121 results on '"Hsi Chu"'
Search Results
2. Data from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Purpose: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation–mediated de novo resistance. Here, we investigated the driver gene mutation–independent mechanism for cetuximab resistance in HNSCC.Experimental Design: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab. Zebrafish model was applied for evaluating the synergistic effect of combinatory drugs for overcoming cetuximab resistance.Results: The cetuximab-resistant HNSCC cells undergo a Snail-induced epithelial–mesenchymal transition. Mechanistically, Snail induces the expression of lymphotoxin-β (LTβ), a TNF superfamily protein that activates NF-κB, and protein arginine methyltransferase 1 (PRMT1), an arginine methyltransferase that methylates EGFR. LTβ interacts with methylated EGFR to promote its ligand-binding ability and dimerization. Furthermore, LTβ activates the NF-κB pathway through a LTβ receptor–independent mechanism. Combination of an EGFR tyrosine kinase inhibitor and a NF-κB inhibitor effectively suppressed cetuximab-resistant HNSCC and interfering with the EGFR–LTβ interaction reverses resistance.Conclusions: Our findings elucidate the mechanism of driver gene mutations–independent mechanism of acquired resistance to cetuximab in HNSCC and also provide potential strategies for combating cetuximab resistance. Clin Cancer Res; 23(15); 4388–401. ©2017 AACR.
- Published
- 2023
3. supplemental information from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Includes legends to 5 supplementary figures, supplementary methods, and supplementary references
- Published
- 2023
4. Figure S1 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Generation and characterization of the cetuximab-resistant head and neck cancer cells
- Published
- 2023
5. Figure S5 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Interaction between LTβ and methylated EGFR activates EGFR and induces cetuximab resistance
- Published
- 2023
6. Figure S2 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Snail locates upstream to LTβ upregulates its expression, and LTβ induces EMT
- Published
- 2023
7. Table S2 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
S2A: Sequence of primers used in real-time PCR, ChIP and sequencing; S2B: List of proteins tested by antibodies and characteristics of the corresponding antibodies
- Published
- 2023
8. Figure S4 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Activation of EGFR and the NF-κB pathway in cetuximab-resistant cells
- Published
- 2023
9. Figure S3 from Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Muh-Hwa Yang, Mien-Chie Hung, Shyh-Kuan Tai, Hsiao-Jung Wang, Hsin-Yi Lan, Wen-Hao Hsu, Chih-Yi Lin, Shih-Pei Wu, Hua-Kuo Lin, Han-Syuan Lin, Pon-Bo Chen, Yang-Hui Ho, Chen-Hsi Chu, Chiou-Hwa Yuh, Wei-Lun Hwang, and Dennis Shin-Shian Hsu
- Abstract
Activation of NF-κB in cetuximab-resistant cells
- Published
- 2023
10. Analyzing Decision-Making Factors of Green Design for Kid’s Toys Based on the Concept of Product Lifecycle
- Author
-
Jui-Che Tu, Ku-Hsi Chu, Ding-Ze Gao, and Chun Yang
- Subjects
green design ,product life cycle ,kid’s toy ,consumption value ,consumption willingness ,Process Chemistry and Technology ,Chemical Engineering (miscellaneous) ,Bioengineering - Abstract
In promoting the SDGs (Sustainable Development Goals), increasing attention has been given to environmental pollution and abnormal climate issues. In particular, a large number of products made of plastic materials have caused harm to the environment. Secondly, with the improvement of average spending power, many parents are more willing to buy toys for their children. However, the lifespan of kid’s toys is often short, and most materials are made of plastic, which also causes issues as they are not easy to break down and are difficult to recycle. This study investigates the concept of the product life cycle in kid’s toys and explores the decision-making factors of green design. First, analysis and induction were conducted through literature collection. Through semi-structured interviews with experts, the design dimensions related to the green design of kid’s toys and the elements that affect the willingness of consumption by consumption values and behavior were obtained. After the questionnaire survey and data analysis, the design factors and purchasing decision factors of green design for the product life cycle and consumption values and behavior of kid’s toys were obtained. Finally, combined with kid’s toy design, green design, product life cycle and consumers’ consumption values and behavior, the decision-making factors for the green design of kid’s toys were extracted, which included (1) using non-toxic materials; (2) designing for maintainability and disassembly of the toy; (3) refining the toys to be artistic and collectable; (4) upgrading the educational functions of toys; (5) improving the recycling of toys; (6) emphasizing green packing; (7) creating a green brand and increasing product visibility; and (8) advocating the value of green design for toys. In addition to supplying green design considerations for kid’s toys to designers and companies, the results can also be used as an important reference with regard to the research topics of product life cycle, toy design and development for the sustainable designs of products.
- Published
- 2022
- Full Text
- View/download PDF
11. Conversion of Paper and Food-rich Municipal Solid Waste Streams to Ethanol through Bioprocessing
- Author
-
Ning Sun, Todd Pray, Jipeng Yan, Chia-Hsi Chu, Ling Liang, Qian He, and Carolina Gutierrez
- Subjects
Municipal solid waste ,Waste management ,Renewable Energy, Sustainability and the Environment ,General Chemical Engineering ,Bioproducts ,Environmental Chemistry ,Environmental science ,General Chemistry ,STREAMS ,Bioprocess - Abstract
This article provides a method to convert landfill-designated municipal solid waste (MSW, paper-rich and food-rich) to bioproducts through integrated bioprocessing, also a way of improving the MSW ...
- Published
- 2020
12. The Fascist Origin of Modern Chinese Criminal Law? Revisiting Attilio Lavagna’s Contribution to the Chinese Penal Code of 1935
- Author
-
Ming-hsi Chu
- Published
- 2022
13. A Study on the Recognition and Memory of Shapes for the Elderly
- Author
-
Ku-Hsi Chu, Jui-Che Tu, and Chang-Franw Lee
- Published
- 2022
14. Discussion on the Teaching Mode of Cooperative Learning from the Perspective of Design Department Students
- Author
-
Ku-Hsi Chu and Jui-Che Tu
- Subjects
Cooperative learning ,Perspective (graphical) ,Mathematics education ,Teaching mode ,Sociology - Published
- 2021
15. Crystal structures of HpSoj–DNA complexes and the nucleoid-adaptor complex formation in chromosome segregation
- Author
-
Cheng-Yi Yen, Min-Guan Lin, Chwan-Deng Hsiao, Chen-Hsi Chu, Bo-Wei Chen, Yuh-Ju Sun, Kai-Zhi Tang, and Lyu-Han Wang
- Subjects
ATPase ,Centromere ,Crystallography, X-Ray ,DNA-binding protein ,Chromosome segregation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Bacterial Proteins ,Structural Biology ,Chromosome Segregation ,Genetics ,Nucleoid ,Binding site ,030304 developmental biology ,Adenosine Triphosphatases ,0303 health sciences ,Binding Sites ,Helicobacter pylori ,biology ,Binding protein ,DNA ,Chromosomes, Bacterial ,Protein superfamily ,DNA-Binding Proteins ,chemistry ,biology.protein ,Biophysics ,030217 neurology & neurosurgery - Abstract
ParABS, an important DNA partitioning process in chromosome segregation, includes ParA (an ATPase), ParB (a parS binding protein) and parS (a centromere-like DNA). The homologous proteins of ParA and ParB in Helicobacter pylori are HpSoj and HpSpo0J, respectively. We analyzed the ATPase activity of HpSoj and found that it is enhanced by both DNA and HpSpo0J. Crystal structures of HpSoj and its DNA complexes revealed a typical ATPase fold and that it is dimeric. DNA binding by HpSoj is promoted by ATP. The HpSoj–ATP–DNA complex non-specifically binds DNA through a continuous basic binding patch formed by lysine residues, with a single DNA-binding site. This complex exhibits a DNA-binding adept state with an active ATP-bound conformation, whereas the HpSoj–ADP–DNA complex may represent a transient DNA-bound state. Based on structural comparisons, HpSoj exhibits a similar DNA binding surface to the bacterial ParA superfamily, but the archaeal ParA superfamily exhibits distinct non-specific DNA-binding via two DNA-binding sites. We detected the HpSpo0J–HpSoj–DNA complex by electron microscopy and show that this nucleoid-adaptor complex (NAC) is formed through HpSoj and HpSpo0J interaction and parS DNA binding. NAC formation is promoted by HpSoj participation and specific parS DNA facilitation.
