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排序方式: 共有260条查询结果,搜索用时 15 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.
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
4.
Preparation of Silicon Carbide/Aluminum Nitride Ceramics Using Organometallic Precursors 总被引:1,自引:0,他引:1
Corinna L. Czekaj Michael L. J. Hackney William J. Hurley Jr. Leonard V. Interrante Gary A. Sigel Paul J. Schields Glen A. Slack 《Journal of the American Ceramic Society》1990,73(2):352-357
Solid solutions of 2H -SiC/AlN can be prepared at temperatures less than 1600°C by rapid pyrolysis ("hot drop") of mixtures of [(Me3 Si)0.80 ((CH2 =CH)MeSi)1.0 (MeHSi)0.35 ] n (VPS) or [MeHSiCH2 ] n (MPCS) with [R2 AlNH2 ]3 , where R=Et, i -Bu or simply by slow pyrolysis of the precursor mixture in the case of [Et2 AlNH2 ]3 . In contrast, slow pyrolysis of mixtures of VPS or MPCS with [ i -Bu2 AlNH2 ]3 yields a composite of 2 H -AlN and 3 C -SiC at 1600°C, which transforms into a single 2 H -SiC/AlN solid solution on heating to 2000°C. The influences of the nature of the precursor and processing conditions on the structure, composition, and purity of the SiC/AlN materials are discussed. 相似文献
5.
Benedikt Ley Corinna Ogonowski Jan Hess Tim Reichling Lin Wan Volker Wulf 《Behaviour & Information Technology》2014,33(8):815-828
Technological infrastructure at home is changing continuously and is becoming increasingly interconnected. Media devices, including the TV set, provide access to the Internet and offer manifold opportunities to consume media on demand. Additionally, personal devices, such as smartphones, also enable flexible consumption and sharing of media. Questions about how these technologies change the user's media usage and how these changes affect the social structure of a household, however, remain largely unanswered. In order to gain insight into the adoption of new technologies into daily routines, we explored these changes in respect of people's media usage in a qualitative long-term Living Lab study. We will present findings regarding personal routines, flexible integration of new devices into existing practices, influences on households as social systems and related issues in device access and collective use. We will highlight potentials and conflicts regarding device shifts and roles; restrictions in device access; social influences in the living room; and individual changes in media consumption. 相似文献
6.
Luis G. Nardin Giulia Andrighetto Rosaria Conte Áron Székely David Anzola Corinna Elsenbroich Ulf Lotzmann Martin Neumann Valentina Punzo Klaus G. Troitzsch 《Autonomous Agents and Multi-Agent Systems》2016,30(6):1117-1147
Protection racketeering groups are powerful, deeply entrenched in multiple societies across the globe, and they harm the societies and economies in which they operate in multiple ways. These reasons make their dynamics important to understand and an objective of both scientific and application-oriented interest. Legal and social norm-based approaches arguably play significant roles in influencing protection racket dynamics. We propose an agent-based simulation model, the Palermo Scenario, to enrich our understanding of these influences and to test the effect of different policies on protection racket dynamics. Our model integrates the legal and the social norm-based approaches and uses a complex normative agent architecture that enables the analysis of both agents’ behaviours and mental normative representations driving behaviour. We demonstrate the usefulness of the model and the benefits of using this complex normative architecture through a case study of the Sicilian Mafia. 相似文献
7.
E Mainini I Martinelli G Morandi S Villa I Stefani C Mazzi 《Canadian Metallurgical Quarterly》1995,18(10):796-799
In order to evaluate the efficacy of a TSH suppressive dose of levothyroxine to reduce the volume of a single thyroid nodule we studied 55 euthyroid patient: 45 (group A) were suppressed with LT4 (mean 1.7 +/- 0.9 micrograms/Kg/day) for 21.3 +/- 5.3 months, and 10 patients (group B) served as controls. All the nodules were "cold" at scintiscanning, solid at ultrasonography and benign by fine-needle aspiration cytology. As responders were assumed the nodules shrinked at the end of treatment of 50% in volume. Thyroid function values (TSH, T4, FT4, T3, FT3, thyroid peroxidase and thyroglobulin antibodies), clinical and ultrasonographic findings were evaluated initially and at the end of the study. A significant nodular volume decrease occurred in 8 treated patients (17.8%) while 37 (82.2%) amongst the group suppressed and all controls showed no change (A vs B = NS). In two untreated patients new nodules were noted; no new nodules were discovered in the treated group (A vs B p < 005). No side effects occurred in any treated patient, even if at the end of treatment a significant T4 and FT4 (p < 0.01) increase was observed. No one onset parameter can predict the response to the therapy. These results suggest that only a small group of patients affected by a single thyroid nodule seems to respond to a TSH suppressive therapy. 相似文献
8.
Joeran Beel Corinna Breitinger Stefan Langer Andreas Lommatzsch Bela Gipp 《User Modeling and User-Adapted Interaction》2016,26(1):69-101
Numerous recommendation approaches are in use today. However, comparing their effectiveness is a challenging task because evaluation results are rarely reproducible. In this article, we examine the challenge of reproducibility in recommender-system research. We conduct experiments using Plista’s news recommender system, and Docear’s research-paper recommender system. The experiments show that there are large discrepancies in the effectiveness of identical recommendation approaches in only slightly different scenarios, as well as large discrepancies for slightly different approaches in identical scenarios. For example, in one news-recommendation scenario, the performance of a content-based filtering approach was twice as high as the second-best approach, while in another scenario the same content-based filtering approach was the worst performing approach. We found several determinants that may contribute to the large discrepancies observed in recommendation effectiveness. Determinants we examined include user characteristics (gender and age), datasets, weighting schemes, the time at which recommendations were shown, and user-model size. Some of the determinants have interdependencies. For instance, the optimal size of an algorithms’ user model depended on users’ age. Since minor variations in approaches and scenarios can lead to significant changes in a recommendation approach’s performance, ensuring reproducibility of experimental results is difficult. We discuss these findings and conclude that to ensure reproducibility, the recommender-system community needs to (1) survey other research fields and learn from them, (2) find a common understanding of reproducibility, (3) identify and understand the determinants that affect reproducibility, (4) conduct more comprehensive experiments, (5) modernize publication practices, (6) foster the development and use of recommendation frameworks, and (7) establish best-practice guidelines for recommender-systems research. 相似文献
9.
Danilo Marimpietri Irma Airoldi Angelo Corso Faini Fabio Malavasi Fabio Morandi 《International journal of molecular sciences》2021,22(8)
The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance. 相似文献
10.
This article investigates the role of natural foods and farming in Nazi Germany. Why did the state encourage Germans to eat and farm more naturally? What did “natural” mean in the context of this genocidal regime? By what means were Germans encouraged to take up these practices and to what degree did they do so? This article explores these questions by tracing the assimilation of natural foods and farming to the regime's racial, political, and economic goals. Eating more naturally, Nazi leaders believed, would promote racial health, boost physical performance, and maximize the efficient use of resources, all qualities needed to fight and win the coming war. Natural foods and farming, in short, belonged to the biopolitics of fascist modernity. The article develops this claim in two sections, one on efforts to make German diets more natural, the other on an early form of organic farming known as biodynamics. The conclusion considers the implications of these findings for food historians more generally. 相似文献