scholarly journals Model-Based Optimization of a Fed-Batch Bioreactor for mAb Production Using a Hybridoma Cell Culture

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5648
Author(s):  
Gheorghe Maria

Production of monoclonal antibodies (mAbs) is a well-known method used to synthesize a large number of identical antibodies, which are molecules of huge importance in medicine. Due to such reasons, intense efforts have been invested to maximize the mAbs production in bioreactors with hybridoma cell cultures. However, the optimal control of such sensitive bioreactors is an engineering problem difficult to solve due to the large number of state-variables with highly nonlinear dynamics, which often translates into a non-convex optimization problem that involves a significant number of decision (control) variables. Based on an adequate kinetic model adopted from the literature, this paper focuses on developing an in-silico (model-based, offline) numerical analysis of a fed-batch bioreactor (FBR) with an immobilized hybridoma culture to determine its optimal feeding policy by considering a small number of control variables, thus ensuring maximization of mAbs production. The obtained time stepwise optimal feeding policies of FBR were proven to obtain better performances than those of simple batch operation (BR) for all the verified alternatives in terms of raw material consumption and mAbs productivity. Several elements of novelty (i–iv) are pointed out in the “conclusions” section (e.g., considering the continuously added biomass as a control variable during FBR).

2021 ◽  
Vol 8 (12) ◽  
pp. 210
Author(s):  
Gheorghe Maria ◽  
Laura Renea

Hybrid kinetic models, linking structured cell metabolic processes to the dynamics of macroscopic variables of the bioreactor, are more and more used in engineering evaluations to derive more precise predictions of the process dynamics under variable operating conditions. Depending on the cell model complexity, such a math tool can be used to evaluate the metabolic fluxes in relation to the bioreactor operating conditions, thus suggesting ways to genetically modify the microorganism for certain purposes. Even if development of such an extended dynamic model requires more experimental and computational efforts, its use is advantageous. The approached probative example refers to a model simulating the dynamics of nanoscale variables from several pathways of the central carbon metabolism (CCM) of E. coli cells, linked to the macroscopic state variables of a fed-batch bioreactor (FBR) used for the tryptophan (TRP) production. The used E. coli strain was modified to replace the PTS system for glucose (GLC) uptake with a more efficient one. The study presents multiple elements of novelty: (i) the experimentally validated modular model itself, and (ii) its efficiency in computationally deriving an optimal operation policy of the FBR.


2018 ◽  
Vol 26 (2) ◽  
pp. 158-169
Author(s):  
Umi Wahidah ◽  
Sri Ayem

This research aimed to examine the effect of the convergence of International Financial Reporting Standards (IFRS) on tax avoidance on companies listed in Indonesia Stock Exchange. Tax avoidance that used in this research was Cash Efective Tax Rate (CETR). This research is also use the control variable to get other different influence that different such as CSR, size, and earning management (EM. This research used populations sector of transport service companies that listed in Indonesia Stock Exchange. The data of this research taken from secondary data that was from the Indonesia Stock Exchange in the form of Indonesian Capital Market Directory (ICMD) and the annual report of the company 2011-2015. The method of collecting sample was purposive sampling technique, the population that to be sampling in this research was populations that has the criteria of a particular sample. Companies that has the criteria of the research sample as many as 78 companies. The method of analysis used in this research is multiple regression analysis. Based on regression testing shows that the convergence of International Financial Reporting Standards (IFRS) has a positiveand significant impact on tax evasion. This shows that IFRS convergence actually improves tax evasion practices. The control variables of firm size and earnings management also significantly influence the application of IFRS in improving tax avoidance practices, while CSR control variables have no role in convergence IFRS in improving tax evasion practice.


