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The invention pertains to a CellDrum electrode arrangement for measuring mechanical stress, comprising a mechanical holder (1 ) and a non-conductive membrane (4), whereby the membrane (4) is at least partially fixed at its circumference to the mechanical holder (1), keeping it in place when the membrane (4) may bend due to forces acting on the membrane (4), the mechanical holder (1) and the membrane (4) forming a container, whereby the membrane (1) within the container comprises an cell- membrane compound layer or biological material (3) adhered to the deformable membrane 4 which in response to stimulation by an agent may exert mechanical stress to the membrane (4) such that the membrane bending stage changes whereby the container may be filled with an electrolyte, whereby an electric contact (2) is arranged allowing to contact said electrolyte when filled into to the container, whereby within a predefined geometry to the fixing of the membrane (4) an electrode (7) is arranged, whereby the electrode (7) is electrically insulated with respect to the electric contact (2) as well as said electrolyte, whereby mechanical stress due to an agent may be measured as a change in capacitance.
In this paper the results of a techno-economic analysis of improved and optimized molten salt solar tower plants (MSSTP plants) are presented. The potential improvements that were analyzed include different receiver designs, different designs of the HTF-system and plant control, increased molten salt temperatures (up to 640°C) and multi-tower systems. Detailed technological and economic models of the solar field, solar receiver and high temperature fluid system (HTF-system) were developed and used to find potential improvements compared to a reference plant based on Solar Two technology and up-to-date cost estimations. The annual yield model calculates the annual outputs and the LCOE of all variants. An improved external tubular receiver and improved HTF-system achieves a significant decrease of LCOE compared to the reference. This is caused by lower receiver cost as well as improvements of the HTF-system and plant operation strategy, significantly reducing the plant own consumption. A novel star receiver shows potential for further cost decrease. The cavity receiver concepts result in higher LCOE due to their high investment cost, despite achieving higher efficiencies. Increased molten salt temperatures seem possible with an adapted, closed loop HTF-system and achieve comparable results to the original improved system (with 565°C) under the given boundary conditions. In this analysis all multi tower systems show lower economic viability compared to single tower systems, caused by high additional cost for piping connections and higher cost of the receivers.
REFERENCES
We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements.
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.
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.
1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described.
2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created.
3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment.
4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.