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Wu G Irvine J Luft C Pressley D Hodge CN Janzen B 《Combinatorial chemistry & high throughput screening》2003,6(4):303-312
Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In addition, microfluidic screening and plate-based screening are compared in terms of reagent consumption, data quality, and ease of operation. 相似文献
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RITVA LINDBERG GORAN SUNDHOLM JOHAN SJö BLOM PETRI AHONEN ESKO I. KAUPPINEN 《Journal of Dispersion Science and Technology》2013,34(1-2):715-722
The zeta-potentials of silica, copper, platinum and gold particles have been measured as a function of pH. The isoelectric points were found to be at pH 3.0, 5.8, 3.0 and 3.5, respectively. In the pH range 3.0 to 5.8 copper and silica particles are oppositely charged and accordingly the coating of silica with copper particles could be demonstrated. In the case of gold and platinum the sign of the charge is such that direct adhesion to silica particles cannot be expected and this was also demonstrated in the case of platinum. 相似文献
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Nam T. Nguyen Edward Greenhalgh Mohd J. Kamaruddin Jaouad El harfi Kim Carmichael Georgios Dimitrakis Samuel W. Kingman John P. Robinson Derek J. Irvine 《Tetrahedron》2014
This paper reports the first detailed study focussed upon identifying the influence that microwave heating (MWH) has upon the mechanic steps involved in the tin catalysed ring-opening of lactones such as ?-caprolactone (CL). Direct comparison of conventional (CH) and microwave (MWH) heated kinetic studies showed that a key factor in the reduction of the polymerisation cycle time with MWH was the elimination of the induction period associated with in situ catalyst manufacture and initiation. NMR studies demonstrated that the most significant mechanistic change contributing to the observed induction time reduction/elimination was faster initiation (i.e., reaction of the initiatior/catalyst complex with the first monomer unit). Consequently, analysis of the dielectric properties of the reaction components predicted that this MWH induced change was related to the selective volumetric heating of both the catalyst and the monomer. Furthermore, this indication of the greater significance of the initiation step in defining the length of the induction period suggests that this is the rate determining step of the process, whether conducted by CH or MWH. Increasing the catalyst concentration was demonstrated to produce significant reductions in reaction heat-up time and to induce a significant (up to 30 °C) overshoot in reaction mixture bulk temperature in with MWH only. Thus supporting the conclusion that selective heating of the organometallic species in the system contributes directly to differences in the reaction conditions and which need to be taken into account when drawing comparisons with CH systems. Consequently, both effects were concluded to be thermally generated from selective volumetric heating. 相似文献
6.
Dibenzyl trisulfide (DTS) is a natural compound with potential cancer-preventive properties occurring in Petiveria alliacea L., an ethnomedicinal plant native to the Americas. Previous studies revealed its inhibitory activity toward cytochrome P450 (CYP)1 enzymes, key in the activation of environmental pollutants. Accordingly, the aim of this study was to design novel DTS analogues, aimed at improving not only inhibitory activity, but also specificity toward CYP1A1. This was achieved by targeting interactions with CYP1A1 residues of identified importance. Three-dimensional structures for the novel analogues were subjected to molecular docking with several CYP isoforms, before being ranked in terms of binding affinity to CYP1A1. With three hydrogen bond donors, two hydrogen bond acceptors, a molecular mass of 361 Da, and a log P of 3.72, the most promising DTS analogue obeys Lipinski's rule of five. Following synthesis and in vitro validation of its CYP1A1-inhibitory properties, this compound may be useful in future cancer-preventive approaches. 相似文献
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We present an experimental realization of Hardy's thought experiment [Phys. Rev. Lett. 68, 2981 (1992)], using photons. The experiment consists of a pair of Mach-Zehnder interferometers that interact through photon bunching at a beam splitter. A striking contradiction is created between the predictions of quantum mechanics and local hidden variables. The contradiction relies on nonmaximally entangled position states of two particles. A Clauser-Horne-type inequality is derived and violated. 相似文献
8.
Nonlinear photonic crystals can be used to provide phase matching for frequency conversion in optically isotropic materials. The phase-matching mechanism proposed here is a combination of form birefringence and phase velocity dispersion in a periodic structure. Since the phase matching relies on the geometry of the photonic crystal, it becomes possible to use highly nonlinear materials. This is illustrated considering a one-dimensional periodic Al0.4Ga0.6As/air structure for the generation of 1.5 microm light. We show that phase-matching conditions used in schemes to create entangled photon pairs can be achieved in photonic crystals. 相似文献
9.
We demonstrate how a beam splitter in combination with different light sources can be used as an optimal universal 1-->2 quantum cloner and as an optimal universal quantum NOT machine for the polarization qubit of a single photon. For the cloning a source of single photons with maximally mixed polarization is required and for the NOT operation a source of maximally entangled photon pairs. We demonstrate both operations with near optimal fidelity. Our scheme can be generalized in a natural way to clone and NOT the spin state of electrons. 相似文献
10.
van Enk SJ 《Physical review letters》2000,84(4):789; author reply 790