BackgroundSirtuins (Sirt), a family of nicotinamide adenine nucleotide (NAD) dependent deacetylases, are implicated in energy metabolism and life span. Among the known Sirt isoforms (Sirt1-7), Sirt3 was identified as a stress responsive deacetylase recently shown to play a role in protecting cells under stress conditions. Here, we demonstrated the presence of Sirt3 in neurons, and characterized the role of Sirt3 in neuron survival under NMDA-induced excitotoxicity.Methodology/Principal FindingsTo induce excitotoxic injury, we exposed primary cultured mouse cortical neurons to NMDA (30 µM). NMDA induced a rapid decrease of cytoplasmic NAD (but not mitochondrial NAD) in neurons through poly (ADP-ribose) polymerase-1 (PARP-1) activation. Mitochondrial Sirt3 was increased following PARP-1 mediated NAD depletion, which was reversed by either inhibition of PARP-1 or exogenous NAD. We found that massive reactive oxygen species (ROS) produced under this NAD depleted condition mediated the increase in mitochondrial Sirt3. By transfecting primary neurons with a Sirt3 overexpressing plasmid or Sirt3 siRNA, we showed that Sirt3 is required for neuroprotection against excitotoxicity.ConclusionsThis study demonstrated for the first time that mitochondrial Sirt3 acts as a prosurvival factor playing an essential role to protect neurons under excitotoxic injury.

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Health management and reliability form a fundamental part of the design and development cycle of electronic products. In this paper compact real-time thermal models are used to predict temperatures of inaccessible locations within the power module. These models are then combined with physics of failure based reliability analysis to provide in-service predictions of crack propagation in solder layers and at the bond wire joints as a result of thermal cycling. The temperature estimates are combined with lifetime based reliability models to provide a tool for life consumption monitoring. Rainflow counting algorithms are applied to the temperature vs. time data to extract the occurrence frequencies of different thermal cycling ranges. Knowledge of the life consumed for each different cycle then allows the remaining life time to be estimated under arbitrary operational conditions. The technique can be employed to provide functions such as life consumption monitoring and prognostic maintenance scheduling.