On Galactic density modeling in the presence of dust extinction

Inferences about the spatial density or phase-space structure of stellar populations in the Milky Way require a precise determination of the effective survey volume. The volume observed by surveys such as Gaia or near-infrared spectroscopic surveys, which have good coverage of the Galactic mid-plane region, is highly complex because of the abundant small-scale structure in the three-dimensional interstellar dust extinction. We introduce a novel framework for analyzing the importance of small-scale structure in the extinction. This formalism demonstrates that the spatially-complex effect of extinction on the selection function of a pencil-beam or contiguous sky survey is equivalent to a low-pass filtering of the extinction-affected selection function with the smooth density field. We find that the angular resolution of current 3D extinction maps is sufficient for analyzing Gaia sub-samples of millions of stars. However, the current distance resolution is inadequate and needs to be improved by an order of magnitude, especially in the inner Galaxy. We also present a practical and efficient method for properly taking the effect of extinction into account in analyses of Galactic structure through an effective selection function. We illustrate its use with the selection function of red-clump stars in APOGEE using and comparing a variety of current 3D extinction maps.Comment: Code available at https://github.com/jobovy/mwdust and at https://github.com/jobovy/apogee-map

Cultures of human tracheal gland cells of mucous or serous phenotype

There are two main epithelial cell types in the secretory tubules of mammalian glands: serous and mucous. The former is believed to secrete predominantly water and antimicrobials, the latter mucins. Primary cultures of human airway gland epithelium have been available for almost 20 yr, but they are poorly differentiated and lack clear features of either serous or mucous cells. In this study, by varying growth supports and media, we have produced cultures from human airway glands that in terms of their ultrastructure and secretory products resemble either mucous or serous cells. Of four types of porous-bottomed insert tested, polycarbonate filters (Transwells) most strongly promoted the mucous phenotype. Coupled with the addition of epidermal growth factor (EGF), this growth support produced “mucous” cells that contained the large electron-lucent granules characteristic of native mucous cells, but lacked the small electron-dense granules characteristic of serous cells. Furthermore, they showed high levels of mucin secretion and low levels of release of lactoferrin and lysozyme (markers of native serous cells). By contrast, growth on polyethylene terephthalate filters (Cyclopore) in medium lacking EGF produced “serous” cells in which small electron-dense granules replaced the electron-lucent ones, and the cells had high levels of lactoferrin and lysozyme but low levels of mucins. Measurements of transepithelial resistance and short-circuit current showed that both “serous” and “mucous” cell cultures possessed tight junctions, had become polarized, and were actively secreting Cl

Nanomolar-potency 'co-potentiator' therapy for cystic fibrosis caused by a defined subset of minimal function CFTR mutants.

Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed 'Class II potentiator') was used with a classical potentiator ('Class I potentiator') such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR

V1647 Orionis: Optical Photometric and Spectroscopic Monitoring Through the 2003-2006 Outburst

We present results from an optical imaging and spectroscopic monitoring campaign on the young, low-mass eruptive variable star V1647 Orionis. The star and associated nebulosity (McNeil's Nebula) were observed over the period February 2004 to February 2006 with observations commencing a few months after the original outburst event occurred. Using the Gemini North telescope, we obtained multi-band optical imaging photometry and medium-resolution long-slit spectroscopy of V1647 Ori on an approximately monthly interval. During this period, V1647 Ori remained at, or close to, peak brightness and then faded by 5 magnitudes to close to its pre-outburst brightness. This implies an outburst timescale of around 27 months. Spectral features seen in both emission and absorption varied considerably during the monitoring period. For example, the Halpha line changed significantly in both intensity and profile. We present and discuss the observed photometric and spectroscopic changes and consider how this eruptive event relates to the early formative stages of low-mass stars.Comment: 59 pages, 22 figure

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF

Modeling Dust and Starlight in Galaxies Observed by Spitzer and Herschel: NGC 628 and NGC 6946

We characterize the dust in NGC628 and NGC6946, two nearby spiral galaxies in the KINGFISH sample. With data from 3.6um to 500um, dust models are strongly constrained. Using the Draine & Li (2007) dust model, (amorphous silicate and carbonaceous grains), for each pixel in each galaxy we estimate (1) dust mass surface density, (2) dust mass fraction contributed by polycyclic aromatic hydrocarbons (PAH)s, (3) distribution of starlight intensities heating the dust, (4) total infrared (IR) luminosity emitted by the dust, and (5) IR luminosity originating in regions with high starlight intensity. We obtain maps for the dust properties, which trace the spiral structure of the galaxies. The dust models successfully reproduce the observed global and resolved spectral energy distributions (SEDs). The overall dust/H mass ratio is estimated to be 0.0082+/-0.0017 for NGC628, and 0.0063+/-0.0009 for NGC6946, consistent with what is expected for galaxies of near-solar metallicity. Our derived dust masses are larger (by up to a factor 3) than estimates based on single-temperature modified blackbody fits. We show that the SED fits are significantly improved if the starlight intensity distribution includes a (single intensity) "delta function" component. We find no evidence for significant masses of cold dust T<12K. Discrepancies between PACS and MIPS photometry in both low and high surface brightness areas result in large uncertainties when the modeling is done at PACS resolutions, in which case SPIRE, MIPS70 and MIPS160 data cannot be used. We recommend against attempting to model dust at the angular resolution of PACS.Comment: To be published in Apj, September 2012. See the full version at http://www.astro.princeton.edu/~ganiano/Papers

Herschel Far-Infrared and Sub-millimeter Photometry for the KINGFISH Sample of Nearby Galaxies

New far-infrared and sub-millimeter photometry from the Herschel Space Observatory is presented for 61 nearby galaxies from the Key Insights on Nearby Galaxies: A Far-Infrared Survey with Herschel (KINGFISH) sample. The spatially-integrated fluxes are largely consistent with expectations based on Spitzer far-infrared photometry and extrapolations to longer wavelengths using popular dust emission models. Dwarf irregular galaxies are notable exceptions, as already noted by other authors, as their 500um emission shows evidence for a sub-millimeter excess. In addition, the fraction of dust heating attributed to intense radiation fields associated with photo-dissociation regions is found to be (21+/-4)% larger when Herschel data are included in the analysis. Dust masses obtained from the dust emission models of Draine & Li are found to be on average nearly a factor of two higher than those based on single-temperature modified blackbodies, as single blackbody curves do not capture the full range of dust temperatures inherent to any galaxy. The discrepancy is largest for galaxies exhibiting the coolest far-infrared colors.Comment: Accepted for publication in Ap