A novel mechanism-based mammalian cell assay for the identification of SH2-domain-specific protein-protein inhibitors

BACKGROUND: Many intracellular signal-transduction pathways are regulated by specific protein-protein interactions. These interactions are mediated by structural domains within signaling proteins that modulate a protein's cellular location, stability or activity. For example, Src-homology 2 (SH2) domains mediate protein-protein interactions through short contiguous amino acid motifs containing phosphotyrosine. As SH2 domains have been recognized as key regulatory molecules in a variety of cellular processes, they have become attractive drug targets. RESULTS: We have developed a novel mechanism-based cellular assay to monitor specific SH2-domain-dependent protein-protein interactions. The assay is based on a two-hybrid system adapted to function in mammalian cells where the SH2 domain ligand is phosphorylated, and binding to a specific SH2 domain can be induced and easily monitored. As examples, we have generated a series of mammalian cell lines that can be used to monitor SH2-domain-dependent activity of the signaling proteins ZAP-70 and Src. We are utilizing these cell lines to screen for immunosuppressive and anti-osteoclastic compounds, respectively, and demonstrate here the utility of this system for the identification of small-molecule, cell-permeant SH2 domain inhibitors. CONCLUSIONS: A mechanism-based mammalian cell assay has been developed to identify inhibitors of SH2-domain-dependent protein-protein interactions. Mechanism-based assays similar to that described here might have general use as screens for cell-permeant, nontoxic inhibitors of protein-protein interactions.     

Textile wastewater treatment and reuse by solar catalysis: results from a pilot plant in Tunisia.

Based on results from bench-scale flow-film-reactors (FFR) and aerated cascade photoreactors, a solar catalytic pilot plant has been built at the site of a textile factory. This plant has an illuminated surface area of 50 m2 and is designed for the treatment of 1 m3 h(-1) of wastewater. The preliminary results are presented and compared with a bench-scale FFR using textile wastewater and dichloroacetic acid. Equivalent degradation kinetics were obtained and it was demonstrated that the solar catalytic technology is able to remove recalcitrant compounds and color. However, on-site optimization is still necessary for wastewater reuse and for an economic application.     

Die Genauigkeit der elektrischen Holzfeuchtemessung nach dem Widerstandsprinzip

To improve the accuracy of resistance-type moisture meters for wood, the sources of error of this method are analyzed. The results from tests of 8 commercial DC moisture meters showed a systematic deviation of ±3,5% MC between the moisture meter readings and the results from oven-drying. Experimental tests with beech proved that the theoretical accuracy depends on the actual moisture content, the scale of random sampling and the differentiation of the moisture-resistance curve. When measuring only once a measuring device properly adjusted for the wood species reaches a minimum accuracy of ±2,5% MC. With an increasing number of measurements, the accuracy can be improved until it reaches the accuracy of the testing equipment (±0.1% MC).     

Schrifttumsberichte

Ohne Zusammenfassung     

Millimeter-wave propagation at street level in an urban environment

Measurements on point-to-point transmission at street level were performed in downtown Denver, CO, with RF probes that operated at 9.6, 28.8, and 57.6 GHz. All probes were mounted on self-contained vehicles, permitting a variety of path scenarios. Information on performance of these channels for propagation in an urban environment on both line-of-sight and non-line-of-sight paths is presented. For non-line-of-sight (non-LOS) paths obstructed by buildings of several common materials, results that showed signal attenuations in excess of 100 dB. When the LOS followed a path directly through clear glass walls, the attenuation was small at all probe frequencies. However, when the glass wall had a metalized coating to reduce ultraviolet and infrared radiation, the attenuation increased by 25 to 50 dB for each metallized layer. In most cases no signals could be detected through steel reinforced concrete or brick buildings     

Schrifttumsberichte

Ohne Zusammenfassung     

Schrifttumsberichte

Ohne Zusammenfassung     

Untersuchungen über den elektrischen Isolationswiderstand von Holzschwellen

The electrical behavior of railway sleepers impregnated with two new wood preservatives (salt type CX-S and creosote type GX) has been tested under service conditions in comparison with sleepers impregnated with standard creosote WEI-Type A. The results achieved are as follows: 1) The main factor influencing the electrical resistance of wooden railway sleepers is moisture content. 2) With regard to the electrical resistance GX oil can be used under outdoor conditions and CX-S salt in tunnels without any objections. 3) The isolation resistance of track sections is less influenced by the resistance of the sleepers than by the resistance of the bedding of the track, especially at low moisture contents, when the resistance of the sleepers is relatively high.     

Characterization of arsenic species in kidney of the clam Tridacna derasa by multidimensional liquid chromatography-ICPMS and electrospray time-of-flight tandem mass spectrometry

The identification of water-soluble arsenic species in a kidney of the Tridacna clam by electrospray quadrupole/time-of-flight mass spectrometry (ES Q-TOF MS) was investigated. The species were isolated by three-dimensional LC (size exclusion-anion exchange-cation exchange); the elution of arsenic was monitored by ICPMS. The average accuracy and precision of the molecular mass measurements, studied for a number of organoarsenic standards, were 22 (negative bias) and 15 ppm, respectively. Structural information was obtained in the tandem Q-TOF mode. A total of 15 organoarsenic species were identified, and 13 of these possessed the dimethylarsinoyl group (8 ribofuranosides, 4 acyclic compounds, and 1 dihydroxyfuran). Four of these species were previously unreported. Arsenobetaine and dimethylarsinic acid were also detected. The major species (accounting for up to 50% water-soluble arsenic) was 5-dimethylarsinoyl-2,3,4-trihydroxypentanoic acid. The metabolic interrelationships of these compounds and their significance are briefly discussed.