Directed Evolution and Mutagenesis of Lysine Decarboxylase from Hafnia alvei AS1.1009 to Improve Its Activity toward Efficient Cadaverine Production

Chen Wang,Kai Zhang,Chen Zhongjun,Heng Cai,Wan Honggui,Ping-Kai Ouyang 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.3

Lysine decarboxylase (LDC) exhibits a significant role in cadaverine (1,5-pentanediamine, diaminopentane) production from lysine. In this study, an error-prone PCR and DNA shuffling were performed to improve the activity of LDC from Hafnia alvei AS1.1009 for cadaverine production. A sensitive high-throughput screening strategy based on a pH indicator was established for directed evolution of LDC. Several improved mutants were obtained from directed evolution and LDCV147F/E583G mutant showed highest activity to catalyze lysine to cadaverine. This mutant showed 1.62-fold high LDC activity when compared to wild-type. Further analysis by site-directed mutagenesis reveled that only the mutant E583G was sufficient for higher catalytic activity. Wild type LDC and mutant LDCE583G were purified by an improved method including hydrophobic chromatography. These purified enzymes were characterized and the kinetic parameters were compared between LDCE583G and WT LDC. Vmax of LDCE583G was 1.32-fold higher than that of WT LDC. Use of LDCE583G mutant showed 1.48-fold improved productivity of cadaverine when compared to wild type. The concentration of cadaverine in E. coli JM109/pTrc99a-ldc2-41 was 63.9 g/L with conversion yield of 93.4% during 5 h. These results indicate that the mutation has positive effects on improving LDC activity and a potential candidate for cadaverine production.

Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn`s Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study

( Chen Wang Chang ),( Shu Chen Wei ),( Jen Wei Chou ),( Tzu Chi Hsu ),( Chiao Hsiung Chuang ),( Ching Pin Lin ),( Wen Hung Hsu ),( Hsu Heng Yen ),( Jen Kou Lin ),( Yi Jen Fang ),( Horng Yuan Wang ),( 대한장연구학회 2014 Intestinal Research Vol.12 No.4

Background/Aims: Only moderate to severe Crohn`s Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria. Methods: A retrospective analysis was conducted in nine medical centers in Taiwan and we collected the results of CD patients receiving adalimumab from Sep 2009 to Mar 2014. The clinical characteristics, response measured by CDAI (Crohn`s Disease Activity Index), adverse events and survival status were recorded and analyzed. CR-70, CR-100, and CR-150 were defined as attaining a CDAI decrease of 70, 100 or 150 points compared with baseline. Results: A total of 103 CD patient records were used in this study. Sixty percent of these patients received combination therapy of adalimumab together with immunomodulators. CR-70 was 68.7%, 74.5% and 88.4% after week 4, 8 and 12 of treatment, respectively. The steroid-free rate, complications and survival were 47.6%, 9.7% and 99% of patients, respectively. In considering the mucosal healing, only 25% patients achieve mucosal healing after treatment for 6 to12 months. Surgery was still needed in 16.5% of patients. Combination treatment of adalimumab with immunomodulators further decreased the level of CDAI at week 8 when compared with the monotherapy. Conclusions: Even under the stringent criteria for using adalimumab, the response rate was comparable to those without stringent criteria. (Intest Res 2014;12:287-292)

Outcomes of limited period of adalimumab treatment in moderate to severe Crohn’s disease patients: Taiwan Society of Inflammatory Bowel Disease Study

( Wei-chen Lin ),( Jen-wei Chou ),( Hsu-heng Yen ),( Wen-hung Hsu ),( Hung-hsin Lin ),( Jen-kou Lin ),( Chiao-hsiung Chuang ),( Tien-yu Huang ),( Horng-yuan Wang ),( Shu-chen Wei ),( Jau-min Wong ) 대한장연구학회 2017 Intestinal Research Vol.15 No.4

Background/Aims: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn’s disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable. Methods: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015. Results: A total of 54 CD patients, with follow-up of more than 6 months after the withdrawal of ADA, were enrolled. The average period of treatment with ADA was 16.7±9.7 months. After discontinuing ADA, 59.3% patients suffered a clinical relapse. In the univariate analysis, the reason for withdrawal was a risk factor for relapse (P=0.042). In the multivariate analysis, current smoker became an important risk factor for relapse (OR, 3.9; 95% CI, 1.2-14.8; P=0.044) and male sex was another risk factor (OR, 2.9; 95% CI, 1.1-8.6; P=0.049). For those 48 patients who received a second round of biologics, the clinical response was seen in 60.4%, and 1 anaphylaxis occurred. Conclusions: Fifty-nine percent of patients experienced a relapse after discontinuing the limited period of ADA treatment, and most of them occurred within 1 year following cessation. Male sex and current smoker were risk factors for relapse. Though 60.4% of the relapse patients responded to ADA again. (Intest Res 2017;15:487-494)

