41 results on '"Hsin-Yun Chang"'
Search Results
2. Large-Volume Focused-Ultrasound Mild Hyperthermia for Improving Blood-Brain Tumor Barrier Permeability Application
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Hsin Chan, Hsin-Yun Chang, Win-Li Lin, and Gin-Shin Chen
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brain tumor ,mild hyperthermia ,transcranial focused ultrasound ,phased array ,multiple foci ,Pharmacy and materia medica ,RS1-441 - Abstract
Mild hyperthermia can locally enhance permeability of the blood-tumor barrier in brain tumors, improving delivery of antitumor nanodrugs. However, a clinical transcranial focused ultrasound (FUS) system does not provide this modality yet. The study aimed at the development of the transcranial FUS technique dedicated for large-volume mild hyperthermia in the brain. Acoustic pressure, multiple-foci, temperature and thermal dose induced by FUS were simulated in the brain through the skull. A 1-MHz, 114-element, spherical helmet transducer was fabricated to verify large-volume hyperthermia in the phantom. The simulated results showed that two foci were simultaneously formed at (2, 0, 0) and (−2, 0, 0) and at (0, 2, 0) and (0, −2, 0), using the phases of focusing pattern 1 and the phases of focusing pattern 2, respectively. Switching two focusing patterns at 5 Hz produced a hyperthermic zone with an ellipsoid of 7 mm × 6 mm × 11 mm in the brain and the temperature was 41–45 °C in the ellipsoid as the maximum intensity was 150 W/cm2 and sonication time was 3 min. The phased array driven by switching two mode phases generated a 41 °C-contour region of 10 ± 1 mm × 8 ± 2 mm × 13 ± 2 mm in the phantom after 3-min sonication. Therefore, we have demonstrated our developed FUS technique for large-volume mild hyperthermia.
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- 2022
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3. Multiple Functions of KBP in Neural Development Underlie Brain Anomalies in Goldberg-Shprintzen Syndrome
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Hsin-Yun Chang, Haw-Yuan Cheng, Ai-Ni Tsao, Chen Liu, and Jin-Wu Tsai
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kinesin-binding protein (KBP) ,KIF1BP ,KIAA1279 ,Goldberg-Shprintzen syndrome ,cortical development ,neuronal migration ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Kinesin-binding protein (KBP; KIF1BP; KIAA1279) functions as a regulator for a subset of kinesins, many of which play important roles in neural development. Previous studies have shown that KBP is expressed in nearly all tissue with cytoplasmic localization. Autosomal recessive mutations in KIAA1279 cause a rare neurological disorder, Goldberg-Shprintzen syndrome (GOSHS), characterized by microcephaly, polymicrogyria, intellectual disability, axonal neuropathy, thin corpus callosum and peripheral neuropathy. Most KIAA1279 mutations found in GOSHS patients are homozygous nonsense mutations that result in KBP loss-of-function. However, it is not fully understood how KBP dysfunction causes these defects. Here, we used in utero electroporation (IUE) to express KBP short hairpin RNA (shRNA) with green fluorescent protein (GFP) in neural progenitor cells of embryonic day (E) 14 mice, and collected brain slices at different developmental stages. By immunostaining of neuronal lineage markers, we found that KBP knockdown does not affect the neural differentiation process. However, at 4 days post IUE, many cells were located in the intermediate zone (IZ). Moreover, at postnatal day (P) 6, about one third of the cells, which have become mature neurons, remained ectopically in the white matter (WM), while cells that have reached Layer II/III of the cortex showed impaired dendritic outgrowth and axonal projection. We also found that KBP knockdown induces apoptosis during the postnatal period. Our findings indicate that loss of KBP function leads to defects in neuronal migration, morphogenesis, maturation, and survival, which may be responsible for brain phenotypes observed in GOSHS.
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- 2019
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4. Identification of genes associated with cortical malformation using a transposon-mediated somatic mutagenesis screen in mice
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I-Ling Lu, Chien Chen, Chien-Yi Tung, Hsin-Hung Chen, Jia-Ping Pan, Chia-Hsiang Chang, Jia-Shing Cheng, Yi-An Chen, Chun-Hung Wang, Chia-Wei Huang, Yi-Ning Kang, Hsin-Yun Chang, Lei-Li Li, Kai-Ping Chang, Yang-Hsin Shih, Chi-Hung Lin, Shang-Yeong Kwan, and Jin-Wu Tsai
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Science - Abstract
Cortical malformations have a variety of causes. Here the authors use transposon mutagenesis to insert mutations into neural stem cells in the developing mouse cortex to screen for new candidate genes for cortical malformation, and validate some targets in human brain tissue.
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- 2018
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5. The Influence of Interactive Art of Visual Music on the Creativity of Science and Engineering Students.
- Author
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Hsin-Yun Chang, Hao-Chiang Lin, Ting-Ting Wu, and Yueh-Min Huang
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- 2019
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6. A Novel SVM-Based Reduced NN Classification Method.
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Chi-Chun Huang and Hsin-Yun Chang
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- 2015
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7. International Variations in Dementia and Alzheimer Disease Diagnosis and Certification Habits and Their Associations With Dementia and Alzheimer Disease Mortality: A Cross-Sectional Study of 38 Countries.
- Author
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Ying-Chen Chi, Wei-Min Chu, Hsin-Yun Chang, and Tsung-Hsueh Lu
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Objective: To examine international variations in national diagnosis and certification habits prefer recording dementia (D) versus Alzhiemer disease (AD) as the underlying cause of death (UCOD) and their associations with mortality rates of dementia and AD. Methods: We calculated proportions of D/D+AD and AD/D+AD deaths as proxies of national diagnosis and certification habits. Pearson correlation coefficients (r) were estimated to assess the associations of proportions with the mortality rates of dementia or AD among adults aged 75 to 84 years across 38 countries. Results: The countries with a high preference for recording dementia as the UCOD were Taiwan and Latvia with proportion of D/D+AD deaths of 92% and 88%, respectively, and those with a high preference for recording AD as the UCOD were Slovenia, Turkey, and Poland with proportion of AD/D+AD deaths of 100%, 99%, and 89%, respectively. The r values for the proportions and mortality rate for dementia and AD were 0.67 (95% CI: 0.44-0.81) and 0.46 (95% CI: 0.16-0.68), respectively. Conclusion: We identified a small number of countries with obvious natonal diagnosis and certification habits preferring dementia or AD and had moderate effects on international variations in the mortality rates of dementia and AD. [ABSTRACT FROM AUTHOR]
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- 2023
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8. A Novel GA-Taguchi-Based Feature Selection Method.
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Cheng-Hong Yang 0001, Chi-Chun Huang, Kuo-Chuan Wu, and Hsin-Yun Chang
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- 2008
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9. A Novel Grey-based Feature Selection Method with One-Feature Reverse Operation.
