RESUMEN
Alzheimer's disease (AD) is a neurological disorder associated with amyloid ß-protein (Aß) assembly into toxic oligomers. In addition to the two predominant alloforms, Aß1-40 and Aß1-42, other C-terminally truncated Aß peptides, including Aß1-38 and Aß1-43, are produced in the brain. Here, we use discrete molecular dynamics (DMD) and a four-bead protein model with amino acid-specific hydropathic interactions, DMD4B-HYDRA, to examine oligomer formation of Aß1-38, Aß1-40, Aß1-42, and Aß1-43. Self-assembly of 32 unstructured monomer peptides into oligomers is examined using 32 replica DMD trajectories for each of the four peptides. In a quasi-steady state, Aß1-38 and Aß1-40 adopt similar unimodal oligomer size distributions with a maximum at trimers, whereas Aß1-42 and Aß1-43 oligomer size distributions are multimodal with the dominant maximum at trimers or tetramers, and additional maxima at hexamers and unidecamers (for Aß1-42) or octamers and pentadecamers (for Aß1-43). The free energy landscapes reveal isoform- and oligomer-order specific structural and morphological features of oligomer ensembles. Our results show that oligomers of each of the four isoforms have unique features, with Aß1-42 alone resulting in oligomers with disordered and solvent-exposed N-termini. Our findings help unravel the structure-function paradigm governing oligomers formed by various Aß isoforms.
Asunto(s)
Péptidos beta-Amiloides , Simulación de Dinámica Molecular , Isoformas de Proteínas , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Humanos , Multimerización de Proteína , Enfermedad de Alzheimer/metabolismo , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismoRESUMEN
Voice-based discussion forums where users can record audio messages which are then published for other users to listen and comment, are often moderated to ensure that the published audios are of good quality, relevant, and adhere to editorial guidelines of the forum. There is room for the introduction of AI-based tools in the moderation process, such as to identify and filter out blank or noisy audios, use speech recognition to transcribe the voice messages in text, and use natural language processing techniques to extract relevant metadata from the audio transcripts. We design such tools and deploy them within a social enterprise working in India that runs several voice-based discussion forums. We present our findings in terms of the time and cost-savings made through the introduction of these tools, and describe the feedback of the moderators towards the acceptability of AI-based automation in their workflow. Our work forms a case-study in the use of AI for automation of several routine tasks, and can be especially relevant for other researchers and practitioners involved with the use of voice-based technologies in developing regions of the world.
RESUMEN
It is well known that oscillating magnetization induces charge current in a circuit via Faraday's law of electromagnetic induction. New physical phenomena by which magnetization dynamics can produce charge current have gained considerable interest recently. For example, moving magnetization textures, such as domain walls, generates charge current through the spin-motive force. Here, we examine an entirely different effect, which couples magnetization and electric field at the interface between an ultrathin metallic ferromagnet and dielectric. We show that this coupling can convert magnetic energy into electrical energy. This phenomenon is the Onsager reciprocal of the voltage-controlled magnetic anisotropy effect. The effect provides a previously unexplored probe to measure the magnetization dynamics of nanomagnets.