This paper presents an algorithm for identifying desirable multiple targets in an intracellular regulation network. The algorithm is based on constrained state feedback and Monte-Carlo simulations. The computational c...This paper presents an algorithm for identifying desirable multiple targets in an intracellular regulation network. The algorithm is based on constrained state feedback and Monte-Carlo simulations. The computational complexity of the algorithm increases linearly with increasing the number of species in a gene regulation system. An estimate is derived for the confidence level of the predicted minimum required perturbation strength when targets are prescribed a priori. The algorithm has been used to analyze the cell cycle of Xenopus frog eggs. The results agree well with available results for single target perturbations, and multitarget interference is usually not equal to the summation of the single-target interferences.展开更多
Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. Th...Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells （hepatocytes for the former and cholangiocytes for the latter）. These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels （CFTR in cholangiocytes and not yet determined in hepatocytes） and aquaporins （AQP8 in hepatocytes and AQP1 in cholangiocytes）, cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.展开更多
基金Supported in part by the Basic Research Foundation of Tsinghua National Laboratory for Information Science and Technology (TNList)the National Natural Science Foundation of China (Nos. 60625305 and 60574008)the National High-Tech Research and Development (863) Program of China (No. 2006AA2Z311)
文摘This paper presents an algorithm for identifying desirable multiple targets in an intracellular regulation network. The algorithm is based on constrained state feedback and Monte-Carlo simulations. The computational complexity of the algorithm increases linearly with increasing the number of species in a gene regulation system. An estimate is derived for the confidence level of the predicted minimum required perturbation strength when targets are prescribed a priori. The algorithm has been used to analyze the cell cycle of Xenopus frog eggs. The results agree well with available results for single target perturbations, and multitarget interference is usually not equal to the summation of the single-target interferences.
基金the "UTE for CIMA project" as well as by a grant from the "Institute de Salud CarlosⅢ" (PI051098). J. M. B. has a grant from the Spanish Ministry of Science and Technology
文摘Primary canalicular bile undergoes a process of fluidization and alkalinization along the biliary tract that is influenced by several factors including hormones, innervation/neuropeptides, and biliary constituents. The excretion of bicarbonate at both the canaliculi and the bile ducts is an important contributor to the generation of the so-called bile-salt independent flow. Bicarbonate is secreted from hepatocytes and cholangiocytes through parallel mechanisms which involve chloride efflux through activation of Cl- channels, and further bicarbonate secretion via AE2/SLC4A2-mediated Cl-/HCO3- exchange. Glucagon and secretin are two relevant hormones which seem to act very similarly in their target cells （hepatocytes for the former and cholangiocytes for the latter）. These hormones interact with their specific G protein-coupled receptors, causing increases in intracellular levels of cAMP and activation of cAMP-dependent Cl- and HCO3- secretory mechanisms. Both hepatocytes and cholangiocytes appear to have cAMP-responsive intracellular vesicles in which AE2/SLC4A2 colocalizes with cell specific Cl- channels （CFTR in cholangiocytes and not yet determined in hepatocytes） and aquaporins （AQP8 in hepatocytes and AQP1 in cholangiocytes）, cAMP-induced coordinated trafficking of these vesicles to either canalicular or cholangiocyte lumenal membranes and further exocytosis results in increased osmotic forces and passive movement of water with net bicarbonate-rich hydrocholeresis.