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Chi-Chun Huang and Hsin-Yun Chang
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- 2008
10. A Novel Hybrid Taguchi-Grey-Based Method for Feature Subset Selection.
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Hsin-Yun Chang and Chung-Shan Sun
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- 2007
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11. Metabolic and Obesity Phenotype Trajectories in Taiwanese Medical Personnel
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Hsin-Yun Chang, Jer-Hao Chang, Yin-Fan Chang, Chih-Hsing Wu, and Yi-Ching Yang
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Male ,Metabolic Syndrome ,Phenotype ,metabolic health ,obesity ,medical personnel ,hospital workers ,Risk Factors ,Health, Toxicology and Mutagenesis ,Health Status ,Public Health, Environmental and Occupational Health ,Humans ,Obesity ,Body Mass Index - Abstract
The distribution of metabolic and obesity phenotypes in Taiwanese medical personnel is unknown. In this study, trajectory analysis with repeated measurements was used to explore the development and associated risk factors of different metabolic and obesity phenotypes in hospital staff from a Taiwanese medical center. The results demonstrated that metabolically unhealthy workers presented with a higher body mass index (BMI) compared with their metabolically healthy counterparts. Male and aged > 40 years hospital workers were more likely to be in a deleterious metabolic/obesity state. Meanwhile, profession and working hours were not significantly associated with the development of certain phenotypes in our study. These results shed light on the necessity of adequate data retrieval regarding working hours, and a nuanced examination of working conditions among different professions. Our findings are helpful for the development of advanced guidance regarding health promotion in hospital workers.
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- 2022
12. A Piezoceramic Sensor for Detection of Focused Ultrasound-Induced Cavitation
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Chen Jiun-Jung, Hsin-Yun Chang, Gin-Shin Chen, and Jung-Chih Chen
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Materials science ,Hydrophone ,business.industry ,Acoustics ,010401 analytical chemistry ,Detector ,Ultrasound ,01 natural sciences ,0104 chemical sciences ,Transducer ,Cavitation ,Electrical and Electronic Engineering ,Wideband ,Center frequency ,business ,Instrumentation ,Voltage - Abstract
Acoustic cavitation plays a key role in blood-brain-barrier opening. Stable cavitation is required for safely transient barrier disruption when inertial cavitation may cause potentially undesirable damage to brain. To ensure the safety, an appropriate passive cavitation detector is needed to monitor cavitation activity during focused ultrasound treatment. The purpose of this study was to develop a passive cavitation detector with high sensitivity at the specific frequency used in blood-brain-barrier opening. The detector was designed with the assistance of pulse-echo response simulations, using the software PiezoCAD. The active transducer of the detector was constructed of two matching layers, a PZT-5A ceramic disk and the titanium backing. The detector was characterized via the pulse-echo measurements and a commercial hydrophone was used to determine the sensitivity of the developed detector. Cavitation experiments were also performed to validate the detector. The experimental results showed that the detector had the center frequency of 1.16 MHz with the bandwidth of 44.8% and its sensitivity was 2.87 V/MPa at 1.0 MHz. In cavitation experiments, 2-MHz focused ultrasound with the focal intensity of 58 W/cm2 and 1461 W/cm2 induced stable cavitation and inertial cavitation in free field, separately. The spectra of the ultrasound signals detected by the detector indicated the occurrence of peak voltages at the subharmonic frequency of 1 MHz and the increase in the level of wideband signals, reflecting stable cavitation and inertial cavitation, respectively. Based on the design guideline of this study, the passive cavitation detector can be developed dedicated for blood-brain-barrier opening.
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- 2019
13. Total synthesis of pseudouridineviaHeck-typeC-glycosylation
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Tun Cheng Chien, Cheng Ping Yu, and Hsin Yun Chang
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chemistry.chemical_classification ,Glycosylation ,Glycal ,Chemistry ,Ligand ,Total synthesis ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Medicinal chemistry ,Catalysis ,Pseudouridine ,0104 chemical sciences ,chemistry.chemical_compound ,Functional group ,Materials Chemistry ,0210 nano-technology ,Protecting group - Abstract
The reaction of 2,4-dimethoxy-5-iodopyrimidine (8) and 3,5-di-O-tert-butyldimethylsilyl protected ribofuranoid glycal 4 was carried out with Pd(OAc)2 as the catalyst, PPh3 as the ligand and Et3N as the base in DMF at 70 °C followed by desilylation to afford exclusively the β-anomer of 5-(2,3-dideoxy-3-oxoribofuranosyl)-2,4-dimethoxypyrimidine (11) in a very good yield. The subsequent protecting group and functional group interconversions furnished pseudouridine (Ψ, 1).
- Published
- 2019
14. Ultrasound Mediates Discharging of Hexagonal Boron Nitride Nanoflakes in Liquid Conditions
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Bikash Chandra Mallick, Gin-Shin Chen, and Hsin-Yun Chang
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History ,Materials science ,Polymers and Plastics ,Substrate (electronics) ,Electrochemistry ,Piezoelectricity ,Exfoliation joint ,Industrial and Manufacturing Engineering ,chemistry.chemical_compound ,chemistry ,Boron nitride ,Ultrasonic sensor ,Business and International Management ,Deformation (engineering) ,Composite material ,Voltage - Abstract
Two-dimensional hexagonal boron nitride has been discovered for piezoelectric property in response to mechanical deformation. However, the quantitative measurement of piezoelectric effects in hexagonal boron nitride and its applicability are still explored. Here, we demonstrated the synthesis of boron nitride nanoflakes by mechanochemical exfoliation and employed the electrochemical method to quantitatively evaluate the piezoelectric performance of the nanoflakes deposited on carbon paper substrate under ultrasonic circumstances. The charge was reached up to 69.29 μC calculated from cyclic voltammogram at 30 mV/s sweep rate under 2.976 MPa induced by ultrasound. The net increased charge was 49.54 μC/mm 2 at 2.976 MPa. The output current was measured up to ~597 pA/mm 2 and positive shift of output voltage shifted from -600 mV to -450 mV. In addition, we observed that the piezoelectric performance linearly increased with pressure induced by ultrasound. Ultrasound-mediated boron nitride nanoflakes paves the new routes for applications of energy and biomedical field.
