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排序方式: 共有322条查询结果,搜索用时 62 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.
Schools often use peer-tutoring as a corrective program for students who are experiencing difficulties academically. Given appropriate behavioral structure, peer-tutoring can become a powerful classwide instructional intervention. An historical perspective on the use of students as teachers for their peers is given in this selective literature review. Also, information on the efficacy of considering behavioral function and structure and data addressing ecobehavioral variables to establish a productive learning environment are provided. The authors emphasize infusing peer-tutoring programs with applied behavior analysis techniques to increase the academic success of large numbers of students cost effectively. Peer-tutoring programs are considered to be a way for applied behavior analysts to gain greater access to American school learning environments. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
3.
C Oddoux E Reich F Axelrod A Blumenfeld C Maayan S Slaugenhaupt J Gusella H Ostrer 《Canadian Metallurgical Quarterly》1995,15(9):817-826
Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the genetic locus and at the same genetic location have been identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve families were analysed for informativeness and of these, seven went on to have prenatal testing (a total of eight fetuses tested). All of these fetuses were predicted to be heterozygous unaffected (FD carriers). Seven fetuses have come to term and are normal. In the absence of a recombinant proband, a panel of three proximal and three distal markers is sufficient to provide informative flanking markers and an 87-96 per cent likelihood of a highly predictive test. In an additional family at 1:4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tightly linked marker D9S58 in conjunction with linkage analysis using data from two unaffected children. Prenatal diagnosis in this family indicated an affected fetus. 相似文献
4.
The neuroprotective actions of cannabidiol and other cannabinoids were examined in rat cortical neuron cultures exposed to toxic levels of the excitatory neurotransmitter glutamate. Glutamate toxicity was reduced by both cannabidiol, a nonpsychoactive constituent of marijuana, and the psychotropic cannabinoid (-)Delta9-tetrahydrocannabinol (THC). Cannabinoids protected equally well against neurotoxicity mediated by N-methyl-D-aspartate receptors, 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid receptors, or kainate receptors. N-methyl-D-aspartate receptor-induced toxicity has been shown to be calcium dependent; this study demonstrates that 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid/kainate receptor-type neurotoxicity is also calcium-dependent, partly mediated by voltage sensitive calcium channels. The neuroprotection observed with cannabidiol and THC was unaffected by cannabinoid receptor antagonist, indicating it to be cannabinoid receptor independent. Previous studies have shown that glutamate toxicity may be prevented by antioxidants. Cannabidiol, THC and several synthetic cannabinoids all were demonstrated to be antioxidants by cyclic voltametry. Cannabidiol and THC also were shown to prevent hydroperoxide-induced oxidative damage as well as or better than other antioxidants in a chemical (Fenton reaction) system and neuronal cultures. Cannabidiol was more protective against glutamate neurotoxicity than either ascorbate or alpha-tocopherol, indicating it to be a potent antioxidant. These data also suggest that the naturally occurring, nonpsychotropic cannabinoid, cannabidiol, may be a potentially useful therapeutic agent for the treatment of oxidative neurological disorders such as cerebral ischemia. 相似文献
5.
The optical properties of gold nanoparticles have been known for a number of years and recent advances in laser power have now allowed the non-linear optical properties to be studied. In this short review paper, the various theories that have been used to describe the optical properties of gold nanoparticles are presented. Methods of preparing gold nanoparticles in glasses are explained briefly, as well as characterization techniques. The optical properties of gold nanoparticles are reviewed, as well as the effects of particle size, shape, concentration and c. 相似文献
6.
A. H. Moinuddin Ahmed Lesley S. Dent Glasser 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》1973,23(6):457-463
α-BaO.Al2O3.4H2O has been synthesised and studied by infrared, X-ray and thermal analytical techniques. The compound of approximate formula BaO.Al2O3.0.5H2O, described in Part III, forms as a dehydration product, and appears to be identical with the compound β-BAH2 described by other workers. A possible explanation for the discrepancy in water content is discussed. 相似文献
7.
M. Hossein Nouri-Sorkhabi Lesley C. Wright David R. Sullivan Philip W. Kuchel 《Lipids》1996,31(7):765-770
31P Nuclear magnetic resonance (NMR) spectra of human erythrocyte lysates dissolved in sodium cholate were acquired. The narrow
resonances of phospholipids were mostly well resolved, allowing identification and accurate quantitative analysis of phospholipid
classes of the erythrocyte membranes. The ether-linked phosphatidylethanolamine components of the erythrocyte membranes were
identified, based on the removal of plasmalogens by acidolysis and of diacyl phospholipid species by degradation using phospholipase
A1. It was also shown that the introduction of double bonds on the acyl chains of phosphatidylcholine shifted the31P NMR resonances to lower frequencies. Quantitative analyses of phospholipids from the spectra were based on their apparent
molar concentrations. The recoveries of phospholipids from erythrocytes were significantly higher than those using conventional
extraction procedures. 相似文献
8.
The effect of trap design, trap color, and a mixture of isothiocyanates on the capture of Ceutorhynchus assimilis (Paykull) was studied in a series of field experiments. Unbaited yellow water traps, a yellow sticky box trap, and a yellow sticky card trap, mounted vertically, or at 45° to the vertical with the yellow card facing upwards were effective for capturing seed weevils, but a horizontal yellow sticky card trap caught few. White, green, and black traps were unattractive. During migratory periods, trap catch could be enhanced two to four times with a lure consisting of a mixture of allyl, 3-butenyl, 4-pentenyl, and 2-phenylethyl isothiocyanates, but this bait did not attract in a trap with ineffective design. The sticky card trap, mounted at 45° to the vertical and baited with the isothiocyanate mixture, may be useful for monitoring movement of C. assimilis during migratory periods. However, during the colonization phase, lures of either a mixture of isothiocyanates or of allyl isothiocyanate alone were not attractive. 相似文献
9.
Angelika Ziegler Sybil M. Macintosh Lesley Torrance William Simon Antony R. Slabas 《Lipids》1997,32(8):805-809
Purified Brassica napus enoyl acyl carrier protein reductase (ENR) was used to select specific antibodies from a library of antibody fragments, single-chain
Fv (scFv), displayed on filamentous phage. Analysis of the selected clones by BstNl fingerprinting and nucleotide sequencing showed that the scFv were derived from three different human VH germline genes. The binding specificities were confirmed by Western blots and ELISA. The scFv preparations reacted with B. napus ENR, but not with β-keto reductase, nor enoyl reductase from Escherichia coli. Analysis of fragments generated by CNBr treatment indicates that the scFv 3.13 recognizes an epitope located within the n-terminal 80 amino acids of the enzyme molecule. The scFv were used to detect ENR directly in extracts of B. napus seeds. 相似文献
10.
Prior research has shown that people are likely to skim information presented digitally with the resultant deleterious effect on accurate mental models of the text. Teaching monitoring strategies and presenting text with adjunct questions are effective strategies for improving the mental models of readers of scientific text, but the two strategies have not been directly compared for studying text read from a computer screen. In the present study, participants were individually tested in two experiments in which they studied computer-based text on the heart and circulatory system while either reading the text with no interruption, answering adjunct inference questions, answering adjunct factual questions, or answering prompts for global or specific monitoring. Reading time was untimed but looking back was not available. Prompting for global monitoring was most effective for improvement of mental models as measured by scores in diagram drawing, concept map construction, factual memory, and generating inferences. Further, global monitoring did not require more time-on-task than the other methods. 相似文献