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A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1093-1109页

作者： Sae-Bom Yoon Hyowon Hong Hee-Jong Lim Ji Hye Choi Yoon Pyo Choi Seong wook Seo Hyuk woo Lee Chong Hak Chae woo-kyu park Hyun Young Kim Daeyoung Jeong Tran Quang De Chang-Seon Myung Heeyeong Cho Therapeutics&Biotechnology Division Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea Department of Pharmacology Chungnam National University College of PharmacyYuseong-guDaejeon 34134Republic of Korea Future Medicine Co. Ltd.Rm616 LH-Business Growth CenterSeongnamGyeonggido 13449Republic of Korea Department of Chemistry College of Natural SciencesCan Tho UniversityCan Tho city 9000Viet Nam

Interleukin-1 receptor-associated kinase 4(IRAK4)is a pivotal enzyme in the Toll-like receptor(TLR)/MYD88 dependent signaling pathway,which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL).Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of ***,proviral integration site for Moloney murine leukemia virus 1(PIM1)functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib *** developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in *** rheumatoid arthritis mouse models,treatment with KIC-0101 significantly ameliorated cartilage damage and ***-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in *** addition,KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 *** results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

关键词： Drug discovery IRAK4 PIM1 NF-κB pathway Rheumatoid arthritis ABC-DLBCL Ibrutinib resistance Dual inhibitor

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Prominent cycling reversibility and kinetics enabled by CaTiO3 protective layer on Zn metal for aqueous Zn-ion batteries

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Journal of Energy Chemistry 2025年第1期100卷 245-258页

作者： Gaeun Lee Yong Nam Ahn Seongjoon So Chanwoo park Jong-Seong Bae Taehyun park Il Tae Kim Jaehyun Hur School of Chemical Biological and Battery Engineering Gachon University Seongnam Busan Center Korea Basic Science Institute

Aqueous Zn-ion batteries （AZIBs） have received considerable attention owing to their various advantages such as safety,low cost,simple battery assembly conditions,and high ionic ***,they still suffer from serious problems,including uncontrollable dendrite growth,corrosion,hydrogen evolution reaction （HER） from water decomposition,electrode passivation,and unexpected *** creation of a uniform artificial nanocrystal layer on the Zn anode surface is a promising strategy for resolving these ***,we propose the use of a perovskite CaTiO3（CTO） protective layer on Zn（CTO@Zn） as a promising approach for improving the performance of *** CTO artificial layer provides an efficient pathway for Zn ion diffusion towards the Zn metal because of the high dielectric constant （εr=180） and ferroelectric characteristics that enable the alignment of dipole moments and redistribute the Zn2+ions in the CTO *** avoiding the direct contact of the Zn anode with the electrolyte solution,the uneven dendrite growth,corrosion,parasitic side reactions,and HER are mitigated,while CTO retains its mechanical and chemical robustness during ***,CTO@Zn demonstrates an improved lifespan in a symmetric cell configuration compared with bare ***@Zn shows steady overpotential （～68 m V） for 1500 h at 1 mA cm-2/0.5 mA h cm-2,excelling bare ***,when paired with the V2O5-C cathode,the CTO@Zn//V2O5-C full battery delivers 148.4 mA h g-1（based on the mass of the cathode） after 300 *** study provides new insights into Zn metal anodes and the development of high-performance AZIBs.

关键词： Artificial layer Dielectric constant Zn metal anode Zinc aqueous battery

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Statistical Downscaling for Multi-Model Ensemble Prediction of Summer Monsoon Rainfall in the Asia-Pacific Region Using Geopotential Height Field

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Advances in Atmospheric Sciences 2008年第5期25卷 867-884页

作者：祝从文 Chung-kyu park woo-Sung LEE Won-Tae YUN Chinese Academy of Meteorological Sciences Asia-Pacific Economic Cooperation Climate Center (APCC) Busan Republic of Korea Canadian Centre for Climate Modelling and Reanalysis Victoria BC Canada Korea Meteorological Administration Seoul Republic of Korea

