20 research outputs found

    Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS): following the water trail from the interstellar medium to oceans

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    Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS) is a space-based, MIDEX-class mission concept that employs a 17-meter diameter inflatable aperture with cryogenic heterodyne receivers, enabling high sensitivity and high spectral resolution (resolving power ≥106) observations at terahertz frequencies. OASIS science is targeting submillimeter and far-infrared transitions of H2O and its isotopologues, as well as deuterated molecular hydrogen (HD) and other molecular species from 660 to 80 μm, which are inaccessible to ground-based telescopes due to the opacity of Earth’s atmosphere. OASIS will have <20x the collecting area and ~5x the angular resolution of Herschel, and it complements the shorter wavelength capabilities of the James Webb Space Telescope. With its large collecting area and suite of terahertz heterodyne receivers, OASIS will have the sensitivity to follow the water trail from galaxies to oceans, as well as directly measure gas mass in a wide variety of astrophysical objects from observations of the ground-state HD line. OASIS will operate in a Sun-Earth L1 halo orbit that enables observations of large numbers of galaxies, protoplanetary systems, and solar system objects during the course of its 1-year baseline mission. OASIS embraces an overarching science theme of “following water from galaxies, through protostellar systems, to oceans.” This theme resonates with the NASA Astrophysics Roadmap and the 2010 Astrophysics Decadal Survey, and it is also highly complementary to the proposed Origins Space Telescope’s objectives

    Induction of interleukin-8 preserves the angiogenic response in HIF-1 alpha-deficient colon cancer cells

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    authorHypoxia inducible factor-1 (HIF-1) is considered a crucial mediator of the cellular response to hypoxia through its regulation of genes that control angiogenesis^1, ^2, ^3, ^4. It represents an attractive therapeutic target^5, ^6 in colon cancer, one of the few tumor types that shows a clinical response to antiangiogenic therapy^7. But it is unclear whether inhibition of HIF-1 alone is sufficient to block tumor angiogenesis^8, ^9. In HIF-1_α knockdown DLD-1 colon cancer cells (DLD-1^HIF-kd), the hypoxic induction of vascular endothelial growth factor (VEGF) was only partially blocked. Xenografts remained highly vascularized with microvessel densities identical to DLD-1 tumors that had wild-type HIF-1_α (DLD-1^HIF-wt). In addition to the preserved expression of VEGF, the proangiogenic cytokine interleukin (IL)-8 was induced by hypoxia in DLD-1^HIF-kd but not DLD-1^HIF-wt cells. This induction was mediated by the production of hydrogen peroxide and subsequent activation of NF-_KB. Furthermore, the KRAS oncogene, which is commonly mutated in colon cancer, enhanced the hypoxic induction of IL-8. A neutralizing antibody to IL-8 substantially inhibited angiogenesis and tumor growth in DLD-1^HIF-kd but not DLD-1^HIF-wt xenografts, verifying the functional significance of this IL-8 response. Thus, compensatory pathways can be activated to preserve the tumor angiogenic response, and strategies that inhibit HIF-1α may be most effective when IL-8 is simultaneously targeted
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