Design of cell expansion processes for adherent-growing cells with mDoE-workflow

Adherent cells, mammalian or human, are ubiquitous for production of viral vaccines, in gene therapy and in immuno-oncology. The development of a cell-expansion process with adherent cells is challenging as scale-up requires the expansion of the cell culture surface. Microcarrier (MC)-based cultures are still predominate. However, the development of MC processes from scratch possesses particular challenges due to their complexity. A novel approach for the reduction of development times and costs of cell propagation processes is the combination of mathematical process models with statistical optimization methods, called model-assisted Design of Experiments (mDoE). In this study, an mDoE workflow was evaluated successfully for the design of a MC-based expansion process of adherent L929 cells at a very early stage of development with limited prior knowledge. At the start, the analytical methods and the screening of appropriate MCs were evaluated. Then, cause-effect relationships (e.g., cell growth related to medium conditions) were worked out, and a mathematical process model was set-up and adapted to experimental data for modeling purposes. The model was subsequently used in mDoE to identify optimized process conditions, which were proven experimentally. An eight-fold increase in cell yield was achieved basically by reducing the initial MC concentration.     

Alternative reproductive tactics in male freshwater fish influence the accuracy of species recognition

Sexual conflict can result in coercive mating. Because males bear low costs of heterospecific mating, coercive males may engage in misdirected mating attempts toward heterospecific females. In contrast, sexual selection through consensual mate choice can cause mate recognition cues among species to diverge, leading to more accurate species recognition. Some species show both coercive mating and mate choice‐associated courtship behaviors as male alternative reproductive tactics. We hypothesized that if the selection pressures on each tactic differ, then the accuracy of species recognition would also change depending on the mating tactic adopted. We tested this hypothesis in the guppy (Poecilia reticulata) and mosquitofish (Gambusia affinis) by a series of choice experiments. Poecilia reticulata and G. affinis males both showed imperfect species recognition and directed all components of mating behavior toward heterospecific females. They tended to direct courtship displays more frequently toward conspecific than heterospecific females. With male P. reticulata, however, accurate species recognition disappeared when they attempted coercive copulation: they directed coercions more frequently toward heterospecific females. We also found that heterospecific sexual interaction had little effect on the fecundity of gravid females, which suggests that prepregnancy interactions likely underpin the exclusion of G. affinis by P. reticulata in our region.     

一类重随机Poisson过程的等待时间的分布密度公式及其在害虫预测预报中的应用

对具有强度过程λｔ（Ｘ）＝Ｘ＾αＶ（ｔ）（α∈Ｒ＋）的重随机Ｐｏｉｓｓｏｎ过程「Ｎｔ：ｔ≥ｔ０」,推导出其等待时间Ｗｎ的分布密度函数ｆＷｎ（ｔ）的表达式;讨论了进一步推广所得结果的途径;利用所得结果解决了一个预测害虫最适防治时刻的问题。     

Chemically controlled aggregation of pluripotent stem cells

Heterogeneity in pluripotent stem cell (PSC) aggregation leads to variability in mass transfer and signaling gradients between aggregates, which results in heterogeneous differentiation and therefore variability in product quality and yield. We have characterized a chemical‐based method to control aggregate size within a specific, tunable range with low heterogeneity, thereby reducing process variability in PSC expansion. This method enables controlled, scalable, stirred suspension‐based manufacturing of PSC cultures that are critical for the translation of regenerative medicine strategies to clinical products.     

Tracheole migration in an insect wing

Summary Insect tissues are supplied with oxygen by a system of long and highly branched cuticular tubes known as tracheae and tracheoles. During the growth of with imaginal discs in moths and butterflies, tracheole cells migrate distally from the base of the disc. Tracheoles radiate in a distal direction through the extracellular space sandwiched between the upper and lower epithelial surfaces of the wing.Migration of most cells is assumed to be governed by forces intrinsic to the cell. However, the movement of tracheoles is apparently a passive process whose motive force resides in adjacent epithelial cells. After epithelial cells are exposed to ecdysteroid hormones, these cells extend basal processes that are attracted to oxygen-rich tracheoles. By applying traction to the tracheoles with which they establish intimate contact, epithelial cells may control the pattern of their distribution within wing tissue.     