The 21-yr ensemble predictions of model precipitation and circulation in the East Asian and western North Pacific （Asia-Pacific） summer monsoon region （0°-50°N, 100° 150°E） were evaluated in nine different AGCM, used in the Asia-Pacific Economic Cooperation Climate Center （APCC） multi-model ensemble seasonal prediction system. The analysis indicates that the precipitation anomaly patterns of model ensemble predictions are substantially different from the observed counterparts in this region, but the summer monsoon circulations are reasonably predicted. For example, all models can well produce the interannual variability of the western North Pacific monsoon index （WNPMI） defined by 850 hPa winds, but they failed to predict the relationship between WNPMI and precipitation anomalies. The interannual variability of the 500 hPa geopotential height （GPH） can be well predicted by the models in contrast to precipitation anomalies. On the basis of such model performances and the relationship between the interannual variations of 500 hPa GPH and precipitation anomalies, we developed a statistical scheme used to downscale the summer monsoon precipitation anomaly on the basis of EOF and singular value decomposition （SVD）. In this scheme, the three leading EOF modes of 500 hPa GPH anomaly fields predicted by the models are firstly corrected by the linear regression between the principal components in each model and observation, respectively. Then, the corrected model GPH is chosen as the predictor to downscale the precipitation anomaly field, which is assembled by the forecasted expansion coefficients of model 500 hPa GPH and the three leading SVD modes of observed precipitation anomaly corresponding to the prediction of model 500 hPa GPH during a 19-year training period. The cross-validated forecasts suggest that this downscaling scheme may have a potential to improve the forecast skill of the precipitation anomaly in the South China Sea, western North Pacific and the East Asia

关键词： summer monsoon precipitation multi-model ensemble prediction statistical downscaling forecast

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Evaluation of early-age strains and stresses in roller-compacted concrete pavement

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Journal of Traffic and Transportation Engineering(English Edition) 2022年第1期9卷 93-105页

作者： Tetsya Sok Young kyu Kim Jun Young park Seung woo Lee Public Infrastructure Department Ministry of Public Works and TransportPhnom Penh 12100Cambodia Institute for Disaster Prevention Gangneung-Wonju National UniversityGangneung-si 25457South Korea Korea Expressway Research Institute Korea Expressway CorporationHwaseong-si 18489South Korea Civil Engineering Department Gangneung-Wonju National UniversityGangneung-si 25457South Korea

In the structural design of a roller-compacted concrete pavement(RCCP), it is crucial to estimate strain and stress developments in the RCCP slab realistically. Since the RCCP mix uses less cement and lower amount of water, shrinkage strain and concrete temperature during the hardening stage are expected to be reduced as compared to those of conventional concrete mixture, resulting in a reduction of the concrete early-age deformation and stress developments in the RCCP slab. In this paper, early-age concrete strain and stress developments in RCCP slab subjected to environmental loads were evaluated. A full-scale test section of RCCP under real climatic conditions was monitored. The early-age total strains,stress-independent strains, shrinkage strains, and coefficient of thermal expansion(CTE) of the RCCP were measured and analyzed. Using the results of measured strains, in-situ CTE and shrinkage strain, and temperature, the early-age concrete stress development is computed by incorporating a viscoelastic property of the early-age concrete. The results revealed that the shrinkage strain of the RCCP is quite low as compared to that of conventional concrete. The early-age stress developments in the RCCP slab are strongly governed by the thermal-induced stresses. Shrinkage-induced stresses were quite small and might be negligible in a preliminary estimation of early-age stress developments in the RCCP slab.

关键词： Road engineering Roller-compacted concrete pavement Concrete strain Concrete stress Shrinkage strain Environmental loads

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Unilateral foveomacular retinitis resembling solar retinopathy among young soldiers in Korean army and associated multimodal imaging findings

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International Journal of Ophthalmology(English edition) 2020年第1期13卷 112-119页

作者： Chang Ki Yoon kyu Hyung park Se Joon woo Department of Ophthalmology Seoul National University College of MedicineSeoul National University Bundang HospitalSeongnam 13620Korea Department of Ophthalmology Hallym University College of MedicineHallym University Kangnam Sacred Heart HospitalSeoul 07441Korea

AIM: To describe the clinical features and multimodal images of unilateral foveomacular retinitis in young Korean soldiers. METHODS: Ten patients having foveomacular retinitis were included. Fluorescein angiography, fundus autofluorescence(FAF), infrared reflectance(IR), and spectral-domain optical coherence tomography(SD-OCT) were ***: All patients were young males experienced insidious visual decline without exposure to bright light. Initial and final vision ranged from hand movement to 20/20(median 20/200) and 20/2000 to 20/20(median 20/500), respectively. Vision decreased in 6 patients while improved in two. Typical macular abnormality was yellow granular spots. SD-OCT showed ellipsoid zone(EZ) or interdigitation zone(IZ) disruption of fovea. The degree of EZ/IZ damage correlated with vision. Lesions were clearly visualized through IR and matched with SD-OCT ***: This is the first case series of foveomacular retinitis diagnosed with multimodal imaging. Foveomacular retinitis should be suspected in sudden unilateral visual decline especially in young soldiers. SD-OCT is the most important diagnostic modality.

