Rings are the most frequently revealed substructure in Atacama Large Millimeter/submillimeter Array (ALMA) dust observations of protoplanetary disks, but their origin is still hotly debated. In this ...paper, we identify dust substructures in 12 disks and measure their properties to investigate how they form. This subsample of disks is selected from a high-resolution (∼0 12) ALMA 1.33 mm survey of 32 disks in the Taurus star-forming region, which was designed to cover a wide range of brightness and to be unbiased to previously known substructures. While axisymmetric rings and gaps are common within our sample, spiral patterns and high-contrast azimuthal asymmetries are not detected. Fits of disk models to the visibilities lead to estimates of the location and shape of gaps and rings, the flux in each disk component, and the size of the disk. The dust substructures occur across a wide range of stellar mass and disk brightness. Disks with multiple rings tend to be more massive and more extended. The correlation between gap locations and widths, the intensity contrast between rings and gaps, and the separations of rings and gaps could all be explained if most gaps are opened by low-mass planets (super-Earths and Neptunes) in the condition of low disk turbulence ( = 10−4). The gap locations are not well correlated with the expected locations of CO and N2 ice lines, so condensation fronts are unlikely to be a universal mechanism to create gaps and rings, though they may play a role in some cases.
We present a high-resolution (∼0 12, ∼16 au, mean sensitivity of 50 Jy beam−1 at 225 GHz) snapshot survey of 32 protoplanetary disks around young stars with spectral type earlier than M3 in the ...Taurus star-forming region using the Atacama Large Millimeter Array. This sample includes most mid-infrared excess members that were not previously imaged at high spatial resolution, excluding close binaries and objects with high extinction, thereby providing a more representative look at disk properties at 1-2 Myr. Our 1.3 mm continuum maps reveal 12 disks with prominent dust gaps and rings, 2 of which are around primary stars in wide binaries, and 20 disks with no resolved features at the observed resolution (hereafter smooth disks), 8 of which are around the primary star in wide binaries. The smooth disks were classified based on their lack of resolved substructures, but their most prominent property is that they are all compact with small effective emission radii (Reff,95% 50 au). In contrast, all disks with Reff,95% of at least 55 au in our sample show detectable substructures. Nevertheless, their inner emission cores (inside the resolved gaps) have similar peak brightness, power-law profiles, and transition radii to the compact smooth disks, so the primary difference between these two categories is the lack of outer substructures in the latter. These compact disks may lose their outer disk through fast radial drift without dust trapping, or they might be born with small sizes. The compact dust disks, as well as the inner disk cores of extended ring disks, that look smooth at the current resolution will likely show small-scale or low-contrast substructures at higher resolution. The correlation between disk size and disk luminosity correlation demonstrates that some of the compact disks are optically thick at millimeter wavelengths.
We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching 4 yr of Kepler time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs, of ...which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new, including two in multiplanet systems (KOI-82.06 and KOI-2926.05) and 10 high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter, which automatically vets the DR25 threshold crossing events (TCEs). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discuss the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK-dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits, and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive.
The K2 Mission: Characterization and Early Results Howell, Steve B.; Sobeck, Charlie; Haas, Michael ...
Publications of the Astronomical Society of the Pacific,
04/2014, Letnik:
126, Številka:
938
Journal Article
Recenzirano
Odprti dostop
The K2 mission will make use of the Kepler spacecraft and its assets to expand upon Kepler's groundbreaking discoveries in the fields of exoplanets and astrophysics through new and exciting ...observations. K2 will use an innovative way of operating the spacecraft to observe target fields along the ecliptic for the next 2-3 years. Early science commissioning observations have shown an estimated photometric precision near 400 ppm in a single 30 minute observation, and a 6-hr photometric precision of 80 ppm (both at V = 12). The K2 mission offers long-term, simultaneous optical observation of thousands of objects at a precision far better than is achievable from ground-based telescopes. Ecliptic fields will be observed for approximately 75 days enabling a unique exoplanet survey which fills the gaps in duration and sensitivity between the Kepler and TESS missions, and offers pre-launch exoplanet target identification for JWST transit spectroscopy. Astrophysics observations with K2 will include studies of young open clusters, bright stars, galaxies, supernovae, and asteroseismology.
