Nano-opto-electro-mechanical switches operated at CMOS-level voltages.

Combining reprogrammable optical networks with complementary metal-oxide semiconductor (CMOS) electronics is expected to provide a platform for technological developments in on-chip integrated optoelectronics. We demonstrate how opto-electro-mechanical effects in micrometer-scale hybrid photonic-plasmonic structures enable light switching under CMOS voltages and low optical losses (0.1 decibel). Rapid (for example, tens of nanoseconds) switching is achieved by an electrostatic, nanometer-scale perturbation of a thin, and thus low-mass, gold membrane that forms an air-gap hybrid photonic-plasmonic waveguide. Confinement of the plasmonic portion of the light to the variable-height air gap yields a strong opto-electro-mechanical effect, while photonic confinement of the rest of the light minimizes optical losses. The demonstrated hybrid architecture provides a route to develop applications for CMOS-integrated, reprogrammable optical systems such as optical neural networks for deep learning.

Bile Acid Sequestration by Cholestyramine Mitigates FGFR4 Inhibition-Induced ALT Elevation.

The FGF19- fibroblast growth factor receptor (FGFR4)-ßKlotho (KLB) pathway plays an important role in the regulation of bile acid (BA) homeostasis. Aberrant activation of this pathway has been described in the development and progression of a subset of liver cancers including hepatocellular carcinoma, establishing FGFR4 as an attractive therapeutic target for such solid tumors. FGF401 is a highly selective FGFR4 kinase inhibitor being developed for hepatocellular carcinoma, currently in phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one, increased BA pool size, decreased serum cholesterol and diarrhea in dogs. FGF401 was also associated with increases of serum aminotransferases, primarily alanine aminotransferase (ALT), in the absence of any observable adverse histopathological findings in the liver, or in any other organs. We hypothesized that the increase in ALT could be secondary to increased BAs and conducted an investigative study in dogs with FGF401 and coadministration of the BA sequestrant cholestyramine (CHO). CHO prevented and reversed FGF401-related increases in ALT in dogs in parallel to its ability to reduce BAs in the circulation. Correlation analysis showed that FGF401-mediated increases in ALT strongly correlated with increases in taurolithocholic acid and taurodeoxycholic acid, the major secondary BAs in dog plasma, indicating a mechanistic link between ALT elevation and changes in BA pool hydrophobicity. Thus, CHO may offer the potential to mitigate elevations in serum aminotransferases in human subjects that are caused by targeted FGFR4 inhibition and elevated intracellular BA levels.