Joel Wm. Parker

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.

A new spectral classification system for the earliest O stars: Definition of type O2

High-quality, blue-violet spectroscopic data are collected for 24 stars that have been classified as type O3 and that display the hallmark N IV and N V lines. A new member of the class is presented; it is the second known in the Cyg OB2 association, and only the second in the northern hemisphere. New digital data are also presented for several of the other stars. Although the data are inhomogeneous, the uniform plots by subcategory reveal some interesting new relationships. Several issues concerning the classification of the hottest O-type spectra are discussed, and new digital data are presented for the five original O3 dwarfs in the Carina Nebula, in which the N IV, N V features are very weak or absent. New spectral types O2 and O3.5 are introduced here as steps toward resolving these issues. The relationship between the derived absolute visual magnitudes and the spectroscopic luminosity classes of the O2–O3 stars shows more scatter than at later O types, at least partly because some overluminous dwarfs are unresolved multiple systems, and some close binary systems of relatively low luminosity and mass emulate O3 supergiant spectra. However, it also appears that the behavior of He II λ4686, the primary luminosity criterion at later O types, responds to other phenomena in addition to luminosity at spectral types O2–O3. There is evidence that these spectral types may correspond to an immediate pre-WN phase, with a correspondingly large range of luminosities and masses. A complete census of spectra classified into the original O3 subcategories considered here (not including intermediate O3/WN types or O3 dwarfs without N IV, N V features) totals 45 stars; 34 of them belong to the Large Magellanic Cloud and 20 of the latter to 30 Doradus.

The stellar content of NGC 346 - A plethora of O stars in the SMC

The stellar content of NGC 346, the largest and brightest H II region in the SMC, was investigated using the results of CCD UBV photometry and spectroscopy. Spectra of 42 blue stars were classified, showing that 33 are of the O type, of which 11 are of type O6.5 or earlier, which is as many early-type O stars known in the rest of the SMC. The results identify 25-30 NGC 346 stars more massive than 25 solar masses, and six stars more massive than 40 solar masses, indicating that the upper-mass cutoff to the IMF is not lower in the SMC than in the Galaxy or the LMC. The presence of evolved 15 solar-mass stars in the NGC 346 indicates that some massive stars formed 15 million yr ago. The results of spatial distribution suggest that star formation began at the southwest side of the association and has spread to where the central cluster lies now, providing an example of sequential star formation in the SMC. 69 refs.

