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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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The expression of cytokeratins (CK), involucrin, vimentin, CD34, and alpha-smooth-muscle actin was studied in fetal and adult hair follicles. The first stage of the developing hair follicle is characterized by palisaded, elongated epithelial cells budding from the epidermal basal layer. These cells express CK5/6, CK14, CK17, CK19, and vimentin. During the following weeks of gestation, different structures in the developing hair follicle can be identified and characterized. The matrical cells display only CK19. The keratinocytes of the outer root sheath express CK5/6, CK14, CK17, CK19, and involucrin; those of the inner root sheath, CK4, CK18, and involucrin; those of the isthmus, the same profile as the ORS. In the infundibulum, the basal-layer keratinocytes express CK5/6, CK14, CK17, and CK19, whereas in the suprabasal layers CK1, CK4, CK10, CK14, and CK17 are seen. The adult hair follicle in anagen fails to express CK19 in the matrical cells and isthmus and both CK17 and CK19 in the infundibulum. These profiles of intermediate filaments and other markers appear to be potentially useful in categorizing neoplasms with apparent follicular differentiation. 相似文献
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SE Edman 《Canadian Metallurgical Quarterly》1996,13(1):4-11
Diagnosis of developmental speech and language disorders in accordance with the ICD-10 is to be based on the psychometric assessment of speech and language performance. In the present study the clinical validity of the Heidelberger Sprachentwicklungstest (HSET) for diagnosing expressive language disorders was assessed by comparing HSET subtest results for 92 children aged 4 to 10 years who had various speech and language disorders with the children's scores on another language test, a cognitive test and clinical findings. The HSET scores differed considerably from the clinical ratings of the severity of the language disturbance. The correlations between the HSET scores and the score on the other language test was also low. Although the correlations of the HSET scores with the performance IQ was low, the correlations with the verbal IQ were high. The implications of these findings for the use of the HSET in diagnosing children with language impairments are discussed. 相似文献
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R Gollamudi Z Feng EO Dillingham SE Bond G Han S Salgia 《Canadian Metallurgical Quarterly》1993,69(4):361-367
This investigation retrospectively examined changes in marital satisfaction following stroke. The relationship between such changes and other pertinent factors were also examined, including severity of aphasia, knowledge of aphasia, number of months after stroke, and length of the marriage. The subjects were 40 spouses of patients with aphasia grouped according to severity of the aphasia (mild, moderate, severe). Spouses completed two different measures of marital satisfaction--the Marital Satisfaction Scale (MSS) and the Marital Comparison Level Index (MCLI). These measures were completed in both a prestroke (retrospective reporting) and a poststroke format to allow for change to be assessed. In addition, a Knowledge of Aphasia questionnaire was completed by the normal spouses to evaluate their understanding of the disorder of aphasia. There was a significant difference between prestroke and poststroke scores on both the MSS and the MCLI, indicating a lower level of satisfaction following the stroke. The amount of change between prestroke and poststroke MSS and MCLI scores was not related to either number of months poststroke or number of years married. Although there was no relationship between changes in prestroke and poststroke scores on the MCLI and Knowledge of Aphasia scores, there was a significant correlation between changes in these scores on the MSS and Knowledge of Aphasia scores. Hence, the more knowledge spouses had regarding aphasia, the less the negative impact the stroke had on marital satisfaction, as measured by the MSS. Results are discussed in terms of the interdisciplinary treatment needs of aphasic patients and the implications for future investigations. 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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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