Optimization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate bayesian approach

Various approaches have been applied to optimize biological product fermentation processes and define design space. In this article, we present a stepwise approach to optimize a Saccharomyces cerevisiae fermentation process through risk assessment analysis, statistical design of experiments (DoE), and multivariate Bayesian predictive approach. The critical process parameters (CPPs) were first identified through a risk assessment. The response surface for each attribute was modeled using the results from the DoE study with consideration given to interactions between CPPs. A multivariate Bayesian predictive approach was then used to identify the region of process operating conditions where all attributes met their specifications simultaneously. The model prediction was verified by twelve consistency runs where all batches achieved broth titer more than 1.53 g/L of broth and quality attributes within the expected ranges. The calculated probability was used to define the reliable operating region. To our knowledge, this is the first case study to implement the multivariate Bayesian predictive approach to the process optimization for the industrial application and its corresponding verification at two different production scales. This approach can be extended to other fermentation process optimizations and reliable operating region quantitation. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1095–1105, 2012     

Modeling spatially explicit forest structural attributes using Generalized Additive Models

We modelled forest composition and structural diversity in the Uinta Mountains, Utah, as functions of satellite spectral data and spatially‐explicit environmental variables through generalized additive models. Measures of vegetation composition and structural diversity were available from existing forest inventory data. Satellite data included raw spectral data from the Landsat Thematic Mapper (TM), a GAP Analysis classified TM, and a vegetation index based on raw spectral data from an advanced very high resolution radiometer (AVHRR). Environmental predictor variables included maps of temperature, precipitation, elevation, aspect, slope, and geology. Spatially‐explicit predictions were generated for the presence of forest and lodgepole cover types, basal area of forest trees, percent cover of shrubs, and density of snags. The maps were validated using an independent set of field data collected from the Evanston ranger district within the Uinta Mountains. Within the Evanston ranger district, model predictions were 88% and 80% accurate for forest presence and lodgepole pine (Pinus contorta), respectively. An average 62% of the predictions of basal area, shrub cover, and snag density fell within a 15% deviation from the field validation values. The addition of TM spectral data and the GAP Analysis TM‐classified data contributed significantly to the models' predictions, while AVHRR had less significance.     

厚蟹属种群形态量度分析

对天津厚蟹6个种群和侧足厚蟹4个种群的33项形态比例参数进行了多元分析和差异系数(CD)计算。聚类分析没有把天津厚蟹和侧足厚蟹作为2个种分开,而是除侧足厚蟹泉州种群外的9个种群聚类到一起,10个种群之间的欧氏遗传距离也表明它们之间有着较近的亲缘关系。判别分析结果显示,除侧足厚蟹泉州种群(88.9%)和天津厚蟹塘沽种群(75.0%)的判别准确率较高外,其余8个种群的判别准确率均较低,且综合判别准确率仅为63.4%,说明各种群之间的形态差异较小。主成分分析的结果表明,天津厚蟹和侧足厚蟹的10个种群基本重叠在一起,也说明它们之间的形态差异较小。差异系数值均小于亚种分类的阈值1.28。在宁波分布的天津厚蟹和侧足厚蟹种群中出现下眼缘隆脊(突起)介于二者之间的中间过渡类型,提示天津厚蟹和侧足厚蟹可能交配并产生后代。天津厚蟹和侧足厚蟹可能为同一个物种,建议将其作为亚种处理。       

C‐terminal lysine processing of human immunoglobulin G2 heavy chain in vivo

Although human IgG heavy chain genes encode a C‐terminal lysine, this residue is mostly absent from the endogenous antibodies isolated from serum. Some low but variable level of C‐terminal lysine is present on therapeutic antibodies expressed in mammalian cell culture systems. Here, we monitored the C‐terminal lysine processing of a recombinant human IgG2 antibody after intravenous injection into human subjects. Peptide mapping of the therapeutic antibody isolated from serum samples by affinity purification was used to quantify the C‐terminal lysine levels over time in vivo. The C‐terminal lysine residue was found to be rapidly lost in vivo with a half life of about an hour (62 min). In vivo C‐terminal lysine processing could be reproduced in vitro, but at a faster rate, by incubating in human serum. Pretreated serum, under conditions used to inactivate carboxypeptidase U, generated in vitro C‐terminal lysine processing rates that more closely matched those in vivo. Endogenous IgG, isolated from human blood, contained very low levels of C‐terminal lysine (～0.02%), consistent with the expected circulating half life of antibodies and the calculated C‐terminal lysine processing rate. Thus, the low residual IgG2 C‐terminal lysine is rapidly processed in vivo and such processing likely occurs on endogenous antibodies in circulation. Biotechnol. Bioeng. 2011;108: 404–412. © 2010 Wiley Periodicals, Inc.     