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- 2021
15. Neutrophil adhesion in brain capillaries contributes to cerebral blood flow deficits in APP/PS1 mice and is dependent on oxidative stress pathways
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Nozomi Nishimura, Kaja Falkenhain, Oliver Bracko, Laibaik Park, Brendah N. Njiru, Madison Swallow, Hsin-Yun Chang, Muhammad Ali, Chris B. Schaffer, Nancy E. Ruiz-Uribe, and Costantino Iadecola
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Neutrophil adhesion ,Epidemiology ,Chemistry ,Health Policy ,medicine.disease_cause ,Cell biology ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Cerebral blood flow ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Oxidative stress - Published
- 2020
16. Disorders of the Serum Sodium Concentration
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Hsin-Yun Chang and Julian L. Seifter
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Body fluid ,Osmole ,Plasma osmolality ,chemistry ,Sodium ,Body water ,Extracellular fluid ,Urine osmolality ,Analytical chemistry ,chemistry.chemical_element ,Fluid compartments - Abstract
The disorders of the sodium concentration [Na+] are body fluid osmolality disorders called dysnatremias. They are so named because our clinical chemistry measurements are obtained from blood plasma, part of the extracellular fluid (ECF), where Na+ is the dominant osmole. Since water is highly permeable to nearly all plasma membranes, and body water osmolality is regulated, it is the amount of the major ECF cation, Na+, and its associated anions that determines the ECF volume. The amount of the major intracellular fluid (ICF) cation, K+, with associated anions determines the volume of the ICF. Thus, accounting for anions that maintain electroneutrality in each compartment, the osmolality of each fluid compartment of the total body water (TBW) is equal to that of TBW itself: $$ \mathrm{Osm}=2\left[\mathrm{ECF}\kern0.5em {\mathrm{Na}}^{+}+\mathrm{ICF}\ {\mathrm{K}}^{+}\right]/\mathrm{TBW} $$ where the units are as follows: Osm, milliosmoles/kg; Na+ and K+, Meq/kg or millimoles/kg.
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- 2020
17. The Influence of Interactive Art of Visual Music on the Creativity of Science and Engineering Students
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Ting-Ting Wu, Hao-Chiang Lin, Hsin-Yun Chang, and Yueh-Min Huang
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Descriptive statistics ,media_common.quotation_subject ,020208 electrical & electronic engineering ,Cognition ,02 engineering and technology ,Interactive art ,Creativity ,020202 computer hardware & architecture ,Test (assessment) ,Visual music ,Engineering education ,ComputingMilieux_COMPUTERSANDEDUCATION ,0202 electrical engineering, electronic engineering, information engineering ,Mathematics education ,Cognitive style ,media_common - Abstract
The main objective of engineering education is to cultivate students to possess capabilities demanded by industries. Of capabilities, creative thinking is the most crucial one. Generally, art-related fields are classified with high creativity while science and engineering are classified as a field dealing with numbers, calculations and realistic phenomena. However, the real-world situation is that students majoring in science and engineering need the skill of creativity to face emerging complicated engineering problems. Our question is that: can art foster creativity of students majoring in science and engineering? This study is to explore link of art and creativity of mater students in science and engineering through the experience of interactive art and aesthetic sense to realize its effect on creativity by using the Processing Software and Leap Motion to create visual and music interactive art works. The total of 70 subjects are students in Colleges of Science and Engineering and College of Electronical Engineering and Computer Science from a university in Taiwan. The research measurement tools are Abbreviated Torrance Test for Adults (ATTA) for pretest-posttest research design and the Study Preference Questionnaire (SPQ) to differentiate the cognitive styles. Using descriptive statistics, One-Sample t test, Paired-samples t test, One-Way ANOVA and Pearson Correlation etc. for statistical analysis. Our findings indicate that students in science and technology fields, their creativity falls on average standard (Creative Index, CI), not particularly outperforming. Different genders, cognition styles and different institutes and colleges of master’s degree students in science and technology demonstrated also no significant differences in creativity. Nevertheless, after introducing the experience of visual and music interactive art works, it has significant effect on the creativity of students in science and technology. The study may provide a cross path of art, science and engineering in STEAM education if conducted further.
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- 2019
18. Disorders of Acid-Base Balance: New Perspectives
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Julian L. Seifter and Hsin-Yun Chang
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Urine chemistry ,Balance (metaphysics) ,medicine.medical_specialty ,Chemistry ,Cognition ,Context (language use) ,Electrolyte excretion ,Combined approach ,Risk analysis (engineering) ,Physical therapy ,medicine ,Acid-Base, Electrolyte and Fluid Alterations: Review ,Organ system ,Electrolyte Disorder - Abstract
Background: Disorders of acid-base involve the complex interplay of many organ systems including brain, lungs, kidney, and liver. Compensations for acid-base disturbances within the brain are more complete, while limitations of compensations are more apparent for most systemic disorders. However, some of the limitations on compensations are necessary to survival, in that preservation of oxygenation, energy balance, cognition, electrolyte, and fluid balance are connected mechanistically. Summary: This review aims to give new and comprehensive perspective on understanding acid-base balance and identifying associated disorders. All metabolic acid-base disorders can be approached in the context of the relative losses or gains of electrolytes or a change in the anion gap in body fluids. Acid-base and electrolyte balance are connected not only at the cellular level but also in daily clinical practice. Urine chemistry is essential to understanding electrolyte excretion and renal compensations. Key Messages: Many constructs are helpful to understand acid-base, but these models are not mutually exclusive. Electroneutrality and the close interconnection between electrolyte and acid-base balance are important concepts to apply in acid-base diagnoses. All models have complexity and shortcuts that can help in practice. There is no reason to dismiss any of the present constructs, and there is benefit in a combined approach.
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- 2016
19. Interaction between Salt-inducible Kinase 2 (SIK2) and p97/Valosin-containing Protein (VCP) Regulates Endoplasmic Reticulum (ER)-associated Protein Degradation in Mammalian Cells
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Chun-Yi Chiang, Bertrand Chin-Ming Tan, Su-Hui Su, Wei-Hao Chen, Ya-Huei Lin, Hsin-Yun Chang, Jing-Yi Huang, Pang-Hung Hsu, Fu-Chia Yang, Sheng-Chung Lee, Hsiao-Ting Wang, and Ming-Daw Tsai
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Valosin-containing protein ,Cell Cycle Proteins ,Protein Serine-Threonine Kinases ,Biology ,Protein degradation ,Endoplasmic-reticulum-associated protein degradation ,Endoplasmic Reticulum ,Biochemistry ,Valosin Containing Protein ,Humans ,Phosphorylation ,Protein kinase A ,Molecular Biology ,Adenosine Triphosphatases ,Kinase ,Endoplasmic reticulum ,Endoplasmic Reticulum-Associated Degradation ,Intracellular Membranes ,Cell Biology ,Cell biology ,HEK293 Cells ,Protein Synthesis and Degradation ,Mutation ,Unfolded protein response ,biology.protein ,HeLa Cells - Abstract
Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element-binding protein-mediated gene expression in various cell types and is the only AMP-activated protein kinase family member known to interact with the p97/valosin-containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can regulate autophagy when proteasomal function is compromised. Here we report that physical and functional interactions between SIK2 and p97/VCP underlie the regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD). SIK2 co-localizes with p97/VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation. Although the expression of wild-type recombinant SIK2 accelerated the degradation and removal of ERAD substrates, the kinase-deficient variant conversely had no effect. Furthermore, down-regulation of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired degradation of ERAD substrates and disruption of ER homeostasis. Collectively, these findings highlight a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells.
