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Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Erratum for: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells.Journal of biological chemistry, 2002 Nov 15;277(46):43623-30. doi: 10.1074/jbc.M203926200. Epub 2002 Sep 5.
In PC12 cells, a well studied model for neuronal differentiation, an elevation in the intracellular cAMP level increases cell survival, stimulates neurite outgrowth, and causes activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). Here we show that an increase in the intracellular cAMP concentration induces tyrosine phosphorylation of two receptor tyrosine kinases, i.e. the epidermal growth factor (EGF) receptor and the high affinity receptor for nerve growth factor (NGF), also termed Trk(A). cAMP-induced tyrosine phosphorylation of the EGF receptor is rapid and correlates with ERK1/2 activation. It occurs also in Panc-1, but not in human mesangial cells. cAMP-induced tyrosine phosphorylation of the NGF receptor is slower and correlates with Akt activation. Inhibition of EGF receptor tyrosine phosphorylation, but not of the NGF receptor, reduces cAMP-induced neurite outgrowth. Expression of dominant-negative Akt does not abolish cAMP-induced survival in serum-free media, but increases cAMP-induced ERK1/2 activation and neurite outgrowth. Together, our results demonstrate that cAMP induces dual signaling in PC12 cells: transactivation of the EGF receptor triggering the ERK1/2 pathway and neurite outgrowth; and transactivation of the NGF receptor promoting Akt activation and thereby modulating ERK1/2 activation and neurite outgrowth.
Erratum in: Correction: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells. Journal of biological chemistry 2020 Oct 23;295(43):14792. doi: 10.1074/jbc.AAC120.016177.
Introduction: This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care.
Methods: A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain.
Results: There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use.
Conclusion: Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686) → γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.
By analyzing an electron-positron collision data sample corresponding to an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy of 3.773 GeV with the BESIII detector, we obtain for the first time the absolute branching fractions for seven 𝐷0 and 𝐷+ hadronic decay modes and search for the hadronic decay 𝐷0→𝐾0𝑆𝐾0𝑆𝜋0 with much improved sensitivity. The results are ℬ(𝐷0→𝐾0𝑆𝜋0𝜋0𝜋0)=(7.64±0.30±0.29)×10−3, (𝐷0→𝐾−𝜋+𝜋0𝜋0𝜋0)=9.54±0.30±0.31)×10−3, ℬ(𝐷0→𝐾0𝑆𝜋+𝜋−𝜋0𝜋0)=(12.66±0.45±0.43)×10−3, ℬ(𝐷+→𝐾0𝑆𝜋+𝜋0𝜋0)=(29.04±0.62±0.87)×10−3, ℬ(𝐷+→𝐾0𝑆𝜋+𝜋+𝜋−𝜋0)=(15.28±0.57±0.60)×10−3, ℬ(𝐷+→𝐾0𝑆𝜋+𝜋0𝜋0𝜋0)=(5.54±0.44±0.32)×10−3, ℬ(𝐷+→𝐾−𝜋+𝜋+𝜋0𝜋0)=(4.95±0.26±0.19)×10−3, and ℬ(𝐷0→𝐾0𝑆𝐾0𝑆𝜋0)<1.45×10−4 at the 90% confidence level. Here, the first uncertainties are statistical, and the second ones are systematic. The newly studied decays greatly enrich the knowledge of the 𝐷→¯𝐾𝜋𝜋𝜋 and 𝐷→¯𝐾𝜋𝜋𝜋𝜋 hadronic decays and open a bridge to access more two-body hadronic 𝐷 decays containing scalar, vector, axial, and tensor mesons in the charm sector.
Luminosities and energies of e⁺e⁻ collision data taken between √s=4.61 GeV and 4.95 GeV at BESIII
(2022)
From December 2019 to June 2021, the BESIII experiment collected about 5.85 fb−1 of data at center-of-mass energies between 4.61 GeV and 4.95 GeV. This is the highest collision energy BEPCII has reached so far. The accumulated e+e− annihilation data samples are useful for studying charmonium(-like) states and charmed-hadron decays. By adopting a novel method of analyzing the production of Λ+cΛ¯−c pairs in e+e− annihilation, the center-of-mass energies are measured with a precision of ∼0.6 MeV. Integrated luminosities are measured with a precision of better than 1\% by analyzing the events of large-angle Bhabha scattering. These measurements provide important inputs to the analyses based on these data samples.