- Published
- 2018
16. Crystal structure of Leptospira leucine-rich repeat 20 reveals a novel E-cadherin binding protein to induce NGAL expression in HK2 cells
- Author
-
Shen-Hsing Hsu, Ya-Chung Tian, Ming-Yang Chang, Li-Feng Chou, Yuh-Ju Sun, Chih-Wei Yang, and Chen-Hsi Chu
- Subjects
Virulence ,Lipocalin ,Leucine-rich repeat ,medicine.disease_cause ,Crystallography, X-Ray ,Leucine-Rich Repeat Proteins ,Biochemistry ,Cell Line ,03 medical and health sciences ,Leptospira ,medicine ,Humans ,Leptospirosis ,Molecular Biology ,030304 developmental biology ,Alanine ,0303 health sciences ,Mutation ,biology ,030306 microbiology ,Chemistry ,Cadherin ,Binding protein ,Proteins ,Cell Biology ,biology.organism_classification ,Cadherins ,Molecular biology ,Carrier Proteins - Abstract
Leptospirosis is the most common zoonotic disease caused by pathogenic Leptospira, which is classified into three groups according to virulence. Its pathogenic and intermediate species contain leucine-rich repeat (LRR) proteins that are rarely expressed in non-pathogenic strains. In this study, we presented the crystal structure of LSS_11580 (rLRR20) from pathogenic L. santarosai serovar Shermani. X-ray diffraction at a resolution of 1.99 Å revealed a horseshoe-shaped structure containing seven α-helices and five β-sheets. Affinity assays indicated that rLRR20 interacts with E-cadherin on the cell surface. Interestingly, its binds to the extracellular (EC) 1 domain in human epithelial (E)-cadherin, which is responsible for binding to another E-cadherin molecule in neighboring cells. Several charged residues on the concave face of LRR20 were predicted to interact with EC1 domain. In the affinity assays, these charged residues were replaced by alanine, and their affinities to E-cadherin were measured. Three vital residues and mutation variants of LRR20, namely D56A, E59A, and E123A, demonstrated significantly reduced affinity to E-cadherin compared with the control. Besides, we also demonstrated that rLRR20 induced the expression of neutrophil gelatinase-associated lipocalin (NGAL) in HK2 cells. The low ability of the three mutation variants to induce NGAL expression further demonstrates this induction. The present findings indicate that LRR20 from pathogenic Leptospira binds to E-cadherin and interacts with its EC1 domain. In addition, its induction of NGAL expression in HK2 cells is associated with acute kidney injury in human.
- Published
- 2020
17. Analyzing the Relevance of Peer Relationship, Learning Motivation, and Learning Effectiveness—Design Students as an Example
- Author
-
Ku Hsi Chu and Jui-Che Tu
- Subjects
media_common.quotation_subject ,Geography, Planning and Development ,education ,TJ807-830 ,Management, Monitoring, Policy and Law ,TD194-195 ,Renewable energy sources ,Learning styles ,Internship ,0502 economics and business ,Mathematics education ,ComputingMilieux_COMPUTERSANDEDUCATION ,Relevance (information retrieval) ,GE1-350 ,ComputingMilieux_MISCELLANEOUS ,media_common ,Enthusiasm ,learning motivation ,Data collection ,Environmental effects of industries and plants ,Renewable Energy, Sustainability and the Environment ,05 social sciences ,design course ,050301 education ,Questionnaire ,peer relationship ,Environmental sciences ,Design education ,Active learning ,learning effectiveness ,050211 marketing ,Psychology ,0503 education - Abstract
In a design department&rsquo, s practice course there are often group exercises that include intensive interactions between students in the classroom or in the internship factory. In addition, students will deepen the interaction between peers due to course groupings or borrowing of model tools, etc. This study intended to carry out a differential analysis and discussion of the differences among design students from different backgrounds under the three factors of peer relationships, learning motivation, and learning effectiveness. The research method was based on literature analysis and a questionnaire survey, and the research objects were sophomores and seniors in four classes. Statistical analysis methods included the independent sample T-test, one-way ANOVA, and factor and cluster analysis, which were used to summarize different learning styles. The results showed that the students had significant differences of varying degrees in the three factor dimensions. Regarding gender, &ldquo, care about classmates&rsquo, lives&rdquo, in peer relationships scored higher for the females than the males, and the rest had no effect. Regarding educational system, &ldquo, care about the classmates&rsquo, life&rdquo, and &ldquo, sharing life trivia&rdquo, was included in peer relationships. &ldquo, keep the enthusiasm in the course of learning&rdquo, was included in the learning motivation. &ldquo, recognition for self-directed learning&rdquo, ability improvement&rdquo, was included in learning effectiveness. The three factors all had significant differences, and the differences for full-time students were higher than for night school students. Regarding grade, there were significant differences in &ldquo, friends will value my comments&rdquo, in peer relationships, &ldquo, understand course content&rdquo, in learning motivation, and &ldquo, data collection ability&rdquo, understanding team member expertise&rdquo, in learning effectiveness, and seniors scored higher than sophomores in these areas. In addition, the ANOVA and post-hoc tests revealed significant differences in learning the processes between different groups. In peer relationships, full-time seniors scored higher than the other groups, in learning motivation and learning effectiveness, full-time seniors scored higher than night school sophomores. In addition, the overall factors of the full-time seniors were higher than those of the other groups. In the analysis of different learning factors, under the premise of the variation of 58.975%, three factors were extracted by principal axis for analysis with Promax rotation. The different learning factors can be summarized in &ldquo, emphasizing ability improvement&rdquo, &ldquo, care about peer friendship&rdquo, careful and active learning&rdquo, Classification of learning styles under the three factor dimensions was based on two-stage cluster analysis to obtain two clustering results, including &ldquo, enthusiastic and friendly&rdquo, active and autonomous&rdquo, The results showed that the mastery of self-learning time and the learning experience performance have a key influence on the learning motivation and learning effectiveness of design students from different backgrounds. In addition, the results also showed a new opportunity for course improvement and teaching innovation at night schools. The final results of this study could be used as an important reference for research on peer relationships, learning motivation, and learning effectiveness in design education.
- Published
- 2020
18. Structure of the sodium-dependent phosphate transporter reveals insights into human solute carrier SLC20
- Author
-
Jia-Yin Tsai, Cheng-Yi Yen, Ruei-Yi Hong, Yuh-Ju Sun, Min-Guan Lin, Chen-Hsi Chu, Chwan-Deng Hsiao, and Ying-Hsuan Chou
- Subjects
0303 health sciences ,Cell signaling ,Multidisciplinary ,biology ,Chemistry ,Sodium ,chemistry.chemical_element ,SciAdv r-articles ,Transporter ,Phosphate ,biology.organism_classification ,Biochemistry ,Solute carrier family ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,Thermotoga maritima ,Pi ,Biophysics ,Inner membrane ,030217 neurology & neurosurgery ,Research Articles ,030304 developmental biology ,Research Article - Abstract
This study presents structure and function of the sodium-dependent phosphate transporter, TmPiT-Pi/Na., Inorganic phosphate (Pi) is a fundamental and essential element for nucleotide biosynthesis, energy supply, and cellular signaling in living organisms. Human phosphate transporter (hPiT) dysfunction causes numerous diseases, but the molecular mechanism underlying transporters remains elusive. We report the structure of the sodium-dependent phosphate transporter from Thermotoga maritima (TmPiT) in complex with sodium and phosphate (TmPiT-Na/Pi) at 2.3-angstrom resolution. We reveal that one phosphate and two sodium ions (Pi-2Na) are located at the core of TmPiT and that the third sodium ion (Nafore) is located near the inner membrane boundary. We propose an elevator-like mechanism for sodium and phosphate transport by TmPiT, with the TmPiT-Na/Pi complex adopting an inward occluded conformation. We found that disease-related hPiT variants carry mutations in the corresponding sodium- and phosphate-binding residues identified in TmPiT. Our three-dimensional structure of TmPiT provides a framework for understanding PiT dysfunction and for future structure-based drug design.
- Published
- 2020
19. Association of pre-hospital theophylline use and mortality in chronic obstructive pulmonary disease patients with sepsis
- Author
-
Yen-Tao Hsu, Hsi Chu, Peter C. Hou, Shuo-Ming Ou, Ran-Chou Chen, Chia-Jen Shih, Raghu Seethala, Sadeq A. Quraishi, Yu-Ning Shih, Gyorgy Frendl, Yung Tai Chen, and Imoigele P. Aisiku
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Taiwan ,030204 cardiovascular system & hematology ,Lower risk ,law.invention ,Sepsis ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Theophylline ,Risk Factors ,law ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Hospital Mortality ,Propensity Score ,Aged ,Aged, 80 and over ,Mechanical ventilation ,COPD ,business.industry ,Proportional hazards model ,Middle Aged ,medicine.disease ,Respiration, Artificial ,Intensive care unit ,Bronchodilator Agents ,Hospitalization ,Intensive Care Units ,030228 respiratory system ,Anesthesia ,Cohort ,Female ,business ,medicine.drug - Abstract
Background Although theophylline has been shown to have anti-inflammatory effects, the therapeutic use of theophylline before sepsis is unknown. The aim of our study was to determine the effect of theophylline on COPD patients presenting with sepsis. Methods This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients with COPD who were hospitalized for sepsis between 2000 and 2011 were divided into theophylline users and non-users. The primary outcome was 30-day mortality. The secondary outcome was in-hospital death, intensive care unit admission, and need for mechanical ventilation. Cox proportional hazard model and conditional logistic regression were used to calculate the risk between groups. Results A propensity score-matched cohort of 51,801 theophylline users and 51,801 non-users was included. Compared with non-users, the 30-day (HR 0.931, 95% CI 0.910–0.953), 180-day (HR 0.930, 95% CI 0.914–0.946), 365-day (HR 0.944, 95% CI 0.929–0.960) and overall mortality (HR 0.965, 95% CI 0.952–0.979) were all significantly lower in theophylline users. Additionally, the theophylline users also had lower risk of in-hospital death (OR 0.895, 95% CI 0.873–0.918) and need for mechanical ventilation (OR 0.972, 95% CI 0.949–0.997). Conclusions Theophylline use is associated with a lower risk of sepsis-related mortality in COPD patients. Pre-hospital theophylline use may be protective to COPD patients with sepsis.
