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HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways

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Protein & Cell 2012年第10期3卷 781-789页

作者： byung-kwon choi Xiumei Cai Bin Yuan Zhao Huang Xuejun Fan Hui Deng Ningyan Zhang Zhiqiang An Texas Therapeutics Institute Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at HoustonHoustonTX 77030USA Department of Biochemistry and Molecular Biology Shanghai Medical CollegeFudan UniversityShanghai 200032China The Methodist Hospital Research Institute HoustonTX 77030USA

Dimerization among the EGFR family of tyrosine kinase receptors leads to allosteric activation of the kinase domains of the *** other members in the family,the kinase domain of HER3 lacks key amino acid residues for catalytic *** a result,HER3 is suggested to serve as an allosteric activator of other EGFR family members which include EGFR,HER2 and *** study the role of intracellular domains in HER3 dimerization and activation of downstream signaling pathways,we constructed HER3/HER2 chimeric receptors by replacing the HER3 kinase domain(HER3-2-3)or both the kinase domain and the C-terminal tail(HER3-2-2)with the HER2 counterparts and expressed the chimeric receptors in Chinese hamster ovary(CHO)*** over expression of the intact human HER3 transformed CHO cells with oncogenic properties such as AKT/ERK activation and increased proliferation and migration,CHO cells expressing the HER3-2-3 chimeric receptor showed significantly reduced HER3/HER2 dimerization and decreased phosphorylation of both AKT and ERK1/2 in the presence of neuregulin-1(NRG-1).In contrast,CHO cells expressing the HER3-2-2 chimeric receptor resulted in a total loss of downstream AKT activation in response to NRG-1,but maintained partial activation of ERK1/*** results demonstrate that the intracellular domains play a crucial role in HER3’s function as an allosteric activator and its role in downstream signaling.

关键词： HER3 HER2 cell proliferation cell migration PI3K/AKT MAPK/ERK1/2

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin byung Gon Kim Jun Young choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Evaluation of Mechanical Properties According to Nb Content of High Strength Steel Manufactured in VIM

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Journal of Materials Science & Technology 2008年第5期24卷 793-796页

作者： byung-Hui choi byung-Ki choi Department of Mechanical Engineering Graduate SchoolChosun UniversityKorea Department of Mechanical Engineering Chosun UniversityGwang-ju 501-750Korea

As the aircraft and aerospace industry and the automobile industry are developed, the demand of reliable materials with high strength and high toughness is steadily increased. The grain miniature method which improves the ductility and the toughness simultaneously under high strength is the miniature of the casting microstructure. In this paper, the Nb which affects the austenite grain miniature is added by 0.00%, 0.03% and 0.06% in this steel and the ingot is manufactured in a vacuum induction melting furnace （VIM）. The casting microstructure and the mechanical property of the maraging steel according to Nb contents are analyzed by conducting the solution annealing and the age hardening after hot rolling. In this result, a specimen containing 0.03% Nb is most miniature. When it does the long time age hardening, the precipitation estimated as the carbide is appeared. The mechanical properties are excellent if a specimen containing 0.06% Nb does the age hardening during 8 h in 482℃.

关键词： High strength steel Maraging steel Nb Vacuum induction melting furnace (VIM)

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Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon choi Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

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Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration

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Neural Regeneration Research 2025年第5期20卷 1414-1415页

作者： Sinwoo Hwang Seunghwan choi Soo-Ho choi Keun-Young Kim Yury I.Miller Won-Kyu Ju Hamilton Glaucoma Center and Shiley Eye Institute The Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCAUSA Department of Medicine University of California San DiegoLa JollaCAUSA National Center for Microscopy and Imaging Research Department of NeurosciencesUniversity of California San DiegoLa JollaCAUSA

Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs *** to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more *** primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.

关键词： irreversible pass primarily

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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Study of Partial Coefficients for Design of Semicircular Breakwaters

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China Ocean Engineering 2010年第1期24卷 29-40页

作者：郄禄文 byung Ho choi College of Civil Engineering Hebei University Department of Civil and Environmental Engineering Sungkyunkwan University300 Chunchun-dongJangan-GuSuwon

In the present study, the reliability design of semicircular breakwater is based on the verification of the rules defined by standard specifications, where partial coefficients are introduced to ensure safety. The reliability of the semicircular breakwaters has been analyzed by using the Hasofer-Lind method to determine the reliability index of structure that has correlated loads, utilizing the long-term observed wave data at a given place. The relation curve between reliability index and safety factor in the traditional design method, as well as the relationships between reliability index and partial coefficients, have been obtained. This paper proposes values of partial coefficients for the design expression of semicircular breakwaters in the cases of anti-sliding and anti-overturning.

