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β-Secretase (memapsin 2; BACE-1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid-β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer's disease (AD). Therefore, β-secretase is a major therapeutic target for the development of inhibitor(More)
—For the development of new 5G systems to operate in bands up to 100 GHz, there is a need for accurate radio propagation models at these bands that currently are not addressed by existing channel models developed for bands below 6 GHz. This document presents a preliminary overview of 5G channel models for bands up to 100 GHz. These have been derived based(More)
beta-Secretase (memapsin 2, BACE1) is an attractive target for the development of inhibitor drugs to treat Alzheimer's disease (AD). Not only does this protease function at the first step in the pathway leading to the production of amyloid-beta (Abeta), its gene deletion produces only mild phenotypes. In addition, beta-secretase is an aspartic protease(More)
β-Secretase is an attractive target of amyloid-reduction therapy for Alzheimer's disease. Currently, no efficacy data is available from clinical trials of β-secretase inhibitors. Treating young transgenic Tg2576 mice with a brain-penetrating β-secretase inhibitor reduced brain amyloid-β by about 50% and rescued the age-related cognitive decline.(More)
Alzheimer disease is intimately linked to an excess amount of amyloid-β (Aβ) in the brain. Thus, therapeutic inhibition of Aβ production is an attractive clinical approach to treat this disease. Here we provide the first direct experimental evidence that the treatment of Tg2576 transgenic mice with an inhibitor of β-secretase, GRL-8234, rescues the(More)
Laulimalide is a cytotoxic natural product that stabilizes microtubules. The compound enhances tubulin assembly, and laulimalide is quantitatively comparable to paclitaxel in its effects on the reaction. Laulimalide is also active in P-glycoprotein overexpressing cells, while isolaulimalide, a congener without the drug's epoxide moiety, was reported to have(More)
We have previously reported structure-based design of memapsin 2 (beta-secretase) inhibitors with high potency. Here we show that two such inhibitors covalently linked to a "carrier peptide" penetrated the plasma membrane in cultured cells and inhibited the production of beta-amyloid (Abeta). Intraperitoneal injection of the conjugated inhibitors in(More)
The metalloprotease activity of lethal factor (LF) from Bacillus anthracis (B. anthracis) is a main source of toxicity in the lethality of anthrax infection. Thus, the understanding of the enzymatic activity and inhibition of B. anthracis LF is of scientific and clinical interests. We have designed, synthesized, and studied a peptide inhibitor of LF,(More)
—Future mobile communications systems are likely to be very different to those of today with new service innovations driven by increasing data traffic demand, increasing processing power of smart devices and new innovative applications. To meet these service demands the telecommunications industry is converging on a common set of 5G requirements which(More)
The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this Perspective, we present properties and stabilities of carbamates, reagents and chemical(More)