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1.
Thin Film Thermoelectric Metal–Organic Framework with High Seebeck Coefficient and Low Thermal Conductivity
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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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FJ Overdyk PM Gramling-Babb JR Handy NI Faller MJ Miller 《Canadian Metallurgical Quarterly》1997,84(1):213-215
Robertsonian translocations, although relatively common as a constitutional genetic aberration, are rarely encountered in leukaemia. We report a case of acute myeloid leukaemia which showed an acquired Robertsonian translocation in the form of der(14;21) by cytogenetic analysis of leukaemic cells. This was confirmed by the PHA-stimulated culture of peripheral blood lymphocytes. A review of the literature identifies only eight reported cases of acquired Robertsonian translocations in leukaemia. In the majority of cases the Robertsonian translocation occurs as a secondary change in a complex abnormal clone, whereas in two out of nine patients reported, including ours, it is found as a sole karyotypic abnormality. 相似文献
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Capers Jones 《Information Systems Management》1994,11(4):28-33
If you don't know the current productivity rates, usage volumes, and other quantitative baseline data for your software operations, then software might not be a key component of the company's core business. The evaluation criteria in this article can help the IS executive determine the outsourcing options for software operations. 相似文献
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Twenty-six patients with an intracardiac myxoma underwent surgical resection at our institution from 1977 through 1992. Left atrial myxoma was diagnosed in 22 patients, left ventricular in 1, right atrial in 2, and right ventricular in 1. Six patients were asymptomatic; preoperative symptoms included dyspnea, arrhythmias, embolic episodes, and syncope. The diagnosis was established with transthoracic echocardiography in all cases but one. Surgery was performed in all cases with the aid of cardiopulmonary bypass with moderate hypothermia and cold crystalloid cardioplegia. One patient with a left ventricular myxoma died in a comatose state during the immediate postoperative period. Long-term clinical and echocardiographic evaluation was performed in 19 patients; results were excellent (all the patients were in New York Heart Association functional class I or II), and no recurrences were documented. The clinical characteristics, diagnostic methods, and surgical approach are presented and discussed. 相似文献
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Current cementing techniques of distal plugging, pulsatile water cleaning of the canal, and retrograde filling with PMMA in a low-viscous state prepared using porosity reduction techniques and then pressurized have been shown to give excellent results at 10 or more years after operation. However, physical and aging characteristics of PMMA do not guarantee that those results will hold up in the 20- to 30-year time frame. Fifteen-year experience with bony ingrowth systems indicate the development of a durable interface without PMMA, although the interface does appear more vulnerable to attack by the biologic reaction to HMWPE debris. Bone remodeling appears more favorable around proximally fixed bone ingrowth prostheses than around distally fixed prostheses. Softening of the physical characteristics of the stem tip may reduce the incidence of thigh pain. Patients with high activity potential and a life expectancy of greater than 25 years should be strongly considered for a proximally fixed bone ingrowth or ongrowth prosthesis. 相似文献
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