Balloon-Assisted Enteroscopy and Capsule Endoscopy in Suspected Small Bowel Crohn’s Disease

Hsu-Heng Yen,Chen-Wang Chang,Jen-Wei Chou,Shu Chen Wei 대한소화기내시경학회 2017 Clinical Endoscopy Vol.50 No.5

Inflammatory bowel diseases are idiopathic inflammatory diseases of two main types, Crohn’s disease and ulcerative colitis. Crohn’s disease can affect the entire gastrointestinal tract, and the distal ileum is involved in up to 70% of patients. Moreover, Crohn’s disease in one-quarter to one-third of patients involves isolation of the small bowel. Due to the nonspecific symptoms and anatomical location of the disease, small bowel Crohn’s disease is a phenotype that is particularly difficult to manage. Since the introduction of capsule endoscopy in 2000 and balloon-assisted enteroscopy in the 21st century, it is now possible to directly inspect for small bowel Crohn’s disease. However, the new modalities still have limitations, such as capsule retention and invasiveness of balloon-assisted enteroscopy. The diagnostic yields of both capsule endoscopy and balloon-assisted enteroscopy are high for patients with suspected small bowel Crohn’s disease. Therefore, earlier use of capsule endoscopy or balloon-assisted enteroscopy can help with the diagnosis and earlier treatment of these patients to avert possible disastrous outcomes.

Survival Benefit of Tamoxifen in Estrogen Receptor-Negative and Progesterone Receptor-Positive Low Grade Breast Cancer Patients

Li-Heng Yang,Hsin-Shun Tseng,Che Lin,Li-Sheng Chen,Shou-Tung Chen,Shou-Jen Kuo,Dar-Ren Chen 한국유방암학회 2012 Journal of breast cancer Vol.15 No.3

Purpose: This study aimed to analyze the efficacy and prognostic significance of adjuvant tamoxifen in breast cancer patients with various hormone receptor statuses. Methods: Typically, 1,260 female breast cancer patients were recruited in this study. The correlation between estrogen receptor (ER)/progesterone receptor (PR) phenotypes and clinical characteristics was investigated, and the survival rate was assessed after 5-year follow-up. Results: The 5-year overall survival (85%) was better in women under the age of 50 years. Patients with ER+/PR+ tumors had a better 5-year survival rate (94%); those with ER-/PR- tumors experienced the worst outcome (74% survival rate); whereas singlepositive cases were in between. In 97 out of 128 patients with ER-/PR+ tumors, tamoxifen was given as adjuvant hormonal therapy, and it increased the survival benefit in the lower grade group in terms of overall survival and disease-free survival (p=0.01 and p=0.03, respectively). Conclusion: For high-grade tumors with ER-/PR+, adjuvant tamoxifen therapy may have no survival benefit, whereas for the patients with low-grade ER-/PR+ tumors, adjuvant tamoxifen therapy is highly suggestive.

Sentiment-Aspect Analysis through Semi-Supervised Topic Modeling

Yong Heng Chen,Wanli Zuo,Hao Yue,Yaojin Lin 보안공학연구지원센터 2015 International Journal of Database Theory and Appli Vol.8 No.6

Sentiment analysis based on the aspects of products or services is designed to explore subjective information such as attitudes and opinions in user-generated reviews. Although a great many of approaches have been proposed in detecting aspects and the relevant aspect-specific sentiments, most of them detect the latent aspects with no proper classifying them or classify them employing unsupervised topic modeling without predicting the sentiment towards these aspects. This paper proposes a novel sentiment-aspect analysis probabilistic modeling framework consisting of Seeding words extraction and semi-supervised topic (SST) model based on Sentence-LDA. More specifically, the proposed methodology starts by capturing seeding words from the websites inherent semi-structured information about products or services description. Then, it employs the captured seeding words to instruct the discovery of aspects and relevant sentiment of products or services simultaneously. Experimental results show that significant improvements have been achieved by the proposed method with respect to other state-of-the-art methods.