- Published
- 2017
20. Study on the Performance of Students' Autonomous Learning from the Course Planning of Design Department
- Author
-
Ku-Hsi Chu, Tsu-Wu Hu, and Shin-Tai Chu
- Subjects
Classroom management ,Clinical study design ,Learning disability ,ComputingMilieux_COMPUTERSANDEDUCATION ,Mathematics education ,medicine ,Portfolio ,Autonomous learning ,medicine.symptom ,Action research ,Psychology ,Independent learning ,Rendering (computer graphics) - Abstract
Through individual teacher action research methods, this study designs two courses for design rendering techniques and portfolio design, and conducts planning and operation of classroom management, teaching strategies and innovative design of teaching materials, and explores students' learning attitude, creative performance and willingness to learn independently. Performance. It is hoped that this will enhance students' psychological self-expectation and gain effective learning and ability development in design performance and willingness to learn independently. Through the teaching guidance, after-school tutoring and awakening students' self-learning and the various stages of the publication of the works, the students' achievement factors and feedback on autonomous learning are obtained. The study found that students will have significant growth in learning performance through guidance and after-school interaction during the course of the course, and thus the awakening of autonomous learning. Unconscious, there are great differences in learning and interaction performance. There are three reasons for this: 1. Insufficient basic ability and lack of self-confidence, learning disabilities, 2. Basic ability, but inertia, 3. Self-feeling and rejection growing up. In addition, students who develop self-learning, regardless of their ability to improve, also have a high degree of interaction, and have significantly grown in their performance and extracurricular knowledge. In this study, the teaching results obtained through the design rendering techniques and portfolio design of the two courses, in addition to improving students' independent learning, but also conducive to the training of students' design ability. The research results provided can also be provided to the planning application and academic research reference of other related design courses.
- Published
- 2019
21. Association of sleep apnoea with chronic kidney disease in a large cohort from Taiwan
- Author
-
Yuan-Hao Lo, Yung Tai Chen, Hsi Chu, Shuo-Ming Ou, Kun Ta Chou, and Chia-Jen Shih
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Retrospective cohort study ,030204 cardiovascular system & hematology ,medicine.disease ,Confidence interval ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,Epidemiology ,Cohort ,medicine ,Physical therapy ,030212 general & internal medicine ,business ,Kidney disease - Abstract
Background and objective Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long-term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension. Methods Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010. Results The sample is composed of 43 434 individuals (8687 patients with SA and 34 747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29–1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68–2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21–3.90, P = 0.01). Conclusion SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See Editorial, page 578
- Published
- 2016
22. Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus
- Author
-
Chih Yu Yang, Szu Yuan Li, Der Cherng Tarng, Shuu Jiun Wang, Hsi Chu, Yi Jung Lee, Chia Jen Shih, Shu-Chen Kuo, Chih Ching Lin, Pei Wen Chao, Yung Tai Chen, Shuo Ming Ou, and Tzeng Ji Chen
- Subjects
Oncology ,medicine.medical_specialty ,endocrine system diseases ,business.industry ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,Hypoglycemia ,medicine.disease ,Lower risk ,Metformin ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,business ,Stroke ,Dipeptidyl peptidase-4 ,medicine.drug - Abstract
In a large observational database study of add-on treatments to metformin, the addition of dipeptidyl peptidase-4 (DPP-4) inhibitors was associated with a lower risk for all-cause mortality, stroke...
- Published
- 2015
23. A study on application of OLED technology in development of product innovation
- Author
-
Shin-Tai Chu, Ku-Hsi Chu, and Tsu-Wu Hu
- Subjects
Space technology ,Engineering drawing ,Product design ,Computer science ,Product innovation ,business.industry ,New product development ,High color ,Task analysis ,business ,Rendering (computer graphics) ,Design technology - Abstract
This research, based on the technical energy of lighting, integrates its application with various product design ideas and introduces OLED technology into different fields to develop new product features and values. This research also use HDT (Human Design Technology) to search user's requirements and check design items of drinking water equipment. The results of this study summarize several application design types: 1. Large Size screen information display application, 2. Improve the illumination design of night instruction, 3. Using OLED high color rendering technology to change the appearance of color products. As for the future product application of OLED technology, this study proposed two points for future research recommendations: 1. For the product surface screen, OLED can provide more diversification of display space technology applications; 2. It's necessary to improve the OLED in the long-term display color decline and the Imprinting phenomenon, in order to implement the application of the product design.
- Published
- 2018
24. Involuntary Non-Voting Stock Due to War: Reflections and Solutions to Remaining Corporate Governance Issues for the Chinese Civil War
- Author
-
Ming-hsi Chu and Kai-Ping Chang
- Subjects
Oppression ,Shareholder ,Property rights ,Voting ,media_common.quotation_subject ,Corporate governance ,One share, one vote ,Legislation ,Business ,Stock (geology) ,media_common ,Law and economics - Abstract
Modern wars have prohibited people from communication with one another for a long time. This separation has actually caused corporate governance problems. As an example, if a significant enough portion of shareholders cannot attend a shareholders’ meeting and vote, not only can no lawful resolutions be made due to mandatory quorum requirements, but those shareholders are easily oppressed by controlling shareholders. How can the law protect the property rights of shareholders who cannot attend such meetings while upholding efficient corporate governance? In this paper, we took the experience of the Chinese Civil War as an example to answer the questions. We did archival work on ad hoc legislation in 1964 and its amendment in 1992 in response to this situation. In addition, we scrutinized the solutions proposed during the legislative process, analysed them from a legal and economics perspective, and offer our own proposal. We found that the 1992 amendment freezes shareholders’ voting rights and deducts their shares when calculating the total number of shares. The involuntary non-voting stock policy deviates from the “one share one vote” principle and causes oppression indirectly; thus, it is obviously not an appropriate measure. We propose that auctioning those shares would be a more efficient and property-right-protective alternative to adopt.
- Published
- 2018
25. Competing Interpreters of International Law in China: Interaction between Legislature and Judiciary in National War Crimes Trials, 1946–1947
- Author
-
Ming-hsi Chu
- Subjects
Politics ,Law ,Political science ,Elite ,Legislature ,Municipal law ,War crime ,International law ,Legal profession ,Supreme court - Abstract
After World War II ended, Nationalist China adjudicated 883 non-major war criminals. To provide grounds for judgment, the Legislative Yuan, the central legislative authority, passed the War Criminal Trial Act (WCTA) in 1946. The WCTA was similar to, but not necessarily the same as, international law. This paper asks: What was the difference between the WCTA, a domestic law, and international law? What did the difference imply? How did the judiciary respond to the WCTA? This paper compares the content of the international and national laws and delves into administrative and judicial archives to answer the questions. This paper found that the WCTA departed from international law in many aspects. It stipulated a broader scope, adopted a stricter liability, and intended to promote Chinese nationalism. At the time, the legislators were not delegates elected by citizens, but specialists appointed by the ruling party, so the WCTA represented the opinion of the political sectors. However, the Judicial Yuan, which was responsible for unifying legal interpretation, limited the scope of the WCTA, hindered the purpose of promoting Chinese nationalism, and restrained the political sector’s revenge on Taiwanese people by interpreting the WCTA per international law. Because Judicial Yuan meetings were composed of Supreme Court senior judges, its interpretations represented the elite legal professionals’ view. The legislature and the judiciary were competing interpreters of international law. This paper concludes that elite legal professionals’ belief in “pursuing a civilized state” triumphed in this competition at the end.
- Published
- 2018
26. Insights into ParB spreading from the complex structure of Spo0J and parS
- Author
-
Chia-En Hsu, Chen-Hsi Chu, Yuh-Ju Sun, Ming-Hsing Lin, and Bo-Wei Chen
- Subjects
DNA, Bacterial ,Models, Molecular ,Molecular Sequence Data ,Plasma protein binding ,Biology ,Crystallography, X-Ray ,Chromosome segregation ,chemistry.chemical_compound ,Bacterial Proteins ,X-Ray Diffraction ,Chromosome Segregation ,Scattering, Small Angle ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Protein Structure, Quaternary ,Peptide sequence ,Spores, Bacterial ,Genetics ,Regulation of gene expression ,Multidisciplinary ,Base Sequence ,Helicobacter pylori ,Sequence Homology, Amino Acid ,Circular bacterial chromosome ,Chromosome ,Biological Sciences ,Cell biology ,Nucleoprotein ,chemistry ,DNA ,Protein Binding - Abstract
Spo0J (stage 0 sporulation protein J, a member of the ParB superfamily) is an essential component of the ParABS (partition system of ParA, ParB, and parS)-related bacterial chromosome segregation system. ParB (partition protein B) and its regulatory protein, ParA, act cooperatively through parS (partition S) DNA to facilitate chromosome segregation. ParB binds to chromosomal DNA at specific parS sites as well as the neighboring nonspecific DNA sites. Various ParB molecules can associate together and spread along the chromosomal DNA. ParB oligomer and parS DNA interact together to form a high-order nucleoprotein that is required for the loading of the structural maintenance of chromosomes proteins onto the chromosome for chromosomal DNA condensation. In this report, we characterized the binding of parS and Spo0J from Helicobacter pylori (HpSpo0J) and solved the crystal structure of the C-terminal domain truncated protein (Ct-HpSpo0J)-parS complex. Ct-HpSpo0J folds into an elongated structure that includes a flexible N-terminal domain for protein-protein interaction and a conserved DNA-binding domain for parS binding. Two Ct-HpSpo0J molecules bind with one parS. Ct-HpSpo0J interacts vertically and horizontally with its neighbors through the N-terminal domain to form an oligomer. These adjacent and transverse interactions are accomplished via a highly conserved arginine patch: RRLR. These interactions might be needed for molecular assembly of a high-order nucleoprotein complex and for ParB spreading. A structural model for ParB spreading and chromosomal DNA condensation that lead to chromosome segregation is proposed.
