3 research outputs found
Design, synthesis and biological evaluation of stereo- and regioisomers of amino aryl esters as multidrug resistance (MDR) reversers
No full textStereo- and regioisomers of a series of N,N-bis(alkanol)amine aryl ester derivatives have been prepared and studied as multidrug resistance (MDR) modulators. The new compounds contain a 2-(methyl)propyl chain combined with a 3-, 5- or 7-methylenes long chain and carry different aromatic ester portions. Thus, these compounds have a methyl group on the 3-methylenes chain and represent branched homologues of previously studied derivatives. The introduction of the methyl group gives origin to a stereogenic center and consequently to (R) and (S) enantiomers. In the pirarubicin uptake assay on K562/DOX cell line these compounds showed good activity and efficacy and in many cases enantioselectivity was observed. Docking studies confirmed the influence of the stereocenter on the interaction in the P-gp pocket. The P-gp interaction mechanism and selectivity towards MRP1 and BCRP were also evaluated on MDCK transfected cells overexpressing the three transporters. Almost all these compounds inhibited both P-gp and BCRP, but only derivatives with specific structural characteristics showed MRP1 activity. Moreover, two compounds, (S)-3 and (R)-7, showed the ability to induce collateral sensitivity (CS) against MDR cells. Therefore, these two CS-promoting agents could be considered interesting leads for the development of selective cytotoxic agents for drug-resistant cells
Results of the first performance tests of the CMS electromagnetic calorimeter
No full textPerformance tests of some aspects of the CMS ECAL were carried out on modules of the "barrel" sub-system in 2002 and 2003. A brief test with high energy electron beams was made in late 2003 to validate prototypes of the new Very Front End electronics. The final versions of the monitoring and cooling systems, and of the high and low voltage regulation were used in these tests. The results are consistent with the performance targets including those for noise and overall energy resolution, required to fulfil the physics programme of CMS at the LHC
Energy resolution of the barrel of the CMS electromagnetic calorimeter
No full textThe energy resolution of the barrel part of the CMS Electromagnetic Calorimeter has been studied using electrons of 20 to 250 GeV in a test beam. The incident electron's energy was reconstructed by summing the energy measured in arrays of 3 × 3 or 5 × 5 channels. There was no significant amount of correlated noise observed within these arrays. For electrons incident at the centre of the studied 3 × 3 arrays of crystals, the mean stochastic term was measured to be 2.8% and the mean constant term to be 0.3%. The amount of the incident electrons' energy which is contained within the array depends on its position of incidence. The variation of the containment with position is corrected for using the distribution of the measured energy within the array. For uniform illumination of a crystal with 120 GeV electrons a resolution of 0.5% was achieved. The energy resolution meets the design goal for the detector
