abundance and the overproduction created by the rp-process for the mass A = 99 is demonstrated by reducing the uncertainty of the proton-separation energy of 100In Sp(100In) by a factor of 2.5.Comment: 14 pages, 9 figure

FU-net: Multi-class Image Segmentation Using Feedback Weighted U-net

In this paper, we present a generic deep convolutional neural network (DCNN) for multi-class image segmentation. It is based on a well-established supervised end-to-end DCNN model, known as U-net. U-net is firstly modified by adding widely used batch normalization and residual block (named as BRU-net) to improve the efficiency of model training. Based on BRU-net, we further introduce a dynamically weighted cross-entropy loss function. The weighting scheme is calculated based on the pixel-wise prediction accuracy during the training process. Assigning higher weights to pixels with lower segmentation accuracies enables the network to learn more from poorly predicted image regions. Our method is named as feedback weighted U-net (FU-net). We have evaluated our method based on T1- weighted brain MRI for the segmentation of midbrain and substantia nigra, where the number of pixels in each class is extremely unbalanced to each other. Based on the dice coefficient measurement, our proposed FU-net has outperformed BRU-net and U-net with statistical significance, especially when only a small number of training examples are available. The code is publicly available in GitHub (GitHub link: https://github.com/MinaJf/FU-net).Comment: Accepted for publication at International Conference on Image and Graphics (ICIG 2019

An Overview of the 13:8 Mean Motion Resonance between Venus and Earth

It is known since the seminal study of Laskar (1989) that the inner planetary system is chaotic with respect to its orbits and even escapes are not impossible, although in time scales of billions of years. The aim of this investigation is to locate the orbits of Venus and Earth in phase space, respectively to see how close their orbits are to chaotic motion which would lead to unstable orbits for the inner planets on much shorter time scales. Therefore we did numerical experiments in different dynamical models with different initial conditions -- on one hand the couple Venus-Earth was set close to different mean motion resonances (MMR), and on the other hand Venus' orbital eccentricity (or inclination) was set to values as large as e = 0.36 (i = 40deg). The couple Venus-Earth is almost exactly in the 13:8 mean motion resonance. The stronger acting 8:5 MMR inside, and the 5:3 MMR outside the 13:8 resonance are within a small shift in the Earth's semimajor axis (only 1.5 percent). Especially Mercury is strongly affected by relatively small changes in eccentricity and/or inclination of Venus in these resonances. Even escapes for the innermost planet are possible which may happen quite rapidly.Comment: 14 pages, 11 figures, submitted to CMD