A multiwavelength study on the high-energy behaviour of Fermi/LAT pulsars

Using archival as well as freshly acquired data, we assess the X-ray behaviour of the Fermi/LAT gamma-ray pulsars listed in the First Fermi source catalog. After revisiting the relationships between the pulsars' rotational energy losses and their X and gamma-ray luminosities, we focus on the distance-indipendent gamma to X-ray flux ratios. When plotting our Fgamma/Fx values as a function of the pulsars' rotational energy losses, one immediately sees that pulsars with similar energetics have Fgamma/Fx spanning 3 decades. Such spread, most probably stemming from vastly different geometrical configurations of the X and gamma-ray emitting regions, defies any straightforward interpretation of the plot. Indeed, while energetic pulsars do have low Fgamma/Fx values, little can be said for the bulk of the Fermi neutron stars. Dividing our pulsar sample into radio-loud and radio-quiet subsamples, we find that, on average, radio-quiet pulsars do have higher values of Fgamma/Fx, implying an intrinsec faintness of their X-ray emission and/or a different geometrical configuration. Moreover, despite the large spread mentioned above, statistical tests show a lower scatter in the radio-quiet dataset with respect to the radio-loud one, pointing to a somewhat more constrained geometry for the radio-quiet objects with respect to the radio-loud ones.Comment: 39 pages, 5 figures, 3 tables. To be published in Astrophysical Journa

Radar sounder evidence of thick, porous sediments in Meridiani Planum and implications for ice‐filled deposits on Mars

Meridiani Planum is one of the most intensely studied regions on Mars, yet little is known about the physical properties of the deposits below those examined by the Opportunity rover. We report the detection of subsurface echoes within the Meridiani Planum deposits from data obtained by the Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) instrument. The delay time between the surface and subsurface returns is indicative of materials with a real dielectric constant of 3.6 ± 0.6. The real dielectric constant is strongly modulated by bulk density. Newly derived compaction relationships for Mars indicate that the relatively low dielectric constant of the Meridiani Planum deposits is consistent with a thick layer of ice‐free, porous, basaltic sand. The unique physiographic and hydrologic setting of Meridiani Planum may have provided an ideal sediment trap for eolian sands. The relatively low gravity and the cold, dry climate that has dominated Mars for billions of years may have allowed thick eolian sand deposits to remain porous and only weakly indurated. Minimally compacted sedimentary deposits may offer a possible explanation for other nonpolar region units with low apparent bulk dielectric constants

MARSIS Subsurface Radar Sounding of Medusae Fossae Formation Deposits on Mars: Ice Rich or Ice Poor, That is the Question

Newly acquired MARSIS radar sounder data shows evidence of layering in all major units of the MFF deposits, establishing another key similarity to PLD

Good practice in health care for migrants: views and experiences of care professionals in 16 European countries

<p>Abstract</p> <p>Background</p> <p>Health services across Europe provide health care for migrant patients every day. However, little systematic research has explored the views and experiences of health care professionals in different European countries. The aim of this study was to assess the difficulties professionals experience in their service when providing such care and what they consider constitutes good practice to overcome these problems or limit their negative impact on the quality of care.</p> <p>Methods</p> <p>Structured interviews with open questions and case vignettes were conducted with health care professionals working in areas with high proportion of migrant populations in 16 countries. In each country, professionals in nine primary care practices, three accident and emergency hospital departments, and three community mental health services (total sample = 240) were interviewed about their views and experiences in providing care for migrant patients, i.e. from first generation immigrant populations. Answers were analysed using thematic content analysis.</p> <p>Results</p> <p>Eight types of problems and seven components of good practice were identified representing all statements in the interviews. The eight problems were: language barriers, difficulties in arranging care for migrants without health care coverage, social deprivation and traumatic experiences, lack of familiarity with the health care system, cultural differences, different understandings of illness and treatment, negative attitudes among staff and patients, and lack of access to medical history. The components of good practice to overcome these problems or limit their impact were: organisational flexibility with sufficient time and resources, good interpreting services, working with families and social services, cultural awareness of staff, educational programmes and information material for migrants, positive and stable relationships with staff, and clear guidelines on the care entitlements of different migrant groups. Problems and good care components were similar across the three types of services.</p> <p>Conclusions</p> <p>Health care professionals in different services experience similar difficulties when providing care to migrants. They also have relatively consistent views on what constitutes good practice. The degree to which these components already are part of routine practice varies. Implementing good practice requires sufficient resources and organisational flexibility, positive attitudes, training for staff and the provision of information.</p

Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) after nine years of operation: A summary

Mars Express, the first European interplanetary mission, carries the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) to search for ice and water in the Martian subsurface. Developed by an Italian-US team, MARSIS transmits low-frequency, wide-band radio pulses penetrating below the surface and reflected by dielectric discontinuities linked to structural or compositional changes. MARSIS is also a topside ionosphere sounder, transmitting a burst of short, narrow-band pulses at different frequencies that are reflected by plasma with varying densities at different altitudes. The radar operates since July 2005, after the successful deployment of its 40 m antenna, acquiring data at altitudes lower than 1200 km. Subsurface sounding (SS) data are processed on board by stacking together a batch of echoes acquired at the same frequency. On ground, SS data are further processed by correlating the received echo with the transmitted waveform and compensating de-focusing caused by the dispersive ionosphere. Ground processing of active ionospheric sounding (AIS) data consists in the reconstruction of the electron density profile as a function of altitude. MARSIS observed the internal structure of Planum Boreum outlining the Basal Unit, an icy deposit lying beneath the North Polar Layered Deposits thought to have formed in an epoch in which climate was markedly different from the current one. The total volume of ice in polar layered deposits could be estimated, and parts of the Southern residual ice cap were revealed to consist of ≈ 10 m of CO2 ice. Radar properties of the Vastitas Borealis Formation point to the presence of large quantities of ice buried beneath the surface. Observations of the ionosphere revealed the complex interplay between plasma, crustal magnetic field and solar wind, contributing to space weather studies at Mars. The presence of three-dimensional plasma structures in the ionosphere was revealed for the first time. MARSIS could successfully operate at Phobos, becoming the first instrument of its kind to observe an asteroid-like body. The main goal pursued by MARSIS, the search for liquid water beneath the surface, remains elusive. However, because of the many factors affecting detection and of the difficulties in identifying water in radar echoes, a definitive conclusion on its presence cannot yet be drawn

Signals from the Metastatic Niche Regulate Early and Advanced Ovarian Cancer Metastasis through miR-4454 Downregulation

Treatment of ovarian cancer is limited by extensive metastasis and yet it remains poorly understood. We have studied the critical step of metastatic colonization in the context of the productive interactions with the metastatic microenvironment with a goal of identifying key regulators. By combining miRNA expression analysis using an organotypic 3D culture model of early ovarian cancer metastasis with that of matched primary and metastatic tumors from 42 patients with ovarian cancer, we identified miR-4454 as a key regulator of both early colonization and advanced metastasis in patients with ovarian cancer. miR-4454 was downregulated in the metastasizing ovarian cancer cells through paracrine signals from microenvironmental fibroblasts, which promoted migration, invasion, proliferation, and clonogenic growth in ovarian cancer cells as well as their ability to penetrate through the outer layers of the omentum. Stable overexpression of miR-4454 decreased metastasis in ovarian cancer xenografts. Its mechanism of action was through the upregulation of its targets, secreted protein acidic and cysteine rich (SPARC) and BCL2 associated athanogene 5 (BAG5), which activated focal adhesion kinase (FAK) signaling, promoted mutant p53 gain of function by its stabilization, and inhibited apoptosis. Because microenvironment-induced downregulation of miR-4454 is essential for early and advanced metastasis, targeting it could be a promising therapeutic approach

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups

Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

We report the detection of pulsed γ-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their γ-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the γ-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the γ-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the γ-ray light curves with high-energy beam models

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery