Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis

AbstractThe differentiation of floor plate cells and motor neurons can be induced by Sonic hedgehog (SHH), a secreted signaling protein that undergoes autoproteolytic cleavage to generate amino- and carboxy-terminal products. We have found that both floor plate cells and motor neurons are induced by the aminoterminal cleavage product of SHH (SHH-N). The threshold concentration of SHH-N required for motor neuron induction is about 5-fold lower than that required for floor plate induction. Higher concentrations of SHH-N can induce floor plate cells at the expense of motor neuron differentiation. Our results suggest that the induction of floor plate cells and motor neurons by the notochord in vivo is mediated by exposure of neural plate cells to different concentrations of the amino-terminal product of SHH autoproteolytic cleavage

A solar-powered reverse osmosis system for high recovery of freshwater from saline groundwater

Desalination of groundwater is essential in arid regions that are remote from both seawater and freshwater resources. Desirable features of a groundwater desalination system include a high recovery ratio, operation from a sustainable energy source such as solar, and high water output per unit of energy and land. Here we propose a new system that uses a solar-Rankine cycle to drive reverse osmosis (RO). The working fluid such as steam is expanded against a power piston that actuates a pump piston which in turn pressurises the saline water thus passing it through RO membranes. A reciprocating crank mechanism is used to equalise the forces between the two pistons. The choice of batch mode in preference to continuous flow permits maximum energy recovery and minimal concentration polarisation in the vicinity of the RO membrane. This study analyses the sizing and efficiency of the crank mechanism, quantifies energy losses in the RO separation and predicts the overall performance. For example, a system using a field of linear Fresnel collectors occupying 1000 m2 of land and raising steam at 200 °C and 15.5 bar could desalinate 350 m3/day from saline water containing 5000 ppm of sodium chloride with a recovery ratio of 0.7

True and intentionally fabricated memories

The aim of the experiment reported here was to investigate the processes underlying the construction of truthful and deliberately fabricated memories. Properties of memories created to be intentionally false - fabricated memories - were compared to properties of memories believed to be true - true memories. Participants recalled and then wrote or spoke true memories and fabricated memories of everyday events. It was found that true memories were reliably more vivid than fabricated memories and were nearly always recalled from a first person perspective. In contrast, fabricated differed from true memories in that they were judged to be reliably older, were more frequently recalled from a third person perspective, and linguistic analysis revealed that they required more cognitive effort to generate. No notable differences were found across modality of reporting. Finally, it was found that, intentionally fabricated memories were created by recalling and then ‘editing’ true memories. Overall, these findings show that true and fabricated memories systematically differ, despite the fact that both are based on true memories

Level Spacing Distribution of Critical Random Matrix Ensembles

We consider unitary invariant random matrix ensembles which obey spectral statistics different from the Wigner-Dyson, including unitary ensembles with slowly (~(log x)^2) growing potentials and the finite-temperature fermi gas model. If the deformation parameters in these matrix ensembles are small, the asymptotically translational-invariant region in the spectral bulk is universally governed by a one-parameter generalization of the sine kernel. We provide an analytic expression for the distribution of the eigenvalue spacings of this universal asymptotic kernel, which is a hybrid of the Wigner-Dyson and the Poisson distributions, by determining the Fredholm determinant of the universal kernel in terms of a Painleve VI transcendental function.Comment: 5 pages, 1 figure, REVTeX; restriction on the parameter stressed, figure replaced, refs added (v2); typos (factors of pi) in (35), (36) corrected (v3); minor changes incl. title, version to appear in Phys.Rev.E (v4

Fredholm Determinants, Differential Equations and Matrix Models

Orthogonal polynomial random matrix models of NxN hermitian matrices lead to Fredholm determinants of integral operators with kernel of the form (phi(x) psi(y) - psi(x) phi(y))/x-y. This paper is concerned with the Fredholm determinants of integral operators having kernel of this form and where the underlying set is a union of open intervals. The emphasis is on the determinants thought of as functions of the end-points of these intervals. We show that these Fredholm determinants with kernels of the general form described above are expressible in terms of solutions of systems of PDE's as long as phi and psi satisfy a certain type of differentiation formula. There is also an exponential variant of this analysis which includes the circular ensembles of NxN unitary matrices.Comment: 34 pages, LaTeX using RevTeX 3.0 macros; last version changes only the abstract and decreases length of typeset versio

Universal Correlations of Coulomb Blockade Conductance Peaks and the Rotation Scaling in Quantum Dots

We show that the parametric correlations of the conductance peak amplitudes of a chaotic or weakly disordered quantum dot in the Coulomb blockade regime become universal upon an appropriate scaling of the parameter. We compute the universal forms of this correlator for both cases of conserved and broken time reversal symmetry. For a symmetric dot the correlator is independent of the details in each lead such as the number of channels and their correlation. We derive a new scaling, which we call the rotation scaling, that can be computed directly from the dot's eigenfunction rotation rate or alternatively from the conductance peak heights, and therefore does not require knowledge of the spectrum of the dot. The relation of the rotation scaling to the level velocity scaling is discussed. The exact analytic form of the conductance peak correlator is derived at short distances. We also calculate the universal distributions of the average level width velocity for various values of the scaled parameter. The universality is illustrated in an Anderson model of a disordered dot.Comment: 35 pages, RevTex, 6 Postscript figure

Discovery of a first-in-class small molecule antagonist against the adrenomedullin-2 receptor: structure–activity relationships and optimization

Class B G-protein-coupled receptors (GPCRs) remain an underexploited target for drug development. The calcitonin receptor (CTR) family is particularly challenging, as its receptors are heteromers comprising two distinct components: the calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of three accessory proteins known as receptor activity-modifying proteins (RAMPs). CLR/RAMP1 forms a CGRP receptor, CLR/RAMP2 forms an adrenomedullin-1 (AM1) receptor, and CLR/RAMP3 forms an adrenomedullin-2 (AM2) receptor. The CTR/RAMP complexes form three distinct amylin receptors. While the selective blockade of AM2 receptors would be therapeutically valuable, inhibition of AM1 receptors would cause clinically unacceptable increased blood pressure. We report here a systematic study of structure–activity relationships that has led to the development of first-in-class AM2 receptor antagonists. These compounds exhibit therapeutically valuable properties with 1000-fold selectivity over the AM1 receptor. These results highlight the therapeutic potential of AM2 antagonists

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release