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comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO kyung PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(IcIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from IcIs in biliary tract cancer(BTc)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTc treated with the IcI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[cI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DcR)of 37.5%(95%cI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(cPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTc was comparable to that of PD-L1-BTc(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTc of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

Electrochemically metal-doped reduced graphene oxide films:Properties and applications

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Journal of Materials Science & Technology 2020年第5期40卷 72-80页

作者： Myung-Sic.chae Tae Ho Lee kyung Rock Son Tae Hoon Park Kyo Seon Hwang Tae Geun Kim School of Electrical Engineering Korea UniversityAnam-ro 145Seongbuk-guSeoul 02841South Korea Department of clinical Pharmacology and Therapeutics College of MedicineKyung Hee UniversitySeoul 02447South Korea

The fine control of doping levels in graphene materials such as reduced graphene oxide(RGO)is important to properly manipulate their ambipolar transport characteristics for various device ***,conventional doping methods involve complex chemical reactions,large-scale doping processes,and poor ***,a simple and controllable electrochemical doping treatment(EDT),performed via the conductive channels created at the RGO surface by the application of an electric field,is introduced to tailor the electrical properties of RGO films.X-ray photoelectron spectroscopy and Raman spectroscopy measurements are performed to detect the presence of Ni atoms in RGO films after the EDT(EDT-RGO).Then,EDT-RGO field-effect transistors(FETs)are fabricated with different doping areas(0 to 100%fractional area)on the RGO active channel to investigate the effect and selective-area doping capability of the *** to p-type doping compensation by the intercalated Ni atoms,the electron mobility of the EDT-RGO FET decreases from 1.40 to 0.12 cm2 V-1s-1 compared with that of the undoped RGO-FET,leading to the conversion from ambipolar to unipolar p-type transfer characteristics.

关键词： Reduced graphene oxide Electrochemical doping treatment Electrical breakdown process Field-effect transistor

Simulation of the extreme waves generated by typhoon Bolaven (1215) in the East china Sea and Yellow Sea

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Acta Oceanologica Sinica 2015年第12期34卷 19-28页

作者： JUN Ki cheon JEONG Weon Mu cHOI Jin Yong PARK Kwang Soon JUNG kyung Tae KIM Mee kyung chae Jang Won QIAO Fangli coastal Disaster Research center Korea Institute of Ocean Science and Technology coastal & Environmental Engineering Division Korea Institute of Ocean Science and Technology Marine Radionuclide Research center Korea Institute of Ocean Science and Technology First Institute of Oceanography State Oceanic Administration

Record-breaking high waves occurred during the passage of the typhoon Bolaven（1215）（TYB） in the East china Sea（EcS） and Yellow Sea（YS） although its intensity did not reach the level of a super *** and directional wave measurements were made using a range of in-situ instruments mounted on an ocean tower and *** order to understand how such high waves with long duration occurred,analyses have been made through measurement and numerical *** winds were generated using the Tc96 typhoon wind model with the best track data calibrated with the *** then the wind fields were blended with the reanalyzed synoptic-scale wind fields for a wave *** fields were simulated using WAM4.5 with adjustment of c_d for gust of winds and bottom friction for the study *** the accuracy of simulations is considerably enhanced,and the computed results are also in better agreement with measured data than *** is found that the extremely high waves evolved as a result of the superposition of distant large swells and high wind seas generated by strong winds from the front/right quadrant of the typhoon *** the typhoon moved at a speed a little slower than the dominant wave group velocity in a consistent direction for two days,the wave growth was significantly enhanced by strong wind input in an extended fetch and non-linear interaction.

关键词： extreme waves typhoon measurements numerical simulation East china Sea

Improvement of machining quality of copper-plated roll mold by controlling temperature variation

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Transactions of Nonferrous Metals Society of china 2011年第A1期21卷 37-41页

作者： Tae-Jin JE Eun-chae JEON Sang-cheon PARK Doo-Sun cHOI kyung-Hyun WHANG Myung-chang KANG Division of Nano-Mechanical Systems Korea Institute of Machinery and Materials Daejeon 305-343 Korea National core Research center for Hybrid Materials Solution Pusan National University

Micro prism film used in LcD industry can be manufactured by roll to roll method with copper-plated roll mold. As copper-plated roll mold is getting larger, pitch error is getting severer. The pitch error drops the quality of micro prism film. The main cause of the pitch error was investigated during machining large roll mold whose machined length was 1 200 mm. The temperature of machining system was elevated during machining roll mold, and this elevation induced thermal expansion of the system. The temperature variation around the roll mold also made thermal expansion of the roll mold. The amount of thermal expansion had strong relationship to the amount of pitch error. Therefore, the roll mold was machined after warming-up of machining system and precise temperature controller around copper-plated roll mold was installed, which minimized the temperature variation. Finally, precise micro prism patterns without pitch error were machined on the large roll mold.

