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141.
142.
In vitro metabolic stability experiments using microsomes or other liver preparations are important components in the discovery and lead-optimization stages of compound selection in the pharmaceutical industry. Currently, liquid chromatography-tandem mass spectrometric (LC-MS/MS) support of in vitro metabolic stability studies primarily involves the monitoring of disappearance of parent compounds, using selected reaction monitoring (SRM) on triple-quadrupole instruments. If moderate to high turnover is observed, separate metabolite identification experiments are then conducted to characterize the biotransformation products. In this paper, we present a novel method to simultaneously perform metabolite screening in addition to the quantitative stability measurements, both within the same chromatographic run. This is accomplished by combining SRM and SRM-triggered, information-dependent acquisition (IDA) of MS/MS spectra on a hybrid triple-quadrupole linear ion trap (QqQLIT) mass spectrometer. Microsomal stability experiments using model compounds, bufuralol, propranolol, imipramine, midazolam, verapamil and diclofenac, were used to demonstrate the applicability of our approach. This SRM + SRM-IDA approach generated metabolic stability results similar to those obtained by conventional SRM-only approach. In addition, MS/MS spectra from potential metabolites were obtained with the enhanced product ion (EPI) scan function of LIT during the same injection. These spectra were correlated to the spectra of parent compounds to confirm the postulated structures. The time-concentration profiles of identified metabolites were also estimated from the acquired data. This approach has been successfully used to support discovery programs. 相似文献
143.
Mathematical Programming - We develop a new family of variance reduced stochastic gradient descent methods for minimizing the average of a very large number of smooth functions. Our... 相似文献
144.
David A. Selck Brian F. Woodfield Juliana Boerio‐Goates Daniel E Austin 《Rapid communications in mass spectrometry : RCM》2012,26(1):78-82
A low‐cost mass spectrometer attachment for thermogravimetric analysis has been constructed from readily available commercial instruments and components. The benefits of this set‐up include excellent mass‐flow repeatability, simple design, and significantly lower adoption cost as opposed to ready‐built commercial solutions. The inclusion of an open source software package allows semi‐automated, highly simplified data analysis. The results from the instrument show excellent sensitivity for small volumes of evolved gas, as well as highly reproducible signal strengths. The GUI‐based software package provides data analysis in a way that is very intuitive and that can be easily modified to work with a broad range of TG instruments. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
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146.
A new magnetic separation idea utilizing several ideas from microfabrication and nanomagnetics is presented. The basic idea comes from our earlier work using asymmetry in obstacles and Brownian motion to effect separation of objetcs [10] by moving them in streams whose angle to the hydrodynamic average velocity is a function of the diffusion coefficient of the object. The device we propose here is not technically a Brownian ratchet device but uses the idea of force which acts at angle to the hydrodynamic flow. In our case, the force is generated by a magnetic field gradient which comes from an array of magnetized wires which lie at an angle 0 to a hydrodynamic field flow. The sum of the hydrodynamic force and the magnetic force create a new vector which as in the case of the Brownian ratchet moves the cell out of the main stream direction. 相似文献
147.
Journal of Statistical Physics - We consider a general stochastic differential delay equation (SDDE) with state-dependent colored noises and derive its limit as the time delays and the correlation... 相似文献
148.
Deposition of calcium carbonate films by a polymer-induced liquid-precursor (PILP) process 总被引:7,自引:0,他引:7
A polypeptide additive has been used to transform the solution crystallization of calcium carbonate to a solidification process of a liquid-phase mineral precursor. In situ observations reveal that polyaspartate induces liquid–liquid phase separation of droplets of a mineral precursor. The droplets deposit on the substrate and coalesce to form a coating, which then solidifies into calcitic tablets and films. Transition bars form during the amorphous to crystalline transition, leading to sectorization of calcite tablets, and the defect textures and crystal morphologies are atypical of solution grown crystals. The formation of nonequilibrium crystal morphologies using an acidic polypeptide may have implications in the field of biomineralization, and the environmentally friendly aspects of this polymer-induced liquid-precursor (PILP) process may offer new techniques for aqueous-based processing of ceramic films, coatings, and particulates. 相似文献
149.
Mathematics and science teacher educators' use of representations of practice: A mixed methods study
Christine K. Austin Karl W. Kosko Jennifer L. Heisler 《School science and mathematics》2023,123(1):14-25
This study sought to explore math and science teacher educators' use of various media to represent practice within methods courses. There is little understanding of why certain media is used over other representations and the rationale for these choices. Specifically, the study focused on the prevalence and familiarity of teacher educators with comics and animations, standard videos, and 360 videos. This mixed methods study utilized a survey and interviews to ascertain math and science teacher educators' level of familiarity and perceived usefulness of representations of practice. Results indicate that standard video is by far the most used representation of practice in methods classes with three themes explaining this finding: access to representations of practice, dimensions of representation, and pertinacity of using representations. Familiarity with representations of practice relates to teacher educators' perceptions of access thereby indicating a need for teacher educators to have better access to representations. Implications of this study include supporting current literature about the relationship between the level of familiarity and perceived usefulness in media along with the potential need for a central platform that houses these representations of practice resources for teacher educators. 相似文献
150.
Francis Austin Wen Sun Xiaoqing Lu 《Communications in Nonlinear Science & Numerical Simulation》2009,14(12):4264-4272
This paper investigates the chaos synchronization of two hyperchaotic systems. Based on Lasalle invariance principle, adaptive schemes are derived to make two unidirectional coupling and mutual coupling hyperchaotic systems asymptotically synchronized whether the parameters are given or uncertain, and unknown parameters are identified simultaneously in the process of synchronization. Numerical simulations of hyperchaotic Chen systems are presented to show the effectiveness of the proposed chaos synchronization schemes. 相似文献