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排序方式: 共有171条查询结果,搜索用时 15 毫秒
1.
Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
2.
Differential emotions theory (DET) proposes that infant facial expressions of emotions are differentiated. To test this hypothesis, the authors examined infant facial expressions longitudinally at 2, 4, and 6 mo of age during face-to-face play and a "still-face" interaction with their mothers. Infant expressions were coded using the Maximally Discriminative Facial Movement Coding System (Max). Consistent with DET, discrete positive expressions occurred more of the time and were of longer duration than blended expressions of positive affect. Contrary to DET, at no age did the proportions or durations of discrete and blended negative expressions differ, and they showed different patterns of developmental change. One is led to either reject or revise DET or else question the adequacy of the Max system. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
3.
Bernhard Beckermann Jorge Bustamante Reinaldo Martínez-Cruz José M. Quesada 《Calcolo》2014,51(2):319-328
For a given $\theta \in (a,b)$ , we investigate the question whether there exists a positive quadrature formula with maximal degree of precision which has the prescribed abscissa $\theta $ plus possibly $a$ and/or $b$ , the endpoints of the interval of integration. This study relies on recent results on the location of roots of quasi-orthogonal polynomials. The above positive quadrature formulae are useful in studying problems in one-sided polynomial $L_1$ approximation. 相似文献
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This paper is concerned with the problem of assessing the stability of linear systems with a single time-delay. Stability analysis of linear systems with time-delays is complicated by the need to locate the roots of a transcendental characteristic equation. In this paper we show that a linear system with a single time-delay is stable independent of delay if and only if a certain rational function parameterized by an integer k and a positive real number T has only stable roots for any finite T≥0 and any k≥2. We then show how this stability result can be further simplified by analyzing the roots of an associated polynomial parameterized by a real number δ in the open interval (0,1). The paper is closed by showing counterexamples where stability of the roots of the rational function when k=1 is not sufficient for stability of the associated linear system with time-delay. We also introduce a variation of an existing frequency-sweeping necessary and sufficient condition for stability independent of delay which resembles the form of a generalized Nyquist criterion. The results are illustrated by numerical examples. 相似文献
6.
Alberto Cornejo Francisco Salgado Julio Caballero Reinaldo Vargas Mario Simirgiotis Carlos Areche 《International journal of molecular sciences》2016,17(8)
Liquid chromatography coupled with mass spectrometry is an outstanding methodology for fast analysis of phenolic compounds in biological samples. Twenty two compounds were quickly and accurately identified in the methanolic extract of the Antarctic lichen Ramalina terebrata for the first time using ultra high pressure liquid chromatography coupled with photodiode array detector and high resolution mass spectrometry (UHPLC-PDA-Q/Orbitrap/MS/MS). In addition, the extract and the four compounds isolated from this species were tested for the inhibitory activity of tau protein aggregation, which is a protein involved in Alzheimer’s disease (AD). All compounds showed null activity with the exception of parietin, which it was able to inhibit aggregation process of tau in a concentration range between 3 µg/mL (10 µM) to 28 µg/mL (100 µM). In addition, we show how parietin interact with tau 306VQIVYK311 hexapeptide inside of the microtubule binding domain (4R) with the help of molecular docking experiments. Finally, the constituents present in the methanolic extract could possibly contribute to the established anti-aggregation activity for this extract and this in-depth analysis of the chemical composition of R. terebrata could guide further research into its medicinal properties and potential uses. 相似文献
7.
Reinaldo Barros Geraldo Plínio Cunha Sathler André Luiz Louren?o Max Seidy Saito Lucio M. Cabral Pabulo Henrique Rampelotto Helena Carla Castro 《International journal of molecular sciences》2014,15(10):17901-17919
Platelets are cytoplasmatic fragments from bone marrow megakaryocytes present in blood. In this work, we review the basis of platelet mechanisms, their participation in syndromes and in arterial thrombosis, and their potential as a target for designing new antithrombotic agents. The option of new biotechnological sources is also explored. 相似文献
8.
Evaluation of potential interfering agents on in vitro methods for the determination of the antioxidant capacity in anthocyanin extracts 下载免费PDF全文
Isadora R. N. de Oliveira Reinaldo F. Teófilo Eduardo B. de Oliveira Afonso M. Ramos Frederico A. R. de Barros Mariza de P. Maia Paulo C. Stringheta 《International Journal of Food Science & Technology》2017,52(2):511-518
The evaluation of the effects of sugars, metals, acids and other antioxidants on the in vitro antioxidant capacity of purified anthocyanin extract by different techniques was the purpose of this study. Three methods and the ways of expressing their results were evaluated: ABTSTEAC (capacity equivalent to Trolox, by ABTS (2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid))), DPPHTEAC (capacity equivalent to Trolox, by DPPH (2,2‐diphenyl‐1‐picrylhydrazyl)), DPPHEC50 (50% reduction in the radical, by DPPH), DPPH%Sca (reduction in the scavenging capacity, by DPPH), FRAPTEAC (capacity equivalent to Trolox, by FRAP (reduction power of iron)) and FRAPEC50 (50% reduction in the radical, by FRAP). The way of expressing DPPH and FRAP results as EC50 showed the greater interfering extent, mainly when the medium contained tartaric and ascorbic acids. The most coherent method was ABTSTEAC in which only ascorbic acid interfered. Ascorbic acid was shown to interfere in all methods; thus, it must be removed prior to determining the in vitro antioxidant capacity of anthocyanins in food materials. 相似文献
9.
Gisele C. Fontanella & Reinaldo Morabito 《International Transactions in Operational Research》2002,9(3):247-259
The computer connection to the Internet is provided by firms known as internet service providers (ISPs). The simplest mode of physical connection is when the user connects to an ISP's service channel by an ordinary telephone line (dial-up). Finding an available channel may not be an easy task, especially during the peak hours of many Brazilian ISPs. This results in a problem for the ISPs, which is how to achieve the most appropriate trade-off between investing in capacity and satisfying the target user service level. This paper analyzes this trade-off based on a three-step approach: (i) determine user arrival and service processes in chosen periods, (ii) select an appropriate queueing model using some simplifying assumptions, and (iii) generate trade-off curves between system performance measures. To illustrate the application of this approach, some results derived from a case study performed at an ISP in Sao Paulo state are given. 相似文献
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