关键词： copper-plated roll mold machining prism pattern temperature variation

High-frequency magnetic stimulation attenuates beta-amyloid protein 1-42 neurotoxicity in organotypic hippocampal slices

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Neural Regeneration Research 2010年第18期5卷 1365-1372页

作者： Don-Kyu Kim Young chul Yoon Soo Ahn chae kyung Mook Seo Tai Ryoon Han Si-Hyun Kang Department of Physical Medicine and Rehabilitation Chung-Ang University College of Medicine Department of Neurology Chung-Ang University College of Medicine Department of Pediatrics Chung-Ang University College of Medicine Department of Physical Medicine and Rehabilitation Seoul National University

Repetitive transcranial magnetic stimulation （rTMS） has been utilized as a therapeutic tool for neurodegenerative disorders including Alzheimer＇s disease. However, the precise mechanisms of its clinical effects remain unknown. β-amyloid （Aβ） exhibits direct neurotoxic effects and is closely related to neuronal degeneration in Alzheimer＇s disease. Therefore, it has been hypothesized that the neuroprotective effects of rTMS are related to the mechanisms of protection against Aβ neurotoxicity. Organotypic hippocampal slices were prepared from 8-day old, Sprague Dawley rats. The tissue slices were exposed to 100 μmol/L Al3142 since day 12 in vitro with and without high-frequency （20 Hz） magnetic stimulation. Magnetic stimulation efficacy was evaluated by measuring neuronal nuclei （NeuN） protein expression and by observing cultures following propidium iodide fluorescence staining and bromodeoxyuridine （BrdU） immunohistochemistry. Lactate dehydrogenase activity was detected in the culture media to evaluate hippocampal neuronal damage. Our results demonstrated that high-frequency magnetic stimulation significantly reversed the reduction of NeuN protein expression because of Aβ1-42 exposure （P 〈 0.05） and significantly reduced the number of damaged cells in the hippocampal slices （P 〈 0.05）. However, lactate dehydrogenase levels and anti-BrdU staining results did not reveal any statistical differences These findings indicate that high-frequency magnetic stimulation might have protective effect on hippocampal neurons from Aβ1-42 neurotoxicity.

关键词： organotypic hippocampus amyloid beta-protein magnetic stimulation nerve degeneration/metabolism nerve degeneration/pathology organ culture techniques rats, Sprague Dawiey

Effects of Bacillus subtilis cSL2 on the composition and functional diversity of the faecal microbiota of broiler chickens challenged with Salmonella Gallinarum

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Journal of Animal Science and Biotechnology 2017年第2期8卷 450-458页

作者： Ju Kyoung Oh Edward Alain B.Pajarillo Jong Pyo chae In Ho Kim Dong Soo Yang Dae-kyung Kang Department of Animal Resources Science Dankook University119 Dandae-roCheonan 31116Republic of Korea Abson Biochem Inc10-1 Yangjimaeul-gilSangrok-guAnsan 15524Republic of Korea

Background： The chicken gastrointestinal tract contains a diverse microbiota whose composition and structure play important roles in gut functionality. In this study, microbial shifts resulting from feed supplementation with Bacillus subtilis cSL2 were evaluated in broilers challenged and unchallenged with Salmonella Gallinarum. To analyse bacterial community composition and functionality, 454 GS-FLX pyrosequencing of 16 S r RNA gene amplicons was ***： The Quantitative Insights into Microbial Ecology（QIIME） pipeline was used to analyse changes in the faecal microbiota over a 24-h period. A total of 718,204 sequences from broiler chickens were recorded and analysed. At the phylum level, Firmicutes, Bacteroidetes, and Proteobacteria were the predominant bacterial taxa. In Salmonellainfected chickens（Sc）, Bacteroidetes were more highly abundant compared to control（Nc） and Bacillus-treated（BT）chickens. At the genus level, in the Nc and BT groups, Lactobacil us was present at high abundance, and the abundance of Turicibacter, unclassified Enterobacteriaceae, and Bacteroides increased in Sc broilers. Furthermore, taxon-independent analysis showed that the Sc and BT groups were compositional y distinct at the end of the 24-h period. Further analysis of functional properties showed that B. subtilis cSL2 administration increased gut-associated energy supply mechanisms（i.e. carbohydrate transport and metabolism） to maintain a stable microbiota and protect gut ***： This study demonstrated that S. Gallinarum infection and B. subtilis cSL2 supplementation in the diet of broiler chickens influenced the diversity, composition, and functional diversity of the faecal microbiota. Moreover, the findings offer significant insights to understand potential mechanisms of Salmonel a infection and the mode of action of probiotics in broiler chickens.