关键词： foveomacular retinitis Korean multimodal imaging solar retinopathy soldiers unilateral

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Fatigue crack in large-scale tubular joints for offshore structures

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Science China(Technological Sciences) 2011年第3期54卷 705-714页

作者： Chul-Hee JO Sung-woo IM Won-Chul CHO Kwan-kyu park Department of Naval Architecture and Ocean Engineering Inha University Research Institute of Industrial Science and Technology Department of Civil & Environmental Engineering Chung-Ang University Samsung Heavy Industry Inc.

Tubular members have been used for constructing offshore structures. Large-scale fatigue tests of welded tubular K-joints under the balanced in-plane bending brace were carried out to investigate the fatigue behavior of API 2W Gr.50 steel produced by POSCO. The experimental results were verified by numerical approaches and compared with the IIW, DnV RP-C203 and API RP 2A-WSD design curves. The test results based on the hot spot stress were in agreement with the design curves. The SCF factor for tubular K-joint was also obtained. The numerical parametric study of the K-joint (using the finite element program) was described and its results were compared with experimental results. The stress effects of various parameters including α, β, γ, τ and θ on the stress in the K-joint were investigated. The stress distribution for each parameter was introduced. The study showed that the maximum stress of the joint varied according to the variation of joint parameters.

关键词： tubular K-joint API 2W Gr.50 hot spot stress SCF fatigue through-thickness crack S-N curve numerical parametric study

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Development of XY scanner with minimized coupling motions for high-speed atomic force microscope

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Journal of Central South University 2011年第3期18卷 697-703页

作者： park Jong-kyu MOON Won-kyu Department of Mechanical Engineering Changwon National University Department of Mechanical Engineering Pohang Univer sity of Science and Technology

The design and fabrication processes of a novel scanner with minimized coupling motions for a high-speed atomic force microscope （AFM） were addressed. An appropriate design modification was proposed through the analyses of the dynamic characteristics of existing linear motion stages using a dynamic analysis program, Recurdyn. Because the scanning speed of each direction may differ, the linear motion stage for a high-speed scanner was designed to have different resonance frequencies for the modes, with one dominant displacement in the desired directions. This objective was achieved by using one-direction flexure mechanisms for each direction and mounting one stage for fast motion on the other stage for slow motion. This unsymmetrical configuration separated the frequencies of two vibration modes with one dominant displacement in each desired direction, and hence suppressed the coupling between motions in two directions. A pair of actuators was used for each axis to decrease the crosstalk between the two motions and give a sufficient force to actuate the slow motion stage, which carried the fast motion stage, A lossy material, such as grease, was inserted into the flexure hinge to suppress vibration problems that occurred when using an input triangular waveforrn. With these design modifications and the vibration suppression method, a novel scanner with a scanning speed greater than 20 Hz is achieved.

关键词： atomic force microscope scanner piezoelectric stack actuator crosstalk flexure hinge

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Effects of design parameters and tension on behavior of a coil using finite element analysis

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Journal of Iron and Steel Research International 2018年第9期25卷 883-891页

作者： kyu-tae parkI Hyun-chul park Department of Mechanical Engineering Pohang Universityof Science and Technology Pohang Gyeongbuk 790-784Korea

During the thin strip coiling process, it is necessary to use a sleeve with a mandrel to prevent excessive deformation of the strip. Stress distribution in the sleeve and in the strip is an important factor that determines the quality of the coil. However, owing to the accumulation of high pressure, it is difficult to determine the stress distribution through experimentation. Thus, stress analysis of the strip coiling process was conducted. Finite element analysis was used to investigate the effects of the weight of the strip and the mandrel on the stress distribution and stress concentration near the starting point of the coil. The radial stress was predicted for a coil with a stacked thickness of 384 mm, which corresponds to a strip length of 1486 m, using the stress analysis model developed in a preceding research. A method was presented to reduce the weight and radial stress of a strip coil. It was found that the deformation of the sleeve can be reduced by decreasing the gap between the mandrel segments. The thickness of the sleeve can be reduced from 120 to 106 mm using the stress analysis results. Furthermore, coiling tension can be reduced by 44% compared to the existing value considering the interlayer slip of the strip coil.

