COMAP Early Science: VIII. A Joint Stacking Analysis with eBOSS Quasars

We present a new upper limit on the cosmic molecular gas density at z = 2.4 − 3.4 obtained using the first year of observations from the CO Mapping Array Project (COMAP). COMAP data cubes are stacked on the 3D positions of 243 quasars selected from the Extended Baryon Oscillation SpectroscopicSurvey (eBOSS) catalog, yielding a 95% upper limit for flux from CO(1-0) line emission of 0.129 Jykm/s. Depending on the balance of the emission between the quasar host and its environment, this value can be interpreted as an average CO line luminosity L′CO of eBOSS quasars of ≤ 1.26 × 1011 K km pc2s−1, or an average molecular gas density ρH2 in regions of the universe containing a quasar of ≤ 1.52 × 108 M⊙ cMpc−3. The L′ CO upper limit falls among CO line luminosities obtained fromindividually-targeted quasars in the COMAP redshift range, and the ρH2 value is comparable to upper limits obtained from other Line Intensity Mapping (LIM) surveys and their joint analyses. Further, we forecast the values obtainable with the COMAP/eBOSS stack after the full 5-year COMAP Pathfinder survey. We predict that a detection is probable with this method, depending on the CO properties of the quasar sample. Based on the achieved sensitivity, we believe that this technique of stacking LIM data on the positions of traditional galaxy or quasar catalogs is extremely promising, both asa technique for investigating large galaxy catalogs efficiently at high redshift and as a technique for bolstering the sensitivity of LIM experiments, even with a fraction of their total expected survey data

COMAP Early Science: VIII. A Joint Stacking Analysis with eBOSS Quasars

We present a new upper limit on the cosmic molecular gas density at $z=2.4-3.4$ obtained using the first year of observations from the CO Mapping Array Project (COMAP). COMAP data cubes are stacked on the 3D positions of 282 quasars selected from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) catalog, yielding a 95% upper limit for flux from CO(1-0) line emission of 0.210 Jy km/s. Depending on the assumptions made, this value can be interpreted as either an average CO line luminosity $L'_\mathrm{CO}$ of eBOSS quasars of $\leq 7.30\times10^{10}$ K km pc$^2$ s$^{-1}$, or an average molecular gas density $\rho_\mathrm{H_2}$ in regions of the universe containing a quasar of $\leq 2.02\times10^8$ M$_\odot$ cMpc$^{-3}$. The $L'_\mathrm{CO}$ upper limit falls among CO line luminosities obtained from individually-targeted quasars in the COMAP redshift range, and the $\rho_\mathrm{H_2}$ value is comparable to upper limits obtained from other Line Intensity Mapping (LIM) surveys and their joint analyses. Further, we forecast the values obtainable with the COMAP/eBOSS stack after the full 5-year COMAP Pathfinder survey. We predict that a detection is probable with this method, depending on the CO properties of the quasar sample. Based on these achieved sensitivities, we believe that this technique of stacking LIM data on the positions of traditional galaxy or quasar catalogs is extremely promising, both as a technique for investigating large galaxy catalogs efficiently at high redshift and as a technique for bolstering the sensitivity of LIM experiments, even with a fraction of their total expected survey data.Comment: 15 pages, 8 figures. To be submitted to Ap

COMAP Early Science: V. Constraints and Forecasts at z∼3z \sim 3

We present the current state of models for the $z\sim3$ carbon monoxide (CO) line-intensity signal targeted by the CO Mapping Array Project (COMAP) Pathfinder in the context of its early science results. Our fiducial model, relating dark matter halo properties to CO luminosities, informs parameter priors with empirical models of the galaxy-halo connection and previous CO(1-0) observations. The Pathfinder early science data spanning wavenumbers $k=0.051$-$0.62\,$Mpc$^{-1}$ represent the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum. Our 95% upper limit on the redshift-space clustering amplitude $A_{\rm clust}\lesssim70\,\mu$K$^2$ greatly improves on the indirect upper limit of $420\,\mu$K$^2$ reported from the CO Power Spectrum Survey (COPSS) measurement at $k\sim1\,$Mpc$^{-1}$. The COMAP limit excludes a subset of models from previous literature, and constrains interpretation of the COPSS results, demonstrating the complementary nature of COMAP and interferometric CO surveys. Using line bias expectations from our priors, we also constrain the squared mean line intensity-bias product, $\langle{Tb}\rangle^2\lesssim50\,\mu$K$^2$, and the cosmic molecular gas density, $\rho_\text{H2}<2.5\times10^8\,M_\odot\,$Mpc$^{-3}$ (95% upper limits). Based on early instrument performance and our current CO signal estimates, we forecast that the five-year Pathfinder campaign will detect the CO power spectrum with overall signal-to-noise of 9-17. Between then and now, we also expect to detect the CO-galaxy cross-spectrum using overlapping galaxy survey data, enabling enhanced inferences of cosmic star-formation and galaxy-evolution history.Comment: Paper 5 of 7 in series. 17 pages + appendix and bibliography (30 pages total); 15 figures, 6 tables; accepted for publication in ApJ; v3 reflects the accepted version with minor changes and additions to tex

