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排序方式: 共有593条查询结果,搜索用时 93 毫秒
1.
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
2.
V. Morandi F. Marabelli V. Amendola M. Meneghetti D. Comoretto 《Advanced functional materials》2007,17(15):2779-2786
Polystyrene artificial opals with few gold nanoparticles (AuNp) embedded in the interstices (doping) are grown by using the meniscus technique starting from a mixed suspension of microspheres and AuNp. Samples having different sphere diameters and nanoparticle loads have been prepared. Their reflectance spectra clearly show a dramatic bathochromic shift of the photonic stop band (up to 1400 cm–1) and a reduction of its full width half maximum, due to an increase of the effective refractive index of about 8 % with respect to bare opals, which is accounted for by analytical theoretical models. Reflectance spectra do not show any direct evidence of AuNp absorption even at the higher AuNp doping level. Nanosecond transient absorption measurements on these systems indicate that a variation of transmission (optical switching) of about 150 % is observed for AuNp doped opals upon photoexcitation with 9 ns laser pulses at 532 nm. No switching is instead observed for bare opals. 相似文献
3.
Vittorio Ghergia 《Sadhana》1992,17(3-4):411-430
Starting from the present state-of-the-art of discrete devices up to the realization of monolithic semiconductor integrated
prototypes, an overview of optoelectronic devices for telecommunications is given. Among discrete devices single frequency
lasers, tunable and multi-sectionDFB lasers andPIN andAPD photodiode detectors are analysed, including the use of new technologies in progress for a second generation of devices.
On the future perspective ofIBCN distribution networks, some economics of the hybrid and monolithic form of integration are attempted. Finally a short outline
of the most recent achievements in monolithic integration is presented, taking into particular consideration the activities
in this field byEEC ESPRIT andRACE programmes. 相似文献
4.
An improved code density test for flash A/D converters is proposed, revealing some dynamic phenomena (e.g., missing codes) hidden by the conventional approach. Formulas are reported for obtaining, from code density, effective noise estimates fully consistent with those provided by waveform analysis. Finally, it is shown that the variance of noise estimates obtained by time-domain analysis may be unacceptably large if the observation window is not properly chosen 相似文献
5.
Vincenzo Augugliaro Vittorio Loddo Ignacio Maldonado Raffaele Molinari 《Solar Energy》2005,79(4):402-408
The photocatalytic oxidation of a common antibiotic, the lincomycin was carried out in aqueous suspensions of polycrystalline TiO2 Degussa P25 irradiated by sunlight. In order to improve the performance of the lincomycin degradation a hybrid system consisting of a solar photoreactor with the photocatalyst in suspension coupled with a membrane module, used to confine both photocatalyst and pollutants in the reaction environment, was tested.A preliminary study was carried out in order to determine some kinetics parameters of the drug photodegradation. The influence of initial substrate concentration on the lincomycin photooxidation rate was investigated. The photooxidation rate follows a pseudo-first order kinetics with respect to the lincomycin concentration under the used experimental conditions. The presence of the membrane reactor allows the catalyst separation and to operate in continuous mode as the membranes rejection for lincomycin and its oxidation products was quite high. 相似文献
6.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
7.
Riccardo Carli Raymond Le Van Mao Claudia L. Blanchi Vittorio Ragaini 《Catalysis Letters》1993,21(3-4):265-274
Gallium species which were incorporated initially in the oxide form, were all in the (+3) oxidation state in the hybrid catalyst and exhibited two types of hydrogen chemisorption sites, shw and shs. The stronger sorption sites shs which predominated at higher gallium dispersion, corresponded probably to the most effective surface configuration for gallium in the aromatization ofn-butane. 相似文献
8.
The conditions for obtaining recrystallization in more ordered modifications are described for an uniaxially oriented sample of isotactic polypropylene, annealed with fixed ends. These recrystallization conditions are related to the conditions of a lamination process. 相似文献
9.
Protecting privacy on the Web is becoming increasingly complicated because of the considerable amount of personal and sensitive information left by users in many locations during their Web browsing and the silent actions of third party sites that collect data, aggregate information and build personal profiles of Internet users in order to provide free and personalized services. On the other hand, most of people are unaware that their information may be collected online, and that, after their aggregation from multiple sources, could be used for secondary purposes, such as linked to allow identification, without user’s notice. 相似文献
10.
Daniel Dominguez Gouvêa Cyro de A. Assis D. Muniz Gilson A. Pinto Alberto Avritzer Rosa Maria Meri Leão Edmundo de Souza e Silva Morganna Carmem Diniz Vittorio Cortellessa Luca Berardinelli Julius C. B. Leite Daniel Mossé Yuanfang Cai Michael Dalton Lucia Happe Anne Koziolek 《Software and Systems Modeling》2013,12(4):765-787
In this paper, we report on our experience with the application of validated models to assess performance, reliability, and adaptability of a complex mission critical system that is being developed to dynamically monitor and control the position of an oil-drilling platform. We present real-time modeling results that show that all tasks are schedulable. We performed stochastic analysis of the distribution of task execution time as a function of the number of system interfaces. We report on the variability of task execution times for the expected system configurations. In addition, we have executed a system library for an important task inside the performance model simulator. We report on the measured algorithm convergence as a function of the number of vessel thrusters. We have also studied the system architecture adaptability by comparing the documented system architecture and the implemented source code. We report on the adaptability findings and the recommendations we were able to provide to the system’s architect. Finally, we have developed models of hardware and software reliability. We report on hardware and software reliability results based on the evaluation of the system architecture. 相似文献