Human endothelial cells can be induced to form capillary-like tubular networks in collagen gels. We have used this in vitro model and representational difference analysis to identify genes involved in the formation of new blood vessels. HESR1 (HEY-1/HRT-1/CHF-2/gridlock), a basic helix-loop-helix protein related to the hairy/enhancer of split/HES family, is absent in migrating and proliferating cultures of endothelial cells but is rapidly induced during capillary-like network formation. HESR1 is detectable in all adult tissues and at high levels in well vascularized organs such as heart and brain. Its expression is also enriched in aorta and purified capillaries. Overexpression of HESR1 in endothelial cells down-regulates vascular endothelial cell growth factor receptor-2 (VEGFR2) mRNA levels and blocks proliferation, migration, and network formation. Interestingly, reduction of expression of HESR1 by antisense oligonucleotides also blocks endothelial cell network formation in vitro. Finally, HESR1 expression is altered in several breast, lung, and kidney tumors. These data are consistent with a temporal model for HESR1 action where down-regulation at the initiation of new vessel budding is required to allow VEGFR2-mediated migration and proliferation, but re-expression of HESR1 is necessary for induction of tubular network formation and continued maintenance of the mature, quiescent vessel.The formation of new blood vessels by angiogenesis is critical to development of normal tissues as well as growth of solid tumors (1, 2). Angiogenesis is a multistep sequence of distinct cellular processes beginning with degradation of extracellular matrix, then proliferation, and migration of endothelial cells (EC), 1 followed by lumen formation and functional maturation (3, 4). Currently, two families of EC-specific growth factors are known to regulate these steps. The vascular endothelial growth factors (VEGFs), together with the more widely expressed and pleiotropic fibroblast growth factors (FGFs), promote EC migration, proliferation, and tube formation (5-9). The second family is composed of angiopoietins (Ang) 1-5, of which Ang-1 and Ang-2, acting through the Tie-2 receptor tyrosine kinase, are known to be critical for the later processes of vessel maturation and stabilization (10 -12). The VEGFs, which can drive all of the early stages of angiogenesis, act through two tyrosine kinase receptors, VEGFR1 (flt-1) (13) and VEGFR2 (KDR/ flk-1) (14). EC also express neuropilin-1 and neuropilin-2, which only bind the VEGF 165 isoform (15).Although transcription factors such as HIF and Tfeb are known to mediate EC responses to specific angiogenic inducers (hypoxia and placental growth, respectively (16, 17)), downstream events coordinating EC responses to general angiogenic growth factors remain unknown. In particular, it is not clear how sequential cellular processes can be triggered by continued or repeated exposure to the same stimulus, although a model for reiterative signaling has been proposed to explain FGFinduced branc...
The Arcminute Microkelvin Imager is a pair of interferometer arrays operating with six frequency channels spanning 13.9-18.2 GHz, for observations on angular scales of 30 arcsec-10 arcmin and for declinations greater than −15 • ; the Small Array has a sensitivity of 30 mJy s −1/2 and the Large Array has a sensitivity of 3 mJy s −1/2 . The telescope is aimed principally at Sunyaev-Zel'dovich imaging of clusters of galaxies. We discuss the design of the telescope and describe and explain its electronic and mechanical systems.
Anomalous Microwave Emission (AME) is a component of diffuse Galactic radiation observed at frequencies in the range ≈ 10-60 GHz. AME was first detected in 1996 and recognised as an additional component of emission in 1997. Since then, AME has been observed by a range of experiments and in a variety of environments. AME is spatially correlated with far-IR thermal dust emission but cannot be explained by synchrotron or free-free emission mechanisms, and is far in excess of the emission contributed by thermal dust emission with the power-law opacity consistent with the observed emission at sub-mm wavelengths. Polarization observations have shown that AME is very weakly polarized ( 1 %). The most natural explanation for AME is rotational emission from ultra-small dust grains ("spinning dust"), first postulated in 1957.
We present new measurements of the power spectra of the E-mode of CMB polarization, the temperature T, the cross-correlation of E and T, and upper limits on the B-mode from 2.5 years of dedicated Cosmic Background Imager (CBI) observations. Both raw maps and optimal signal images in the uv-plane and real space show strong detections of the E-mode (11.7 sigma for the EE power spectrum overall) and no detection of the B-mode. The power spectra are used to constrain parameters of the flat tilted adiabatic Lambda-CDM models: those determined from EE and TE bandpowers agree with those from TT, a powerful consistency check. There is little tolerance for shifting polarization peaks from the TT-forecast locations, as measured by the angular sound crossing scale theta = 100 ell_s = 1.03 +/- 0.02 from EE and TE cf. 1.044 +/- 0.005 with the TT data included. The scope for extra out-of-phase peaks from subdominant isocurvature modes is also curtailed. The EE and TE measurements of CBI, DASI and BOOMERANG are mutually consistent, and, taken together rather than singly, give enhanced leverage for these tests.Comment: 15 pages, 9 figures, submitted to ApJ -- Accepted version. The fine-bin spectrum, covariance matrix, and window functions are now available on the web (suitable for use in COSMOMC) at: http://www.astro.caltech.edu/~tjp/CBI/data2006/index.html The pipeline in the previous version inadvertently omitted one antenna, so the new spectrum contains ~15% more data. We emphasize that previous results were in no way biased, and that the (small) changes to the spectrum solely reflect the inclusion of the additional data. Numbers and figures in the paper have been updated correspondingly. All maps now have color bar
We present deep Ka‐band (ν≈ 33 GHz) observations of the cosmic microwave background (CMB) made with the extended Very Small Array (VSA). This configuration produces a naturally weighted synthesized FWHM beamwidth of ∼11 arcmin, which covers an ℓ range of 300 to 1500. On these scales, foreground extragalactic sources can be a major source of contamination to the CMB anisotropy. This problem has been alleviated by identifying sources at 15 GHz with the Ryle Telescope and then monitoring these sources at 33 GHz using a single‐baseline interferometer collocated with the VSA. Sources with flux densities ≳20 mJy at 33 GHz are subtracted from the data. In addition, we calculate a statistical correction for the small residual contribution from weaker sources that are below the detection limit of the survey. The CMB power spectrum corrected for Galactic foregrounds and extragalactic point sources is presented. A total ℓ range of 150–1500 is achieved by combining the complete extended array data with earlier VSA data in a compact configuration. Our resolution of Δℓ≈ 60 allows the first three acoustic peaks to be clearly delineated. This is achieved by using mosaiced observations in seven regions covering a total area of 82 deg2. There is good agreement with the Wilkinson Microwave Anisotropy Probe (WMAP) data up to ℓ= 700 where WMAP data run out of resolution. For higher ℓ values out to ℓ= 1500, the agreement in power spectrum amplitudes with other experiments is also very good despite differences in frequency and observing technique.
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