The JWST UNCOVER Treasury survey: Ultradeep NIRSpec and NIRCam ObserVations before the Epoch of Reionization

In this paper we describe the survey design for the Ultradeep NIRSpec and NIRCam ObserVations before the Epoch of Reionization (UNCOVER) Cycle 1 JWST Treasury program, which executed its early imaging component in November 2022. The UNCOVER survey includes ultradeep ($\sim29-30\mathrm{AB}$) imaging of $\sim$45 arcmin$^2$ on and around the well-studied Abell 2744 galaxy cluster at $z=0.308$ and will follow-up ${\sim}500$ galaxies with extremely deep low-resolution spectroscopy with the NIRSpec/PRISM during the summer of 2023. We describe the science goals, survey design, target selection, and planned data releases. We also present and characterize the depths of the first NIRCam imaging mosaic, highlighting previously unparalleled resolved and ultradeep 2-4 micron imaging of known objects in the field. The UNCOVER primary NIRCam mosaic spans 28.8 arcmin$^2$ in seven filters (F115W, F150W, F200W, F277W, F356W, F410M, F444W) and 16.8 arcmin$^2$ in our NIRISS parallel (F115W, F150W, F200W, F356W, and F444W). To maximize early community use of the Treasury data set, we publicly release full reduced mosaics of public JWST imaging including 45 arcmin$^2$ NIRCam and 17 arcmin$^2$ NIRISS mosaics on and around the Abell 2744 cluster, including the Hubble Frontier Field primary and parallel footprints.Comment: 17 pages, 8 figures, 4 tables, submitted to ApJ, comments welcome (v2 with full author list in metadata

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

UNCOVER:Ultra-deep NIRCam and NIRSpec Observations Before the Epoch of Reionization

We propose an efficient public Treasury program that immediately establishes a NIRCam imaging deep field and ultra-deep low-resolution NIRSpec/PRISM follow-up spectroscopy in the gravitational lensing cluster Frontier Field Abell 2744. Assisted by strong lensing, these observations reach 1-2 magnitudes fainter than even the deepest ERS & GTO programs. Such depths are essential to achieve two core science goals of JWST: finding First Light galaxies during the Dark Ages at z>10 and studying the ultra-low luminosity galaxies at later times that were responsible for reionization. Offering the community early access to deep imaging of 4000 z>6 galaxies and spectroscopy of 500 galaxies ensures that this envisioned flagship science is guaranteed early in the mission, establishes from the start a vibrant and diverse user base for the observatory, and optimizes the efficiency of JWST by providing targets for higher resolution spectroscopic follow up in subsequent cycles. In support of this, we included imaging parallels to enhance the deep imaging legacy on and around the cluster. Beyond the immediate science goals, these data will support a broad array of legacy science including stellar mass complete studies to z=10, the role of dust obscuration at high redshift, and the various pathways of quenching star formation. Our experienced team commits to rapidly releasing the imaging to the public before the Cycle 2 deadline followed by the delivery of a joint photometric and spectroscopic database

Stepwise molecular display utilizing icosahedral and helical complexes of phage coat and decoration proteins in the development of robust nanoscale display vehicles

A stepwise addition protocol was developed to display cargo using bacteriophage P22 capsids and the phage decorator (Dec) protein. Three-dimensional image reconstructions of frozen-hydrated samples of P22 particles with nanogold-labeled Dec bound to them revealed the locations of the N- and C- termini of Dec. Each terminus is readily accessible for molecular display through affinity tags such as nickel-nitrilotriacetic acid, providing a total of 240 cargo-binding sites. Dec was shown by circular dichroism to be a β–sheet rich protein, and fluorescence anisotropy binding experiments demonstrated that Dec binds to P22 heads with high (~110 nM) affinity. Dec also binds to P22 nanotubes, which are helically symmetric assemblies that form when the P22 coat protein contains the F170A amino acid substitution. Several classes of tubes with Dec bound to them were visualized by cryo-electron microscopy and their three-dimensional structures were determined by helical reconstruction methods. In all instances, Dec trimers bound to P22 capsids and nanotubes at positions where three neighboring capsomers (oligomers of six coat protein subunits) lie in close proximity to one another. Stable interactions between Dec and P22 allow for the development of robust, nanoscale size, display vehicles