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A formal physical cluster theory for an imperfect gas, valid for an arbitrary definition of a ``physical cluster,'' is described. The role of the definition of the physical cluster is stressed. For a particular definition of the physical cluster, which may be appropriate in nucleation theory, the Helmholtz free energy of 13-, 43-, 60-, 70-, 80-, 87-, and 100-atom argon clusters is calculated in the classical limit for temperatures ranging from absolute zero to 100°K using Monte Carlo techniques. It is found that a cluster's free energy is almost independent of its definition provided that the definition is reasonable and the temperature is sufficiently low. The results are compared with the predictions using the harmonic approximation.

. Extracellular matrix stimulates reactive oxygen species production and increases pancreatic cancer cell survival through 5-lipoxygenase and NADPH oxidase. Am J Physiol Gastrointest Liver Physiol 289: G1137-G1147, 2005. First published July 21, 2005 doi:10.1152/ajpgi.00197.2005.-The extracellular matrix (ECM) facilitates pancreatic cancer cells survival, which is of central importance for pancreatic adenocarcinoma that is highly fibrotic. Here, we show that reactive oxygen species (ROS) mediate the prosurvival effect of ECM in human pancreatic cancer cells. Fibronectin and laminin stimulated ROS production and NADPH oxidase activation in pancreatic cancer cells. Both pharmacological and molecular approaches show that fibronectin stimulated ROS production through activation of NADPH oxidase and NADPH oxidase-independent pathways and that 5-lipoxygenase (5-LO) mediates both these pathways. Analyses of the mechanisms of ROS production by ECM proteins and growth factors indicate that activation of NADPH oxidase (Nox4) is a common mechanism employed both by ECM proteins and growth factors to increase ROS in pancreatic cancer cells. We also found that Nox4 is present in human pancreatic adenocarcinoma tissues and that these tissues display membrane NADPH oxidase activity. ECM proteins and growth factors activate NADPH oxidase through different mechanisms; in contrast to ECM proteins, growth factors activate NADPH oxidase through 5-LO-independent mechanisms. Inhibition of 5-LO or NADPH oxidase with pharmacological inhibitors of these enzymes and with Nox4 or 5-LO antisense oligonucleotides markedly stimulated apoptosis in cancer cells cultured on fibronectin. Our results indicate that ROS generation via 5-LO and downstream NADPH oxidase mediates the prosurvival effect of ECM in pancreatic cancer cells. These mechanisms may play an important role in pancreatic cancer resistance to treatments and thus represent novel therapeutic targets. pancreas REACTIVE OXYGEN SPECIES (ROS) are highly reactive O 2 metabolites that include superoxide radical (O 2 Ϫ ⅐), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical (HO⅐) (44). Whereas ROS are classically thought of as cytotoxic and mutagenic (23, 33), recent evidence suggests that ROS such as superoxide and H 2 O 2 serve as regulators in signal transduction pathways (38). ROS are involved in proliferation, cell death, and adhesion pathways (7,9,39,42). The targets of ROS include such key signaling molecules as transcription factor NF-kB, MAPKs, and tyrosine phosphatases (10,15,46,55).In phagocytes, large amounts of ROS are produced during the oxidative burst by plasma membrane NAD(P)H oxidase, a well-characterized multicomponent enzyme with gp91 phox and p22phox catalytic subunits that together form an integral complex called flavocytochrome b 558 (3, 4). Nonphagocytic cells also produce significant amounts of ROS, albeit much smaller than in phagocytes (4,5,25). In nonphagocytic cells, ROS are produced by mitochondria as well as by a number of ROS-generating plasma membrane and cy...

Accurate potentials for ground state krypton-krypton and xenon-xenon interactions are derived using a wide range of experimental evidence including second virial coefficients, gas transport properties, solid state data, known long-range interactions, spectroscopic information on dimers, and new measurements of differential scattering cross sections. In calculating solid-state properties account is taken of long-range many-body interactions. The use of the potentials permits a critical intercomparison of various kinds of experimental data. A ``corresponding states'' comparison of the shapes of the potentials for different inert gas pairs is given. It is concluded that contributions of overlap-dependent many-body interactions to condensed-phase properties of argon, krypton, and xenon are very small.

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In viral myocarditis, inflammation and destruction of cardiac myocytes leads to fibrosis, causing progressive impairment in cardiac function. Here we show the etiologic importance of serine elastase activity in the pathophysiology of acute viral myocarditis and the therapeutic efficacy of an elastase inhibitor. In DBA/2 mice inoculated with the encephalomyocarditis virus, a more than 150% increase in myocardial serine elastase activity is observed. This is suppressed by a selective serine elastase inhibitor, ZD0892, which is biologically effective after oral administration. Mice treated with this compound had little evidence of microvascular constriction and obstruction associated with myocarditis-induced ischemia reperfusion injury, much less inflammation and necrosis, only mild fibrosis and myocardial collagen deposition, and normal ventricular function, compared with the infected nontreated group.

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