- Published
- 2013
20. Fault-Tolerance and Minimum Cost Placement of Bistatic Radar Sensors for Belt Barrier Coverage
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Hsin-Yun Chang, Louis Kao, Kai-Po Chang, and Chiuyuan Chen
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- 2016
21. A novel DCX missense mutation in a family with X-linked lissencephaly and subcortical band heterotopia syndrome inherited from a low-level somatic mosaic mother: Genetic and functional studies
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Heather C Mefford, Hsin Yun Chang, Shih Wen Li, Yao Chung Chang, Meng-Han Tsai, Ting Ying Fu, Pei Wen Kuo, Candace T. Myers, Jin Wu Tsai, and Wei Che Lin
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0301 basic medicine ,Adult ,Doublecortin Domain Proteins ,Male ,Parents ,Doublecortin Protein ,Genotype ,Mutant ,Mutation, Missense ,Lissencephaly ,Classical Lissencephalies and Subcortical Band Heterotopias ,medicine.disease_cause ,Polymerase Chain Reaction ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,medicine ,Missense mutation ,Humans ,Child ,Sanger sequencing ,Genetics ,Mutation ,biology ,Mosaicism ,Neuropeptides ,Wild type ,General Medicine ,DNA ,medicine.disease ,Doublecortin ,Pedigree ,030104 developmental biology ,Pediatrics, Perinatology and Child Health ,biology.protein ,symbols ,Female ,Neurology (clinical) ,Microtubule-Associated Proteins ,030217 neurology & neurosurgery - Abstract
Purpose To study the genetics and functional alteration of a family with X-linked lissencephaly and subcortical band heterotopia. Methods Five affected patients (one male with lissencephaly, four female with subcortical band heterotopia) and their relatives were studied. Sanger sequencing of DCX gene, allele specific PCR and molecular inversion probe technique were performed. Mutant and wild type of the gene products, namely doublecortin, were expressed in cells followed by immunostaining to explore the localization of doublecortin and microtubules in cells. In vitro microtubule-binding protein spin-down assay was performed to quantify the binding ability of doublecortin to microtubules. Key findings We identified a novel DCX mutation c.785A > G, p.Asp262Gly that segregated with the affected members of the family. Allele specific PCR and molecular inversion probe technique demonstrated that the asymptomatic female carrier had an 8% mutant allele fraction in DNA derived from peripheral leukocytes. This mother had 7 children, 4 of whom were affected and all four affected siblings carried the mutation. Functional study showed that the mutant doublecortin protein had a significant reduction of its ability to bind microtubules. Significance Low level mosaicism could be a cause of inherited risk from asymptomatic parents for DCX related lissencephaly-subcortical band heterotopia spectrum. This is particularly important in terms of genetic counselling for recurrent risk of future pregnancies. The reduced binding affinity of mutant doublecortin may contribute to developmental malformation of the cerebral cortex.
- Published
- 2016
22. Antibacterial Activities of Tellurium Nanomaterials
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Huan-Tsung Chang, Chia-Hsin Lee, Hsin-Yun Chang, and Zong-Hong Lin
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Cell Survival ,Reducing agent ,Organic Chemistry ,Inorganic chemistry ,chemistry.chemical_element ,Nanoparticle ,General Chemistry ,medicine.disease_cause ,Biochemistry ,Anti-Bacterial Agents ,Cell Line ,Nanostructures ,Nanomaterials ,chemistry ,Reagent ,Escherichia coli ,medicine ,Animals ,Humans ,Tellurium ,Antibacterial activity ,Escherichia coli Infections ,Antibacterial agent - Abstract
We prepared four differently shaped Te nanomaterials (NMs) as antibacterial reagents against Escherichia coli. By controlling the concentrations of hydrazine (N(2)H(4)) as reducing agent, NaCl, and temperature, we prepared Te nanowires, nanopencils, nanorices, and nanocubes. These four Te NMs resulted in a live/dead ratio of E. coli cells of less than 0.1, which is smaller than that of Ag nanoparticles. The order of antibacterial activity against E. coli is nanocubes ≈ nanorices > nanopencils ≈ nanowires. This is in good agreement with the concentration order of tellurite (TeO(3)(2-)) ions released from Te NMs in E. coli cells, revealing that TeO(3)(2-) ions account for the antibacterial activity of the four Te NMs. We found that spherical Te nanoparticles (32 nm in diameter) with TeO(3)(2-) ions were formed in the E. coli cells. Compared to Ag nanoparticles that are commonly used as antibacterial reagents, Te NMs have higher antibacterial activity and lower toxicity. Thus, Te NMs hold great practical potential as a new and efficient antibacterial agent.
- Published
- 2012
23. Selective Tellurium Nanowire-based Sensors for Mercury(II) in Aqueous Solution
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Chih-Ching Huang, Hsin-Yun Chang, Yen-Fei Lee, Yu-Lun Hunga, and Tsao-Yen Wei
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Detection limit ,Aqueous solution ,Chemistry ,Metal ions in aqueous solution ,Desorption ,Inorganic chemistry ,Analytical chemistry ,chemistry.chemical_element ,General Chemistry ,Tellurium ,Spectroscopy ,Dissolution ,Ion - Abstract
We have developed a simple, colorimetric, and label-free tellurium nanowire (Te NW)-based probe for the detection of mercuryions (Hg(II)) in aqueoussolution, operating on the principle of strong hybridization and galvanic replacement reaction of Te–Hg. The Te NWs (length: 920 nm; diameter: 20 nm) reacted with Hg(II) to induce dissolution and aggregation of the Te NWs. As a result, the absorption band of the Te NWs in a solution undergoes a decrease in the presence of Hg(II). Energy-dispersive X-ray spectroscopy and surface-assisted laser desorption/ionization measurements demonstrated the presence of Hg on the Te NWs. The Te NW probe specifically and sensitively detected Hg(II) ions under optimal concentrations of pH, temperature, and sodiumdodecyl sulfate (SDS) concentration. When using a mixture of Te NWs (3.0 nM) and SDS (5M) in 5 mM sodium phosphate (pH 4) at 50 °C, this sensor provides a limit of detection of 0.5 nMfor Hg(II) (signal-to-noiseratioof 3) with high selectivity(atleast100 fold over other metal ions). Our approach abrogates the need for complicated chemosensors or sophisticated equipment. This cost-effective sensing system allows the rapid and simple determination of the concentrations of Hg(II) ions in real samples (in this case, river, lake, and tap water samples).