关键词： partial coefftcient reliability index correlated variables semicircular breakwater

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Wave-Tide-Surge Coupled Simulation for Typhoon Maemi

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China Ocean Engineering 2013年第2期27卷 141-158页

作者： byung Ho choi byung Il Min Kyeong Ok Kim Jin Hee Yuk Department of Civil and Environmental Engineering Sungkyunkwan University Marine Environments & Conservation Research Division Korea Institute of Ocean Science & Technology Supercomputing Center Korea Institute of Science and Technology Information

The main task of this study focuses on studying the effect of wave-current interaction on currents, storm surge and wind wave as well as effects of current induced wave refraction and current on waves by using numerical models which consider the bottom boundary layer and sea surface roughness parameter for shallow and smooth bed area around Korean Peninsula. The coupled system （unstructured-mesh SWAN wave and ADCIRC） run on the same unstructured mesh. This identical and homogeneous mesh allows the physics of wave-circulation interactions to be correctly resolved in both models. The unstructured mesh can be applied to a large domain allowing all energy from deep to shallow waters to be seamlessly followed. There is no nesting or overlapping of structured wave meshes, and no interpolation is required. In response to typhoon Maemi （2003）, all model components were validated independently, and shown to provide a faithful representation of the system＇s response to this storm. The waves and storm surge were allowed to develop on the continental shelf and interact with the complex nearshore environment. The resulting modeling system can be used extensively for prediction of the typhoon surge. The result show that it is important to incorporate the wave-current interaction effect into coastal area in the wave-tide-surge coupled model. At the same time, it should consider effects of depth-induced wave breaking, wind field, currents and sea surface elevation in prediction of waves. Specially, we found that：（1） wave radiation stress enhanced the current and surge elevation otherwise wave enhanced nonlinear bottom boundary layer decreased that, （2） wind wave was significantly controlled by sea surface roughness thus we cautiously took the experimental expression. The resulting modeling system can be used for hindcasting （prediction） the wave-tide-surge coupled environments at complex coastline, shallow water and fine sediment area like areas around Korean Peninsula.

关键词： typhoon Maemi finite element model tide-surge-wave coupling

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Optimal seismic retrofit model for steel moment resisting frames with brittle connections

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Earthquake Engineering and Engineering Vibration 2018年第4期17卷 835-847页

作者： Hyo Seon Park Se Woon choi byung Kwan Oh Department of Architectural Engineering Yonsei University Center for Structural Health Care Technology in Building Yonsei University Department of Architecture Catholic University of Daegu Department of Civil and Environmental Engineering Princeton University

Based on performance-based seismic engineering, this paper proposes an optimal seismic retrofit model for steel moment resisting frames（SMRFs） to generate a retrofit scheme at minimal cost. To satisfy the acceptance criteria for the Basic Safety Objective（BSO） specified in FEMA 356, the minimum number of upgraded connections and their locations in an SMRF with brittle connections are determined by evolutionary computation. The performance of the proposed optimal retrofitting model is evaluated on the basis of the energy dissipation capacities, peak roof drift ratios, and maximum interstory drift ratios of structures before and after retrofitting. In addition, a retrofit efficiency index, which is defined as the ratio of the increment in seismic performance to the required retrofitting cost, is proposed to examine the efficiencies of the retrofit schemes derived from the model. The optimal seismic retrofit model is applied to the SAC benchmark examples for threestory and nine-story SMRFs with brittle connections. Using the retrofit efficiency index proposed in this study, the optimal retrofit schemes obtained from the model are found to be efficient for both examples in terms of energy dissipation capacity, roof drift ratio, and maximum inter-story drift ratio.

关键词： steel moment resisting frame performance-based seismic engineering optimal seismic retrofit evolutionarycomputation

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Three-Dimensional Numerical Model for Tsunami Propagation Passing Through An Obstacle

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China Ocean Engineering 2006年第3期20卷 509-516页

作者： Sung Jin HONG byung Ho choi Fumihiko IMAMURA Department of Civil and Environmental Engineering Sungkyunkwan University Chunchun-dong 300 Jangan-gu Suwon 440-746 Korea Disaster Control Research Center Graduate School of Engineering Tohoku University Aoba 06 Sendai 980-8579 Japan

A three-dimensional numerical tsunami model is developed to analyze the nonlinear behavior of flow around obstacles with the Marker and Cell （MAC） method based on the Navier-Stokes equations. Tnrough a comparison with experimental data for the cases of dam break and solitary wave propagation, verification of the three-dimensional numerical model is given. Numerical experiment is performed for the analysis of the nonlinear behavior of flow around obstacles and compared with experimental data. The velocity and pressure around obstacles are presented with sufficient accuracy for tstmami propagation passing through an obstacle.

关键词： three-dimensional numericxtl model tsunami Navier-Stokes equations Marker and Ceml (MAC) method

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