The "trimorbidity" of substance use disorder and mental and physical illness is associated with living in precarious housing or homelessness. The extent to which substance use increases risk of ...psychosis and both contribute to mortality needs investigation in longitudinal studies. A community-based sample of 437 adults (330 men, mean SD age 40.6 11.2 years) living in Vancouver, Canada, completed baseline assessments between November 2008 and October 2015. Follow-up was monthly for a median 6.3 years (interquartile range 3.1-8.6). Use of tobacco, alcohol, cannabis, cocaine, methamphetamine, and opioids was assessed by interview and urine drug screen; severity of psychosis was also assessed. Mortality (up to November 15, 2018) was assessed from coroner's reports and hospital records. Using data from monthly visits (mean 9.8, SD 3.6) over the first year after study entry, mixed-effects logistic regression analysis examined relationships between risk factors and psychotic features. A past history of psychotic disorder was common (60.9%). Nonprescribed substance use included tobacco (89.0%), alcohol (77.5%), cocaine (73.2%), cannabis (72.8%), opioids (51.0%), and methamphetamine (46.5%). During the same year, 79.3% of participants reported psychotic features at least once. Greater risk was associated with number of days using methamphetamine (adjusted odds ratio aOR 1.14, 95% confidence interval CI 1.05-1.24, p = 0.001), alcohol (aOR 1.09, 95% CI 1.01-1.18, p = 0.04), and cannabis (aOR 1.08, 95% CI 1.02-1.14, p = 0.008), adjusted for demographic factors and history of past psychotic disorder. Greater exposure to concurrent month trauma was associated with increased odds of psychosis (adjusted model aOR 1.54, 95% CI 1.19-2.00, p = 0.001). There was no evidence for interactions or reverse associations between psychotic features and time-varying risk factors. During 2,481 total person years of observation, 79 participants died (18.1%). Causes of death were physical illness (40.5%), accidental overdose (35.4%), trauma (5.1%), suicide (1.3%), and unknown (17.7%). A multivariable Cox proportional hazard model indicated baseline alcohol dependence (adjusted hazard ratio aHR 1.83, 95% CI 1.09-3.07, p = 0.02), and evidence of hepatic fibrosis (aHR 1.81, 95% CI 1.08-3.03, p = 0.02) were risk factors for mortality. Among those under age 55 years, a history of a psychotic disorder was a risk factor for mortality (aHR 2.38, 95% CI 1.03-5.51, p = 0.04, adjusted for alcohol dependence at baseline, human immunodeficiency virus HIV, and hepatic fibrosis). The primary study limitation concerns generalizability: conclusions from a community-based, diagnostically heterogeneous sample may not apply to specific diagnostic groups in a clinical setting. Because one-third of participants grew up in foster care or were adopted, useful family history information was not obtainable. In this study, we found methamphetamine, alcohol, and cannabis use were associated with higher risk for psychotic features, as were a past history of psychotic disorder, and experiencing traumatic events. We found that alcohol dependence, hepatic fibrosis, and, only among participants <55 years of age, history of a psychotic disorder were associated with greater risk for mortality. Modifiable risk factors in people living in precarious housing or homelessness can be a focus for interventions.
Summary Background Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, ...randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy. Methods Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both, were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy, with a permuted block size of six. The primary endpoint was progression-free survival, assessed via a blinded, independent central review. The study was designed to be terminated after 290 events of progression. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00410124. Findings All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed (101 37% events in the everolimus group, 90 65% in the placebo group; hazard ratio 0·30, 95% CI 0·22–0·40, p<0·0001; median progression-free survival 4·0 95% CI 3·7–5·5 vs 1·9 1·8–1·9 months). Stomatitis (107 40% patients in the everolimus group vs 11 8% in the placebo group), rash (66 25% vs six 4%), and fatigue (53 20% vs 22 16%) were the most commonly reported adverse events, but were mostly mild or moderate in severity. Pneumonitis (any grade) was detected in 22 (8%) patients in the everolimus group, of whom eight had pneumonitis of grade 3 severity. Interpretation Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies. Funding Novartis Oncology.
Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is ...driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB-mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II-induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion.
Summary Background Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a ...particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. Methods We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995–2012), the Netherlands (2006–12), Italy (1995–2004), Scotland (1989–98), and England (2002–09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. Findings We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r2 =0·95, Ireland r2 =0·99, Italy r2 =0·95, the Netherlands r2 =0·99, and Scotland r2 =0·97; overall r2 =0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5–5·0), with similar estimates for men (4·6, 4·3–4·9) and women (5·0, 4·5–5·5). Interpretation A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. Funding UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the Ministry of Health and Ministry of Education, University, and Research in Italy; the Motor Neurone Disease Association of England, Wales, and Northern Ireland; and the European Commission (Seventh Framework Programme).
Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold ...exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.
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