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.

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.

Anterior Retropharyngeal Cage Distraction and Fixation for Basilar Invagination: “The Wedge Technique”

Sushil Patkar 대한척추신경외과학회 2019 Neurospine Vol.16 No.2

Objective: Surgery is indicated for basilar invagination (BI) in symptomatic patients. In many patients, symptoms and signs occur due to an upward-migrated and malaligned odontoid with fixed or mobile atlantoaxial instability. Posterior distraction and fixation of the atlantoaxial joints has evolved to become the standard of care, but has some inherent morbidity. In this study, we propose that the unilateral anterior submandibular retropharyngeal approach with customized wedge-shaped titanium cages inserted into both atlantoaxial joints and anterior atlantoaxial fixation with a plate screw construct is a safer and easier option in many cases of BI. Methods: From February 2014 to February 2019, 52 patients (age range, 15–78 years; 40 males and 12 females) with symptomatic BI with atlantoaxial dislocation and minimal sagittal facetal inclination and only mild Chiari malformation without syringomyelia were offered anterior submandibular retropharyngeal atlantoaxial distraction and fixation surgery. Results: Neurological improvement occurred in 80% of patients, while the neurological status of 20% remained unchanged. No patients worsened, and no major complications or mortality was observed. Conclusion: In properly selected cases of symptomatic BI, anterior wedge cage distraction with anterior atlantoaxial fixation is a safe and simple option.

Radical surgery for stage IV gallbladder cancers: Treatment strategies in patients with limited metastatic burden

Shraddha Patkar,Swapnil Patel,Mufaddal Kazi,Mahesh Goel 한국간담췌외과학회 2023 Annals of hepato-biliary-pancreatic surgery Vol.27 No.2

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

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

Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial

Cheolmin Shin(Cheolmin Shin),Sang Won Jeon(Sang Won Jeon),Seung-Hoon Lee(Seung-Hoon Lee),Chi-Un Pae(Chi-Un Pae),Narei Hong(Narei Hong),Hyun Kook Lim(Hyun Kook Lim),Ashwin A. Patkar(Ashwin A. Patkar ) 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Objective: Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression. Methods: Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. Results: Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p = 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences. Conclusion: Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.

Simultaneous resection of synchronous colorectal liver metastasis: Feasibility and development of a prediction model

Mufaddal Kazi,Shraddha Patkar,Prerak Patel,Aditya Kunte,Ashwin Desouza,Avanish Saklani,Mahesh Goel 한국간담췌외과학회 2023 Annals of hepato-biliary-pancreatic surgery Vol.27 No.1

Backgrounds/Aims: Timing of resection for synchronous colorectal liver metastasis (CRLM) has been debated for decades. The aim of the present study was to assess the feasibility of simultaneous resection of CRLM in terms of major complications and develop a prediction model for safe resections. Methods: A retrospective single-center study of synchronous, resectable CRLM, operated between 2013 and 2021 was conducted. Upper limit of 95% confidence interval (CI) of major complications (≥ grade IIIA) was set at 40% as the safety threshold. Logistic regression was used to determine predictors of morbidity. Prediction model was internally validated by bootstrap estimates, Harrell’s C-index, and correlation of predicted and observed estimates. Results: Ninety-two patients were operated. Of them, 41.3% had rectal cancers. Major hepatectomy (≥ 4 segments) was performed for 25 patients (27.2%). Major complications occurred in 20 patients (21.7%, 95% CI: 13.8%–31.5%). Predictors of complications were the presence of comorbidities and major hepatectomy (area under the ROC curve: 0.692). Unacceptable level of morbidity (≥ 40%) was encountered in patients with comorbidities who underwent major hepatectomy. Conclusions: Simultaneous bowel and CRLM resection appear to be safe. However, caution should be exercised when combining major liver resections with bowel resection in patients with comorbid conditions.

