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排序方式: 共有572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.
V. Morandi F. Marabelli V. Amendola M. Meneghetti D. Comoretto 《Advanced functional materials》2007,17(15):2779-2786
Polystyrene artificial opals with few gold nanoparticles (AuNp) embedded in the interstices (doping) are grown by using the meniscus technique starting from a mixed suspension of microspheres and AuNp. Samples having different sphere diameters and nanoparticle loads have been prepared. Their reflectance spectra clearly show a dramatic bathochromic shift of the photonic stop band (up to 1400 cm–1) and a reduction of its full width half maximum, due to an increase of the effective refractive index of about 8 % with respect to bare opals, which is accounted for by analytical theoretical models. Reflectance spectra do not show any direct evidence of AuNp absorption even at the higher AuNp doping level. Nanosecond transient absorption measurements on these systems indicate that a variation of transmission (optical switching) of about 150 % is observed for AuNp doped opals upon photoexcitation with 9 ns laser pulses at 532 nm. No switching is instead observed for bare opals. 相似文献
3.
Bonto-Kane Maria Vicente A. Chin Alvin Mc Carthy Sheila Srikulwong Mayuree Timmins Paul J. 《Pervasive Computing, IEEE》2007,6(4)
Pervasive computing is as much about the user as it is about the technology. So, the Fifth International Conference on Pervasive Computing emphasized desirability rather than just feasibility. Featured themes included user benefits, human-computer interaction, group and social interactions, context awareness, finding and positioning people and objects, and personal privacy. 相似文献
4.
Ronald R. Delyser Sheila S. Thompson Jerry Edelstein Corinne Lengsfeld Albert J. Rosa Paul J. Rullkoetter Robert Whitman Margaret Whitt 《工程教育杂志》2003,92(3):269-273
A team of faculty members at the University of Denver changed the learning environment in key courses in the Department of Engineering from predominately teacher centered to student centered. Through this funded project new grading methods were implemented, classrooms were renovated and wired with studio layouts to facilitate learning, the Engineering Circuits Laboratory was rewired and instrumented for automated data acquisition and reporting, and two new pedagogical approaches were developed. At the onset of the project, six goals were established related to student learning. The introduction of industry standard hardware and software provided students with unprecedented hands‐on experience and project related activities stimulated faculty innovations in other current and future courses. Assessment results indicate that the new grading system improved the clarity of expectations for students before assignments were given resulting in increased reported motivation for learning in many courses. Even though course GPAs did not always reflect higher achievement on graded work, faculty members firmly believe that deeper understanding was achieved because more complex material was assimilated. 相似文献
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6.
Thompson Karin E.; Malow Robert M.; Corrigan Sheila A.; Sorensen James L. 《Canadian Metallurgical Quarterly》1992,6(2):67
Drug users are particularly at risk for contracting the human immunodeficiency virus and serve as a major mechanism for spreading the virus to other sectors of the population. As a result drug abuse treatment and potential behavioral change strategies are primary public health issues. The purpose of this article is to review the contributions included in this special edition, which represent an effort to describe the most current thinking in the field with a blend of theoretical, review, and empirical articles. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
7.
Emery Robert E.; Matthews Sheila G.; Kitzmann Katherine M. 《Canadian Metallurgical Quarterly》1994,62(1):124
A 1-yr follow-up study was conducted on families randomly assigned to settle custody disputes either in mediation or through adversary procedures. Consistent with Time 1 reports, at Time 2 fathers who mediated were substantially more satisfied than were fathers who litigated. Fathers who mediated also complied more with child support orders. Contrary to prediction, the greater satisfaction and compliance of fathers did not lead to increased satisfaction among mothers who mediated. In contrast to Time 1, at follow-up mothers who mediated were significantly less satisfied than were mothers who litigated, but selective attrition may account for these differences. The psychological adjustment of mothers and fathers was not significantly different between settlement groups at Time 2, but mothers in both groups reported less satisfaction with dispute settlement and less dysphoria at Time 2 than they had reported at Time 1. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
8.
An improved code density test for flash A/D converters is proposed, revealing some dynamic phenomena (e.g., missing codes) hidden by the conventional approach. Formulas are reported for obtaining, from code density, effective noise estimates fully consistent with those provided by waveform analysis. Finally, it is shown that the variance of noise estimates obtained by time-domain analysis may be unacceptably large if the observation window is not properly chosen 相似文献
9.
Leitenberg Harold; Rosen James C.; Gross Janet; Nudelman Sheila; Vara Linda S. 《Canadian Metallurgical Quarterly》1988,56(4):535
A controlled study evaluating the effectiveness of exposure plus response-prevention treatment of bulimia nervosa was conducted in a sample of 47 women. This was a four-group comparison involving three treatment conditions and a waiting-list control group. The three treatment conditions were (a) exposure plus response prevention conducted in a single setting (clinic), (b) exposure plus response prevention conducted in multiple settings (clinic, patients' homes, and restaurants), and (c) cognitive–behavioral therapy without exposure plus response prevention. All treatment was provided to groups of 3 patients at a time. Outcome was evaluated at posttreatment and at a 6-month follow-up. The three treatment groups improved significantly on most outcome measures, whereas the waiting-list control group showed little change. At follow-up, there was a slightly better outcome on vomiting behavior and amount of food consumed in one of the test meals for the exposure plus response-prevention groups relative to the no-exposure group. However, on all other measures, the degree of improvement from pretreatment to follow-up was the same for all three treatment groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
10.