Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.

This paper describes the fabrication of a wireless, passive sensor based on an inductive-capacitive resonant circuit, and its application for in situ monitoring of the quality of dry, packaged food such as cereals, and fried and baked snacks. The sensor is made of a planar inductor and capacitor printed on a paper substrate. To monitor food quality, the sensor is embedded inside the food package by adhering it to the package's inner wall; its response is remotely detected through a coil connected to a sensor reader. As food quality degrades due to increasing humidity inside the package, the paper substrate absorbs water vapor, changing the capacitor's capacitance and the sensor's resonant frequency. Therefore, the taste quality of the packaged food can be indirectly determined by measuring the change in the sensor's resonant frequency. The novelty of this sensor technology is its wireless and passive nature, which allows in situ determination of food quality. In addition, the simple fabrication process and inexpensive sensor material ensure a low sensor cost, thus making this technology economically viable.

A series of semiconducting small molecules with bithiophene or bis‐3,4‐ethylenedioxythiophene cores are designed and synthesized. The molecules display stable reversible oxidation in solution and can be reversibly oxidized in the solid state with aqueous electrolyte when functionalized with polar triethylene glycol side chains. Evidence of promising ion injection properties observed with cyclic voltammetry is complemented by strong electrochromism probed by spectroelectrochemistry. Blending these molecules with high molecular weight polyethylene oxide (PEO) is found to improve both ion injection and thin film stability. The molecules and their corresponding PEO blends are investigated as active layers in organic electrochemical transistors (OECTs). For the most promising molecule:polymer blend (P4E4:PEO), p‐type accumulation mode OECTs with µA drain currents, μS peak transconductances, and a µC* figure‐of‐merit value of 0.81 F V−1 cm−1 s−1 are obtained.

Abstract

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