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21.
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
22.
Identification of vivianite,an unusual blue pigment,in a sixteenth century painting and its implications
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António João Cruz Erica Eires Luís Dias Teresa Desterro Carla Rego 《Color research and application》2018,43(2):177-183
Vivianite, a blue pigment employed in the past practically only in Northern and Central Europe, but with very limited use, was identified in an early sixteenth century painting, stylistically with Flemish features, from a church in Portugal. The identification of this iron phosphate mineral was made by SEM‐EDS based on the atomic ratio between phosphorus and iron in layers of blue paint (area analysis) and in particles of these same layers (spot analysis). This painting, about which there is no document to prove its authorship, becomes the first case, known in detail, of a sixteenth century painting containing vivianite. Moreover, this find and the presence of a chalk ground, also identified, strongly support the hypothesis of being a Flemish painting. 相似文献
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Locke Davenport Huyer Serena Mandla Yufeng Wang Scott B. Campbell Bess Yee Christian Euler Benjamin F. Lai A. Dawn Bannerman Dawn S. Y. Lin Miles Montgomery Kayla Nemr Timothy Bender Slava Epelman Radhakrishnan Mahadevan Milica Radisic 《Advanced functional materials》2021,31(6):2003341
Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA. 相似文献
26.
In this work it is presented a study on the residence time distribution (RTD) of particles in a co-current pilot-plant spray dryer operated with a rotary atomization system. A nuclear technique is applied to investigate the RTD responses of spray dryers. The methodology is based on the injection of a radioisotope tracer in the feed stream followed by the monitoring of its concentration at the outlet stream. The experiments were performed during the drying of aqueous suspensions of gadolinium oxide. The RTD responses obtained experimentally presented good reproducibility, indicating that the technique applied is well suited to investigating fluid-dynamics of spray dryers. In addition to the experimental investigation, a mathematical model was used to describe the RTD experimental curves. 相似文献
27.
Ana M. García José M. Villora Diego A. Moreno Carlos Ranninger Pío Callejas M. Flora Barba 《Journal of the American Ceramic Society》2003,86(12):2200-2202
The objective of this research was to study the removal of cadmium and lead from an aqueous solution through a biological treatment. For this purpose a glass-ceramic material was manufactured from industrial and urban wastes. Biofilms of microorganisms found in wastewater were developed on its surface, and continuous tests were conducted in the presence and absence of the biofilm to analyze the glass-ceramic's ability to remove the heavy metals from an aqueous environment. The results suggest that this bioremediation process, developed on an industrial scale, could represent an alternative to the chemical processes currently used. 相似文献
28.
JJ Jiménez-Nácher N de Alonso B Vega A del Río JL Moya V Barrios A Hurtado 《Canadian Metallurgical Quarterly》1993,193(6):290-292
Pericardial effusion (PE) as a hypothyroidism associated sign, is something that can be found with relative frequency; nevertheless, cardiac tamponade (CT) as the first sign of this disease may be considered exceptional especially in young patients. We report a 31 years old woman with clinical symptoms and signs of CT that in the forward workshop was diagnosed of primary hypothyroidism as cause of the CT. We shortly describe the case and review the literature, emphasizing the importance of the knowledge of CT trigger factors in myxedematous PE, as well as its usual benign evolution with hormonal treatment, without recurrences of the CT after pericardiocentesis is performed. This justify a conservative approach, in spite of the slow resolution of the PE what can take as long as 1.5 years. 相似文献
29.
NM Forones M Tanaka D Machado JB Falc?o M Giovanoni 《Canadian Metallurgical Quarterly》1997,34(1):3-6
Female SJL mice are more susceptible than male mice to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP)-specific T lymphocytes. In the present study, we examined mechanisms involved in this gender-related difference in disease susceptibility. MBP-specific T lymphocytes derived from spleens of males during the effector phase of adoptive EAE produced significantly higher levels of IL-10, an anti-inflammatory cytokine in EAE. A protective effect of testosterone was then shown. Females implanted with dihydrotestosterone pellets demonstrated a significantly less severe course of EAE as compared with females implanted with placebo pellets. Finally, MBP-specific T lymphocytes derived from dihydrotestosterone-implanted females produced significantly higher levels of IL-10 than those from placebo. Together these data indicate that testosterone exerts a protective effect in EAE that is mediated at least in part by enhanced production of IL-10 by autoantigen-specific T lymphocytes. 相似文献
30.
AI Quintero Del Río 《Canadian Metallurgical Quarterly》1997,89(1-3):12-14
Motor vehicle accidents are the main cause of death and disability between 1 and 4 years of age. Since 1980 the Academy of Pediatrics has been promoting the correct use of car seats. The major reason that car seats are not fulfilling their full potential is their incorrect or lack of use. In order to evaluate parental knowledge about car seat use for children and their actual use in the population visiting HURRA, a survey was performed which demonstrated that only 57.6% of the parents interviewed had infant car seats and that only 83.3% of owners actually use it. As many as 94.4% had correct knowledge about car seat use, but the majority of correct information was not provided by the medical staff. The majority of parents use seat belts for their own protection but a significantly smaller percentage use car seats for their own children. 相似文献