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排序方式: 共有666条查询结果,搜索用时 15 毫秒
1.
Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
2.
D Averill D Blockus B Brabson J Brom C Jung H Ogren DR Rust M Derrick P Kooijman JS Loos B Musgrave LE Price J Repond K Sugano B Cork C Akerlof J Chapman D Errede MT Ken DI Meyer H Neal D Nitz R Thun R Tschirhart S Abachi P Baringer BG Bylsma R DeBonte D Koltick EH Low RL McIlwain DH Miller CR Ng EI Shibata 《Canadian Metallurgical Quarterly》1989,39(1):123-137
3.
4.
Yoon-Ha Jeong Seong-Kue Jo Bong-Hoon Lee Sugano T. 《Electron Device Letters, IEEE》1995,16(3):109-111
High performance enhancement mode InP MISFET's have been successfully fabricated by using the sulfide passivation for lower interface states and with photo-CVD grown P3N5 film used as gate insulator. The MISFET's thus fabricated exhibited exhibited pinch-off behavior with essentially no hysteresis. Furthermore the device showed a superior stability of drain current. Specifically under the gate bias of 2 V for 104 seconds the room temperature drain current was shown to reduce from the initial value merely by 2.9% at the drain voltage of 4 V. The effective electron mobility and extrinsic transconductance are found to be about 2300 cm 2/V·s and 2.7 mS/mm, respectively. The capacitance-voltage characteristics of the sulfide passivated InP MIS diodes show little hysteresis and the minimum density of interface trap states as low as 2.6×1014/cm2 eV has been attained 相似文献
5.
6.
Color‐vision deficiency is a relatively common genetic condition, which often leads to the obstruction of necessary information in colored images. It is important to minimize such inconvenient effects in communication using colored images from a universal design perspective. The universal design principle stipulates that all environments and products should be usable by all people, regardless of age, physical attributes, and ability. This article proposes a method to detect color combinations in a given image that would confuse color dichromats, and suggests a way in which to modify them to make the image easily distinguishable for both normal and dichromatic observers. Confusing color combinations were detected based on a color‐difference calculation using simulations of how the color would appear to dichromats. The confusing colors were then modified based on the minimization of an evaluation function, which was defined as the sum of the degree of confusion and the degree of color change from the original image. Several colored images obtained by the proposed method were compared with the originals by red–green dichromatic observers who judged them to be clearer, thereby confirming that the proposed method was effective for color rendering for universal design. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 203–211, 2008 相似文献
7.
Time-series primitive static states for detailing work state and flow of human-operated work machine
This paper proposes a quantification method for a comprehensive work flow in construction work for describing work states in more detail on the basis of analyzing state transitions of primitive static states (PSS), which consist of 16 symbolic work states defined by using on-off state of the lever operations and joint loads for the manipulator and end-effector. On the basis of the state transition rules derived from a transition-condition analysis, practical state transitions (PST), which are common and frequent transitions in arbitrary construction work, are defined. PST can be classified into essential state transition (EST) or nonessential state transitions (NST). EST extracts common phases of work progress and estimates positional relations between a manipulator and an object. NST reveals wasted movements that degrade the efficiency and quality of work. To evaluate comprehensive work flows modeled by combining EST and NST, work-analysis experiments using our instrumented setup were conducted. Results indicate that all the PSS definitely changes on the basis of PST under various work conditions, and work analysis using EST and NST easily reveals work characteristics and untrained tasks related to wasted movements. 相似文献
8.
Hitomi Natomi Toshihito Saitoh Kentaro Sugano Masao Iwamori Masahisa Fukayama Yoshitaka Nagai 《Lipids》1993,28(8):737-742
The composition of the glycosphingolipids of the human gastrointestinal tract was studied. The major neutral glycosphingolipids
were ceramide monohexosides (e.g., GalCer, GlcCer), LacCer, Gb3Cer, Gb4Cer and more polar ones with more than four sugars, whereas neither Gg3Cer nor Gg4Cer were present. The acidic glycosphingolipids consisted of sulfatides and gangliosides such as GM3, GM1, GD3 and GD1a. Also a large amount of sulfatides was found in the gastric mucosa and duodenum. The concentrations of sulfatides in the
fundic mucosa, antral mucosa and duodenum amounted to 416.0, 933.8 and 682.9 nmol/g of dry weight, respectively, exceeding
those in the gastric mucosa and kidney of other mammals. The major molecular species of the sulfatides were identified as
I3SO3-GalCer with hydroxylated longer-chain fatty acids based on the analyses by gas-liquid chromatography and negative ion fast-atom
bombardment mass spectrometry. In contrast, gangliosides in these regions showed a tendency to be lower than sulfatides, and
the molar ratios of sulfatides to gangliosides were about 2.0, whereas those in other parts were less than 0.5. A high content
of sulfatides in the gastric and duodenal mucosa, where mucosa is easily insulted by acid, pepsin and bile salts, may be closely
related to their roles in mucosal protection.
The nomenclature used for gangliosides and other glycosphingolipids follows the system of Svennerholm (Ref. 1) and the recommendation
of the IUPAC-IUB Commission (Ref. 2), respectively. 相似文献
9.
Shigeki Habaue Momoko AsaiMasatake Morita Yoshio OkamotoHiroshi Uyama Shiro Kobayashi 《Polymer》2003,44(18):5195-5200
α-Methylenemacrolides having various groups, such as aromatic, ether, and amine, were enzymatically, anionically, and radically polymerized. The polymerization with the lipase catalyst successfully afforded polymers only through the ring-opening process, whereas the vinyl polymerizations selectively proceeded by using anionic and radical initiators. The polyesters obtained by the enzymatic polymerization have a polymerizable methacrylic methylene group in the main-chain, in addition to the aromatic and polar groups, and were further radically polymerized to quantitatively produce a cross-linked polymer gel. 相似文献
10.
Sakayu Shimizu Kengo Akimoto Yoshifumi Shinmen Hiroshi Kawashima Michihiro Sugano Hideaki Yamada 《Lipids》1991,26(7):512-516
Incubation with sesame oil increases the mycelial dihomo-γ-linolenic acid content of an arachidonic acid-producing fungus,Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989)J. Am. Oil Chem. Soc. 66, 237–241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments
with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits
Δ5 desaturase at low concentrations, but does not inhibit Δ6, Δ9 and Δ12 desaturases. Kinetic analysis showed that (+)-sesamin
is a noncompetitive inhibitor (Ki for rat liver Δ5 desaturase, 155 μM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin, also inhibited only Δ5 desaturases
of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or
its oil are specific inhibitors of Δ5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.
On leave from Suntory Ltd. 相似文献