有关生物技术成果转化的调查研究(上)

本文通过对中国科学院等研究机构的生物技术研究人员进行问卷调查,定性的描述了目前生物技术成果转化的总体状况和存在问题,运用相关统计分析方法阐明阻碍成果转化的因素及其结构,并提出相关解决策略 。     

Microbial 2,3-butanediol production: a state-of-the-art review

2,3-Butanediol is a promising bulk chemical due to its extensive industry applications. The state-of-the-art nature of microbial 2,3-butanediol production is reviewed in this paper. Various strategies for efficient and economical microbial 2,3-butanediol production, including strain improvement, substrate alternation, and process development, are reviewed and compared with regard to their pros and cons. This review also summarizes value added derivatives of biologically produced 2,3-butanediol and different strategies for downstream processing. The future prospects of microbial 2,3-butanediol production are discussed in light of the current progress, challenges, and trends in this field. Guidelines for future studies are also proposed.     

单克隆抗体生产过程中二硫键还原成因及预防方法

单克隆抗体生产过程中二硫键的还原是生物制药领域中的一个常见技术难题,可产生低分子量碎片,影响产品质量,导致蛋白纯度降低、稳定性下降,影响药物的安全性和有效性。抗体二硫键还原实质上是由细胞内的硫氧还蛋白系统和谷胱甘肽系统引起的可逆氧化还原反应,并与具体生产过程参数有关。近年来,随着抗体药物和哺乳动物细胞培养工艺规模的发展,二硫键还原问题频繁发生。为解决此问题,研究人员不断尝试并建立了多种预防方法以保证产品质量。概述了抗体二硫键结构、二硫键还原的主要成因及生产过程中的形成因素,重点阐述了消除或减缓抗体二硫键还原的方法、对策,并列举了几种可行的过程分析技术,以期为单克隆抗体药物生产制造工艺的进一步优化提供参考。     

Gene microarray analysis of expression profiles in Suberoyllanilide hyroxamic acid-treated Dendritic cells

Objective

The purpose of this study is to provide a further theoretical basis for the role of Suberoyllanilide hyroxamic acid (SAHA) affect on Dendritic cells (DCs).

基于分布式水文模型的水源涵养不同功能评估方法——以渭河涵养区为例

为了实现水源涵养量计算和不同功能的综合评估,基于分布式水文模型(WEP-L)提出了一种新方法,即利用WEP-L模型计算次降水过程中降水量和地表产流、冠层截留量的差值作为水源涵养量,并分别评估削洪(地表径流量)、补枯(地下径流量)、维持植被生态系统用水(植被蒸腾量)等不同水源涵养功能的评估方法。为了验证该方法的合理性,以渭河流域咸阳站以上区域为例,对比了该方法和InVEST模型方法的计算结果,由于两种方法在评估内容和使用模型上都存在差异,为了保证计算结果的可比性,先对比了基于相同评价内容的WEP-L模型法I和InVEST模型方法,再对比了基于不同评价内容的WEP-L模型法I和WEP-L模型法II,结论如下:基于相同评价内容的WEP模型法I和InVEST模型法计算结果数值接近,研究区2000-2018年水源涵养量年均值分别为12.43 mm(5.76亿m³)和12.08 mm(5.6亿m³),两种方法所得结果空间分布特征相似,稍有差异之处与InVEST模型的参数没有经过本地化处理有关;基于不同评价内容的WEP-L模型法Ⅰ和WEP-L模型法II计算结果数值相差较大,研究区2000-2018年水源涵养量均值分别为12.43 mm和432.57 mm,空间分布特征上有差异的地方分布于研究区的北部、东部及东北部,主要与两种方法评价时是否考虑蒸散发有关。WEP-L模型法II评估结果中削洪、补枯、维持植被生态系统用水等功能多年变化趋势分别为:2006-2010年期间增加、2012年以后下降以及增加。2012年后补枯功能和维持植被生态系统用水功能之间可能存在权衡关系。通过不同方法计算结果差异原因分析,证明了基于WEP-L模型的不同涵养功能评估方法的合理性,其结果也可为渭河涵养区水资源和生态保护策略的制定提供更多依据。     

Bacterial populations on brewery filling hall surfaces as revealed by next-generation sequencing

Due to the presence of moisture and nutrients, brewery filling line surfaces are susceptible to unwanted microbial attachment. Knowledge of the attaching microbes will aid in designing hygienic control of the process. In this study the bacterial diversity present on brewery filling line surfaces was revealed by next generation sequencing. The two filling lines studied maintained their characteristic bacterial community throughout three sampling times (13–163 days). On the glass bottle line, γ-proteobacteria dominated (35–82% of all OTUs), whereas on the canning line α-, β- and γ-proteobacteria and actinobacteria were most common. The most frequently detected genera were Acinetobacter, Propinobacterium and Pseudomonas. The halophilic genus Halomonas was commonly detected, which might be due to its tolerance to alkaline foam cleaners. This study has revealed a detailed overall picture of the bacterial groups present on filling line surfaces. Further effort should be given to determine the efficacy of washing procedures on different bacterial groups.     

