A metric for predicting binaural speech intelligibility in stationary noise and competing speech maskers

One criterion in the design of binaural sound scenes in audio production is the extent to which the intended speech message is correctly understood. Object-based audio broadcasting systems have permitted sound editors to gain more access to the metadata (e.g., intensity and location) of each sound source, providing better control over speech intelligibility. The current study describes and evaluates a binaural distortion-weighted glimpse proportion metric -- BiDWGP -- which is motivated by better-ear glimpsing and binaural masking level differences. BiDWGP predicts intelligibility from two alternative input forms: either binaural recordings or monophonic recordings from each sound source along with their locations. Two listening experiments were performed with stationary noise and competing speech, one in the presence of a single masker, the other with multiple maskers, for a variety of spatial configurations. Overall, BiDWGP with both input forms predicts listener keyword scores with correlations of 0.95 and 0.91 for single- and multi-masker conditions, respectively. When considering masker type separately, correlations rise to 0.95 and above for both types of maskers. Predictions using the two input forms are very similar, suggesting that BiDWGP can be applied to the design of sound scenes where only individual sound sources and their locations are available

Polyol pathway impairs the function of SERCA and RyR in ischemic-reperfused rat hearts by increasing oxidative modifications of these proteins

A number of studies have shown that the polyol pathway, consisting of aldose reductase (AR) and sorbitol dehydrogenase (SDH), contributes to ischemia-reperfusion (I/R)-induced myocardial infarction due to depletion of ATP. In this report we show that the polyol pathway in I/R heart also contributes to the impairment of sacro/endoplasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR), two key players in Ca2+ signaling that regulate cardiac contraction. Rat hearts were isolated and retrogradely perfused with either Krebs' buffer containing 1 ?M AR inhibitor, zopolrestat, or 200 nM SDH inhibitor, CP-170,711, and challenged by 30 min of regional ischemia and 45 min of reperfusion. We found that post-ischemic contractile function of the isolated perfused hearts was improved by pharmacological inhibition of the polyol pathway. I/R-induced contractile dysfunction is most likely due to impairment in Ca2+ signaling and the activities of SERCA and RyR. All these abnormalities were significantly ameliorated by treatment with ARI or SDI. We showed that the polyol pathway activities increase the level of peroxynitrite, which enhances the tyrosine nitration of SERCA and irreversibly modifies it to form SERCAC674-SO3H. This leads to reduced level of S-glutathiolated SERCA, contributing to its inactivation. The polyol pathway activities also deplete the level of GSH, leading to decreased active RyR, the S-glutathiolated RyR. Thus, in I/R heart, inhibition of polyol pathway improved the function of SERCA and RyR by protecting them from irreversible oxidation. © 2009 Elsevier Ltd.link_to_subscribed_fulltex

Protein O-GlcNAcylation is required for fibroblast growth factor signaling in Drosophila

Glycosylation is essential for growth factor signaling through N-glycosylation of ligands and receptors and the biosynthesis of proteoglycans as co-receptors. Here, we show that protein O-GlcNAcylation is crucial for fibroblast growth factor (FGF) signaling in Drosophila. We found that nesthocker (nst) encodes a phosphoacetylglucosamine mutase and that nst mutant embryos exhibited low amounts of intracellular uridine 5′-diphosphate–N-acetylglucosamine (UDP-GlcNAc), which disrupted protein O-GlcNAcylation. Nst was required for mitogen-activated protein kinase (MAPK) signaling downstream of FGF but not MAPK signaling activated by epidermal growth factor. nst was dispensable for the function of the FGF ligands and the FGF receptor’s extracellular domain but was essential in the signal-receiving cells downstream of the FGF receptor. We identified the adaptor protein Downstream of FGF receptor (Dof), which interacts with the FGF receptor, as the relevant target for O-GlcNAcylation in the FGF pathway, suggesting that protein O-GlcNAcylation of the activated receptor complex is essential for FGF signal transduction