Application of affinity capillary electrophoresis for charge heterogeneity profiling of biopharmaceuticals

Charge heterogeneity profiling is important for the quality control (QC) of biopharmaceuticals. Because of the increasing complexity of these therapeutic entities [1], the development of alternative analytical techniques is needed. In this work, flow‐through partial‐filling affinity capillary electrophoresis (FTPFACE) has been established as a method for the analysis of a mixture of two similar monoclonal antibodies (mAbs). The addition of a specific ligand results in the complexation of one mAb in the co‐formulation, thus changing its migration time in the electric field. This allows the characterization of the charged variants of the non‐shifted mAb without interferences. Adsorption of proteins to the inner capillary wall has been circumvented by rinsing with guanidine hydrochloride before each injection. The presented FTPFACE approach requires only very small amounts of ligands and provides complete comparability with a standard CZE of a single mAb.     

Contrasting Response of Two Dipolar Fluorescence Probes in a Leucine‐Based Organogel and Its Implications

The microenvironments of a leucine‐based organogel are probed by monitoring the fluorescence behavior of coumarin 153 (C153) and 4‐aminophthalimide (AP). The steady‐state data reveals distinctly different locations of the two molecules in the gel. Whereas AP resides close to the hydroxyl moieties of the gelator and engages in hydrogen‐bonding interactions, C153 is found in bulk‐toluene‐like regions. In contrast to C153, AP exhibits excitation‐wavelength‐dependent emission, indicating that the environments of the hydrogen‐bonded AP molecules are not all identical. A two‐component fluorescence decay of AP in gel, unlike C153, supports this model. A time‐resolved fluorescence anisotropy study of the rotational motion of the molecules also reveals the strong association of only AP with the gelator. That AP influences the critical gelation concentration implies its direct involvement in the gel‐formation process. The results highlight the importance of guest–gelator interactions in gels containing guest molecules.     

交互作用偏差对双系统估计量的影响

虽然双系统估计量目前是人口普查质量评估领域估计总体实际人口数的主要方法,但其内在固有的缺陷却依然存在,即由于人口普查与其质量评估调查不独立引起的交互作用偏差使其低估或高估人口数。独立性假设失败源于在普查及其质量评估调查中登记的因果相关性,以及在普查及质量评估调查中登记概率的异质性。Bell模型是当前公认的测算交互作用偏差的有效方法。该方法建立在0-17岁及成年女性的双系统估计值不存在交互作用偏差的假设条件下。利用美国普查局提供的2010年资料全面展示了双系统估计量交互作用偏差的测算过程。实证结果表明,黑人成年男性的双系统估计值存在显著的交互作用偏差。研究有助于我国在未来人口普查质量评估工作中意识到交互作用偏差的存在,把测算的交互作用偏差添加到双系统估计量估计的人口数中,并依据修正后的双系统估计值计算人口普查净误差。     

Dynamics of a Diffusion Malaria Model With Vector-Bias北大核心CSCD

为了探讨季节性、蚊子叮咬的偏好性和人类的扩散对疟疾传播的影响,该文提出了一个部分退化的周期反应扩散模型.利用动力系统的持续性理论,研究了模型关于基本再生数R₀的阈值动力学.即当R₀<1时,疾病灭绝;而当R₀>1时,疾病一致持续,且会发生季节性的流行.数值上发现了忽略空间异质性和蚊子叮咬的偏好性会低估疾病传染的风险.     

Evaluation of defect induced surface heterogeneity in Metal-Organic Framework materials with alkali dopants employing adsorption isotherm modelling

In this article, an assessment of surface structural heterogeneity in porous metal organic framework (MOF) structure has been demonstrated by employing the methane and carbon-dioxide adsorption isotherms data. The virgin MIL-101-(Cr) MOF was synthesized by the hydrothermal method and defects were induced in the MOF structure by doping with various alkali (K, Na, Li) cations. The synthesized MOFs were characterized by XRD, SEM, EDX and BET measurement techniques. In order to understand the defect induced surface heterogeneity by alkali cation dopants, the surface energy distributions for CH₄ and CO₂ adsorptions on MOFs were measured by Dubinin – Astakhov model equation. The surface heterogeneity is mainly controlled by the limiting uptakes of adsorbates, the polarizability of adsorbates and the adsorbate-adsorbent interaction energy.     

软夹硬力学不均匀焊接接头疲劳裂纹闭合行为的实验研究

力学性能不均匀是焊接接头的三大待征之一，本文采用柔度法研究了不同硬夹层宽度的软夹硬力学不均匀焊接接头疲劳裂纹的闭俣行为。研究结果表明，裂纹尖端附近软区的局部屈服在疲劳载荷卸载过程中促使裂纹闭合。随着硬夹层宽度的减小，这一影响越来越明显。     

Multi-Stage Upscaling: Selection of Suitable Methods

Reservoirs are often composed of an assortment of rock types giving rise to permeability heterogeneities at a variety of length-scales. To predict fluid flow at the full-field scale, it is necessary to be aware of these different types of heterogeneity, to recognise which are likely to have important effects on fluid flow, and to capture them by upscaling. In fact, we may require a series of stages of upscaling to go from small-scales (mm or cm) to a full-field model. When there are two (or more) phases present, we also need to know how these heterogeneities interact with fluid forces (capillary, viscous and gravity). We discuss how these effects may be taken into account by upscaling. This study focusses on the effects of steady-state upscaling for viscous-dominated floods and tests carried out on a range of 2D models are described. Upscaling errors are shown to be reduced slightly by the increase in numerical dispersion at the coarse scale. We select a combination of three different upscaling methods, and apply this approach to a model of a North Sea oil reservoir in a deep marine environment. Six different genetic units (rock types) were identified, including channel sandstone and inter-bedded sandstone and mudstone. These units were modelled using different approaches, depending on the nature of the heterogeneities. Our results show that the importance of small-scale heterogeneity depends on the large-scale distribution of the rock types. Upscaling may not be worthwhile in sparsely distributed genetic units. However, it is important in the dominant rock type, especially if there is good connectivity through the unit between the injector wells (or aquifer) and the producer wells.This revised version was published online in May 2005. In the previous version one of the authors name was missing.     

Numerical implementation of composite Koiter shells including membrane/bending coupling coefficientsImplémentation numérique des coques composites de Koiter prenant en considération les coefficients de couplage membrane/flexions

We propose a way for determining the generalized coefficients of rigidity – some of which are membrane/bending coupling coefficients – which appear in the deformation energy of the Koiter model of thin shells. This is concerned with a heterogeneous material in the thickness direction. A new program to compute these coefficients is implemented in the finite element code Modulef, in order to simulate problems of thin multilayered shells with linearly elastic anisotropic layers. We propose an example of an inhibited multilayered thin shell, with hyperbolic middle surface, involving a composite material with unidirectional fibres. To cite this article: H. Ranarivelo, C. R. Mecanique 330 (2002) 273–278.     

Real-Space Renormalization Estimates for Two-Phase Flow in Porous Media

We present a spatial renormalization group algorithm to handle immiscibletwo-phase flow in heterogeneous porous media. We call this algorithmFRACTAM-R, where FRACTAM is an acronym for Fast Renormalization Algorithmfor Correlated Transport in Anisotropic Media, and the R stands for relativepermeability. Originally, FRACTAM was an approximate iterative process thatreplaces the L × L lattice of grid blocks, representing the reservoir,by a (L/2) × (L/2) one. In fact, FRACTAM replaces the original L× L lattice by a hierarchical (fractal) lattice, in such a way thatfinding the solution of the two-phase flow equations becomes trivial. Thistriviality translates in practice into computer efficiency. For N=L ×L grid blocks we find that the computer time necessary to calculatefractional flow F(t) and pressure P(t) as a function of time scales as N^1.7 for FRACTAM-R. This should be contrasted with thecomputational time of a conventional grid simulator N^2.3. The solution we find in this way is an accurateapproximation to the direct solution of the original problem.