Utility of Expert-Based Knowledge for Predicting Wildlife-Vehicle Collisions

ABSTRACT Wildlife-vehicle collisions have important ecological, economic, and social effects. In North America and across northern Europe, moose (Alces alces) are one of the largest ungulates hit by motor vehicles. The force and increasing frequency of these collisions has resulted in a commitment by wildlife and transportation agencies to limit or reduce causal factors. In an effort to improve these mitigation strategies, we used the most readily available source of knowledge of collision factors, expert opinion, to develop a series of models that explained and predicted location of moose-vehicle collisions (MVC). We developed expert-based models using the Analytical Hierarchy Process (AHP) and we used a structured survey approach where experts could assess criteria relevancy, weight criteria, and review weights for consistency. We hypothesized that collisions were the product of habitat- or driver-related factors and we formulated the survey accordingly. We used the receiver operating characteristic to validate the resulting models and the Kappa index of agreement to quantify differences among spatial predictions originating from the experts. Local and nonlocal experts weighted the moose habitat classification as the most important criterion for identifying MVC. Among driver-related criteria, speed limit was weighted as the most important factor. Overall, habitat-based models were more proficient than driver-based models in predicting MVC within Mount Revelstoke and Glacier National Parks, Canada. Both local and nonlocal expert models were excellent predictors of MVC, with local experts slightly outperforming nonlocal experts. Considering that habitat-related criteria were more powerful for predicting MVC, and that habitat can vary considerably across study areas, we suggest that local experts be used when possible. The AHP is a valuable tool for wildlife, highway, and park managers to better understand why and where wildlife-vehicle collisions occur. Adopting this process, our data suggested that MVC were most strongly correlated with highway attractants associated with habitat. Vegetation management or alternative routing could minimize spatial juxtaposition of moose and motor vehicles.     

Ranking the indicators of building performance and the users’ risk via Analytical Hierarchy Process (AHP): Case of Malaysia

The need to optimise the performance of buildings has increased consequently due to the expansive supply of facilities in higher education building (HEB). Hence, a proper performance assessment as a proactive measure may help university building in achieving performance optimization. However, the current maintenance programs or performance evaluation in the HEB is a systemic and cyclic process where maintenance is considered as an operational issue and not as opposed to a strategic issue. Hence, this paper proposed a Building Performance Risk Rating Tool (BPRT) as an improved measure for building performance evaluation by addressing the users' risk in health and safety aspects. The BPRT was developed from the result of a rating index using the Analytical Hierarchy Process (AHP) method. A total of 12 facilities management (FM) experts and practitioners were involved in the rating process. The subjective weightings were analysed by using the AHP computer software programme, the Expert Choice 11. The result of the AHP had successfully assigned weighting scores to all performance-risk indicators, with five indicators ranked as the most critical indicators; structural stability (14.9%), fire prevention services (9.1%), building-related illnesses (7.4%), emergency exits (6.8%), and electrical services (6.3%). The final indication to the assessed building using the BPRT provided a rating classification in terms of the following: “Excellent”, “Good”, “Medium”, “Low”, or “Poor”, which suggested further actions to improve the performance of the building, as well as to mitigate the users’ health and safety risks. Hence, the establishment of the BPRT was successfully employed as an aid of improvement towards the current performance assessment of HEB by emerging the concept of building performance and risk into a numerical strategic approach.     

Process analytical technology tools for perfusion cell culture

During cell cultivation processes for the production of biopharmaceuticals, good process performance and good product quality can be ensured by online monitoring of critical process parameters (e.g. temperature, pH, or dissolved oxygen). These data can be used in real‐time for process control, as suggested by the process analytical technology (PAT) initiative. Today, solutions for real‐time monitoring of parameters such as concentrations of cells, main nutrients, and metabolism by‐products are developing, but applications of these more complex tools in industrial settings are still limited. Here, we evaluated the use of dielectric spectroscopy (DS) and near‐infrared spectroscopy (NIRS) as PAT tools for a perfusion PER.C6^® cultivation process. We showed that DS enabled predictions of viable cell density from the cultivation vessel, with a root mean square error of prediction (RMSEP) of 4.4% of the calibration range. Additionally, predictions of glucose and lactate concentrations from the cultivation vessel (RMSEP of 10 and 14%, respectively) and from the perfusion stream (RMSEP of 12 and 10%, respectively) were achieved with NIRS. We also showed that the perfusion stream offers great opportunities for noninvasive, yet frequent process monitoring. Accurate online monitoring of critical process parameters with PAT tools is the essential first step toward increased control of process output.