Patchy Interspecific Sequence Similarities Efficiently Identify Positive cis-Regulatory Elements in the Sea Urchin

We demonstrate that interspecific sequence conservation can provide a systematic guide to the identification of functional cis-regulatory elements within a large expanse of genomic DNA. The test was carried out on the otx gene of Strongylocentrotus purpuratus. This gene plays a major role in the gene regulatory network that underlies endomesoderm specification in the embryo. The cis-regulatory organization of the otx gene is expected to be complex, because the gene has three different start sites (X. Li, C.-K. Chuang, C.-A. Mao, L. M. Angerer, and W. H. Klein, 1997, Dev. Biol. 187, 253–266), and it is expressed in many different spatial domains of the embryo. BAC recombinants containing the otx gene were isolated from Strongylocentrotus purpuratus and Lytechinus variegatus libraries, and the ordered sequence of these BACs was obtained and annotated. Sixty kilobases of DNA flanking the gene, and included in the BAC sequence from both species, were scanned computationally for short conserved sequence elements. For this purpose, we used a newly constructed software package assembled in our laboratory, “FamilyRelations.” This tool allows detection of sequence similarities above a chosen criterion within sliding windows set at 20–50 bp. Seventeen partially conserved regions, most a few hundred base pairs long, were amplified from the S. purpuratus BAC DNA by PCR, inserted in an expression vector driving a CAT reporter, and tested for cis-regulatory activity by injection into fertilized S. purpuratus eggs. The regulatory activity of these constructs was assessed by whole-mount in situ hybridization (WMISH) using a probe against CAT mRNA. Of the 17 constructs, 11 constructs displayed spatially restricted regulatory activity, and 6 were inactive in this test. The domains within which the cis-regulatory constructs were expressed are approximately consistent with results from a WMISH study on otx expression in the embryo, in which we used probes specific for the mRNAs generated from each of the three transcription start sites. Four separate cis-regulatory elements that specifically produce endomesodermal expression were identified, as well as ubiquitously active elements, and ectoderm-specific elements. We confirm predictions from other work with respect to target sites for specific transcription factors within the elements that express in the endoderm

The Rapid Outbursting Star GM Cep: An EX-or in Tr 37?

We present optical, IR and millimeter observations of the solar-type star 13-277, also known as GM Cep, in the 4 Myr-old cluster Tr 37. GM Cep experiences rapid magnitude variations of more than 2 mag at optical wavelengths. We explore the causes of the variability, which seem to be dominated by strong increases in the accretion, being similar to EX-or episodes. The star shows high, variable accretion rates (up to ~10$^{-6}$ Msun/yr), signs of powerful winds, and it is a very fast rotator (Vsini~43 km/s). Its strong mid-IR excesses reveal a very flared disk and/or a remnant envelope, most likely out of hydrostatic equilibrium. The 1.3 millimeter fluxes suggest a relatively massive disk (Mdisk~0.1 Msun). Nevertheless, the millimeter mass is not enough to sustain increased accretion episodes over large timescales, unless the mass is underestimated due to significant grain growth. We finally explore the possibility of GM Cep having a binary companion, which could trigger disk instabilities producing the enhanced accretion episodes.Comment: 43 pages, including 10 figures, ApJ in pres

