In recent studies of transgenic models of Alzheimer's disease (AD), it has been reported that antibodies to aged beta amyloid peptide 1±42 (Ab 1242 ) solutions (mixtures of Ab monomers, oligomers and amyloid ®brils) cause conspicuous reduction of amyloid plaques and neurological improvement. In some cases, however, neurological improvement has been independent of obvious plaque reduction, and it has been suggested that immunization might neutralize soluble, non®brillar forms of Ab. It is now known that Ab toxicity resides not only in ®brils, but also in soluble proto®brils and oligomers. The current study has investigated the immune response to low doses of Ab 1242 oligomers and the characteristics of the antibodies they induce. Rabbits that were injected with Ab 1242 solutions containing only monomers and oligomers produced antibodies that preferentially bound to assembled forms of Ab in immunoblots and in physiological solutions. The antibodies have proven useful for assays that can detect inhibitors of oligomer formation, for immuno¯uorescence localization of cell-attached oligomers to receptor-like puncta, and for immunoblots that show the presence of SDS-stable oligomers in Alzheimer's brain tissue. The antibodies, moreover, were found to neutralize the toxicity of soluble oligomers in cell culture. Results support the hypothesis that immunizations of transgenic mice derive therapeutic bene®t from the immunoneutralization of soluble Ab-derived toxins. Analogous immuno-neutralization of oligomers in humans may be a key in AD vaccines.

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Alzheimer's disease is the most common cause of dementia in older individuals with compelling evidence favoring neuron dysfunction and death triggered by assembled forms of A beta(1-42). While large neurotoxic amyloid fibrils have been known for years, recent studies show that soluble protofibril and A beta(1-42)-derived diffusible ligands (ADDLs) may also be involved in neurotoxicity. In the present work, dot-blot immunoassays discriminating ADDLs from monomers were used to screen libraries of per-substituted beta-cyclodextrin (beta-CD) derivatives for inhibition of ADDLs formation. Libraries were prepared from per-6-iodo-beta-CD by treatment with various amine nucleophiles. The most active library tested (containing >2000 derivatives) was derived from imidazole, N, N-dimethylethylenediamine and furfurylamine, which at 10 microM total library, inhibited ADDLs formation (10 nM A beta(1-42)) over a period of 4 hours. The latter was confirmed by a western blot assay showing decreased amounts of the initially formed A beta(1-42) tetramer. These preliminary experiments suggest that derivatized forms of beta-CD can interfere with the oligomerization process of A beta(1-42).

Although monolayer transition metal dichalcogenides (TMDs) have direct bandgaps, the low room-temperature photoluminescence quantum yields (QYs), especially under high pump intensity, limit their practical applications. Here, we use a simple photoactivation method to enhance the room-temperature QYs of monolayer MoS2 grown on to silica micro/nanofibers by more than two orders of magnitude in a wide pump dynamic range. The high-density oxygen dangling bonds released from the tapered micro/nanofiber surface are the key to this strong enhancement of QYs. As the pump intensity increases from 10−1 to 104 W cm−2, our photoactivated monolayer MoS2 exhibits QYs from ~30 to 1% while maintaining high environmental stability, allowing direct lasing with greatly reduced thresholds down to 5 W cm−2. Our strategy can be extended to other TMDs and offers a solution to the most challenging problem toward the realization of efficient and stable light emitters at room temperature based on these atomically thin materials.

The solubilities of oleanolic acid (OA) and ursolic acid (UA) in ethanol + sodium hydroxide + water mixed solvents were measured at different temperatures (283.2, 298.2, 293.2, 298.2, 303.2, 308.2, 313.2, 318.2, and 323.2 K). The solubility of OA in the mixed solvents increased with temperature. However, the solubility of UA in the mixed solvents first increased with temperature, and then decreased with temperature. The solubilities of both OA and UA increased with the initial mole fraction of ethanol in the mixed solvents. The addition of NaOH could improve the solubilities of OA and UA in the aqueous ethanol solution. The solubility of OA was correlated with temperature by the van’t Hoff model, the modified Apelblat model and the λh model, and the results indicated that the λh model had better correlation. The solubility of UA was correlated with temperature only by an empirical cubic equation.