It has long been recognized that cationic nanoparticles induce cell membrane permeability. Recently, it has been found that cationic nanoparticles induce the formation and/or growth of nanoscale holes in supported lipid bilayers. In this paper we show that non-cytotoxic concentrations of cationic nanoparticles induce 30-2000 pA currents in 293A and KB cells, consistent with a nanoscale defect such as a single hole or group of holes in the cell membrane ranging from 1 to 350 nm 2 in total area. Other forms of nanoscale defects, including the nanoparticle porating agents adsorbing onto or intercalating into the lipid bilayer are also consistent; although the size of the defect must increase to account for any reduction in ion conduction, as compared to a water channel. An individual defect forming event takes 1 -100 ms, while membrane resealing may occur over tens of seconds. Patchclamp data provide direct evidence for the formation of nanoscale defects in living cell membranes. The cationic polymer data are compared and contrasted with patch-clamp data obtained for AMO-3, a small molecule that is proposed to make well-defined 3.4 nm holes in lipid bilayers. Here, we observe data that are consistent with AMO-3 making ~3 nm holes in living cell membranes.

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With the rapid development of the Internet, many manufacturers nowadays are increasingly adopting a dual-channel to sell their products, i.e., the traditional retail channel and online direct channel. In this paper, we focus on retail service, manufacturer's direct service and quality effort, and present an analytical framework to examine the optimal decisions in dual-channel supply chain between the manufacturer and the retailer. Considering the efficacy of different supply chain structures, centralized and decentralized models are established. By using the backwards induction and the twostage optimization technique in Stackelberg game, the corresponding analytical equilibrium solutions are obtained. Our analysis shows that the degree of customer loyalty to the direct channel strongly influences the manufacturer's and the retailer's services and quality strategies in the decentralized dualchannel supply chain, but not in the centralized model. Our results also point out that compared to centralized model, for any given selling price, the ratio of profit margins of selling one unit in the direct and retail channels determines the retailer's service strategy; and the manufacturer will raise the level of direct channel service, but put less effort on quality improvement in the decentralized model. Finally, numerical examples present the contrasting view that disparate interests within a dual-channel supply chain can actually realize improving outcomes.Mathematics Subject Classification. 90B05, 90C29.

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