Effects of macro vs. micro initialization and ocean initial-condition memory on the evolution of ensemble spread in the CESM2 large ensemble.

Unlabelled: "Single Model initial-condition Large Ensembles" (SMILEs) conducted with Earth system models have transformed our ability to quantify internal climate variability and forced climate change at local and regional scales. An important consideration in their experimental design is the choice of initialization procedure as this influences the duration of initial-condition memory, with implications for interpreting the temporal evolution of both the ensemble-mean and ensemble-spread. Here we leverage the strategic design of the 100-member Community Earth System Model version 2 (CESM2) SMILE to investigate the dependence of ensemble spread on the method of initialization (micro- vs.

Discovery of (2,4)-4-(()-2-Amino-3-methylbutanamido)-2-(4-boronobutyl)pyrrolidine-2-carboxylic Acid (AZD0011), an Actively Transported Prodrug of a Potent Arginase Inhibitor to Treat Cancer.

Arginase is a promising immuno-oncology target that can restore the innate immune response. However, it's highly polar active site often requires potent inhibitors to mimic amino acids, leading to poor passive permeability and low oral exposure. Using structure-based drug design, we discovered a novel proline-based arginase inhibitor () that was potent but had low oral bioavailability in rat.

Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach.

There is considerable interest in understanding the developmental origins and health implications of individual differences in brain structure and function. In this pre-registered study we demonstrate that a hidden subgroup within the general population-people with synesthesia (e.g.

Design and Synthesis of Acyclic Boronic Acid Arginase Inhibitors.

Arginase has long been a target of interest in immuno-oncology, but discovering an orally bioavailable inhibitor is severely constrained by the requisite boronic acid pharmacophore. We began our drug discovery campaign by building off the β-position of the literature inhibitor ABH (). A divergent synthesis with an Ireland-Claisen rearrangement as the key step allowed access to numerous compounds, some of which we crystallized in the active site of arginase 2.

The role of dissolved organic carbon in Great Smoky Mountains National Park streams impacted by long-term acid deposition.

Following reductions in acid deposition in the Great Smoky Mountains National Park (GRSM) since the 2000s, many streams remain acidic and the role of organic acids (OA) remains unknown due to limited OA data. This study investigated dissolved organic carbon (DOC) concentrations as a surrogate for OA across GRSM and its relationships with watershed characteristics, seasons, flow, and stream chemistry. Baseflow water samples were collected from seven watersheds for 2 years and stormflow samples from three watersheds for 1 year.