46 research outputs found

    Lung epithelial stem cells and their niches : Fgf10 takes center stage

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    Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)

    Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

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    Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2‱−, generate Al superoxides [Al(O2‱)](H2O5)]+ 2. Semireduced AlO2‱ radicals deplete mitochondrial Fe and promote generation of H2O2, O2 ‱ − and OH‱. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

    Search for Higgs Boson Pair Production in the Four b Quark Final State in Proton-Proton Collisions at root s=13 TeV

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    Search for invisible decays of the Higgs boson produced via vector boson fusion in proton-proton collisions at root s=13 TeV

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

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    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-

    Inclusive and differential cross section measurements of single top quark production in association with a Z boson in proton-proton collisions at √s = 13 TeV

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    Copyright © CERN, for the benefit of the CMS Collaboration. Inclusive and differential cross sections of single top quark production in association with a Z boson are measured in proton-proton collisions at a center-of-mass energy of 13 TeV with a data sample corresponding to an integrated luminosity of 138 fb−1 recorded by the CMS experiment. Events are selected based on the presence of three leptons, electrons or muons, associated with leptonic Z boson and top quark decays. The measurement yields an inclusive cross section of 87.9+7.5−7.3(stat)+7.3−6.0(syst) fb for a dilepton invariant mass greater than 30 GeV, in agreement with standard model (SM) calculations and represents the most precise determination to date. The ratio between the cross sections for the top quark and the top antiquark production in association with a Z boson is measured as 2.37+0.56−0.42(stat)+0.27−0.13(syst). Differential measurements at parton and particle levels are performed for the first time. Several kinematic observables are considered to study the modeling of the process. Results are compared to theoretical predictions with different assumptions on the source of the initial-state b quark and found to be in agreement, within the uncertainties. Additionally, the spin asymmetry, which is sensitive to the top quark polarization, is determined from the differential distribution of the polarization angle at parton level to be 0.54 ± 0.16 (stat) ± 0.06 (syst), in agreement with SM predictions.SCOAP3

    Search for long-lived particles decaying to leptons with large impact parameter in proton-proton collisions at root s=13 TeV

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    Copyright © CERN for the benefit of the CMS collaboration 2022. A search for new long-lived particles decaying to leptons using proton–proton collision data produced by the CERN LHC at s√=13TeV is presented. Events are selected with two leptons (an electron and a muon, two electrons, or two muons) that both have transverse impact parameter values between 0.01 and 10cm and are not required to form a common vertex. Data used for the analysis were collected with the CMS detector in 2016, 2017, and 2018, and correspond to an integrated luminosity of 118 (113)fb−1 in the ee channel (eÎŒ and ΌΌ channels). The search is designed to be sensitive to a wide range of models with displaced eÎŒ, ee, and ΌΌ final states. The results constrain several well-motivated models involving new long-lived particles that decay to displaced leptons. For some areas of the available phase space, these are the most stringent constraints to date.SCOAP3
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