生理房室药动学模型

生理药动学模型较ｎ房室模型能更准确地描述药物在体内的处置过程,但在实际应用中由于其计算结果有较大的误差而限制其应用和推广．在生理模型中,某一组织器官中血液分布容积相对于单位时间的血流量来说,如果太大,就去给计算结果带来较大的误差．本文提出的生理房室模型可以减小这种误差,从而更准确地模拟药物在体内的处置过程．文中对一组模拟的生理和生化参数分别求出了生理房室模型和生理模型的数值解．通过两组解的比较,说明生理房室模型可以描述药物在体内处置过程中的细微变化．     

利用制糖废蜜流加培养酵母的动力学研究

研究了以廉价原料糖蜜流加培养酵母的生产工艺,确定了最佳工艺参数,并根据酵母在流加培养过程中比生长速率和耗糖速率的变化,对动态的糖流加工艺进行研究,得出了流加培养的动力学模型,然后通过流加培养过程中实际糖流加曲线对所提出的模型进行验证。研究结果表明,流加培养模型能较好地反映酵母流加培养过程中糖流加的规律,对酵母的流加培养具有一定的指导意义。     

双碳源单细胞蛋白间歇培养及流加培养的动力学模型

应用非结构的逻辑增殖模型研究了两种酵母的单碳源和双碳源单细胞蛋白间歇培养的动力学,用改进的逻辑增殖模型研究了双碳源流加培养过程的动力学,从实验数据拟合了动力学模型参数,模型计算值与实验数据吻合良好。     

遗传算法优化真菌深层培养过程神经网络模型物的研究

提出一种简单的真菌深层培养过程网络模型。输入变量为可在线测量的排气中的二氧化碳浓度,网络权数采用遗传算法进行优化训练。所获神经网络模型能准确预测培养过程的状态变量。研究表明遗传算法训练此类神经网络系统是可行的。     

微囊化K562细胞生长周期及代谢特性的研究

以K562细胞为模型,分别进行微囊化和游离培养,运用流式细胞术考察两种培养体系下细胞周期和生长代谢变化;建立数学模型,模拟了两种培养体系下细胞的生长活性和代谢特性。实验发现：微囊化培养过程中的K562细胞处于DNA合成期（S期）的百分含量显著高于游离培养,并且细胞保持较高的增殖活性。模型计算表明,所建模型动力学参数能够很好地描述微囊化和游离两种培养体系下细胞的代谢情况;对细胞活性的理论计算表明,微囊化的细胞具有较高的增殖和代谢活性,同时细胞能够较长时间保持此活性;模型参数表明,两种培养体系下,葡萄糖对细胞生长的影响无显著差别 (k^Free_L≈k^APA_L),乳酸对游离培养细胞的生长具有明显抑制作用,但对微囊化培养细胞抑制作用较小(kFreeL>≈kAPAL)。     

灰树花深层培养的生长动力学与计算机模拟

研究了灰树花的生长特性,建立了灰树花的生长速率模型和基质消耗动力学模型;并运用SIMULINK仿真环境,建立了灰树花在培养过程中的主要因素通气量和pH对菌丝生物影响的模型,结果表明,模拟结果较理想。     

遗传算法优化真菌深层培养过程神经网络模型的研究

提出一种简易的真菌深层培养过程网络模型。输入变量为可在线测量的排气中的二氧化碳浓度,网络权数采用遗传算法进行优化训练。所获神经网络模型能准确预测培养过程的状态变量(生物量浓度,产物浓度等)。研究表明遗传算法训练此类神经网络系统是可行的。     

