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BACKGROUND/PURPOSE OF THE STUDY Vitamin D3-deficiency is common in patients with chronic liver-disease and may promote disease progression. Vitamin D3-administration has thus been proposed as a therapeutic approach. Vitamin D3 has immunomodulatory effects and may modulate autoimmune liver-disease such as primary sclerosing cholangitis. Although various(More)
We present a graphical toolset for verifying AADL models, which are gaining widespread acceptance in aerospace, automobile and avionics industries for comprehensively specifying safety-critical systems by capturing functional, probabilistic and hybrid aspects. Analyses are implemented on top of mature model checking tools and range from requirements(More)
This paper presents the tool COMICS 1.0, which performs model checking and generates counterexamples for DTMCs. For an input DTMC, COMICS computes an abstract system that carries the model checking information and uses this result to compute a critical subsystem, which induces a counterexample. This abstract subsystem can be refined and concretized(More)
—Model checkers for concurrent probabilistic systems have become very popular within the last decade. The study of long-run average behavior has however received only scant attention in this area, at least from the implementation perspective. This paper studies the problem of how to efficiently realize an algorithm for computing optimal long-run average(More)
This paper is an introductory survey of available methods for the computation and representation of probabilistic counterexamples for discrete-time Markov chains and probabilistic automata. In contrast to traditional model checking, probabilistic counterexamples are sets of finite paths with a critical probability mass. Such counterexamples are not obtained(More)
Counterexamples for property violations have a number of important applications like supporting the debugging of erroneous systems and verifying large systems via counterexample-guided abstraction refinement. In this paper, we propose the usage of minimal critical subsystems of discrete-time Markov chains and Markov decision processes as counterexamples for(More)
Taurolithocholic acid (TLCA) is a potent cholestatic agent. Our recent work suggested that TLCA impairs hepatobiliary exocytosis, insertion of transport proteins into apical hepatocyte membranes, and bile flow by protein kinase Cepsilon (PKCepsilon)-dependent mechanisms. Products of phosphatidylinositol 3-kinases (PI3K) stimulate PKCepsilon. We studied the(More)
BACKGROUND & AIMS Glycochenodeoxycholate (GCDC) and taurolithocholate (TLC) are hepatotoxic and cholestatic bile salts, whereas tauroursodeoxycholate (TUDC) is cytoprotective and anticholestatic. Yet they all act, in part, through phosphatidylinositol-3-kinase(PI3K)-dependent mechanisms ("PI3K-paradox"). Hepatocytes express three catalytic PI3K Class I(More)
UNLABELLED NorUDCA (24-norursodeoxycholic acid), the C₂₃-homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP-binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver,(More)
Apoptosis induced by hydrophobic bile acids is thought to contribute to liver injury during cholestasis. Caspase-6 is an executioner caspase that also appears to have regulatory functions in hematopoetic cell lines. We aimed to elucidate the role of caspase-6 in bile acid-induced apoptosis. The major human hydrophobic bile acid, glycochenodeoxycholic acid(More)