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排序方式: 共有1620条查询结果,搜索用时 15 毫秒
21.
AP Krapcho E Menta A Oliva R Di Domenico L Fiocchi ME Maresch CE Gallagher MP Hacker G Beggiolin FC Giuliani G Pezzoni S Spinelli 《Canadian Metallurgical Quarterly》1998,41(27):5429-5444
The synthesis and antitumor evaluation of 2, 5-disubstituted-indazolo[4,3-gh]isoquinolin-6(2H)-ones (9-aza-APs) are described. The key intermediates in the synthesis are benz[g]isoquinoline-5,10-diones which are substituted at positions 6 and 9 with groups of different nucleofugacity for SNAr displacements. The initial displacement of fluoride by a substituted hydrazine leads to the pyrazole analogues. Substitution of the remaining leaving group by an amine or BOC-protected amines leads to the 9-aza-APs 12. These analogues were converted into their maleate or hydrochloride salts 13. In two cases, namely, 13x and 13z, sidearm buildup was also employed in the synthetic pathway. In vitro evaluation of 9-aza-APs against the human colon tumor cell line LoVo uncovered for most of the compounds a cytotoxic potency lower than that of DuP-941 or mitoxantrone and comparable to that of doxorubicin. Only analogues 13c, 13n, and 13ff were as cytotoxic as DuP-941. Interestingly, while DuP-941 was highly cross-resistant in the LoVo cell line resistant to doxorubicin (LoVo/Dx), the 9-aza-APs carrying a distal lipophilic tertiary amine moiety in both chains were capable of overcoming the MDR resistance induced in this cell line. The 9-aza-APs show outstanding in vivo antitumor activity against both systemic P388 murine leukemia and MX-1 human mammary carcinoma transplanted in nude mice. At their optimal dosages, congeners 13a-c, 13f, 13n, 13q, 13x, and 13dd were highly effective against P388 leukemia with T/C% of 200-381, while the T/C% value of DuP-941 was 147. In the MX-1 tumor model, 24 compounds elicited percentages of tumor weight inhibitions (TWI) ranging from 50% to 99%. Congeners 13d, 13k, 13l, 13x, 13z, and 13ee emerged as the most effective ones, with TWI% 96, simliar to that of DuP-941 (TWI% = 95). On the basis of their efficacy profile in additional experimental tumors and lack of cardiotoxicity in preclinical models, two congeners have surfaced as potential clinical candidates. 相似文献
22.
FC Tulunay HO Onaran H Ergün A Ucar S Usanmaz K Embil M Tulunay 《Canadian Metallurgical Quarterly》1998,48(11):1068-1071
Phenprobamate (CAS 673-31-4) is a centrally acting skeletal-muscle relaxant agent. There are only two studies in the literature about the pharmacokinetics of phenoprobamate in man. The inconsistency between the results of these studies can be attributed partly to the different analytical methodologies used. A sensitive, specific and reproducible HPLC-assay, which may increase the reliability of the pharmacokinetic studies of phenprobamate in plasma, has been developed recently. The objective of this investigation was to assess the single-dose kinetics of phenprobamate in human and to determine the pharmacokinetic parameters of clinical and regulatory concern. The plasma pharmacokinetics of phenprobamate have been investigated following single oral administration at a dose of 800 mg in eleven healthy volunteers. 相似文献
23.
S. O. Hyatt B. S. Chao H. Yamauchi 《Journal of Materials Science: Materials in Electronics》1992,3(1):41-47
TiN films were deposited on (100)-Si substrates by RF-reactive sputtering. The effects of processing parameters and substrate orientation on the stoichiometry, resistivity and microstructure of reactively sputtered TiN thin films were investigated. The RF-power was fixed at 50 W, and the nitrogen content in the working gas was adjusted so that target nitridation occurred at a relatively low nitrogen content, 2.6% N2, in a fixed total flow rate of gases of 46.25 standard cubic centimetres (sccm). The N2 percentage was varied from 2.6% to 15.4%. The films were continuous and 200 nm thick. Films deposited with the substrate facing the target exhibited 111-texturing, while films on substrates lying in the same plane of the target surface had 100-texturing. Both X-rays photoelectron spectroscopy and high-resolution detailed scans of the Auger electron energy spectrum were used for the stoichiometry determination. On the 100-textured TiN films, the N/Ti ratio was 1.0 at low N2 flow rates; the N/Ti ratio rapidly increased with N2 flow rate, and then levelled off. The films had resistivities ranging from 85 to 1340 µ cm, and the functional dependence of both N/Ti and the resistivity values behaved similarly with increasing N2. X-ray single-line profile analysis of the 200-reflection indicated that the average crystallite size decreased and the average strain increased with increasing nitrogen content in the working gas. The Si/TiN structures were heat treated in the temperature range from 300 to 600°C in a quartz tube under 1 atm (105Pa) of flowing high purity Ar gas. Heat treatment at 300°C did not affect the TiN film integrity, while treatment at 400–600°C resulted in void-type defects. 相似文献
24.