- Published
- 2015
27. Risk of tuberculosis among healthcare workers in an intermediate-burden country: A nationwide population study
- Author
-
Szu Yuan Li, Hsi Chu, Yu Ning Shih, Yi Jung Lee, Yen Tao Hsu, Shu-Chen Kuo, Chia Jen Shih, Der Cherng Tarng, Shuo Ming Ou, Ran Chou Chen, and Yung Tai Chen
- Subjects
Adult ,Male ,Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,Tuberculosis ,Health Personnel ,health care facilities, manpower, and services ,education ,Population ,Antitubercular Agents ,Taiwan ,Cohort Studies ,Young Adult ,Risk Factors ,Environmental health ,Epidemiology ,medicine ,Humans ,Developing Countries ,Tuberculosis, Pulmonary ,History of tuberculosis ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,medicine.disease ,Infectious Diseases ,Population study ,Female ,business ,Follow-Up Studies ,Cohort study - Abstract
Summary Objective The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. Methods A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000–2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. Results The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs . 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08–2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02–2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37–4.72) compared to the matched cohort. Conclusions HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.
- Published
- 2014
28. Long-Term Clinical Outcome of Major Adverse Cardiac Events in Survivors of Infective Endocarditis
- Author
-
Hsi Chu, Shuo Ming Ou, Yi Jung Lee, Der Cherng Tarng, Shu-Chen Kuo, Yung Tai Chen, Szu Yuan Li, Chia Jen Shih, Wu Chang Yang, Pei Wen Chao, and Chih Yu Yang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Population ,Myocardial Infarction ,Sudden cardiac death ,Risk Factors ,Physiology (medical) ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Endocarditis ,Survivors ,Myocardial infarction ,education ,Intensive care medicine ,Stroke ,Aged ,Heart Failure ,education.field_of_study ,business.industry ,Arrhythmias, Cardiac ,Middle Aged ,medicine.disease ,Death, Sudden, Cardiac ,Heart failure ,Infective endocarditis ,Female ,Morbidity ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
Background— Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results— A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion— Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.
- Published
- 2014
29. Impact of Beta‐Blocker Initiation Timing on Mortality Risk in Patients With Diabetes Mellitus Undergoing Noncardiac Surgery: A Nationwide Population‐Based Cohort Study
- Author
-
Hsi Chu, Lung Wen Tsai, and Ray Jade Chen
- Subjects
Male ,Time Factors ,Databases, Factual ,Epidemiology ,beta‐blocker ,030204 cardiovascular system & hematology ,Cohort Studies ,Propanolamines ,surgery ,0302 clinical medicine ,Risk Factors ,Odds Ratio ,Medicine ,Hospital Mortality ,030212 general & internal medicine ,Carvedilol ,Original Research ,Diabetes, Type 2 ,Middle Aged ,Bisoprolol ,Surgical Procedures, Operative ,diabetes mellitus ,Female ,Cardiology and Cardiovascular Medicine ,Metoprolol ,medicine.drug ,medicine.medical_specialty ,medicine.drug_class ,Adrenergic beta-Antagonists ,Carbazoles ,Taiwan ,Perioperative Care ,03 medical and health sciences ,Internal medicine ,Diabetes mellitus ,Humans ,Mortality ,Propensity Score ,Beta blocker ,Aged ,business.industry ,Odds ratio ,Perioperative ,Protective Factors ,medicine.disease ,Surgery ,Atenolol ,Diabetes Mellitus, Type 2 ,Propensity score matching ,business - Abstract
Background Relevant clinical studies have been small and have not convincingly demonstrated whether the perioperative initiation of beta‐blockers should be considered in patients with diabetes mellitus undergoing noncardiac surgery. Methods and Results In this nationwide propensity score–matched study, we included patients with diabetes mellitus undergoing noncardiac surgery between 2000 and 2011 from Taiwan's National Health Insurance Research Database. Patients were classified as beta‐blocker and non–beta‐blocker cohorts. We further stratified beta‐blocker users into cardioprotective beta‐blocker (atenolol, bisoprolol, metoprolol, or carvedilol) and other beta‐blocker users. To investigate time of initiation of beta‐blocker use, initiation time was stratified into 2 periods (>30 and ≤30 days preoperatively). The outcomes of interest were in‐hospital and 30‐day mortality. After propensity score matching, we identified 50 952 beta‐blocker users and 50 952 matched controls. Compared with non–beta‐blocker users, cardioprotective beta‐blocker users were associated with lower risks of in‐hospital (odds ratio 0.75, 95% CI 0.68–0.82) and 30‐day (odds ratio 0.75, 95% CI 0.70–0.81) mortality. Among initiation times, only the use of cardioprotective beta‐blockers for >30 days was associated with decreased risk of in‐hospital (odds ratio 0.72, 95% CI 0.65–0.78) and 30‐day (odds ratio 0.72, 95% CI 0.66–0.78) mortality. Of note, use of other beta‐blockers for ≤30 days before surgery was associated with increased risk of both in‐hospital and 30‐day mortality. Conclusions The use of cardioprotective beta‐blockers for >30 days before surgery was associated with reduced mortality risk, whereas short‐term use of beta‐blockers was not associated with differences in mortality in patients with diabetes mellitus.
- Published
- 2017
30. Crystal structures of starch binding domain from Rhizopus oryzae glucoamylase in complex with isomaltooligosaccharide: Insights into polysaccharide binding mechanism of CBM21 family
- Author
-
Yuh-Ju Sun, Shih-Wei Lin, Ting-Ying Jiang, Kun-Mou Li, Chen-Hsi Chu, and Margaret Dah-Tsyr Chang
- Subjects
chemistry.chemical_classification ,biology ,Isomaltooligosaccharide ,Starch ,Rhizopus oryzae ,biology.organism_classification ,Polysaccharide ,Biochemistry ,Polysaccharide binding ,chemistry.chemical_compound ,chemistry ,Structural Biology ,Hydrolase ,Binding site ,Molecular Biology ,Starch binding - Abstract
Glucoamylases are responsible for hydrolysis of starch and polysaccharides to yield β-d-glucose. Rhizopus oryzae glucoamylase (RoGA) is composed of an N-terminal starch binding domain (SBD) and a C-terminal catalytic domain connected by an O-glycosylated linker. Two carbohydrate binding sites in RoSBD have been identified, site I is created by three highly conserved aromatic residues, Trp47, Tyr83, and Tyr94, and site II is built up by Tyr32 and Phe58. Here, the two crystal structures of RoSBD in complex with only α-(1,6)-linked isomaltotriose (RoSBD-isoG3) and isomaltotetraose (RoSBD-isoG4) have been determined at 1.2 and 1.3 A, respectively. Interestingly, site II binding is observed in both complexes, while site I binding is only found in the RoSBD-isoG4 complex. Hence, site II acts as the recognition binding site for carbohydrate and site I accommodates site II to bind isoG4. Site I participates in sugar binding only when the number of glucosyl units of oligosaccharides is more than three. Taken together, two carbohydrate binding sites in RoSBD cooperate to reinforce binding mode of glucoamylase with polysaccharides as well as the starch. Proteins 2014; 82:1079–1085. © 2013 Wiley Periodicals, Inc.
- Published
- 2013
31. Long-term risks of cardiovascular events in patients with chronic kidney disease who survived sepsis
- Author
-
Hsi Chu and Yung-Tai Chen
- Subjects
education.field_of_study ,medicine.medical_specialty ,business.industry ,Population ,Hazard ratio ,medicine.disease ,Confidence interval ,Sepsis ,Internal medicine ,Heart failure ,medicine ,In patient ,Myocardial infarction ,education ,Intensive care medicine ,business ,Kidney disease - Abstract
BACKGROUND We aimed to examine the risk of subsequent cardiovascular events in patients with CKD discharged after sepsis. METHODS Using the data on CKD patients from Taiwan9s National Health Insurance Research Database, we identified sepsis subjects who survived between 2000 and 2010, and each survivor was propensity-score-matched to one nonsepsis hospitalized controls.Cox regression models were used to estimate the hazard ratios of clinical outcomes, including major adverse cardiovascular events, all-cause death and hospitalization for heart failure. RESULTS Among 66,961 sepsis survivors,. sepsis survivors in comparison to matched hospitalized nonsepsis control subjects, had greater risks of major adverse cardiovascular events (HR, 1.35; 95% confidence interval [CI], 1.31–1.38), myocardial infarction (HR, 1.39; 95% CI, 1.32–1.47) ischemic stroke (HR, 1.46; 95% CI, 1.40–1.52), all-cause mortality (HR, 1.56; 95% CI, 1.54–1.58), and hospitalization for heart failure (HR, 1.55; 95% CI, 1.51–1.59). CONCLUSIONS Our findings highlight that sepsis in CKD population was associated with significantly increased risk of cardiovascular events among survivors.
