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- no (257)
Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.
Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.
Analysis Of Base Isolated Liquid Storage Tanks With 3D Fsi-Analysis As Well As Simplified Approaches
(2017)
Tanks are preferably designed, for cost-saving reasons, as circular, cylindrical, thin-walled shells. In case of seismic excitation, these constructions are highly vulnerable to stability failures. An earthquake-resistant design of rigidly supported tanks for high seismic loading demands, however, uneconomic wall thicknesses. A cost-effective alternative can be provided by base isolation systems. In this paper, a simplified seismic design procedure for base isolated tanks is introduced, by appropriately modifying the standard mechanical model for flexible, rigidly supported tanks. The non-linear behavior of conventional base isolation systems becomes an integral part of a proposed simplified process, which enables
the assessment of the reduced hydrodynamic forces acting on the tank walls and the corresponding stress distribution. The impulsive and convective actions of the liquid are taken into account. The validity of this approach is evaluated by
employing a non-linear fluid-structure interaction algorithm of finite element method. Special focus is placed on the boundary conditions imposed from the base isolation and the resulting hydrodynamic pressures. Both horizontal and vertical
component of ground motion are considered in order to study the principal effects of the base isolation on the pressure distribution of the tank walls. The induced rocking effects associated with elastomeric bearings are discussed. The results
manifest that base isolated tanks can be designed for seismic loads by means of the proposed procedure with sufficient accuracy, allowing to dispense with numerically expensive techniques.
Für Auftragschweißaufgaben existiert eine Vielzahl an verfahrenstechnischen
Prozessvarianten, die je nach Charakteristik und Anwendungsfall
ausgewählt werden. Ein Nachteil der vorwiegend verwendeten Metall-
Schutzgasschweißprozesse (MSG) für das Auftragschweißen ist durch die
direkte Kopplung von Drahtvorschub zu Energieeintrag gegeben. Die vorgestellte
Zweidraht-Prozessvariante kann durch die Ausbildung eines übertragenen
und eines nicht-übertragenen Lichtbogens die elektrische Leistung
beider Lichtbögen variieren und damit einen direkten Einfluss auf
die Prozessgrößen Abschmelzleistung und Aufschmelzgrad nehmen. Im
Speziellen besteht über die Entkopplung von Drahtvorschub zu Schweißstromstärke
die Möglichkeit eines niederenergetischen Betriebs trotz hoher
Drahtvorschubgeschwindigkeit. Damit lassen sich Aufschmelzgrade
unter 2% umsetzen und Abschmelzleistungen bis zu 15 kg/h realisieren.
Multi-dimensional fragility analysis of a RC building with components using response surface method
(2017)
Conventional fragility curves describe the vulnerability of the main structure under external hazards. However, in complex structures such as nuclear power plants, the safety or the risk depends also on the components associated with a system. The classical fault tree analysis gives an overall view of the failure and contains several subsystems to the main event, however, the interactions in the subsystems are not well represented. In order to represent the interaction of the components, a method suggested by Cimellaro et al. (2006) using multidimensional performance limit state functions to obtain the system fragility curves is adopted. This approach gives the possibility of deriving the cumulative fragility taking into account the interaction of the response of different components. In this paper, this approach is used to evaluate seismic risk of a representative electrical building infrastructure, including the component, of a nuclear power plant. A simplified model of the structure, with nonlinear material behavior is employed for the analysis in Abaqus©. The input variables considered are the material parameters, boundary conditions and the seismic input. The variability of the seismic input is obtained from selected ground motion time histories of spectrum compatible synthetic ccelerograms. Unlike the usual Monte Carlo methods used for the probabilistic analysis of the structure, a computationally effective response surface method is used. This method reduces the computational effort of the calculations by reducing the required
number of samples.