Molecules with ALMA at Planet-forming Scales (MAPS). VI. Distribution of the small organics HCN, C2H, and H2CO

Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, and MR/T040726/1). J.D.I. acknowledges support from the Science and Technology Facilities Council of the United Kingdom (STFC) under ST/T000287/1.Small organic molecules, such as C2H, HCN, and H2CO, are tracers of the C, N, and O budget in protoplanetary disks. We present high-angular-resolution (10-50 au) observations of C2H, HCN, and H2CO lines in five protoplanetary disks from the Molecules with ALMA at Planet-forming Scales (MAPS) ALMA Large Program. We derive column density and excitation temperature profiles for HCN and C2H, and find that the HCN emission arises in a temperate (20-30 K) layer in the disk, while C2H is present in relatively warmer (20-60 K) layers. In the case of HD 163296, we find a decrease in column density for HCN and C2H inside one of the dust gaps near ~83 au, where a planet has been proposed to be located. We derive H2CO column density profiles assuming temperatures between 20 and 50 K, and find slightly higher column densities in the colder disks around T Tauri stars than around Herbig Ae stars. The H2CO column densities rise near the location of the CO snowline and/or millimeter dust edge, suggesting an efficient release of H2CO ices in the outer disk. Finally, we find that the inner 50 au of these disks are rich in organic species, with abundances relative to water that are similar to cometary values. Comets could therefore deliver water and key organics to future planets in these disks, similar to what might have happened here on Earth. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). XVIII. Kinematic substructures in the disks of HD 163296 and MWC 480

Funding: K.Z., K.R.S., J.H., J.B., J.B.B., and I.C. acknowledge the support of NASA through Hubble Fellowship grants HST-HF2-51401.001, HST-HF2-51419.001, HST-HF2-51460.001-A, HSTHF2-51427.001-A, HST-HF2-51429.001-A, and HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. A.S.B. acknowledges the studentship funded by the Science and Technology Facilities Council of the United Kingdom (STFC). C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1).We explore the dynamical structure of the protoplanetary disks surrounding HD 163296 and MWC 480 as part of the Molecules with ALMA at Planet-forming Scales (MAPS) large program. Using the J = 2-1 transitions of 12CO, 13CO, and C18O imaged at spatial resolutions of ~0"15 and with a channel spacing of 200 m s-1, we find perturbations from Keplerian rotation in the projected velocity fields of both disks (≲5% of the local Keplerian velocity), suggestive of large-scale (tens of astronomical units in size), coherent flows. By accounting for the azimuthal dependence on the projection of the velocity field, the velocity fields were decomposed into azimuthally averaged orthogonal components, vφ, vr, and vz. Using the optically thick 12CO emission as a probe of the gas temperature, local variations of ≍3 K (≍5% relative changes) were observed and found to be associated with the kinematic substructures. The MWC 480 disk hosts a suite of tightly wound spiral arms. The spirals arms, in conjunction with the highly localized perturbations in the gas velocity structure (kinematic planetary signatures), indicate a giant planet, ~1 MJup, at a radius of ≍245 au. In the disk of HD 163296, the kinematic substructures were consistent with previous studies of Pinte et al. and Teague et al. advocating for multiple ~1 MJup planets embedded in the disk. These results demonstrate that molecular line observations that characterize the dynamical structure of disks can be used to search for the signatures of embedded planets. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). II. CLEAN strategies for synthesizing images of molecular line emission in protoplanetary disks

Funding: I.C. was supported by NASA through NASA Hubble Fellowship grant No. HST-HF2-51405.001-A, awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1) J.D.I. acknowledges support from STFC under ST/T000287/1.The Molecules with ALMA at Planet-forming Scales Large Program (MAPS LP) surveyed the chemical structures of five protoplanetary disks across more than 40 different spectral lines at high angular resolution (0"15 and 0"30 beams for Bands 6 and 3, respectively) and sensitivity (spanning 0.3-1.3 mJy beam-1 and 0.4-1.9 mJy beam-1 for Bands 6 and 3, respectively). In this article, we describe the multistage workflow-built around the CASA tclean image deconvolution procedure-that we used to generate the core data product of the MAPS LP: the position-position-velocity image cubes for each spectral line. Owing to the expansive nature of the survey, we encountered a range of imaging challenges: some are familiar to the submillimeter protoplanetary disk community, like the need to use an accurate CLEAN mask, and others are less well known, like the incorrect default flux scaling of the CLEAN residual map first described by Jorsater & van Moorsel (the "JvM effect"). We distill lessons learned into recommended workflows for synthesizing image cubes of molecular emission. In particular, we describe how to produce image cubes with accurate fluxes via "JvM correction," a procedure that is generally applicable to any image synthesized via CLEAN deconvolution but is especially critical for low signal-to-noise ratio (S/N) emission. We further explain how we used visibility tapering to promote a common, fiducial beam size and contextualize the interpretation of S/N when detecting molecular emission from protoplanetary disks. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Molecules with ALMA at Planet-forming Scales (MAPS). XV. Tracing protoplanetary disk structure within 20 au

Funding: J.B., J.B.B., I.C., J.H., K. R.S., and K.Z. acknowledge support by NASA through the NASA Hubble Fellowship grant Nos. HST-HF2-51427.001-A, HST-HF2- 51429.001-A, HST-HF2-51405.001-A, HST-HF2-51460.001-A, HST-HF2-51419.001, and HST-HF2-51401.001, awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Incorporated, under NASA contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds and from the Science and Technology Facilities Council (grant Nos. ST/R000549/1 and ST/T000287/1). A.S.B acknowledges the studentship funded by the Science and Technology Facilities Council of the United Kingdom (STFC). J.D.I. acknowledges support from the Science and Technology Facilities Council of the United Kingdom (STFC) under ST/T000287/1.Constraining the distribution of gas and dust in the inner 20 au of protoplanetary disks is difficult. At the same time, this region is thought to be responsible for most planet formation, especially around the water ice line at 3–10 au. Under the assumption that the gas is in a Keplerian disk, we use the exquisite sensitivity of the Molecules with ALMA at Planet-forming Scales (MAPS) ALMA large program to construct radial surface brightness profiles with a ∼3 au effective resolution for the CO isotopologue J = 2–1 lines using the line velocity profile. IM Lup reveals a central depression in 13CO and C18O that is ascribed to a pileup of ∼500 M⊕ of dust in the inner 20 au, leading to a gas-to-dust ratio of around 10) and that the dust gap is gas-rich enough to have optically thick C18O. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). IV. Emission surfaces and vertical distribution of molecules

Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1).The Molecules with ALMA at Planet-forming Scales (MAPS) Large Program provides a unique opportunity to study the vertical distribution of gas, chemistry, and temperature in the protoplanetary disks around IM Lup, GM Aur, AS 209, HD 163296, and MWC 480. By using the asymmetry of molecular line emission relative to the disk major axis, we infer the emission height (z) above the midplane as a function of radius (r). Using this method, we measure emitting surfaces for a suite of CO isotopologues, HCN, and C2H. We find that 12CO emission traces the most elevated regions with z/r ∼< 0.3 , while emission from the less abundant 13CO and C18O probes deeper into the disk at altitudes of z/r ~< 0.2 . C2H and HCN have lower opacities and signal-to-noise ratios, making surface fitting more difficult, and could only be reliably constrained in AS 209, HD 163296, and MWC 480, with z/r ~< 0.1 , i.e., relatively close to the planet-forming midplanes. We determine peak brightness temperatures of the optically thick CO isotopologues and use these to trace 2D disk temperature structures. Several CO temperature profiles and emission surfaces show dips in temperature or vertical height, some of which are associated with gaps and rings in line and/or continuum emission. These substructures may be due to local changes in CO column density, gas surface density, or gas temperatures, and detailed thermochemical models are necessary to better constrain their origins and relate the chemical compositions of elevated disk layers with those of planet-forming material in disk midplanes. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). V. CO gas distributions