关键词： Strip coiling process Structural analysis Finite element method Mandrel Coiling tension

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Long-term outcomes of focal laser photocoagulation for the treatment of polypoidal choroidal vasculopathy

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International Journal of Ophthalmology(English edition) 2021年第9期14卷 1402-1407页

作者： Sooyeon Choe Hyun Goo Kang kyu Hyung park Christopher Seungkyu Lee Se Joon woo Department of Ophthalmology Seoul National University College of MedicineSeoul National University HospitalSeoul 03080Republic of Korea Department of Ophthalmology Institute of Vision ResearchGangnam Severance HospitalYonsei University College of MedicineSeoul 06273Republic of Korea Department of Ophthalmology Seoul National University Bundang HospitalSeongnam 13620Republic of Korea Department of Ophthalmology Institute of Vision ResearchSeverance HospitalYonsei University College of MedicineSeoul 03722Republic of Korea

AIM:To evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy(PCV).METHODS:Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2 y after focal laser photocoagulation *** patients were diagnosed with PCV using indocyanine green angiography,and eyes with other comorbid ocular diseases were *** measurement outcomes of the study were the post-treatment regression and recurrence of polyps,complications,and changes in visual *** t-test was performed to compare visual outcome before and after the ***:The mean age of the 13 patients was 70.2±5.5 y,and the follow-up period was 72.3±31.0(range,25-118)*** eyes had juxtafoveal polyps and 10 eyes had extrafoveal *** the 13 eyes,9 eyes(69.2%)had regression of polyps 1.7±1.2(range,0.9-4)mo after focal laser *** eyes(55.6%)showed recurrence of polyps during the follow-up periods,and the recurrence period was 12.8±18.9(range,1.9-48)*** subretinal hemorrhage occurred in two eyes(15.4%)27 and 72 d after laser treatment,*** were no statistically significant differences in visual acuities at baseline;1,2,3 y post-treatment(all P>0.05);and last follow-up(0.63±0.5,0.73±0.70,0.67±0.57,0.75±0.7,and 0.95±0.8 log MAR,respectively).CONCLUSION:Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term ***,it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

关键词： long-term efficacy polypoidal choroidal vasculopathy focal laser photocoagulation

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Metabolic syndrome is associated with erosive esophagitis

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World Journal of Gastroenterology 2008年第35期14卷 5442-5447页

作者： Jung Ho park Dong IL park Hong Joo Kim Yong kyun Cho Chong IL Sohn woo kyu Jeon Byung Ik Kim Department of Medicine Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulSouth Korea

AIM： To clarify whether insulin resistance and metabolic syndrome are risk factors for erosive esophagitis.METHODS： A case-control study was performed using the database of the Kangbuk Samsung Hospital Medical Screening Center.RESULTS： A total of 1679 cases of erosive esophagitis and 3358 randomly selected controls were included. Metabolic syndrome was diagnosed in 21% of the cases and 12% of the controls （P 〈 0.001）. Multiple logistic regressions confirmed the association between erosive esophagitis and metabolic syndrome （Odds ratio, 1.25; 95% CI, 1.04-1.49）. Among the components of metabolic syndrome, increased waist circumference, elevated serum triglyceride levels and hypertension were significant risk factors for erosive esophagitis （all P 〈 0.01）. Furthermore, increased insulin resistance （Odds ratio, 0.91; 95% CI, 0.85-0.98） and fatty liver, as diagnosed by ultrasonography （odds ratio, 1.39; 95% CI, 1.20-1.60）, were also related to erosive esophagitis even afl：er adjustment for a series of confounding factors.CONCLUSION： Metabolic syndrome and increased insulin resistance are associated with an increased risk of developing erosive esophagitis.

关键词： Metabolic syndrome Erosive esophagitis Insulin resistance Fatty liver

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