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排序方式: 共有252条查询结果,搜索用时 15 毫秒
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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
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Juliana Cristina Castro Giseli Cristina Pante Bruno Martins Centenaro Rafaela Takako Ribeiro De Almeida Eduardo Jorge Pilau Benedito Prado Dias Filho 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2020,37(9):1531-1541
ABSTRACT There is an increasing demand for fungi control in grains, especially toxigenic. Also, there is growing concern on the use of synthetic fungicides; thus alternatives are needed. The aim of this study was to evaluate the antifungal and antimycotoxigenic action of essential oils (EOs) from Zingiber officinale, Cinnamomum zeylanicum and Cymbopogon martinii against Fusarium verticillioides, a spoilage and toxigenic fungus. Essential oils were first chemically characterised by gas chromatography coupled to mass spectrometry, and their antioxidant potential was measured by the DPPH, ABTS and FRAP methods. Minimum inhibitory concentration (MIC) and disc diffusion were used to assess antifungal activity. Scanning electron microscopy was used to evaluate morphological changes in the fungus. Antimycotoxigenic activity of the EOs against the production of fumonisin B1 and B2 by F. verticillioides was evaluated using ultra-high-performance liquid chromatography system. Z. officinale, C. zeylanicum and C. martinii EOs were predominantly composed by zingiberene and geranial; eugenol; and geraniol, respectively. All the EOs had high antioxidant power, especially that from C. zeylanicum. The MICs were 250, 500 and 2,000 µg mL?1 for C. zeylanicum, C. martinii and Z. officinale EOs, respectively. Mycelial reduction of F. verticillioides was observed when EOs were used, and the lowest activity was detected in the Z. officinale EO. Overall, the tested EOs promoted structural damage to the fungal cell wall, decreased conidia size and mycelial reduction. Antimycotoxigenic evaluation of the EOs evidenced a significant reduction (p < .05) in the production of fumonisins B1 and B2 with all the EOs evaluated in the study. These results suggest that especially C. zeylanicum and C. martinii EOs are highly useful for controlling F. verticillioides and fumonisins production. 相似文献
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Francisco Regis Machado Nascimento Aldemar Martínez González Electo Eduardo Silva Lora Albert Ratner Jose Carlos Escobar Palacio Rafaela Reinaldo 《International Journal of Hydrogen Energy》2021,46(36):18740-18766
Thermochemical conversion by gasification process is one of the most relevant technologies for energy recovery from solid fuel, with an energy conversion efficiency better than other alternatives like combustion and pyrolysis. Nevertheless, the most common technology used in the last decades for thermochemical conversion of solid fuel through gasification process, such as coal, agriculture residues or biomass residues are the fluidized bed or bubbling fluidized bed system. For these gasification technologies, an inert bed material is fed into reactor to improve the homogenization of the particles mixture and increase the heat transfer between solid fuel particles and the bed material. The fluidized bed reactors usually operate at isothermal bed temperatures in the range of 700–1000 °C, providing a suitable contact between solid and gas phases. In this way, chemical reactions with high conversion yield, as well as an intense circulation and mixing of the solid particles are encouraged. Moreover, a high gasification temperature favours carbon conversion efficiency, increasing the syngas production and energy performance of the gasifier. However, the risk of eutectic mixtures formation and its subsequent melting process are increased, and hence the probability of bed agglomeration and the system collapse could be increased, mainly when alkali and alkaline earth metals-rich biomasses are considered. Generally, bed agglomeration occurs when biomass-derived ash reacts with bed material, and the lower melting temperature of ash components promotes the formation of highly viscous layers, which encourages the progressive agglomerates creation, and consequently, the bed collapse and system de-fluidization. Taking into account the relevance of this topic to ensure the normal gasification process operating, this paper provides several aspects about bed agglomeration, mostly for biomass gasification systems. In this way, chemistry and mechanism of bed agglomeration, as well as, some methods for in-situ detection and prediction of the bed agglomeration phenomenon are reviewed and discussed. 相似文献
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Daniella Murador Anna Rafaela Braga Diogo Da Cunha 《Critical reviews in food science and nutrition》2018,58(2):169-177
The aim of this study was to review prior studies that have evaluated the effects of cooking techniques on polyphenol levels and antioxidant activity in vegetables and to release a meta-analysis of the findings. Meta-analysis with a random effect model was conducted using the weighted response ratios (R*) that were calculated for each experiment. Baking (R* = 0.51), blanching (R* = 0.94), boiling (R* = 0.62), microwaving (R* = 0.54) and pressure cooking (R* = 0.47) techniques precipitated significant reductions in the polyphenol levels. Significant decreases in the antioxidant activity levels were noted after baking (R* = 0.45) and boiling (R* = 0.76), while significant increases were observed after frying (R* = 2.26) and steaming (R* = 1.52). 相似文献
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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
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Rafaela da Rosa Cardoso Edson Pinheiro de Lima Sergio E. Gouvea da Costa 《Journal of Manufacturing Systems》2012
AMT selection and adoption processes have been extensively studied. Topics that include financial and human factors, productivity, and coordination of the AMT implementation establish a substantial content of the present research agenda. The purpose of this paper is to study the organizational factors that influence the AMT implementation, considering a manufacturing strategy context and an analysis based on an organizational design framework. The research strategy is based on ‘empirical iterations’ using survey secondary data, experts’ interviews information and multiple case studies. The results show that there is a set of recommendations, which strongly influence the AMT implementation. Companies require a structured and integrative approach for the AMT implementation in order to take advantage of all their individual and systemic benefits. The set of proposed AMT recommendations for integrating these technologies to the organizational design are framed by structural, process and contextual aspects. 相似文献
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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
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About 80% of the chemical products are still based on crude oil. Bio-based materials will increasingly gain importance. As the fraction of oxygen is normally higher in biomass than in crude oil as well as in the derived conventional products, this implies a need to develop new synthesis pathways. Depending on the types of new synthesis pathways, the effects of a complete raw-material change on land and exergy use differ. Here, different synthesis pathways starting from glucose and plant oil to different kinds of end products are evaluated utilizing material and exergy balances. These evaluations are carried out under today's and future conditions and constraints, like yield, demand of organic chemicals and world population. The analysis in this paper shows that the land and energy use can be significantly reduced, if the products are adapted to the chemical structure of their bio-based feedstock. 相似文献