We report a measurement of the cross section for the process e+e−→π+π−J/ψ around the X(3872) mass in search for the direct formation of e+e−→X(3872) through the two-photon fusion process. No enhancement of the cross section is observed at the X(3872) peak and an upper limit on the product of electronic width and branching fraction of X(3872)→π+π−J/ψ is determined to be Γee×B(X(3872)→π+π−J/ψ)<7.5×10−3eV at 90% confidence level under an assumption of total width of 1.19±0.21 MeV. This is an improvement of a factor of about 17 compared to the previous limit. Furthermore, using the latest result of B(X(3872)→π+π−J/ψ), an upper limit on the electronic width Γee of X(3872) is obtained to be <0.32eV at the 90% confidence level.
Using a sample of (10.09 ± 0.04) × 109 J/ψ decays collected with the BESIII detector, partial wave analyses of the decay J/ψ → γK0SK0Sπ0 are performed within the K0SK0Sπ0 invariant mass region below 1.6 GeV/c2. The covariant tensor amplitude method is used in both mass independent and mass dependent approaches. Both analysis approaches exhibit dominant pseudoscalar and axial vector components, and show good consistency for the other individual components. Furthermore, the mass dependent analysis reveals that the K0SK0 Sπ0 invariant mass spectrum for the pseudoscalar component can be well described with two isoscalar resonant states using relativistic Breit-Wigner model, i.e., the η(1405) with a mass of 1391.7±0.7+11.3 −0.3 MeV/c 2 and a width of 60.8±1.2+5.5 −12.0 MeV, and the η(1475) with a mass of 1507.6±1.6+15.5−32.2 MeV/c2 and a width of 115.8±2.4 +14.8 −10.9 MeV. The first and second uncertainties are statistical and systematic, respectively. Alternate models for the pseudoscalar component are also tested, but the description of the K0SK0Sπ0invariant mass spectrum deteriorates significantly.
Using a data sample of (448.1±2.9)×106 𝜓(3686) decays collected at an 𝑒+𝑒− center-of-mass energy of 3.686 GeV by the BESIII detector at Beijing Electron Positron Collider II, we report an observation of the hindered electromagnetic Dalitz decay 𝜓(3686)→𝑒+𝑒−𝜂𝑐 with a significance of 7.9𝜎. The branching fraction is determined to be ℬ(𝜓(3686)→𝑒+𝑒−𝜂𝑐)=(3.77±0.40stat±0.18syst)×10−5, agreeing well with the prediction of the vector meson dominance model. This is the first measurement of the electromagnetic Dalitz transition between the 𝜓(3686) and the 𝜂𝑐, which provides new insight into the electromagnetic properties of this decay, and offers new opportunities to measure the absolute branching fractions of 𝜂𝑐 decays.
A measurement of the 𝐶𝑃-even fraction of the decay 𝐷0→𝜋+𝜋−𝜋+𝜋− is performed with a quantum-correlated 𝜓(3770)→𝐷¯𝐷 data sample collected by the BESIII experiment, corresponding to an integrated luminosity of 2.93 fb−1. Using a combination of 𝐶𝑃 eigenstates, 𝐷→𝜋+𝜋−𝜋0 and 𝐷→𝐾0𝑆,𝐿𝜋+𝜋− as tagging modes, the 𝐶𝑃-even fraction is measured to be 𝐹4𝜋+=0.735±0.015±0.005, where the first uncertainty is statistical and the second is systematic. This is the most precise determination of this quantity to date. It provides valuable model-independent input for the measurement of the angle 𝛾 of the Cabibbo-Kobayashi-Maskawa matrix with 𝐵±→𝐷𝐾± decays, and for time-dependent studies of 𝐶𝑃 violation and mixing in the 𝐷0−¯𝐷0 system.
By analyzing 𝑒+𝑒− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy √𝑠=3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic 𝐷0(+) decays involving multiple pions. The highest four branching fractions obtained are ℬ(𝐷0→𝜋+𝜋−𝜋0) = (1.343±0.013stat±0.016syst)%, ℬ(𝐷0→𝜋+𝜋−2𝜋0) = (1.002±0.019stat±0.024syst)%, ℬ(𝐷+→2𝜋+𝜋−𝜋0) = (1.165±0.021stat±0.021syst)%, and ℬ(𝐷+→2𝜋+𝜋−2𝜋0) = (1.074±0.040stat±0.030syst)%. The 𝐶𝑃 asymmetries for the six decays with highest signal yields are also determined and found to be compatible with zero.
