Degradation of nerve agents by an organophosphate-degrading agent (OpdA)

Enzyme-catalysed degradation of the nerve agents tabun, sarin, ethyl sarin and soman by three variants of an organophosphate-degrading enzyme was studied at low concentrations of nerve agent. The concentration of nerve agent at a given time was determined by its ability to inhibit the enzyme acetylcholinesterase. Experiments were conducted in 96-well microtitre plates. Values of the ratio of k(cat) (turnover number) to K(m) (Michaelis-Menten constant) were calculated. For tabun, this value (for the most effective OpdA variant) exceeded any value published to date for other enzymes. The value was within an order of magnitude for the highest value reported for sarin, but there appears to be no published value for ethyl sarin for comparison. The OpdA enzymes were relatively inefficient in degrading soman.     

Prediction of cement-based mortars compressive strength using machine learning techniques

Neural Computing and Applications - The application of artificial neural networks in mapping the mechanical characteristics of the cement-based materials is underlined in previous investigations....     

Noradrenaline release and the effect of endogenous activation of the phospholipase C/protein kinase C signalling pathway in rat atria

Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children <8 kg had more bleeding and required more coagulation products than children >8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children <8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing >8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. Implications: Children <8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.     

Comprehension-monitoring skills in learning-disabled children.

Compared comprehension-monitoring skills of learning disabled (LD) and normal elementary school children. Comprehension monitoring, the ability to evaluate one's level of understanding incoming messages, was assessed in the context of a game-learning task. Ss were 12 younger LD boys (7–8 yrs old), 12 older LD boys (9–10 yrs old), and 12 younger and 10 older normal boys matched on age and IQ. No age effects were observed. The major finding was that relative to the matched normal Ss, LD Ss were deficient in comprehension-monitoring skills. (5 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein kinase C involvement in maintenance and modulation of noradrenaline release in the mouse brain cortex

1. The role of protein kinase C in the modulation of noradrenaline release was investigated in mouse cortical slices which were pre-incubated with [3H]-noradrenaline. The aim was to investigate the hypothesis that protein kinase C is activated during high levels of transmitter release to maintain transmitter output. 2. The protein kinase C activators, phorbol myristate acetate (0.01-0.3 microM) and to a greater extent 4 beta-phorbol 12,13-dibutyrate (0.01-0.3 microM) significantly enhanced stimulation-induced noradrenaline release whereas 4 alpha-phorbol 12,13-dibutyrate (0.1 microM) which does not activate protein kinase C was without effect. The effect of the protein kinase C activator, phorbol myristate acetate, on noradrenaline release was attenuated by the protein kinase C inhibitor, polymyxin B (21 microM) which by itself inhibited stimulation-induced noradrenaline release. 3. Protein kinase C was down-regulated by 10 h exposure of the cortical slices to 4 beta-phorbol 12,13-dibutyrate (1 microM). In this case the facilitatory effect of 4 beta-phorbol 12,13-dibutyrate (0.1 microM) on noradrenaline release was abolished as was the inhibitory effect produced by polymyxin B. This indicates that polymyxin B was acting selectively at protein kinase C. 4. The inhibitory effect of polymyxin B on noradrenaline release, when expressed as a percentage of the appropriate frequency control, was constant at 1, 5 and 10 Hz. Furthermore, the ratio of release at 5 Hz to that at 10 Hz was not altered by protein kinase C down-regulation, indicating that there is no additional effect of protein kinase C at higher stimulation frequencies. 5. When transmitter release was elevated by blocking alpha 2-adrenoceptor auto-inhibition with idazoxan (0.1 microM) or K+ channels with tetraethylammonium (300 microM), the elevation in transmitter release was significantly attenuated by protein kinase C down-regulation, suggesting an involvement of protein kinase C. 6. We conclude that protein kinase C is involved in the modulation of noradrenaline release over a wide range of stimulation frequencies, in addition to a role when noradrenaline release is elevated by presynaptic mechanisms.     

Anti-pterins as tools to characterize the function of tetrahydrobiopterin in NO synthase

Nitric oxide synthases (NOS) are homodimeric enzymes that NADPH-dependently convert L-arginine to nitric oxide and L-citrulline. Interestingly, all NOS also require (6R)-5,6,7, 8-tetrahydro-L-biopterin (H4Bip) for maximal activity although the mechanism is not fully understood. Basal NOS activity, i.e. that in the absence of exogenous H4Bip, has been attributed to enzyme-associated H4Bip. To elucidate further H4Bip function in purified NOS, we developed two types of pterin-based NOS inhibitors, termed anti-pterins. In contrast to type II anti-pterins, type I anti-pterins specifically displaced enzyme-associated H4Bip and inhibited H4Bip-stimulated NOS activity in a fully competitive manner but, surprisingly, had no effect on basal NOS activity. Moreover, for a number of different NOS preparations basal activity (percent of Vmax) was frequently higher than the percentage of pterin saturation and was not affected by preincubation of enzyme with H4Bip. Thus, basal NOS activity appeared to be independent of enzyme-associated H4Bip. The lack of intrinsic 4a-pterincarbinolamine dehydratase activity argued against classical H4Bip redox cycling in NOS. Rather, H4Bip was required for both maximal activity and stability of NOS by binding to the oxygenase/dimerization domain and preventing monomerization and inactivation during L-arginine turnover. Since anti-pterins were also effective in intact cells, they may become useful in modulating states of pathologically high nitric oxide formation.     

Development of comprehension monitoring as a function of context.

Two studies with 59 Ss (preschoolers–4th graders) explored the effects of stimulus factors on children's ability to monitor comprehension of messages as listeners in a referential communication situation. Results of Exp I show that both complexity of the stimulus array and degree of message ambiguity affected performances. In line with previous findings, 4th graders but not younger Ss showed evidence of effective comprehension monitoring. Data from Exp II show that when conducive stimulus conditions were arranged, even 1st graders demonstrated considerable skill in comprehension monitoring. In addition to investigating comprehension monitoring per se, the studies also examined the role of comprehension monitoring in directing the overall comprehension process. (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High-entropy oxides: Harnessing crystalline disorder for emergent functionality

High-entropy materials defy historical materials design paradigms by leveraging chemical disorder to kinetically stabilize novel crystalline solid solutions comprised of many end-members. Formulational diversity results in local crystal structures that are seldom found in conventional materials and can strongly influence macroscopic physical properties. Thermodynamically prescribed chemical flexibility provides a means to tune such properties. Additionally, kinetic metastability results in many possible atomic arrangements, including both solid-solution configurations and heterogeneous phase assemblies, depending on synthesis conditions. Local disorder induced by metastability, and extensive cation solubilities allowed by thermodynamics combine to give many high-entropy oxide systems utility as electrochemical, magnetic, thermal, dielectric, and optical materials. Though high-entropy materials research is maturing rapidly, much remains to be understood and many compositions still await discovery, exploration, and implementation.