The membrane bioreactor: a novel tool to grow anammox bacteria as free cells

In a membrane bioreactor (MBR), fast growth of anammox bacteria was achieved with a sludge residence time (SRT) of 12 days. This relatively short SRT resulted in a--for anammox bacteria--unprecedented purity of the enrichment of 97.6%. The absence of a selective pressure for settling, and dedicated cultivation conditions led to growth in suspension as free cells and the complete absence of flocs or granules. Fast growth, low levels of calcium and magnesium, and possibly the presence of yeast extract and a low shear stress are critical for the obtainment of a completely suspended culture consisting of free anammox cells. During cultivation, a population shift was observed from Candidatus "Brocadia" to Candidatus "Kuenenia stuttgartiensis." It is hypothesized that the reason for this shift is the higher affinity for nitrite of "Kuenenia." The production of anammox bacteria in suspension with high purity and productivity makes the MBR a promising tool for the cultivation and study of anammox bacteria.     

What can observational data reveal about metacommunity processes?

A key challenge for community ecology is to understand to what extent observational data can be used to infer the underlying community assembly processes. As different processes can lead to similar or even identical patterns, statistical analyses of non‐manipulative observational data never yield undisputable causal inference on the underlying processes. Still, most empirical studies in community ecology are based on observational data, and hence understanding under which circumstances such data can shed light on assembly processes is a central concern for community ecologists. We simulated a spatial agent‐based model that generates variation in metacommunity dynamics across multiple axes, including the four classic metacommunity paradigms as special cases. We further simulated a virtual ecologist who analysed snapshot data sampled from the simulations using eighteen output metrics derived from beta‐diversity and habitat variation indices, variation partitioning and joint species distribution modelling. Our results indicated two main axes of variation in the output metrics. The first axis of variation described whether the landscape has patchy or continuous variation, and thus was essentially independent of the properties of the species community. The second axis of variation related to the level of predictability of the metacommunity. The most predictable communities were niche‐based metacommunities inhabiting static landscapes with marked environmental heterogeneity, such as metacommunities following the species sorting paradigm or the mass effects paradigm. The most unpredictable communities were neutral‐based metacommunities inhabiting dynamics landscapes with little spatial heterogeneity, such as metacommunities following the neutral or patch sorting paradigms. The output metrics from joint species distribution modelling yielded generally the highest resolution to disentangle among the simulated scenarios. Yet, the different types of statistical approaches utilized in this study carried complementary information, and thus our results suggest that the most comprehensive evaluation of metacommunity structure can be obtained by combining them.     

Performance evaluation of fault detection methods for wastewater treatment processes

Several methods to detect faults have been developed in various fields, mainly in chemical and process engineering. However, minimal practical guidelines exist for their selection and application. This work presents an index that allows for evaluating monitoring and diagnosis performance of fault detection methods, which takes into account several characteristics, such as false alarms, false acceptance, and undesirable switching from correct detection to non-detection during a fault event. The usefulness of the index to process engineering is demonstrated first by application to a simple example. Then, it is used to compare five univariate fault detection methods (Shewhart, EWMA, and residuals of EWMA) applied to the simulated results of the Benchmark Simulation Model No. 1 long-term (BSM1_LT). The BSM1_LT, provided by the IWA Task Group on Benchmarking of Control Strategies, is a simulation platform that allows for creating sensor and actuator faults and process disturbances in a wastewater treatment plant. The results from the method comparison using BSM1_LT show better performance to detect a sensor measurement shift for adaptive methods (residuals of EWMA) and when monitoring the actuator signals in a control loop (e.g., airflow). Overall, the proposed index is able to screen fault detection methods.