Extracting science from surveys of our Galaxy

Our knowledge of the Galaxy is being revolutionised by a series of photometric, spectroscopic and astrometric surveys. Already an enormous body of data is available from completed surveys, and data of ever increasing quality and richness will accrue at least until the end of this decade. To extract science from these surveys we need a class of models that can give probability density functions in the space of the observables of a survey -- we should not attempt to "invert" the data from the space of observables into the physical space of the Galaxy. Currently just one class of model has the required capability, so-called "torus models". A pilot application of torus models to understanding the structure of the Galaxy's thin and thick discs has already produced two significant results: a major revision of our best estimate of the Sun's velocity with respect to the Local Standard of Rest, and a successful prediction of the way in which the vertical velocity dispersion in the disc varies with distance from the Galactic plane.Comment: 13 pages. Invited review to appear in Pramana - journal of physics (Indian Academy of Sciences

Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, we evaluate the potential for T cell recognition of HERV elements in myeloid malignancies by mapping transcribed HERV genes and generating a library of 1169 potential antigenic HERV-derived peptides predicted for presentation by 4 HLA class I molecules. Using DNA barcode-labeled MHC-I multimers, we find CD8+ T cell populations recognizing 29 HERV-derived peptides representing 18 different HERV loci, of which HERVH-5, HERVW-1, and HERVE-3 have more profound responses; such HERV-specific T cells are present in 17 of the 34 patients, but less frequently in healthy donors. Transcriptomic analyses reveal enhanced transcription of the HERVs in patients; meanwhile DNA-demethylating therapy causes a small and heterogeneous enhancement in HERV transcription without altering T cell recognition. Our study thus uncovers T cell recognition of HERVs in myeloid malignancies, thereby implicating HERVs as potential targets for immunotherapeutic therapies

Identification and characterization of a rich population of CD34mesenchymal stem/stromal cells in human parotid, sublingual and submandibular glands

Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34+ cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34+ SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34+ cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34+ derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review.

BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work. The funders had no role in data analysis, preparation of the manuscript or decision to publish.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014440

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Measurement of the inclusive and differential Higgs boson production cross sections in the decay mode to a pair of τ Leptons in pp collisions at sqrt[s]=13 TeV

Measurements of the inclusive and differential fiducial cross sections of the Higgs boson are presented, using the τ lepton decay channel. The differential cross sections are measured as functions of the Higgs boson transverse momentum, jet multiplicity, and transverse momentum of the leading jet in the event, if any. The analysis is performed using proton-proton collision data collected with the CMS detector at the LHC at a center-of-mass energy of 13  TeV and corresponding to an integrated luminosity of 138  fb^{-1}. These are the first differential measurements of the Higgs boson cross section in the final state of two τ leptons. In final states with a large jet multiplicity or with a Lorentz-boosted Higgs boson, these measurements constitute a significant improvement over measurements performed in other final states

Observation of triple J/ψ meson production in proton-proton collisions

Data availability: Tabulated results are provided in the HEPData record for this analysis71. Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in CMS data preservation, re-use and open access policy.Code availability: The CMS core software is publically available at https://github.com/cms-sw/cmssw.Copyright . Protons consist of three valence quarks, two up-quarks and one down-quark, held together by gluons and a sea of quark-antiquark pairs. Collectively, quarks and gluons are referred to as partons. In a proton-proton collision, typically only one parton of each proton undergoes a hard scattering – referred to as single-parton scattering – leaving the remainder of each proton only slightly disturbed. Here, we report the study of double- and triple-parton scatterings through the simultaneous production of three J/ψ mesons, which consist of a charm quark-antiquark pair, in proton-proton collisions recorded with the CMS experiment at the Large Hadron Collider. We observed this process – reconstructed through the decays of J/ψ mesons into pairs of oppositely charged muons – with a statistical significance above five standard deviations. We measured the inclusive fiducial cross-section to be 272+141−104(stat)±17(syst)fb, and compared it to theoretical expectations for triple-J/ψ meson production in single-, double- and triple-parton scattering scenarios. Assuming factorization of multiple hard-scattering probabilities in terms of single-parton scattering cross-sections, double- and triple-parton scattering are the dominant contributions for the measured process.SCOAP3.Change history: 27 February 2023A Correction to this paper has been published: https://doi.org/10.1038/s41567-023-01992-

Measurement of the Higgs boson production via vector boson fusion and its decay into bottom quarks in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2308.01253v2 [hep-ex], https://arxiv.org/abs/2308.01253v2 . 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/HIG-22-009 (CMS Public Pages). Report number: CMS-HIG-22-009, CERN-EP-2023-110.A measurement of the Higgs boson (H) production via vector boson fusion (VBF) and its decay into a bottom quark-antiquark pair (bb¯) is presented using proton-proton collision data recorded by the CMS experiment at s√ = 13 TeV and corresponding to an integrated luminosity of 90.8 fb−1. Treating the gluon-gluon fusion process as a background and constraining its rate to the value expected in the standard model (SM) within uncertainties, the signal strength of the VBF process, defined as the ratio of the observed signal rate to that predicted by the SM, is measured to be μqqHHbb¯ = 1.01 +0.55−0.46. The VBF signal is observed with a significance of 2.4 standard deviations relative to the background prediction, while the expected significance is 2.7 standard deviations. Considering inclusive Higgs boson production and decay into bottom quarks, the signal strength is measured to be μincl.Hbb¯ = 0.99 +0.48−0.41, corresponding to an observed (expected) significance of 2.6 (2.9) standard deviations.SCOAP3, STFC; Marie-Curie program and the European Research Council and Horizon 2020 Gran

Search for electroweak production of charginos and neutralinos at s\sqrt{s} = 13 TeV in final states containing hadronic decays of WW, WZ, or WH and missing transverse momentum

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy”.A preprint version of this article is archived at: arXiv:2205.09597v2 [hep-ex], https://arxiv.org/abs/2205.09597v2 . Comments: Replaced with the published version. Added the journal reference. 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/SUS-21-002 (CMS Public Pages). Report number: CMS-SUS-21-002, CERN-EP-2022-031This Letter presents a search for direct production of charginos and neutralinos via electroweak interactions. The results are based on data from proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb^{-1}. The search considers final states with large missing transverse momentum and pairs of hadronically decaying bosons WW, WZ, and WH, where H is the Higgs boson. These bosons are identified using novel algorithms. No significant excess of events is observed relative to the expectations from the standard model. Limits at the 95% confidence level are placed on the cross section for production of mass-degenerate wino-like supersymmetric particles χ~±1 and χ~02, and mass-degenerate higgsino-like supersymmetric particles χ~±1, χ~02, and χ~03. In the limit of a nearly-massless lightest supersymmetric particle χ~01, wino-like particles with masses up to 870 and 960 GeV are excluded in the cases of χ~02 → Zχ~01 and χ~02 → Hχ~01, respectively, and higgsino-like particles are excluded between 300 and 650 GeV.SCOAP3