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Contamination of therapeutic human immunoglobulin preparations with apolipoprotein H (β2‐glycoprotein I) 下载免费PDF全文
Friedrich Lackner Gerhard Beck Stephanie Eichmeir Manfred Gemeiner Karin Hummel Dieter Pullirsch Ebrahim Razzazi‐Fazeli Alexandra Seifner Ingrid Miller 《Electrophoresis》2014,35(4):515-521
Polyclonal immunoglobulin (Ig) concentrates are important biological medicinal products and the assurance of their quality and safety is crucial. In our present approach we used proteomic methods to check the purity of commercial Ig products of different origin. The experimental setup included nonreducing 2DE or DIGE combined with MALDI‐TOF and the thrombin generation assay, a routine safety test for pharmaceutical Ig preparations, and was complemented by a specific immunoassay. 2DE patterns displayed contaminations with trace amounts of human apolipoprotein H (Apo‐H), transferrin, albumin, and its fragments. In contrast to the latter, Apo‐H is a protein that is active in the coagulation cascade, and thus a potential involvement in thromboembolic events in vivo cannot be excluded. It was found by 2DE and MALDI‐TOF to be a contaminant of several Ig preparations. Spiking experiments of Ig preparations with pure Apo‐H demonstrated an Apo‐H concentration dependent increase in thrombin generation assay values. Traces of Apo‐H are possibly also contributing to unwanted side effects, as already known for factor XIa. The significance of Apo‐H contaminations for these side effects might be verified by detailed analyses of pharmacovigilance data. 相似文献
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Xiayi Hu Enzo Mangano Daniel Friedrich Hyungwoong Ahn Stefano Brandani 《Adsorption》2014,20(1):121-135
A systematic study of the diffusion mechanism of CO2 in commercial 13X zeolite beads is presented. In order to gain a complete understanding of the diffusion process of CO2, kinetic measurements with a zero length column (ZLC) system and a volumetric apparatus have been carried out. The ZLC experiments were carried out on a single bead of zeolite 13X at 38 °C at a partial pressure of CO2 of 0.1 bar, conditions representative of post-combustion capture. Experiments with different carrier gases clearly show that the diffusion process is controlled by the transport inside the macropores. Volumetric measurements using a Quantachrome Autosorb system were carried out at different concentrations. These experiments are without a carrier gas and the low pressure measurements show clearly Knudsen diffusion control in both the uptake cell and the bead macropores. At increasing CO2 concentrations the transport mechanism shifts from Knudsen diffusion in the macropores to a completely heat limited process. Both sets of experiments are consistent with independent measurements of bead void fraction and tortuosity and confirm that under the range of conditions that are typical of a carbon capture process the system is controlled by macropore diffusion mechanisms. 相似文献
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The fitting of finite mixture models is an ill-defined estimation problem, as completely different parameterizations can induce similar mixture distributions. This leads to multiple modes in the likelihood, which is a problem for frequentist maximum likelihood estimation, and complicates statistical inference of Markov chain Monte Carlo draws in Bayesian estimation. For the analysis of the posterior density of these draws, a suitable separation into different modes is desirable. In addition, a unique labelling of the component specific estimates is necessary to solve the label switching problem. This paper presents and compares two approaches to achieve these goals: relabelling under multimodality and constrained clustering. The algorithmic details are discussed, and their application is demonstrated on artificial and real-world data. 相似文献
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