Integration of the GTM T2 model into a full sized simulator for human-in-the-loop testing

This document presents the work to develop a human-in-the-loop flight simulator. The document outlines the building of a Simulink library that connects with the GTM T2 dynamics model, X-Plane, cockpit gauges, and cockpit controls. The inner workings of each block and the computer code that handles the communication between Simulink and the environment is also presented, in an effort to aid in expandability and adaptation beyond the current implementation. The inner workings of basic cockpit gauge display are presented and detailed to aid in future iterations. Finally, a completed system consisting of the Simulink system, X-Plane visuals, and cockpit controls and display is shown to have more than acceptable real-time performance for use in validation of a flight control system

Regulation of rat hepatic phosphatidylcholine biosynthesis

Several model systems were investigated to elucidate the mechanisms by which rat liver phosphatidylcholine synthesis is controlled. CTP: phosphocholine cytidylyltransferase was clearly the key regulatory enzyme for phosphatidylcholine formation from choline. This ambiquitous enzyme was detected in both the cytosolic and microsomal fractions of rat liver, although the majority of the cytidylyltransferase occurred in the soluble fraction. The distribution of cytidylyltransferase between these fractions was altered when the rate of phosphatidylcholine synthesis was perturbed. Translocation of cytidylyltransferase was observed in rat liver during early development, with starvation and during a diurnal rhythm. A redistribution of cytidylyltransferase was also detected in isolated hepatocytes which were treated with glucagon, cAMP analogues or fatty acids bound to albumin. The rate of phosphatidylcholine synthesis was found to reflect the amount of microsomal cytidylyltransferase activity. The inhibition of phosphatidylcholine synthesis by glucagon or cAMP analogues was likely due to phosphorylation and inhibition of the cytidylyltransferase. Several lines of evidence indicated that the cytidylyltransferase in fresh rat liver cytosol was probably phosphorylated and activated upon dephosphorylation by endogenous phosphoprotein phosphatases or alkaline phosphatase from hog intestine. Although the phosphorylation of cytidylyltransferase was apparently kinetically "silent", dephosphorylation resulted in an increased affinity of the enzyme for membranes. Fatty acids stimulated de novo phosphatidylcholine synthesis by acceleration of the cytidylyl-transferase-catalyzed reaction. Fatty acids and their CoA derivatives were shown to stimulate the cytosolic cytidylyltransferase activity. However, these compounds failed to activate partially purified cytidylyltransferase appreciably. Apparently, fatty acids, like dephosphorylation, enhanced the tenacity of cytidylyltransferase for membranes. Upon binding to membranes, cytidylyltransferase activity could be elevated up to 45-fold, and the affinity of the enzyme for the substrate, CTP, was increased 20-fold. The influence of glucagon, cAMP analogues and fatty acids on the synthesis of phosphatidylcholine by successive N-methylation was also examined in isolated rat hepatocytes. Glucagon and cAMP analogues inhibited the methylation pathway in these cells, but the activity of microsomal phosphatidylethanolamine methyltransferase was elevated. Fatty acids also reduced the formation of phosphatidylcholine from phosphatidylethanolamine. Fatty acids and their CoA derivatives directly inhibited the phosphatidylethanolamine methyltransferase in rat liver microsomes. The coordinate control of hepatic phosphatidylcholine synthesis by cAMP and fatty acids may be important during starvation when the intracellular levels of these compounds are increased.Medicine, Faculty ofBiochemistry and Molecular Biology, Department ofGraduat

Signalling pathways: Kinase connections on the cellular intranet

AbstractThe yeast mating factor-activated protein kinase pathway is a paradigm for understanding related pathways that transduce diverse signals. New studies of multicellular organisms, however, indicate higher levels of integration of these pathways within networks

Long-Term Effect of Heat Shock Protein 60 from Actinobacillus actinomycetemcomitans on Epithelial Cell Viability and Mitogen-Activated Protein Kinases

Our previous studies showed that bacterial heat shock protein 60 (hsp60) induces cultured epithelial cell proliferation within 24 h. Here we investigated the long-term effects of heat shock protein 60 isolated from Actinobacillus actinomycetemcomitans on skin keratinocyte (HaCaT cell line) viability and the cell signaling involved. Prolonged incubation in the presence of hsp60 increased the rate of epithelial cell death. The number of viable cells in hsp60-treated culture was 37% higher than the number in the control at 24 h but 27% lower at 144 h. A kinetics study of the effect of hsp60 on the phosphorylation of mitogen-activated protein kinases (MAPKs) involving Western blotting with phospho-specific antibodies showed that in addition to a transient early increase in p38 levels, a second peak appeared in keratinocytes 24 h after the addition of hsp60. In contrast, prolonged incubation with hsp60 caused a decrease in the level of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) compared with that in the controls, possibly as a result of protein phosphatase activity. We found that hsp60 increased the levels of several phosphatases, including MAP-2, which strongly dephosphorylates ERK1/2. Moreover, hsp60 increased the level of tumor necrosis factor alpha (TNF-α) in culture medium in a dose-dependent manner. TNF-α added to culture showed a cytotoxic effect on epithelial cells, particularly with longer incubation periods. TNF-α also induced the phosphorylation of p38. Finally, our results show that bacterial hsp60 inhibited stress-induced synthesis of cellular hsp60. Therefore, several cell behavior changes caused by long-term exposure to bacterial hsp60 may lead to impaired epithelial cell viability