NPI‐2358 ( 1 ) is a potent antimicrotubule agent that was developed from a natural diketopiperazine, phenylahistin, which is currently in Phase I clinical trials as an anticancer drug. To understand the precise recognition mechanism of tubulin by this agent, we focused on its potent derivative, KPU‐244 ( 2 ), which has been modified with a photoreactive benzophenone structure, and biotin‐tagged KPU‐244 derivatives ( 3 and 4 ), which were designed and synthesized for tubulin photoaffinity labeling. Introduction of the biotin structure at the p′‐position of the benzophenone ring in 2 exhibited reduced, but significant biological activities with tubulin binding, tubulin depolymerization and cytotoxicity in comparison to the parent KPU‐244. Therefore, tubulin photoaffinity labeling studies of biotin‐derivatives 3 and 4 were performed by using Western blotting analysis after photoirradiation with 365 nm UV light. The results indicated that tubulin was covalently labeled by these biotin‐tagged photoprobes. The labeling of compound 4 was competitively inhibited by the addition of diketopiperazine 1 or colchicine, and weakly inhibited by the addition of vinblastine. The results suggest that photoaffinity probe 4 specifically recognizes tubulin at the same binding site as anticancer drug candidate 1 , and this leads to the disruption of microtubules. Probe 4 serves well as a useful chemical probe for potent antimicrotubule diketopiperazines, much like phenylahistin, and it also competes for the colchicine‐binding site. 相似文献
A system of numerical flow simulation with an automated mesh generator and parallelized solver was developed and applied to the flow-field inside an optical disc drive. In this simulation system, a uniformly spaced Cartesian grid is used to reduce time and automatically generate a mesh from CAD data for complicated geometries, such as optical disc drives. The simulation results of optical disc drives are validated by particle image velocimetry (PIV) and pressure-distribution measurements. The measured velocity distributions above a rotating disc and around a pick-up unit show quantitative agreement with the simulated distributions. For the pressure distributions on a top case of an optical disc drive, although there is an error of 10% between simulated and measured results, the position of the peaks and distribution of pressure show good agreement. Comparing both sets of measurements, the simulation results in a Cartesian grid system are sufficiently accurate to enable the flow-field to be quantitatively assessed. This numerical flow simulation is applied to investigate the detailed flow-field in a commercial optical disc drive. 相似文献
Chromosome aberrations affecting 3q27 are among the most frequent non-random abnormalities in non-Hodgkin's lymphomas (NHL), especially the diffuse, large cell type. Recently, an association between BCL6 rearrangement and frequent extranodal lesions, rare bone marrow infiltration and a favorable clinical outcome was reported. We performed molecular studies of the BCL6 gene in 54 patients with NHL. Twelve patients (22%) with rearranged BCL6 genes were selected for histological, clinical, molecular, and cytogenetic studies. Ten of these cases were diffuse, large cell type lymphoma, one a follicular lymphoma, and one a mantle cell lymphoma (MCL). All cases were of the B-cell type and this is the first time a rearranged BCL6 gene has been found in an MCL. Cytogenetic data for 10 cases were available and the partner sites of the 3q27 translocation were determined in 7 of 10 patients. These locations were variable, including 6p21.3, 9p22, and 14q11 in addition to the immunoglobulin loci 14q32 (IGH), 2p12 (IGK), and 22q11 (IGL). The heterogeneity in partner sites is distinct from other lymphoma subgroups and may suggest that the genetic events are not uniform among patients with BCL6 rearrangements. 相似文献
A new scaling technique was developed in the present work to investigate the image integration of consumers, taking advantage of the recent visual and object-oriented programming technology. Employed visual stimuli were the logos (and the accompanying symbolic marks, if any) of the four leading cosmetic makers, the logos of their brands and the photos of their product packages of skincare items targeted at young females. 19 females subjects evaluated the stimuli with respect to four, five and eight items for the corporate (Clmg), the brand (Blmg) and the package (Plmg) images. The image inheritance was analyzed on the internally anchored items. In addition, external anchores were employed to facilitate the Kansei processing in part of the Bimg evaluations. The major findings included the contrasting patterns exhibited by two makers both in the maker/brand discrepancies and in the image inheritances. Among the important issues to be considered in the future work are the mediation effect of the matching task and the class structure of evaluative items like those employed in AHP.
Abstract— Novel anode layer plasma within minimum chamber space was developed for non‐contact alignment process. The plasma‐treated polyimide (PI) surface showed no particle contamination and no micro‐scratches. Surface morphology was investigated by using scanning electron microscope (SEM), an atomic force microscope (AFM), and X‐ray photoemission spectroscopy. The different oxygen‐to‐carbon ratio ([O]/[C] ratio) for XPS spectra indicated a composition change after plasma treatment. Surface pretilt angles were varied from 0 to 2.1° under different plasma exposure times. Finally, a prototype 20.8‐in. QXGA IPS‐mode gray‐scale medical liquid‐crystal display was successfully demonstrated with high contrast ratio, excellent uniformity, and wide viewing angle using this new plasma‐beam‐alignment technique. 相似文献
We investigated whether beta-amyloid (Abeta)-like immunoreactivity was seen in the brains of newborn piglets. The immunoreactivity for Abeta(1-42) and Abeta(1-40) proteins, but not Abeta precursor protein, was present in CD68-positive perivascular cells of the hippocampus and in parts of the meninges. It was colocalized with immunoreactivity for receptor for advanced glycation end product and tumor necrosis factor-alpha. The protein with a molecular mass of 27 kDa, which was recognized by the Abeta antibodies, was identified as triosephosphate isomerase (TPI) with sequence homology to Abeta peptides by N-terminal amino acid sequencing, mass fingerprint analysis using matrix-associated laser desorption/ionization mass spectrometry, and Western blotting. Western blotting assay also revealed that detectable expression of Abeta proteins were not seen in the piglet brains. These findings indicate that TPI with sequence homology to Abeta peptides accumulates in perivascular cells of the microglia/macrophage lineage located around arterial vessels of the newborn piglet hippocampus. 相似文献