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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
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.
David J. Lawrence Brianna L. Smith Cameron D. Collard Keyton A. Elliott Kyle L. Fakhoury Jeffery D. Mangold Anna N. Soyka 《International Journal of Hydrogen Energy》2021,46(2):1642-1655
Monolithically-integrated tandem photoanodes were fabricated on substrates consisting of epitaxial n-GaAs1-xPx (x ? 0.32) grown on n+-GaAs wafers. A p+-n junction photovoltaic (PV) cell was first formed by zinc diffusion into the n-GaAs0.68P0.32 from a deposited ZnO coating. After diffusion the ZnO serves as a transparent electrical contact to the resulting p+-GaAs0.68P0.32 surface layer. Transparent, conducting SnO2:F provides chemical and mechanical protection for the ZnO and the underlying PV cell, and it electrically connects this cell to a top BiVO4 photocatalyst layer. In some photoanodes, a WO3 thin film was interposed between the SnO2:F and BiVO4. All oxide coatings were produced by ultrasonic spray pyrolysis except WO3, which was spin coated. Unassisted (unbiased) solar water splitting was achieved, with a solar-to-hydrogen efficiency approaching 2%, without addition of any co-catalyst to the BiVO4 surface. This work can provide insights to other researchers regarding scalable, low cost approaches for the planar monolithic integration of oxide photoanode materials with PV cells to create new tandem devices. 相似文献
23.
Kinetic,thermodynamic parameters and in vitro digestion of tannase from Aspergillus tamarii URM 7115
Amanda Reges de Sena Tonny Cley Campos Leite Talita Camila Evaristo da Silva Nascimento Anna Carolina da Silva Catiane S. Souza Antônio Fernando de Mello Vaz 《Chemical Engineering Communications》2018,205(10):1415-1431
Tannase is an enzyme used in various industries and produced by a large number of microorganisms. The aim of this study was to evaluate tannase production to determine the biochemical, kinetic, and thermodynamic properties and to simulate tannase in vitro digestion. The tannase-producing fungal strain was isolated from “jamun” leaves and identified as Aspergillus tamarii. Temperature at 26°C for 67?h was the best combination for maximum tannase activity (6.35-fold; initial activity in Plackett–Burman design—15.53?U/mL and average final activity in Doehlert design—98.68?U/mL). The crude extract of tannase was optimally active at 40°C, pH 5.5 and 6.5. Moreover, tannase was stimulated by Na+, Ca2+, Mg2+, and Mn2+. The half-life at 40°C lasted 247.55?min. The free energy of Gibbs, enthalpy, and entropy, at 40°C, was 81.47, 16.85, and ?0.21?kJ/mol?·?K, respectively. After total digestion, 123.95% of the original activity was retained. Results suggested that tannase from A. tamarii URM 7115 is an enzyme of interest for industrial applications, such as gallic acid production, additive for feed industry, and for beverage manufacturing, due to its catalytic and thermodynamic properties. 相似文献
24.
From an experimental and theoretical investigation of the continuity of influent inorganic suspended solids (ISS) along the links connecting the primary settling tank (PST), fully aerobic or N removal activated sludge (AS) and anaerobic and aerobic sludge digestion unit operations, it was found that the influent wastewater (fixed) ISS concentration is conserved through primary sludge anaerobic digestion, activated sludge and aerobic digestion unit operations. However, the measured ISS flux at different stages through a series of wastewater treatment plant (WWTP) unit operations is not equal to the influent ISS flux, because the ordinary heterotrophic organisms (OHO) biomass contributes to the ISS flux by differing amounts depending on the active fraction of the VSS solids at that stage. 相似文献
25.
Role stress has received a lot of research attention in psychological, sociological, and organizational studies over the last several decades. Based on a literature review of about 300 journal articles, this article examines prominent consequences of role stress. Specific focus is on researching differences in relationships between facets of role stress (i.e., role ambiguity, role conflict, and role overload) and frequently cited consequences using techniques of meta-analysis. Findings indicate that each role stress facet has a different relationship with the eight consequences studied. Role stress research can benefit from looking at each facet individually in addition to role stress generally. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
26.
The objective of this study was to compare methane production and characteristics of digested material in anaerobic digestion concepts according to the Animal By-Products Regulation (ABP-Regulation) of the EC (hygienisation of biowaste for 1 hour at 70 degrees C, particle size < 12 mm) and Finnish national regulations (treatment temperature 55 degrees C, feeding interval 24 h, hydraulic retention time (HRT) 20 d, particle size < 40 mm) and with small variations in treatment methods for treating manure and biowaste. Moreover, the survival of three different salmonella bacteria in these processes was studied. Hygienisation of biowaste prior to digestion at 35 degrees C enhanced methane production by 14-18% compared to similar treatment without hygienisation. The differences in treatment temperature, HRT and hygienisation of biowaste prior to digestion did not significantly affect the characteristics of digested material. The concepts according to the ABP-Regulation and Finnish national regulations were effective in destroying salmonella bacteria to an undetectable level. 相似文献
27.
