This state of affairs leads to a great imbalance between the available information on positive vs. negative interaction data. Such an imbalance constitutes a severe problem when fitting a predictive model. For example, for some SH2 domains, the information on real interactions can be up to 15 times more abundant than the information on the lack of interaction. It is known that in these conditions predictive systems produce suboptimal results. We propose a semi-supervised iterative approach to tackle all these issues. We devise a non-linear support vector machine model for each of 51 human SH2 domain. These models can successfully exploit the information on the dependency between position specific amino acids. To tackle the problem of data imbalance, we developed a simple yet effective approach to make the best use of various types of experimental interaction measurements.Liver ischemia and subsequent reperfusion, which can occur in T/HS and resuscitation, lead to inflammatory liver injury as well as to the systemic elaboration of inflammatory mediators and subsequent multiple organ dysfunction. Liver hypoxia is a primary feature of HS in experimental models. Hypoxic stress, however, is but one of a variety of stresses encountered by hepatocytes in settings such as T/HS and I/R. We therefore reasoned that the analysis of synthesis and secretion of inflammatory mediators by stressed hepatocytes would help in our understanding of the pathophysiology of T/HS and other conditions characterized, at least in part, by hepatic stress. Our key finding is that a combined in vitro/in silico analysis of the dynamics of synthesis and secretion of multiple inflammatory mediators points to the chemokine MCP-1 as a central coordinator of the inflammatory response of stressed hepatocytes. Pursuing this in vitro/in silico-derived hypothesis allowed us to segregate blunt trauma patients based on circulating levels of MCP-1. Ginsenoside-Ro Importantly, this segregation of patients would have proven ineffective if performed based solely on the patients’normotensive/hypotensive status post-injury. Chemokines are small cytokine-like, heparin-binding molecules help orchestrate immune and stem cell infiltration into the liver in response to both acute and chronic injuries. Hepatic chemokines are released during inflammatory injury, and play a key role in the activation and proliferation of liver-resident cells. In our studies, multiple chemokines were synthesized with diverse time courses by stressed hepatocytes. MCP-1 was first identified as a monocyte-specific chemoattractant, and was later shown to attract memory T lymphocytes and NK cells. Binding to its seven-transmembrane Gprotein-coupled receptor CCR2 results in signaling events that lead to the recruitment of monocytes in a variety of in vivo experimental models of infection and injury. In addition to recruiting monocytes, MCP-1 can also activate macrophages and endothelial cells and has been implicated in the attraction of neutrophils and the generation of neutrophil-dependent tissue damage. Lu et al. showed that despite normal numbers of circulating leukocytes and resident macrophages, MCP-12/2 mice were specifically Dexrazoxane hydrochloride unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration, indicating that MCP-1 is essential for monocyte recruitment and the expression of cytokines related to T helper responses in vivo.