This Letter reports the first extraction of individual antineutrino spectra from 235 U and 239 Pu fission and an improved measurement of the prompt energy spectrum of reactor antineutrinos at Daya Bay. The analysis uses 3.5 × 10 6 inverse beta-decay candidates in four near antineutrino detectors in 1958 days. The individual antineutrino spectra of the two dominant isotopes, 235 U and 239 Pu, are extracted using the evolution of the prompt spectrum as a function of the isotope fission fractions. In the energy window of 4-6 MeV, a 7% (9%) excess of events is observed for the 235 U (239 Pu) spectrum compared with the normalized Huber-Mueller model prediction. The significance of discrepancy is 4.0σ for 235 U spectral shape compared with the Huber-Mueller model prediction. The shape of the measured inverse beta-decay prompt energy spectrum disagrees with the prediction of the Huber-Mueller model at 5.3σ. In the energy range of 4-6 MeV, a maximal local discrepancy of 6.3σ is observed.

Objective To assess the value of ovarian volume and follicle number in the diagnosis of polycystic ovary syndrome (PCOS)

Pulmonary arterial hypertension (PAH) causes pathological increase in pulmonary vascular resistance, leading to right-heart failure and eventual death. Previously, phosphodiesterase-10 (PDE10) was reported to be a promising target for PAH based on the studies with a nonselective PDE inhibitor papaverine, but little progress has been made to confirm the practical application of PDE10 inhibitors. To validate whether PAH is ameliorated by PDE10 inhibition rather than other PDE isoforms, here we report an integrated strategy to discover highly selective PDE10 inhibitors as chemical probes. Structural optimization resulted in a PDE10 inhibitor 2b with subnanomolar affinity and good selectivity of >45 000-fold against other PDEs. The cocrystal structure of the PDE10–2b complex revealed an important H-bond interaction between 2b and Tyr693. Finally, compound 2b significantly decreased the arterial pressure in PAH rats and thus validated the potential of PDE10 as a novel anti-PAH target. These findings suggest that PDE10 inhibition may be a viable treatment option for PAH.

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