Atmospheric CO is thought to play a fundamental role in Earth's climate regulation. Yet, for much of Earth's geological past, atmospheric CO has been poorly constrained, hindering our understanding of transitions between cool and warm climates. Beginning ~370 million years ago in the Late Devonian and ending ~260 million years ago in the Permian, the Late Palaeozoic Ice Age was the last major glaciation preceding the current Late Cenozoic Ice Age and possibly the most intense glaciation witnessed by complex lifeforms.
View Article and Find Full Text PDFBackground: Neurohormonal blocking drugs, like beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), are recommended for treating anthracycline-induced left ventricular dysfunction (AILVD). However, there is limited evidence supporting their benefit. Therefore, this study evaluated associations of neurohormonal blockers and other clinical factors with recovery of left ventricular ejection fraction (LVEF) in patients with AILVD.
View Article and Find Full Text PDFInhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC value of 47 pM and is 10 times more potent than ARV-471.
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