A Herschel study of NGC 650

As part of the Herschel guaranteed time key project Mass loss of Evolved StarS (MESS) we have imaged a sample of planetary nebulae. In this paper we present the Photodetector Array Camera and Spectrometer (PACS) and Spectral and Photometric Imaging Receiver (SPIRE) images of the classical bipolar planetary nebula NGC 650. We used these images to derive a temperature map of the dust. We also constructed a photoionization and dust radiative transfer model using the spectral synthesis code Cloudy. To constrain this model, we used the PACS and SPIRE fluxes and combined them with hitherto unpublished International Ultraviolet Explorer (IUE) and Spitzer InfraRed Spectrograph (IRS) spectra as well as various other data from the literature. A temperature map combined with a photoionization model were used to study various aspects of the central star, the nebula, and in particular the dust grains in the nebula. The central star parameters are determined to be Teff = 208 kK and L = 261 L⊙ assuming a distance of 1200 pc. The stellar temperature is much higher than previously published values. We confirm that the nebula is carbon-rich with a C/O ratio of 2.1. The nebular abundances are typical for a type IIa planetary nebula. With the photoionization model we determined that the grains in the ionized nebula are large (assuming single-sized grains, they would have a radius of 0.15 μm). Most likely these large grains were inherited from the asymptotic giant branch phase. The PACS 70/160 μm temperature map shows evidence of two radiation components heating the grains. The first component is direct emission from the central star, while the second component is diffuse emission from the ionized gas (mainly Lyα). We show that previous suggestions of a photo-dissociation region surrounding the ionized region are incorrect. The neutral material resides in dense clumps inside the ionized region. These may also harbor stochastically heated very small grains in addition to the large grains

Herschel imaging of the dust in the Helix nebula (NGC 7293)

Aims. In our series of papers presenting the Herschel imaging of evolved planetary nebulae, we present images of the dust distribution in the Helix nebula (NGC 7293). / Methods. Images at 70, 160, 250, 350, and 500 μm were obtained with the PACS and SPIRE instruments on board the Herschel satellite. / Results. The broadband maps show the dust distribution over the main Helix nebula to be clumpy and predominantly present in the barrel wall. We determined the spectral energy distribution of the main nebula in a consistent way using Herschel, IRAS, and Planck flux values. The emissivity index of β = 0.99 ± 0.09, in combination with the carbon rich molecular chemistry of the nebula, indicates that the dust consists mainly of amorphous carbon. The dust excess emission from the central star disk is detected at 70 μm and the flux measurement agrees with previous measurement. We present the temperature and dust column density maps. The total dust mass across the Helix nebula (without its halo) is determined to be 3.5 × 10-3 M⊙ at a distance of 216 pc. The temperature map shows dust temperatures between 22 K and 42 K, which is similar to the kinetic temperature of the molecular gas, confirming that the dust and gas co-exist in high density clumps. Archived images are used to compare the location of the dust emission in the far infrared (Herschel) with the ionized (GALEX and Hβ) and molecular (H2) component. The different emission components are consistent with the Helix consisting of a thick walled barrel-like structure inclined to the line of sight. The radiation field decreases rapidly through the barrel wall

Herschel images of NGC 6720: H-2 formation on dust grains

Herschel PACS and SPIRE images have been obtained of NGC 6720 (the Ring nebula). This is an evolved planetary nebula with a central star that is currently on the cooling track, due to which the outer parts of the nebula are recombining. From the PACS and SPIRE images we conclude that there is a striking resemblance between the dust distribution and the H2 emission, which appears to be observational evidence that H2 forms on grain surfaces. We have developed a photoionization model of the nebula with the Cloudy code which we used to determine the physical conditions of the dust and investigate possible formation scenarios for the H2. We conclude that the most plausible scenario is that the H2 resides in high density knots which were formed after the recombination of the gas started when the central star entered the cooling track. Hydrodynamical instabilities due to the unusually low temperature of the recombining gas are proposed as a mechanism for forming the knots. H2 formation in the knots is expected to be substantial after the central star underwent a strong drop in luminosity about one to two thousand years ago, and may still be ongoing at this moment, depending on the density of the knots and the properties of the grains in the knots