25.
Hisao Ichijo Tetsuro Suehiro Aizo Yamauchi Shigeo Ogawa Masanori Sakurai Nobuo Fujii 《应用聚合物科学杂志》1982,27(5):1665-1674
A poly(vinyl alcohol) (PVA) fiber support incorporating various aminoacetal functional groups has been developed for immobilizing enzymes. The aminated PVA fiber seems to adsorb enzymes with electrostatic force of attraction; thus the immobilization procedure is simple. By the use of this fiber having immobilized enzymes, the reaction between enzymes and substrates is nearly independent of the size of subtstrates. This newly developed type of fiber, which is formed by a mass superfine fibers (SFF), each measuring 1 μm or less in diameter, permits much more increased surface area than the conventional enzyme immobilization supports. Our studies of the properties of the fiber for immobilization of enzymes show the following results: (1) SFF has a greater ability for the immobilization of invertase than ordinary fibers; (2) dimethyl-aminated SFF has the best performance for the immobilization of invertase. From these results, it is concluded that the dimethyl-aminated SFF is an excellent support for the immobilization of invertase. 相似文献
26.
α-Tocopherol was reacted with methyl linoleateperoxyl radicals at 37°C. The peroxyl radicals were generated by the reaction
of methyl linoleate with a free radical initiator, 2,2′-azobis(2,4-dimethylvaleronitrile). The primary products of α-tocopherol with methyl linoleate-peroxyl radicals were isolated by
reversephase and normal-phase high performance liquid chromatography (HPLC), and their structures were characterized by ultraviolet
(UV), infrared (IR),1H and13C nuclear magnetic resonance (NMR) and mass spectrometry (MS). There were four stereoisomers of methyl 13-(8a-peroxy-α-tocopherone)-9(Z),11(E)-octadecadienoate and four stereoisomers of methyl9-(8a-peroxy-α-tocopherone)-10(E),12(Z)-octadecadienoate. 相似文献
27.
Yamauchi Toshihiro Akao Yohei Yoshitani Ryota Nakamura Yuichi Hashimoto Masaki 《International Journal of Information Security》2021,20(4):461-473
International Journal of Information Security - Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator... 相似文献
28.
Takashi Yamauchi Jinsil Hwaryoung Seo Noel Jett Greg Parks Casady Bowman 《International journal of human-computer interaction》2013,29(12):911-921
Computer cursor and mouse activities such as moving, pointing, selecting, and dragging are essential parts of everyday interactions. Yet it is unknown how men and women differ in the way they move computer cursors. This study examines gender differences in movements of computer cursors. In one experiment, the authors measured trajectories of computer cursors every 20 ms in a simple choice-reaching task and tested the extent to which movement features related to controlling and targeting diverge between male and female participants. Results showed significant gender differences in cursor motions. Female participants deviated from the straight path toward the target location to a larger degree than did male participants, and female participants showed more backward motions (deviating backward from the target location) than did male participants. Implications for sources of these gender differences, user interface and input device design, and musculoskeletal disorders in women are also discussed. 相似文献
29.
FC Blow KL Barry BJ BootsMiller LA Copeland R McCormick S Visnic 《Canadian Metallurgical Quarterly》1998,32(5):311-319
Within a fungal species, a subset of individuals may have more than the minimal complement of chromosomes. If the extra chromosomes are composed primarily of DNA not found in all representatives of the species, they are most appropriately referred to as supernumerary chromosomes. The patterns of repeated DNA sequences on certain supernumerary chromosomes suggest that they have a different evolutionary history from the essential chromosomes in the same genome. Supernumerary chromosomes can carry functional genes and, in at least two fungal species, genes on such chromosomes play important roles in host-pathogen interactions. Supernumerary chromosomes that confer an adaptive advantage in certain habitats, such as the ability to cause disease on a specific host, may be referred to as "conditionally dispensable" chromosomes in order to reflect their importance in some, but not all, growth conditions. In addition to describing the structural and functional characteristics of known supernumerary chromosomes in fungi, this review discusses the relative merits of the terms that have been used to describe them, and establishes experimental criteria for their identification. 相似文献
30.
GW Gao SH Lin YF Lin LK Diang KC Lu FC Yu SD Shieh 《Canadian Metallurgical Quarterly》1996,57(6):438-442
Despite a general national decline in criminal activities in the 1990s, juvenile criminal offenses continue to increase, (including violent, property, and delinquency acts). In addition increased numbers of children are being held in juvenile jails. It is all but impossible for pediatric health providers to think that "their patients" and "their practices" are immune from the epidemic of crime that affects and is caused by "just kids." 相似文献