Performance monitoring of a mammalian cell based bioprocess using Raman spectroscopy

Being able to predict the final product yield at all stages in long-running, industrial, mammalian cell culture processes is vital for both operational efficiency, process consistency, and the implementation of quality by design (QbD) practices. Here we used Raman spectroscopy to monitor (in terms of glycoprotein yield prediction) a fed-batch fermentation from start to finish. Raman data were collected from 12 different time points in a Chinese hamster ovary (CHO) based manufacturing process and across 37 separate production runs. The samples comprised of clarified bioprocess broths extracted from the CHO cell based process with varying amounts of fresh and spent cell culture media. Competitive adaptive reweighted sampling (CoAdReS) and ant colony optimization (ACO) variable selection methods were used to enhance the predictive ability of the chemometric models by removing unnecessary spectral information. Using CoAdReS accurate prediction models (relative error of predictions between 2.1% and 3.3%) were built for the final glycoprotein yield at every stage of the bioprocess from small scale up to the final 5000 L bioreactor. This result reinforces our previous studies which indicate that media quality is one of the most significant factors determining the efficiency of industrial CHO-cell processes. This Raman based approach could thus be used to manage production in terms of selecting which small scale batches are progressed to large-scale manufacture, thus improving process efficiency significantly.     

Optimal Groomings with Grooming Ratios Six and Seven

Grooming uniform all‐to‐all traffic in optical (SONET) rings with grooming ratio C requires the determination of a decomposition of the complete graph into subgraphs each having at most C edges. The drop cost of such a grooming is the total number of vertices of nonzero degree in these subgraphs, and the grooming is optimal when the drop cost is minimum. The determination of optimal C‐groomings has been considered for , and completely solved for . For , it has been shown that the lower bound for the drop cost of an optimal C‐grooming can be attained for almost all orders with 5 exceptions and 308 possible exceptions. For , there are infinitely many unsettled orders; especially the case is far from complete. In this paper, we show that the lower bound for the drop cost of a 6‐grooming can be attained for almost all orders by reducing the 308 possible exceptions to 3, and that the lower bound for the drop cost of a 7‐grooming can be attained for almost all orders with seven exceptions and 16 possible exceptions. Moreover, for the unsettled orders, we give upper bounds for the minimum drop costs.     

Forwarding and optical indices of 4-regular circulant networks

An all-to-all routing in a graph G is a set of oriented paths of G, with exactly one path for each ordered pair of vertices. The load of an edge under an all-to-all routing R is the number of times it is used (in either direction) by paths of R, and the maximum load of an edge is denoted by $\pi (G,R)$. The edge-forwarding index $\pi (G)$ is the minimum of $\pi (G,R)$ over all possible all-to-all routings R, and the arc-forwarding index $\overrightarrow{\pi }(G)$ is defined similarly by taking direction into consideration, where an arc is an ordered pair of adjacent vertices. Denote by $w(G,R)$ the minimum number of colours required to colour the paths of R such that any two paths having an edge in common receive distinct colours. The optical index $w(G)$ is defined to be the minimum of $w(G,R)$ over all possible R, and the directed optical index $\overrightarrow{w}(G)$ is defined similarly by requiring that any two paths having an arc in common receive distinct colours. In this paper we obtain lower and upper bounds on these four invariants for 4-regular circulant graphs with connection set $\{\pm 1,\pm s\}$, $1<s<n/2$. We give approximation algorithms with performance ratio a small constant for the corresponding forwarding index and routing and wavelength assignment problems for some families of 4-regular circulant graphs.     

On the induced‐fit mechanism of substrate‐enzyme binding structures of nylon‐oligomer hydrolase

We present a detailed computational investigation of the induced‐fit motion in a nylon‐oligomer hydrolase (NylB) upon substrate binding. To this aim, we resort on the recently introduced parallel cascade selection molecular dynamics approach, allowing for an accelerated access to the set of conformational changes from an open‐ to a closed‐state structure to form the enzyme‐substrate complex in a specific induce‐fit mechanism. The structural investigation is quantitatively complemented by free energy analyses within the umbrella sampling algorithm accompanied by weighted histogram analysis. We find that the stabilization free energy is about 1.4 kcal/mol, whereas the highest free energy barrier to be overcome is about 2.3 kcal/mol. Conversely, the energetic contribution for the substrate binding is about 20 kcal/mol, as estimated from Generalized Born/Surface Area. This means that the open‐close induced‐fit motion could occur frequently once the substrate binds to the open state of NylB. © 2014 Wiley Periodicals, Inc.     

