Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise

Skeletal muscles comprise a substantial portion of whole body mass and are integral for locomotion and metabolic health. Increasing age is associated with declines in both muscle mass and function (e.g. strength‐related performance, power) with declines in muscle function quantitatively outweighing those in muscle volume. The mechanisms behind these declines are multi‐faceted involving both intrinsic age‐related metabolic dysregulation and environmental influences such as nutritional and physical activity. Ageing is associated with a degree of ‘anabolic resistance’ to these key environmental inputs, which likely accelerates the intrinsic processes driving ageing. On this basis, strategies to sensitize and/or promote anabolic responses to nutrition and physical activity are likely to be imperative in alleviating the progression and trajectory of sarcopenia. Both resistance‐ and aerobic‐type exercises are likely to confer functional and health benefits in older age, and a clutch of research suggests that enhancement of anabolic responsiveness to exercise and/or nutrition may be achieved by optimizing modifications of muscle‐loading paradigms (workload, volume, blood flow restriction) or nutritional support (e.g. essential amino acid/leucine) patterns. Nonetheless, more work is needed in which a more holistic view in ageing studies is taken into account. This should include improved characterization of older study recruits, that is physical activity/nutritional behaviours, to limit confounding variables influencing whether findings are attributable to age, or other environmental influences. Nonetheless, on balance, ageing is associated with declines in muscle mass and function and a partially related decline in aerobic capacity. There is also good evidence that metabolic flexibility is impaired in older age

Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks

Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems (benchmarking) becomes critical to provide users with an assessment of the accuracy expected when these methods are applied within their domain of applicability, and developers with a way to assess the expected impact of new methodologies. These assessments require construction of a benchmark - a set of well-prepared, high quality systems with corresponding experimental measurements designed to ensure the resulting calculations provide a realistic assessment of expected performance when these methods are deployed within their domains of applicability. To date, the community has not yet adopted a common standardized benchmark, and existing benchmark reports suffer from a myriad of issues, including poor data quality, limited statistical power, and statistically deficient analyses, all of which can conspire to produce benchmarks that are poorly predictive of real-world performance. Here, we address these issues by presenting guidelines for (1) curating experimental data to develop meaningful benchmark sets, (2) preparing benchmark inputs according to best practices to facilitate widespread adoption, and (3) analysis of the resulting predictions to enable statistically meaningful comparisons among methods and force fields

Measurement of ISR-FSR interference in the processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma

Charge asymmetry in processes e+ e- --> mu+ mu- gamma and e+ e- --> pi+ pi- gamma is measured using 232 fb-1 of data collected with the BABAR detector at center-of-mass energies near 10.58 GeV. An observable is introduced and shown to be very robust against detector asymmetries while keeping a large sensitivity to the physical charge asymmetry that results from the interference between initial and final state radiation. The asymmetry is determined as afunction of the invariant mass of the final-state tracks from production threshold to a few GeV/c2. It is compared to the expectation from QED for e+ e- --> mu+ mu- gamma and from theoretical models for e+ e- --> pi+ pi- gamma. A clear interference pattern is observed in e+ e- --> pi+ pi- gamma, particularly in the vicinity of the f_2(1270) resonance. The inferred rate of lowest order FSR production is consistent with the QED expectation for e+ e- --> mu+ mu- gamma, and is negligibly small for e+ e- --> pi+ pi- gamma.Comment: 32 pages,29 figures, to be submitted to Phys. Rev.

Observation of time-reversal violation in the B0 meson system

The individually named authors work collectively as The BABAR Collaboration. Copyright @ 2012 American Physical Society.Although CP violation in the B meson system has been well established by the B factories, there has been no direct observation of time-reversal violation. The decays of entangled neutral B mesons into definite flavor states (B0 or B¯¯¯0), and J/ψK0L or cc¯K0S final states (referred to as B+ or B−), allow comparisons between the probabilities of four pairs of T-conjugated transitions, for example, B¯¯¯0→B− and B−→B¯¯¯0, as a function of the time difference between the two B decays. Using 468×106 BB¯¯¯ pairs produced in Υ(4S) decays collected by the BABAR detector at SLAC, we measure T-violating parameters in the time evolution of neutral B mesons, yielding ΔS+T=−1.37±0.14(stat)±0.06(syst) and ΔS−T=1.17±0.18(stat)±0.11(syst). These nonzero results represent the first direct observation of T violation through the exchange of initial and final states in transitions that can only be connected by a T-symmetry transformation.DOE and NSF (USA), NSERC (Canada), CEA and CNRS-IN2P3 (France), BMBF and DFG(Germany), INFN (Italy), FOM (The Netherlands), NFR (Norway), MES (Russia), MINECO (Spain), STFC (United Kingdom). Individuals have received support from the Marie Curie EIF (European Union), the A. P. Sloan Foundation (USA) and the Binational Science Foundation (USA-Israel)

Branching fraction and form-factor shape measurements of exclusive charmless semileptonic B decays, and determination of |V_{ub}|

