Backgrounds and Aims:Bentonite is commonly added to white wines to remove the grape proteins responsible for haze formation. Despite being effective, this technique has drawbacks; thus, new solutions are desirable. The ability of carrageenan and pectin to remove heat-unstable grape proteins, and the impact that such addition has on the physicochemical and sensorial profile of a wine were assessed. Methods and Results: Carrageenan and pectin were added separately or in combination to a Chardonnay juice prior to fermentation. Both adsorbents removed proteins (up to 75%), thus increasing wine protein stability. Carrageenan was more effective than pectin at increasing wine protein stability. Conclusions: Pectin and carrageenan removed protein and partially stabilized the samples of the wine. Significance of the Study: Pre-fermentation addition of pectin or carrageenan may provide the wine industry with an alternative protein stabilization procedure. AbbreviationsCIELAB Commission Internationale de l'Eclairage Lab transmission values L* a* b*; NTU nephelometric turbidity units; Tukey-Kramer HSD test Tukey-Kramer honestly significance difference test.

Necroptosis has been implicated in a variety of disease states, and RIPK3 is one of the kinases identified to play a critical role in this signaling pathway. In an effort to identify RIPK3 kinase inhibitors with a novel profile, mechanistic studies were incorporated at the hit triage stage. Utilization of these assays enabled identification of a Type II DFG-out inhibitor for RIPK3, which was confirmed by protein crystallography. Structure-based drug design on the inhibitors targeting this previously unreported conformation enabled an enhancement in selectivity against key off-target kinases.

A total synthesis of cylindramide A has been completed in 19 steps. The key step of the synthesis is a tandem ring-opening-ring-closing-cross metathesis that converts a readily available norbornene into an advanced intermediate.

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Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.