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61.
R Wrigglesworth CS Walpole S Bevan EA Campbell A Dray GA Hughes I James KJ Masdin J Winter 《Canadian Metallurgical Quarterly》1996,39(25):4942-4951
Structural features of three regions of the capsaicin molecule necessary for agonist properties were delineated by a previously reported modular approach. These in vitro agonist effects were shown to correlate with analgesic potency in rodent models. Combination of optimal structural features from each of these regions of the capsaicin molecule have led to highly potent agonists (eg., 1b). Evaluation in vivo established that 1b had analgesic properties but poor oral activity, short duration of action, and excitatory side effects which precluded further development of this compound. Preliminary metabolism studies had shown that the phenol moiety of 1b was rapidly glucuronidated in vivo, providing a possible explanation for the poor pharmacokinetic profile. Subsequent specific modification of the phenol group led to compounds 2a-j, which retained in vitro potency. The in vivo profiles of two representatives of this series, 2a,h, were much improved over the "parent" phenol series, and they are candidates for development as analgesic agents. 相似文献
62.
CS Albretsen 《Canadian Metallurgical Quarterly》1996,116(30):3640-3642
Roald Amundsen is the most famous of the Norwegian polar explorers. His ancestors came from a group of islands south-east of the Oslofjord. From being fishermen and sailors, they progressed to becoming captains and shipowners in the course of two generations. Amundsen's father, Jens, stayed at sea until his ship went down with all the crew. Roald was 14 years of age at the time, the youngest of four competing brothers. Jens had left the close-knit local family community before that, and bought a flat in the capital, Oslo, so that his sons could get a better education. Roald's mother wanted him to study medicine. He did as she wished for a time, but was not at all interested. When his mother died, he abruptly left the university and went to sea, which had been the tradition in his family for decades. As a young boy he was an admirer of Sir John Franklin and his explorers of the Northwest Passage. Fridtjof Nansen became his ideal. The biographies about Roald Amundsen are very diverging--some hold him a hero, others reflect a strongly critical attitude. Here, the author tries to define his personality and places him firmly within the narcissistic domain. His tendency to seek the company of married women, but to take immediate flight when they really became interested reflects an Oedipus complex from before puberty. The tragic death of his father, the sea captain, may have been a supposition; puberty can be seen as a period of coping with ambivalence towards an earlier idealized father. His genius combined ambitious goals with a sharp eye for details as regards the equipment used in his expeditions. In his travels in the Arctic and the Antartic he was driven forward by the energy of the nation. His heroic death, trying to save his earlier "enemy", Nobile, was probably caused by an urge for self-destruction. 相似文献
63.
The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis. 相似文献
64.
CS Walpole R Wrigglesworth S Bevan EA Campbell A Dray IF James KJ Masdin MN Perkins J Winter 《Canadian Metallurgical Quarterly》1993,36(16):2381-2389
Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency. 相似文献
65.
The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+. 相似文献
66.
A distinction is suggested between the notions ‘information tare’, the role of which is played by the signals or letters forming the message, and ‘information’, which may be contained in such messages. It is shown that Shannon's definition of the amount of information is, in fact, the definition of the volume of information tare, whereas the amount of information itself may be measured as the volume of information tare of the maximally compact message used for its recording. This allows one to express both the volume of information tare, H, and the amount of information, B, in the same units of measurement–bits–and for any message B≤H. Some consequences of these views are analysed. 相似文献
67.
Minimizing photodecomposition of flavin adenine dinucleotide fluorescence by the use of pulsed LEDs
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Dynamic alterations in flavin adenine dinucleotide (FAD) fluorescence permit insight into energy metabolism‐dependent changes of intramitochondrial redox potential. Monitoring FAD fluorescence in living tissue is impeded by photobleaching, restricting the length of microfluorimetric recordings. In addition, photodecomposition of these essential electron carriers negatively interferes with energy metabolism and viability of the biological specimen. Taking advantage of pulsed LED illumination, here we determined the optimal excitation settings giving the largest fluorescence yield with the lowest photobleaching and interference with metabolism in hippocampal brain slices. The effects of FAD bleaching on energy metabolism and viability were studied by monitoring tissue pO2, field potentials and changes in extracellular potassium concentration ([K+]o). Photobleaching with continuous illumination consisted of an initial exponential decrease followed by a nearly linear decay. The exponential decay was significantly decelerated with pulsed illumination. Pulse length of 5 ms was sufficient to reach a fluorescence output comparable to continuous illumination, whereas further increasing duration increased photobleaching. Similarly, photobleaching increased with shortening of the interpulse interval. Photobleaching was partially reversible indicating the existence of a transient nonfluorescent flavin derivative. Pulsed illumination decreased FAD photodecomposition, improved slice viability and reproducibility of stimulus‐induced FAD, field potential, [K+]o and pO2 changes as compared to continuous illumination. 相似文献
68.
《材料的重要性》是《景观设计理论》的一段节选。《景观设计理论》旨在不使用专业术语或其他领域假说的前提下,结合景观设计过程向学生介绍内在理论思想。《材料的重要性》是本书的五章之一。每一章针对特定理论,解释了其基础和来源,探讨了它对设计的重要性,列举了20—21世纪与其相关的设计案例,整理了该理论的辩论(尤其是有关现代和后现代思想),最后还有相关阅读材料清单和需要学生们思考的问题。本文分为如下3个部分:第一部分,物质性,介绍“辩证唯物主义”“媒介即信息”“物质实践”和“编码”等理论及其在设计中的运用;第二部分,通过“建构表达”“地貌代理人策略”“石材的面层”“材料的暗示”“人造,但不是伪造”等理论,介绍材料的真实性及其在设计中的运用;第三部分,复写理论及应用,包括“剩余物”“复写的展示性”“未来的复写”和“虚构的复写”等内容。 相似文献
69.
本文提出一种智能体分层决策结构模型,试图通过分层决策技术有效地解决动态、不确定环境中的智能体的实时决策问题。本模型的高层采用BDI结构,以便为较长期任务的规划和推理提供充分的支持;模型的底层采用反应式结构,以保证对短期实时任务的及时响应。实验结果表明了这种分层模型在某些复杂任务领域中的有效性。 相似文献
70.
Brachial artery flow-mediated vasodilation is increasingly used as a measure of endothelial function. High resolution ultrasound provides a noninvasive method to observe this flow-mediated vasodilation by monitoring the diameter of the artery over time following a transient flow stimulus. Since hundreds of ultrasound images are required to continuously monitor brachial diameter for the 2-3 min during which the vasodilator response occurs, an automated diameter estimation is desirable. However, vascular ultrasound images suffer from structural noise caused by the constructive and destructive interference of the backscattered signals, and the true boundaries of interest that define the diameter are frequently obscured by the multiple-layer structure of the vessel wall. These problems make automated diameter estimation strategies based on the detection of the vessel wall boundary difficult. We obtain a robust automated measurement of the vasodilator response by automatically locating the artery using a variable window method, which gives both the lumen center and width. The vessel wall boundary is detected by a global constraint deformable model, which is insensitive to the structural noise in the boundary area. The ambiguity between the desired boundary and other undesired boundaries is resolved by a spatiotemporal strategy. Our method provides excellent reproducibility both for interreader and intrareader analyzes of percent change in diameter, and has been successfully used in analyzing over 4000 brachial flow-mediated vasodilation scans from several medical centers in the United States. 相似文献