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1.
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
2.
Mauro Zammarano John R. Shields Isaac Leventon Ickchan Kim Shonali Nazare Andre Thompson Rick D. Davis Artur Chernovsky Matthew Bundy 《火与材料》2021,45(1):114-126
Herein, we describe a reduced‐scale test (“Cube” test), measuring the fire performance of specimens including a fire barrier (FB) and a flammable core material, which acts as the main fuel load. The specimen is intended to reproduce a cross‐section of a composite product where heat/mass transfer occurs primarily in a direction perpendicular to the FB. The Cube test procedure and benefits are discussed in this work by adopting residential upholstery furniture as an exemplary study. One flexible polyurethane foam, one polypropylene cover fabric, and 10 commercially available FBs were selected. They were used to compare the fire performance of FBs, measured in terms of peak of heat release rate, in the ASTM E1474‐14 standard test and the newly developed Cube test. Edge effects severely affected the performance of FBs in the ASTM E1474‐14 standard test but not in the Cube test. Furthermore, appropriate test conditions were determined in the Cube test to measure the so‐called “wetting point,” that is, the time and value of heat release rate measured when flammable liquid products were first observed on the bottom of the specimen. The relevance of the “wetting point” in terms of full‐scale fire performance and failure mechanism of FBs is discussed. 相似文献
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Aika Davis P. Barry Ryan Jordan A. Cohen Debra Harris Marilyn Black 《Indoor air》2021,31(5):1473-1483
Upholstered furniture is often manufactured with polyurethane foam (PUF) containing flame retardants (FRs) to prevent the risk of a fire and/or to meet flammability regulations, however, exposure to certain FRs and other chemicals have been linked to adverse health effects. This study developed a new methodology for evaluating volatile organic compound (VOC) and FR exposures to users of upholstered furniture by simulating use of a chair in a controlled exposure chamber and assessing the health significance of measured chemical exposure. Chairs with different fire-resistant technologies were evaluated for VOC and FR exposures via inhalation, ingestion, and dermal contact exposure routes. Data show that VOC exposure levels are lower than threshold levels defined by the US and global indoor air criteria. Brominated FRs were not detected from the studied chairs. The organophosphate FRs added to PUF were released into the surrounding air (0.4 ng/m3) and as dust (16 ng/m2). Exposure modeling showed that adults are exposed to FRs released from upholstered furniture mostly by dermal contact and children are exposed via dermal and ingestion exposure. Children are most susceptible to FR exposure/dose (2 times higher average daily dose than adults) due to their frequent hand to mouth contact. 相似文献
6.
Metallurgical and Materials Transactions B - The influence of Mn segregation that occurs during casting on recrystallization kinetics has been explored for a C-Mn automotive steel. A homogenization... 相似文献
7.
R. Peter Richards Mirjan Žorž John Rakovan Quintin Wight Jim Houran 《Rocks & Minerals》2018,93(6):495-497
8.
Daylon Black Ryan Harper Patrick Ward Jacob Davlin Omar Bentancourt Donald Plumlee Jim Browning 《International Journal of Applied Ceramic Technology》2020,17(5):2393-2406
A low temperature co-fired ceramic (LTCC) material system has been used to develop a protype field emission cathode structure for use in an experimental magnetron oscillator. The structure is designed for used with 30 gated field emission array (GFEA) die electrically connected through silver metal traces and electrical vias. To approximate a cylinder, the cathode structure (48 mm long and 13.7 mm in diameter) is comprised of 10 faceted plates which cover the GFEA dies. Slits in the facet plates allow electron injection. The GFEA die (3 mm × 8 mm) are placed in axial columns of 3 and spaced azimuthally around a cylindrical support structure in a staggered configuration resulting in 10 azimuthal locations. LTCC manufacturing techniques were developed in order to fabricate the newly designed cathode with seven layers wrapped to form the cylinder with electrical traces and vias. Two different cathode wrapping techniques and two different via filling techniques were studied and compared. Two different facet plate manufacturing techniques were studied. Finally, four different support stand configurations for firing the cylindrical structure were also compared with a square post stand having the best circularity and linearity measurements of the fired structure. 相似文献
9.
Using nanoparticles to carry and delivery anticancer drugs holds much promise in cancer therapy, but nanoparticles per se are lacking specificity. Active targeting, that is, using specific ligands to functionalize nanoparticles, is attracting much attention in recent years. Aptamers, with their several favorable features like high specificity and affinity, small size, very low immunogenicity, relatively low cost for production, and easiness to store, are one of the best candidates for the specific ligands of nanoparticle functionalization. This review discusses the benefits and challenges of using aptamers to functionalize nanoparticles for active targeting and especially presents nearly all of the published works that address the topic of using aptamers to functionalize nanoparticles for targeted drug delivery and cancer therapy. 相似文献
10.
Sang Moon Lee Nong Xu John R. Grace Anwu Li C. Jim Lim Sung Su Kim Farzam Fotovat Achim Schaadt Robin J. White 《Journal of the European Ceramic Society》2018,38(1):211-219
NaA zeolite membranes were synthesised in the secondary growth hydrothermal method based on the seeding of the inner surface of a ceramic α-alumina tube. The impacts of crystallisation time and zeolite precursor concentration (in H2O) were investigated. The structure and stability of the prepared NaA zeolite membranes were also investigated with operating temperatures, times and pressures. The results indicate that the optimal synthesis gel molar composition was 3Na2O: 2SiO2: Al2O3: 200H2O. This led to cubic-shaped NaA zeolite which showed good stability. The optimal NaA zeolite membrane had H2O and CH3OH fluxes of 2.77 and 0.19 kg/m2h, with H2O/H2 and CH3OH/H2 separation factors of ∞ and 0.09 at a temperature of 30 °C. The NaA zeolite membrane had high thermal stability, but poor separation performance at high temperature (240 °C). The results suggested that the H2 permeation flux is significantly influenced by preferential adsorption of vapour in the NaA zeolite membrane. 相似文献