- Published
- 2011
24. Modeling and experimental analysis of the hyperelastic thin film nitinol
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Youngjae Chun, Hsin-yun Chang, Michael C. Emmons, Gregory P. Carman, Po-Yu Lin, Daniel S. Levi, and Kotekar P. Mohanchandra
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Materials science ,Large deformation ,business.industry ,Mechanical Engineering ,Structural engineering ,Finite element method ,Buckling ,Hyperelastic material ,General Materials Science ,Electronics ,Thin film ,Composite material ,business ,Parametric statistics - Abstract
Many flexible electronic devices or endovascular biomedical devices require large deformation; however, potential materials produce limited elastic response, that is, 10% when 400% is required. In this article, a finite element model is used to design a hyperelastic thin film nitinol structure containing geometric fenestrations. The hyperelastic response is dependent upon geometric factors that produce buckling. Parametric studies provide the influence-specific parameters have on buckling load. These results are used to select three designs to manufacture and test. Experimental results indicate that elongations greater than 700% are possible.
- Published
- 2011
25. Gold nanoparticle-based colorimetric assays for coagulation-related proteins and their inhibition reactions
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Chih-Ching Huang, Yi-You Chen, Yu-Lun Hung, Hsin-Yun Chang, and Chao-Wei Tseng
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Adult ,Biomedical Engineering ,Biophysics ,Nanoparticle ,Biosensing Techniques ,Fibrinogen ,Sensitivity and Specificity ,Young Adult ,Thrombin ,Electrochemistry ,medicine ,Humans ,Colorimetry ,Detection limit ,Chromatography ,Chemistry ,technology, industry, and agriculture ,General Medicine ,Coagulation ,Biochemistry ,Colloidal gold ,Nanoparticles ,Gold ,Naked eye ,Biotechnology ,medicine.drug - Abstract
In this paper, we describe two simple, label-free, homogenous assays using gold nanoparticles (Au NPs)-one to detect coagulation-related proteins and the other to screen inhibition reactions. The first nanosensor functions on the basis of the fact that thrombin catalyzes fibrinogen to form long-chain fibrins, which then induce aggregation of Au NPs. We applied this sensor to study the interactions of thrombin, inhibitors, cofactors, and antidotes. We further used thrombin-conjugated Au NPs (Thr-Au NPs) to analyze the levels of fibrinogen in plasma samples via fibrinogen-induced aggregation of Thr-Au NPs. The limit of detection (LOD; S/N=3) of this sensor for fibrinogen in plasma was 10nM. The Thr-Au NP probe provided quantitative results for fibrinogen in plasma samples that correlated (R(2)=0.97) with those obtained using a clinical von Clauss clotting rate assay. In addition, the Thr-Au NP-based sensor could be used to monitor thrombin concentrations in plasma samples under physiological conditions. Compared with conventional assays, these label-free assays offer several advantages, such as rapid and simple readout by the naked eye or by UV-vis absorption spectroscopy.
- Published
- 2011
26. A novel grey‐based feature ranking method for feature subset selection
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Hsin-yun Chang, Cheng-Hong Yang, and Chi-Chun Huang
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Computer science ,business.industry ,General Engineering ,Pattern recognition ,Feature selection ,computer.software_genre ,Feature (computer vision) ,Selection method ,Artificial intelligence ,Data mining ,business ,computer ,Feature ranking ,Selection (genetic algorithm) - Abstract
In this paper, a novel grey‐based feature ranking method for feature subset selection is proposed. The classification effectiveness of each attribute of a specific classification problem is proposed and then each attribute can be ranked. Features with higher classification effectiveness are more important and relevant and thus considered as the final feature subset for pattern classification. Experiments performed on various application domains are reported to demonstrate the performance of the proposed approach. The proposed approach yields better performance than other existing feature subset selection methods and is helpful for improving the classification accuracy in pattern classification.
- Published
- 2008
27. Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1
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Han-Yi Chou, Fu-Chia Yang, Chia-Wei Lee, Bertrand Chin-Ming Tan, Hsin-Yun Chang, and Sheng-Chung Lee
- Subjects
Cytoplasm ,Transcription, Genetic ,macromolecular substances ,Mitogen-activated protein kinase kinase ,Protein Serine-Threonine Kinases ,Biochemistry ,environment and public health ,Histone Deacetylases ,Multienzyme Complexes ,Humans ,ASK1 ,c-Raf ,Protein Phosphatase 2 ,Phosphorylation ,Molecular Biology ,Cell Proliferation ,biology ,MAP kinase kinase kinase ,MEF2 Transcription Factors ,Cyclin-dependent kinase 2 ,Cell Biology ,Protein phosphatase 2 ,enzymes and coenzymes (carbohydrates) ,HEK293 Cells ,Calcium-Calmodulin-Dependent Protein Kinase Type 1 ,Gene Expression Regulation ,embryonic structures ,Cyclin-dependent kinase complex ,biology.protein ,Cyclin-dependent kinase 9 ,Carboxylic Ester Hydrolases ,Gene Deletion ,Signal Transduction - Abstract
Salt-inducible kinase 2 (SIK2) is the only AMP-activated kinase (AMPK) family member known to interact with protein phosphatase 2 (PP2A). However, the functional aspects of this complex are largely unknown. Here we report that the SIK2-PP2A complex preserves both kinase and phosphatase activities. In this capacity,SIK2 attenuates the association of the PP2A repressor, the protein phosphatase methylesterase-1 (PME-1), thus preserving the methylation status of the PP2A catalytic subunit. Furthermore, the SIK2-PP2A holoenzyme complex dephosphorylates and inactivates Ca2(+)/calmodulin-dependent protein kinase I (CaMKI), an upstream kinase for phosphorylating PME-1/Ser(15). The functionally antagonistic SIK2-PP2A and CaMKI and PME-1 networks thus constitute a negative feedback loop that modulates the phosphatase activity of PP2A. Depletion of SIK2 led to disruption of the SIK2-PP2A complex, activation of CaMKI, and downstream effects, including phosphorylation of HDAC5/Ser(259), sequestration of HDAC5 in the cytoplasm, and activation of myocyte-specific enhancer factor 2C (MEF2C)-mediated gene expression. These results suggest that the SIK2-PP2A complex functions in the regulation of MEF2C-dependent transcription. Furthermore, this study suggests that the tightly linked regulatory loop comprised of the SIK2-PP2A and CaMKI and PME-1 networks may function in fine-tuning cell proliferation and stress response.
