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The ABC transporter Mdl1p, a structural and functional homologue of the transporter associated with antigen processing (TAP) plays an important role in intracellular peptide transport from the mitochondrial matrix of Saccharomyces cerevisiae. To characterize the ATP hydrolysis cycle of Mdl1p, the nucleotide-binding domain (NBD) was overexpressed in Escherichia coli and purified to homogeneity. The isolated NBD was active in ATP binding and hydrolysis with a turnover of 25 ATP per minute and a Km of 0.6 mm and did not show cooperativity in ATPase activity. However, the ATPase activity was non-linearly dependent on protein concentration (Hill coefficient of 1.7), indicating that the functional state is a dimer. Dimeric catalytic transition states could be trapped either by incubation with orthovanadate or beryllium fluoride, or by mutagenesis of the NBD. The nucleotide composition of trapped intermediate states was determined using [alpha-32P]ATP and [gamma-32P]ATP. Three different dimeric intermediate states were isolated, containing either two ATPs, one ATP and one ADP, or two ADPs. Based on these experiments, it was shown that: (i) ATP binding to two NBDs induces dimerization, (ii) in all isolated dimeric states, two nucleotides are present, (iii) phosphate can dissociate from the dimer, (iv) both nucleotides are hydrolyzed, and (v) hydrolysis occurs in a sequential mode. Based on these data, we propose a processive-clamp model for the catalytic cycle in which association and dissociation of the NBDs depends on the status of bound nucleotides.
Measurements of the pT-dependent flow vector fluctuations in Pb-Pb collisions at sNN−−−√=5.02 TeV using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the pT-dependent flow vector fluctuations at sNN−−−√=5.02 TeV with two-particle correlations. Significant pT-dependent fluctuations of the V⃗ 2 flow vector in Pb-Pb collisions are found across different centrality ranges, with the largest fluctuations of up to ∼15% being present in the 5% most central collisions. In parallel, no evidence of significant pT-dependent fluctuations of V⃗ 3 or V⃗ 4 is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than 5σ significance in central collisions. These observations in Pb-Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high pT, which might be biased by pT-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system.
The two-particle momentum correlation functions between charm mesons (D∗± and D±) and charged light-flavor mesons (π± and K±) in all charge-combinations are measured for the first time by the ALICE Collaboration in high-multiplicity proton-proton collisions at a center-of-mass energy of s√=13 TeV. For DK and D∗K pairs, the experimental results are in agreement with theoretical predictions of the residual strong interaction based on quantum chromodynamics calculations on the lattice and chiral effective field theory. In the case of Dπ and D∗π pairs, tension between the calculations including strong interactions and the measurement is observed. For all particle pairs, the data can be adequately described by Coulomb interaction only, indicating a shallow interaction between charm and light-flavor mesons. Finally, the scattering lengths governing the residual strong interaction of the Dπ and D∗π systems are determined by fitting the experimental correlation functions with a model that employs a Gaussian potential. The extracted values are small and compatible with zero.
The two-particle momentum correlation functions between charm mesons (D∗± and D±) and charged light-flavor mesons (π± and K±) in all charge-combinations are measured for the first time by the ALICE Collaboration in high-multiplicity proton–proton collisions at a center-of-mass energy of √s = 13 TeV. For DK and D∗K pairs, the experimental results are in agreement with theoretical predictions of the residual strong interaction based on quantum chromodynamics calculations on the lattice and chiral effective field theory. In the case of Dπ and D∗π pairs, tension between the calculations including strong interactions and the measurement is observed. For all particle pairs, the data can be adequately described by Coulomb interaction only, indicating a shallow interaction between charm and light-flavor mesons. Finally, the scattering lengths governing the residual strong interaction of the Dπ and D∗π systems are determined by fitting the experimental correlation functions with a model that employs a Gaussian potential. The extracted values are small and compatible with zero.
Using 448.1 × 106 ψ(3686) decays collected with the BESIII detector at the BEPCII e+e− storage rings, the branching fractions and angular distributions of the decays χcJ → Ξ−Ξ¯¯¯¯+ and Ξ0Ξ¯¯¯¯0 (J = 0, 1, 2) are measured based on a partial-reconstruction technique. The decays χc1 → Ξ0Ξ¯¯¯¯0 and χc2 → Ξ0Ξ¯¯¯¯0 are observed for the first time with statistical significances of 7σ and 15σ, respectively. The results of this analysis are in good agreement with previous measurements and have significantly improved precision.
The process e+e−→ϕη is studied at 22 center-of-mass energy points (√s) between 2.00 and 3.08 GeV using 715 pb−1 of data collected with the BESIII detector. The measured Born cross section of e+e−→ϕη is found to be consistent with BABAR measurements, but with improved precision. A resonant structure around 2.175 GeV is observed with a significance of 6.9σ with mass (2163.5±6.2±3.0) MeV/c2 and width (31.1+21.1−11.6±1.1) MeV, where the first uncertainties are statistical and the second are systematic.
Based on an e+e− collision data sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at √s=3.773 GeV, the first amplitude analysis of the singly Cabibbo-suppressed decay D+→K+K0Sπ0 is performed. From the amplitude analysis, the K∗(892)+K0S component is found to be dominant with a fraction of (57.1±2.6±4.2)%, where the first uncertainty is statistical and the second systematic. In combination with the absolute branching fraction B(D+→K+K0Sπ0) measured by BESIII, we obtain B(D+→K∗(892)+K0S)=(8.69±0.40±0.64±0.51)×10−3, where the third uncertainty is due to the branching fraction B(D+→K+K0Sπ0). The precision of this result is significantly improved compared to the previous measurement. This result also differs from most of theoretical predictions by about 4σ, which may help to improve the understanding of the dynamics behind.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.178 to 4.600 GeV, we study the process eþe− → π0Xð3872Þγ and search for Zcð4020Þ0 → Xð3872Þγ. We find no significant signal and set upper limits on σðeþe− → π0Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ and σðeþe− → π0Zcð4020Þ0Þ · BðZcð4020Þ0 → Xð3872ÞγÞ · BðXð3872Þ → πþπ−J=ψÞ for each energy point at 90% confidence level, which is of the order of several tenths pb.
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.