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HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

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This paper reports the development of a series of 5-aroylindolyl-substituted hydroxamic acids. N-Hydroxy-4-((5-(4-methoxybenzoyl)-1 H-indol-1-yl)methyl)benzamide (6) has potent inhibitory selectivity against histone deacetylase 6 (HDAC6) with an IC value of 3.92 nM. It decreases not only the level of phosphorylation of tau proteins but also the aggregation of tau proteins. Compound 6 also shows neuroprotective activity by triggering ubiquitination. In animal models, compound 6 is able to ameliorate the impaired learning and memory, and it crosses the blood-brain barrier after oral administration. Compound 6 can be developed as a potential treatment for Alzheimer's disease in the future.

An earthquake process includes pre-seismic stress accumulation, co-seismic rock rupture and post-seismic elastic and/or viscoelastic rebound. Although co-seismic and post-seismic deformations have been readily observed using the global positioning system (GPS), detecting pre-seismic stress accumulation hidden in time-series data remains challenging. This study applies the Hilbert-Huang transform to extract non-linear and nonstationary pre-earthquake deformation data from GPS records for central Taiwan. By converting the derived surface deformation into horizontal azimuths, the randomly oriented GPS-azimuths are reoriented in a similar direction several days before and after earthquakes due to loading and rebound stress, respectively. Analytical results demonstrate that the stress accumulation and release along the entire course of an earthquake process provide significant evidence supporting the seismic rebound theory. This finding would be applicable to areas with dense GPS networks and active plate interactions. Surface deformations detected by the proposed analytical technique have encouraging potential for mitigating future seismic hazards.