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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.
BAIS: A Bayesian Artificial Immune System for the effective handling of building blocks 总被引:1,自引:0,他引:1
Significant progress has been made in theory and design of Artificial Immune Systems (AISs) for solving hard problems accurately. However, an aspect not yet widely addressed by the research reported in the literature is the lack of ability of the AISs to deal effectively with building blocks (partial high-quality solutions coded in the antibody). The available AISs present mechanisms for evolving the population that do not take into account the relationship among the variables of the problem, potentially causing the disruption of high-quality partial solutions. This paper proposes a novel AIS with abilities to identify and properly manipulate building blocks in optimization problems. Instead of using cloning and mutation to generate new individuals, our algorithm builds a probabilistic model representing the joint probability distribution of the promising solutions and, subsequently, uses this model for sampling new solutions. The probabilistic model used is a Bayesian network due to its capability of properly capturing the most relevant interactions among the variables. Therefore, our algorithm, called Bayesian Artificial Immune System (BAIS), represents a significant attempt to improve the performance of immune-inspired algorithms when dealing with building blocks, and hence to solve efficiently hard optimization problems with complex interactions among the variables. The performance of BAIS compares favorably with that produced by contenders such as state-of-the-art Estimation of Distribution Algorithms. 相似文献
65.
Pattern classification with mixtures of weighted least-squares support vector machine experts 总被引:1,自引:1,他引:0
Clodoaldo A. M. Lima André L. V. Coelho Fernando J. Von Zuben 《Neural computing & applications》2009,18(7):843-860
Support Vector Machine (SVM) classifiers are high-performance classification models devised to comply with the structural risk minimization principle and to properly exploit the kernel artifice of nonlinearly mapping input data into high-dimensional feature spaces toward the automatic construction of better discriminating linear decision boundaries. Among several SVM variants, Least-Squares SVMs (LS-SVMs) have gained increased attention recently due mainly to their computationally attractive properties coming as the direct result of applying a modified formulation that makes use of a sum-squared-error cost function jointly with equality, instead of inequality, constraints. In this work, we present a flexible hybrid approach aimed at augmenting the proficiency of LS-SVM classifiers with regard to accuracy/generalization as well as to hyperparameter calibration issues. Such approach, named as Mixtures of Weighted Least-Squares Support Vector Machine Experts, centers around the fusion of the weighted variant of LS-SVMs with Mixtures of Experts models. After the formal characterization of the novel learning framework, simulation results obtained with respect to both binary and multiclass pattern classification problems are reported, ratifying the suitability of the novel hybrid approach in improving the performance issues considered. 相似文献
66.
Luiz Augusto da Cruz Meleiro Fernando José Von Zuben Rubens Maciel Filho 《Engineering Applications of Artificial Intelligence》2009,22(2):201-215
In the present work, a constructive learning algorithm was employed to design a near-optimal one-hidden layer neural network structure that best approximates the dynamic behavior of a bioprocess. The method determines not only a proper number of hidden neurons but also the particular shape of the activation function for each node. Here, the projection pursuit technique was applied in association with the optimization of the solvability condition, giving rise to a more efficient and accurate computational learning algorithm. As each activation function of a hidden neuron is defined according to the peculiarities of each approximation problem, better rates of convergence are achieved, guiding to parsimonious neural network architectures. The proposed constructive learning algorithm was successfully applied to identify a MIMO bioprocess, providing a multivariable model that was able to describe the complex process dynamics, even in long-range horizon predictions. The resulting identification model was considered as part of a model-based predictive control strategy, producing high-quality performance in closed-loop experiments. 相似文献
67.
A precise calculation of the amount of intraalveolar fluid is the basis of a quantitative analysis of intraalveolar compounds. Different approaches have been made to cover this important problem. Here, we report a comparative study with five markers: 99mTc-DTPA, 51Cr-EDTA, inulin, urea, and methylene blue in animal experiments as well as in human experiments. The marker substances were added to the lavage fluid, and the "dilution" of the markers, i.e., the alveolar fluid, was calculated. The results showed that in animals with healthy lungs the tracer methods are able to calculate amounts of intraalveolar fluid that are comparable to morphologic findings. In animals as well as in humans, methylene blue and inulin were shown to be useless in determining alveolar fluid volume compared with the tracer methods. In humans, the calculations with the urea method and with Tc-DTPA were in the same magnitude, but there was no individual correlation. We conclude that, at present, the methods to quantitate alveolar fluid volume lack precision and add nothing to a deeper understanding of alveolar biology. 相似文献
68.