- Published
- 2016
32. Lymphotoxin-β Interacts with Methylated EGFR to Mediate Acquired Resistance to Cetuximab in Head and Neck Cancer
- Author
-
Wen Hao Hsu, Han Syuan Lin, Chen Hsi Chu, Wei Lun Hwang, Chiou Hwa Yuh, Chih Yi Lin, Hsiao Jung Wang, Mien Chie Hung, Shyh Kuan Tai, Yang Hui Ho, Hsin Yi Lan, Pon Bo Chen, Shih Pei Wu, Muh Hwa Yang, Hua Kuo Lin, and Dennis Shin Shian Hsu
- Subjects
0301 basic medicine ,Lymphotoxin-beta ,Cancer Research ,Protein-Arginine N-Methyltransferases ,Epithelial-Mesenchymal Transition ,Cetuximab ,Drug resistance ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,neoplasms ,Protein Kinase Inhibitors ,Zebrafish ,Mutation ,Squamous Cell Carcinoma of Head and Neck ,Head and neck cancer ,NF-kappa B ,Cancer ,Zebrafish Proteins ,medicine.disease ,Head and neck squamous-cell carcinoma ,Xenograft Model Antitumor Assays ,digestive system diseases ,ErbB Receptors ,Repressor Proteins ,Disease Models, Animal ,030104 developmental biology ,Lymphotoxin ,Oncology ,Cell culture ,Drug Resistance, Neoplasm ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Carcinoma, Squamous Cell ,Snail Family Transcription Factors ,medicine.drug - Abstract
Purpose: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation–mediated de novo resistance. Here, we investigated the driver gene mutation–independent mechanism for cetuximab resistance in HNSCC. Experimental Design: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab. Zebrafish model was applied for evaluating the synergistic effect of combinatory drugs for overcoming cetuximab resistance. Results: The cetuximab-resistant HNSCC cells undergo a Snail-induced epithelial–mesenchymal transition. Mechanistically, Snail induces the expression of lymphotoxin-β (LTβ), a TNF superfamily protein that activates NF-κB, and protein arginine methyltransferase 1 (PRMT1), an arginine methyltransferase that methylates EGFR. LTβ interacts with methylated EGFR to promote its ligand-binding ability and dimerization. Furthermore, LTβ activates the NF-κB pathway through a LTβ receptor–independent mechanism. Combination of an EGFR tyrosine kinase inhibitor and a NF-κB inhibitor effectively suppressed cetuximab-resistant HNSCC and interfering with the EGFR–LTβ interaction reverses resistance. Conclusions: Our findings elucidate the mechanism of driver gene mutations–independent mechanism of acquired resistance to cetuximab in HNSCC and also provide potential strategies for combating cetuximab resistance. Clin Cancer Res; 23(15); 4388–401. ©2017 AACR.
- Published
- 2016
33. Structures ofHelicobacter pyloriuridylate kinase: insight into release of the product UDP
- Author
-
Yuh-Ju Sun, Ming-Hsing Lin, Mu-Hsuan Liu, Pin-Chen Chen, Yi-Chuan Li, Chen-Hsi Chu, and Chwan-Deng Hsiao
- Subjects
Models, Molecular ,GTP' ,Stereochemistry ,Dimer ,Molecular Sequence Data ,Random hexamer ,Crystallography, X-Ray ,Protein Structure, Secondary ,Uridine Diphosphate ,chemistry.chemical_compound ,Adenosine Triphosphate ,Structural Biology ,Transferase ,Amino Acid Sequence ,Binding Sites ,Helicobacter pylori ,Chemistry ,Uridylate kinase ,General Medicine ,carbohydrates (lipids) ,Biochemistry ,Helix ,Guanosine Triphosphate ,Protein Multimerization ,Nucleoside-Phosphate Kinase ,Sequence Alignment - Abstract
Uridylate kinase (UMPK; EC 2.7.4.22) transfers the γ-phosphate of ATP to UMP, forming UDP. It is allosterically regulated by GTP. Structures of Helicobacter pylori UMPK (HpUMPK) complexed with GTP (HpUMPK-GTP) and with UDP (HpUMPK-UDP) were determined at 1.8 and 2.5 Å resolution, respectively. As expected, HpUMPK-GTP forms a hexamer with six GTP molecules at its centre. Interactions between HpUMPK and GTP are made by the β3 strand of the sheet, loop β3α4 and the α4 helix. In HpUMPK-UDP, the hexameric symmetry typical of UMPKs is absent. Only four of the HpUMPK molecules bind UDP; the other two HpUMPK molecules are in the UDP-free state. The asymmetric hexamer of HpUMPK-UDP, which has an exposed dimer interface, may assist in UDP release. Furthermore, the flexibility of the α2 helix, which interacts with UDP, is found to increase when UDP is absent in HpUMPK-UDP. In HpUMPK-GTP, the α2 helix is too flexible to be observed. This suggests that GTP binding may affect the conformation of the α2 helix, thereby promoting UDP release.
- Published
- 2012
34. Molecular Evolution and Functional Diversification of Fatty Acid Desaturases after Recurrent Gene Duplication in Drosophila
- Author
-
Shu Fang, Cheng-Ruei Lee, Kuang-Hsi Chu, Chau-Ti Ting, Chuan-Chan Wang, and Shun-Chern Tsaur
- Subjects
Fatty Acid Desaturases ,Lineage (evolution) ,Biology ,Evolution, Molecular ,positive selection ,Molecular evolution ,Gene Duplication ,Gene duplication ,Genetics ,Animals ,Gene family ,Molecular Biology ,Gene ,Phylogeny ,Research Articles ,Ecology, Evolution, Behavior and Systematics ,Synteny ,fatty acid desaturase ,biology.organism_classification ,Drosophila melanogaster ,Fatty acid desaturase ,pheromonal diversity ,biology.protein ,cuticular hydrocarbon ,Drosophila - Abstract
Frequent gene duplications in the genome incessantly supply new genetic materials for functional innovation presumably driven by positive Darwinian selection. This mechanism in the desaturase gene family has been proposed to be important in triggering the pheromonal diversification in insects. With the recent completion of a dozen Drosophila genomes, a genome-wide perspective is possible. In this study, we first identified homologs of desaturase genes in 12 Drosophila species and noted that while gene duplication events are relatively frequent, gene losses are not scarce, especially in the desat1-desat2-desatF clade. By reconciling the gene tree with species phylogeny and the chromosomal synteny of the sequenced Drosophila genomes, at least one gene loss in desat2 and a minimum of six gene gains (resulting in seven desatF homologs, alpha-eta), three gene losses and one relocation in desatF were inferred. Upon branching off the ancestral desat1 lineage, both desat2 and desatF gained novel functions through accelerating protein evolution. The amino acid residues under positive selection located near the catalytic sites and the C-terminal region might be responsible for altered substrate selectivity between closely related species. The association between the expression pattern of desatF-alpha and the chemical composition of cuticular hydrocarbons implies that the ancestral function of desatF-alpha is the second desaturation at the four carbons after the first double bond in diene synthesis, and the shift from bisexual to female-specific expression in desatF-alpha occurred in the ancestral lineage of Drosophila melanogaster subgroup. A relationship between the number of expressed desatF homologs and the diene diversification has also been observed. These results suggest that the molecular diversification of fatty acid desaturases after recurrent gene duplication plays an important role in pheromonal diversity in Drosophila.
- Published
- 2009
35. Kinetic and structural properties of triosephosphate isomerase fromHelicobacter pylori
- Author
-
Haimei Huang, Yi-Ju Lai, Yuh-Ju Sun, and Chen-Hsi Chu
- Subjects
chemistry.chemical_classification ,Helicobacter pylori ,Protein Conformation ,Isomerase ,Biology ,Crystallography, X-Ray ,Biochemistry ,Triosephosphate isomerase ,Kinetics ,chemistry.chemical_compound ,Protein structure ,Enzyme ,Bacterial Proteins ,chemistry ,Structural Biology ,Mutation ,TIM barrel ,Molecular replacement ,Cloning, Molecular ,Molecular Biology ,Alpha helix ,Triose-Phosphate Isomerase ,Dihydroxyacetone phosphate - Abstract
Triosephosphate isomerase (TIM) catalyzes the interconversion between dihydroxyacetone phosphate and D-glyceraldehyde-3-phosphate in the glycolysis-gluconeogenesis metabolism pathway. The Helicobacter pylori TIM gene (HpTIM) was cloned, and HpTIM was expressed and purified. The enzymatic activity of HpTIM for the substrate GAP was determined (K(m) = 3.46 +/- 0.23 mM and k(cat) = 8.8 x 10(4) min(-1)). The crystal structure of HpTIM was determined by molecular replacement at 2.3 A resolution. The overall structure of HpTIM was (beta/alpha)beta(beta/alpha)(6), which resembles the common TIM barrel fold, (beta/alpha)(8); however, a helix is missing after the second beta-strand. The conformation of loop 6 and binding of phosphate ion suggest that the determined structure of HpTIM was in the "closed" state. A highly conserved Arg-Asp salt bridge in the "DX(D/N)G" motif of most TIMs is absent in HpTIM because the sequence of this motif is "(211)SVDG(214)." To determine the significance of this salt bridge to HpTIM, four mutants, including K183S, K183A, D213Q, and D213A, were constructed and characterized. The results suggest that this conserved salt bridge is not essential for the enzymatic activity of HpTIM; however, it might contribute to the conformational stability of HpTIM.
