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Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations

Chinese Medical Journal 2014年第8期127卷 1482-1486页

作者： Juang Jyh-Ming Jimmy Chen Ching-Yu Yeh Huei-Ming chiu wei-yih Yu Chih-Chieh Liu Yen-Bin Tsai Chia-Ti Lo Li-wei Yeh Shih-Fan Sherri Lai Ling-Ping Cardiovascular Center and Division of Cardiology Department of Internal Medicine Department of Anesthesiology Department of Environmental and Occupational Medicine Division of Endocrinology and Metabolism Department of Internal Medicine Taiwan University Hospital and Taiwan University College of Medicine Taipei Taiwan China

Background Congenital long QT syndrome （LQTS） is an ion channelopathy associated with genetic mutations. It is well known that most LQTS patients （91%） have a single mutation. The purpose of this study was to investigate the clinical characteristics of congenital LQTS patients with bigenic mutations in Taiwan, China. Methods Congenital LQTS patients were recruited consecutively at Taiwan University Hospital in Taiwan from 2003 to 2009. The diagnosis of LQTS was defined by an LQTS Schwartz score greater than 4. Mutation screening in KCNQ1, KCNH2, KCNE1, and SCN5A was performed using direct sequencing. Results Three of 16 LQTS patients （18.7%） were identified with bigenic mutations. One patient had missense mutations in KCNQ1 and KCNH2, the second in KCNQ1 and KCNE1, and the third in KCNH2 and SCN5A. The mean age at onset of LQTS for patients with bigenic mutations was （17±3） years, and all of these patients were female. Two of them experienced seizure and one presented with syncope, although one of them had a family history of syncope. The mean QTc interval was （515＋17） ms, similar to those with single mutation or SNPs （（536~74） ms, P=-0.63）. Compared to those LQTS patients with single mutation or SNPs, a significantly higher percentage of LQTS patients with bigenic mutations presented with seizure and were younger at onset of the first index event （P=0.03 and 0.001, respectively）, but lower percentage of them presented with sudden cardiac death （P=0.03）. Conclusions Although the percentage of bigenic mutations in LQTS is less than 10% in Caucasian populations, we identified 3 of 16 LQTS patients （18.7%, 95% confidence interval： 0.04-0.46） with bigenic mutations in Taiwan. However, the sevedtv of their clinical presentations was not hioher than those patients with sinele mutation or SNPs.

关键词： long QTsyndrome genetic mutation Taiwan Chinese

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Conundrum of vitamin D on glucose and fuel homeostasis

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World Journal of Diabetes 2021年第9期12卷 1363-1385页

作者： Maria Mercedes Chang Villacreses Rudruidee Karnchanasorn Panadeekarn Panjawatanan Horng-yih Ou Ken C chiu Department of Clinical Diabetes Endocrinologyand MetabolismCity of Hope National Medical CenterDuarteCA 91010United States Division of Endocrinology Metabolism and NutritionDepartment of Internal MedicineHarbor-UCLA Medical CenterTorranceCA 90509United States Division of Endocrinology Department of MedicineUniversity of Kansas Medical CenterKansas CityKS 66160United States Department of Internal Medicine Bassett Medical CenterCooperstownNY 13326United States Department of Internal Medicine National Cheng Kung University HospitalNational Cheng Kung UniversityTainan 700Taiwan

As an endocrine hormone,vitamin D plays an important role in bone health and calcium *** the past two decades,the non-calcemic effects of vitamin D were extensively *** the effect of vitamin D on beta cell function were known for some time,the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among ***,to date,studies remain inconclusive and controversial,in part,due to a lack of understanding of the threshold effects of vitamin *** this review,a critical examination of interventional trials of vitamin D in prevention of diabetes is *** use of vitamin D for bone loss,the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D75 nmol/L(30 ng/mL).Furthermore,no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D>100 nmol/L(40 ng/mL).Further studies are required to confirm these observations.

