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Despite progress in defining a pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction. METHODS: Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic function and memory recall. RESULTS: Scyllo-inositol, but not its stereoisomer, chiro-inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human Abeta. Cerebroventricular injection into rats of the soluble Abeta oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo-inositol via the drinking water fully prevented oligomer-induced errors. INTERPRETATION: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity.

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Results are presented for e(+) scattering by H- in the impact energy range 0less than or equal toE(0)less than or equal to10 eV. These include integrated cross sections for Ps formation in the 1s, 2s, and 2p states, as well as in an aggregate of states with ngreater than or equal to3, and for direct ionization. Differential cross sections for Ps formation in the 1s, 2s, and 2p states are also exhibited. The calculations are based on a coupled pseudostate approach employing 19 Ps pseudostates centered on the e(+). It is found that Ps formation in the 2p state dominates that in the 1s or 2s states below 8 eV, that formation in states with ngreater than or equal to3 exceeds the sum of the n=1 and n=2 cross sections above 2.5 eV, and that direct ionization outstrips total Ps formation above 6.3 eV. The threshold law (E-0-->0) for exothermic Ps formation, which includes the cases Ps(1s), Ps(2s), and Ps(2p), is shown to be 1/E-0.

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First steps are taken to model the electrochemical deposition of metals in nanometer-sized cavities. In the present work, the electrochemical deposition of Cu atoms in nanometer-sized holes dug on Au(111) is investigated through Monte Carlo simulations using the embedded atom method to represent particle interactions. By sweeping the chemical potential of Cu, a cluster is allowed to grow within the hole rising four atomic layers above the surface. Its lateral extension remains confined to the area defined by the borders of the original defect. (C) 2004 Elsevier B.V. All rights reserved.