The Metabolic Inhibition Model Which Predicts the Intestinal Absorbability and Metabolizability of Drug: Theory and Experiment

The intestinal absorption of analgesic peptides (leucine enkephalin and kyotorphin) and modified peptides in rat were studied. Although these peptides were not absorbed, the absorbability (absorption clearance) of these peptides were increased in the presence of peptidase inhibitors. In order to kinetically analyze these phenomena, we proposed the metabolic inhibition model, which incorporated the metabolic clearance (metabolizability) with the absorption clearance. Metabolic activity was determined with intestinal homogenates. The higher the metabolic clearance was, the lower was the absorption clearance. The relationships between the absorption clearance and the metabolic clearance of the experimental data as well as of the theoretical values were hyperbolic. This model predicted the maximum absorption clearances of cellobiose-coupled leucine enkephalin (0.654 μl/min/cm) and kyotorphin (0.247 μl/min/cm). Details of the experimental methods are described

Deploying decision criteria in a cyclical decision process for the product planning phase

During the planning process of future products or the future product portfolio, ideas for future market opportunities are generated and within a parallel decision process, the best ones are selected. This paper presents a method for the decision process during that product planning process. The focus is on the selection and weighting of the decision criteria. The method is applicable for planning processes with reoccurring decision steps. Therefore a block model is introduced: in every decision step a new block, compromising a set of criteria is added to the existing blocks and thus more and more integrated decisions can be made about the planning alternatives. Based on that the criteria are weighted consecutively in order to assure consistency between the different decision steps. Therefore we show rules for deriving the weighting factors of decision criteria in that additive decision process

A new approach to the definition of self-damping for stranded cables

Aim of the paper is to propose a new approach for the determination of the so termed self-damping, or internal damping, of metallic cables. The formulation is developed starting from a recent mechanical model of a strand, from which the hysteretic bending behavior of stranded cables is derived. Each wire of the cable is individually modeled as an elastic curved thin rod. A kinematic model is defined to relate the axial strain and bending curvature of the strand to the generalized strains of the wire. The interaction among the wires belonging to adjacent layers is then studied by neglecting deformations of the contact surfaces and assuming a classic Amontons–Coulomb friction law. In the adopted strand mechanical model a function is derived, which defines the domain of admissible values of the wire axial force to prevent sliding. A simplified model of the cable hysteretic bending behavior is then derived from the cyclic response predicted with the adopted mechanical formulation of the strand, leading to a closed-form upper-bound estimate of the energy dissipated when the cable cross section is subjected to alternate bending. This expression is used as the starting block for the definition of an analytical equation giving an upper-bound estimate of the cable self-damping. The predictions of the proposed model are compared to available data resulting from experiments and empirical literature equations: the comparison is extended to a wide range of strands and parameters that characterize practically most of the configuration commonly used in overhead electrical lines

The bacterial SoxAX cytochromes

SoxAX cytochromes are heme-thiolate proteins that play a key role in bacterial thiosulfate oxidation, where they initiate the reaction cycle of a multi-enzyme complex by catalyzing the attachment of sulfur substrates such as thiosulfate to a conserved cysteine present in a carrier protein. SoxAX proteins have a wide phylogenetic distribution and form a family with at least three distinct types of SoxAX protein. The types of SoxAX cytochromes differ in terms of the number of heme groups present in the proteins (there are diheme and triheme versions) as well as in their subunit structure. While two of the SoxAX protein types are heterodimers, the third group contains an additional subunit, SoxK, that stabilizes the complex of the SoxA and SoxX proteins. Crystal structures are available for representatives of the two heterodimeric SoxAX protein types and both of these have shown that the cysteine ligand to the SoxA active site heme carries a modification to a cysteine persulfide that implicates this ligand in catalysis. EPR studies of SoxAX proteins have also revealed a high complexity of heme dependent signals associated with this active site heme; however, the exact mechanism of catalysis is still unclear at present, as is the exact number and types of redox centres involved in the reaction