Treatment for castration-resistant prostate cancer (CRPC) primarily involves the suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling, or lineage plasticity that drives emergence of AR-independent phenotypes.
View Article and Find Full Text PDFThe global seasonal cycle of energy in Earth's climate system is quantified using observations and reanalyses. After removing long-term trends, net energy entering and exiting the climate system at the top of the atmosphere (TOA) should agree with the sum of energy entering and exiting the ocean, atmosphere, land, and ice over the course of an average year. Achieving such a balanced budget with observations has been challenging.
View Article and Find Full Text PDFSatellite observations from the Clouds and the Earth's Radiant Energy System show that Earth's energy imbalance has doubled from 0.5 ± 0.2 Wm during the first 10 years of this century to 1.
View Article and Find Full Text PDFThis study uses an oceanic energy budget to estimate the ocean heat transport convergence in the North Atlantic during 2005-2018. The horizontal convergence of the ocean heat transport is estimated using ocean heat content tendency primarily derived from satellite altimetry combined with space gravimetry. The net surface energy fluxes are inferred from mass-corrected divergence of atmospheric energy transport and tendency of the ECMWF ERA5 reanalysis combined with top-of-the-atmosphere radiative fluxes from the clouds and the Earth's radiant energy system project.
View Article and Find Full Text PDFCirculating tumor DNA (ctDNA) in plasma cell free DNA (cfDNA) of cancer patients is associated with poor prognosis, but is challenging to detect from low plasma volumes. In metastatic castration-resistant prostate cancer (mCRPC), ctDNA assays are needed to prognosticate outcomes of patients treated with androgen receptor (AR) inhibitors. We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone.
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