The Herschel view of the on-going star formation in the Vela-C molecular cloud

As part of the Herschel guaranteed time key program 'HOBYS', we present the photometric survey of the star forming region Vela-C, one of the nearest sites of low-to-high-mass star formation in the Galactic plane. Vela-C has been observed with PACS and SPIRE in parallel mode between 70 um and 500 um over an area of about 3 square degrees. A photometric catalogue has been extracted from the detections in each band, using a threshold of 5 sigma over the local background. Out of this catalogue we have selected a robust sub-sample of 268 sources, of which 75% are cloud clumps and 25% are cores. Their Spectral Energy Distributions (SEDs) have been fitted with a modified black body function. We classify 48 sources as protostellar and 218 as starless. For two further sources, we do not provide a secure classification, but suggest they are Class 0 protostars. From SED fitting we have derived key physical parameters. Protostellar sources are in general warmer and more compact than starless sources. Both these evidences can be ascribed to the presence of an internal source(s) of moderate heating, which also causes a temperature gradient and hence a more peaked intensity distribution. Moreover, the reduced dimensions of protostellar sources may indicate that they will not fragment further. A virial analysis of the starless sources gives an upper limit of 90% for the sources gravitationally bound and therefore prestellar. We fit a power law N(logM) prop M^-1.1 to the linear portion of the mass distribution of prestellar sources. This is in between that typical of CO clumps and those of cores in nearby star-forming regions. We interpret this as a result of the inhomogeneity of our sample, which is composed of comparable fractions of clumps and cores.Comment: 9 pages, 7 figures, accepted by A&

The prescribed mean curvature equation in weakly regular domains

We show that the characterization of existence and uniqueness up to vertical translations of solutions to the prescribed mean curvature equation, originally proved by Giusti in the smooth case, holds true for domains satisfying very mild regularity assumptions. Our results apply in particular to the non-parametric solutions of the capillary problem for perfectly wetting fluids in zero gravity. Among the essential tools used in the proofs, we mention a \textit{generalized Gauss-Green theorem} based on the construction of the weak normal trace of a vector field with bounded divergence, in the spirit of classical results due to Anzellotti, and a \textit{weak Young's law} for $(\Lambda,r_{0})$-minimizers of the perimeter.Comment: 23 pages, 1 figure --- The results on the weak normal trace of vector fields have been now extended and moved in a self-contained paper available at: arXiv:1708.0139

<i>Herschel</i> observations of B1-bS and B1-bN: two first hydrostatic core candidates in the Perseus star-forming cloud

We report far-infrared Herschel observations obtained between 70 μm and 500 μm of two star-forming dusty condensations, [HKM99] B1-bS and [HKM99] B1-bN, in the B1 region of the Perseus star-forming cloud. In the western part of the Perseus cloud, B1-bS is the only source detected in all six PACS and SPIRE photometric bands, but it is not visible in the Spitzer map at 24 μm. B1-bN is clearly detected between 100 μm and 250 μm. We have fitted the spectral energy distributions of these sources to derive their physical properties, and find that a simple greybody model fails to reproduce the observed spectral energy distributions. At least a two-component model is required, consisting of a central source surrounded by a dusty envelope. The properties derived from the fit, however, suggest that the central source is not a Class 0 object. We then conclude that while B1-bS and B1-bN appear to be more evolved than a pre-stellar core, the best-fit models suggest that their central objects are younger than a Class 0 source. Hence, they may be good candidates to be examples of the first hydrostatic core phase. The projected distance between B1-bS and B1-bN is a few Jeans lengths. If their physical separation is close to this value, this pair would allow studying the mutual interactions between two forming stars at a very early stage of their evolution

Herschel observations of embedded protostellar clusters in the Rosette Molecular Cloud

