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

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).     

连续时间马尔可夫决策过程的折扣模型

本文考虑的是转移速率族任意且费用率函数可能无界的连续时间马尔可夫决策过程的折扣模型．放弃了传统的要求相应于每个策略的　Ｑ　－过程唯一等条件,而首次考虑相应每个策略的　Ｑ　－过程不一定唯一,　转移速率族也不一定保守,　费用率函数可能无界,　且允许行动空间非空任意的情形．　本文首次用"α－折扣费用最优不等式"更新了传统的α－折扣费用最优方程,并用"最优不等式"和新的方法,不仅证明了传统的主要结果即最优平稳策略的存在性,　而且还进一步探讨了（　∈＞０　　）－最优平稳策略,具有单调性质的最优平稳策略,　以及（∈≥０）　－最优决策过程的存在性,　得到了一些有意义的新结果．　最后,　提供了一个迁移率受控的生灭系统例子,　它满足本文的所有条件,　而传统的假设（见文献［１－１４］）均不成立．     

展望21世纪风能的利用与发展

本介绍了国内外风能利用的现状,并对我国未来风能的利用与发展提出了很多建设性的意见,诸如：发展目标的确立,政策、法规体系的建立,技术性能的提高及新产品的开发,经济鼓励政策及其实施,产业化体系的建设等。     

THE ECONOMICS OF TIMBER SUPPLY: AN ANALYTICAL SYNTHESIS OF MODELING APPROACHES

The joint supply of timber and other services from forest environments plays a central role in most forest land debates. This paper defines a general conceptual model of timber supply that provides the context for discussing both individual harvest choice and aggregate supply models. While the structure and breadth of these models has developed considerably over the last twenty years, unresolved issues remain. Supply formulations that account for the quality and vintage distribution of forest capital will be necessary for improving medium- and long-run forecasts. This will be especially important for examining the potential impacts of structural changes in forest production and timber markets. In addition, consistent aggregation of individual owners to total supply will be required to address changing forest land ownership patterns.     

Time,Complex Systems,and Public Policy: A Theoretical Foundation for Adaptive Policy Making

Nonlinear Dynamics, Psychology, and Life Sciences - Can public policy development and implementation be improved by closely tracking and coordinating its timing with that of the regulated sector?...     

An optimal service rate in a Poisson arrival queue with two-stage service policy*

We consider a two-stage service policy for a Poisson arrival queueing system. The idle server starts to work with ordinary service rate when a customer arrives. If the number of customers in the system reaches N, the service rate gets faster and continues until the system becomes empty. Otherwise, the server finishes the busy period with ordinary service rate. After assigning various operating costs to the system, we show that there exists a unique fast service rate minimizing the long-run average cost per unit time.This work was supported by Korea Research Foundation Grant(KRF-2002-070-C00021).     

Optimal strategy policy in batch arrival queue with server breakdowns and multiple vacations

This paper considers a like-queue production system in which server vacations and breakdowns are possible. The decision-maker can turn a single server on at any arrival epoch or off at any service completion. We model the system by an M^[x]/M/1 queueing system with N policy. The server can be turned off and takes a vacation with exponential random length whenever the system is empty. If the number of units waiting in the system at any vacation completion is less than N, the server will take another vacation. If the server returns from a vacation and finds at least N units in the system, he immediately starts to serve the waiting units. It is assumed that the server breaks down according to a Poisson process and the repair time has an exponential distribution. We derive the distribution of the system size through the probability generating function. We further study the steady-state behavior of the system size distribution at random (stationary) point of time as well as the queue size distribution at departure point of time. Other system characteristics are obtained by means of the grand process and the renewal process. Finally, the expected cost per unit time is considered to determine the optimal operating policy at a minimum cost. The sensitivity analysis is also presented through numerical experiments.     

Production systems with interruptions, arbitrary topology and finite buffers

We consider a production system with finite buffers and arbitrary topology where service time is subject to interruptions in one of three ways, viz. machine breakdown, machine vacations or Npolicy. We develop a unified approximation (analytical) methodology to calculate the throughput of the system using queueing networks together with decomposition, isolation and expansion techniques. The methodology is rigorously tested covering a large experimental region. Orthogonal arrays are used to design the experiments in order to keep the number of experiments manageable. The results obtained using the approximation methodology are compared to the simulation results. The ttests carried out to investigate the differences between the two results show that they are statistically insignificant. Finally, we test the methodology by applying it to several arbitrary topology networks. The results show that the performance of the approximation methodology is consistent, robust and produces excellent results in a variety of experimental conditions.     

Applications of SMP Bounds to Multi-class Traffic in High-speed Networks

In this paper, we consider the stochastic fluid-flow model of a single node in a high-speed telecommunication network handling multi-class traffic. The node has multiple buffers, one for each class of traffic. The contents of these buffers are multiplexed onto a single output channel using one of the service scheduling policies: the Timed Round Robin Policy or the Static Priority Service Policy. The Quality of Service requirements for each class are based on cell loss probabilities. Using effective bandwidth methodologies and the recently developed bounds for semi-Markov modulated traffic, we solve call admission control problems for the two service scheduling policies at this node. We compare the performance of the effective bandwidth methodologies and the SMP bounds technique. We also numerically compare the performance of the two service scheduling policies.