Characterising the Gravitational Instability in Cooling Accretion Discs

We perform numerical analyses of the structure induced by gravitational instabilities in cooling gaseous accretion discs. For low enough cooling rates a quasi-steady configuration is reached, with the instability saturating at a finite amplitude in a marginally stable disc. We find that the saturation amplitude scales with the inverse square root of the cooling parameter beta = t_cool / t_dyn, which indicates that the heating rate induced by the instability is proportional to the energy density of the induced density waves. We find that at saturation the energy dissipated per dynamical time by weak shocks due is of the order of 20 per cent of the wave energy. From Fourier analysis of the disc structure we find that while the azimuthal wavenumber is roughly constant with radius, the mean radial wavenumber increases with radius, with the dominant mode corresponding to the locally most unstable wavelength. We demonstrate that the density waves excited in relatively low mass discs are always close to co-rotation, deviating from it by approximately 10 per cent. This can be understood in terms of the flow Doppler-shifted phase Mach number -- the pattern speed self-adjusts so that the flow into spiral arms is always sonic. This has profound effects on the degree to which transport through self-gravity can be modelled as a viscous process. Our results thus provide (a) a detailed description of how the self-regulation mechanism is established for low cooling rates, (b) a clarification of the conditions required for describing the transport induced by self-gravity through an effective viscosity, (c) an estimate of the maximum amplitude of the density perturbation before fragmentation occurs, and (d) a simple recipe to estimate the density perturbation in different thermal regimes.Comment: 16 pages, 22 figures. Accepted for publication in MNRAS 11 November 200

Crystallographic structure of ultrathin Fe films on Cu(100)

We report bcc-like crystal structures in 2-4 ML Fe films grown on fcc Cu(100) using scanning tunneling microscopy. The local bcc structure provides a straightforward explanation for their frequently reported outstanding magnetic properties, i.e., ferromagnetic ordering in all layers with a Curie temperature above 300 K. The non-pseudomorphic structure, which becomes pseudomorphic above 4 ML film thickness is unexpected in terms of conventional rules of thin film growth and stresses the importance of finite thickness effects in ferromagnetic ultrathin films.Comment: 4 pages, 3 figures, RevTeX/LaTeX2.0

An Exactly Solvable Model of N Coupled Luttinger Chains

We calculate the exact Green function of a special model of N coupled Luttinger chains with arbitrary interchain hopping t_{perp}. The model is exactly solvable via bosonization if the interchain interaction does not fall off in the direction perpendicular to the chains. For any finite N we find Luttinger liquid behavior and explicitly calculate the anomalous dimension gamma^(N). However, the Luttinger liquid state does not preclude coherent interchain hopping. We also show that gamma^(N) -> 0 for N -> infinity, so that in the limit of infinitely many chains we obtain a Fermi liquid.Comment: accepted for publication in Phys. Rev.

Performance of Newtonian filters in detecting gravitational waves from coalescing binaries

Coalescing binary systems are one of the most promising sources of gravitational waves. The technique of matched filtering used in the detection of gravitational waves from coalescing binaries relies on the construction of accurate templates. Until recently filters modelled on the quadrupole or the Newtonian approximation were deemed sufficient. Recently it was shown that post-Newtonian effects contribute to a secular growth in the phase difference between the actual signal and its corresponding Newtonian template. In this paper we investigate the possibility of compensating for the phase difference caused by the post-Newtonian terms by allowing for a shift in the Newtonian filter parameters. We find that Newtonian filters perform adequately for the purpose of detecting the presence of the signal for both the initial and the advanced LIGO detectors.Comment: Revtex 9 pages + 6 figures ( Can be obtained by "anonymous" ftp from 144.16.31.1 in dir /pub/rbs. Submitted to Physical Review D. IUCAA 1

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

A Method for Calculating the Structure of (Singular) Spacetimes in the Large

A formalism and its numerical implementation is presented which allows to calculate quantities determining the spacetime structure in the large directly. This is achieved by conformal techniques by which future null infinity (\Scri{}^+) and future timelike infinity ($i^+$) are mapped to grid points on the numerical grid. The determination of the causal structure of singularities, the localization of event horizons, the extraction of radiation, and the avoidance of unphysical reflections at the outer boundary of the grid, are demonstrated with calculations of spherically symmetric models with a scalar field as matter and radiation model.Comment: 29 pages, AGG2

Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease

IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E−5 and chromosome 14, rs4902762, BETA = 0.12, P = 5.76E−6) and one for eosinophil count (rs72797327, BETA = −0.10, P = 1.41E−6). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P = 0.2763, I2 = 24, I2 − P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = −0.10, P = 8.64E−6 and rs11739623 (r2 = 0.96 with rs72797327) BETA = −0.23, P = 1.74E−29, respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels