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61.
Li J Chen SY Murphy BJ Flynn N Seethala R Slusarchyk D Yan M Sleph P Zhang H Humphreys WG Ewing WR Robl JA Gordon D Tino JA 《Bioorganic & medicinal chemistry letters》2008,18(14):4072-4074
The first enantioselective synthesis of (d)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid 3 was achieved. The incorporation of the titled compound into growth hormone secretagogue (GHS) compounds resulted in new analogs 10 and 16, both of which had significantly increased in vitro potency. The compound 10 also showed improved in vivo efficacy as well as pharmacokinetic properties in rat models. 相似文献
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Wang H Ruan Z Li JJ Simpkins LM Smirk RA Wu SC Hutchins RD Nirschl DS Van Kirk K Cooper CB Sutton JC Ma Z Golla R Seethala R Salyan ME Nayeem A Krystek SR Sheriff S Camac DM Morin PE Carpenter B Robl JA Zahler R Gordon DA Hamann LG 《Bioorganic & medicinal chemistry letters》2008,18(11):3168-3172
Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series. 相似文献
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Electrical activation of mouse oocytes 总被引:3,自引:0,他引:3
Activation of the oocyte is the least efficient step in nuclear transplantation in the rabbit. We report the influence of age of oocytes, field strength, pulse duration and number, and shape of field on the rate of activation of mouse oocytes by electrical pulses. Regardless of oocyte age, activation rates were similar over a wide range of field strengths and pulse durations. Aged oocytes activated at a higher rate than recently ovulated oocytes (32 vs 3%), which lysed more frequently (13 vs 2%). Fragmentation rate was also higher among aged oocytes (42 vs 6%). The rate of activation increased with the number of pulses, from 9% with a single pulse, to 61% with six pulses. It also increased with the interval between pulses. Comparison of activation chamber geometries showed that the rate of activation was higher in a nonuniform field than in a uniform field and, for a particular field strength, varied from one electrode gap to another. These observations indicate that the rate of activation can be greatly increased by multiple electrical pulses. The activation rate also varied with consistent field strength in chambers with different electrode configurations. 相似文献
65.
D. E. Hanes R. W. Worobo P. A. Orlandi D. H. Burr M. D. Miliotis M. G. Robl J. W. Bier M. J. Arrowood J. J. Churey G. J. Jackson 《Applied microbiology》2002,68(8):4168-4172
This study evaluated the efficacy of UV irradiation on the inactivation of Cryptosporidium parvum oocysts in fresh apple cider. Cider was inoculated with oocysts and exposed to 14.32 mJ of UV irradiation/cm2. Oocyst viability was assessed with the gamma interferon gene knockout (GKO) mouse and infant BALB/cByJ mouse models. All GKO mice challenged with UV-treated cider demonstrated no morbidity or mortality, and infant BALB/c mice challenged with treated cider were negative for the presence of C. parvum. In contrast, the GKO mice challenged with non-UV-treated inoculated cider died and the parasite was detected in the ileums of all challenged infant mice. This study shows that UV irradiation can be used to inactivate C. parvum in fresh apple cider. 相似文献
66.
The effects of spermatozoa:uterine epithelial cell interactions in vitro on various sperm functions were studied using monolayers of uterine epithelial cells, endometrial stromal cells and fetal fibroblasts. Epithelial and stromal cells were isolated from uteri of rabbits in estrus, while fibroblasts were derived from 12-d-old rabbit fetuses. Twenty-nine to 31 h after culture initiation, washed, ejaculated rabbit spermatozoa were incubated with epithelial cells, uterine stromal or fetal fibroblastic cells, medium or conditioned medium. Sperm viability and loss of acrosome were measured after 10 to 20 h of incubation. Progressive sperm motility and fertilizing ability, which was assessed by an in vivo fertilization assay, were determined after 12 h co-culture. Sperm viability decreased throughout the culture period and was not affected by treatment. Sperm co-cultured with epithelial cells or incubated in medium had fewer acrosomes after 20 h than after 10 h. Fewer sperm co-cultured with stromal or fibroblastic cells lost their acrosomes. Progressive motility was positively affected by sperm-epithelium interaction as 39% of the co-cultured sperm were motile compared with 18% of the sperm incubated in media. In vivo fertilization experiments suggested that sperm incubated with epithelial cells or in medium had similar fertilizing ability. The co-culture of sperm with uterine cells provides an in vitro model to evaluate the effect of gamete-genital tract interaction on sperm function. 相似文献
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