毕克卷转虫Ammonia beccarii(Linnaeus,1758)的室内培养:温度和食物浓度对房室生长和摄食硅藻的影响

毕克卷转虫Ammonia beccarii(Linnaeus,1758)是潮间带和陆架浅海沉积物中常见的底栖有孔虫类群,但因活体培养困难,国际间对其基础生物学研究甚少。本工作成功对A.beccarii建立了室内培养,采用食物移除法测定其对硅藻的摄食率,探讨了温度和食物浓度对其房室生长和摄食率的影响。实验显示A.beccarii成体每次繁殖可产生约50—100个子代幼体,2个月左右完成2个壳圈(约15个房室)的生长,达到成体的3—4个壳圈(20个房室以上)约需3—5个月。此外,A.beccarii的房室生长受不同培养温度的影响,20°C下房室长径和短径的增长皆快于15°C:15°C长、短径的平均增长率分别为0.99、0.93μm d-1;20°C壳体长、短径的平均增长率分别为2.21、2.10μm d-1,温度较低时壳体生长呈常见的椭圆形体态,温度升高壳体较大且胖圆。在温度为12、15、18、21、24°C和硅藻浓度200—1 000cells mm-2的培养条件下,A.beccarii的摄食率对硅藻浓度的响应模型各参数均有统计显著性,最大摄食率(Imax)和半饱和食物浓度(k)均随温度的升高而降低。随着温度的升高,Imax由12°C的1 014.23diatoms ind.-1 h-1降低到24°C时的656.26diatoms ind.-1 h-1,k由195.77diatoms mm-2降低到92.65diatoms mm-2,摄食率(I)的变化范围约为50—1 000diatom ind.-1 h-1。推测12—15°C可能为A.beccarii的最适温度范围,此温度也与野外调查黄、东海陆架表层沉积物中A.beccarii的丰度分布高值时的环境温度区间相符。本研究结果显示A.beccarii在海洋底栖生态系统中对摄食藻类具有一定的生态学功能,并具有喜好低温的特性。     

表达TNFR-Fc融合蛋白的GS-CHO细胞动态流加培养过程的设计

人肿瘤坏死因子受体Ⅱ-Fc融合蛋白在治疗风湿性、类风湿性关节炎方面拥有广阔的市场前景和巨大的经济价值。本实验以表达TNFR-Fc融合蛋白的GS-CHO细胞为研究对象,结合细胞生长代谢特性和动力学参数分析,以葡萄糖为关键控制参数,通过测定培养上清的葡萄糖浓度对培养过程中的葡萄糖消耗进行及时的预测,调整流加速率,形成了以满足细胞生长代谢需要为基本原则的动态流加培养过程设计模型。在此控制模型指导下,建立了高效的流加培养过程。使最大活细胞密度和最大融合蛋白浓度分别达9.4×106cells/mL和207mg/L,较批次培养分别提高了3.4倍和3倍。本研究所采用的研究方法和控制策略为优化GS-CHO细胞培养过程和TNFR-Fc融合蛋白成功迈向产业化奠定了基础。     

悬浮培养玫瑰茄细胞的生长行为及动力学方程的建立

以培养多年的玫瑰茄（Hibiscus sabdariffaL.)白色细胞株为材料,在以3％蔗糖为碳源,植物生长调节剂为4．5μmol/L2,4-D（2,4－二氯苯氧乙酸）,2．3μmol/L Kt（Kinetin,细胞激动素）的悬浮培养条件下,研究了玫瑰茄细胞的生长及泛醌积累动态、培养液PH值的变化以及培养过程中玫瑰茄细胞对碳源、氮源、磷源的消耗动态,并以此数据建立了悬浮培养玫瑰茄细胞的生长、蔗糖消耗、泛醌形成的非结构动力学模型,经验证表明,模型与实际情况有较高的拟合度。     

Compartmental culture of embryonic stem cell-derived neurons in microfluidic devices for use in axonal biology

Axonal pathology has been clearly implicated in neurodegenerative diseases making the compartmental culture of neurons a useful research tool. Primary neurons have already been cultured in compartmental microfluidic devices but their derivation from an animal is a time-consuming and difficult work and has a limit in their sources. Embryonic stem cell (ESC)-derived neurons (ESC_Ns) overcome this limit, since ESCs can be renewed without limit and can be differentiated into ESC_Ns by robust and reproducible protocols. In this research, ESC_Ns were derived from mouse ESCs in compartmental microfluidic devices, and their axons were isolated from the somal cell bodies. Once embryoid bodies (EBs) were localized in the microfluidic culture chamber, ESC_Ns spread out from the EBs and occupied the cell culture chamber. Their axons traversed the microchannels and finally were isolated from the somata, providing an arrangement comparable to dissociated primary neurons. This ESC_N compartmental microfluidic culture system not only offers a substitute for the primary neuron counterpart system but also makes it possible to make comparisons between the two systems.     