We report the results of a study of the exclusive charmless semileptonic decays, B^0 --> pi^- l^+ nu, B^+ --> pi^0 l^+ nu, B^+ --> omega l^+ nu, B^+ --> eta l^+ nu and B^+ --> eta^' l^+ nu, (l = e or mu) undertaken with approximately 462x10^6 B\bar{B} pairs collected at the Upsilon(4S) resonance with the BABAR detector. The analysis uses events in which the signal B decays are reconstructed with a loose neutrino reconstruction technique. We obtain partial branching fractions in several bins of q^2, the square of the momentum transferred to the lepton-neutrino pair, for B^0 --> pi^- l^+ nu, B^+ --> pi^0 l^+ nu, B^+ --> omega l^+ nu and B^+ --> eta l^+ nu. From these distributions, we extract the form-factor shapes f_+(q^2) and the total branching fractions BF(B^0 --> pi^- l^+ nu) = (1.45 +/- 0.04_{stat} +/- 0.06_{syst})x10^-4 (combined pi^- and pi^0 decay channels assuming isospin symmetry), BF(B^+ --> omega l^+ nu) = (1.19 +/- 0.16_{stat} +/- 0.09_{syst})x10^-4 and BF(B^+ --> eta l^+ nu) = (0.38 +/- 0.05_{stat} +/- 0.05_{syst})x10^-4. We also measure BF(B^+ --> eta^' l^+ nu) = (0.24 +/- 0.08_{stat} +/- 0.03_{syst})x10^-4. We obtain values for the magnitude of the CKM matrix element V_{ub} by direct comparison with three different QCD calculations in restricted q^2 ranges of B --> pi l^+ nu decays. From a simultaneous fit to the experimental data over the full q^2 range and the FNAL/MILC lattice QCD predictions, we obtain |V_{ub}| = (3.25 +/- 0.31)x10^-3, where the error is the combined experimental and theoretical uncertainty.Comment: 35 pages, 14 figures, submitted to PR

Evidence for the η_b(1S) Meson in Radiative Υ(2S) Decay

We have performed a search for the η_b(1S) meson in the radiative decay of the Υ(2S) resonance using a sample of 91.6 × 10^6 Υ(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_γ = 609.3^(+4.6)_(-4.5)(stat)±1.9(syst) MeV, corresponding to an η_b(1S) mass of 9394.2^(+4.8)_(-4.9)(stat) ± 2.0(syst) MeV/c^2. The branching fraction for the decay Υ(2S) → γη_b(1S) is determined to be [3.9 ± 1.1(stat)^(+1.1)_(-0.9)(syst)] × 10^(-4). We find the ratio of branching fractions B[Υ(2S) → γη_b(1S)]/B[Υ(3S) → γη_b(1S)]= 0.82 ± 0.24(stat)^(+0.20)_(-0.19)(syst)

Measurement of B(B-->X_s {\gamma}), the B-->X_s {\gamma} photon energy spectrum, and the direct CP asymmetry in B-->X_{s+d} {\gamma} decays

The photon spectrum in B --> X_s {\gamma} decay, where X_s is any strange hadronic state, is studied using a data sample of (382.8\pm 4.2) \times 10^6 e^+ e^- --> \Upsilon(4S) --> BBbar events collected by the BABAR experiment at the PEP-II collider. The spectrum is used to measure the branching fraction B(B --> X_s \gamma) = (3.21 \pm 0.15 \pm 0.29 \pm 0.08)\times 10^{-4} and the first, second, and third moments = 2.267 \pm 0.019 \pm 0.032 \pm 0.003 GeV,, )^2> = 0.0484 \pm 0.0053 \pm 0.0077 \pm 0.0005 GeV^2, and )^3> = -0.0048 \pm 0.0011 \pm 0.0011 \pm 0.0004 GeV^3, for the range E_\gamma > 1.8 GeV, where E_{\gamma} is the photon energy in the B-meson rest frame. Results are also presented for narrower E_{\gamma} ranges. In addition, the direct CP asymmetry A_{CP}(B --> X_{s+d} \gamma) is measured to be 0.057 \pm 0.063. The spectrum itself is also unfolded to the B-meson rest frame; that is the frame in which theoretical predictions for its shape are made.Comment: 37 pages, 19 postscript figures, submitted to Phys. Rev. D. No analysis or results have changed from previous version. Some changes to improve clarity based on interactions with Phys. Rev. D referees, including one new Figure (Fig. 13), and some minor wording/punctuation/spelling mistakes fixe

Precise Measurement of the e+ e- --> pi+ pi- (gamma) Cross Section with the Initial-State Radiation Method at BABAR

A precise measurement of the cross section of the process $e^+e^-\to\pi^+\pi^-(\gamma)$ from threshold to an energy of 3GeV is obtained with the initial-state radiation (ISR) method using 232fb$^{-1}$ of data collected with the BaBar detector at $e^+e^-$ center-of-mass energies near 10.6GeV. The ISR luminosity is determined from a study of the leptonic process $e^+e^-\to\mu^+\mu^-(\gamma)\gamma_{\rm ISR}$, which is found to agree with the next-to-leading-order QED prediction to within 1.1%. The cross section for the process $e^+e^-\to\pi^+\pi^-(\gamma)$ is obtained with a systematic uncertainty of 0.5% in the dominant $\rho$ resonance region. The leading-order hadronic contribution to the muon magnetic anomaly calculated using the measured $\pi\pi$ cross section from threshold to 1.8GeV is $(514.1 \pm 2.2({\rm stat}) \pm 3.1({\rm syst}))\times 10^{-10}$.Comment: 58 pages, 56 figures, to be submitted to Phys. Rev.

Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-

In a sample of 471 million BB events collected with the BABAR detector at the PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is either e+e- or mu+mu-. We report results on partial branching fractions and isospin asymmetries in seven bins of di-lepton mass-squared. We further present CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi resonance. We find no evidence for CP or lepton-flavor violation. The partial branching fractions and isospin asymmetries are consistent with the Standard Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.