The atmosphere of Pluto as observed by New Horizons

New Horizons unveils the Pluto system In July 2015, the New Horizons spacecraft flew through the Pluto system at high speed, humanitys first close look at this enigmatic system on the outskirts of our solar system. In a series of papers, the New Horizons team present their analysis of the encounter data downloaded so far: Moore et al. present the complex surface features and geology of Pluto and its large moon Charon, including evidence of tectonics, glacial flow, and possible cryovolcanoes. Grundy et al. analyzed the colors and chemical compositions of their surfaces, with ices of H2O, CH4, CO, N2, and NH3 and a reddish material which may be tholins. Gladstone et al. investigated the atmosphere of Pluto, which is colder and more compact than expected and hosts numerous extensive layers of haze. Weaver et al. examined the small moons Styx, Nix, Kerberos, and Hydra, which are irregularly shaped, fast-rotating, and have bright surfaces. Bagenal et al. report how Pluto modifies its space environment, including interactions with the solar wind and a lack of dust in the system. Together, these findings massively increase our understanding of the bodies in the outer solar system. They will underpin the analysis of New Horizons data, which will continue for years to come. Science, this issue pp. 1284, 10.1126/science.aad9189, 10.1126/science.aad8866, 10.1126/science.aae0030, & 10.1126/science.aad9045 Pluto’s atmosphere is cold, rarefied, and made mostly of nitrogen and methane, with layers of haze. INTRODUCTION For several decades, telescopic observations have shown that Pluto has a complex and intriguing atmosphere. But too little has been known to allow a complete understanding of its global structure and evolution. Major goals of the New Horizons mission included the characterization of the structure and composition of Pluto’s atmosphere, as well as its escape rate, and to determine whether Charon has a measurable atmosphere. RATIONALE The New Horizons spacecraft included several instruments that observed Pluto’s atmosphere, primarily (i) the Radio Experiment (REX) instrument, which produced near-surface pressure and temperature profiles; (ii) the Alice ultraviolet spectrograph, which gave information on atmospheric composition; and (iii) the Long Range Reconnaissance Imager (LORRI) and Multispectral Visible Imaging Camera (MVIC), which provided images of Pluto’s hazes. Together, these instruments have provided data that allow an understanding of the current state of Pluto’s atmosphere and its evolution. RESULTS The REX radio occultation determined Pluto’s surface pressure and found a strong temperature inversion, both of which are generally consistent with atmospheric profiles retrieved from Earth-based stellar occultation measurements. The REX data showed near-symmetry between the structure at ingress and egress, as expected from sublimation driven dynamics, so horizontal winds are expected to be weak. The shallow near-surface boundary layer observed at ingress may arise directly from sublimation. The Alice solar occultation showed absorption by methane and nitrogen and revealed the presence of the photochemical products acetylene and ethylene. The observed nitrogen opacity at high altitudes was lower than expected, which is consistent with a cold upper atmosphere. Such low temperatures imply an additional, but as yet unidentified, cooling agent. A globally extensive haze extending to high altitudes, and with numerous embedded thin layers, is seen in the New Horizons images. The haze has a bluish color, suggesting a composition of very small particles. The observed scattering properties of the haze are consistent with a tholin-like composition. Buoyancy waves generated by winds flowing over orography can produce vertically propagating compression and rarefaction waves that may be related to the narrow haze layers. Pluto’s cold upper atmosphere means atmospheric escape must occur via slow thermal Jeans’ escape. The inferred escape rate of nitrogen is ~10,000 times slower than predicted, whereas that of methane is about the same as predicted. The low nitrogen loss rate is consistent with an undetected Charon atmosphere but possibly inconsistent with sublimation/erosional features seen on Pluto’s surface, so that past escape rates may have been much larger at times. Capture of escaping methane and photochemical products by Charon, and subsequent surface chemical reactions, may contribute to the reddish color of its north pole. CONCLUSION New Horizons observations have revolutionized our understanding of Pluto’s atmosphere. The observations revealed major surprises, such as the unexpectedly cold upper atmosphere and the globally extensive haze layers. The cold upper atmosphere implies much lower escape rates of volatiles from Pluto than predicted and so has important implications for the volatile recycling and the long-term evolution of Pluto’s atmosphere. MVIC image of haze layers above Pluto’s limb. About 20 haze layers are seen from a phase angle of 147°. The layers typically extend horizontally over hundreds of kilometers but are not exactly horizontal. For example, white arrows on the left indicate a layer ~5 km above the surface, which has descended to the surface at the right. Observations made during the New Horizons flyby provide a detailed snapshot of the current state of Pluto’s atmosphere. Whereas the lower atmosphere (at altitudes of less than 200 kilometers) is consistent with ground-based stellar occultations, the upper atmosphere is much colder and more compact than indicated by pre-encounter models. Molecular nitrogen (N2) dominates the atmosphere (at altitudes of less than 1800 kilometers or so), whereas methane (CH4), acetylene (C2H2), ethylene (C2H4), and ethane (C2H6) are abundant minor species and likely feed the production of an extensive haze that encompasses Pluto. The cold upper atmosphere shuts off the anticipated enhanced-Jeans, hydrodynamic-like escape of Pluto’s atmosphere to space. It is unclear whether the current state of Pluto’s atmosphere is representative of its average state—over seasonal or geologic time scales.

LRO-LAMP observations of the LCROSS impact plume.

Watering the Moon About a year ago, a spent upper stage of an Atlas rocket was deliberately crashed into a crater at the south pole of the Moon, ejecting a plume of debris, dust, and vapor. The goal of this event, the Lunar Crater Observation and Sensing Satellite (LCROSS) experiment, was to search for water and other volatiles in the soil of one of the coldest places on the Moon: the permanently shadowed region within the Cabeus crater. Using ultraviolet, visible, and near-infrared spectroscopy data from accompanying craft, Colaprete et al. (p. 463; see the news story by Kerr; see the cover) found evidence for the presence of water and other volatiles within the ejecta cloud. Schultz et al. (p. 468) monitored the different stages of the impact and the resulting plume. Gladstone et al. (p. 472), using an ultraviolet spectrograph onboard the Lunar Reconnaissance Orbiter (LRO), detected H2, CO, Ca, Hg, and Mg in the impact plume, and Hayne et al. (p. 477) measured the thermal signature of the impact and discovered that it had heated a 30 to 200 square-meter region from ∼40 kelvin to at least 950 kelvin. Paige et al. (p. 479) mapped cryogenic zones predictive of volatile entrapment, and Mitrofanov et al. (p. 483) used LRO instruments to confirm that surface temperatures in the south polar region persist even in sunlight. In all, about 155 kilograms of water vapor was emitted during the impact; meanwhile, the LRO continues to orbit the Moon, sending back a stream of data to help us understand the evolution of its complex surface structures. A controlled spacecraft impact into a crater in the lunar south pole plunged through the lunar soil, revealing water and other volatiles. On 9 October 2009, the Lunar Crater Observation and Sensing Satellite (LCROSS) sent a kinetic impactor to strike Cabeus crater, on a mission to search for water ice and other volatiles expected to be trapped in lunar polar soils. The Lyman Alpha Mapping Project (LAMP) ultraviolet spectrograph onboard the Lunar Reconnaissance Orbiter (LRO) observed the plume generated by the LCROSS impact as far-ultraviolet emissions from the fluorescence of sunlight by molecular hydrogen and carbon monoxide, plus resonantly scattered sunlight from atomic mercury, with contributions from calcium and magnesium. The observed light curve is well simulated by the expansion of a vapor cloud at a temperature of ~1000 kelvin, containing ~570 kilograms (kg) of carbon monoxide, ~140 kg of molecular hydrogen, ~160 kg of calcium, ~120 kg of mercury, and ~40 kg of magnesium.