Activity of Pseudomonas aeruginosa in biofilms: Steady state

Aerobic glucose metabolism by Pseudomonas aeruginosa in steady-state biofilms at various substrate loading rates and reactor dilution rates was investigated. Variables monitored were substrate (glucose), biofilm cellular density, biofilm extracellular polymeric substance (EPS) density, and suspended cellular and EPS concentrations. A mathematical model developed to describe the system was compared to experimental data. Intrinsic yield and rate coefficients included in the model were obtained from suspended continuous culture studies of glucose metabolism by P. aeruginosa. Experimental data compared well with the mathematical model, suggesting that P. aeruginosa does not behave differently in steady-state biofilm cultures, where diffusional resistance is negligible, than in suspended cultures. This implies that kinetic and stoichiometric coefficients for P. aeruginosa derived in suspended continuous culture can be used to describe steady-state biofilm processes.     

Artificial neural network modelling of a large-scale wastewater treatment plant operation

Artificial Neural Networks (ANNs), a method of artificial intelligence method, provide effective predictive models for complex processes. Three independent ANN models trained with back-propagation algorithm were developed to predict effluent chemical oxygen demand (COD), suspended solids (SS) and aeration tank mixed liquor suspended solids (MLSS) concentrations of the Ankara central wastewater treatment plant. The appropriate architecture of ANN models was determined through several steps of training and testing of the models. ANN models yielded satisfactory predictions. Results of the root mean square error, mean absolute error and mean absolute percentage error were 3.23, 2.41 mg/L and 5.03% for COD; 1.59, 1.21 mg/L and 17.10% for SS; 52.51, 44.91 mg/L and 3.77% for MLSS, respectively, indicating that the developed model could be efficiently used. The results overall also confirm that ANN modelling approach may have a great implementation potential for simulation, precise performance prediction and process control of wastewater treatment plants.     

Mathematical modelling of immunity to malaria

A comparison of two epidemiological models of immunity to malaria shows that different characterizations of immunity boosted by exposure to infection generate qualitatively different results. Attempts to control disease by reducing transmission or increasing the recovery rate can produce an increase in prevalence in the compartmental model with discrete epidemiological states. However, the parasite density always decreases in response to disease control in the model with continuous epidemiological variables. Each model accounts for some epidemiological patterns. The increase in prevalence seen in the compartmental model is in accord with observed effects of variation in transmission. Parasite suppression in areas of antimalarial drug use is consistent with the effect of an increased recovery rate in the density model. Future work should combine the two approaches, perhaps by using the compartmental model over the low to moderate range of infection rates and switching to the density model at high infection rates. In any case, the validation of models needs to take account of the usage of antimalarial drugs as well as the intensity of transmission.     

On stochastic compartmental modeling

This communication contains a proof of the fact that the coefficient of variation of the contents of a compartment of a stochastic compartmental model with deterministic rate parameters is small for large populations. We can therefore conclude that the use of stochastic compartmental models is not of great consequence in the case of systems involving large populations when only the randomness of the transfer mechanism is considered.     

Indistinguishability and identifiability analysis of linear compartmental models.

Two compartmental model structures are said to be indistinguishable if they have the same input-output properties. In cases in which available a priori information is not sufficient to specify a unique compartmental model structure, indistinguishable model structures may have to be generated and their attributes examined for relevance. An algorithm is developed that, for a given compartmental model, investigates the complete set of models with the same number of compartments and the same input-output structure as the original model, applies geometrical rules necessary for indistinguishable models, and test models meeting the geometrical criteria for equality of transfer functions. Identifiability is also checked in the algorithm. The software consists of three programs. Program 1 determines the number of locally identifiable parameters. Program 2 applies several geometrical rules that eliminate many (generally most) of the candidate models. Program 3 checks the equality between system transfer functions of the original model and models being tested. Ranks of Jacobian matrices and submatrices and other criteria are used to check patterns of moment invariants and local identifiability. Structural controllability and structural observability are checked throughout the programs. The approach was successfully used to corroborate results from examples investigated by others.     

On the identification by filtering techniques of a biologicaln-compartment model in which the transport rate parameters are assumed to be stochastic processes

In this paper biological compartmental models are considered which take into account the intrinsic randomness of the transport rate parameters and their possible variability in time. An identification procedure is presented for the estimation of the stochastic processes representing the transport rate parameters of a compartmental model from a noisy input-output experiment. The problem is formulated in terms of nonlinear filtering. A simple model is discussed for the case in which the transport rate parameters are independent of each other. The possibility of testing possible important features of the behavior of the transport rate parameters is also evidenced.