Physical and chemical complexity in high-mass star-forming regions with ALMA. I. Overview and evolutionary trends of physical properties

In this study, we investigate how physical properties, such as the density and temperature profiles, evolve on core scales through the evolutionary sequence during high-mass star formation ranging from protostars in cold infrared dark clouds to evolved UCHII regions. We observed 11 high-mass star-forming regions with ALMA at 3 mm wavelengths. Based on the 3 mm continuum morphology and recombination line emission, tracing locations with free-free (ff) emission, the fragmented cores analyzed in this study are classified into either dust or dust+ff cores. In addition, we resolve three cometary UCHII regions with extended 3 mm emission that is dominated by free-free emission. The temperature structure and radial profiles (T~r^-q ) are determined by modeling molecular emission of CH3CN and CH313CN with XCLASS and by using the HCN-to- HNC intensity ratio as probes for the gas kinetic temperature. The density profiles (n~r^-p ) are estimated from the 3 mm continuum visibility profiles. The masses M and H2 column densities N(H2) are then calculated from the 3 mm dust continuum emission. Results. We find a large spread in mass and peak H2 column density in the detected sources ranging from 0.1-150 Msun and 10^23 - 10^26 cm-2 , respectively. Including the results of the CORE and CORE-extension studies (Gieser et al. 2021, 2022) to increase the sample size, we find evolutionary trends on core scales for the temperature power-~law index q increasing from 0.1 to 0.7 from infrared dark clouds to UCHII regions, while for the the density power-law index p on core scales, we do not find strong evidence for an evolutionary trend. However, we find that on the larger clump scales throughout these evolutionary phases the density profile flattens from p = 2.2 to p = 1.2. (abridged)Comment: 21 pages, 10 figures, submitted to A&

ALMA Observations of Molecular Line Emission from High-excitation Bipolar Planetary Nebulae

We present early results from our program of ALMA Band 6 (1.3mm) molecular line mapping of a sample of nearby, well-studied examples of high-excitation, bipolar/pinched-waist and molecule-rich planetary nebulae (Hubble 5 and NGC 2440, 2818, 2899, 6302, and 6445). We have mapped these planetary nebulae (PNe) in isotopologues of CO as well as various molecular line tracers of high-energy irradiation, such as HCN, CN, HNC, and HCO+, with the complementary goals of establishing nebular kinematics as well as the zones of UV-heated and X-ray-ionized molecular gas within each nebula. The resulting high-resolution ALMA molecular emission-line maps reveal the regions of high-excitation bipolar PNe in which molecular gas, presumably ejected during asymptotic giant branch stages of the PN progenitor stars, survives and evolves chemically. We present a summary of molecular species detected to date in the sample nebulae, and we use example results for one PN (NGC 6455) to demonstrate the power of the ALMA data in revealing the structures, kinematics, and compositions of the equatorial molecular tori that are a common feature of the sample objects.Comment: 6 pages, 4 figures, accepted for IAU Proceedings Series (IAUS 384

Density distributions, magnetic field structures, and fragmentation in high-mass star formation

[Context] The fragmentation of high-mass star-forming regions depends on a variety of physical parameters, including density, the magnetic field, and turbulent gas properties.[Aims] We evaluate the importance of the density and magnetic field structures in relation to the fragmentation properties during high-mass star formation.[Results] Based on the IRAM 30 m data, we infer density distributions n ∝ r−p of the regions with typical power-law slopes p around ~1.5. There is no obvious correlation between the power-law slopes of the density structures on larger clump scales (~1 pc) and the number of fragments on smaller core scales (<0.1 pc). Comparing the large-scale single-dish density profiles to those derived earlier from interferometric observations at smaller spatial scales, we find that the smaller-scale power-law slopes are steeper, typically around ~2.0. The flattening toward larger scales is consistent with the star-forming regions being embedded in larger cloud structures that do not decrease in density away from a particular core. The magnetic fields of several regions appear to be aligned with filamentary structures that lead toward the densest central cores. Furthermore, we find different polarization structures; some regions exhibit central polarization holes, whereas other regions show polarized emission also toward the central peak positions. Nevertheless, the polarized intensities are inversely related to the Stokes I intensities, following roughly a power-law slope of ∝ SI−0.62. We estimate magnetic field strengths between ~0.2 and ~4.5 mG, and we find no clear correlation between magnetic field strength and the fragmentation level of the regions. A comparison of the turbulent to magnetic energies shows that they are of roughly equal importance in this sample. The mass-to-flux ratios range between ~2 and ~7, consistent with collapsing star-forming regions.[Conclusions] Finding no clear correlations between the present-day large-scale density structure, the magnetic field strength, and the smaller-scale fragmentation properties of the regions, indicates that the fragmentation of high-mass star-forming regions may not be affected strongly by the initial density profiles and magnetic field properties. However, considering the limited evolutionary range and spatial scales of the presented CORE analysis, future research directions should include density structure analysis of younger regions that better resemble the initial conditions, as well as connecting the observed intermediate-scale magnetic field structure with the larger-scale magnetic fields of the parental molecular clouds.R.K. acknowledges financial support via the Heisenberg Research Grant funded by the German Research Foundation (DFG) under grant no. KU 2849/9. A.P. is grateful to Gilberto Gómez and Enrique Vázquez-Semadeni for very insightful discussions. A.P. acknowledges financial support from the UNAM-PAPIIT IG100223 grant, the Sistema Nacional de Investigadores of CONAHCyT, and from the CONAHCyT project number 86372 of the ‘Ciencia de Frontera 2019’ program, entitled ‘Citlalcóatl: a multiscale study at the new frontier of the formation and early evolution of stars and planetary systems’, México. A.S.M. acknowledges support from the RyC2021-032892-I and PID2020-117710GB-I00 grants funded by MCIN/AEI/10.13039/501100011033 and by the European Union ‘NextGenerationEU’/PRTR, as well as the program Unidad de Excelencia María de Maeztu CEX2020-001058-M. J.D.S. acknowledges funding by the European Research Council via the ERC Synergy Grant “ECOGAL – Understanding our Galactic ecosystem: From the disk of the Milky Way to the formation sites of stars and planets” (project ID 855130).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2020-001058-M).Peer reviewe

