Robust Control of Continuous Bioprocesses

This paper deals with robust control of continuous bioprocesses. According to the material balance equations of continuous bioprocesses, a uniform framework for mathematical modeling of this class of processes is first presented. Then a robust controller is designed by using the H∞ mixed sensitivity method for the biotechnology processes. The corresponding control objective is described as the development of a robust reference-tracking control structure with the best possible disturbance compensation, able to cope with variations in key process parameters. Finally, the proposed robust control strategy is applied to bio-dissimilation process of glycerol to 1, 3-propanediol. Simulation results are given which show that the designed robust controller makes the system have a favourable robust tracking performance

Optimization of Continuous Bioconversion Process of Glycerol to 1,3-Propanediol

This paper addresses the optimization of continuous bioconversion process of glycerol to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae. The studied bioprocess is a complex nonlinear system that involves the gene regulation for dha regulon, enzyme-catalytic kinetics on the reductive pathway, the active transport of glycerol and (passive) diffusion of 1,3-PD across the cell membrane, and the inhibition of glycerol dehydratase (GDHt) and 1,3-propanediol oxidoreductase (PDOR) by 3-hydroxypropionaldehy (3-HPA). We first propose a nonlinear optimization model that can maximize the production rate of 1,3-PD. Then the optimal solution of this optimization problem is obtained by using an interior point method. In this approach a sequence of barrier problems are solved iteratively. We finally obtain the maximum production rate of 1,3-PD increased more than 22.86 times its initial value

An Improved Geometric Programming Approach for Optimization of Biochemical Systems

This paper proposes an improved geometric programming approach to address the optimization of biochemical systems. In the proposed method we take advantage of a special and interesting class of nonlinear kinetic models known as generalized mass action (GMA) models. In most situations optimization problems with GMA models are nonconvex and difficult problems to solve for global optimality. To deal with this difficulty, in this work, some transformation strategy is first used to convert the optimization problem with GMA models into an equivalent problem. Then a convexification technique is applied to transform this resulting optimization problem into a series of standard geometric programming problems that can be solved to reach a global solution. Two case studies are presented to demonstrate the advantages of the proposed method in terms of computational efficiency

A Two-Stage Method for Parameter Identification of a Nonlinear System in a Microbial Batch Process

This paper deals with the parameter identification of a microbial batch process of glycerol to 1,3-propanediol (1,3-PD). We first present a parameter identification model for the excess kinetics of a microbial batch process of glycerol to 1,3-PD. This model is a nonlinear dynamic optimization problem that minimizes the sum of the least-square and slope errors of biomass, glycerol, 1,3-PD, acetic acid, and ethanol. Then, a two-stage method is proposed to efficiently solve the presented dynamic optimization problem. In this method, two nonlinear programming problems are required to be solved by a genetic algorithm. To calculate the slope of the experimental concentration data, an integral equation of the first kind is solved by using the Tikhonov regularization. The proposed two-stage method could not only optimally identify the model parameters of the biological process, but could also yield a smaller error between the measured and computed concentrations than the single-stage method could, with a decrease of about 52.79%. A comparative study showed that the proposed two-stage method could obtain better identification results than the single-stage method could

Current status of diagnosis and treatment of bladder cancer in China – Analyses of Chinese Bladder Cancer Consortium database

AbstractObjectiveTo investigate current status of diagnosis and treatment of bladder cancer in China.MethodsA database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected.ResultsThe average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy.ConclusionDisease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China