Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development

Hyperon signatures in the PANDA experiment at FAIR

We present a detailed simulation study of the signatures from the sequential decays of the triple-strange pbar p -> Ω+Ω- -> K+ΛbarK- Λ -> K+pbarπ+K-pπ- process in the PANDA central tracking system with focus on hit patterns and precise time measurement. We present a systematic approach for studying physics channels at the detector level and develop input criteria for tracking algorithms and trigger lines. Finally, we study the beam momentum dependence on the reconstruction efficiency for the PANDA detector

Measurement of proton electromagnetic form factors in the time-like region using initial state radiation at BESIII

The electromagnetic process is studied with the initial-state-radiation technique using 7.5 fb−1 of data collected by the BESIII experiment at seven energy points from 3.773 to 4.600 GeV. The Born cross section and the effective form factor of the proton are measured from the production threshold to 3.0 GeV/ using the invariant-mass spectrum. The ratio of electric and magnetic form factors of the proton is determined from the analysis of the proton-helicity angular distribution

Amplitude analysis and branching fraction measurement of D+s→K−K+π+π0

Relative fractions and phases of the intermediate decays are determined. With the detection efficiency estimated by the results of the amplitude analysis, the branching fraction of Dþ s → K−Kþπþπ0 decay is measured to be ð5.42 0.10stat 0.17systÞ%

Partial wave analysis of J/ψ→γη′η′

Using a sample of (10.09±0.04)×109 J/ψ events collected with the BESIII detector, a partial wave analysis of J/ψ→γη′η′ is performed.The masses and widths of the observed resonances and their branching fractions are reported. The main contribution is from J/ψ→γf0(2020) with f0(2020)→η′η′, which is found with a significance of greater than 25σ. The product branching fraction B(J/ψ → γf0(2020))⋅B(f0(2020) → η′η′ is measured to be (2.63±0.06(stat.) + 0.31−0.46(syst.))×10−4

Search for the decay D0→π0ν¯ν

We present the first experimental search for the rare charm decay D0→π0ν¯ν. It is based on an e+e− collision sample consisting of 10.6×10^6 pairs of D0¯D0 mesons collected by the BESIII detector at √s=3.773 GeV, corresponding to an integrated luminosity of 2.93 fb^−1. A data-driven method is used to ensure the reliability of the background modeling. No significant D0→π0ν¯ν signal is observed in data and an upper limit of the branching fraction is set to be 2.1×10^-4 at the 90% confidence level. This is the first experimental constraint on charmed-hadron decays into dineutrino final states

Amplitude analysis and branching fraction measurement of Ds+→K+K−π+D_s^+ → K^+ K^− π^+

Utilizing a data set corresponding to an integrated luminosity of 6.32~$\rm fb^{-1}$, recorded by the BESIII detector at center-of-mass energies between 4.178 and 4.226~GeV, we perform an amplitude analysis of the decay $D_{s}^{+} \to K_{S}^{0}\pi^{+}\pi^{0}$ and determine the relative fractions and phase differences of different intermediate processes, which include $K_{S}^{0}\rho(770)^{+}$, $K_{S}^{0}\rho(1450)^{+}$, $K^{*}(892)^{0}\pi^{+}$, $K^{*}(892)^{+}\pi^{0}$, and $K^{*}(1410)^{0}\pi^{+}$. Using a double-tag technique, and making an efficiency correction that relies on our knowledge of the phase-space distribution of the decays coming from the amplitude analysis, the absolute branching fraction is measured to be $\mathcal{B}(D_{s}^{+} \to K_{S}^{0}\pi^{+}\pi^{0})=(5.43\pm0.30_{\text{stat}}\pm 0.15_{\text{syst}})\times 10^{-3}$