Primary hepatic neuroendocrine tumours of liver- a rarity: Single centre analysis of 13 patients

Amir Parray,Shraddha Patkar,Mahesh Goel 한국간담췌외과학회 2020 Annals of hepato-biliary-pancreatic surgery Vol.24 No.1

Backgrounds/Aims: Primary hepatic neuroendocrine tumours (PHNETs) are a rarity and this rarity imparts management complexities. Methods: A retrospective analysis of prospectively maintained liver database from 2009 to 2018 was performed and patients with PHNETs were identified and studied for clinical, imaging and pathological features, surgical outcomes, disease free and overall survival. Results: Thirteen patients of PHNET were identified following rigorous investigational protocols, which constituted 0.6% of all liver tumours (2095) in our series. The median age of patients was 50 years (14-65), with male to female ratio of 9:4. Eight patients (62%) underwent hepatic resections as primary treatment, while 5 (38%) patients received peptide receptor radiotherapy, trans-arterial chemotherapy, trans-arterial radiotherapy or a combination of these. In the surgical group at a median follow up of 36 months (range 5-114 months), 4 (50%) patients were alive without disease and disease free survival was 20 months. Median OS in surgical group was 47 months (40-53, 95% confidence interval) that was better but not statistically significant from that of non-surgical treatment group (36 months). Conclusions: PHNETs are rare tumours that require multidisciplinary treatment approach. Liver directed surgery centred management leads to better clinical outcomes in these selected patients.

Hepatocellular carcinoma metastasis to the buccal mucosa masquerading as oral cavity malignancy: Case report of a rare entity

Shravan Nadkarni,Shraddha Patkar,Rajgopal Acharya,Aekta Shah,Swapnil Patel,Amir Parray,Mahesh Goel 한국간담췌외과학회 2020 Annals of hepato-biliary-pancreatic surgery Vol.24 No.1

Hepatocellular carcinoma, a disease of the developing world, is known to present with extrahepatic metastases. Most common site being the lungs, it is not uncommon for metastases to present at unusual sites like the rectum, spleen and the diaphragm, among others. Metastases to the oral cavity is rare, with the most common primaries being lung, breast and the kidney. Metastases of a hepatocellular carcinoma to the oral cavity is a rare entity with extremely limited data in literature. We present one such unique case of oral cavity metastases from a hepatocellular carcinoma who presented to the Division of Head and Neck Oncology services of our hospital with a large oral cavity lesion, on subsequent workup of which, a hepatocellular carcinoma was identified. Awareness of this possibility can aid in accurate diagnosis and early management of a condition associated with an advanced stage at presentation and poorer prognosis.

Pain and Depression:What Links do we Know?

Aayushman Misra,박근영,Ashwin Patkar,심동석,배치운 대한우울조울병학회 2010 우울조울병 Vol.8 No.1

Pain may be caused by various medical illnesses, for example, fibromyalgia, diabetic neuropathy, herpetic neuralgia,trigeminal neuralgia, and irritable bowel syndrome. It is not uncommon to see such patients simultaneously suffering significant depressive symptoms in clinical practice. In addition, pain and depression commonly share pathophysiologies and clinical manifestations. Patients with depression present with emotional symptoms (depressed mood, sadness, and apathy, etc) and/or physical symptoms (pain, fatigue, and dizziness, etc), since the disorder is multi-faceted. In particular, a reciprocal relationship exists between painful physical symptoms and depression. Data suggest that approximately 65% of depressed patients may have accompanied painful physical symptoms and vice versa. In fact patients showing 2 or more pain symptoms may increase the risk of developing clinical depression than in those without pain symptoms. The co-occurrence of pain and depression may worsen not only clinical outcomes but also occupational, social, and global functioning of such patients. These findings clearly indicate that clinicians must be aware of the common co-occurrence of pain and depression in order to effectively treat and enhance remission for their patients with this comorbidity. Although there have been no clear etiological findings in relation with pain symptoms and depression, possible links between pain and depression may exist in the central and peripheral nervous systems. Both serotonin and norepinephrine are principal neurotransmitters in the ascending and descending pathways as well as in frontal and limbic regions involving in the pathophysiology of both pain and depression. Other biological markers also have overlapping roles in both conditions. As seen in diagnostic criteria for major depressive disorder (MDD), some depressive symptoms are also commonly seen in patients with pain symptoms such as lack of energy and insomnia. Familial aggregation studies have also suggested higher prevalence of MDD in pain symptoms than in general population. In conclusion, pain and depression may share common neuronal pathways, neurochemical findings, principal neurotransmitters and symptomatologies as well as have reciprocal impacts on each clinical course and treatment outcomes. Better understanding on the relationship between pain and depression may shed a light on the further roadmap for diagnosis and management for both conditions in clinical practice.