- Published
- 2008
36. Adenocarcinoma of the Lung Presenting as a Mycetoma With an Air Crescent Sign
- Author
-
Yuh Min Chen, Lan-Fu Wang, Reury-Perng Perng, and Hsi Chu
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Air crescent sign ,medicine.medical_specialty ,Lung Neoplasms ,Standardized uptake value ,Adenocarcinoma ,Critical Care and Intensive Care Medicine ,Diagnosis, Differential ,Lesion ,Bronchoscopy ,medicine ,Humans ,Crescent sign ,Pneumonectomy ,Lung cancer ,Aged, 80 and over ,Tomography, Emission-Computed, Single-Photon ,Lung Diseases, Fungal ,medicine.diagnostic_test ,business.industry ,Respiratory disease ,medicine.disease ,Positron emission tomography ,Mycetoma ,Radiology ,medicine.symptom ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,Chest radiograph - Abstract
An 89-year-old man was admitted to the hospital due to intermittent anterior chest wall pain for > 1 month. A chest radiograph obtained on November 9, 2004, demonstrated a mass with an irregular border, inside a thin-walled cavity, located in the superior segment of the left lower lobe. A chest CT scan revealed an irregular thin-walled cavity, 5.9 × 5.4 × 4 cm in size, with an air-crescent sign in the superior segment of the left lower lobe, and an intracavitary fungus ball-like mass. A bronchoscopic examination was performed, revealing only external compression of the left lower lobe bronchial lumen. Cultures from both the brushing cytology and brushing fungus specimens were negative. Since the patient was a heavy smoker and the chest radiograph obtained 23 months before had revealed no active pulmonary lesion, neoplastic growth was still highly suspected. Thus, an 18 F-fluoro-2-deoxyglucose positron emission tomography study was performed on November 25, and a mass with a slightly increased standard uptake value (3.17; cutoff value, 2.5) was found. He received a left lower lobe lobectomy on December 23, and a tumor with many septum-like structures connecting the surrounding pulmonary parenchymal tissue was found in the superior segment of the left lower lobe. The final pathologic diagnosis was adenocarcinoma of the lung (pT2N0M0). Thus, even though the chest radiograph and chest CT scan showed a typical air-crescent sign ( ie , mass inside a cavity) favoring a mycetoma, the physician should still keep in mind that lung cancer may also unusually present in this way.
- Published
- 2007
37. Helicobacter pylori cell binding factor 2: Insights into domain motion
- Author
-
Chwan-Deng Hsiao, Vankadari Naveen, Bo Wei Chen, Yen Chun Tsai, Yuh-Ju Sun, and Chen Hsi Chu
- Subjects
0301 basic medicine ,Models, Molecular ,Protein domain ,Plasma protein binding ,Biology ,Crystallography, X-Ray ,Protein Structure, Secondary ,03 medical and health sciences ,Bacterial Proteins ,Protein Domains ,X-Ray Diffraction ,Structural Biology ,Scattering, Small Angle ,Amino Acid Sequence ,Binding site ,Peptide sequence ,Peptidylprolyl isomerase ,Binding Sites ,030102 biochemistry & molecular biology ,Helicobacter pylori ,Sequence Homology, Amino Acid ,Periplasmic space ,Peptidylprolyl Isomerase ,030104 developmental biology ,Biochemistry ,Chaperone (protein) ,Biophysics ,biology.protein ,Electrophoresis, Polyacrylamide Gel ,Protein Multimerization ,Bacterial outer membrane ,Molecular Chaperones ,Protein Binding - Abstract
Helicobacter pylori cell binding factor 2 (HpCBF2) is an antigenic virulence factor belonging to the SurA-like peptidyl-prolyl cis-trans isomerase family with implications for pathogenicity in the human gastrointestinal tract. HpCBF2 possesses PPIase activity and could act as a periplasmic chaperone to regulate outer membrane protein assembly. Here, we measured the isomerization and chaperone activity of HpCBF2, and determined the crystal structure of HpCBF2 in complex with an inhibitor, indole-2-carboxylic acid (I2CA), at 2.4A resolution. HpCBF2-I2CA forms a homodimer encasing a large central hydrophobic cavity with a basket-like structure, and each monomer contains a PPIase and a chaperone domain. In the HpCBF2-I2CA dimer, the two PPIase domains separate by a distance of 22.8A, while the two chaperone domains arrange in a domain-swap manner. The PPIase domains bound with I2CA ligand face towards the chaperone domains and are shielded by surrounding hydrophobic residues. With the aid of SAXS experiments, we also revealed domain motion between the apo- and I2CA-bound states of HpCBF2. The domain motion in HpCBF2 might be necessary for the isomerization activity of PPIase and the accommodation of the unfolded and partially folded peptides to refold by chaperone domain.
- Published
- 2015
38. Association of sleep apnoea with chronic kidney disease in a large cohort from Taiwan
- Author
-
Hsi, Chu, Chia-Jen, Shih, Shuo-Ming, Ou, Kun-Ta, Chou, Yuan-Hao, Lo, and Yung-Tai, Chen
- Subjects
Adult ,Male ,Incidence ,Taiwan ,Middle Aged ,Sleep Apnea Syndromes ,Risk Factors ,Case-Control Studies ,Hypertension ,Diabetes Mellitus ,Humans ,Female ,Renal Insufficiency, Chronic ,Proportional Hazards Models ,Retrospective Studies - Abstract
Recent observational studies have shown that sleep apnoea (SA) is associated with increased risk of incident CKD. However, the contribution of SA relative to common traditional CKD risk factors remains unknown. The aims of this study were to investigate the long-term risk of incident CKD events following SA diagnosis and compare the relative contributions of SA, diabetes and hypertension.Data were retrieved from Taiwan's National Health Insurance Research Database during the period between 2000 and 2010 for this retrospective cohort study. The cohorts are composed of patients (age ≥ 20 years) newly diagnosed with SA and matched subjects without SA. The two cohorts were followed until the occurrence of CKD, death or the end of 2010.The sample is composed of 43,434 individuals (8687 patients with SA and 34,747 matched non-SA subjects). A total of 157 new CKD events in patients with SA and 298 events in the matched non-SA cohort were recorded during a mean follow-up period of 3.9 years (incidence rates, 4.5 and 2.2/per 1000 person-years). The risk of CKD development was greater among patients with SA than in the matched non-SA cohort (adjusted hazard ratio (aHR) 1.58, 95% confidence interval ( CI): 1.29-1.94). The contribution of SA to the CKD hazard was similar to that of hypertension (aHR 1.17, 95% CI: 0.68-2.01, P = 0.56), whereas that of diabetes remained significantly higher (aHR 2.17, 95% CI: 1.21-3.90, P = 0.01).SA was associated with an increase in the risk of CKD incidence similar to that of hypertension. See article, page 578.
- Published
- 2015
39. Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on major adverse cardiac events in patients with newly diagnosed type 2 diabetes: a nationwide study
- Author
-
Shuo-Ming Ou, Hsi Chu, Yung Tai Chen, and Chia-Jen Shih
- Subjects
Male ,medicine.medical_specialty ,Population ,Taiwan ,Angiotensin-Converting Enzyme Inhibitors ,Type 2 diabetes ,urologic and male genital diseases ,Angiotensin Receptor Antagonists ,Internal medicine ,Diabetes mellitus ,medicine ,Prevalence ,Humans ,cardiovascular diseases ,Myocardial infarction ,Intensive care medicine ,education ,Adverse effect ,Propensity Score ,Stroke ,Retrospective Studies ,education.field_of_study ,biology ,business.industry ,Incidence ,Hazard ratio ,Angiotensin-converting enzyme ,Middle Aged ,medicine.disease ,Prognosis ,Diabetes Mellitus, Type 2 ,Hypertension ,biology.protein ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
article i nfo Background:Guidelinesforhypertensionmanagementrecommendeitherangiotensin-convertingenzymeinhib- itors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line therapies for diabetes population. No head- to-head trial has been conducted to determine the priority of ACEI/ARB use for major adverse cardiac events (MACEs) in diabetes mellitus. Methods: Data on patients with newly diagnosed diabetes treated with ACEIs or ARBs were collected from Taiwan's National Health Insurance Research Database for the period 2000-2010. A total of 30,777 ARB users and 21,436 ACEI users were identified. One ARB user was matched to one ACEI user by propensity score. Intention-to-treat (ITT) and as-treated (AT) models were used. The primary outcomes were myocardial infarc- tion, ischemic stroke, and all-cause mortality. The secondary outcomes were hospitalization for acute kidney in- jury and hyperkalemia. Findings: Compared with ACEI users (n = 21,436), ARB users (n = 30,777) showed no significant difference in the outcomes of myocardial infarction (hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.80 to 1.07), ische- mic stroke (HR: 0.95; 95% CI: 0.87 to 1.04), or all-cause mortality (HR: 0.95; 95% CI: 0.89 to 1.01) in the ITT anal- ysis. The risks of hospitalization for acute kidney injury and hyperkalemia also did not differ between groups. ACEI and ARB use also had similar effects on MACEs and adverse effects in the AT analysis. Conclusions: This large cohort study supports the comparative effectiveness of ACEIs and ARBs in terms of MACE outcomes in patients with incident diabetes.
- Published
- 2015
40. Impact of severe acute respiratory syndrome on the status of lung cancer chemotherapy patients and a correlation of the signs and symptoms
- Author
-
Reury Perng Perng, Hsi Chu, Chun-Ming Tsai, Yuh Min Chen, and Jacqueline Whang-Peng
- Subjects
Severe acute respiratory syndrome (SARS) ,Pulmonary and Respiratory Medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Isolation (health care) ,medicine.medical_treatment ,Taiwan ,non-small cell lung cancer (NSCLC) ,Severe Acute Respiratory Syndrome ,Article ,Patient Isolation ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Chemotherapy ,Humans ,Prospective Studies ,skin and connective tissue diseases ,Lung cancer ,Non-small-cell lung cancer (NSCLC) ,Clinical Trials as Topic ,business.industry ,fungi ,Respiratory disease ,Fear ,medicine.disease ,Surgery ,body regions ,Clinical trial ,Attitude ,Oncology ,Patient Compliance ,Severe acute respiratory syndrome ,Viral disease ,business - Abstract
Our aim was to describe the impact of severe acute respiratory syndrome (SARS) on the status and chemotherapy of non-small-cell lung cancer (NSCLC) patients who had entered clinical trials, and to review how to differentiate the signs and symptoms of SARS from lung cancer and its treatment-related toxicities. A prospective case series involving 79 NSCLC patients who were enrolled in clinical trials undergoing chemotherapy at Taipei Veterans General Hospital, between April 1 and July 15, 2003, was studied. Whether or not there existed a delay, omission, or refusal of scheduled chemotherapy, was recorded. Whether or not our patients had been suspected of or treated as having SARS, was recorded. The patients filled out questionnaires regarding lung cancer treatment and the risk of getting SARS from the hospital. Among these patients, five were placed in an isolation unit to rule out SARS infection during this period of time, and no patient was documented to have suffered from a SARS infection after examinations. Of 373 scheduled chemotherapy injections in 79 patients, a delay in treatment occurred only 10 times. Three patients refused further chemotherapy because of a fear of getting SARS if they visited the hospital. Fifty-eight patients responded to our questionnaires. Thirty-seven patients (63.8%) were afraid of visiting hospital during this SARS infection period. Twenty-one patients (36.2%) felt that a SARS infection was more severe and fatal than their lung cancer. In conclusion, SARS is a new disease entity that is highly contagious. Its clinical manifestations overlap with the signs and symptoms of lung cancer. Thus, a clear differentiation between the two conditions is needed, especially for those patients who are under active anti-cancer treatment.
