Optimization of Switching Time from Growth to Product Formation for Maximum Productivity of Recombinant Escherichia coli Fermentation

Patkar, Anant Y.,Shin, Pyong K.,Seo, Jin Ho 한국산업미생물학회 1990 한국미생물·생명공학회지 Vol.18 No.4

유전자 조작된 세포 발효공정의 생산수율을 최대화하기 위하여 세포의 성장속도와 제품 생성속도간의 상반관계를 고려하여야 한다. 유전자 조작된 E. coli 발효에 있어, 최적화 이론을 적용하여 두 속도의 가중치를 결정함으로써 생산수율의 최대화를 꾀하였다. 성장저해제의 농도는 비성장속도를 조절하고 결국 융합된 유전자의 발현속도를 조절하는 변수로 사용된다. 이런 system의 특성을 위하여 간단한 unstructured model을 사용하였다. 이론적 해석에 의하면, 최적조절곡선은 초기의 높은 세포성장속도에 이어서 낮은 성장속도와 더불어 높은 물질생성속도를 보이는 두 단계로 구성된다. 물질생성속도가 세포성장속도에 대해 서로 다른 의존도를 보이는 대표적인 두 가지 경우에 대해, 수식계산을 통해 세포성장에서 물질생성으로 전환시키는 시기를 결정하였다. 물질생성속도가 세포생장속도에 민감한 경우 최적화 조작을 시행했을 때 단순 회분식 발효에 비해 최종생산물 농도가 약 60% 증가함을 알 수 있었다. Maximization of productivity of recombinant cell fermentations requires consideration of the inverse relationship between the host cell growth rate and product formation rate. The problem of maximizing a weighted performance index was solved by using optimal control theory for recombinant E. coli fermentation. Concentration of a growth inhibitor was used as a control variable to manipulate the specific growth rate, and consequently the cloned-gene expression rate. Using a simple unstructured model to describe the main characteristics of this system, theoretical analysis showed that the optimal control profile results in an initial high growth rate phase followed bya low growth rate and high product formation rate phase. Numerical calculations were done to determine optimal switching times from the growth to the production stage for two representative cases corresponding to different dependency of the product formation rate on the growth rate. For the case when product formation rate is sensitive to the specific growth rate, the optimized operation yields about 60% increase in the final product concentration compared with a simple batch fermentation.

연구발표초록 ( 생물화공 ) : 유전자 재조작된 효모로부터 Invertase 생산을 위한 포도당 농도의 최적화

Anant Patkar,서진호 ( Jin Ho Seo ) 한국화학공학회 1990 춘계학술발표회 Vol.- No.-

DEVELOPMENT OF A COMPUTER ALGORITHM BASED ON A CONJUGATE GRADIENT APPROACH FOR OPTIMIZATION OF FED - BATCH FERMENTATIONS

Patkar, Anant,Lee, Dong Hoon,SEO, JIN HO 한국화학공학회 1993 Korean Journal of Chemical Engineering Vol.10 No.3

The problem of optimization of fed-batch fermentations using the substrate feed rate as the control variable is singular in nature. Previous approaches, including the boundary condition iteration method and transformation to a nonsingular problem using a different control variable, do not work well for solving optimization of systems governed by more than four differential equations. The applicability of a first-order conjugate gradient algorithm for optimizing fed-batch fermentations was tested for systems of varing complexity. This approach does not need any variable transformation or a priori knowledge of the control arc sequence. Constraints on the feed rate are handled in a simple and direct manner. The algorithm worked very well for three, four, and five-dimensional singular systems. The correctness of the optimal profile was judged by observing the variation in the sign of the gradient of the Hamiltonian. The gradient was found to be zero during the singular period and had the appropriate sign on the boundary arcs. The optimization method based on conjugated gradient approach can be complementary to the boundary condition iteration method for determination of the exact optimum profile.

Development of a Computer Algorithm Based on a Conjugate Gradient Approach for Optimization of Fed - Batch Fermentations

Anant Patkar,Dong Hoon Lee,Jin Ho Seo 한국화학공학회 1993 화학공업과 기술 Vol.11 No.6

N/A The problem of optimization of fed-batch fermentations using the substrate feed rate as the contrcl variable is singular in nature. Previous approaches, including the boundary condition iteration method and transformation to a nonsingular problem using a different control variable, do not work well for solving optimization of systems governed by more than four differential equations. The applicability of a first-order conjugate gradient algorithm for optimizing fed-batch fermentations was tested for systems of oaring complexity. This approach does not need any variable transformation or a priori knowledge of the control arc sequence. Constraints on the feed rate are handled in a simple and direct manner. The algorithm worked very well for three, four, and five-dimensional singular systems. The correctness of the optimal profile was judged by observing the variation in the sign of the gradient of the Hamiltonian. The gradient was found to be zero during the singular period and had the appropriate sign on the boundary ares. The optimization method based on conjugated gradient approach can be complementary to the boundary condition iteration method for determination of the exact optimum profile.

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

Vikas Ostwal,Arvind Sahu,Anant Ramaswamy,Bhawna Sirohi,Subhadeep Bose,Vikas Talreja,Mahesh Goel,Shraddha Patkar,Ashwin Desouza,Shailesh V. Shrikhande 대한위암학회 2017 Journal of gastric cancer Vol.17 No.1

EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

Development of a Computer Algorithm Based on a Conjugate Gradient Approach for Optimization of Fed - Batch Fermentations

SEO, JIN HO,Lee, Dong Hoon,Patkar, Anant 한국화학공학회 1993 NICE Vol.11 No.6

The problem of optimization of fed-batch fermentations using the substrate feed rate as the contrcl variable is singular in nature. Previous approaches, including the boundary condition iteration method and transformation to a nonsingular problem using a different control variable, do not work well for solving optimization of systems governed by more than four differential equations. The applicability of a first-order conjugate gradient algorithm for optimizing fed-batch fermentations was tested for systems of oaring complexity. This approach does not need any variable transformation or a priori knowledge of the control arc sequence. Constraints on the feed rate are handled in a simple and direct manner. The algorithm worked very well for three, four, and five-dimensional singular systems. The correctness of the optimal profile was judged by observing the variation in the sign of the gradient of the Hamiltonian. The gradient was found to be zero during the singular period and had the appropriate sign on the boundary ares. The optimization method based on conjugated gradient approach can be complementary to the boundary condition iteration method for determination of the exact optimum profile.

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

Ostwal, Vikas,Sahu, Arvind,Ramaswamy, Anant,Sirohi, Bhawna,Bose, Subhadeep,Talreja, Vikas,Goel, Mahesh,Patkar, Shraddha,Desouza, Ashwin,Shrikhande, Shailesh V. The Korean Gastric Cancer Association 2017 Journal of gastric cancer Vol.17 No.1

Purpose: Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods: We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results: Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions: EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resections, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.