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1.
Jakeria Mohd Rafiuddin Toh Rou Jun Chen Xiao-Bo Cole Ivan S. 《Journal of Applied Electrochemistry》2022,52(6):1021-1044
Journal of Applied Electrochemistry - Organic corrosion inhibitors have become competent alternatives to hazardous chrome conversion coatings due to their rapid adsorption over metal surfaces in... 相似文献
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Dr. Louise M. Sternicki Dr. Jim Nonomiya Dr. Miaomiao Liu Dr. Melinda M. Mulvihill Dr. Ronald J. Quinn 《ChemMedChem》2021,16(14):2206-2210
PRO teolysis TA rgeting C himeras (PROTACs) promote the degradation, rather than inhibition, of a drug target as a mechanism for therapeutic treatment. Bifunctional PROTAC molecules allow simultaneous binding of both the target protein and an E3-Ubiquitin ligase, bringing the two proteins into close spatial proximity to allow ubiquitinylation and degradation of the target protein via the cell's endogenous protein degradation pathway. We utilized native mass spectrometry (MS) to study the ternary complexes promoted by the previously reported PROTAC GNE-987 between Brd4 bromodomains 1 and 2, and Von Hippel Lindeau E3-Ubiquitin Ligase. Native MS at high resolution allowed us to measure ternary complex formation as a function of PROTAC concentration to provide a measure of complex affinity and stability, whilst simultaneously measuring other intermediate protein species. Native MS provides a high-throughput, low sample consumption, direct screening method to measure ternary complexes for PROTAC development. 相似文献
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Christopher R Fellin Steven M Adelmund Dylan G Karis Ryan T Shafranek Robert J Ono Cecilia G Martin Trevor G Johnston Cole A DeForest Alshakim Nelson 《Polymer International》2019,68(7):1238-1246
We describe the synthesis, characterization and direct‐write 3D printing of triblock copolymer hydrogels that have a tunable response to temperature and shear stress. In aqueous solutions, these polymers utilize the temperature‐dependent self‐association of poly(alkyl glycidyl ether) ‘A’ blocks and a central poly(ethylene oxide) segment to create a physically crosslinked three‐dimensional network. The temperature response of these hydrogels was dependent upon composition, chain length and concentration of the ‘A’ block in the copolymer. Rheological experiments confirmed the existence of sol–gel transitions and the shear‐thinning behavior of the hydrogels. The temperature‐ and shear‐responsive properties enabled direct‐write 3D printing of complex objects with high fidelity. Hydrogel cytocompatibility was also confirmed by incorporating HeLa cells into select hydrogels resulting in high viabilities over 24 h. The tunable temperature response and innate shear‐thinning properties of these hydrogels, coupled with encouraging cell viability results, present an attractive opportunity for additive manufacturing and tissue engineering applications. © 2018 Society of Chemical Industry 相似文献
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Moral conflict theory explains deep moral differences and patterns of communication commonly associated with such conflicts. Moral conflict is defined as a struggle between humans, but we argue that the objects of contention in such intractable conflicts, including texts, physical objects, and places, assume a force of their own. We use actor–network theory to help explain this eventuality and to expand our understanding of moral conflict. Combining actor–network theory literature with moral conflict theory literature helps us understand the complexity of moral orders and the networks of actors involved in the construction of moral conflict. This expansion of literature also allows us to conceive of more possibilities for transcendent discourse. 相似文献
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Dr. Samuel H. Henager Stephanie Henriquez Dr. Daniel R. Dempsey Prof. Philip A. Cole 《Chembiochem : a European journal of chemical biology》2020,21(1-2):64-68
The activity and localization of PTEN, a tumor suppressor lipid phosphatase that converts the phospholipid PIP3 to PIP2, is governed in part by phosphorylation on a cluster of four Ser and Thr residues near the C terminus. Prior enzymatic characterization of the four monophosphorylated (1p) PTENs by using classical expressed protein ligation (EPL) was complicated by the inclusion of a non-native Cys at the ligation junction (aa379), which may alter the properties of the semisynthetic protein. Here, we apply subtiligase-mediated EPL to create wt 1p-PTENs. These PTENs are more autoinhibited than previously appreciated, consistent with the role of Tyr379 in driving autoinhibition. Alkaline phosphatase sensitivity analysis revealed that these autoinhibited 1p conformations are kinetically labile. In contrast to the Cys mutant 1p-PTENs, which are poorly recognized by an anti-phospho-PTEN antibody, three of the four wt 1p-PTENs are recognized by a commonly used anti-phospho-PTEN antibody. 相似文献
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Anna M. Schoepf Dr. Stefan Salcher Verena Hohn Florina Veider Prof. Dr. Petra Obexer Prof. Dr. Ronald Gust 《ChemMedChem》2020,15(12):1067-1077
New strategies to eradicate cancer stem cells in chronic myeloid leukemia (CML) include a combination of imatinib with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Recently, we identified the partial PPARγ agonist telmisartan as effective sensitizer of resistant K562 CML cells to imatinib treatment. Here, the importance of the heterocyclic core on the cell death-modulating effects of the telmisartan-derived lead 4′-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid ( 3 b ) was investigated. Inspired by the pharmacodynamics of HYL-6d and the selective PPARγ ligand VSP-51, the benzimidazole was replaced by a carbazole or an indole core. The results indicate no correlation between PPARγ activation and sensitization of resistant CML cells to imatinib. The 2-COOH derivatives of the carbazoles or indoles achieved low activity at PPARγ, while the benzimidazoles showed 60-100 % activation. Among the 2-CO2CH3 derivatives, only the ester of the lead ( 2 b ) slightly activated PPARγ. Sensitizing effects were further observed for this non-cytotoxic 2 b (80 % cell death), and to a lesser extent for the lead 3 b or the 5-Br-substituted ester of the benzimidazoles ( 5 b ). 相似文献
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Lihua Lou Weijie Yu Ronald J. Kendall Ernest Smith Seshadri S. Ramkumar 《应用聚合物科学杂志》2020,137(30):49213
A tensile properties testing study was conducted to understand the influence of thickness, cross-head speed (speed of testing), gauge length (GL; specimen test length), and sample shape on important tensile properties of polyvinyl alcohol (PVA) nanofiber webs. The effects of each testing parameter on load at break, extension at break, Young's modulus, and tensile stress–strain curve of PVA nanofiber webs are analyzed. The Welch two sample t-tests show the significant difference among tested data. Using interaction plots, two-way analysis of variance, and margin mean plots, the interaction effects among testing parameters have been analyzed. Of all the factors, cross-head speed, the interaction among GL, and sample thickness (GL: Thickness) and the interaction among GL, testing speed and sample thickness (GL: Speed: Thickness) have significant influence on the tensile properties of PVA nanofiber webs. Moreover, the hypothesized model of mechanism of tensile strain–stress curve of PVA nanofiber webs has been proposed. Based on the model, the tensile strain–stress curve can be split into three stages: linear elastic, partial break up, and complete breakage. This study will provide a better understanding of tensile testing parameters' effects and their interaction effects on the tensile properties of nanowebs. 相似文献