Exact boundary conditions in numerical relativity using multiple grids: scalar field tests

Cauchy-Characteristic Matching (CCM), the combination of a central 3+1 Cauchy code with an exterior characteristic code connected across a time-like interface, is a promising technique for the generation and extraction of gravitational waves. While it provides a tool for the exact specification of boundary conditions for the Cauchy evolution, it also allows to follow gravitational radiation all the way to infinity, where it is unambiguously defined. We present a new fourth order accurate finite difference CCM scheme for a first order reduction of the wave equation around a Schwarzschild black hole in axisymmetry. The matching at the interface between the Cauchy and the characteristic regions is done by transfering appropriate characteristic/null variables. Numerical experiments indicate that the algorithm is fourth order convergent. As an application we reproduce the expected late-time tail decay for the scalar field.Comment: 14 pages, 5 figures. Included changes suggested by referee

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

Translational Modeling in Schizophrenia:Predicting Human Dopamine D2 Receptor Occupancy

OBJECTIVES: To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs.METHODS: A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses.RESULTS: Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol.CONCLUSIONS: The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.</p

Early Development of the Central and Peripheral Nervous Systems Is Coordinated by Wnt and BMP Signals

The formation of functional neural circuits that process sensory information requires coordinated development of the central and peripheral nervous systems derived from neural plate and neural plate border cells, respectively. Neural plate, neural crest and rostral placodal cells are all specified at the late gastrula stage. How the early development of the central and peripheral nervous systems are coordinated remains, however, poorly understood. Previous results have provided evidence that at the late gastrula stage, graded Wnt signals impose rostrocaudal character on neural plate cells, and Bone Morphogenetic Protein (BMP) signals specify olfactory and lens placodal cells at rostral forebrain levels. By using in vitro assays of neural crest and placodal cell differentiation, we now provide evidence that Wnt signals impose caudal character on neural plate border cells at the late gastrula stage, and that under these conditions, BMP signals induce neural crest instead of rostral placodal cells. We also provide evidence that both caudal neural and caudal neural plate border cells become independent of further exposure to Wnt signals at the head fold stage. Thus, the status of Wnt signaling in ectodermal cells at the late gastrula stage regulates the rostrocaudal patterning of both neural plate and neural plate border, providing a coordinated spatial and temporal control of the early development of the central and peripheral nervous systems

In Vitro Differentiation of Mouse Embryonic Stem Cells into Neurons of the Dorsal Forebrain

Pluripotent embryonic stem cells (ESCs) are able to differentiate into all cell types in the organism including cortical neurons. To follow the dynamic generation of progenitors of the dorsal forebrain in vitro, we generated ESCs from D6-GFP mice in which GFP marks neocortical progenitors and neurons after embryonic day (E) 10.5. We used several cell culture protocols for differentiation of ESCs into progenitors and neurons of the dorsal forebrain. In cell culture, GFP-positive cells were induced under differentiation conditions in quickly formed embryoid bodies (qEBs) after 10–12 day incubation. Activation of Wnt signaling during ESC differentiation further stimulated generation of D6-GFP-positive cortical cells. In contrast, differentiation protocols using normal embryoid bodies (nEBs) yielded only a few D6-GFP-positive cells. Gene expression analysis revealed that multiple components of the canonical Wnt signaling pathway were expressed during the development of embryoid bodies. As shown by immunohistochemistry and quantitative qRT-PCR, D6-GFP-positive cells from qEBs expressed genes that are characteristic for the dorsal forebrain such as Pax6, Dach1, Tbr1, Tbr2, or Sox5. qEBs culture allowed the formation of a D6-GFP positive pseudo-polarized neuroepithelium with the characteristic presence of N-cadherin at the apical pole resembling the structure of the developing neocortex

In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity

Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these neuromesodermal progenitors (NMPs) can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signalling, timed to emulate in vivo development. Similar to NMPs in vivo, these cells co-express the neural factor Sox2 and the mesodermal factor Brachyury and differentiate into neural and paraxial mesoderm in vitro and in vivo. The neural cells produced by NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. This is consistent with the shared origin of spinal cord and somites and the distinct ontogeny of the anterior and posterior nervous system. Systematic analysis of the transcriptome during differentiation identifies the molecular correlates of each of the cell identities and the routes by which they are obtained. Moreover, we take advantage of the system to provide evidence that Brachyury represses neural differentiation and that signals from mesoderm are not necessary to induce the posterior identity of spinal cord cells. This indicates that the mesoderm inducing and posteriorising functions of Wnt signalling represent two molecularly separate activities. Together the data illustrate how reverse engineering normal developmental mechanisms allows the differentiation of specific cell types in vitro and the analysis of previous difficult to access aspects of embryo development

Speckle Interferometry of Nearby Multiple Stars. IV. Measurements in 2004 and New Orbits

The results of speckle interferometric observations of 104 binary and 6 triple stars performed at the BTA 6 m telescope in 2004 October are presented. Nearby low-mass stars are mostly observed for the program, among which 59 there are new binaries recently discovered by the Hipparcos astrometric satellite. Concurrently with the diffraction-limited position measurements we obtained 154 brightness ratio measurements of binary and multiple star components in different bands of the visible spectrum. New, first-resolved binaries are the symbiotic star CH Cyg with a weak companion at 0.043'' separation and the pair of red dwarfs, GJ 913 = HIP 118212. In addition, we derived the orbital parameters for two interferometric systems: the CN-giant pair HD 210211 = HIP 109281 (P=10.7 yr) and the G2V-K2V binary GJ 9830 = HIP 116259 (P=15.7 yr).Comment: 11 pages, 2 figures, accepted to Astrophysical Bulleti

A Compiled Catalogue of Spectroscopically Determined Elemental Abundances for Stars with Accurate Parallaxes. I.Magnesium

We present a compiled catalogue of effective temperatures, surface gravities, iron and magnesium abundances, distances, velocity components, and orbital elements for stars in the solar neighborhood. The atmospheric parameters and iron abundances are averages of published values derived from model synthetic spectra for a total of about 2000 values in 80 publications. Our relative magnesium abundances were found from 1412 values in 31 publications for 876 dwarfs and subgiants using a three-step iteration averaging procedure, with weights assigned to each source of data as well as to each individual determination and taking into account systematic deviations of each scale relative to the reduced mean scale. The estimated assumed completeness for data sources containing more than five stars, up to late December 2003, exceeds 90%. For the vast majority of stars in the catalogue, the spatial velocity components were derived from modern high-precision astrometric observations, and their Galactic orbit elements were computed using a three-component model of the Galaxy, consisting of a disk, a bulge, and a massive extended halo.Comment: Accepted for Astron. Rep. 2005, v.49, No.5, p.405-416, 12 pages, 10 figure