Amyloid-β (Aβ) is a 39–42 residue protein produced by the cleavage of the amyloid precursor protein (APP), which subsequently aggregates to form cross-β amyloid fibrils that are a hallmark of Alzheimer’s disease (AD). The most prominent forms of Aβ are Aβ1–40 and Aβ1–42, which differ by two amino acids (I and A) at the C-terminus. However, Aβ42 is more neurotoxic and essential to the etiology of AD. Here, we present an atomic resolution structure of a monomorphic form of AβM01–42 amyloid fibrils derived from over 500 13C−13C, 13C−15N distance and backbone angle structural constraints obtained from high field magic angle spinning NMR spectra. The structure (PDB ID: 5KK3) shows that the fibril core consists of a dimer of Aβ42 molecules, each containing four β-strands in a S-shaped amyloid fold, and arranged in a manner that generates two hydrophobic cores that are capped at the end of the chain by a salt bridge. The outer surface of the monomers presents hydrophilic side chains to the solvent. The interface between the monomers of the dimer shows clear contacts between M35 of one molecule and L17 and Q15 of the second. Intermolecular 13C−15N constraints demonstrate that the amyloid fibrils are parallel in register. The RMSD of the backbone structure (Q15–A42) is 0.71 ± 0.12 Å and of all heavy atoms is 1.07 ± 0.08 Å. The structure provides a point of departure for the design of drugs that bind to the fibril surface and therefore interfere with secondary nucleation and for other therapeutic approaches to mitigate Aβ42 aggregation.

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Faster than ultrafast: A new sequence combining “ultrafast” single‐shot 2D NMR and parallel receiving technologies is presented. The potential of the resulting parallel ultrafast 2D spectroscopy (PUFSY) NMR experiments is shown by simultaneously collecting homo‐ and heteronuclear correlation information for 1H–19F systems (see picture) and a 1H–31P system.

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This is a repository copy of Self-consistent The carrier transition rates and subband populations for a GaAs/AlGaAs quantum cascade laser operating in the mid-infrared frequency range are calculated by solving the rate equations describing the electron densities in each subband self-consistently. These calculations are repeated for a range of temperatures from 20 to 300 K. The lifetime of the upper laser level found by this self-consistent method is then used to calculate the gain for this range of temperatures. At a temperature of 77 K, the gain of the laser is found to be 34 cm Ϫ1 /͑kA/cm Ϫ2 ͒, when only electron-longitudinal-optical phonon transitions are considered in the calculation. The calculated gain decreases to 19.6 cm Ϫ1 /͑kA/cm Ϫ2 ͒ when electron-electron transition rates are included, thus showing their importance in physical models of these devices. Further analysis shows that thermionic emission could be occurring in real devices.