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
69.
H. Von Spittler 《Zeitschrift für Jagdwissenschaft》1972,18(2):76-95
Zusammenfassung Nach kurzer referierender Darstellung einiger Anmerkungen über die Nahrungsbiologie, Vermehrungsrate und Besatzermittlung des Fuchses wird der zeitlich-räumliche Verlauf, den die Tollwut in Nordrhein-Westfalen genommen hat, aufgezeigt, wobei herausgestellt wird, daß im wesentlichen die waldreicheren Mittelgebirgslagen des Landes von ihr erfaßt worden sind. An Hand der Streckenergebnisse wird sodann erörtert, in welchem Ausmaß der Fuchsbesatz in den einzelnen betroffenen Kreisen durch die Tollwut reduziert worden ist. Es zeigt sich, daß prozentual der stärkste Rückgang in den Kreisen zu verzeichnen ist, die zuvor die höchsten Strekken aufzuweisen hatten.Sowohl bei den Hasen- als auch bei den Rebhuhnstrecken kommt es in den gleichen Jahren, in denen die Fuchsstrecken abnahmen, zu einer sprunghaften Aufwärtsentwicklung in der Mehrzahl der von der Tollwut heimgesuchten Kreise, wobei sich eine signifikante Proportionalität zwischen Rückgang des Fuchses und Zunahme von Hase und Rebhuhn erkennen läßt.Durch Gegenüberstellung der Streckenergebnisse für Fuchs, Hase und Rebhuhn aus den Kreisen Meschede, Schleiden und Dinslaken wird erläutert, daß die Zunahme der Niederwildstrecken in den Jahren nach Auftreten der Tollwut in erster Linie auf den Rückgang des Fuchses zurückzuführen ist. Günstigere Witterung vermag sich erst sekundär auszuwirken.Auf die Erfordernis einer intensiven Bejagung des Fuchses wird hingewiesen.
Summary The food biology, the reproduction rate of the fox, and the ascertainment of density are briefly presented, after which the time-space development of rabies is discussed; rabies are to be found largely in the forested, sub-alpine mountain areas of the state. As a result of the harvest, the extent to which the fox populations in specific areas are reduced by rabies is examined. It can be shown that the largest percentage decreases occur in areas where the harvest had previously been highest.In the same years that the fox harvest declined, a sudden increase in hare as well as partridge harvests were observed in the majority of rabies-infected areas; a significant correlation between the decrease in foxes and increase in hare and partridge was discerned.Comparison of the harvests of fox, hare und partridge in the districts Meschede, Schleiden and Dinslaken reveals that the increase in small game harvests in the years after the appearance of rabies is primarily a result of the decline in the number of foxes. Favorable weather conditions can have only a secondary effect.The importance of intensive hunting of foxes was emphasized.
Résumé Après un rappel bibliographique à propos de la biologie alimentaire, du taux de reproduction et de l'effectif du Renard, l'évolution dans l'espace et le temps de la Rage en Rhénanie-Westphalie est décrite. Il en ressort que ce sont les régions forestières montagneuses qui sont essentiellement concernées par cette épizootie. L'examen des tableaux du Renard permet par ailleurs de constater que la décimation de cette espèce été proportionellement la plus forte dans les districts où, avant la lutte anti-rabique, les tableauxe étaient les plus élevés.Dans la plupart des secteurs où régnait l'épidémie de Rage, les tableaux en Lièvre et en Perdrix augmentaient brusquement lorsque les tableaux en Renard commençaient à diminuer, ces deux valeurs étant en corrélation négative et significative.L'examen des tableaux du Renard, du Lièvre et de la Perdrix dans des districts de Meschede, Schleiden et Dinslaken montre clairement que l'augmentation des tableaux en petit gibier au cours des années suivant l'apparition de la Rage résulte en premier lieu de la régression du Renard et accessoirement de conditions météorologiques plus favorables.La nécessité d'une chasse intensive du Renard est soulignée.相似文献
70.