- Published
- 2004
41. Effect of the use of low and high potency statins and sepsis outcomes
- Author
-
Shuo Ming Ou, Hsi Chu, Pei Wen Chao, Shu Yu Ou, Szu Yuan Li, Yi Jung Lee, Shu-Chen Kuo, Chia Jen Shih, and Yung Tai Chen
- Subjects
Male ,medicine.medical_specialty ,Statin ,National Health Programs ,medicine.drug_class ,Pain medicine ,Taiwan ,Comorbidity ,Kaplan-Meier Estimate ,Critical Care and Intensive Care Medicine ,Risk Assessment ,Sepsis ,Insurance Claim Review ,Anesthesiology ,medicine ,Potency ,Humans ,cardiovascular diseases ,Hospital Mortality ,Intensive care medicine ,Propensity Score ,Aged ,Proportional Hazards Models ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Outcome and Process Assessment, Health Care ,lipids (amino acids, peptides, and proteins) ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business - Abstract
Although statins have been shown to have cholesterol-lowering effects, their pleiotropic benefits on sepsis remain a matter of debate. In addition, the influence of statin potency on sepsis-related mortality has never been explored. The aim of our study was to determine the sepsis outcomes of low- and high-potency statin users and non-users.This nationwide, population-based, propensity score-matched analysis used data from the linked administrative databases of Taiwan's National Health Insurance program. Patients were hospitalized for sepsis between 2000 and 2010. All-cause mortality and major adverse consequences of sepsis, such as in-hospital death, intensive care unit admission, shock events, and the use of mechanical ventilation, were assessed. Patients were divided into high-potency statin users (at least 10 mg rosuvastatin, at least 20 mg atorvastatin, or at least 40 mg simvastatin), low-potency statin users (all other statin treatments), and non-users.A propensity score-matched cohort of 27,792 statin users and 27,792 non-users was included. Of 27,792 statin users, 9,785 (35.2 %) were treated with high-potency statins and 18,007 (64.8 %) were treated with low-potency statins. The 1-year mortality risk was significantly lower among both low-potency [adjusted hazard ratio (aHR) 0.89, 95 % confidence interval (CI) 0.85-0.93] and high-potency (aHR 0.80, 95 % CI 0.75-0.86) statin users compared with non-users. The risks of mortality and adverse consequences of sepsis were lower among high-potency than among low-potency statin users.High-potency statin use is associated with a lower risk of sepsis-related mortality compared with low-potency statin use.
- Published
- 2014
42. Effect of statin therapy on mortality in patients with infective endocarditis
- Author
-
Ten Fang Yang, Yung Tai Chen, Shuo Ming Ou, Chia Jen Shih, Hsi Chu, Lung Wen Tsai, and Szu Yuan Li
- Subjects
Male ,medicine.medical_specialty ,Statin ,medicine.drug_class ,Taiwan ,Comorbidity ,Lower risk ,Internal medicine ,Cause of Death ,medicine ,Endocarditis ,Humans ,Hospital Mortality ,Propensity Score ,Cause of death ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,Infective endocarditis ,Cardiology ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
The aim of our study was to determine whether pre-emptive statin therapy was associated with improved outcome of infective endocarditis (IE). We conducted a nationwide, population-based, propensity score-matched cohort study with the Taiwan's National Health Insurance Research Database. All patients with IE between January 2000 and December 2010 were enrolled. The primary outcome was in-hospital mortality. The secondary outcome included all-cause mortality within the first 3 months, 6 months, and one year after the diagnosis of IE. Among 13,584 patients with IE, we applied propensity score-matching on a 1:4 ratio, in which 370 statin users were matched to 1,480 statin non-users. Compared with statin non-users, statin users had a significantly lower risk of in-hospital mortality (adjusted hazard ratio [aHR] 0.65, 95% confidence interval [CI], 0.49–0.86). The reduction in mortality from IE remained significant for follow-up 3 months (aHR 0.68, 95% CI, 0.53–0.88), 6 months (aHR 0.73, 95% CI, 0.58–0.91), and 12 months (aHR 0.68, 95% CI, 0.55–0.84). Statin therapy was associated with a reduced risk of ICU admission rates, shock events, the need for mechanical ventilation, but not significantly with the need for heart valvular replacement surgery. In conclusion, our study found that statin therapy is associated with a reduced risk of in-hospital and subsequent mortality of IE.
- Published
- 2014
43. Strength predictions for interlocking microridges fabricated with different geometries
- Author
-
Lung-Hsi Chu, Quanfang Chen, and Gregory P. Carman
- Subjects
Microelectromechanical systems ,Materials science ,Precision engineering ,business.industry ,Mechanical Engineering ,Structural engineering ,Isotropic etching ,Finite element method ,Computer Science::Other ,Surface micromachining ,Flexural strength ,Etching (microfabrication) ,Dry etching ,Electrical and Electronic Engineering ,Composite material ,business - Abstract
This paper analytically evaluates the strength of microcomponents fabricated using both wet and dry etching techniques. A finite element model (nanometer meshed) coupled with a macroscopically accepted energy criterion is used to predict the strength of four different microridge structures (geometries). Agreement between analytical predictions and experimental data on single crystal silicon is excellent and validates the use of macroscopic models to predict the strength of micromachined components fabricated with a wide range of processes. The model is used to evaluate design parameters such as the influence of height and ridge material on strength properties. The analytical portion of the study suggests that optimum ridge height exists to maximize the strength and by choosing tougher materials, the strength of the ridges may be improved by an order of magnitude. However, the significant strength improvement is not validated experimentally. The simulation results confirm that the geometries rather than etching flaws are critical issues when dealing with strength of micromachined components. Furthermore, standard macroscopic methods can be used to predict the strength of MEMS components at the micron size level.
- Published
- 2001
44. Synthesis of 5-Halogeno-6-amino-2′-deoxyurldines and their Analogs as Potential Inhibitors of Thymidine Phosphorylase
- Author
-
Ming Yu WangChu, Bai Chuan Pan, Shih Hsi Chu, Zhi Hao Chen, and Edward Chu
- Subjects
Human colon cancer ,Biochemistry ,Cell culture ,Chemistry ,Genetics ,Ic50 values ,Cytotoxic T cell ,Thymidine phosphorylase ,Molecular biology ,In vitro cell culture - Abstract
5-Halogeno-6-amino-2′-deoxyuridines were synthesized from 2′-deoxyuridine as potential thymidine phosphorylase (ThdPase) inhibitors. Among the compounds synthesized, 5-bromo-6-amino-2′-deoxyuridine (6) and 5-iodo-6-amino-2′-deoxyuridine (9) were found to inhibit ThdPase activity with IC50 values of 1.3 μM and 6.5 μM, respectively. In vitro cell culture studies showed that compound (6) can significantly enhance the cytotoxic effects of 5-fluoro-2′-deoxyuridine against a human colon cancer HCT-8 cell line.
- Published
- 1998
45. Synthesis of racemic and enantiomerically pure 2′-thia-2′,3′-dideoxycytidine as potential anti-hepatitis B virus agents
- Author
-
Bai-Chuan Pan, Yung-Chi Cheng, and Shih-Hsi Chu
- Subjects
Hepatitis B virus ,Chemistry ,Stereochemistry ,2'3' dideoxycytidine ,Organic Chemistry ,medicine ,Human hepatitis B virus ,medicine.disease_cause - Abstract
A novel class of nucleosides with the C1, atom bonded to three hetero atoms was synthesized. 2′-Thia-2′,3′-dideoxycytidine was the pilot compound of this series. (±)-β-2′-Thia-1′,3′-dideoxycytidine (6) and (±)-α-2′-thia-2′,3′-dideoxycytidine (7) were synthesized from (±)-3-mercapto-1,2-propanediol. The synthesis of the enantiomerically pure 2′-thia-2′,3′-dideoxycytidines (α-D-form, β-D-form, α-1-form and β-L-form) from optically pure (S)-(2,2-dimethyl-1,3-dioxalan-yl)methyl p-toluenesulfonate (8) and its (R)-isomer 18 was also described. The preliminary biological results showed that (+)-β-D-2′-thia-2′,3′-dideoxycytidine (26) was the most active against human hepatitis B virus with an ED50 of 3 μM.