The Herschel OB young stellar objects survey (HOBYS) has observed the Rosette molecular cloud, providing an unprecedented view of its star formation activity. These new far-infrared data reveal a population of compact young stellar objects whose physical properties we aim to characterise. We compiled a sample of protostars and their spectral energy distributions that covers the near-infrared to submillimetre wavelength range. These were used to constrain key properties in the protostellar evolution, bolometric luminosity, and envelope mass and to build an evolutionary diagram. Several clusters are distinguished including the cloud centre, the embedded clusters in the vicinity of luminous infrared sources, and the interaction region. The analysed protostellar population in Rosette ranges from 0.1 to about 15 Msun with luminosities between 1 and 150 Lsun, which extends the evolutionary diagram from low-mass protostars into the high-mass regime. Some sources lack counterparts at near- to mid-infrared wavelengths, indicating extreme youth. The central cluster and the Phelps & Lada 7 cluster appear less evolved than the remainder of the analysed protostellar population. For the central cluster, we find indications that about 25% of the protostars classified as Class I from near- to mid-infrared data are actually candidate Class 0 objects. As a showcase for protostellar evolution, we analysed four protostars of low- to intermediate-mass in a single dense core, and they represent different evolutionary stages from Class 0 to Class I. Their mid- to far-infrared spectral slopes flatten towards the Class I stage, and the 160 to 70um flux ratio is greatest for the presumed Class 0 source. This shows that the Herschel observations characterise the earliest stages of protostellar evolution in detail.Comment: Astronomy & Astrophysics letter, 6 pages, 4 figures, accepted for publication in the Special Issue for Herschel first result

final overall survival and other efficacy and safety results from ascend 3 phase ii study of ceritinib in alki naive patients with alk rearranged nsclc

Abstract Introduction The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)–naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results. Methods Eligible patients (including those with asymptomatic or neurologically stable brain metastases) received oral ceritinib (750 mg/day, fasted). The primary end point was investigator-assessed overall response rate (ORR). Secondary end points were Blinded Independent Review Committee–assessed ORR; investigator- and Blinded Independent Review Committee–assessed overall intracranial response rate, duration of response, time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory end points included patient-reported outcomes. Results Of the 124 patients enrolled, 122 (98.4%) had received previous antineoplastic medications (31 patients [25.0%] received at least three regimens), and 49 (39.5%) had baseline brain metastases. The median follow-up time (data cutoff: January 22, 2018) was 52.1 (range, 48.4–60.1) months. The investigator-assessed ORR was 67.7% (95% confidence interval [CI]: 58.8–75.9), and the median PFS was 16.6 months (95% CI: 11.0–23.2). The median OS was 51.3 months (95% CI: 42.7–55.3). Most common adverse events (all grades, ≥60% of patients, all-causality) were diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an adverse event leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment. Conclusions Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies

The International-Trade Network: Gravity Equations and Topological Properties

This paper begins to explore the determinants of the topological properties of the international - trade network (ITN). We fit bilateral-trade flows using a standard gravity equation to build a "residual" ITN where trade-link weights are depurated from geographical distance, size, border effects, trade agreements, and so on. We then compare the topological properties of the original and residual ITNs. We find that the residual ITN displays, unlike the original one, marked signatures of a complex system, and is characterized by a very different topological architecture. Whereas the original ITN is geographically clustered and organized around a few large-sized hubs, the residual ITN displays many small-sized but trade-oriented countries that, independently of their geographical position, either play the role of local hubs or attract large and rich countries in relatively complex trade-interaction patterns

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

MEF2C-MYOCD and Leiomodin1 Suppression by miRNA-214 Promotes Smooth Muscle Cell Phenotype Switching in Pulmonary Arterial Hypertension.

