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1.
Lissy Z. F. Gross Mariana Sacerdoti Prof. Albrecht Piiper Prof. Stefan Zeuzem Dr. Alejandro E. Leroux Dr. Ricardo M. Biondi 《ChemMedChem》2020,15(18):1682-1690
Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein. 相似文献
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Christian P. Romero Jonathan I. Avila Edgardo Cisternas Guerau B. Cabrera Alejandro L. Cabrera Kristiaan Temst Margriet J. Van Bael 《Journal of Materials Science》2007,42(18):7667-7672
Hydrogen desorption curves were obtained from a sample composed of a square arrangement of Co dots with average diameter of
4.4 μm, separated by a distance of 11.6 μm. A macroscopic sample of Co dots grown on a 2.5 × 2.5 cm Si substrate was made
by standard lithographic techniques and used in these experiments. Thermal programmed desorption (TPD) was performed under
ultra-high vacuum conditions. Hydrogen TPD curves were obtained from a 1 × 1 cm Co dots samples displaying a maximum of intensity
at 425 K. Hydrogen TPD curve was also obtained from 1 cm× 1 cm samples of Co films and Co foils for comparison. The hydrogen
TPD curves have decreasing intensity from the Co foils to the Co dots and finally to the Co films. This indicates that there
are more sites for hydrogen adsorption on the Co dots than in the Co films. This is a surprising result because there is approximately
8.7 times less Co atoms exposed in the Co dots that in the Co film sample. A desorption energy of 27 kcal/mol was obtained
for the Co dots suggesting that hydrogen is adsorbed on an hcp hollow site of the Co dot crystalline structure. 相似文献
4.
This paper shows a few possibilities for the application of Community OR in a Third World country based on experience in Venezuela. These possibilities are discussed in a framework of the relationship between the state and community organizations. Emphasis lies in showing that Community OR in Venezuela requires a deep critical commitment to emancipation in order to help community organizations develop in a rather hostile environment. Lastly, results in dealing with community organizations in Venezuela using the Interpretive Systemology approach are presented. 相似文献
5.
In this article, we analyze a co-operative multi-thread search-based optimization strategy, where each solver thread represents a different optimization algorithm (or the same one with different settings), and they are all controlled by a centralized co-ordinator. We also propose the use of memory to keep track of both the state of the individual threads and the obtained solutions. Based on this memory, a very simple fuzzy rule base is used to control the system behavior.We also present the results of three computational experiments. The first of these checks the strategy by comparing it with an independent search strategy and a sequential algorithm, and the superiority of the co-operative scheme is confirmed. The second analyzes how definition of the threads affects the quality of the results, and the importance of there being a balanced set between intensification and diversification is corroborated. The third explores the use of memory with two different fuzzy rules, and the results indicate that the best combination is to use memory together with two rules (solver dependent and solver independent ones) (although this combination should not be activated at the beginning of the search in order to avoid premature convergence). 相似文献
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The Grid shows itself as a globally distributed computing environment, in which hardware and software resources are virtualized to transparently provide applications with vast capabilities. Just like the electrical power grid, the Grid aims at offering a powerful yet easy‐to‐use computing infrastructure to which applications can be easily ‘plugged’ and efficiently executed. Unfortunately, it is still very difficult to Grid‐enable applications, since current tools force users to take into account many details when adapting applications to run on the Grid. In this paper, we survey some of the recent efforts in providing tools for easy gridification of applications and propose several taxonomies to identify approaches followed in the materialization of such tools. We conclude this paper by describing common features among the proposed approaches, and by pointing out open issues and future directions in the research and development of gridification methods. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
8.
Thermodynamic principles, involving mainly: (1) minimum reversible work of separation and (2) second-law analysis that accounts for irreversibility, are used to synthesize separation trains. These principles lead to a development and classification into two groups of many of the heuristics appearing in the literature. An efficient algorithm based on reversible thermodynamics leads to optimal structures for simple acyclic trains. Complex structures are efficiently synthesized by algorithms using reversible thermodynamics and second-law analysis. The procedures presented are depth-first algorithms. The optimal structures developed are shown to be strongly influenced by feed and product compositions. 相似文献
9.
Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se. 相似文献
10.
PF Eire D Vallejo JL Sastre MA Rodriguez M Garrido 《Canadian Metallurgical Quarterly》1998,33(12):1820-1821
Mesenteric venous thrombosis (MVT) after appendicectomy has not been reported in the pediatric literature. This complication is associated with significant morbidity and mortality rates in adults. The report of this case attempts to analyze the features found in an appendicectomized child documented by radiological examination and surgery before and after starting heparin therapy. Anticoagulation treatment should be started as soon as possible and continued for a long time to decrease the risk of relapse. 相似文献