Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration. 相似文献
A wide range of parameters was investigated by numerical calculations concerning their impact on DC stray current corrosion of reinforced concrete (RC) structures. A simplified model geometry was used to extract the relevant parameters and their interaction in terms of stray current-affected structures. This study mainly focuses on RC structures that are fitted with cathodic protection installations. The findings reveal a complex interaction between the investigated parameters. The possible relevance of further parameters, which is not the subject of this study, was emphasised. 相似文献
Possible Approaches to the Prediction of Residence Time Distributions Although the experimental determination of residence time distributions is based on a black-box method, the signal shape also permits certain conclusions to be drawn about the internal conditions. However, if it is to provide a sole basis for elucidating process steps in a plant this method is soon overtaxed. A deeper theoretical penetration of the pertinent transport processes opens up the way ahead. However, since residence time distributions are based on mass-oriented considerations, substantial advances in fluid mechanics, where location-based considerations predominate, have not led to improved predictive capability. Yet the computer power now available offers a variety of ways of calculating residence-time distributions for a known flow profile, thus permitting a step in the direction of better predictability of residence time distributions. This article presents utilisable methods and evaluates them with regard to their demands on time and effort and their predictive power. Problems arising in connection with the models are discussed. 相似文献
Ten of the main European gas Companies decided to carry out the second intercomparison exercise of high pressure test facilities within GERG (Groupe Européen de Recherches Gazières). The survey has compared the performances of 8 high pressure gas flow laboratories in the period autumn 1998–autumn 1999.
The aim was to check to what extent results obtained at the various laboratories are comparable and to reveal possible ways of improving the performances. Tests have been carried out using three transfer standard packages of three different diameters. The considered performance parameters have been: (1) agreement of results between laboratories, (2) short term stability and (3) day to day reproducibility of the reference flow.
The following main conclusions have been drawn:
• The majority of the laboratories involved in the intercomparison produced very accurate results. Despite the involvement of five independent traceability chains, 92.5% of the test results are within a band of ±0.25%.
• For most facilities the short term fluctuations are of the order of ±0.1%. Individual facilities may perform even better.
• This exercise allowed us to confirm the good results of the previous campaign and to identify some items to improve future intercomparisons.
Author Keywords: Intercomparison; Transfer standard package; Laboratory; Meter 相似文献
This article investigates the short‐term relationship between media coverage, stock prices, and trading volumes of eight listed German companies. A content analysis of news reports about the selected companies and a secondary analysis of the daily changes in closing prices and the trading volumes of these companies were combined in a time‐series design. After ARIMA‐modeling each of them, the results suggest that media coverage rather reflects than shapes the development at stock exchanges from a short‐term perspective (2 months). There were almost no hints for a widespread media effect, that is, an impact on so many investors that it will result in a measurable change in stock prices or trading volumes. Finally, theoretical and methodological consequences for exploring widespread media effects are discussed.相似文献
The topic of this paper is minimum cost operative planning of pressurized water supply networks over a finite horizon and under reliable demand forecast. Since this is a very hard problem, it is desirable to employ sophisticated mathematical algorithms, which in turn calls for carefully designed models with suitable properties. The paper develops a nonlinear mixed integer model and a nonlinear programming model with favorable properties for gradient-based optimization methods, based on smooth component models for the network elements. In combination with further nonlinear programming techniques (Burgschweiger et al. in ZIB Report ZR-05-31, Zuse Institute Berlin, 2005), practically satisfactory near-optimum solutions even for large networks can be generated in acceptable time using standard optimization software on a PC workstation. Such an optimization system is in operation at Berliner Wasserbetriebe. 相似文献
Scientific-visualization tools can make time-varying simulations easier to understand. The growing efficiency of today's high-performance computers enables simulation of physical phenomena with a high temporal resolution. Consequently, visualization systems require efficient navigation in the temporal dimension. This 3D user interface employs direct-manipulation metaphors for temporal navigation in scientific visualizations. By interacting with objects using their 3D trajectory, users can navigate in time by specifying spatial inputs. This article is part of a special issue on 3D user interfaces. 相似文献