The Architecture of the GW Ori Young Triple Star System and Its Disk: Dynamical Masses, Mutual Inclinations, and Recurrent Eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main sequence hierarchical triple star system GW Ori. A forward-modeling of the ${}^{13}$CO and C${}^{18}$O $J$=2-1 transitions permits a measurement of the total stellar mass in this system, $5.29 \pm 0.09\,M_\odot$, and the circum-triple disk inclination, $137.6 \pm 2.0^\circ$. Optical spectra spanning a 35 year period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a $241.50\pm0.05$ day period; a tertiary companion orbits that inner pair with a $4218\pm50$ day period. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system ($M_\mathrm{A} \approx 2.7\,M_\odot$, $M_\mathrm{B} \approx 1.7\,M_\odot$, $M_\mathrm{C} \approx 0.9\,M_\odot$) and find strong evidence that at least one (and likely both) stellar orbital planes are misaligned with the disk plane by as much as $45^\circ$. A $V$-band light curve spanning 30 years reveals several new $\sim$30 day eclipse events 0.1-0.7~mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is $\sim$1 Myr old.Comment: 26 pages, 15 figures, accepted to Ap

Alternatively activated macrophage-derived RELM-α is a negative regulator of type 2 inflammation in the lung

Differentiation and recruitment of alternatively activated macrophages (AAMacs) are hallmarks of several inflammatory conditions associated with infection, allergy, diabetes, and cancer. AAMacs are defined by the expression of Arginase 1, chitinase-like molecules, and resistin-like molecule (RELM) α/FIZZ1; however, the influence of these molecules on the development, progression, or resolution of inflammatory diseases is unknown. We describe the generation of RELM-α–deficient (Retnla−/−) mice and use a model of T helper type 2 (Th2) cytokine-dependent lung inflammation to identify an immunoregulatory role for RELM-α. After challenge with Schistosoma mansoni (Sm) eggs, Retnla−/− mice developed exacerbated lung inflammation compared with their wild-type counterparts, characterized by excessive pulmonary vascularization, increased size of egg-induced granulomas, and elevated fibrosis. Associated with increased disease severity, Sm egg–challenged Retnla−/− mice exhibited elevated expression of pathogen-specific CD4+ T cell–derived Th2 cytokines. Consistent with immunoregulatory properties, recombinant RELM-α could bind to macrophages and effector CD4+ Th2 cells and inhibited Th2 cytokine production in a Bruton's tyrosine kinase–dependent manner. Additionally, Retnla−/− AAMacs promoted exaggerated antigen-specific Th2 cell differentiation. Collectively, these data identify a previously unrecognized role for AAMac-derived RELM-α in limiting the pathogenesis of Th2 cytokine-mediated pulmonary inflammation, in part through the regulation of CD4+ T cell responses

Comprehensive analysis of promoter-proximal RNA polymerase II pausing across mammalian cell types

Background: For many genes, RNA polymerase II stably pauses before transitioning to productive elongation. Although polymerase II pausing has been shown to be a mechanism for regulating transcriptional activation, the extent to which it is involved in control of mammalian gene expression and its relationship to chromatin structure remain poorly understood. Results: Here, we analyze 85 RNA polymerase II chromatin immunoprecipitation (ChIP)-sequencing experiments from 35 different murine and human samples, as well as related genome-wide datasets, to gain new insights into the relationship between polymerase II pausing and gene regulation. Across cell and tissue types, paused genes (pausing index > 2) comprise approximately 60 % of expressed genes and are repeatedly associated with specific biological functions. Paused genes also have lower cell-to-cell expression variability. Increased pausing has a non-linear effect on gene expression levels, with moderately paused genes being expressed more highly than other paused genes. The highest gene expression levels are often achieved through a novel pause-release mechanism driven by high polymerase II initiation. In three datasets examining the impact of extracellular signals, genes responsive to stimulus have slightly lower pausing index on average than non-responsive genes, and rapid gene activation is linked to conditional pause-release. Both chromatin structure and local sequence composition near the transcription start site influence pausing, with divergent features between mammals and Drosophila. Most notably, in mammals pausing is positively correlated with histone H2A.Z occupancy at promoters. Conclusions: Our results provide new insights into the contribution of RNA polymerase II pausing in mammalian gene regulation and chromatin structure. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-0984-2) contains supplementary material, which is available to authorized users