Funding: K.Z., K.R.S., J.H., J.B., J.B.B., and I.C. acknowledge the support of NASA through Hubble Fellowship grants HST-HF2-51401.001, HST-HF2-51419.001, HST-HF2-51460.001-A, HST-HF2-51427.001-A, HST-HF2-51429.001-A, and HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds and from the Science and Technology Facilities Council (grant Nos. ST/R000549/1, ST/T000287/1, and MR/T040726/1).Here we present high-resolution (15-24 au) observations of CO isotopologue lines from the Molecules with ALMA on Planet-forming Scales (MAPS) ALMA Large Program. Our analysis employs observations of the (J = 2-1) and (1-0) lines of 13CO and C18O and the (J = 1-0) line of C17O for five protoplanetary disks. We retrieve CO gas density distributions, using three independent methods: (1) a thermochemical modeling framework based on the CO data, the broadband spectral energy distribution, and the millimeter continuum emission; (2) an empirical temperature distribution based on optically thick CO lines; and (3) a direct fit to the C17O hyperfine lines. Results from these methods generally show excellent agreement. The CO gas column density profiles of the five disks show significant variations in the absolute value and the radial shape. Assuming a gas-to-dust mass ratio of 100, all five disks have a global CO-to-H2 abundance 10-100 times lower than the interstellar medium ratio. The CO gas distributions between 150 and 400 au match well with models of viscous disks, supporting the long-standing theory. CO gas gaps appear to be correlated with continuum gap locations, but some deep continuum gaps do not have corresponding CO gaps. The relative depths of CO and dust gaps are generally consistent with predictions of planet-disk interactions, but some CO gaps are 5-10 times shallower than predictions based on dust gaps. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). I. Program overview and highlights

Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, Science and Technology Facilities Council of the United Kingdom (STFC), and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1).Planets form and obtain their compositions in dust- and gas-rich disks around young stars, and the outcome of this process is intimately linked to the disk chemical properties. The distributions of molecules across disks regulate the elemental compositions of planets, including C/N/O/S ratios and metallicity (O/H and C/H), as well as access to water and prebiotically relevant organics. Emission from molecules also encodes information on disk ionization levels, temperature structures, kinematics, and gas surface densities, which are all key ingredients of disk evolution and planet formation models. The Molecules with ALMA at Planet-forming Scales (MAPS) ALMA Large Program was designed to expand our understanding of the chemistry of planet formation by exploring disk chemical structures down to 10 au scales. The MAPS program focuses on five disks-around IM Lup, GM Aur, AS 209, HD 163296, and MWC 480-in which dust substructures are detected and planet formation appears to be ongoing. We observed these disks in four spectral setups, which together cover ~50 lines from over 20 different species. This paper introduces the Astrophysical Journal Supplement's MAPS Special Issue by presenting an overview of the program motivation, disk sample, observational details, and calibration strategy. We also highlight key results, including discoveries of links between dust, gas, and chemical substructures, large reservoirs of nitriles and other organics in the inner disk regions, and elevated C/O ratios across most disks. We discuss how this collection of results is reshaping our view of the chemistry of planet formation.Publisher PDFPeer reviewe

A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages. Depletion of folylpolyglutamate synthetase (FPGS), which normally promotes intracellular accumulation and activity of natural folates and methotrexate, is linked to methotrexate and 5-fluorouracil resistance and its association with relapse illustrates the need for improved intervention strategies. Here, we describe a novel antifolate (C1) that, like methotrexate, potently inhibits dihydrofolate reductase and downstream one-carbon metabolism. Contrary to methotrexate, C1 displays optimal efficacy in FPGS-deficient contexts, due to decreased competition with intracellular folates for interaction with dihydrofolate reductase. We show that FPGS-deficient patient-derived CRC organoids display enhanced sensitivity to C1, whereas FPGS-high CRC organoids are more sensitive to methotrexate. Our results argue that polyglutamylation-independent antifolates can be applied to exert selective pressure on FPGS-deficient cells during chemotherapy, using a vulnerability created by polyglutamylation deficiency

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies