Cleavage of endogenous gamma ENaC and elevated abundance of alpha ENaC are associated with increased Na+ transport in response to apical fluid volume expansion in human H441 airway epithelial cells

Using human H441 airway epithelial cells cultured at air–liquid interface (ALI), we have uniquely correlated the functional response to apical fluid volume expansion with the abundance and cleavage of endogenous α- and γENaC proteins in the apical membrane. Monolayers cultured at ALI rapidly elevated I(sc) when inserted into fluid-filled Ussing chambers. The increase in I(sc) was not significantly augmented by the apical addition of trypsin, and elevation was abolished by the protease inhibitor aprotinin and an inhibitor of the proprotein convertase, furin. These treatments also increased the IC(50) amiloride indicating that the effect was via inhibition of highly Na(+)-selective ENaC channels. Apical fluid, 5–500 μl for 1 h in culture, increased the spontaneous starting I(sc) in a dose-dependent manner, whilst maximal fluid-induced I(sc) in the Ussing chamber was unchanged. Apical fluid expansion increased the abundance of 63–65-kDa αENaC proteins in the apical membrane. However, this could not be attributed to increased cleavage as protease inhibitors had no effect on the ratio of cleaved to non-cleaved (90 kDa) αENaC proteins. Instead, fluid expansion increased αENaC abundance in the membrane. In contrast, function correlated well with γENaC cleavage at known sites by furin and extracellular proteases. Interestingly, cleavage of γENaC was associated with increased retrieval from the membrane via the proteosomal pathway. Thus, the response to apical fluid volume expansion in H441 airway epithelial cells involves cleavage of γENaC, and changes in α- and γENaC protein abundance at the apical membrane. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00424-011-0982-x) contains supplementary material, which is available to authorized users

Plasmonic nanogap enhanced phase-change devices with dual electrical-optical functionality

This is the final version. Available from American Association for the Advancement of Science via the DOI in this record. Modern-day computers rely on electrical signaling for the processing and storage of data, which is bandwidth-limited and power hungry. This fact has long been realized in the communications field, where optical signaling is the norm. However, exploiting optical signaling in computing will require new on-chip devices that work seamlessly in both electrical and optical domains, without the need for repeated electrical-to-optical conversion. Phase-change devices can, in principle, provide such dual electrical-optical operation, but assimilating both functionalities into a single device has so far proved elusive owing to conflicting requirements of size-limited electrical switching and diffraction-limited optical response. Here, we combine plasmonics, photonics, and electronics to deliver an integrated phase-change memory cell that can be electrically or optically switched between binary or multilevel states. Crucially, this device can also be simultaneously read out both optically and electrically, offering a new strategy for merging computing and communications technologies.European CommissionEPSRCDeutsche ForschungsgemeinschaftEuropean Research CouncilEuropean Union’s Horizon 2020 research and innovation progra

A Randomized Clinical Trial Comparing Individual Cognitive Behavioral Therapy and Child-Centered Therapy for Child Anxiety Disorders

This study compared individual cognitive behavioral therapy (CBT) and a supportive child-centered therapy (CCT) for child anxiety disorders on rates of treatment response and recovery at posttreatment and 1-year follow-up, as well as on real-world measures of emotional functioning. Youth (N = 133; ages 9–14) with anxiety disorders (generalized, separation, and/or social anxiety) were randomized using a 2:1 ratio to CBT (n = 90) or CCT (n = 43), which served as an active comparison. Treatment response and recovery at posttreatment and 1-year follow-up were assessed by Independent Evaluators, and youth completed ecological momentary assessment of daily emotions throughout treatment. The majority of youth in both CBT and CCT were classified as treatment responders (71.1% for CBT, 55.8% for CCT), but youth treated with CBT were significantly more likely to fully recover, no longer meeting diagnostic criteria for any of the targeted anxiety disorders and no longer showing residual symptoms (66.7% for CBT vs. 46.5% for CCT). Youth treated with CBT also reported significantly lower negative emotions associated with recent negative events experienced in daily life during the latter stages of treatment relative to youth treated with CCT. Furthermore, a significantly higher percentage of youth treated with CBT compared to CCT were in recovery at 1-year follow-up (82.2% for CBT vs. 65.1% for CCT). These findings indicate potential benefits of CBT above and beyond supportive therapy on the breadth, generalizability, and durability of treatment-related gains

Experimental Research on the Shear Connectors in Foam Concrete

In order to improve the longitudinal shear resistance between foam concrete and C-Channels, an investigation is carried out on the shear connectors in foam concrete with cold-formed steel double C-Channels embedment. Twenty-four tests have been carried out in two groups. Two types of connectors: flange connectors and web connectors are installed using self-drilling screws for a rapid construction. The experimental results show that they can effectively improve the longitudinal shear-resist capacity of the concrete. After the experiment, the specimens are dismantled for an interior observation. Based on the observation, the form of damage, the failure mechanism was discovered, and the equation of longitudinal shear capacity was developed. It is concluded that the failure involves independent slippage between two C-Channels and the shear connection fractures. Since the composite structure requires sufficient slip between the two materials, these types of shear connectors will have good enhancement for this type of composite structures subjected to dynamic loads