No abstract

alpha-Ketoglutaramate, a deaminated metabolite of glutamine not previously identified in biological tissues, was measured in the cerebrospinal fluid of human subjects and found to be increased three- to tenfold in patients with hepatic coma. When perfused into the cerebral lateral ventricles of rats, alpha-ketoglutaramate (10 mM) depressed the animals' nocturnal locomotor activity, and at higher doses induced circling behavior and myoclonus. The concentration of alpha-ketoglutaramate in cerebrospinal fluid appears to be a reliable diagnostic indicator of hepatic coma, and its accumulation may contribute to the pathogenesis of this disease.

Myotonic muscular dystrophy is a genetic disease characterized mainly by muscle atrophy and myotonia, a repetitive electrical activity of muscle. In the present study, the possible role of apamin-sensitive K+ channels in the genesis of myotonia was investigated. Apamin is a peptide from bee venom that specifically blocks small conductance Ca(2+)-activated K+ channels. The injection of a small amount of apamin (20-30 microliters, 10 mumol/L) into the thenar muscle of myotonic dystrophy patients decreased the basal electrical activity during the electromyogram in the 6 patients studied. Myotonic discharges after muscle percussion were more difficult to trigger and of smaller intensity and duration. In 2 controls and in 2 patients with generalized myotonia, as well as in 1 patient with myotonia congenita (where the defect is in chloride channels), apamin had no effect. These results suggest that apamin-sensitive K+ channels participate in the mechanism that generates myotonia in myotonic dystrophy.

Different sets of parameters and conceptualizations of a basin can give equally good results in terms of predefined objective functions. Therefore, a need exists to tackle equifinality and quantify the uncertainty bands of a model. In this paper we use the concepts of equifinality, identifiability and uncertainty to propose a simple method aimed at constraining the equifinal parameters and reducing the uncertainty bands of model outputs, and obtaining physically possible and reasonable models. Additionally, the uncertainty of equifinal solutions is quantified to estimate the amount by which output uncertainty can be reduced by knowing how to discard most of the equifinal solutions of a model. As a study case, a conceptual model of the Chillán basin in Chile is carried out. From the study it is concluded that using identifiability analysis makes it possible to constrain equifinal solutions with reduced uncertainty and realistic models, resulting in a framework that can be recommended to practitioners, especially due to the simplicity of the method. En outre, l'incertitude de solutions équivalentes est quantifiée pour estimer dans quelle mesure l'incertitude de sortie peut être réduite en sachant comment rejeter la plupart des solutions équivalentes d'un modèle. Comme étude de cas, nous avons construit un modèle conceptuel du bassin du Chillán au Chili. De cette étude, nous concluons que l'utilisation de l'analyse d'identifiabilité permet de contraindre les solutions équivalentes avec une incertitude réduite et des modèles réalistes, ce qui définit un cadre pouvant être recommandé aux praticiens, en particulier en raison de la simplicité de la méthode.

Supply chain management literature calls for coordination between the different members of the chain. Materials should be moved from one supplier to the next according to a just-in-time schedule. In this paper we develop an evolutionary algorithm (EA) for optimal synchronization of supply chains. In developing our algorithm, we use the economic delivery and scheduling model and analyze supply chains dealing with multiple-components. We test the performance of the proposed EA and show that it provides optimal, or near optimal, solutions for a wide range of problems. The EA is shown to be much faster at solving large problems than an enumeration procedure and exhibits robust behavior when tested on a variety of different problem parameters. q