COMAP Early Science: VII. Prospects for CO Intensity Mapping at Reionization

We introduce COMAP-EoR, the next generation of the Carbon Monoxide Mapping Array Project aimed at extending CO intensity mapping to the Epoch of Reionization. COMAP-EoR supplements the existing 30 GHz COMAP Pathfinder with two additional 30 GHz instruments and a new 16 GHz receiver. This combination of frequencies will be able to simultaneously map CO(1--0) and CO(2--1) at reionization redshifts ($z\sim5-8$) in addition to providing a significant boost to the $z\sim3$ sensitivity of the Pathfinder. We examine a set of existing models of the EoR CO signal, and find power spectra spanning several orders of magnitude, highlighting our extreme ignorance about this period of cosmic history and the value of the COMAP-EoR measurement. We carry out the most detailed forecast to date of an intensity mapping cross-correlation, and find that five out of the six models we consider yield signal to noise ratios (S/N) $\gtrsim20$ for COMAP-EoR, with the brightest reaching a S/N above 400. We show that, for these models, COMAP-EoR can make a detailed measurement of the cosmic molecular gas history from $z\sim2-8$, as well as probe the population of faint, star-forming galaxies predicted by these models to be undetectable by traditional surveys. We show that, for the single model that does not predict numerous faint emitters, a COMAP-EoR-type measurement is required to rule out their existence. We briefly explore prospects for a third-generation Expanded Reionization Array (COMAP-ERA) capable of detecting the faintest models and characterizing the brightest signals in extreme detail.Comment: Paper 7 of 7 in series. 19 pages, 10 figures, to be submitted to Ap

COMAP Early Science: I. Overview

The CO Mapping Array Project (COMAP) aims to use line intensity mapping of carbon monoxide (CO) to trace the distribution and global properties of galaxies over cosmic time, back to the Epoch of Reionization (EoR). To validate the technologies and techniques needed for this goal, a Pathfinder instrument has been constructed and fielded. Sensitive to CO(1-0) emission from $z=2.4$-$3.4$ and a fainter contribution from CO(2-1) at $z=6$-8, the Pathfinder is surveying $12$ deg$^2$ in a 5-year observing campaign to detect the CO signal from $z\sim3$. Using data from the first 13 months of observing, we estimate $P_\mathrm{CO}(k) = -2.7 \pm 1.7 \times 10^4\mu\mathrm{K}^2 \mathrm{Mpc}^3$ on scales $k=0.051-0.62 \mathrm{Mpc}^{-1}$ - the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum. Based on these observations alone, we obtain a constraint on the amplitude of the clustering component (the squared mean CO line temperature-bias product) of $\langle Tb\rangle^2<49$ $\mu$K$^2$ - nearly an order-of-magnitude improvement on the previous best measurement. These constraints allow us to rule out two models from the literature. We forecast a detection of the power spectrum after 5 years with signal-to-noise ratio (S/N) 9-17. Cross-correlation with an overlapping galaxy survey will yield a detection of the CO-galaxy power spectrum with S/N of 19. We are also conducting a 30 GHz survey of the Galactic plane and present a preliminary map. Looking to the future of COMAP, we examine the prospects for future phases of the experiment to detect and characterize the CO signal from the EoR.Comment: Paper 1 of 7 in series. 18 pages, 16 figures, submitted to Ap

iCLIP: Protein-RNA interactions at nucleotide resolution.

RNA-binding proteins (RBPs) are key players in the post-transcriptional regulation of gene expression. Precise knowledge about their binding sites is therefore critical to unravel their molecular function and to understand their role in development and disease. Individual-nucleotide resolution UV crosslinking and immunoprecipitation (iCLIP) identifies protein-RNA crosslink sites on a genome-wide scale. The high resolution and specificity of this method are achieved by an intramolecular cDNA circularization step that enables analysis of cDNAs that truncated at the protein-RNA crosslink sites. Here, we describe the improved iCLIP protocol and discuss critical optimization and control experiments that are required when applying the method to new RBPs

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

Protein–RNA specificity by high-throughput principal component analysis of NMR spectra

Defining the RNA target selectivity of the proteins regulating mRNA metabolism is a key issue in RNA biology. Here we present a novel use of principal component analysis (PCA) to extract the RNA sequence preference of RNA binding proteins. We show that PCA can be used to compare the changes in the nuclear magnetic resonance (NMR) spectrum of a protein upon binding a set of quasi-degenerate RNAs and define the nucleobase specificity. We couple this application of PCA to an automated NMR spectra recording and processing protocol and obtain an unbiased and high-throughput NMR method for the analysis of nucleobase preference in protein–RNA interactions. We test the method on the RNA binding domains of three important regulators of RNA metabolism

Diagnosis and management of dementia with Lewy bodies:Fourth consensus report of the DLB Consortium

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support