Plant functional types and climate in a southern African savanna

Abstract. A system of easily defined plant functional types for a dry savanna is presented and related to climate data. To predict possible changes of vegetation in response to climate change, a system of functional attributes is developed. The attributes are based on both structural and functional characteristics and are chosen to be related to climatic conditions. plant functional types are defined as assemblages of plant species having similar combinations of plant functional attributes. Direct and indirect gradient analyses of a test data set show that the plant functional types as well as the vegetation described from them are strongly associated with total annual precipitation, precipitation of the wettest month and a moisture index (all related to soil moisture) and with temperature of the coldest month.     

贝伐珠单抗生物类似药质量相似性评价探讨*

贝伐珠单抗是研发热度最高的生物类似药之一,在梳理国内23家贝伐珠单抗生物类似药厂家研发数据和原研厂家研究数据的基础上,结合目前国内外生物类似药相关指导原则的理念以及相关文献,从生物类似药相似性评价一般原则、贝伐珠单抗关键质量属性识别和相似性评价几个方面,对贝伐珠单抗生物类似药质量相似性的技术评价要点进行初步探讨。     

An overview of osteoporosis for the practising prosthodontist

doi:10.1111/j.1741‐2358.2009.00324.x
An overview of osteoporosis for the practising prosthodontist Osteoporosis is an insidious and common bone disorder of the modern age, as a result of the rapidly increasing number of older people in the total population. It has long been concluded that this disease has definite deleterious effects on the stomatognathic system and is therefore of major concern to a Prosthodontist. If features on a dental radiograph, which are the most commonly required radiographs, can be detected regularly and consistently, it would place a prosthodontist in a position to refer the patient for timely management and also modify his treatment plan, greatly improving the prognosis. Available literature was therefore reviewed for pathophysiology, dental radiographic screening measures, implications and management of osteoporosis from the perspective of a prosthodontist.     

Assessment of two biomass estimation methods for aquatic vegetation growing on the Amazon Floodplain

Studies of macrophyte productivity in the Amazon region are limited by accessibility and costs; hence, they may suffer from reduced sample size and representation. The present study compares a phenometric (indirect) method and a subsampling (direct) method in terms of accuracy and applicability to estimation of aquatic macrophyte biomass in the Amazon. The results show that phenometric models were not as effective as selective subsampling for the estimation of macrophyte biomass under the studied conditions. Phenometric models performed more acceptably for predicting emergent biomass, and less for submerged and total biomass (r² = 0.77, p < 0.05, RMSE = 200-600 g/m² dry mass). Improvements in r² by using species-specific phenometric models were mostly not significant. Phenotypic variation across the studied region was large enough to preclude the generalization of phenometric relationships into accurate numeric models, while the direct subsampling method was able to account for this variation (RMSE < 500 g/m² dry mass). Subsampling also allowed a significant reduction on the physical effort of biomass sampling, which directly translated into wider and more complete sampling. We suggest that direct subsampling presents the best trade-off between accuracy and coverage for macrophyte biomass measurement in the Amazon floodplain.     

Is abundance a species attribute? An example with haematophagous ectoparasites

Population density is a fundamental property of a species and yet it varies among populations of the same species. The variation comes from the interplay between intrinsic features of a species that tend to produce repeatable density values across all populations of the same species and extrinsic environmental factors that differ among localities and thus tend to produce spatial variation in density. Is inter-population variation in density too large for density to be considered a true species character? We addressed this question using data on abundance (number of parasites per individual host, i.e. equivalent to density) of fleas ectoparasitic on small mammals. The data included samples of 548 flea populations, representing 145 flea species and obtained from 48 different geographical regions. Abundances of the same flea species on the same host species, but in different regions, were more similar to each other than expected by chance, and varied significantly among flea species, with 46% of the variation among samples accounted by differences between flea species. Thus, estimates of abundance are repeatable within the same flea species. The same repeatability was also observed, but to a lesser extent, across flea genera, tribes and subfamilies. Independently of the identity of the flea species, abundance values recorded on the same host species, or in the same geographical region, also showed significant statistical repeatability, though not nearly as strong as that associated with abundance values from the same flea species. There were also no strong indications that regional differences in abiotic variables were an important determinant of variation in abundance of a given flea species on a given host species. Abundance thus appears to be a true species trait in fleas, although it varies somewhat within bounds set by species-specific life history traits.