Comprehensive two‐dimensional gas chromatography coupled with static headspace sampling to analyze volatile compounds: Application to almonds

The hyphenation of static headspace sampling with comprehensive 2D GC equipped with a modulator based on capillary flow technology and a flame ionization detector was used to separate and identify 43 representative target volatile compounds (light hydrocarbons, carbonyls, pyrazines, alcohols, furans, and benzenes) frequently detected in the roasting process of nuts. Five column combinations with differing degrees of orthogonality (one conventional and four inverted phase sets) were tested in order to obtain the best conditions for analyzing these volatile compounds. Optimization of the working conditions for each of the different column combinations was performed by means of a central composite design. The best results in terms of separation and differentiation among the different chemical groups were achieved with a combination of inverted phase columns (first dimension: highly polar, INNOWax; second dimension: mid‐polar, ZB‐35). Additionally, a reference template was developed to provide an effective and rapid analysis of the target compounds. Finally, the proposed method was successfully employed to identify volatile compounds in raw and roasted almond samples from the Spanish cultivar Largueta.     

Monolithically integrated 64‐channel silicon hybrid demultiplexer enabling simultaneous wavelength‐ and mode‐division‐multiplexing

A compact 64‐channel hybrid demultiplexer based on silicon‐on‐insulator nanowires is proposed and demonstrated experimentally to enable wavelength‐division‐multiplexing and mode‐division‐multiplexing simultaneously in order to realize an ultra‐large capacity on‐chip optical‐interconnect link. The present hybrid demultiplexer consists of a 4‐channel mode multiplexer constructed with cascaded asymmetrical directional‐couplers and two bi‐directional 17 × 17 arrayed‐waveguide gratings (AWGs) with 16 channels. Here each bi‐directional AWG is equivalent as two identical 1 × 16 AWGs. The measured excess loss and the crosstalk for the monolithically integrated 64‐channel hybrid demultiplexer are about ‐5 dB and ‐14 dB, respectively. Better performance can be achieved by minimizing the imperfections (particularly in AWGs) during the fabrication processes.

     

基于改进免疫遗传算法的近红外光谱变量选择方法

该文在免疫遗传算法（IGA）的基础上,提出一种改进免疫遗传算法（iIGA）用于近红外光谱波长变量的选择。该算法舍去了原算法中固定抗体相似度阈值的思想,取而代之的是抗体相似度阈值自适应,同时引入精英保留策略和贪心算法思想,使得算法朝着正确的方向进行局部性探优。将该算法在玉米的淀粉和蛋白质含量数据集上进行实验测试,建立偏最小二乘（PLS）分析模型,并与IGA、遗传算法（GA）以及全谱方法进行了对比。结果表明,在玉米淀粉含量的预测上,iIGA相较于原IGA算法,预测集均方根误差（RMSEP）从0.312 0降至0.298 0,预测集预测精度提升4.5%;在玉米蛋白质含量的预测上,RMSEP从0.124 4降至0.110 3,预测集预测精度提升11.3%。分别对预测淀粉和蛋白质模型的RMSEP值进行显著性检验,F值分别为165.22和182.05,P值分别为9.5 × 10－23和4.5 × 10－24,P值均小于0.05,因此,iIGA能显著提升模型预测精度。     

An evaluation method for nanoscale wrinkle

In this paper, a spectrum-based wrinkling analysis method via two-dimensional Fourier transformation is proposed aiming to solve the difficulty of nanoscale wrinkle evaluation. It evaluates the wrinkle characteristics including wrinkling wavelength and direction simply using a single wrinkling image. Based on this method, the evaluation results of nanoscale wrinkle characteristics show agreement with the open experimental results within an error of 6%. It is also verified to be appropriate for the macro wrinkle evaluation without scale limitations. The spectrum-based wrinkling analysis is an effective method for nanoscale evaluation, which contributes to reveal the mechanism of nanoscale wrinkling.