Quantitative Comparison of Dense-Core Amyloid Plaque Accumulation in Amyloid-β Protein Precursor Transgenic Mice.

There exist several dozen lines of transgenic mice that express human amyloid-β protein precursor (AβPP) with Alzheimer's disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD.

Design Optimization of Hybrid-Switch Soft-Switching Inverters Using Multiscale Electrothermal Simulation.

A multiscale electrothermal simulation approach is presented to optimize the design of a hybrid switch soft-switching inverter using a library of dynamic electrothermal component models parameterized in terms of electrical, structural, and material properties. Individual device area, snubber capacitor, and gate drive timing are used to minimize the total loss of the soft-switching inverter module subject to the design constraints including total device area and minimum on-time consideration. The proposed multiscale electrothermal simulation approach allows for a large number of parametric studies involving multiple design variables to be considered, drastically reducing simulation time.

Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration.

The accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer's disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here we show that Aβ oligomers can be assigned to one of at least two classes (type 1 and type 2) based on their temporal, spatial, and structural relationships to amyloid fibrils.