关键词： Vitamin D Glucose metabolism Diabetes mellitus Insulin sensitivity Beta

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Transactive Energy and Flexibility Provision in Multi-microgrids Using Stackelberg Game

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CSEE Journal of Power and Energy Systems 2023年第2期9卷 505-515页

作者： weiqi Hua Hao Xiao wei Pei wei-Yu chiu Jing Jiang Hongjian Sun Peter Matthews Department of Engineering Science University of OxfordOxford OX13PJUK Institute of Electrical Engineering Chinese Academy of SciencesBeijing 100190China MOCaRL Lab Department of Electrical EngineeringNational Tsing Hua UniversityHsinchu 300044Chinese Taiwan Department of Mathematics Physics and Electrical EngineeringUniversity of NorthumbriaNewcastleNE18STUK Department of Engineering Durham UniversityDurhamDH13LEUK

Aggregating demand side flexibility is essential to complementing the inflexible and variable renewable energy supply in achieving low carbon energy *** of demand side flexibility,e.g.,dispatchable generators,storage,and flexible loads,can be structured in a form of microgrids and collectively provided to utility grids through transactive energy in local energy *** paper proposes a framework of local energy markets to manage this transactive energy and facilitate the flexibility *** distribution system operator aims to achieve local energy balance by scheduling the operation of multi-microgrids and determining the imbalance *** microgrid traders aim to maximize profits for their prosumers through dispatching flexibility sources and participating in localised energy *** decision making and interactions between a distribution system operator and multiple microgrid traders are formulated as the Stackelberg game-theoretic *** studies using the IEEE 69-bus distribution system demonstrate the effectiveness of the developed model in terms of facilitating local energy balance and reducing dependency on the utility grids.

关键词： Demand side flexibility game theory multimicrogrid prosumer smart grid transactive energy

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Role of hepatitis A virus in diabetes mellitus

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World Journal of Diabetes 2021年第11期12卷 1928-1941页

作者： James Lin Horng-yih Ou Rudruidee Karnchanasorn Raynald Samoa Lee-Ming Chuang Ken C chiu Department of Gastroenterology City of Hope National Medical CenterDuarteCA 91010United States Division of Endocrinology and Metabolism Department of Internal MedicineNational Cheng-Kung University Medical College and HospitalTainan 700Taiwan Division of Endocrinology Metabolism and GeneticsDepartment of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160United States Department of Clinical Diabetes Endocrinologyand MetabolismDiabetes and Metabolism Research InstituteCity of Hope National Medical CenterDuarteCA 91010United States Division of Endocrinology Metabolism and NutritionDepartment of Internal MedicineHarbor-UCLA Medical CenterTorranceCA 90502United States of America Department of Internal Medicine National Taiwan University HospitalTaipei 102Taiwan Graduate Institute of Preventive Medicine School of Public HealthTaipei 102Taiwan

BACKGROUND Although much information is available regarding hepatitis C virus infection and diabetes,less is known about the relationship between hepatitis A virus(HAV)infection and *** To examine the roles of HAV in diabetes *** This cross-sectional study population included data from the National Health and Nutrition Examination Survey collected between *** subjects(≥20 years old)with available body mass index measurements,defined diabetes status,history of HAV vaccination,and HAV serology were *** vaccination was based on self-reported *** HAV immunization was defined as the presence of both vaccination and anti-HAV *** infection was defined by the absence of vaccination but presence of anti-hepatitis A *** odds ratio(OR)for diabetes with 95%confidence intervals(95%CI)was calculated for each HAV status and then adjusted for *** tests,based on different definitions of diabetes,were performed to verify the *** Among 19942 subjects,4229 subjects(21.21%)received HAV vaccination and HAV antibody was present in 9224 subjects(46.25%).Although HAV infection was associated with an increased risk of diabetes(OR:1.13;95%CI:1.08-1.18),HAV vaccination was not associated with diabetes(OR:1.06;95%CI:0.95-1.18),and successful HAV immunization had no impact on the risk of diabetes(OR:1.11;95%CI:0.97-1.27).Thus,HAV infection was an unlikely cause of ***,in non-vaccinated subjects,diabetes increased the risk of HAV infection by 40%(OR:1.40,95%CI:1.27-1.54).CONCLUSION An association between HAV infection and diabetes is observed which is best explained by an increased risk of HAV infection in diabetic *** subjects are more susceptible to ***,HAV vaccination is highly recommended in diabetic patients.

