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排序方式: 共有316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.
B. A. Young J. R. Williams S. W. Deiker S. T. Ruggiero B. Cabrera 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》2004,520(1-3):307-310
We summarize a continuing investigation into using ion implantation to alter the transition temperature of superconducting thin films. The primary motivation for the work presented here was to study the feasibility of using magnetic ion doping to replace the bi-layer Tc control process currently used for certain cryogenic detector applications at National Institute for Standards and Technology. The results from work with various ion species implanted into aluminum, molybdenum, titanium and tungsten host films are presented. 相似文献
3.
Differential emotions theory (DET) proposes that infant facial expressions of emotions are differentiated. To test this hypothesis, the authors examined infant facial expressions longitudinally at 2, 4, and 6 mo of age during face-to-face play and a "still-face" interaction with their mothers. Infant expressions were coded using the Maximally Discriminative Facial Movement Coding System (Max). Consistent with DET, discrete positive expressions occurred more of the time and were of longer duration than blended expressions of positive affect. Contrary to DET, at no age did the proportions or durations of discrete and blended negative expressions differ, and they showed different patterns of developmental change. One is led to either reject or revise DET or else question the adequacy of the Max system. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
4.
S. Rombetto Yu. N. Ovchinnikov V. Corato P. Silvestrini E. Esposito C. Granata M. Russo R. Russo B. Ruggiero 《Open Systems & Information Dynamics》2007,14(2):209-216
We study the resonant quantum behaviour of a macroscopic superconducting system interacting with an external field. First
we consider the resonant tunneling assisted by microwave frequency in the moderate underdamped quantum regime. Then we consider
the resonant process in the extreme underdamped limit. In both regimes we have investigated a small frequency range, where
resonant phenomena take place. The transition probability W from the left to the right potential well has been numerically
calculated for an rf-SQUID as function of the external flux φ
x
for both regimes. Results indicate that, in a proper frequency and φ
x
range, the transition probability W can present two or three resonant peaks, depending on the damping regime. 相似文献
5.
F. La Via G. Galvagno F. Giannazzo A. Ruggiero L. Calcagno M. Mauceri G. Pistone G. Abbondanza A. Veneroni L. Zamolo G.L. Valente 《Microelectronic Engineering》2006,83(1):48-50
The results of a new epitaxial process using an industrial 6 × 2″ wafer reactor with the introduction of HCl during the growth have been reported. A complete reduction of silicon nucleation in the gas phase has been observed even for high silicon dilution parameters (Si/H2 > 0.05%) and an increase of the growth rate until about 20 μm/h has been measured. Photoluminescence at room temperature and at 50 K was used for defects quantification and distribution. On these wafers grown using HCl high voltage Schottky diodes have been realized. The diodes were analyzed by current-voltage (I-V) characteristics. 相似文献
6.
Bernhard Beckermann Jorge Bustamante Reinaldo Martínez-Cruz José M. Quesada 《Calcolo》2014,51(2):319-328
For a given $\theta \in (a,b)$ , we investigate the question whether there exists a positive quadrature formula with maximal degree of precision which has the prescribed abscissa $\theta $ plus possibly $a$ and/or $b$ , the endpoints of the interval of integration. This study relies on recent results on the location of roots of quasi-orthogonal polynomials. The above positive quadrature formulae are useful in studying problems in one-sided polynomial $L_1$ approximation. 相似文献
7.
In our previous studies, we found that circulating thyroid hormone levels alter cholesterol partition between plasma and erythrocytes
by changing the phospholipid content of erythrocytes (Ruggiero, F.M.,et al. (1984)Horm. Metabol. Res. 16, 37–40; Ruggiero, F.M.,et al. (1987)Lipids 22, 148–151). As an extension of this work, we now followed the exchange of free cholesterol between plasma and erythrocytes
in control, hyperthyroid and hypothyroid rats under various experimental conditionsin vitro. In control rats, erythrocytes incubated with plasma at 37°C for 4 hr lose 10% of cholesterol which was esterified by lecithin:
cholesterol acyltransferase (LCAT) present in the plasma. In hyperthyroid rats, erythrocytes incubated with plasma lose 30%
of cholesterol within the same time. By contrast, in the case of hypothyroid rats incubation for 4 hr was necessary to transfer
24% of free cholesterol from plasma to erythrocytes. Inhibition of cholesterol esterification did not affect the loss of erythrocyte
cholesterol in control and in hyperthyroid rats. Ca2+ increased the LCAT activity in the plasma of these rats. The findings shed light on the role of thyroid hormones in regulating
cholesterol levels in plama through active cholesterol transfer between plasma and erythrocytes. 相似文献
8.
9.
This paper is concerned with the problem of assessing the stability of linear systems with a single time-delay. Stability analysis of linear systems with time-delays is complicated by the need to locate the roots of a transcendental characteristic equation. In this paper we show that a linear system with a single time-delay is stable independent of delay if and only if a certain rational function parameterized by an integer k and a positive real number T has only stable roots for any finite T≥0 and any k≥2. We then show how this stability result can be further simplified by analyzing the roots of an associated polynomial parameterized by a real number δ in the open interval (0,1). The paper is closed by showing counterexamples where stability of the roots of the rational function when k=1 is not sufficient for stability of the associated linear system with time-delay. We also introduce a variation of an existing frequency-sweeping necessary and sufficient condition for stability independent of delay which resembles the form of a generalized Nyquist criterion. The results are illustrated by numerical examples. 相似文献
10.
M. D. R. Pizzigallo A. Napola M. Spagnuolo P. Ruggiero 《Journal of Materials Science》2004,39(16-17):5455-5459
The influence of the presence of humic acids of different origin on the catalytic transformation of pentachlorophenol (PCP) by two metal oxides, ferrihydrite and birnessite, using mechanochemical contact was studied. The mechanochemical dry contact with light grinding of PCP and birnessite was more effective than that observed in the presence of ferrihydrite (approximately 70 and 40% of PCP removal after 20 days, respectively). The removal of PCP by birnessite and ferrihydrite was significantly enhanced in the presence of humic acid (HA). The different origin of humic acids (agricultural, forest and commercial) showed a slight influence on the overall reaction. The commercial HA, when mixed with birnessite, was more effective in reducing PCP concentration compared to the others two HAs investigated. The transformation process in the presence of birnessite with and without HA was accompanied by the release of four chlorides per molecule of PCP transformed. 相似文献