1988 ◽  
Author(s):  
Hsin-Ying Lin ◽  
John C. Lewis ◽  
Richard H. Luecke
Keyword(s):  

Water ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1520
Author(s):  
Zheng Jiang ◽  
Quanzhong Huang ◽  
Gendong Li ◽  
Guangyong Li

The parameters of water movement and solute transport models are essential for the accurate simulation of soil moisture and salinity, particularly for layered soils in field conditions. Parameter estimation can be achieved using the inverse modeling method. However, this type of method cannot fully consider the uncertainties of measurements, boundary conditions, and parameters, resulting in inaccurate estimations of parameters and predictions of state variables. The ensemble Kalman filter (EnKF) is well-suited to data assimilation and parameter prediction in Situations with large numbers of variables and uncertainties. Thus, in this study, the EnKF was used to estimate the parameters of water movement and solute transport in layered, variably saturated soils. Our results indicate that when used in conjunction with the HYDRUS-1D software (University of California Riverside, California, CA, USA) the EnKF effectively estimates parameters and predicts state variables for layered, variably saturated soils. The assimilation of factors such as the initial perturbation and ensemble size significantly affected in the simulated results. A proposed ensemble size range of 50–100 was used when applying the EnKF to the highly nonlinear hydrological models of the present study. Although the simulation results for moisture did not exhibit substantial improvement with the assimilation, the simulation of the salinity was significantly improved through the assimilation of the salinity and relative solutetransport parameters. Reducing the uncertainties in measured data can improve the goodness-of-fit in the application of the EnKF method. Sparse field condition observation data also benefited from the accurate measurement of state variables in the case of EnKF assimilation. However, the application of the EnKF algorithm for layered, variably saturated soils with hydrological models requires further study, because it is a challenging and highly nonlinear problem.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Nigar Ahmed ◽  
Ajeet kumar Bhatia ◽  
Syed Awais Ali Shah

PurposeThe aim of this research is to design a robust active disturbance attenuation control (RADAC) technique combined with an extended high gain observer (EHGO) and low pass filter (LPF).Design/methodology/approachFor designing a RADAC technique, the sliding mode control (SMC) method is used. Since the standard method of SMC exhibits a chattering phenomenon in the controller, a multilayer sliding mode surface is designed for avoiding the chattering. In addition, to attenuate the unwanted uncertainties and disturbances (UUDs), the techniques of EHGO and LPF are deployed. Besides acting as a patch for disturbance attenuation, the EHGO design estimates the state variables. To investigate the stability and effectiveness of the designed control algorithm, the stability analysis followed by the simulation study is presented.FindingsThe major findings include the design of a chattering-free RADAC controller based on the multilayer sliding mode surface. Furthermore, a criterion of integrating the LPF scheme within the EHGO scheme is also developed to attenuate matched and mismatched UUDs.Practical implicationsIn practice, the quadrotor flight is opposed by different kinds of the UUDs. And, the model of the quadrotor is a highly nonlinear underactuated model. Thus, the dynamics of the quadrotor model become more complex and uncertain due to the additional UUDs. Hence, it is necessary to design a robust disturbance attenuation technique with the ability to estimate the state variables and attenuate the UUDs and also achieve the desired control objectives.Originality/valueDesigning control methods to attenuate the disturbances while assuming that the state variables are known is a common practice. However, investigating the uncertain plants with unknown states along with the disturbances is rarely taken in consideration for the control design. Hence, this paper presents a control algorithm to address the issues of the UUDs as well as investigate a criterion to reduce the chattering incurred in the controller due to the standard SMC algorithm.


2011 ◽  
Vol 2011 ◽  
pp. 1-11
Author(s):  
Aili Cheng ◽  
John Peterson ◽  
Pallavi Chitturi

One of the key issues in robust parameter design is to configure the controllable factors to minimize the variance due to noise variables. However, it can sometimes happen that the number of control variables is greater than the number of noise variables. When this occurs, two important situations arise. One is that the variance due to noise variables can be brought down to zero The second is that multiple optimal control variable settings become available to the experimenter. A simultaneous confidence region for such a locus of points not only provides a region of uncertainty about such a solution, but also provides a statistical test of whether or not such points lie within the region of experimentation or a feasible region of operation. However, this situation requires a confidence region for the multiple-solution factor levels that provides proper simultaneous coverage. This requirement has not been previously recognized in the literature. In the case where the number of control variables is greater than the number of noise variables, we show how to construct critical values needed to maintain the simultaneous coverage rate. Two examples are provided as a demonstration of the practical need to adjust the critical values for simultaneous coverage.


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