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排序方式: 共有1380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
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Locke Davenport Huyer Serena Mandla Yufeng Wang Scott B. Campbell Bess Yee Christian Euler Benjamin F. Lai A. Dawn Bannerman Dawn S. Y. Lin Miles Montgomery Kayla Nemr Timothy Bender Slava Epelman Radhakrishnan Mahadevan Milica Radisic 《Advanced functional materials》2021,31(6):2003341
Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA. 相似文献
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TP Hopp 《Canadian Metallurgical Quarterly》1995,4(9):1851-1859
Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway. 相似文献
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PURPOSE: Ultrasound estimated bladder weight was compared before and after surgery for benign prostatic hyperplasia (BPH) to reveal a possible reversible change in bladder hypertrophy. MATERIALS AND METHODS: Ultrasound estimated bladder weight was measured before and after subcapsular (17) or transurethral (16) prostatectomy in 33 male patients with BPH. Sequential changes in the American Urological Association symptom score and urinary flow rate were also examined. RESULTS: Along with a significant improvement in the American Urological Association symptom scores and maximum flow rate, ultrasound estimated bladder weight decreased from 52.9 +/- 22.6 to 31.6 +/- 15.8 gm. in 12 weeks after treatment. In all but 4 patients (29 of 33, or 87.9%) ultrasound estimated bladder weight decreased to less than 35.0 gm. in 12 weeks after treatment. Interestingly, in all patients with an initial ultrasound estimated bladder weight of greater than 80 gm. the bladder weight still remained at an abnormally high level 12 weeks after treatment. CONCLUSIONS: Bladder hypertrophy was completely reversible after the surgical treatment of the obstruction in the majority of patients with BPH. The measurement of ultrasound estimated bladder weight was of value in monitoring therapeutic effects in BPH patients. An extraordinarily high ultrasound estimated bladder weight of 80 gm. or more might suggest degenerative and irreversible pathological changes in the bladder detrusor. 相似文献
6.
This article reviews the current status and future prospects for glass-ionomer materials. These materials are of two chemical types: the older, self-hardening cements, which set by an acid-base neutralization reaction to give relatively brittle materials; and the newer, resin-modified cements, which set partly by polymerization and partly by neutralization. Compared with the self-hardening cements, the latter materials have improved esthetics, improved resistance to moisture, and greater toughness. Both types of glass-ionomer cement bond well to enamel and dentin and release a clinically useful amount of fluoride. They have been used in a variety of applications: as liners or bases, for luting of stainless steel crowns, for Class V restorations in permanent teeth, and for Class II and Class III restorations in primary teeth. The resin-modified glass-ionomers are particularly promising for these latter uses, although it is too early to be sure whether their long-term durability is sufficient. Self-hardening glass-ionomer materials are likely to retain specific niches of clinical application, including in their metal-reinforced and cermet-containing forms. 相似文献
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KL Gatford TP Fletcher IJ Clarke PC Owens KJ Quinn PE Walton PA Grant BJ Hosking AR Egan EN Ponnampalam 《Canadian Metallurgical Quarterly》1996,74(6):1314-1325
The effects of sex and age on patterns of circulating somatotropin (ST) concentration and plasma IGF-I, IGF-II, insulin, and IGF binding protein-3 (IGFBP-3) were studied in ram, wether, and ewe lambs (n = 7 or 8) sampled at mean ages of 81 (I1) and 158 d (I2). Between 81 and 158 d of age, rams grew more rapidly than wethers (P < .01), and wethers grew more rapidly than ewes (P < .01). The sex differences in growth were reflected in empty body weight at slaughter: rams > wethers > ewes (P < .05). Mean plasma ST concentrations, ST pulse amplitude, and integrated plasma ST concentrations were greater (P < .05) in rams than in ewes at I1 and I2. Characteristics of the ST plasma profile in wethers were generally intermediate between those of rams and ewes. The interpulse interval was greater in ewes than in wethers at I2. The IGF-I and IGFBP-3 concentrations were greater in rams than in ewes at both sampling times. Plasma IGF-II was greater in ewes than in rams at I2. Mean plasma ST was approximately two thirds less at I2 than at I1 regardless of sex. Mean plasma ST and IGF-I at both ages were positively correlated with growth. Mean plasma ST at I2 was negatively correlated with fatness at slaughter. Sex and age significantly affected patterns of circulating ST and concentrations of IGF-I and IGFBP-3 in prepubertal growing lambs, under conditions for which growth rates and composition were also sexually dimorphic. 相似文献
10.
Yu Yang Hugo Bender Kai Arstila Bart Swinnen Bert Verlinden Ingrid De Wolf 《Microelectronics Reliability》2008,48(8-9):1517-1520
Focused ion beam (FIB) and nano-probing were applied for failure analysis of three-dimensional stacked circuits with copper through-silicon-vias between the stacked chips. The failure analysis was done after high temperature storage and thermal cycling tests. Passive voltage contrast in FIB allowed to pinpoint the open sites. FIB cross-sections showed the presence of opens at the bottom of the copper vias. The failure cause was suspected to be an interlayer particle, which was confirmed by optical profilometry. Nano-probing was used on another sample to pinpoint the failure location through the measurement of the local resistance within the daisy chains. The failure was traced out to be related with surface contamination. 相似文献