Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle, and metabolic physiology. The model is constructed from empirical data obtained from peer-reviewed physiological literature. All model details, including variables, parameters, and quantitative relationships, are described in Extensible Markup Language (XML) files. The executable (HumMod.exe) parses the XML and displays the results of the physiological simulations. The XML description of physiology in HumMod's modeling environment allows investigators to add detailed descriptions of human physiology to test new concepts. Additional or revised XML content is parsed and incorporated into the model. The model accurately predicts both qualitative and quantitative changes in clinical and experimental responses. The model is useful in understanding proposed physiological mechanisms and physiological interactions that are not evident, allowing one to observe higher level emergent properties of the complex physiological systems. HumMod has many uses, for instance, analysis of renal control of blood pressure, central role of the liver in creating and maintaining insulin resistance, and mechanisms causing orthostatic hypotension in astronauts. Users simulate different physiological and pathophysiological situations by interactively altering numerical parameters and viewing time-dependent responses. HumMod provides a modeling environment to understand the complex interactions of integrative physiology. HumMod can be downloaded at http://hummod.org

Threonine 161 phosphorylation of p34cdc2 and its equivalent threonine 160 in p33cdk2 by cdk-activating kinase (CAK) is essential for the activation of these cyclin-dependent kinases. We have studied the expression and associated kinase activity of p40MOl5, the catalytic subunit of CAK, during Xenopus oogenesis, meiotic maturation, and early development to understand in more detail how cdk kinases are regulated during these events. We find that p40M°15 is a stable protein with a half-life >16 h that is accumulated during oogenesis. p4OMOl5 protein and its associated CAK activity are localized predominantly to the germinal vesicle; however, a small but significant proportion is found in the cytoplasm. The amount of p4oMO15 detected in stage VI oocytes remains unchanged through meiotic maturation, fertilization, and early embryogenesis. Significantly, p4OMO15 was found to be constitutively active during oogenesis, meiotic maturation, and the rapid mitotic cycles of early development. This suggests that regulation of p34cdc2 and p33cdk2 activity during cell cycle progression does not involve changes in the level or activity of p4OMOl5/CAK.

Angus Laing is currently a lecturer at the