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961.
The application of an active braze alloy (ABA) known as Copper ABA® (Cu–3.0Si–2.3Ti–2.0Al wt.%) to join Al2O3 to Kovar® (Fe–29Ni–17Co wt.%) has been investigated. This ABA was selected to increase the operating temperature of the joint beyond the capabilities of typically used ABAs such as Ag–Cu–Ti-based alloys. Silica present as a secondary phase in the Al2O3 at a level of ~5 wt.% enabled the ceramic component to bond to the ABA chemically by forming a layer of Si3Ti5 at the ABA/Al2O3 interface. Appropriate brazing conditions to preserve a near-continuous Si3Ti5 layer on the Al2O3 and a continuous Fe3Si layer on the Kovar® were found to be a brazing time of ≤15 min at 1025 °C or ≤2 min at 1050 °C. These conditions produced joints that did not break on handling and could be prepared easily for microscopy. Brazing for longer periods of time, up to 45 min, at these temperatures broke down the Si3Ti5 layer on the Al2O3, while brazing at ≥1075 °C for 2–45 min broke down the Fe3Si layer on the Kovar® significantly. Further complications of brazing at ≥1075 °C included leakage of the ABA out of the joint and the formation of a new brittle silicide, Ni16Si7Ti6, at the ABA/Al2O3 interface. This investigation demonstrates that it is not straightforward to join Al2O3 to Kovar® using Copper ABA®, partly because the ranges of suitable values for the brazing temperature and time are quite limited. Other approaches to increase the operating temperature of the joint are discussed. 相似文献
962.
Leila Takahashi-Ruiz Joseph D. Morris Phillip Crews Tyler A. Johnson April L. Risinger 《Molecules (Basel, Switzerland)》2022,27(13)
Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (−)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (−)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but is significantly more persistent due to its covalent binding. We also provide the first reported in vivo antitumor evaluation of (−)-zampanolide where we determine that it has potent and persistent antitumor efficacy when delivered intratumorally. Future work on zampanolide to further evaluate its pharmacophore and determine ways to improve its systemic therapeutic window would make this compound a potential candidate for clinical development through its ability to circumvent taxane-resistance mechanisms. 相似文献
963.
964.
Phillip Jackson Martin Diefenbach Ragampeta Srinivas Detlef Schroeder Helmut Schwarz 《ChemInform》2000,31(28):no-no
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option. 相似文献
965.
Dr. Phillip M. Danby Andrew Jeong Dr. Lyann Sim Dr. Ryan P. Sweeney Jacob F. Wardman Ryan Karimi Dr. Andreas Geissner Dr. Liam J. Worrall Prof. Dr. Jolene. P. Reid Prof. Dr. Natalie C. J. Strynadka Prof. Dr. Stephen G. Withers 《Angewandte Chemie (International ed. in English)》2023,62(21):e202301258
Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis. 相似文献
966.
Dr. Mengting Liu Dr. Masao Ohashi Qingyang Zhou Dr. Jacob N. Sanders Prof. Erin P. McCauley Prof. Phillip Crews Prof. K. N. Houk Prof. Yi Tang 《Angewandte Chemie (International ed. in English)》2023,62(40):e202311266
We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)-azonazine A from marine-derived Aspergillus insulicola. Formation of the hexacyclic benzofuranoindoline ring system from cyclo-(l -Trp-N-methyl-l -Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole-substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs. 相似文献