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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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The effects of static,oscillating, and oscillating with dwell time retort motions on the rate of heat penetration of a food simulant processed in a pouch 下载免费PDF全文
Mollye S. MacNaughton William S. Whiteside James R. Rieck Ronald L. Thomas 《Journal of Food Processing and Preservation》2018,42(1)
The objective of this work was to study the effect of three different retort motions on the rate of heat penetration in pouches. Pouches were processed in a water spray batch retort system using static, oscillating continuously at a speed of 10.5 rotations per minute (RPM) with an angle of 15 degrees, and oscillating at 10.5 rpm at a 15 degree angle with a 15‐s hold. There was no difference in the rate of between static and oscillating processes (p > .05). There was a difference in the between static and oscillating with a hold processes (p < .05). At a 90% confidence interval, there was also a difference between the rate of heat penetration between the oscillating and oscillating with a hold processes (p > .05, p = .056). The location of the pouches on the retort rack did not influence the rate of heat penetration within the three methods or between the three methods (p > .05).
Practical applications
Despite novel technological developments for creating sterile shelf stable products, thermal processing is still the most reliable method. Creating innovation within thermal processing by using different methods of motion to create faster heating profiles can improve the quality of products. This research can be used for optimizing retort processes for food products in pouches. Processing with motion has been seen to reduce the processing time which can increase nutrient retention, reduce thermal abuse, and ultimately save money and increase production. Retort food manufacturers can use oscillating and hold motion to make higher quality products in less time than static motion. 相似文献5.
Sharon E Mason Keena A. E. Mullen Steven P. Washburn Kevin L. Anderson Ronald E. Baynes 《Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment》2018,35(9):1716-1727
Organic dairy products are the second largest sector of the organic food market. Organic dairy products come from United States Department of Agriculture (USDA) certified organic dairy cattle that meet USDA organic standards. Organic dairy cattle in the US cannot be treated with antibiotics for mastitis, one of the costliest diseases of dairy cattle, and thus effective alternatives are needed. When any compound (medication or other non-food product) is used in a food producing animal, a withhold time for that compound that meets US Food and Drug Administration (FDA) standards for food safety must be applied to the animal and its products (like milk). However, there are no US FDA products approved for mastitis that maintain USDA certified organic dairy cattle’s organic status. Thus, we studied the pharmacokinetics of 3 compounds (garlic, thymol and carvacrol) used on organic both healthy and mastitic organic dairy cattle. We also used this information to estimate a milk withhold time using methods consistent with US FDA requirements. For thymol intra-mammary and carvacrol intra-mammary or topical administration, all compounds were partially absorbed into the body from the milk or skin. Thymol and carvacrol are measurable in plasma (at 0.0183 and 0.0202 µg/mL, respectively) after intramammary administration with similar elimination half lives of 1.7 h. Milk concentrations of thymol and carvacrol are much higher at 2.958 and 4.487 µg/mL in healthy cattle, respectively. Concentrations are not significantly different in cows with mastitis as compared to those in healthy cows. Despite these compounds being natural products, they should have a withhold time for milk of at least 24 h after administration. For garlic, levels remained below the limit of detection in milk and plasma and thus no withdrawal time appears to be needed for milk. 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
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Scott J. Robertson Marina B. Ruggles-Wrenn Randall S. Hay Theodore Shillig Ronald Mitchell Brian Kroeger Logan Gumucio 《Journal of the American Ceramic Society》2020,103(2):1358-1371
A facility for testing SiC fiber tows in static fatigue and creep at elevated temperatures in air and steam was developed. Static fatigue of Hi-Nicalon™-S fibers was investigated at 800°C-1100°C at applied stresses between 115 and 1250 MPa in air, in Si(OH)4(g)-saturated steam, and in unsaturated steam. Fibers tested in Si(OH)4(g)-saturated steam and in air had silica scales throughout the test sections, but those tested in unsaturated steam did not develop scales near the steam injection point. Fiber lifetimes in static fatigue were shortest in unsaturated steam, intermediate in Si(OH)4(g)-saturated steam, and longest in air. Failure strains did not exceed 0.3%. Steady-state strain rates and static fatigue lifetimes are modelled empirically by the Monkman-Grant relationship. Failure mechanisms are discussed. 相似文献
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