- Published
- 2014
28. Reversible Acetylation Regulates Salt-inducible Kinase (SIK2) and Its Function in Autophagy*
- Author
-
Hsin Yun Chang, Ching-Jin Chang, Pang-Hung Hsu, Hui Yu Sun, Ya Huei Lin, Wei Hao Chen, Jing Yi Huang, Sheng-Chung Lee, Chau-Chung Han, Fu-Chia Yang, Gunn-Guang Liou, Ming-Daw Tsai, Bertrand Chin-Ming Tan, and James C.K. Shen
- Subjects
Mutation, Missense ,Biology ,Mitogen-activated protein kinase kinase ,Protein Serine-Threonine Kinases ,Histone Deacetylase 6 ,Biochemistry ,Histone Deacetylases ,MAP2K7 ,Cell Line ,Autophagy ,Humans ,ASK1 ,Kinase activity ,Molecular Biology ,Inclusion Bodies ,MAP kinase kinase kinase ,Cyclin-dependent kinase 4 ,Lysine ,Cyclin-dependent kinase 2 ,Acetylation ,Cell Biology ,Amino Acid Substitution ,Protein Synthesis and Degradation ,biology.protein ,Cyclin-dependent kinase 9 ,Lysosomes ,Protein Processing, Post-Translational - Abstract
Salt-inducible kinase 2 (SIK2) is a serine/threonine protein kinase belonging to the AMP-activated protein kinase (AMPK) family. SIK2 has been shown to function in the insulin-signaling pathway during adipocyte differentiation and to modulate CREB-mediated gene expression in response to hormones and nutrients. However, molecular mechanisms underlying the regulation of SIK2 kinase activity remains largely elusive. Here we report a dynamic, post-translational regulation of its kinase activity that is coordinated by an acetylation-deaceytlation switch, p300/CBP-mediated Lys-53 acetylation inhibits SIK2 kinase activity, whereas HDAC6-mediated deacetylation restores the activity. Interestingly, overexpression of acetylation-mimetic mutant of SIK2 (SIK2-K53Q), but not the nonacetylatable K53R variant, resulted in accumulation of autophagosomes. Further consistent with a role in autophagy, knockdown of SIK2 abrogated autophagosome and lysosome fusion. Consequently, SIK2 and its kinase activity are indispensable for the removal of TDP-43Δ inclusion bodies. Our findings uncover SIK2 as a critical determinant in autophagy progression and further suggest a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis. Background: Salt-inducible kinase (SIK) 2 is an AMP-activated protein kinase family kinase that mediates hormonal and nutrient signaling but has no known link to cellular stress response. Results: p300/CBP and HDAC6 reciprocally regulates Lys-53 acetylation of SIK2, consequently impacting its activity and function in autophagosome maturation. Conclusion: SIK2 kinase activity, via a acetylation-based regulatory switch, contributes to autophagy progression. Significance: SIK2 may be linked to neurodegenerative or protein aggregate disorders.
- Published
- 2013
29. Using rhodamine 6G-modified gold nanoparticles to detect organic mercury species in highly saline solutions
- Author
-
Yu-Fen Huang, Tung-Ming Hsiung, Hsin-Yun Chang, and Chih-Ching Huang
- Subjects
MERCURE ,Analytical chemistry ,chemistry.chemical_element ,Nanoparticle ,Metal Nanoparticles ,Signal-To-Noise Ratio ,Sodium Chloride ,Fluorescence spectroscopy ,Fluorescence ,Rhodamine 6G ,chemistry.chemical_compound ,Environmental Chemistry ,Animals ,Bovine serum albumin ,Ions ,Aqueous solution ,biology ,Rhodamines ,Fishes ,Water ,Serum Albumin, Bovine ,General Chemistry ,Mercury ,Methylmercury Compounds ,Mercury (element) ,Solutions ,chemistry ,Colloidal gold ,biology.protein ,Gold ,Nuclear chemistry - Abstract
We developed a gold nanoparticle (Au NP)-based fluorescence sensor for the detection of mercury ions in aqueous solutions. After introducing bovine serum albumin (BSA) to a solution of rhodamine 6G (R6G) and 3-mercaptopropionic acid (MPA)-modified Au NPs, the as-prepared BSA@R6G/MPA-Au NP probe could sense mercury ions under high salt conditions. This probe operated through a mechanism involving mercury species depositing onto the surfaces of the Au NPs and releasing R6G molecules into the solution, causing the fluorescence intensity of the BSA@R6G/MPA-AuNP solution to increase. We improved the selectivity of the nanosensor by adding masking agents (ethylenediamine tetraacetic acid (EDTA) and Na2S) or tellurium nanowires (Te NWs) to the sample solutions. In the presence of 1.0 mM EDTA and 10 μM Na2S, the selectivities of this system toward phenylmercury (PhHg(I)) over other metal ions and mercury species were greater than 200- and 10-fold, respectively. The limit of detection (LOD), at a signal-to-noise ratio of 3, for PhHg(I) was 20 nM. Selective detection of the total organic mercury (methylmercury (MeHg(I)), ethylmercury (EtHg(I)), and PhHg(I)) was possible when using the BSA@R6G/MPA-Au NPs in conjunction with Te NWs (3.0 nM). The selectivity of this nanosensor system for the total organic mercury over Hg(II) was remarkably high (100-fold) with an LOD for organic mercury of 10 nM. We also demonstrated the feasibility of using the developed nanosensor for rapid determination of mercury species in river, sea, and tap water as well as in fish samples.
- Published
- 2011
30. Computational Modeling and Experimental Characterization of Hyperelastic Thin Film NiTi for Neurovascular Microstent Applications
- Author
-
Allan W. Tulloch, Daniel S. Levi, Colin Kealey, Michael C. Emmons, Kotekar P. Mohanchandra, Peter F. Lawrence, Hsin-yun Chang, Myunghoon Seong, Youngjae Chun, Po-Yu Lin, Gregory P. Carman, and David A. Rigberg
- Subjects
Stress (mechanics) ,Materials science ,Buckling ,business.industry ,Nickel titanium ,Hyperelastic material ,Structural engineering ,Thin film ,business ,Neurovascular bundle ,Finite element method ,Characterization (materials science) - Abstract
A novel hyperelastic thin film NiTi covered neurovascular microstent was developed for treating wide-neck and fusiform neurovascular aneurysms. This device requires 300–500% recoverable elongation for both collapsing and deployment. Nonlinear buckling and static analysis of Finite Element Modeling (FEM: ANSYS software used) was applied for obtaining critical buckling stress and critical strain values depending on thickness, strut width and pore height. A maximum theoretical critical strain for one geometry as high as 316% while a different experimentally tested film was found to strain 600% elastically without any signs of permanent deformation.Copyright © 2010 by ASME
- Published
- 2010
31. A Novel GA-Taguchi-Based Feature Selection Method
- Author
-
Chi-Chun Huang, Kuo-Chuan Wu, Hsin-yun Chang, and Cheng-Hong Yang
- Subjects
business.industry ,Feature (computer vision) ,Genetic algorithm ,Crossover ,Search problem ,Local search (optimization) ,Feature selection ,Pattern recognition ,Artificial intelligence ,Orthogonal array ,business ,Selection (genetic algorithm) ,Mathematics - Abstract
This work presents a novel GA-Taguchi-based feature selection method. Genetic algorithms are utilized with randomness for "global search" of the entire search space of the intractable search problem. Various genetic operations, including crossover, mutation, selection and replacement are performed to assist the search procedure in escaping from sub-optimal solutions. In each iteration in the proposed nature-inspired method, the Taguchi methods are employed for "local search" of the entire search space and thus can help explore better feature subsets for next iteration. The two-level orthogonal array is utilized for a well-organized and balanced comparison of two levels for features--a feature is or is not selected for pattern classification--and interactions among features. The signal-to-noise ratio (SNR) is then used to determine the robustness of the features. As a result, feature subset evaluation efforts can be significantly reduced and a superior feature subset with high classification performance can be obtained. Experiments are performed on different application domains to demonstrate the performance of the proposed nature-inspired method. The proposed hybrid GA-Taguchi-based approach, with wrapper nature, yields superior performance and improves classification accuracy in pattern classification.