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Physical and chemical properties during high-mass star formation

This thesis is dedicated to the characterization of the physical and chemical properties in high-mass star-forming regions. I use interferometric observations at 1 and 3 mm wavelengths with the NOrthern Extended Millimeter Array (NOEMA) and Atacama Large Millimeter/submillimeter Array (ALMA) of a sample of high-mass star-forming regions at different evolutionary stages ranging from infrared dark clouds, high-mass protostellar objects, hot molecular cores, to ultra-compact HII regions. At angular resolutions <1 arcsec, the physical and chemical properties of individual fragmented cores can be studied on scales <0.1 pc using both continuum and molecular line emission. Molecule properties, for example, the column density and rotation temperature, are derived using the eXtended CASA Line Analysis Software Suite (XCLASS) of species such as SO, OCS, SiO, H2 CO, CH3CN, and CH3OH. I determine for a statistical sample of cores radial temperature and density profiles (T ∼ r^-q and n ∼ r^-p , respectively), masses M, and molecular column densities N. Chemical timescales τchem are estimated using the physical-chemical model MUlti Stage CLoud codE (MUSCLE). There is a high degree of fragmentation in the regions and the spatial morphology of the continuum emission is diverse, where in some regions there is a single isolated core, while in other regions, for example, filamentary structures that have many embedded cores are found. The molecular content of individual cores have local chemical variations and with MUSCLE this chemical differentiation can be explained by the cores being at slightly different evolutionary stages. By combining the results of the in total 31 high-mass star-forming regions that were observed with either NOEMA or ALMA at high angular resolution and that were analyzed within this thesis, evolutionary trends of the physical core properties are found. The temperature profile q steepens from q ≈ 0.1 to q ≈ 0.7 and the density profile p1 on clump scales (0.1 - 1 pc) flattens from p1 ≈ 2.2 to p1 ≈ 1.2 with time as the cores evolve. No evolutionary trend is found for the density profile p2 on core scales (<0.1 pc), with p2 ≈ 2, indicating that all of the analyzed cores are collapsing to form (high-mass) stars. These results provide invaluable observational constraints to test theoretical formation models of high-mass stars

Fragmentation and disk formation in high-mass star formation: The IRAM large program CORE

The IRAM CORE large program combines data from NOEMA and the IRAM 30m telescope to study a diverse set of physical and chemical processes during the formation of high-mass stars. Here, we present a selected compilation of exciting results obtained during the survey

JOYS: Disentangling the warm and cold material in the high-mass IRAS 23385+6053 cluster

Context: High-mass star formation occurs in a clustered mode where fragmentation is observed from an early stage onward. Young protostars can now be studied in great detail with the recently launched James Webb Space Telescope (JWST). Aims: We study and compare the warm (>100 K) and cold (<100 K) material toward the high-mass star-forming region (HMSFR) IRAS 23385+6053 (IRAS 23385 hereafter) combining high-angular-resolution observations in the mid-infrared (MIR) with the JWST Observations of Young protoStars (JOYS) project and with the NOrthern Extended Millimeter Array (NOEMA) at millimeter (mm) wavelengths at angular resolutions of ≈0.″2–1.″0. Methods: We investigated the spatial morphology of atomic and molecular species using line-integrated intensity maps. We estimated the temperature and column density of different gas components using H2 transitions (warm and hot component) and a series of CH3CN transitions as well as 3 mm continuum emission (cold component). Results: Toward the central dense core of IRAS 23385, the material consists of relatively cold gas and dust (≈50 K), while multiple outflows create heated and/or shocked H2 and show enhanced temperatures (≈400 K) along the outflow structures. An energetic outflow with enhanced emission knots of [Fe II] and [Ni II] suggests J-type shocks, while two other outflows have enhanced emission of only H2 and [S I] caused by C-type shocks. The latter two outflows are also more prominent in molecular line emission at mm wavelengths (e.g., SiO, SO, H2CO, and CH3OH). Data of even higher angular resolution are needed to unambiguously identify the outflow-driving sources given the clustered nature of IRAS 23385. While most of the forbidden fine structure transitions are blueshifted, [Ne II] and [Ne III] peak at the source velocity toward the MIR source A/mmA2 suggesting that the emission is originating from closer to the protostar. Conclusions: The warm and cold gas traced by MIR and mm observations, respectively, are strongly linked in IRAS 23385. The outflows traced by MIR H2 lines have molecular counterparts in the mm regime. Despite the presence of multiple powerful outflows that cause dense and hot shocks, a cold dense envelope still allows star formation to further proceed. To study and fully understand the spatially resolved MIR properties, a representative sample of low- and high-mass protostars has to be probed using JWST.ISSN:0004-6361ISSN:1432-074

Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits

Background: Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. Methods: For each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression. Results: Of the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27-20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10-16 to 1.9 × 10-3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10-7 to 3.0 × 10-4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis. Conclusions: We demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common

Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration

PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD Genomics Consortium's 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) drive'' the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD