A Residue-specific Shift in Stability and Amyloidogenicity of Antibody Variable Domains

Variable (V) domains of antibodies are essential for antigen recognition by our adaptive immune system. However, some variants of the light chain V domains (V_L) form pathogenic amyloid fibrils in patients. It is so far unclear which residues play a key role in governing these processes. Here, we show that the conserved residue 2 of V_L domains is crucial for controlling its thermodynamic stability and fibril formation. Hydrophobic side chains at position 2 stabilize the domain, whereas charged residues destabilize and lead to amyloid fibril formation. NMR experiments identified several segments within the core of the V_L domain to be affected by changes in residue 2. Furthermore, molecular dynamic simulations showed that hydrophobic side chains at position 2 remain buried in a hydrophobic pocket, and charged side chains show a high flexibility. This results in a predicted difference in the dissociation free energy of ∼10 kJ mol⁻¹, which is in excellent agreement with our experimental values. Interestingly, this switch point is found only in V_L domains of the κ family and not in V_Lλ or in V_H domains, despite a highly similar domain architecture. Our results reveal novel insight into the architecture of variable domains and the prerequisites for formation of amyloid fibrils. This might also contribute to the rational design of stable variable antibody domains.     

液滴微流控芯片系统中微液滴特性表征及氨基酸检测应用

基于液滴微流控芯片的检测和筛选系统,因其具有通量高、成本低等显著特点,近年来备受关注。该系统生成的微液滴(皮升体积)具有直径均一、大小可控、互不交融(单分散性)等特性,它作为微反应器可以进行微生物及其代谢物包埋实验和高通量检测。因此,研究微液滴的相关特性及其应用具有重要意义。文中在液滴微流控芯片系统搭建的基础上,对重要氨基酸(谷氨酸、苯丙氨酸、色氨酸和酪氨酸)分别进行了微液滴包埋实验,研究了包埋微液滴的重要特性参数(如稳定性、扩散性等),探索了包埋微液滴对氨基酸检测分选的应用。实验表明,文中搭建的液滴微流控芯片系统可以稳定、均一地生成微液滴,微液滴大小可根据需要控制在2 0-5 0μm之间,微液滴间无交叉污染,包埋氨基酸的微液滴的检测筛选速度大约为每分钟6 0 0个。这个研究为高通量分析和筛选产氨基酸的微生物奠定了基础。     

Prediction of diffusion coefficients of plasmids

The ability to predict diffusion coefficients is important in the design, analysis, and operation of plasmid downstream processing operations such as membrane and fixed-bed chromatography. A correlation is proposed to predict the diffusion coefficient, D, of supercoiled plasmid DNA molecules in dilute solutions on the basis of the molecular weight, M, or size. Experimental data (18 points) collected from the literature confirmed the proposed variation of D with plasmid molecular weight as D proportional, variant M(-2/3), for molecules within the 1,800-287,100 base-pair range. The correlation was able to estimate the available experimental results with an average error of 6.3%.     

A note on path-based variable selection in the penalized proportional hazards model

We propose an efficient and adaptive shrinkage method for variableselection in the Cox model. The method constructs a piecewise-linearregularization path connecting the maximum partial likelihoodestimator and the origin. Then a model is selected along thepath. We show that the constructed path is adaptive in the sensethat, with a proper choice of regularization parameter, thefitted model works as well as if the true underlying submodelwere given in advance. A modified algorithm of the least-angle-regressiontype efficiently computes the entire regularization path ofthe new estimator. Furthermore, we show that, with a properchoice of shrinkage parameter, the method is consistent in variableselection and efficient in estimation. Simulation shows thatthe new method tends to outperform the lasso and the smoothly-clipped-absolute-deviationestimators with moderate samples. We apply the methodology todata concerning nursing homes.     

Modeling of glycerol production by fermentation in different reactor states

A kinetic model of glycerol production by fermentation with the osmophilic yeast Candida krusei was studied firstly by analogies to published works. Considering that the glycerol produced competes with glucose, as a second carbon source for energy maintenance, mathematical models of glucose utilization and glycerol accumulation were modified further. By adjusting only two variable macrokinetic parameters, K_S and β, the model simulations could fit experimental data well when the reactor was changed from Airlift Loop Reactor in different scale or airlift mode to Stirred Vessel. To avoid a significant reduction in glycerol production in the latter fermentation stage, the final condition of the fermentation, determined by the concentration ratio of glycerol to glucose, was also investigated in four different Reactor States. The kinetic models and simulation results can provide certain reference for scale up of glycerol production by fermentation.     

中国森林生物量的估算：对Fang et al.

 Science杂志于2001年发表了方精云等人关于中国森林植被碳库及其变化的论文(Fang et al., 2001, 291: 2320～2322)。该文利用大量的生物量实测数据,结合使用中国50年来的森林资源清查资料及相关的统计资料,基于生物量换算因子连续函数法,研究了中国森林植被碳库及其时空变化。这是一个大时空尺度的工作,涉及一些大尺度生态学研究的原理、方法以及尺度转换问题。由于篇幅所限,论文并未详细说明这些问题。为了帮助理解大尺度生态学研究的方法和思路,本文给出了论文中涉及生物量计算的理论基础,对     

逐步对应分析及中国少数民族人群体态特征研究

介绍了逐步对应分析方法,给出了变量选择和误差估计的标准,并分析了中国26个少数民族人群体态特征。     

Implementing Probabilistic Risk Assessment in USEPA Superfund Program

Application of probabilistic risk analysis to human health and ecological risk assessment is a young science. Probabilistic risk assessment (PRA), as exemplified by Monte Carlo Analysis (MCA), is more suitable to quantify the confidence or level of uncertainty in risk estimates compared with the traditional point estimate approach. Within the United States Environmental protection Agency (USEPA) the Office of Emergency and Remedial Response (OERR) is implementing PRA as part of the Superfund administrative reform activities. The OERR is completing a guidance document accompanied by a workbook. OERR is continuing its outreach effort to present PRA to the public and USEPA staff, and is organizing a training course. This paper presents an overview of the OERR's PRA implementation effort to date.     

ChooseMaterials.pl，控制变量挑选实验材料的perl脚本

用Perl语言编写了一个脚本--ChooseMaterials．pl,通过计算两个材料特定某几列数据之间增加或减少的百分数水平,达到控制变量突出关键因子的作用,方便生物学工作者选取材料,做进一步的实验或分析。