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排序方式: 共有2345条查询结果,搜索用时 15 毫秒
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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
3.
BS Kendrick BS Chang T Arakawa B Peterson TW Randolph MC Manning JF Carpenter 《Canadian Metallurgical Quarterly》1997,94(22):11917-11922
Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra. 相似文献
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Leslie Lamport 《Acta Informatica》1980,14(1):21-37
Summary Hoare's logical system for specifying and proving partial correctness properties of sequential programs is generalized to concurrent programs. The basic idea is to define the assertion {P} S {Q} to mean that if execution is begun anywhere in S with P true, then P will remain true until S terminates, and Q will be true if and when S terminates. The predicates P and Q may depend upon program control locations as well as upon the values of variables. A system of inference rules and axiom schemas is given, and a formal correctness proof for a simple program is outlined. We show that by specifying certain requirements for the unimplemented parts, correctness properties can be proved without completely implementing the program. The relation to Pnueli's temporal logic formalism is also discussed. 相似文献
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Leslie E. Chipman Benjamin B. Bederson Jennifer A. Golbeck 《Behaviour & Information Technology》2004,23(1):1-9
The SlideBar is a physical linear input device for absolute position control of 1° of freedom, consisting of a physical slider with a graspable knob positioned near or attached to the keyboard. Its range of motion is directly mapped to a one dimensional input widget such as a scrollbar. The SlideBar provides absolute position control in one dimension, is usable in the non-dominant hand in conjunction with a pointing device, and offers constrained passive haptic feedback. These characteristics make the device appropriate for the common class of tasks characterized by one-dimensional input and constrained range of operation. An empirical study of three devices (SlideBar, mouse controlled scrollbar, and mousewheel) shows that for common scrolling tasks, the SlideBar has a significant advantage over a standard mouse controlled scrollbar in user preference. In addition, users tended to prefer it over the mousewheel (without statistical significance). 相似文献
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An experimental study of the planar-flow melt-spinning process was performed in order to gain a better understanding of the
steady-state production of microcrystalline and amorphous ribbons. The dependence of the thickness of the ribbon product,T, on process parameters (wheel speed,U, nozzle/wheel gap,G, overpressure, ΔP, nozzle-slot breadth,R, and nozzle-slot width,W) was determined using an apparatus designed to deliver reproducible results. Thicknesses were reproducible to within 5%–8%.
Guided by dimensional analysis, the non-dimensional thickness (T/G) was found to depend, within the experimental error, only on a non-dimensional pressure drop (ΔP/ρU
2) and slot breadth (R/G) for fixed thermal conditions. Data from the literature and our data, which considerably extend the range, correlate consistently
on this basis. In contrast to the steady behaviour, the limits within which a uniform ribbon can be formed depend on a larger
set of parameters; this dependence is sketched with the available data. Finally, a variety of observed ribbon surface textures
(free meniscus side) is catalogued. 相似文献
10.
Albert Lamperti Alan Conger Leslie Delaney Marvin Sodicoff 《Drug development and industrial pharmacy》1994,20(12):1971-1989
ABSTRACT
Our transdermal permeation studies of radioprotectors in permeation-enhancing vehicles led us to hypothesize that radiation-induced hair loss could be reduced by topical application of radioprotectors. In the present study we used a hair regrowth assay in “plucked” mice to measure the radioprotective effectiveness of WR-1065, cysteine and TEMPOL when they were dissolved in a variety of vehicles, i.e., saline, dimethyl formamide (DMF), propylene glycol (PG), dimethyl sulfoxide (DMSO), ethanol. Protector effectiveness varied with radiation dose and vehicles. At 600 R, WR-1065 or cysteine, in any vehicle, reduced radiation-induced baldness scores; at 800 R, only WR-1065 in DMF and cysteine in saline, produced some protection. TEMPOL in ethanol produced protection at both the 600 and 800 R. Results suggest that suitably chosen topical application of protector/vehicle combinations can reduce radiation-induced hair loss. 相似文献
Our transdermal permeation studies of radioprotectors in permeation-enhancing vehicles led us to hypothesize that radiation-induced hair loss could be reduced by topical application of radioprotectors. In the present study we used a hair regrowth assay in “plucked” mice to measure the radioprotective effectiveness of WR-1065, cysteine and TEMPOL when they were dissolved in a variety of vehicles, i.e., saline, dimethyl formamide (DMF), propylene glycol (PG), dimethyl sulfoxide (DMSO), ethanol. Protector effectiveness varied with radiation dose and vehicles. At 600 R, WR-1065 or cysteine, in any vehicle, reduced radiation-induced baldness scores; at 800 R, only WR-1065 in DMF and cysteine in saline, produced some protection. TEMPOL in ethanol produced protection at both the 600 and 800 R. Results suggest that suitably chosen topical application of protector/vehicle combinations can reduce radiation-induced hair loss. 相似文献