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141.
Nathan A. Lacher Rachel K. Roberts Yan He Holly Cargill Katrina M. Kearns Heidi Holovics Margaret N. Ruesch 《Journal of separation science》2010,33(2):218-227
Capillary gel electrophoresis (CGE) methods with UV detection were developed for reduced and non‐reduced mAb analysis. These methods can be used to evaluate mAb purity, offering more reproducible quantitation compared with that of traditional SDS‐PAGE methods. These CGE methods have been utilized as platform technology for bioprocess development, formulation development, mAb characterization, drug substance/drug product release testing as well as a required methodology for stability testing. We have found these CGE methods to be applicable across a platform of mAbs in preclinical and clinical development, with the majority of mAbs requiring no modification to the method conditions. This methodology has been ICH validated and transferred to several supporting organizations. The data presented herein describes the development of CGE methodology, platform application to mAb purity analysis, ICH validation, reliability metrics, and considerations on technology enhancement for improved performance and throughput. 相似文献
142.
Oluwatosin O. Dada Lauren M. Ramsay Jane A. Dickerson Nathan Cermak Rong Jiang Cuiru Zhu Norman J. Dovichi 《Analytical and bioanalytical chemistry》2010,397(8):3305-3310
We report a multiplexed capillary electrophoresis system employing an array of 32 capillaries with a micromachined sheath-flow
cuvette as the detection chamber. The sample streams were simultaneously excited with a 473-nm laser beam, and the fluorescence
emission was imaged on a CCD camera with a pair of doublet achromat lens. The instrument produced mass detection limits of
380 ± 120 yoctomoles for fluorescein in zone electrophoresis. Capillary isoelectric focusing of fluorescent standards produced
peaks with an average width of 0.0029 ± 0.0008 pH. Capillary coating stability limits the reproducibility of the analysis. 相似文献
143.
Uranium-carbon bond reactivity has been investigated with the bis(tethered silylalkyl) uranium metallocene (η5:κ1-C5Me4SiMe2CH2)2U, 1. Tert-butyl nitrile, tBuCN, inserts into both of the tethered U-C bonds to produce the bis(tethered ketimide) complex [η5:κ1-C5Me4SiMe2CH2C(tBu)N]2U, 2, which has unusually bent U-N-C bond angles. Carbon dioxide also inserts into both U-C bonds of 1 yielding the bis(tethered carboxylate) (C5Me4SiMe2CH2CO2)2U, 3. Neither PhCCPh nor PhCCH insert into the U-C bonds, but PhCCH cleaves the silylalkyl tethers in 1 to generate (C5Me4SiMe3)1? ligands in the complex (C5Me4SiMe3)2U(CCPh)2, 4. 相似文献
144.
Biechele TL Camp ND Fass DM Kulikauskas RM Robin NC White BD Taraska CM Moore EC Muster J Karmacharya R Haggarty SJ Chien AJ Moon RT 《Chemistry & biology》2010,17(11):1177-1182
To identify new protein and pharmacological regulators of Wnt/β-catenin signaling, we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the β-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in?vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance β-catenin signaling. The unexpected regulation of β-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug. 相似文献
145.
Nathan A. Lacher Qian Wang Rachel K. Roberts Heidi J. Holovics Serdar Aykent Michael R. Schlittler Melissa R. Thompson Charles W. Demarest 《Electrophoresis》2010,31(3):448-458
A CGE method for monitoring the disulfide isomer distribution characteristic of IgG2 MAbs is presented. Disulfide heterogeneity of MAbs has been studied using various chromatographic and electrophoretic methods. Although CGE operates using a different selectivity mechanism from that of sorption chromatographic techniques, similar trends are present in the data, which allow the CGE method to be used as a complementary method for studying disulfide isomer distribution. This article focuses on the optimization of a capillary‐based gel electrophoresis method that can be used to support antibody development including bioprocess optimization, antibody characterization, release, and formulation stability assessment. 相似文献
146.
On the basis of the extended Huygens-Fresnel principle and the unified theory of coherence and polarization of light we determine the changes in various polarization properties of stochastic beams propagating through the turbulent clear-water ocean. The ocean-induced fluctuations in the refractive index are described via the recently developed power spectrum which takes into account both temperature and salinity variations. Numerical examples of changes in the spectral density, the degree of polarization and in the polarization ellipse are given for electromagnetic Gaussian Schell-model beams. We demonstrate, in particular, how polarization of the propagating beam is affected by statistical properties of the source and by several parameters of oceanic turbulence. We find that propagation of light beams in the oceanic turbulence resembles that in the atmospheric turbulence qualitatively, however evolution and asymptotic saturation of polarization in the oceanic turbulence occurs at much shorter distances. 相似文献
147.
Using a simple discrete laser model that incorporates only gain and loss, we showed that lasers with homogeneous gain can have multiwavelength continuous wave output if the loss element is a saturable transmitter. The intensity-dependent loss provides an adaptive balance to the different gain values at different wavelengths. The output power spectrum of the multiwavelength laser will be flat if the laser operates near a peak of the transmission of the intensity-dependent loss. 相似文献
148.
Photomechanical actuation is demonstrated in two coupled liquid crystal elastomer photomechanical optical devices (PODs) acting in series. The response function of an individual POD is characterized and used to predict the temporal response of the coupled system. The predicted coupled-system response agrees with the experiment for several waveforms and frequencies, suggesting that large-scale integration of photomechanical devices is possible. 相似文献
149.
Nathan Lanfear Raquel M. López Sergei K. Suslov 《Journal of Russian Laser Research》2011,32(4):352-361
We transform the time-dependent Schrödinger equation for the most general variable quadratic Hamiltonians into a standard autonomous form. As a result, the time evolution of exact wave functions of generalized harmonic oscillators is determined in terms of the solutions of certain Ermakov and Riccatitype systems. In addition, we show that the classical Arnold transform is naturally connected with Ehrenfest’s theorem for generalized harmonic oscillators. 相似文献
150.
Yuan J Mei CS Madore B McDannold NJ Panych LP 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2011,210(1):38-43
The purpose of this study is to develop a fast and accurate temperature mapping method capable of both fat suppression and reduced field-of-view (rFOV) imaging, using a two-dimensional spatially-selective RF (2DRF) pulse. Temperature measurement errors caused by fat signals were assessed, through simulations. An 11×1140μs echo-planar 2DRF pulse was developed and incorporated into a gradient-echo sequence. Temperature measurements were obtained during focused ultrasound (FUS) heating of a fat-water phantom. Experiments both with and without the use of a 2DRF pulse were performed at 3T, and the accuracy of the resulting temperature measurements were compared over a range of TE values. Significant inconsistencies in terms of measured temperature values were observed when using a regular slice-selective RF excitation pulse. In contrast, the proposed 2DRF excitation pulse suppressed fat signals by more than 90%, allowing good temperature consistency regardless of TE settings. Temporal resolution was also improved, from 12 frames per minute (fpm) with the regular pulse to 28 frames per minute with the rFOV excitation. This technique appears promising toward the MR monitoring of temperature in moving adipose organs, during thermal therapies. 相似文献