Using e+e− annihilation data sets collected with the BESIII detector, we measure the cross sections of the processes e+e−→e+e− and e+e−→μ+μ− at fifteen center-of-mass energy points in the vicinity of the J/ψ resonance. By a simultaneous fit to the measured, center-of-mass energy dependent cross sections of the two processes, the combined quantities ΓeeΓee/Γtot and ΓeeΓμμ/Γtot are determined to be (0.346±0.009) and (0.335±0.006) keV, respectively, where Γee, Γμμ, and Γtot are the electronic, muonic, and total decay widths of the J/ψ resonance, respectively. Using the resultant ΓeeΓμμ/Γtot and ΓeeΓee/Γtot, the ratio Γee/Γμμ is calculated to be 1.031±0.015, which is consistent with the expectation of lepton universality within about two standard deviations. Assuming lepton universality and using the branching fraction of the J/ψ leptonic decay measured by BESIII in 2013, Γtot and Γll are determined to be (93.0±2.1) and (5.56±0.11) keV, respectively, where Γll is the average leptonic decay width of the J/ψ resonance.
Observation of 𝜒𝑐𝐽→Λ¯Λ𝜂
(2022)
By analyzing (448.1±2.9)×106 𝜓(3686) events collected with the BESIII detector operating at the BEPCII collider, the decays of 𝜒𝑐𝐽→Λ
¯Λ𝜂 (𝐽=0, 1, and 2) are observed for the first time with statistical significances of 13.9𝜎, 6.7𝜎, and 8.2𝜎, respectively. The product branching fractions of 𝜓(3686)→𝛾𝜒𝑐𝐽 and 𝜒𝑐𝐽→Λ¯Λ𝜂 are measured. Dividing by the world averages of the branching fractions of 𝜓(3686)→𝛾𝜒𝑐𝐽, the branching fractions of 𝜒𝑐𝐽→Λ¯Λ𝜂 decays are determined to be (2.31±0.30±0.21)×10−4, (5.86±1.38±0.68)×10−5, and (1.05±0.21±0.15)×10−4 for 𝐽=0, 1 and 2, respectively, where the first uncertainties are statistical and the second systematic.
Using a sample of (448.1±2.9)×106 𝜓(3686) decays collected with the BESIII detector at BEPCII, we report an observation of Ξ− transverse polarization with a significance of 7.3𝜎 in the decay 𝜓(3686)→Ξ− ¯Ξ+ (Ξ−→Λ𝜋−, ¯Ξ+→¯Λ𝜋+, Λ→𝑝𝜋−, ¯Λ→¯𝑝𝜋+). The relative phase of the electric and magnetic form factors is determined to be ΔΦ=(0.667±0.111±0.058) rad. This is the first measurement of the relative phase for a 𝜓(3686) decay into a pair of Ξ−¯Ξ+ hyperons. The Ξ− decay parameters (𝛼Ξ−, 𝜙Ξ−) and their conjugates (𝛼¯Ξ+, 𝜙¯Ξ+), the angular-distribution parameter 𝛼𝜓, and the strong-phase difference 𝛿𝑝−𝛿𝑠 for Λ𝜋− scattering are measured to be consistent with previous BESIII results.
The radiative hyperon decay Λ→nγ is studied using (10087±44)×106 J/ψ events collected with the BESIII detector operating at BEPCII. The absolute branching fraction of the decay Λ→nγ is determined with a significance of 5.6σ to be [0.832±0.038(stat.)±0.054(syst.)]×10−3, which lies significantly below the current PDG value. By analyzing the joint angular distribution of the decay products, the first determination of the decay asymmetry αγ is reported with a value of −0.16±0.10(stat.)±0.05(syst.).
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay 𝜂𝑐(2𝑆)→3(𝜋+𝜋−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 𝜓(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of 𝜂𝑐(2𝑆) are (3643.4±2.3 (stat)±4.4 (syst)) MeV/𝑐2 and (19.8±3.9 (stat)±3.1 (syst)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]×ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)] is measured to be (9.2±1.0 (stat)±1.2 (syst))×10−6. Using ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]=(7.0+3.4−2.5)×10−4, we obtain ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)]=(1.31±0.15 (stat)±0.17 (syst) (+0.64−0.47) (extr))×10−2, where the third uncertainty is from ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]. We also measure the 𝜒𝑐𝐽→3(𝜋+𝜋−) (𝐽=0, 1, 2) decays via 𝜓′→𝛾𝜒𝑐𝐽 transitions. The branching fractions are ℬ[𝜒𝑐0→3(𝜋+𝜋−)]=(2.080±0.006 (stat)±0.068 (syst))×10−2, ℬ[𝜒𝑐1→3(𝜋+𝜋−)]=(1.092±0.004 (stat)±0.035 (syst))×10−2, and ℬ[𝜒𝑐2→3(𝜋+𝜋−)]=(1.565±0.005 (stat)±0.048 (syst))×10−2.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686)→γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.