this clone were often debilitated by underlying diseases, such as cancer. Due to the increased public health interest about MRSAST398, further studies should be conducted to record risk factors from infected or colonized patients by this lineage such as routes of transmission and association with animals. Severely elevated core temperature, as well as organ and tissue damage resulting from environmental heat exposure. Environmental heat exposure is one of the most deadly natural hazards in the United States with,200 deaths per year. In the past two decades, extreme heat exposure claimed more American lives than the combined effects of hurricanes, lightning, earthquakes, floods and tornadoes. HS is also an international hazard as demonstrated by the high incidence of death during the 2003 heat wave in France. Clinical and experimental evidence suggests that the pathophysiological responses to HS are the result of a systemic inflammatory response syndrome that ensues following HS collapse. The SIRS is regarded as a response to bacteria and/or endotoxin leakage across ischemicdamaged gut epithelial barrier membranes, which stimulates cytokine and other inflammatory pathways that are thought to mediate a variety of pathophysiological responses. The liver has been implicated as an early key player in the heat-induced SIRS based on its function as a major site of endotoxin clearance. Cytokines are important regulators of the acute-phase response to inflammation/AbMole Pamidronate disodium pentahydrate injury and have been implicated as mediators of the SIRS with HS. Accompanying elevations in cytokines, organ and tissue damage are common manifestations of the HS syndrome. The liver is a major immune organ known to produce and respond to cytokines during inflammation and damage to this organ is primarily observed in long-term survivors of HS. However, it is unknown if liver damage is a consequence of direct thermal injury or cytokineinduced pathophysiological changes associated with the SIRS, indicating the importance of correlating changes in circulating cytokine levels with inflammatory changes occurring at the organ and/or tissue level. Helwig and Leon determined plasma, liver, and spleen mRNA accumulation patterns for the IL-1 family members in mice following HS; increased IL-1a, IL-1b, and IL-1 receptor subtype I and subtype II mRNA accumulation in the liver and spleen suggested these organs may contribute to circulating IL-1 family protein levels following HS, but the absence of studies on protein translation that include protein tagging precluded a conclusive association. The mediators involved in progression of the HS syndrome and the intricate map of interactions between them form a complex system that can only be truly understood using a systems approach. Although several computational models of acute inflammation exist, the aim of this study was to incorporate a level of AbMole Nitroprusside disodium dihydrate mechanistic detail that was not previously incorporated into these models. Therefore, we developed a mathematical model that integrates relevant biological knowledge with our novel experimental data from wild-type mice to identify testable hypotheses that will delineate the molecular mechanisms mediating the complex etiology of the heat-induced SIRS. This mechanistic dynamic model describes intra- and extracellular changes in cytokine signaling pathways under HS and was fitted to genomic and proteomic 
data of wild-type mice by means of global optimization techniques. Model validation was performed using a completely different set of data from TNFR KO mice that were not used for calibration purposes, but demonstrate the predictive capabilities of our framework.