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51.
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
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S.K. Vimala Bharathi M. Maria Leena J.A. Moses C. Anandharamakrishnan 《International Journal of Food Science & Technology》2020,55(3):1238-1245
The usage of cling wraps is emerging as an easy and cost-effective approach to protect fresh-cut fruits and vegetables from dust, whilst improving visual appeal on retail counters. This study focused on developing an alternate, protein-based packaging material as a food grade cling wrap for food packaging applications. Zein-based cling wraps were produced, and their physical and mechanical characteristics were evaluated and compared with conventionally used chitosan biopolymer films and commercial synthetic polymer films. Antioxidant potential of the prepared films was studied, and the effectiveness of the developed films as anti-browning cling wraps was evaluated using studies conducted on fresh-cut apple slices at ambient conditions. Anti-browning effects were in par with polymeric counterparts; however, zein cling wraps could better prevent weight loss in apple slices. Zein-based films can be adopted as biodegradable food grade cling wraps as an alternative to chitosan and synthetic polymeric materials. 相似文献
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H.C. Weigele L. Gygax A. Steiner B. Wechsler J.-B. Burla 《Journal of dairy science》2018,101(3):2370-2382
Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection. 相似文献
55.
F. Schröder R. M. Ward A. R. Walpole R. P. Turner M. M. Attallah J.-C. Gebelin 《Materials Science & Technology》2015,31(3):372-384
Linear friction welding of the Ti6Al4V alloy is studied. A new definition of the energy input rate is proposed, based on an integration over time of the in-plane force and velocity; a strong correlation with the upset rate is then found. The effective friction coefficient is estimated to be 0·5±0·1 for varying frequencies and amplitudes, with only a weak dependence on the processing conditions displayed. A model is proposed that accounts for both the conditioning and equilibrium stages of the process, which is shown to be in good agreement with the experimental data. The model is used to study the mechanism by which the flash is formed. A criterion is proposed by which the rippled nature of its morphology can be predicted. 相似文献
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Freddy A. Bernal Dr. Marcel Kaiser Prof. Dr. Bernhard Wünsch Prof. Dr. Thomas J. Schmidt 《ChemMedChem》2020,15(1):68-78
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model. 相似文献
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