Detection of anhydrous hydrochloric acid, HCl, in IRC+10216 with the Herschel SPIRE and PACS spectrometers Detection of HCI in IRC+10216

We report on the detection of anhydrous hydrochloric acid (hydrogen chlorine, HCl) in the carbon-rich star IRC +10216 using the spectroscopic facilities onboard the Herschel satellite. Lines from J = 1–0 up to J = 7–6 have been detected. From the observed intensities, we conclude that HCl is produced in the innermost layers of the circumstellar envelope with an abundance relative to H2 of 5 × 10-8 and extends until the molecules reach its photodissociation zone. Upper limits to the column densities of AlH, MgH, CaH, CuH, KH, NaH, FeH, and other diatomic hydrides have also been obtained

Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency. RESULTS: We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsible for the germline RAS-opathies. These variants were more frequent in high-flow than low-flow VMs. In vitro characterization and 2 transgenic zebrafish AVM models that recapitulated the human phenotype validated the pathogenesis of the mutant alleles. Importantly, treatment of AVM-BRAF mutant zebrafish with the BRAF inhibitor vemurafinib restored blood flow in AVM. CONCLUSION: Our findings uncover a major cause of sporadic VMs of different clinical types and thereby offer the potential of personalized medical treatment by repurposing existing licensed cancer therapies. FUNDING: This work was funded or supported by grants from the AVM Butterfly Charity, the Wellcome Trust (UK), the Medical Research Council (UK), the UK National Institute for Health Research, the L'Oreal-Melanoma Research Alliance, the European Research Council, and the National Human Genome Research Institute (US)

Challenges to curing primary brain tumours

Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment

The effects of warming on the ecophysiology of two co-existing kelp species with contrasting distributions

The northeast Atlantic has warmed significantly since the early 1980s, leading to shifts in species distributions and changes in the structure and functioning of communities and ecosystems. This study investigated the effects of increased temperature on two co-existing habitat-forming kelps: Laminaria digitata, a northern boreal species, and Laminaria ochroleuca, a southern Lusitanian species, to shed light on mechanisms underpinning responses of trailing and leading edge populations to warming. Kelp sporophytes collected from southwest United Kingdom were maintained under 3 treatments: ambient temperature (12 °C), +3 °C (15 °C) and +6 °C (18 °C) for 16 days. At higher temperatures, L. digitata showed a decline in growth rates and Fv/Fm, an increase in chemical defence production and a decrease in palatability. In contrast, L. ochroleuca demonstrated superior growth and photosynthesis at temperatures higher than current ambient levels, and was more heavily grazed. Whilst the observed decreased palatability of L. digitata held at higher temperatures could reduce top-down pressure on marginal populations, field observations of grazer densities suggest that this may be unimportant within the study system. Overall, our study suggests that shifts in trailing edge populations will be primarily driven by ecophysiological responses to high temperatures experienced during current and predicted thermal maxima, and although compensatory mechanisms may reduce top-down pressure on marginal populations, this is unlikely to be important within the current biogeographical context. Better understanding of the mechanisms underpinning climate-driven range shifts is important for habitat-forming species like kelps, which provide organic matter, create biogenic structure and alter environmental conditions for associated communities

Pathways between Primary Production and Fisheries Yields of Large Marine Ecosystems

The shift in marine resource management from a compartmentalized approach of dealing with resources on a species basis to an approach based on management of spatially defined ecosystems requires an accurate accounting of energy flow. The flow of energy from primary production through the food web will ultimately limit upper trophic-level fishery yields. In this work, we examine the relationship between yield and several metrics including net primary production, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production. We also evaluate the relationship between yield and two additional rate measures that describe the export of energy from the pelagic food web, particle export flux and mesozooplankton productivity. We found primary production is a poor predictor of global fishery yields for a sample of 52 large marine ecosystems. However, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production were positively associated with yields. The latter two measures provide greater mechanistic insight into factors controlling fishery production than chlorophyll concentration alone. Particle export flux and mesozooplankton productivity were also significantly related to yield on a global basis. Collectively, our analyses suggest that factors related to the export of energy from pelagic food webs are critical to defining patterns of fishery yields. Such trophic patterns are associated with temperature and latitude and hence greater yields are associated with colder, high latitude ecosystems

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

Advances in understanding and treating ADHD

Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability