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71.
TJ Tucker SF Brady WC Lumma SD Lewis SJ Gardell AM Naylor-Olsen Y Yan JT Sisko KJ Stauffer BJ Lucas JJ Lynch JJ Cook MT Stranieri MA Holahan EA Lyle EP Baskin IW Chen KB Dancheck JA Krueger CM Cooper JP Vacca 《Canadian Metallurgical Quarterly》1998,41(17):3210-3219
As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site. 相似文献
72.
Oryzacystatins (OCs) are protease inhibitors (PIs) that inhibit Colorado potato beetle (CPB) digestive proteases, and transgenic potato plants containing these PIs are currently under test. However, OCs could interfere with the digestive system of beneficial insects. Protease activity and susceptibility to class-specific protease inhibitors were studied in protein extracts of Perillus bioculatus, a stinkbug predator that has shown potential for biological control of the CPB. At physiological pH, the analysis of protease activity showed that up to 90% of P. bioculatus protease activity is of the cysteine type. All active life stages of the predator were tested, and electrophoretic characterization detected no major qualitative variation in protease pattern between stages. Protease activity in extracts of P. bioculatus nymphs was significantly reduced, up to 70%, by the two recombinant cystatins from rice (OCI and OCII), and by stefin A, a PI encoded by a human gene. These results clearly indicate that cysteine PIs are active not only against the CPB digestive protease complex, but also against proteases of one of its most important natural predators. 相似文献
73.
Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans
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75.
Bissessur H. Charlet G. Idler W. Simonneau C. Borne S. Pierre L. Dischler R. De Barros C. Tran P. 《Electronics letters》2002,38(8):377-379
50 GHz-spaced 80 × 40 Gbit/s WDM transmission over 300 km of TeraLightTM fibre is demonstrated without polarisation demultiplexing, using the PSBT format. A record capacity of 3.2 Tbit/s is thus achieved over the C-band only, with a spectral efficiency of 0.8 bit/s/Hz 相似文献
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77.
For all teens, the process of moving from childhood to adulthood is challenging. For young people with disabilities, transitioning to independence presents even more challenges. Barriers to successful transition for young people with disabilities include low expectations by parents and other significant people in the community, lack of knowledge of existing career and vocational education services, and lack of self-advocacy skills. This article provides an overview of issues related to transitioning to adult independence and offers suggestions for assessment, planning, and intervention that can help nurses be effective partners with families and other caregivers in transition efforts. Nurses caring for children with disabilities can help families see strengths in their children and develop realistic, developmentally-appropriate expectations for skill development, attitudes, and behaviors that will promote self-sufficiency in adulthood. Nurses can help families think about possibilities for independence and refer families to community resources that can help young people with disabilities pursue postsecondary education, obtain and maintain jobs, and live independently. 相似文献
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79.
WA Latzka MN Sawka SJ Montain GS Skrinar RA Fielding RP Matott KB Pandolf 《Canadian Metallurgical Quarterly》1998,84(6):1858-1864
This study examined the efficacy of glycerol and water hyperhydration (1 h before exercise) on tolerance and cardiovascular strain during uncompensable exercise-heat stress. The approach was to determine whether 1-h preexercise hyperhydration (29.1 ml H2O/kg lean body mass with or without 1.2 g/kg lean body mass of glycerol) provided a physiological advantage over euhydration. Eight heat-acclimated men completed three trials (control euhydration before exercise, and glycerol and water hyperhydrations) consisting of treadmill exercise-heat stress (ratio of evaporative heat loss required to maximal capacity of climate = 416). During exercise ( approximately 55% maximal O2 uptake), there was no difference between glycerol and water hyperhydration methods for increasing (P < 0.05) total body water. Glycerol hyperhydration endurance time (33. 8 +/- 3.0 min) was longer (P < 0.05) than for control (29.5 +/- 3.5 min), but was not different (P > 0.05) from that of water hyperhydration (31.3 +/- 3.1 min). Hyperhydration did not alter (P > 0.05) core temperature, whole body sweating rate, cardiac output, blood pressure, total peripheral resistance, or core temperature tolerance. Exhaustion from heat strain occurred at similar core and skin temperatures and heart rates in each trial. Symptoms at exhaustion included syncope and ataxia, fatigue, dyspnea, and muscle cramps (n = 11, 10, 2, and 1 cases, respectively). We conclude that 1-h preexercise glycerol hyperhydration provides no meaningful physiological advantage over water hyperhydration and that hyperhydration per se only provides the advantage (over euhydration) of delaying hypohydration during uncompensble exercise-heat stress. 相似文献
80.
In this study, symptom (item) level data were used to perform a psychometric analysis of the DSM-III-R personality disorders (PDs). Determined for each PD criteria set were convergent validity, discriminant validity, and internal consistency. The results indicated that the majority of the PD criteria sets (6 of the 11 ) possessed adequate convergent validity, although discriminant validity was problematic for most of these disorders. Internal consistency was also weak for the PD criteria sets, with only 3 of the 11 exceeding a minimum cutoff score of .70. The present study employed a methodology modeled after the one reported by Morey (1988a), and the results of the two studies were highly similar. Consistent findings across the two data sets can be taken to reflect the actual psychometric properties of the DSM-III-R PDs. The success of our replication demonstrates the potential that large-scale psychometric investigations hold for aiding the development and refinement of the DSM PDs. 相似文献