The Ultraviolet and Optical Spectra of Metal‐deficient O Stars in the Small Magellanic Cloud1

ABSTRACT An ultraviolet and optical spectral atlas of 15 O stars in the Small Magellanic Cloud (SMC) is presented and described. The echelle data have resolving powers of order 104; they were obtained with the Hubble Space Telescope Space Telescope Imaging Spectrograph in the UV, and at the Anglo‐Australian Telescope or the European Southern Observatory 3.6 m in the optical. The ultimate objective is to develop metal‐deficient templates for the interpretation of distant starbursts, but here we discuss interesting new properties of the SMC stars themselves, revealed by the high quality of these data. The SMC metal deficiency produces anomalously weak stellar‐wind profiles along the entire O main sequence, as well as at intermediate luminosities; the first intermediate Si iv λ1400 wind profile in the SMC is shown. The second known Of star in the SMC displays wind peculiarities that are identical to those of its spectral classmate, again likely due to the low systemic metallicity. Several objects display mar...

The stellar content of LH 9 and 10 (N11) in the LMC - A case for sequential star formation

The young OB associations Lucke-Hodge 9 and 10 are studied with UBV photometry that is independent of reddening to determine the IMF directly from star counts. The temperature and reddening of the stars are determined which, in conjunction with the spectroscopic classification of the earliest stars, is employed to place the stellar groups on the theoretical H-R diagram. Observations are also presented of the highly compact H II region/knot N11A and the multiple system HD 32228, and LH 9 and 10 are compared. The Lyman ionizing flux calculated at 4.9-7.2 x 10 exp 50/s agrees well with flux required to generate the H-alpha luminosity of the H II region. LH 10 has a much flatter slope, a higher ratio of higher-mass to lower-mass stars, and greater reddening than LH 9, and LH 10 contains all of the O stars earlier than O6. It is concluded that LH 9 is older than LH 10 and probably contributed to the initiation of star formation in LH 10.

Two-stage starbursts in the Large Magellanic Cloud : N11 as a once and future 30 Doradus

A recent, detailed study of the stellar content in the LMC giant shell H II region N11 has revealed a distinct, dual structural morphology, which is remarkably analogous to that emerging from current IR imaging of 30 Doradus. In both regions, the energetic stellar activity from an initial, massive, centrally condensed starburst has apparently triggered a secondary burst around its periphery about 2 × 10 6 years later, but in N11 the entire process is more advanced than in 30 Dor by 2 × 10 6 years. That is, N11 appears to be an evolved 30 Dor

The binary Kuiper-belt object 1998 WW31

The recent discovery of a binary asteroid during a spacecraft fly-by generated keen interest, because the orbital parameters of binaries can provide measures of the masses, and mutual eclipses could allow us to determine individual sizes and bulk densities. Several binary near-Earth, main-belt and Trojan asteroids have subsequently been discovered. The Kuiper belt—the region of space extending from Neptune (at 30 astronomical units) to well over 100 AU and believed to be the source of new short-period comets—has become a fascinating new window onto the formation of our Solar System since the first member object, not counting Pluto, was discovered in 1992 (ref. 13). Here we report that the Kuiper-belt object 1998 WW31 is binary with a highly eccentric orbit (eccentricity e ≈ 0.8) and a long period (about 570 days), very different from the Pluto/Charon system, which was hitherto the only previously known binary in the Kuiper belt. Assuming a density in the range of 1 to 2 g cm-3, the albedo of the binary components is between 0.05 and 0.08, close to the value of 0.04 generally assumed for Kuiper-belt objects.

The OB associations of 30 Doradus in the Large Magellanic Cloud. I - Stellar observations and data reductions

UBV photometry is presented for 2400 stars in the OB associations of 30 Doradus in the Large Magellanic Cloud, and I discuss new spectroscopic observations of 54 stars including 24 O stars. The CCD fields cover an area of 50 square arcminutes in the central region. The entire catalog (exclusive of the dense core cluster R 136) is photometrically complete to V = B = 18 mag and U = 17 mag, although the completeness magnitudes are fainter for regions with less nebular contamination.