Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth

AbstractErbB2 is a ligand-less member of the ErbB receptor family that functions as a coreceptor with EGFR, ErbB3, and ErbB4. Here, we describe an approach to target ErbB2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders ErbB2's recruitment into ErbB ligand complexes. Inhibition of ligand-dependent ErbB2 signaling by 2C4 occurs in both low- and high-ErbB2-expressing systems. Since the ErbB3 receptor contains an inactive tyrosine kinase domain, 2C4 is very effective in blocking heregulin-mediated ErbB3-ErbB2 signaling. We demonstrate that the in vitro and in vivo growth of several breast and prostate tumor models is inhibited by 2C4 treatment

What the disjunctivist is right about

There is a traditional conception of sensory experience on which the experiences one has looking at, say, a cat could be had by someone merely hallucinating a cat. Disjunctivists take issue with this conception on the grounds that it does not enable us to understand how perceptual knowledge is possible. In particular, they think, it does not explain how it can be that experiences gained in perception enable us to be in ‘cognitive contact’ with objects and facts. I develop this chal- lenge to the traditional conception and then show that it is possible to accommo- date an adequate account of cognitive contact in keeping with the traditional conception. One upshot of the discussion is that experiences do not bear the explanatory burden placed upon them by disjunctivists

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/1/onco0795-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/2/onco0795-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139937/3/onco0795.pd

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

Vetting of 384 TESS Objects of Interest with TRICERATOPS and Statistical Validation of 12 Planet Candidates

We present TRICERATOPS, a new Bayesian tool that can be used to vet and validate TESS Objects of Interest (TOIs). We test the tool on 68 TOIs that have been previously confirmed as planets or rejected as astrophysical false positives. By looking in the false positive probability (FPP) -- nearby false positive probability (NFPP) plane, we define criteria that TOIs must meet to be classified as validated planets (FPP < 0.015 and NFPP < 10^-3), likely planets (FPP 10^-1). We apply this procedure on 384 unclassified TOIs and statistically validate 12, classify 125 as likely planets, and classify 52 as likely nearby false positives. Of the 12 statistically validated planets, 9 are newly validated. TRICERATOPS is currently the only TESS vetting and validation tool that models transits from nearby contaminant stars in addition to the target star. We therefore encourage use of this tool to prioritize follow-up observations that confirm bona fide planets and identify false positives originating from nearby stars.Comment: Accepted to A

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

An overview of MODIS capabilities for ocean science observations

The Moderate Resolution Imaging Spectroradiometer (MODIS) will add a significant new capability for investigating the 70% of the Earth's surface that is covered by oceans, in addition to contributing to the continuation of a decadal scale time series necessary for climate change assessment in the oceans. Sensor capabilities of particular importance for improving the accuracy of ocean products include high SNR and high stability for narrow or spectral bands, improved onboard radiometric calibration and stability monitoring, and improved science data product algorithms. Spectral bands for resolving solar-stimulated chlorophyll fluorescence and a split window in the 4-/spl mu/m region for SST will result in important new global ocean science products for biology and physics. MODIS will return full global data at 1-km resolution. The complete suite of Levels 2 and 3 ocean products is reviewed, and many areas where MODIS data are expected to make significant, new contributions to the enhanced understanding of the oceans' role in understanding climate change are discussed. In providing a highly complementary and consistent set of observations of terrestrial, atmospheric, and ocean observations, MODIS data will provide important new information on the interactions between Earth's major components