- Published
- 1997
46. Resistance to 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine Derivatives Is Generated by Mutations at Multiple Sites in the HIV-1 Reverse Transcriptase
- Author
-
John P. Bader, Sharon Yeagy-Bargo, Shih-Hsi Chu, Bai-Chuan Pan, Owen S. Weislow, Robert W. Buckheit, Douglas L. Mayers, Stephen H. Hughes, Paul L. Boyer, and Valerie Fliakas-Boltz
- Subjects
Pyridines ,Mutagenesis (molecular biology technique) ,Biology ,Antiviral Agents ,Virus ,Cell Line ,Structure-Activity Relationship ,chemistry.chemical_compound ,Virology ,Humans ,Structure–activity relationship ,Nevirapine ,Binding site ,Uracil ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Drug Resistance, Microbial ,RNA-Directed DNA Polymerase ,Molecular biology ,HIV Reverse Transcriptase ,Recombinant Proteins ,Reverse transcriptase ,Amino acid ,Thymine ,chemistry ,HIV-2 ,HIV-1 ,Mutagenesis, Site-Directed ,Reverse Transcriptase Inhibitors ,Zidovudine - Abstract
Virus isolates resistant to 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) and a highly potent HEPT derivative, [1-benzyloxymethyl-5-ethyl-6-(α-pyridylthio)uracil] (NSC 648400, E-BPTU), were selected in cell culture. Cross-resistance evaluation indicated that the two drug resistant virus isolates were phenotypically distinct from one another although each of the virus isolates was resistant to both of the HEPT derivatives The virus isolate resistant to NSC 648400 had a single amino acid change in the reverse transcriptase (Y181C) which resulted in cross-resistance to all of the nonnucleoside reverse transcriptase inhibitors evaluated, with the exception of calanolide A. The NSC 648400-resistant virus isolate exhibited 15-fold enhanced sensitivity to calanolide A. The virus isolate selected in the presence of HEPT exhibited a single amino acid change (P236L) which was not cross- resistant to other nonnucleoside RT inhibitors tested with the exception of the two HEPT derivatives. This HEPT-resistant virus isolate exhibited enhanced sensitivity (5- to 10-fold) to thiazolobenzimidazole. We have used both virus isolates with defined single amino acid changes in the RT and bacterially expressed RTs with site-directed amino acid substitutions to test the effects of a wide variety of mutations on the activity of NSC 648400 Single mutations at amino acids 101, 103, 106, 181, or 236 yielded virus with high resistance (>20-fold) to NSC 648400, while lower levels of resistance were seen with mutations at amino acids 98, 100, or 108. These results suggest that several changes in the conformation of the nonnucleoside inhibitor binding site of the HIV-1 reverse transcriptase can affect the inhibitory activity of the HEPT class of compounds.
- Published
- 1995
47. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Terms of Major Cardiovascular Disease Outcomes in Elderly Patients
- Author
-
Yung Tai Chen, Pei Wen Chao, Tzeng Ji Chen, Szu Yuan Li, Shu Chen Kuo, Chia Jen Shih, Shuu Jiun Wang, Shu Chen Chien, Hsi Chu, Der Cherng Tarng, Yi Jung Lee, and Shuo Ming Ou
- Subjects
medicine.medical_specialty ,biology ,business.industry ,Hazard ratio ,Retrospective cohort study ,Angiotensin-converting enzyme ,General Medicine ,medicine.disease ,Heart failure ,Internal medicine ,Cohort ,medicine ,biology.protein ,cardiovascular diseases ,Myocardial infarction ,Intensive care medicine ,Adverse effect ,business ,Mace - Abstract
Renin and aldosterone activity levels are low in elderly patients, raising concerns about the benefits and risks of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARB) use. However, data from direct comparisons of the effects of ACEIs on ARBs in the elderly population remain inconclusive. In this nationwide study, all patients aged ≥ 70 years were retrieved from the Taiwan National Health Insurance database for the period 2000 to 2009 and were followed up until the end of 2010. The ARB cohort (12,347 patients who continuously used ARBs for ≥ 90 days) was matched to ACEI cohort using high-dimensional propensity score (hdPS). Intention-to-treat (ITT) and as-treated (AT) analyses were conducted. In the ITT analysis, after considering death as a competing risk, the ACEI cohort had similar risks of myocardial infarction (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.79–1.06), ischemic stroke (HR 0.98, 95% CI 0.90–1.07), and heart failure (HR 0.93, 95% CI 0.83–1.04) compared with the ARB cohort. No difference in adverse effects, such as acute kidney injury (HR 0.99, 95% CI 0.89–1.09) and hyperkalemia (HR 1.02, 95% CI 0.87–1.20), was observed between cohorts. AT analysis produced similar results to those of ITT analysis. We were unable to demonstrate a survival difference between cohorts (HR 1.03, 95% CI 0.88–1.21) after considering drug discontinuation as a competing risk in AT analysis. Our study supports the notion that ACEI and ARB users have similar risks of major adverse cardiovascular events (MACE), even in elderly populations.
- Published
- 2015
48. Synthesis and anti-hiv-1 activities of 6-arylthio and 6-arylselenoacyclonucleosides
- Author
-
Yung-Chi Cheng, Shih-Hsi Chu, Ginger E. Dutschman, Elizabeth C. Rowe, Giovanna Piras, Bai-Chuan Pan, and Zhi-Hao Chen
- Subjects
Anti hiv 1 ,Diselenide ,chemistry.chemical_compound ,Therapeutic index ,Chemistry ,Stereochemistry ,Organic Chemistry ,Electrophile ,Disulfide bond ,Ether ,Biological activity ,Diphenyl diselenide ,Combinatorial chemistry - Abstract
6-Arylthio and 6-arylselenoacyclonucleosides was synthesized and tested for the ability to inhibit replication of HIV-1. Lithiation of acyclonucleosides with LDA followed by reaction with the electrophiles phenyl disulfide, diphenyl diselenide, 2,2′-dipyrdyl disulfide or 2,2′-dipyridyl diselenide afforded 6-(arylthio or arylseleno)acyclonucleosides 5a-c, 6, 7, 9, 15a-c, 17a-c. Compounds 19a-c and 20a-c were obtained by deprotection of corresponding TBDMS derivatives. Dehydrated products 16a, and 18a-c were also formed during the reactions. 5-Ethyl-6-(α-pyridylthio or α-pyridylseleno) disubstituted acyclouracils 6 and 7 were more active against HIV-1 in both MT-2 and CEM-IW cell lines than AZT, DDC, DDI or D4T. The EC50 of 6 against HIV-1 in CEM-IW cell was in the nanomolar range with a therapeutic index of 1100.
- Published
- 1994
49. Thermal analysis of poly(acrylic acid)/poly(oxyethylene) blends
- Author
-
Bret Berner and Chia-Hsi Chu
- Subjects
chemistry.chemical_classification ,Materials science ,Polymers and Plastics ,technology, industry, and agriculture ,General Chemistry ,Polymer ,Surfaces, Coatings and Films ,Amorphous solid ,Crystallinity ,chemistry.chemical_compound ,Differential scanning calorimetry ,chemistry ,Phase (matter) ,Polymer chemistry ,Materials Chemistry ,Thermal analysis ,Glass transition ,Acrylic acid - Abstract
Blends between poly(acrylic acid) and two different poly(oxyethylenes), (1) polyethylene glycol (PEG-1000) and (2) poly(oxyethylene) (20) sorbitan monooleate (Tween-80), were studied by differential scanning calorimetry. The glass transition temperatures, Tg, of the various compositions of these blends were found to follow Fox's equation. At room temperature, blends containing no more than 60% PEG-1000 were amorphous and exhibited only a single glass transition. For these blends with PEG-1000, the glass transition temperatures for the annealed samples were higher than for the quenched samples due to the formation of a PEG crystalline phase. It was also found that addition of an amorphous polymer such as poly(acrylic acid) significantly reduced the degree of crystallinity of a semicrystalline polymer such as poly(oxyethylene). The Tween-80 systems did not show phase separation at room temperature. The compatibility between this poly(acrylic acid) and this poly(oxyethylene) was attributed to hydrogen bonding and to the lower crystalline lattice energy of this poly(oxyethylene) through its effect on its ideal solution solubility. © 1993 John Wiley & Sons, Inc.
- Published
- 1993
50. ChemInform Abstract: Synthesis of 5-Benzyl and 5-Benzyloxybenzyl-3′-azido-2′,3′- dideoxyuridine and Their Analogues as Potential Anti-AIDS Agents
- Author
-
Bai-Chuan Pan, Shih-Hsi Chu, Z.-Y. Weng, Elizabeth C. Rowe, and Zhi-Hao Chen
- Subjects
chemistry.chemical_compound ,chemistry ,Stereochemistry ,Nucleic acid ,Uracil ,Epimer ,General Medicine ,3'-azido-2'-3'-dideoxyuridine - Abstract
5-Benzyl and 5-benzyloxybenzyl-substituted 3′-azido-2′,3′-dideoxyuridine, (8a and 8b), 3′-halogeno-2′,3′-dideoxyuridine, 9a, 9b, 10a, 10b, 11a and 11b, and 2′,3′-dideoxyuridine, 12a and 12b, of Scheme I were synthesized as potential anti AIDS agents. Synthesis of epimers of 8a and 8b, 5-benzyl- and 5-benzyloxybenzyl-1-(3′-azido-2′,3′-dideoxy-β-D-threo-pentafuranosyl)uracil, 15a and 15b, and 5-benzyl- and 5-benzyloxy-5′-azido-2′,5′-dideoxyuridine, 16a and 16b, shown in Scheme II, were also reported.
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.