- Published
- 2008
32. A Novel Hybrid Taguchi-Grey-Based Method for Feature Subset Selection
- Author
-
Chung-Shan Sun and Hsin-Yun Chang
- Subjects
Selection (relational algebra) ,business.industry ,Classification procedure ,Pattern recognition ,computer.software_genre ,k-nearest neighbors algorithm ,Matrix (mathematics) ,Taguchi methods ,Feature (machine learning) ,Data mining ,Artificial intelligence ,Orthogonal array ,business ,computer ,Mathematics - Abstract
In this paper, a novel hybrid Taguchi-Grey-based method for feature subset selection is proposed. The two-level orthogonal array is employed in the proposed method to provide a well-organized and balanced comparison of two levels of each feature (i.e., the feature is selected for pattern classification or not) and interactions among all features in a specific classification problem. That is, this two-dimensional matrix is mainly used to reduce the feature subset evaluation efforts prior to the classification procedure. Accordingly, the grey-based nearest neighbor rule and the signal-to-noise ratio (SNR) are used to evaluate and optimize the features of the specific classification problem. In this manner, important and relevant features can be identified for pattern classification. Experiments performed on different application domains are reported to demonstrate the performance of the proposed hybrid Taguchi-Grey-based method. It can be easily seen that the proposed method yields superior performance and is helpful for improving the classification accuracy in pattern classification.
- Published
- 2007
33. A Novel Grey-Based Feature Ranking Method for Feature Subset Selection
- Author
-
Hsin-yun Chang, Cheng-Hong Yang, and Chi-Chun Huang
- Subjects
Computer science ,business.industry ,Feature extraction ,Pattern recognition ,computer.software_genre ,k-nearest neighbors algorithm ,Feature (computer vision) ,Feature (machine learning) ,Data mining ,Artificial intelligence ,business ,computer ,Feature ranking ,Selection (genetic algorithm) - Abstract
In this paper, a novel grey-based feature ranking method for feature subset selection is proposed. Experiments performed on various application domains are reported to demonstrate the performance of the proposed approach. It can be easily seen that the proposed approach yields high performance and is helpful for pattern classification.
- Published
- 2006
34. Extracellular Acid-Base Balance and Ion Transport Between Body Fluid Compartments.
- Author
-
Seifter, Julian L. and Hsin-Yun Chang
- Subjects
- *
ACID-base imbalances , *EXTRACELLULAR fluid , *CONDUCTIVITY of electrolytes , *ION transport (Biology) , *CELL physiology - Abstract
Clinical assessment of acid-base disorders depends on measurements made in the blood, part of the extracellular compartment. Yet much of the metabolic importance of these disorders concerns intracellular events. Intracellular and interstitial compartment acid-base balance is complex and heterogeneous. This review considers the determinants of the extracellular fluid pH related to the ion transport processes at the interface of cells and the interstitial fluid, and between epithelial cells lining the transcellular contents of the gastrointestinal and urinary tracts that open to the external environment. The generation of acid-base disorders and the associated disruption of electrolyte balance are considered in the context of these membrane transporters. This review suggests a process of internal and external balance for pH regulation, similar to that of potassium. The role of secretory gastrointestinal epithelia and renal epithelia with respect to normal pH homeostasis and clinical disorders are considered. Electroneutrality of electrolytes in the ECF is discussed in the context of reciprocal changes in Cl- or non Cl- anions and HCO3-. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
35. Disorders of Acid-Base Balance: New Perspectives.
- Author
-
Seifter, Julian L. and Hsin-Yun Chang
- Published
- 2017
- Full Text
- View/download PDF
36. Synthesis of nitrogen-doped graphene by pyrolysis of ionic-liquid-functionalized graphene
- Author
-
Quang Duc Truong, Hsin Yun Chang, Yong-Chien Ling, and Jen-Yu Liu
- Subjects
Electrolysis ,Materials science ,Graphene ,Graphene foam ,Nanotechnology ,General Chemistry ,law.invention ,chemistry.chemical_compound ,Chemical engineering ,chemistry ,Electrical resistivity and conductivity ,law ,Ionic liquid ,Materials Chemistry ,Pyrolysis ,Graphene nanoribbons ,Graphene oxide paper - Abstract
Nitrogen-doped graphene with up to 22.1% N/C atom and 7.15 × 104 Sm−1 electrical conductivity was synthesized by ionic-liquid-assisted electrolysis with subsequent thermal annealing of the resultant ionic-liquid-functionalized graphene sheet.
