A Cost-based Importance Measure for System Components: An Extension of the Birnbaum Importance

In reliability engineering, component importance measures are used to prioritise components in a system for purposes such as reliability improvement and maintenance planning. Existing importance measures have paid little attention to the costs incurred by maintaining a system and its components within a given time period. Cost-effectiveness analysis, however, is critically important in increasingly competitive markets. This paper proposes a new cost-based importance measure which considers costs incurred by maintaining a system and its components within a finite time horizon. Possible extensions are discussed and examples are given to show the use of the new measure

Redox Pioneer: Professor Irwin Fridovich

Dr. Irwin Fridovich (Ph.D., 1955) is recognized here as a Redox Pioneer because as first/last author he has published at least 1 paper on antioxidant/redox biology that has been cited over 1000 times and has published at least 10 papers each cited over 100 times. In collaboration with his graduate student, Joe McCord, Dr. Fridovich discovered the activity of superoxide dismutase (SOD). Subsequently, he and his colleagues demonstrated that the enzyme is ubiquitous among aerobic biota and comprises a critical defense against oxidative stress. With coworkers, Dr. Fridovich identified the first physiological targets of superoxide, the iron–sulfur clusters of dehydratases. They also showed that SOD is just one of several strategies by which cells fend off oxidative stress. It is now clear that organisms are chronically exposed to endogenous superoxide; further, microbes, plants, and mammals all employ superoxide as a weapon to poison their competitors. Thus, the achievement of Fridovich's laboratory was not only the seminal discovery of SOD but also the painstaking work over the subsequent decades that illuminated its place in biology. Antioxid. Redox Signal. 14, 355–340

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Critical Issues and Future Directions: Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution. Antioxid. Redox Signal. 20, 2416–2436