Interpreting the Si II and C II line spectra from the COS Legacy Spectroscopic SurveY using a virtual galaxy from a high-resolution radiation-hydrodynamic simulation

Observations of low-ionization state (LIS) metal lines provide crucial insights into the interstellar medium of galaxies, yet, disentangling the physical processes responsible for the emerging line profiles is difficult. This work investigates how mock spectra generated using a single galaxy in a radiation-hydrodynamical simulation can help us interpret observations of a real galaxy. We create 22,500 C II and Si II spectra from the virtual galaxy at different times and through multiple lines of sight and compare them with the 45 observations of low-redshift star-forming galaxies from the COS Legacy Spectroscopic SurveY (CLASSY). We find that the mock profiles provide accurate replicates to the observations of 38 galaxies with a broad range of stellar masses ($10^6$ to $10^9$ $M_\odot$) and metallicities (0.02 to 0.55 $Z_\odot$). Additionally, we highlight that aperture losses explain the weakness of the fluorescent emission in several CLASSY spectra and must be accounted for when comparing simulations to observations. Overall, we show that the evolution of a single simulated galaxy can produce a large diversity of spectra whose properties are representative of galaxies of comparable or smaller masses. Building upon these results, we explore the origin of the continuum, residual flux, and fluorescent emission in the simulation. We find that these different spectral features all emerge from distinct regions in the galaxy's ISM, and their characteristics can vary as a function of the viewing angle. While these outcomes challenge simplified interpretations of down-the-barrel spectra, our results indicate that high-resolution simulations provide an optimal framework to interpret these observations.Comment: Accepted for publication in Ap

CLASSY VIII: Exploring the Source of Ionization with UV ISM diagnostics in local High-zz Analogs

In the current JWST era, rest-frame UV spectra play a crucial role in enhancing our understanding of the interstellar medium (ISM) and stellar properties of the first galaxies in the epoch of reionization (EoR, $z>6$). Here, we compare well-known and reliable optical diagrams sensitive to the main ionization source (i.e., star formation, SF; active galactic nuclei, AGN; shocks) to UV counterparts proposed in the literature - the so-called ``UV-BPT diagrams'' - using the HST COS Legacy Archive Spectroscopic SurveY (CLASSY), the largest high-quality, high-resolution and broad-wavelength range atlas of far-UV spectra for 45 local star-forming galaxies. In particular, we explore where CLASSY UV line ratios are located in the different UV diagnostic plots, taking into account state-of-the-art photoionization and shock models and, for the first time, the measured ISM and stellar properties (e.g., gas-phase metallicity, ionization parameter, carbon abundance, stellar age). We find that the combination of C III] $\lambda\lambda$1907,9 He II $\lambda1640$ and O III] $\lambda$1666 can be a powerful tool to separate between SF, shocks and AGN at sub-solar metallicities. We also confirm that alternative diagrams without O III] $\lambda$1666 still allow us to define a SF-locus with some caveats. Diagrams including C IV $\lambda\lambda$1548,51 should be taken with caution given the complexity of this doublet profile. Finally, we present a discussion detailing the ISM conditions required to detect UV emission lines, visible only in low gas-phase metallicity (12+log(O/H) $\lesssim8.3$) and high ionization parameter (log($U$) $\gtrsim-2.5$) environments. Overall, CLASSY and our UV toolkit will be crucial in interpreting the spectra of the earliest galaxies that JWST is currently revealing.Comment: 31 pages, submitted to ApJ, comments welcom

The COS Legacy Archive Spectroscopy SurveY (CLASSY) Treasury Atlas

Far-ultraviolet (FUV; ~1200-2000 angstroms) spectra are fundamental to our understanding of star-forming galaxies, providing a unique window on massive stellar populations, chemical evolution, feedback processes, and reionization. The launch of JWST will soon usher in a new era, pushing the UV spectroscopic frontier to higher redshifts than ever before, however, its success hinges on a comprehensive understanding of the massive star populations and gas conditions that power the observed UV spectral features. This requires a level of detail that is only possible with a combination of ample wavelength coverage, signal-to-noise, spectral-resolution, and sample diversity that has not yet been achieved by any FUV spectral database. We present the COS Legacy Spectroscopic SurveY (CLASSY) treasury and its first high level science product, the CLASSY atlas. CLASSY builds on the HST archive to construct the first high-quality (S/N_1500 >~ 5/resel), high-resolution (R~15,000) FUV spectral database of 45 nearby (0.002 < z < 0.182) star-forming galaxies. The CLASSY atlas, available to the public via the CLASSY website, is the result of optimally extracting and coadding 170 archival+new spectra from 312 orbits of HST observations. The CLASSY sample covers a broad range of properties including stellar mass (6.2 < logM_star(M_sol) < 10.1), star formation rate (-2.0 < log SFR (M_sol/yr) < +1.6), direct gas-phase metallicity (7.0 < 12+log(O/H) < 8.8), ionization (0.5 < O_32 < 38.0), reddening (0.02 < E(B-V < 0.67), and nebular density (10 < n_e (cm^-3) < 1120). CLASSY is biased to UV-bright star-forming galaxies, resulting in a sample that is consistent with z~0 mass-metallicity relationship, but is offset to higher SFRs by roughly 2 dex, similar to z >~2 galaxies. This unique set of properties makes the CLASSY atlas the benchmark training set for star-forming galaxies across cosmic time.Comment: Accepted for publication in Ap

Analysis of protein-coding genetic variation in 60,706 humans

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes