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排序方式: 共有1085条查询结果,搜索用时 31 毫秒
1.
Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
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We define the very rich language of composed conditionals on a three‐valued logic and use this language as the communication tool between man and machine. Communication takes place for three reasons: knowledge acquisition, query, and response. Learning, thinking, and answering questions are of a pure information theoretical nature. The pivot of this knowledge processing concept is the amount of information (bit) we receive if a conditional becomes true. We follow an axiomatic approach to information theory rather than the classical probabilistic approach of Shannon; information comes first, and then comes probability. In the light of this philosophy, query and response experience new interpretations. Both, acquisition and response are realized by maximizing entropy and minimizing relative entropy, respectively. The iterative solution of these mathematical optimization problems gives new insights into the adaptation of prior knowledge to new information. Our expert system shell SPIRIT supports this kind of knowledge processing, which will be established by suitable examples. © 2003 Wiley Periodicals, Inc. 相似文献
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Gabriele Pannocchia Author Vitae Author Vitae Stephen J. Wright Author Vitae 《Automatica》2007,43(5):852-860
Partial enumeration (PE) is presented as a method for treating large, linear model predictive control applications that are out of reach with available MPC methods. PE uses both a table storage method and online optimization to achieve this goal. Versions of PE are shown to be closed-loop stable. PE is applied to an industrial example with more than 250 states, 32 inputs, and a 25-sample control horizon. The performance is less than 0.01% suboptimal, with average speedup factors in the range of 80-220, and worst-case speedups in the range of 4.9-39.2, compared to an existing MPC method. Small tables with only 25-200 entries were used to obtain this performance, while full enumeration is intractable for this example. 相似文献
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Christoph Beierle Gabriele Kern-Isberner 《Annals of Mathematics and Artificial Intelligence》2012,65(2-3):123-158
Different forms of semantics have been proposed for conditionals of the form “Usually, if A then B”, ranging from quantitative probability distributions to qualitative approaches using plausibility orderings, possibility distributions, or conditional objects. Atomic-bound systems, also called big-stepped probabilities, allow qualitative reasoning with probabilities, aiming at bridging the gap between qualitative and quantitative argumentation and providing a model for the nonmonotonic reasoning system P. By using Goguen and Burstall’s notion of institutions for the formalization of logical systems, we elaborate precisely which formal connections exist among big-stepped probabilities, standard probabilities, and qualitative logics. Based on our investigations, we also develop two variants of conditional objects, one of them having a simpler semantics while still providing a model for system P. 相似文献
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The ionic conductivity of pressed pellets of dehydrated synthetic analcime, sodalite and offretite was determined by a.c. measurements within the range 10 Hz to 10 MHz. The ionic conductivity values of those zeolites exchanged with various monovalent cations were determined by the complex impedance plane method. The conduction activation energies range between 63 and 101 kJ mol–1. Sodium analcime shows the best ionic conductivity, namely 1.8×10–4–1 cm–1 at 400° C. A comparison with the conductivity of other ion-conducting solids was made. 相似文献
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Water vapour is soluted in liquid CaO-Al2O3-slags as OH?-ion. To determine the diffusion coefficient a capillary technique is used. Roughly 5 cm long platinum capillaries filled with liquid slag are equilibrated at 1500 and 1600 °C and bar different times and then are quenched in liquid D2O. By dividing these capillaries into roughly 3 mm long segments enough sample substance is won to obtain FT-IR spectra of the OH-band. From measurement of the integral extinction of the OH-band and OH?-concentration profile through the capillary is obtained. FT-IR-spectroscopy is very suitable for this capillary technique because it needs only very little sample substance. 相似文献
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A new fast radix-p-algorithm (p 2) for the discrete cosine transform (DCT) and its inverse is presented. It is based on the divide-and-conquer method and on the arithmetic with Chebyshev polynomials. The algorithm can be applied for the efficient calculation of DCT's of arbitrary transform lengths and for the implementation of other discrete Vandermonde transforms withO(N logN) arithmetical operations. 相似文献
10.
Simonetta Pazzaglia Barbara Tanno Francesca Antonelli Paola Giardullo Gabriele Babini Prabal Subedi Omid Azimzadeh Zohaib N. Khan Kateryna Oleksenko Fabian Metzger Christine von Toerne Damien Traynor Dinesh Medipally Aidan D. Meade Munira Kadhim Fiona M. Lyng Soile Tapio Anna Saran Mariateresa Mancuso 《International journal of molecular sciences》2021,22(8)
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health. 相似文献