Retinoic acid regulates avian lung branching through a molecular network

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rar alpha, and rar beta) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgf beta 2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rar beta, meis2, hoxb5, tgf beta 2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgf beta 2, and id2 spatial distribution; to increase rar beta, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal-distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.The authors would like to thank Ana Lima for slide sectioning and Rita Lopes for contributing to the initiation of this project. This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the Project POCI-01-0145-FEDER-007038; and by the Project NORTE-01-0145- FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe

A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯

Measurement of the mass dependence of the transverse momentum of lepton pairs in Drell–Yan production in proton–proton collisions at √s = 13TeV

Data Availability Statement This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032 &filename=CMSDataPolicyV1.2.pdf &version=2 CMS data preservation, re-use and open access policy.]A preprint version of the article is available at arXiv:2205.04897v2 [hep-ex], https://arxiv.org/abs/2205.04897v2. Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SMP-20-003 (CMS Public Pages). Report number: CMS-SMP-20-003, CERN-EP-2022-053.The double differential cross sections of the Drell–Yan lepton pair (ℓ+ℓ- , dielectron or dimuon) production are measured as functions of the invariant mass mℓℓ , transverse momentum pT(ℓℓ) , and φη∗ . The φη∗ observable, derived from angular measurements of the leptons and highly correlated with pT(ℓℓ) , is used to probe the low- pT(ℓℓ) region in a complementary way. Dilepton masses up to 1 TeV are investigated. Additionally, a measurement is performed requiring at least one jet in the final state. To benefit from partial cancellation of the systematic uncertainty, the ratios of the differential cross sections for various mℓℓ ranges to those in the Z mass peak interval are presented. The collected data correspond to an integrated luminosity of 36.3 fb-1 of proton–proton collisions recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV . Measurements are compared with predictions based on perturbative quantum chromodynamics, including soft-gluon resummation.SCOAP3

Measurement of the differential tt¯ production cross section as a function of the jet mass and extraction of the top quark mass in hadronic decays of boosted top quarks

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in https://cms-docdb.cern.ch/cgibin/PublicDocDB/RetrieveFile?docid=6032 &filename=CMSDataPolicyV1.2.pdf &version=2.]A measurement of the jet mass distribution in hadronic decays of Lorentz-boosted top quarks is presented. The measurement is performed in the lepton + jets channel of top quark pair production (tt¯ ) events, where the lepton is an electron or muon. The products of the hadronic top quark decay are reconstructed using a single large-radius jet with transverse momentum greater than 400GeV . The data were collected with the CMS detector at the LHC in proton-proton collisions and correspond to an integrated luminosity of 138fb−1 . The differential tt¯ production cross section as a function of the jet mass is unfolded to the particle level and is used to extract the top quark mass. The jet mass scale is calibrated using the hadronic W boson decay within the large-radius jet. The uncertainties in the modelling of the final state radiation are reduced by studying angular correlations in the jet substructure. These developments lead to a significant increase in precision, and a top quark mass of 173.06±0.84GeV.SCOAP

Search for dark matter produced in association with a leptonically decaying Z boson in proton–proton collisions at s√=13TeV

A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton–proton collision data at a center-of-mass energy of 13TeV, collected by the CMS experiment at the LHC in 2016–2018, corresponding to an integrated luminosity of 137fb−1. The search uses the decay channels Z→ee and Z→μμ. No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.SCOAP

Measurements of Higgs boson production in the decay channel with a pair of ττ leptons in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2204.12957v2 [hep-ex], https://arxiv.org/abs/2204.12957v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures and tables, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-19-010 (CMS Public Pages). Report number: CMS-HIG-19-010, CERN-EP-2022-027.Measurements of Higgs boson production, where the Higgs boson decays into a pair of τ leptons, are presented, using a sample of proton-proton collisions collected with the CMS experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb^{−1}. Three analyses are presented. Two are targeting Higgs boson production via gluon fusion and vector boson fusion: a neural network based analysis and an analysis based on an event categorization optimized on the ratio of signal over background events. These are complemented by an analysis targeting vector boson associated Higgs boson production. Results are presented in the form of signal strengths relative to the standard model predictions and products of cross sections and branching fraction to τ leptons, in up to 16 different kinematic regions. For the simultaneous measurements of the neural network based analysis and the analysis targeting vector boson associated Higgs boson production signal strengths are found to be 0.82 ± 0.11 for inclusive Higgs boson production, 0.67 ± 0.19 (0.81 ± 0.17) for the production mainly via gluon fusion (vector boson fusion), and 1.79 ± 0.45 for vector boson associated Higgs boson production.SCOAP3