We present near-UV transmission spectroscopy of the highly irradiated transiting exoplanet WASP-12b, obtained with the Cosmic Origins Spectrograph on the Hubble Space Telescope. The spectra cover ...three distinct wavelength ranges: NUVA (2539-2580 A), NUVB (2655-2696 A), and NUVC (2770-2811 A). Three independent methods all reveal enhanced transit depths attributable to absorption by resonance lines of metals in the exosphere of WASP-12b. Light curves of total counts in the NUVA and NUVC wavelength ranges show a detection at a 2.5{sigma} level. We detect extra absorption in the Mg II {lambda}{lambda}2800 resonance line cores at the 2.8{sigma} level. The NUVA, NUVB, and NUVC light curves imply effective radii of 2.69 {+-} 0.24 R {sub J}, 2.18 {+-} 0.18 R {sub J}, and 2.66 {+-} 0.22 R {sub J} respectively, suggesting the planet is surrounded by an absorbing cloud which overfills the Roche lobe. We detect enhanced transit depths at the wavelengths of resonance lines of neutral sodium, tin, and manganese, and at singly ionized ytterbium, scandium, manganese, aluminum, vanadium, and magnesium. We also find the statistically expected number of anomalous transit depths at wavelengths not associated with any known resonance line. Our data are limited by photon noise, but taken as a whole the results are strong evidence for an extended absorbing exosphere surrounding the planet. The NUVA data exhibit an early ingress, contrary to model expectations; we speculate this could be due to the presence of a disk of previously stripped material.
NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and ...maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
Abstract
The time-variable velocity fields of solar-type stars limit the precision of radial-velocity determinations of their planets’ masses, obstructing detection of Earth twins. Since 2015 July, ...we have been monitoring disc-integrated sunlight in daytime using a purpose-built solar telescope and fibre feed to the HARPS-N stellar radial-velocity spectrometer. We present and analyse the solar radial-velocity measurements and cross-correlation function (CCF) parameters obtained in the first 3 yr of observation, interpreting them in the context of spatially resolved solar observations. We describe a Bayesian mixture-model approach to automated data-quality monitoring. We provide dynamical and daily differential-extinction corrections to place the radial velocities in the heliocentric reference frame, and the CCF shape parameters in the sidereal frame. We achieve a photon-noise-limited radial-velocity precision better than 0.43 m s−1 per 5-min observation. The day-to-day precision is limited by zero-point calibration uncertainty with an RMS scatter of about 0.4 m s−1. We find significant signals from granulation and solar activity. Within a day, granulation noise dominates, with an amplitude of about 0.4 m s−1 and an autocorrelation half-life of 15 min. On longer time-scales, activity dominates. Sunspot groups broaden the CCF as they cross the solar disc. Facular regions temporarily reduce the intrinsic asymmetry of the CCF. The radial-velocity increase that accompanies an active-region passage has a typical amplitude of 5 m s−1 and is correlated with the line asymmetry, but leads it by 3 d. Spectral line-shape variability thus shows promise as a proxy for recovering the true radial velocity.
Extended gas clouds have been previously detected surrounding the brightest known close-in transiting hot Jupiter exoplanets, HD 209458 b and HD 189733 b; we observed the distant but more extreme ...close-in hot Jupiter system, WASP-12, with Hubble Space Telescope (HST). Near-UV (NUV) transits up to three times deeper than the optical transit of WASP-12 b reveal extensive diffuse gas, extending well beyond the Roche lobe. Our spectra reveal significantly enhanced absorption (greater than 3sigma below the median) at ~200 individual wavelengths on each of two HST visits; 65 of these wavelengths are consistent between the two visits, using a strict criterion for velocity matching that excludes matches with velocity shifts exceeding ~20 km s super(-1). Our Visit 2 NUV light curves show evidence for a stellar flare. We show that some of the possible transit detections in resonance lines of rare elements may be due instead to non-resonant transitions in common species. We present optical observations and update the transit ephemeris.
Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital ...to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
HD 189733 is a K2 dwarf, orbited by a giant planet at 8.8 stellar radii. In order to study magnetospheric interactions between the star and the planet, we explore the large-scale magnetic field and ...activity of the host star. We collected spectra using the ESPaDOnS and the NARVAL spectropolarimeters, installed at the 3.6-m Canada–France–Hawaii telescope and the 2-m Telescope Bernard Lyot at Pic du Midi, during two monitoring campaigns (2007 June and 2008 July). HD 189733 has a mainly toroidal surface magnetic field, having a strength that reaches up to 40 G. The star is differentially rotating, with latitudinal angular velocity shear of dΩ= 0.146 ± 0.049 rad d−1, corresponding to equatorial and polar periods of 11.94 ± 0.16 d and 16.53 ± 2.43 d, respectively. The study of the stellar activity shows that it is modulated mainly by the stellar rotation (rather than by the orbital period or the beat period between the stellar rotation and the orbital periods). We report no clear evidence of magnetospheric interactions between the star and the planet. We also extrapolated the field in the stellar corona and calculated the planetary radio emission expected for HD 189733b, given the reconstructed field topology. The radio flux we predict in the framework of this model is time variable and potentially detectable with LOFAR.
ABSTRACT
Based on HARPS-N radial velocities (RVs) and TESS photometry, we present a full characterization of the planetary system orbiting the late G dwarf TOI-561. After the identification of three ...transiting candidates by TESS, we discovered two additional external planets from RV analysis. RVs cannot confirm the outer TESS transiting candidate, which would also make the system dynamically unstable. We demonstrate that the two transits initially associated with this candidate are instead due to single transits of the two planets discovered using RVs. The four planets orbiting TOI-561 include an ultra-short period (USP) super-Earth (TOI-561 b) with period Pb = 0.45 d, mass Mb = 1.59 ± 0.36 M⊕ and radius Rb = 1.42 ± 0.07 R⊕, and three mini-Neptunes: TOI-561 c, with Pc = 10.78 d, Mc = 5.40 ± 0.98 M⊕, Rc = 2.88 ± 0.09 R⊕; TOI-561 d, with Pd = 25.6 d, Md = 11.9 ± 1.3 M⊕, Rd = 2.53 ± 0.13 R⊕; and TOI-561 e, with Pe = 77.2 d, Me = 16.0 ± 2.3 M⊕, Re = 2.67 ± 0.11 R⊕. Having a density of 3.0 ± 0.8 g cm−3, TOI-561 b is the lowest density USP planet known to date. Our N-body simulations confirm the stability of the system and predict a strong, anti-correlated, long-term transit time variation signal between planets d and e. The unusual density of the inner super-Earth and the dynamical interactions between the outer planets make TOI-561 an interesting follow-up target.
A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that ...voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creER
; Lepr
mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.
Access to healthcare is a requirement for human well-being that is constrained, in part, by the allocation of healthcare resources relative to the geographically dispersed human population
. ...Quantifying access to care globally is challenging due to the absence of a comprehensive database of healthcare facilities. We harness major data collection efforts underway by OpenStreetMap, Google Maps and academic researchers to compile the most complete collection of facility locations to date. Leveraging the geographically variable strengths of our facility datasets, we use an established methodology
to characterize travel time to healthcare facilities in unprecedented detail. We produce maps of travel time with and without access to motorized transport, thus characterizing travel time to healthcare for populations distributed across the wealth spectrum. We find that just 8.9% of the global population (646 million people) cannot reach healthcare within one hour if they have access to motorized transport, and that 43.3% (3.16 billion people) cannot reach a healthcare facility by foot within one hour. Our maps highlight an additional vulnerability faced by poorer individuals in remote areas and can help to estimate whether individuals will seek healthcare when it is needed, as well as providing an evidence base for efficiently distributing limited healthcare and transportation resources to underserved populations both now and in the future.
Epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas, with direct or indirect activation of EGFR able to trigger tumour growth. We demonstrate significant activation of both ...signal transducer and activator of transcription (STAT)3 and its upstream activator Janus kinase (JAK)2, in high-grade ovarian carcinomas compared with normal ovaries and benign tumours. The association between STAT3 activation and migratory phenotype of ovarian cancer cells was investigated by EGF-induced epithelial-mesenchymal transition (EMT) in OVCA 433 and SKOV3 ovarian cancer cell lines. Ligand activation of EGFR induced a fibroblast-like morphology and migratory phenotype, consistent with the upregulation of mesenchyme-associated N-cadherin, vimentin and nuclear translocation of beta-catenin. This occurred concomitantly with activation of the downstream JAK2/STAT3 pathway. Both cell lines expressed interleukin-6 receptor (IL-6R), and treatment with EGF within 1 h resulted in a several-fold enhancement of mRNA expression of IL-6. Consistent with that, EGF treatment of both OVCA 433 and SKOV3 cell lines resulted in enhanced IL-6 production in the serum-free medium. Exogenous addition of IL-6 to OVCA 433 cells stimulated STAT3 activation and enhanced migration. Blocking antibodies against IL-6R inhibited IL-6 production and EGF- and IL-6-induced migration. Specific inhibition of STAT3 activation by JAK2-specific inhibitor AG490 blocked STAT3 phosphorylation, cell motility, induction of N-cadherin and vimentin expression and IL6 production. These data suggest that the activated status of STAT3 in high-grade ovarian carcinomas may occur directly through activation of EGFR or IL-6R or indirectly through induction of IL-6R signalling. Such activation of STAT3 suggests a rationale for a combination of anti-STAT3 and EGFR/IL-6R therapy to suppress the peritoneal spread of ovarian cancer.
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