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排序方式: 共有247条查询结果,搜索用时 296 毫秒
71.
Gallant M Beaulieu C Berthelette C Colucci J Crackower MA Dalton C Denis D Ducharme Y Friesen RW Guay D Gervais FG Hamel M Houle R Krawczyk CM Kosjek B Lau S Leblanc Y Lee EE Levesque JF Mellon C Molinaro C Mullet W O'Neill GP O'Shea P Sawyer N Sillaots S Simard D Slipetz D Stocco R Sørensen D Truong VL Wong E Wu J Zaghdane H Wang Z 《Bioorganic & medicinal chemistry letters》2011,21(1):288-293
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Frenette R Blouin M Brideau C Chauret N Ducharme Y Friesen RW Hamel P Jones TR Laliberté F Li C Masson P McAuliffe M Girard Y 《Bioorganic & medicinal chemistry letters》2002,12(20):3009-3013
A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models. 相似文献
74.
Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic-polyribocytidilic acid (poly I:C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin- but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease. 相似文献
75.
Computational model for airflow through the upper airway of a horse was developed. Previous flow models for human airway do not hold true for horses due to significant differences in anatomy and the high Reynolds number of flow in the equine airway. Moreover, models that simulate the entire respiratory cycle and emphasize on pressures inside the airway in relation to various anatomical diseases are lacking. The geometry of the airway was created by reconstructing images obtained from computed tomography scans of a thoroughbred racehorse. Different geometries for inhalation and exhalation were used for the model based on the difference in the nasopharynx size during the two phases of respiration. The Reynolds averaged Navier-Stokes equations were solved for the isothermal flow with the standard k-epsilon model for turbulence. Transient pressure boundary conditions for the entire breathing cycle were obtained from past experimental studies on live horses. The flow equations were solved in a commercial finite volume solver. The flow rates, computed based on the applied pressure conditions, were compared to experimentally measured flow rates for model validation. Detailed analysis of velocity, pressure, and turbulence characteristics of the flow was done. Velocity magnitudes at various slices during inhalation were found to be higher than corresponding velocity magnitudes during exhalation. The front and middle parts of the nasopharynx were found to have minimum intraluminal pressure in the airway during inhalation. During exhalation, the pressures in the soft palate were higher compared to those in the larynx, epiglottis, and nasopharynx. Turbulent kinetic energy was found to be maximum at the entry to the airway and gradually decreased as the flow moved inside the airway. However, turbulent kinetic energy increased in regions of the airway with abrupt change in area. Based on the analysis of pressure distribution at different sections of the airway, it was concluded that the front part of the nasopharynx requires maximum muscular activity to support it during inhalation. During exhalation, the soft palate is susceptible to displacements due to presence of high pressures. These can serve as critical information for diagnosis and treatment planning of diseases known to affect the soft palate and nasopharynx in horses, and can potentially be useful for human beings. 相似文献
76.
G P Kenny F D Reardon W Zaleski M L Reardon F Haman M B Ducharme 《Journal of applied physiology》2003,94(6):2350-2357
Seven subjects (1 woman) performed an incremental isotonic test on a Kin-Com isokinetic apparatus to determine their maximal oxygen consumption during bilateral knee extensions (Vo(2 sp)). A multisensor thermal probe was inserted into the left vastus medialis (middiaphysis) under ultrasound guidance. The deepest sensor (tip) was located approximately 10 mm from the femur and deep femoral artery (T(mu 10)), with additional sensors located 15 (T(mu 25)) and 30 mm (T(mu 40)) from the tip. Esophageal temperature (T(es)) was measured as an index of core temperature. Subjects rested in an upright seated position for 60 min in an ambient condition of 22 degrees C. They then performed 15 min of isolated bilateral knee extensions (60% of Vo(2 sp)) on a Kin-Com, followed by 60 min of recovery. Resting T(es) was 36.80 degrees C, whereas T(mu 10), T(mu 25), and T(mu 40) were 36.14, 35.86, and 35.01 degrees C, respectively. Exercise resulted in a T(es) increase of 0.55 degrees C above preexercise resting, whereas muscle temperature of the exercising leg increased by 2.00, 2.37, and 3.20 degrees C for T(mu 10), T(mu 25), and T(mu 40), respectively. Postexercise T(es) showed a rapid decrease followed by a prolonged sustained elevation approximately 0.3 degrees C above resting. Muscle temperature decreased gradually over the course of recovery, with values remaining significantly elevated by 0.92, 1.05, and 1.77 degrees C for T(mu 10), T(mu 25), and T(mu 40), respectively, at end of recovery (P < 0.05). These results suggest that the transfer of residual heat from previously active musculature may contribute to the sustained elevation in postexercise T(es). 相似文献
77.
APP N端片段的神经营养作用 总被引:6,自引:0,他引:6
APP是β-淀粉样肽的前体蛋白,由695-770个氨基酸经,春N端水解产物可分沁至细胞外环境。AP具有促进神经细胞生长作用,其中319-335肽段即APP17肽能提高动物的学习记忆能力。其他APP片段是否具有神经营养功能未见报道。本研究通过观察APP N端片段对人神经母细胞瘤株SY5Y生长的影响以及对实验性糖尿病动物行为的影响,希望APP促进神经细胞生长的其他肽段。用化学合肥APP N端多肽片段,以SY5Y细胞MTT代谢率、细胞计数、LDH漏出率和实验性糖尿病小鼠水迷宫试验结果为观察指标。结果APP64肽、29肽、11肽均有促进SY5Y细胞生长的作用,APP11肽可提高糖尿病动物水迷宫测试成绩,说明可溶性APP的N端可能具有神经营养作用,我们认为保持此作用的最短片段为APP11肽,此肽段的发现为进一步研究APP的构效关系奠定了基础。 相似文献
78.
鸟苷发酵过程的多尺度问题研究 总被引:4,自引:0,他引:4
以鸟苷发酵为对象,在生物反应器中以多尺度问题的角度,对在线计算机数据进行相关分析,结合中间代谢物及有关酶活性的检测,建立了以代谢流为核心的多尺度调控方法;又通过与代谢流迁移有关的动态化学计量分析,实现了对批式发酵过程的时变系统估算,建立了主体代谢与产物形成的支路代谢间,包括能量与物质流的关系模型;最后,把具有不同生产能力菌株的关键基因与基因库数据进行了序列比较,发现了本文研究的菌株已具备高产能力,即编码sAMP合成酶的基因发生移码突变以及pur操纵子的多处突变,而中心代谢流迁移是过程优化的关键。对开展微生物功能基因组学的研究和工业过程优化的问题进行了探讨,作者提出有必要从生物反应器的系统生物学高度来认识和解决所面临的问题。 相似文献
79.
开花植物具有多样性的生殖系统,其中单性花的形成是促进异交、避免自交衰退、保持遗传多样性的重要途径。单性花物种分布于被子植物不同进化分支上的事实表明,物种的雌雄异花性可能是通过不同的机制进化形成的。本文从花发育、性染色体、植物激素和环境因素四个方面,阐述了被子植物性别分化调控机制的研究进展。 相似文献
80.