关键词： Bacillus subtilis Broiler chicken Microbiome Salmonel a Gallinarum 16S rRNA gene

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE

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cell Research 2006年第12期16卷 923-939页

作者： kyung L chin Delia c Tang Griffin P Rodgers Molecular and clinical Hematology Branch (McHB) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)National Institutes of HealthBethesdaMD 20892USA

We utilized a unique culture system to analyze the expression patterns of gene,protein,and cell surface antigen,and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoieticstem cells(HScs)in response to cytokine ***-specific fragments(266)identified from five populationsof cytokine-stimulated HScs were categorized into three groups:(1)expressed specifically in a single cell population;(2)expressed in two cell populations,and(3)expressed in three or more populations. Of 145 defined cDNAs,three(2%)were novel *** two-dimensional gel electrophoresis and flow cytometry analyses showed overlappedand distinguished protein expression profiles in the cell populations *** process mapping of mRNAsexpressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended 'core processes,'whereas genes specifically expressed in either lineage alone were related to specific processes or cellular *** this study support the hypothesis that committed HScs(E14 or G14)cells can still be redirected to develop intomyeloid or erythroid cells when erythropoietin(EPO)is replaced with granulocyte-colony stimulating factor(G-cSF)under erythroid-cultured condition or G-cSF with EPO in myeloid-cultured environment,*** results sug-gest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenanceand switching in hematopoiesis.

关键词： lineage switching hematopoietic stem cells erythroid/myeloid differentiation co-expression biological processes cytokines

Electric resistivity of partially ionized plasma in the lower solar atmosphere

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Research in Astronomy and Astrophysics 2021年第9期21卷 193-201页

作者： Jongchul chae Yuri ELitvinenko Astronomy Program Department of Physics and AstronomySeoul National UniversitySeoul 08826Korea Department of Mathematics University of WaikatoP.B.3105Hamilton 3240New Zealand

The lower solar atmosphere is a gravitationally stratified layer of partially ionized *** calculate the electric resistivity in the solar photosphere and chromosphere,which is the key parameter that controls the rate of magnetic reconnection in a Sweet-Parker current *** calculation takes into account the collisions between ions and hydrogen atoms as well as the electron-ion collisions and the electron-hydrogen atom *** find that under the typical conditions of the quiet Sun,electric resistivity is determined mostly by the electron-hydrogen atom collisions in the photosphere,and mostly by the ion-hydrogen collisions,*** diffusion,in the *** magnetic reconnection events with strong magnetic fields,the ambipolar diffusion,however,may be insignificant because the heating by the reconnection itself may lead to the full ionization of hydrogen *** conclude that ambipolar diffusion may be the most important source of electric resistivity responsible for the magnetic flux cancelation and energy release in chromospheric current sheets that can keep a significant fraction of neutral hydrogen atoms.

关键词： plasmas atomic processes magnetohydrodynamics(MHD) Sun:atmosphere Sun:chromosphere

corticotropin-releasing factor stimulates colonic motility via muscarinic receptors in the rat

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World Journal of Gastroenterology 2017年第21期23卷 3825-3831页

作者： kyung-Jo Kim Ki Bae Kim Soon Man Yoon Joung-Ho Han Hee Bok chae Seon Mee Park Sei Jin Youn Department of Gastroenterology University of Ulsan College of Medicine Asan Medical Center Department of Internal Medicine Chungbuk National University College of Medicine

AIM To measure exogenous corticotropin-releasing factor(cRF)-induced motility of the isolated rat colon and to demonstrate the effect of pharmacologic inhibition on cRF-induced motility. METHODS The isolated vascularly-perfused rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers in the proximal and distal colon. At first, exogenous cRF was administered in a stepwise manner and the concentration of cRF yielding maximal colonic motility was selected. After recording basal colonic motility, hexamethonium, phentolamine, propranolol, atropine and tetrodotoxin were infused into the isolated colon. Initially, only the test drug was infused; then, cRF was added. The motility index was expressed as percentage change over basal level. RESULTS Administration of 1.4, 14.4, 144 and 288 pmol/L cRF progressively increased colonic motility in the proximal and distal colon. Infusion of atropine or tetrodotoxin reduced cRF-induced motility of both the proximal and distal colon, whereas hexamethonium, phentolamine and propranolol had no *** cRF-induced colonic motility appears to be mediated by local cholinergic signaling via muscarinic receptors. Muscarinic receptors are potential targets for counteracting cRF-induced colonic hypermotility.

关键词： Gastrointestinal motility Rats Stress colon corticotropin-releasing factor