Mutual intercropping-inspired co-silanization to graft well-oriented organosilane as adhesion promotion nanolayer for flexible conductors

Yi-Hsuan Chen,Yi-Hsiang Lai,Ping-Heng Wu,Li-Syuan Chen,Yung-Sen Lin,Chih-Ming Chen 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.83 No.-

Surface metallization of polymer substrate andfilm adhesion are crucial to the development offlexibleelectronics. This study demonstrates the co-silanization engineering on the polyimide (PI)film by mutualintercropping of two organosilane molecules to improve their grafting orientability and enhance theadsorbability toward the PI substrate and loaded metal atoms. The mutual intercropping-inspired cosilanizationengineering is implemented by using 3-[(trimethylsilyl)ethynyl]pyridine (TEP) as asupporting organosilane to spatially confine the grafting orientation of the supported aminosilane, 3-[2-(2-aminoethylamino)ethylamino]propyl-trimethoxysilane (ETAS), leading to the formation of a wellorientedorganosilane composite nanolayer as adhesion promotion layer forflexible conductors. Theflexible Cu conductor electrolessly deposited on the PIfilm by co-silanization shows improved adhesionstrength (0.9 kgf/cm) compared to those based on mono-silanization (0.51 kgf/cm) and sputtered Ta/Cu(0.4 kgf/cm). Superior deformability (bendability) was also achieved for the co-silanized Cu/PI sample byretaining good electrical property after bending cycle up to 1000.

Enhancing User Involvement Studies Using a Scenario Co-build Approach

Chun-Hsien Chen,Nai-Feng Chen,Li Pheng Khoo,Chun-Heng Ho 한국디자인학회 2015 디자인학연구 Vol.28 No.1

Relation between the local structure and solid solubility of the layered material LiMO2 (M=Co, Ni, Fe) in Li2MnO3

Chen Hou,Xiang Xiao,Yi-Ran Xing,Le-Le Yu,Yong-Heng Si,Han Lu,Yu-Juan Zhao 대한금속·재료학회 2022 ELECTRONIC MATERIALS LETTERS Vol.18 No.1

Although low solid solubility and activity of LiFeO2in xLi2MnO3·(1–x)LiFeO2 limit its practical application, it still has thepotential to become a new-generation cathode material without cobalt or nickel for Li-ion batteries. In order to understand theeffects of the local structures of different LiMO2(M = Co, Ni, Fe) layered materials on their solid solubility in Li2MnO3,partialdensities of states are calculated to determine the Jahn–Teller distortion in the layered cathode material, and the first-principlescalculation method based on density functional theory is used to optimize and compare the local structures of LiCoO2,LiNiO2,LiFeO2,LiMnO2,and Li2MnO3. The degrees of distortion of the transition metal–oxygen (M–O) and lithium–oxygen (Li–O)octahedra in the crystal structure of the material are evaluated. It is clear that the solid solubility of layered materials is relatedto the bond lengths and degrees of distortion of the M–O and Li–O octahedra. Among them, the similar bond length of LiNiO2and Li2MnO3and the high distortion of NiO6enhance the solid solubility of LiNiO2in Li2MnO3. Owing to the absence ofJahn–Teller distortion in LiFeO2and LiCoO2,the FeO6and CoO6octahedra are slightly distorted, thereby decreasing thesolid solubility of LiMO2(M = Fe, Co) in Li2MnO3. Understanding the relation between intra-octahedral distortion and solidsolubility provides simple and efficient evidence for comparing the solid solubilities of different LiMO2layered materials inthe Li2MnO3of Li-rich cathode materials. This study can be used as a reference for component design in Li-rich materials.

Updated Meta-analysis on HER2 Polymorphisms and Risk of Breast Cancer: Evidence from 32 Studies

Chen, Wei,Yang, Heng,Tang, Wen-Ru,Feng, Shi-Jun,Wei, Yun-Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Several studies have been performed to investigate the association of the HER2 Ile655Val polymorphism and breast cancer risk. However, the results were inconsistent. To understand the precise relationship, a meta-analysis was here conducted. Materials and Methods: A search of PubMed conducted to investigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, of which 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals were used to assess any association. Results: In the overall analysis, the HER2 Ile655Val polymorphism was associated with breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominant genetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model. On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111, 95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asians and Africans in any of the genetic models. Conclusions: In summary, our meta-analysis findings suggest that the HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwide populations with additive and dominant models, but not a recessive model.