关键词： Vaccination Immunization Viral hepatitis Liver Glucose metabolism Diabetes mellitus

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Observing the evolution of graphene layers at high current density

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Nano Research 2016年第12期9卷 3663-3670页

作者： Chun-wei Huang Jui-Yuan Chen Chung-Hua chiu Cheng-Lun Hsin Tseung-Yuen Tseng Wen-wei Wu Department of Materials Science and Engineering Chiao Tung University 1001 University Road Hsinchiu 30010 Taiwan China Department of Electrical Engineering Central University Chung-Li City Taoyuan 32001 Taiwan China Department of Electronics Engineering and Institute of Electronics Chiao Tung University 1001 University Road Hsinchiu 30010 Taiwan China

Graphene has demonstrated its potential in several practical applications owing to its remarkable electronic and physical properties. In this study, we successfully fabricated a suspended graphene device with a width down to 20 nm. The morphological evolution of graphene under various electric field effects was systematically examined using an in-situ transmission electron microscope （TEM）. The hourglass-shaped graphene sample instantly broke apart at 7.5 mA, indicating an impressive breakdown current density. The current-carrying capacity was calculated to be -1.6 × 10^9 ***-2, which is several orders higher than that of copper. The current-carrying capacity depended on the resistivity of graphene. In addition, atomic volume changes occurred in the multilayer graphene samples due to surface diffusion and Ostwald ripening （OR）, indicating that the breakdown mechanism is well approximated by the electric field. This study not only provides a theory to explain the breakdown behavior but also presents the effects on materials contacted with a graphene layer used as the transmission path.

关键词： graphene breakdown high current density in-situ transmissionelectron microscope (TEM) Ostwald ripening

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A Survey on Mixed Spin P-Fields

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Chinese Annals of Mathematics,Series B 2017年第4期38卷 869-882页

作者： Huai-Liang CHANG Jun LI wei-Ping LI chiu-Chu Melissa LIU Department of Mathematics Hong Kong University of Science and Technology Hong Kong China. Shanghai Center for Mathematical Sciences Fudan University Shanghai 200433 China Department of Mathematics Stanford University Stanford CA 94305-2125 USA. Department of Mathematics Columbia University New York NY 10027 USA.

The mixed spin P-fields （MSP for short） theory sets up a geometric platform to relate Gromov-Witten invariants of the quintic three-fold and Fan-Jarvis-Ruan-Witten invariants of the quintic polynomial in five variables. It starts with Wittens vision and the P-fields treatment of GW invariants and FJRW invaxiants. Then it briefly discusses the master space technique and its application to the set-up of the MSP moduli. Some key results in MSP theory are explained and some examples are provided.

关键词： Mixed Spin P-fields GW invariants FJRW invariants P-fields Cosection localization

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Population-based carrier screening and prenatal diagnosis of fragile X syndrome in East Asian populations

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Journal of Genetics and Genomics 2021年第12期48卷 1104-1110页

作者： Qiwei Guo yih-Yuan Chang Chien-Hao Huang Yu-Shan Hsiao Yu-Chiao Hsiao I-Fan chiu Yulin Zhou Haixia Zhang Tsang-Ming Ko United Diagnostic and Research Center for Clinical Genetics Women and Children's HospitalSchool of Medicine&School of Public HealthXiamen UniversityXiamenFujian 361102China Genephile Bioscience Laboratory Ko's Obstetrics and GynecologyTaipei 100TaiwanChina Biofast Biotechnology Co. Ltd.XiamenFujian 361102China

Identification of carriers of fragile X syndrome(FXS) with the subsequent prenatal diagnosis and knowledge of FXS-associated genetic profiles are essential for intervention in specific populations. We report the results of carrier screening of 39,458 East Asian adult women and prenatal diagnosis from 87 FXS *** prevalence of FXS carriers and full mutation fetuses was estimated to be 1/581 and 1/3124 in East Asian populations, respectively. We confirmed the validity of the current threshold of CGG trinucleotide repeats for FMR1 categorization;the integral risks of full mutation expansion were approximately 6.0%,43.8%, and 100% for premutation alleles with 55—74, 75—89, and ≥ 90 CGG repeats, respectively. The protective effect of AGG(adenine-guanine-guanine nucleotides) interruption in East Asian populations was validated, which is important in protecting premutation alleles with 75—89 CGG repeats from full mutation expansion. Finally, family history was shown not an effective indicator for FXS carrier screening in East Asian populations, and population-based screening was more cost-effective. This study provides an insight into the largest carrier screening and prenatal diagnosis for FXS in East Asian populations to date. The FXSassociated genetic profiles of East Asian populations are delineated, and population-based carrier screening is shown to be promising for FXS intervention.