Restoration ecophysiology: an ecophysiological approach to improve restoration strategies and outcomes in severely disturbed landscapes

As human activities destroy and degrade the world's ecosystems at unprecedented scales, there is a growing need for evidence-based methods for ecological restoration if we are to preserve biodiversity and ecosystem services. Mining represents one of the most severe anthropogenic disturbances, often necessitating intensive intervention to restore the most basic attributes of native ecosystems. Despite examples of successful mine-site restoration, re-establishing native vegetation in these degraded landscapes remains a significant challenge. Plant ecophysiology-the study of the interactions between plants and the environment-can provide a useful framework for evaluating and guiding mine-site restoration. By understanding the physiological mechanisms that allow plants to establish and persist in these highly disturbed environments, practitioners may be able to improve restoration outcomes. Specifically, methods in plant ecophysiology can inform site preparation and the selection of plant material for restoration projects, aid in monitoring restoration progress by providing additional insight into plant performance, and ultimately improve our ability to predict restoration trajectories. Here, we review the challenges and benefits of integrating an ecophysiological perspective to mine-site restoration in Western Australia, a global hotspot of biodiversity and mining operations. Using case studies and examples from the region's diverse ecosystems, we illustrate how an ecophysiological approach can guide the restoration of some of the world's most severely disturbed landscapes. With careful selection of study species and traits and consideration of the specific environmental conditions and stressors within a site, the restoration ecophysiology framework outlined here has the potential to inform restoration strategies across ecosystems

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems

Main objective: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration: ClinicalTrials.gov Identifier:&nbsp;NCT04506528&nbsp;(https://clinicaltrials.gov/ct2/show/NCT04506528).</p

The architecture of the GW Ori Young triple-star system and its disk : dynamical masses, mutual inclinations, and recurrent eclipses

We present spatially and spectrally resolved Atacama Large Millimeter/submillimeter Array (ALMA) observations of gas and dust orbiting the pre-main-sequence hierarchical triple-star system GW Ori. A forward modeling of the 13CO and C18O J = 2-1 transitions permits a measurement of the total stellar mass in this system, 5.29+/- 0.09 M⊙ , and the circumtriple disk inclination, 137 o. 6+/- 2 o.  0. Optical spectra spanning a 35 yr period were used to derive new radial velocities and, coupled with a spectroscopic disentangling technique, revealed that the A and B components of GW Ori form a double-lined spectroscopic binary with a period of 241.50 ± 0.05 days; a tertiary companion orbits that inner pair with a period of 4218 ± 50 days. Combining the results from the ALMA data and the optical spectra with three epochs of astrometry in the literature, we constrain the individual stellar masses in the system (MA ≈ 2.7 M⊙ , MB ≈ 1.7 M⊙ , MC ≈ 0.9 M⊙) and find strong evidence that at least one of the stellar orbital planes (and likely both) is misaligned with the disk plane by as much as 45°. A V-band light curve spanning 30 yr reveals several new ∼30-day eclipse events 0.1-0.7 mag in depth and a 0.2 mag sinusoidal oscillation that is clearly phased with the AB-C orbital period. Taken together, these features suggest that the A-B pair may be partially obscured by material in the inner disk as the pair approaches apoastron in the hierarchical orbit. Lastly, we conclude that stellar evolutionary models are consistent with our measurements of the masses and basic photospheric properties if the GW Ori system is ∼1 Myr old.Peer reviewe

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM- CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens

Digital Words: Moving Forward with Measuring the Readability of Online Texts

The readability of a digital text can influence people’s information acquisition (Wikipedia articles), online security (how-to articles), and even health (WebMD). Readability metrics can also alter search rankings and are used to evaluate AI system performance. However, prior work on measuring readability has significant gaps, especially for HCI applications. Prior work has (a) focused on grade-school texts, (b) ignored domain-specific, jargon-heavy texts (e.g., health advice), and (c) failed to compare metrics, especially in the context of scaling to use with online corpora. This paper addresses these shortcomings by comparing well-known readability measures and a novel domain-specific approach across four different corpora: crowd-worker generated stories, Wikipedia articles, security and privacy advice, and health information. We evaluate the convergent, discriminant, and content validity of each measure and detail tradeoffs in domain-specificity and participant burden. These results provide a foundation for more accurate readability measurements in HCI