BACKGROUND: Vascular hyperproliferative disorders are characterized by excessive smooth muscle cell (SMC) proliferation leading to vessel remodeling and occlusion. In pulmonary arterial hypertension (PAH), SMC phenotype switching from a terminally differentiated contractile to synthetic state is gaining traction as our understanding of the disease progression improves. While maintenance of SMC contractile phenotype is reportedly orchestrated by a MEF2C-myocardin (MYOCD) interplay, little is known regarding molecular control at this nexus. Moreover, the burgeoning interest in microRNAs (miRs) provides the basis for exploring their modulation of MEF2C-MYOCD signaling, and in turn, a pro-proliferative, synthetic SMC phenotype. We hypothesized that suppression of SMC contractile phenotype in pulmonary hypertension is mediated by miR-214 via repression of the MEF2C-MYOCD-leiomodin1 (LMOD1) signaling axis. METHODS AND RESULTS: In SMCs isolated from a PAH patient cohort and commercially obtained hPASMCs exposed to hypoxia, miR-214 expression was monitored by qRT-PCR. miR-214 was upregulated in PAH- vs. control subject hPASMCs as well as in commercially obtained hPASMCs exposed to hypoxia. These increases in miR-214 were paralleled by MEF2C, MYOCD and SMC contractile protein downregulation. Of these, LMOD1 and MEF2C were directly targeted by the miR. Mir-214 overexpression mimicked the PAH profile, downregulating MEF2C and LMOD1. AntagomiR-214 abrogated hypoxia-induced suppression of the contractile phenotype and its attendant proliferation. Anti-miR-214 also restored PAH-PASMCs to a contractile phenotype seen during vascular homeostasis. CONCLUSIONS: Our findings illustrate a key role for miR-214 in modulation of MEF2C-MYOCD-LMOD1 signaling and suggest that an antagonist of miR-214 could mitigate SMC phenotype changes and proliferation in vascular hyperproliferative disorders including PAH

Reactor-based Neutrino Oscillation Experiments

The status of neutrino oscillation searches employing nuclear reactors as sources is reviewed. This technique, a direct continuation of the experiments that proved the existence of neutrinos, is today an essential tool in investigating the indications of oscillations found in studying neutrinos produced in the sun and in the earth's atmosphere. The low-energy of the reactor \nuebar makes them an ideal tool to explore oscillations with small mass differences and relatively large mixing angles. In the last several years the determination of the reactor anti-neutrino flux and spectrum has reached a high degree of accuracy. Hence measurements of these quantities at a given distance L can be readily compared with the expectation at L = 0, thus testing \nuebar disappearance. While two experiments, Chooz and Palo Verde, with baselines of about 1 km and thus sensitive to the neutrino mass differences associated with the atmospheric neutrino anomaly, have collected data and published results recently, an ambitious project with a baseline of more than 100 km, Kamland, is preparing to take data. This ultimate reactor experiment will have a sensitivity sufficient to explore part of the oscillation phase space relevant to solar neutrino scenarios. It is the only envisioned experiment with a terrestrial source of neutrinos capable of addressing the solar neutrino puzzle.Comment: Submitted to Reviews of Modern Physics 34 pages, 39 figure

A <i>Herschel</i> and BIMA study of the sequential star formation near the W 48A H II region

We present the results of Herschel HOBYS (Herschel imaging survey of OB Young Stellar objects) photometric mapping combined with Berkeley Illinois Maryland Association (BIMA) observations and additional archival data, and perform an in-depth study of the evolutionary phases of the star-forming clumps in W 48A and their surroundings. Age estimates for the compact sources were derived from bolometric luminosities and envelope masses, which were obtained from the dust continuum emission, and agree within an order of magnitude with age estimates from molecular line and radio data. The clumps in W 48A are linearly aligned by age (east-old to west-young): we find a ultra-compact (UC) H II region, a young stellar object (YSO) with class II methanol maser emission, a YSO with a massive outflow and finally the NH2D prestellar cores from Pillai et al. This remarkable positioning reflects the (star) formation history of the region. We find that it is unlikely that the star formation in the W 48A molecular cloud was triggered by the UC H II region and discuss the Aquila supershell expansion as a major influence on the evolution of W 48A. We conclude that the combination of Herschel continuum data with interferometric molecular line and radio continuum data is important to derive trustworthy age estimates and interpret the origin of large-scale structures through kinematic information