关键词： AGG interruption East Asian population Fragile X syndrome Population-based carrier screening Prenatal diagnosis Cost-effectiveness analysis

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Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes

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Journal of Molecular Cell Biology 2014年第6期8卷 458-472页

作者： Shu-Yi wei Ting-Er Lin wei-Li Wang Pei-Ling Lee Min-Chien Tsai Jeng-Jiann chiu Institute of Cellular and System Medicine 'National' Health Research Institutes Miaoli 350 Department of Physiology and Biophysics 'National' Defense Medical Center Taipei 114 Institute of Biomedical Engineering 'National' Tsing Hua University Hsinchu 300 Institute of Biomedical Engineering 'National' Cheng Kung University Tainan 701

T-tym phocyte migration under flow is critical for immune responses, but the mechanisms by which flow modulates the migratory beha- viors of T-lymphocytes remain unclear. Human peripheral blood T-lymphocytes （PBTLs）, when stimulated with phorboL 12-myristate 13-acetate （PMA）, stretched their ceU bodies dramatically and moved alongthe flow direction. In contrast, stromal ceil-derived factor- lα-stimulated PBTI.s deformed and migrated in a random manner. Here we elucidated the molecular mechanisms underlying flow- induced directionality and deformation of PMA-stimulated PBTLs. PMA primed PBTLs for polarization under flow, with protein kinase C （PKC）-δ enriched in the leading edge, PKC-β1 in the microtubuie organizing center, and PKC-1311 in the uropod and peripheral region. PKC-δ regulated cell protrusions in the leading edge through Tiaml/Racl/caLmoduUn, whereas PKC-β regulated RhoA/Rho- associated kinase activity and microtubule stability to modulate uropod contractility and detachment. Our findings indicate that PKC-δ and -β coordinate in the cell Leading edge and uropod, respectively, to modu｜ate the directionality and deformability of migratory T-Lymphocytes under flow.

关键词： deformability directionality migration PKCs T-lymphocyte

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Learning of medical pharmacology via innovation:a personal experience at McMaster and in Asia

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Acta Pharmacologica Sinica 2004年第9期25卷 84-92页

作者： chiu-yin KWAN Canada Department of Medicine HSC-4N40 Faculty of Health Sciences Hamilton L8N 3Z5 McMaster University Ontario

Pharmacology in the traditional medical curriculum has been treated as a discrete "preclinical" discipline identifying itself distinctly different from the other preclinical sciences or clinical subjects in knowledge base as well as learning/teaching instructions. It is usually run in series with other pre-clinical courses (eg, anatomy, biochemistry, physiology etc), but in parallel with other paraclinical courses such as pathology, microbiology and community medicine. Clinical pharmacology was only introduced relatively recently designed to overcome the perceived deficiency in "preclinical" pharmacology regarding its therapeutic relevance and application to medicine. In many universities, both preclinical and clinical pharmacology courses co-exist, usually independently offered by two separate, sometimes non-interacting Departments of Pharmacology and Clinical Pharmacology. In this model, pharmacology is generally taught in a teacher-centered, discipline-oriented, and knowledge-based curriculum. Further

关键词： problem-based learning pharmacology medical education self-directed learning small group tutorial

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Nonlinear dynamical characteristics of bed load motion

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Science China(Technological Sciences) 2006年第3期49卷 365-384页

作者： chiu-On Ng Department of Mechanical Engineering the University of Hong Kong Hong Kong China

Bed forms of various kinds that evolve naturally on the bottom of sandy coasts and rivers are a result of the kinematics of bed load transport. Based on the group motion of particles in the bed load within the bottom layer, a study on the nonlinear dy- namics of bed load transport is presented in this paper. It is found that some development stages, such as the initiation, the equilibrium sediment transport, and the transition from a smooth bed to sand dunes, can be accounted for by different states in the nonlinear sys- tem of the bed load transport. It is verified by comparison with experimental data reported by Laboratoire Nationae D’Hydraulique, Chatou, France, that the evolution from a smooth bed to sand dunes is determined by mutation in the bed load transport. This paper pre- sents results that may offer theoretical explanations to the experimental observations. It is also an attempt to apply the state-of-the-art nonlinear science to the classical sediment transport mechanics.

关键词： bed load, bed form, nonlinear dynamics.

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