ARTICLE | doi:10.20944/preprints201912.0359.v1
Subject: Earth Sciences, Geophysics Keywords: ocean waves; double-frequency microseisms; continental margin; continental slope
Online: 27 December 2019 (07:59:29 CET)
This study presents an exploration into identifying the interactions between ocean waves and the continental margin in the origination of double-frequency (DF, 0.1-0.5 Hz) microseisms recorded at 33 stations across East Coast of USA (ECUSA) during a ten-day period of ordinary ocean wave climate. Daily primary vibration directions are calculated in three frequency bands and projected as great circles passing through each station. In each band, the great circles from all stations exhibit largest spatial density primarily near the continental slope in the western North Atlantic Ocean. Generation mechanisms of three DF microseism events are explored by comparing temporal and spatial variations of the DF microseisms with the migration patterns of ocean wave fronts in Wavewatch III hindcasts. Correlation analyses are conducted by comparing the frequency compositions of and calculating the correlation coefficients between the DF microseisms and the ocean waves recorded at selected buoys. The observations and analyses lead to a hypothesis that the continental slope causes wave reflection, generating low frequency DF energy and that the continental shelf is where high frequency DF energy is mainly generated in ECUSA. The hypothesis is supported by the primary vibration directions being mainly perpendicular to the strike of the continental slope.
ARTICLE | doi:10.20944/preprints201808.0516.v1
Subject: Chemistry, Medicinal Chemistry Keywords: ALK5 inhibitor; TGF-β; kinase assay; selectivity; docking
Online: 30 August 2018 (05:52:08 CEST)
The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC50 value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.