Spirooxindol-1,3-oxazine Alkaloids: Highly Potent and Selective Antitumor Agents Evolved from Iterative Structure Optimization

Spirooxindole-1,3-oxazines are a small and structurally unique class of spirooxindole alkaloids. To date, only four of these compounds have been isolated from natural sources, and their biological properties remained unknown thus far. Dioxyreserpine is a synthetic spirooxindole-1,3-oxazine, that can readily be prepared from the Rauvolfia alkaloid (–)-reserpine by catalytic photooxygenation. While dioxyreserpine itself was now identified as a moderately effective antitumoral agent, structurally modified analogs of it emerged as a new class of highly potent and selective growth inhibitors of various human cancers, including pancreatic cancers. Systematic structural optimization ultimately led to an inhibitor displaying low-micromolar IC₅₀-values against six cancer cell lines as well as selective apoptosis induction in vitro.     

Recent Progress in Developing a LiOH-Based Reversible Nonaqueous Lithium–Air Battery

The realization of practical nonaqueous lithium–air batteries (LABs) calls for novel strategies to address their numerous theoretical and technical challenges. LiOH formation/decomposition has recently been proposed as a promising alternative route to cycling LABs via Li₂O₂. Herein, the progress in developing LiOH-based nonaqueous LABs is reviewed. Various catalytic systems, either soluble or solid-state, that can activate a LiOH-based electrochemistry are compared in detail, with emphasis in providing an updated understanding of the oxygen reduction and evolution reactions in nonaqueous media. We identify the key factors that can switch the cell chemistry between Li₂O₂ and LiOH and highlight the debate around these routes, as well as rationalize potential causes for these opposing opinions. The identities of the reaction intermediates, activity of redox mediators and additives, location of reaction interfaces, causes of parasitic reactions, as well as the effect of CO₂ on the LiOH electrochemistry, all play a critical role in altering the relative rates of a series of interconnected reactions and all warrant further investigation.     

Testing the validity of the Networked Hazard Analysis and Risk Management System (Net-HARMS)

Testing the validity of newly developed methods is a critical component of human factors and ergonomics (HFE) practice. The Networked Hazard Analysis and Risk Management System (Net-HARMS) is a recently developed systems thinking-based risk assessment method which supports the identification of task and emergent risks across overall work systems. This article reports on a validity study of the Net-HARMS method in which outputs were compared to an expert analysis developed by the first two authors of this paper, with review by subject matter experts. The findings show that individual participant performance was poor for both groups yet when both group's analyses were pooled, validity significantly improved. Further, a subject matter expert analysis of the false alarms identified by participants showed that they may in fact represent credible risks. It is concluded that the Net-HARMS method achieved high levels of validity when participants analyses are pooled. The implications for risk assessment and the validity of HFE methods are discussed.