- Published
- 2013
37. A Novel Grey-Based Feature Ranking Method for Feature Subset Selection.
- Author
-
Chi-Chun Huang, Hsin-Yun Chang, and Cheng-Hong Yang
- Published
- 2006
- Full Text
- View/download PDF
38. Using Rhodamine 6G-Modified Gold Nanoparticles To Detect Organic Mercury Species in Highly Saline Solutions.
- Author
-
Hsin-Yun Chang, Tung-Ming Hsiung, Yu Fen Huang, and Chih-Ching Huang
- Subjects
- *
NANOSCIENCE , *MERCURY , *FLUORESCENCE , *CHEMICAL detectors , *SALTWATER solutions , *SOLUTION (Chemistry) - Abstract
We developed a gold nanoparticle (Au NP)-based fluorescence sensor for the detection of mercury ions in aqueous solutions. After introducing bovine serum albumin (BSA) to a solution of rhodamine 6G (R6G) and 3-mercaptopropionic acid (MPA)-modified Au NPs, the as-prepared BSA@R6G/MPA-Au NP probe could sense mercury ions under high salt conditions. This probe operated through a mechanism involving mercury species depositing onto the surfaces of the Au NPs and releasing R6G molecules into the solution, causing the fluorescence intensity of the BSA@R6G/MPA-AuNP solution to increase. We improved the selectivity of the nanosensor by adding masking agents (ethylenediamine tetraacetic acid (EDTA) and Na2S) or tellurium nanowires (Te NWs) to the sample solutions. In the presence of 1.0 mM EDTA and 10 μM Na2S, the selectivities of this system toward phenylmercury (PhHg(I)) over other metal ions and mercury species were greater than 200- and 10-fold, respectively. The limit of detection (LOD), at a signal-to-noise ratio of 3, for PhHg(I) was 20 nM. Selective detection of the total organic mercury (methylmercury (MeHg(I)), ethylmercury (EtHg(I)), and PhHg(I)) was possible when using the BSA@R6G/MPA-Au NPs in conjunction with Te NWs (3.0 nM). The selectivity of this nanosensor system for the total organic mercury over Hg(II) was remarkably high (100-fold) with an LOD for organic mercury of 10 nM. We also demonstrated the feasibility of using the developed nanosensor for rapid determination of mercury species in river, sea, and tap water as well as in fish samples. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
39. Interaction between Salt-inducible Kinase 2 and Protein Phosphatase 2A Regulates the Activity of Calcium/ Calmodulin-dependent Protein Kinase I and Protein Phosphatase Methylesterase-1.
- Author
-
Chia-Wei Lee, Fu-Chia Yang, Hsin-Yun Chang, Hanyi Chou, Bertrand Chin-Ming Tan, and Sheng-Chung Lee
- Subjects
- *
PROTEIN kinases , *PHOSPHOPROTEIN phosphatases , *GENE expression , *CELL proliferation , *METHYLESTERASES , *CYTOLOGICAL research , *CALMODULIN - Abstract
Salt-inducible kinase 2 (SIK2) is the only AMP-activated kinase (AMPK) family member known to interact with protein phosphatase 2 (PP2A). However, the functional aspects of this complex are largely unknown. Here we report that the SIK2 ⋅ PP2A complex preserves both kinase and phosphatase activities. In this capacity, SIK2 attenuates the association of the PP2A repressor, the protein phosphatase methylesterase-1 (PME-1), thus preserving the methylation status of the PP2A catalytic subunit. Furthermore, the SIK2 ⋅ PP2A holoenzyme complex dephosphorylates and inactivates Ca2+/calmodulin-dependent protein kinase I (CaMKI), an upstream kinase for phosphorylating PME-1/Ser15. The functionally antagonistic SIK2 ⋅ PP2A and CaMKI and PME-1 networks thus constitute a negative feedback loop that modulates the phosphatase activity of PP2A. Depletion of SIK2 led to disruption of the SIK2 ⋅ PP2A complex, activation of CaMKI, and downstream effects, including phosphorylation of HDAC5/Ser259, sequestration of HDAC5 in the cytoplasm, and activation of myocyte-specific enhancer factor 2C (MEF2C)-mediated gene expression. These results suggest that the SIK2 ⋅ PP2A complex functions in the regulation of MEF2C-dependent transcription. Furthermore, this study suggests that the tightly linked regulatory loop comprised of the SIK2 ⋅ PP2A and CaMKI and PME-1 networks may function in fine-tuning cell proliferation and stress response. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
40. Interaction between Salt-inducible Kinase 2 (SIK2) and p97/Valosin-containing Protein (VCP) Regulates Endoplasmic Reticulum(ER)-associated Protein Degradation in Mammalian Cells.
- Author
-
Fu-Chia Yang, Ya-Huei Lin, Wei-Hao Chen, Jing-Yi Huang, Hsin-Yun Chang, Su-Hui Su, Hsiao-TingWang, Chun-Yi Chiang, Pang-Hung Hsu, Ming-Daw Tsai, Tan, Bertrand Chin-Ming, and Sheng-Chung Lee
- Subjects
- *
ENDOPLASMIC reticulum , *ORGANELLES , *PROTEOLYSIS , *PROTEIN metabolism , *MAMMALIAN cell cycle - Abstract
Salt-inducible kinase 2 (SIK2) is an important regulator of cAMP response element-binding protein-mediated gene expression in various cell types and is the only AMP-activated protein kinase family member known to interact with the p97/valosin-containing protein (VCP) ATPase. Previously, we have demonstrated that SIK2 can regulate autophagy when proteasomal function is compromised. Here we report that physical and functional interactions between SIK2 and p97/VCP underlie the regulation of endoplasmic reticulum (ER)-associated protein degradation (ERAD). SIK2 co-localizeswith p97/VCP in the ER membrane and stimulates its ATPase activity through direct phosphorylation. Although the expression of wild-type recombinant SIK2 accelerated the degradation and removal of ERADsubstrates, the kinase-deficient variant conversely had no effect. Furthermore, down-regulation of endogenous SIK2 or mutation of the SIK2 target site on p97/VCP led to impaired degradation of ERAD substrates and disruption of ER homeostasis. Collectively, these findings highlight a mechanism by which the interplay between SIK2 and p97/VCP contributes to the regulation of ERAD in mammalian cells. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
41. Reversible Acetylation Regulates Salt-inducible Kinase (SIK2) and Its Function in Autophagy.
- Author
-
Fu-Chia Yang, Chin-Ming Tan, Bertrand, Wei-Hao Chen, Ya-Huei Lin, Jing-Yi Huang, Hsin-Yun Chang, Hui-Yu Sun, Pang-Hung Hsu, Gunn-Guang Liou, Shen, James, Ching-Jin Chang, Chau-Chung Han, Ming-Daw Tsai, and Sheng-Chung Lee
- Subjects
- *
ACETYLATION , *PROTEIN kinases , *AUTOPHAGY , *THREONINE , *FAT cells , *LYSOSOMES , *HOMEOSTASIS - Abstract
Salt-inducible kinase 2 (SIK2) is a serine/threonine protein kinase belonging to the AMP-activated protein kinase (AMPK) family. SIK2 has been shown to function in the insulin-signaling pathway during adipocyte differentiation and to modulate CREB-mediated gene expression in response to hormones and nutrients. However, molecular mechanisms underlying the regulation of SIK2 kinase activity remains largely elusive. Here we report a dynamic, post-translational regulation of its kinase activity that is coordinated by an acetylation-deaceytlation switch, p300/CBP-mediated Lys-53 acetylation inhibits SIK2 kinase activity, whereas HDAC6-mediated deacetylation restores the activity. Interestingly, overexpression of acetylation- mimetic mutant of SIK2 (SIK2-K53Q), but not the nonacetylatable K53R variant, resulted in accumulation of autophagosomes. Further consistent with a role in autophagy, knockdown of SIK2 abrogated autophagosome and lysosome fusion. Consequently, SIK2 and its kinase activity are indispensable for the removal of TDP-43Δ inclusion bodies. Our findings uncover SIK2 as a critical determinant in autophagy progression and further suggest a mechanism in which the interplay among kinase and deacetylase activities contributes to cellular protein pool homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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