Real-time multimedia applications have to use forward error correction (FEC) anderror concealment techniques to cope with
losses in today’s best-effort Internet. The efficiency of these solutions is known however to depend on the correlation between
losses in the media stream. In this paper we investigate how the packet size distribution affects the packet loss process,
that is, the distribution of the number of lost packets in a block, the related FEC performance and the average loss run length.
We present mathematical models for the loss process of the MMPP+M/D/1/K and the MMPP+M/M/1/K queues; we validate the models
via simulations, and compare the results to simulation results with an MPEG-4 coded video trace. We conclude that the deterministic
packet size distribution (PSD) not only results in lower stationary loss probability than the exponential one, but also gives
a less correlated loss process, both at a particular average link load and at a particular stationary loss probability as
seen by the media stream.Our results show that for applications that can only measure the packet loss probability, the effects
of the PSD on FEC performance are higher in access networks, where a single multimedia stream might affect the multiplexing
behavior. Our results show that the effects of the PSD on FEC performance are higher in access networks, where a single multimedia
stream might affect the multiplexing behavior and thus can improve the queuing performance by decreasing the variance of its
PSD. 相似文献
28.
Jean-Fran?ois Blais Nathalie Meunier Guy Mercier Patrick Drogui Rajeshwar Dayal Tyagi 《Canadian Metallurgical Quarterly》2004,130(5):516-525
This research is related to a preindustrial pilot scale study of the performance of the simultaneous sewage sludge digestion and metal leaching (SSDML) process for decontamination and stabilization of sewage sludge. Ten batch tests were carried out in two 4?m3 bioreactors under various conditions of operation. Results indicated that the addition of 1.0 to 1.5?g?S0/L, which is the equivalent of approximately 30 to 50?kg?S0 per tons dry sludge, is sufficient to obtain conditions of acidity (pH<2.5) and oxido-reduction potential greater than 500 mV necessary for an effective solubilization of toxic metals. The final average of metal solubilization in the output sludge during the SSDML process varied in the following ranges: 25–78% Cd, 9–32% Cr, 48–100% Cu, 77–99% Mn, 15–53% Ni, 12–47% Pb, and 66–100% Zn. The N, P, and K contents were also preserved in the decontaminated sludge. Moreover, the use of low concentrations of elemental sulfur makes it possible to obtain decontaminated sludge with a low total sulfur content (1.4–1.5% S) compatible with agricultural use. The suspended solids removal calculated for the SSDML process was slightly lower, (2.5±0.4)% volatile suspended solids per day, than those reached using standard aerobic digestion. Finally, the SSDML process was found to be effective in removing bad odors and in the destruction (99–100%) of indicator bacteria. 相似文献
29.
Branislav Radjenovi? Jae Koo Lee Marija Radmilovi?-Radjenovi? 《Computer Physics Communications》2006,174(2):127-132
Level set method [S. Osher, J. Sethian, J. Comput. Phys. 79 (1988) 12] is a highly robust and accurate computational technique for tracking moving interfaces in various application domains. It originates from the idea to view the moving front as a particular level set of a higher dimensional function, so the topological merging and breaking, sharp gradients and cusps can form naturally, and the effects of curvature can be easily incorporated. The resulting equations, describing interface surface evolution, are of Hamilton-Jacobi type and they are solved using techniques developed for hyperbolic equations. In this paper we describe an extension of the sparse field method for solving level set equations in the case of non-convex Hamiltonians, which are common in the simulations of the profile surface evolution during plasma etching and deposition processes. Sparse field method itself, developed by Whitaker [R. Whitaker, Internat. J. Comput. Vision 29 (3) (1998) 203] and broadly used in image processing community, is an alternative to the usual combination of narrow band and fast marching procedures for the computationally effective solving of level set equations. The developed procedure is applied to the simulations of 3D feature profile surface evolution during plasma etching process, that include the effects of ion enhanced chemical etching and physical sputtering, which are the primary causes of the Hamiltonian non-convexity. 相似文献
30.
On the effect of spatial variances in historical rainfall time series to CSO performance evaluation.
Historical, high-resolution rain series are the backbone of modern combined sewer overflow (CSO) structure design. These rain series are the input to the computational estimation of the performance of the measures with respect to CSO pollution abatement. However, those historical precipitation measurements are available at only a few locations. Frequently rain series have to be used from gauging stations at a significant distance. In order to judge and to compensate for this influence an estimate between rain characteristics and combined sewer outflow (CSO) performance indicators would be useful. In this paper such correlations have been sought for a collection of 37 rain series covering large areas of Europe. It was found that the mean annual rain volume can explain most of the variances for the performance indicators Number of overflows and CSO volume. For explaining the spatial differences in the efficiency of the CSO structure another rain characteristic, i.e. the maximum event with a return period of one year, is to be used. 相似文献