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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

Current status and challenges for cell-cultured milk technology: a systematic review

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Journal of Animal Science and Biotechnology 2024年第5期15卷 1778-1792页

作者： hyuk Cheol kwon Hyun Su Jung Vahinika Kothuri sung Gu Han Department of Food Science and Biotechnology of Animal Resources Konkuk UniversitySeoulRepublic of Korea

Cellular agriculture is an innovative technology for manufacturing sustainable agricultural products as an alternative to traditional *** most cellular agriculture is predominantly centered on the production of cultured meat,there is a growing demand for an understanding of the production techniques involved in dairy products within cellular *** review focuses on the current status of cellular agriculture in the dairy sector and technical challenges for cell-cultured milk *** agriculture technology in the dairy sector has been classified into fermentation-based and animal cell culture-based cellular ***,various companies synthesize milk components through precision fermentation ***,several startup companies are pursuing animal cell-based technology,driven by public concerns regarding genetically modified organisms in precision fermentation ***,this review offers an up-to-date exploration of animal cell-based cellular agriculture to produce milk components,specifically emphasizing the structural,functional,and productive aspects of mammary epithelial cells,providing new information for industry and academia.

关键词： Cell culture system Cell-cultured milk Mammary epithelial cells Precision fermentation

Bevacizumab plus infusional 5-fluorouracil,leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy:A pilot study

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World Journal of Gastroenterology 2007年第46期13卷 6231-6235页

作者： hyuk-Chan kwon sung Yong Oh Suee Lee sung-Hyun Kim Hyo-Jin Kim Departments of Internal Medicine Dong-A University College of MedicineBusan 602-715Korea

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

关键词： Bevacizumab Irinotecan Leucovorin,5-fluorouracil Colorectal cancer

Key-Value Store Coupled with an Operating System for Storing Large-Scale Values

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Computers, Materials & Continua 2022年第11期73卷 3333-3350页

作者： Jeonghwan Im hyuk-Yoon kwon Graduate School of Data Science Seoul National University of Science and TechnologySeoulKorea Department of Industrial Engineering Graduate School of Data ScienceResearch Center for Electrical and Information ScienceSeoul National University of Science and TechnologySeoulKorea

The key-value store can provide flexibility of data types because it does not need to specify the data types to be stored in advance and can store any types of data as the value of the key-value *** types of studies have been conducted to improve the performance of the key-value store while maintaining its ***,the research efforts storing the large-scale values such as multimedia data files(e.g.,images or videos)in the key-value store were *** this study,we propose a new key-value store,WR-Store++aiming to store the large-scale values ***,it provides a new design of separating data and index by working with the built-in data structure of the Windows operating system and the file *** utilization of the built-in data structure of the Windows operating system achieves the efficiency of the key-value store and that of the file system extends the limited space of the storage *** also present chunk-based memory management and parallel processing of WR-Store++to further improve its performance in the GET *** the experiments,we show that WR-Store++can store at least 32.74 times larger datasets than the existing baseline key-value store,WR-Store,which has the limitation in storing large-scale data ***,in terms of processing efficiency,we show that WR-Store++outperforms not only WR-Store but also the other state-ofthe-art key-value stores,LevelDB,RocksDB,and BerkeleyDB,for individual key-value operations and mixed workloads.

关键词： Key-value stores large-scale values chunk-based memory management parallel processing

Variations in dynamic recrystallization behavior and mechanical properties of AZ31 alloy with extrusion temperature

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Journal of Magnesium and Alloys 2023年第7期11卷 2351-2365页

作者： Jae Won Cha sung hyuk Park School of Materials Science and Engineering Kyungpook National UniversityDaegu 41566Republic of Korea

This study investigates the effects of extrusion temperature on the dynamic recrystallization(DRX)behavior of a Mg-3Al-1Zn-0.3Mn(AZ31,wt%)alloy during hot extrusion and on the microstructural characteristics and mechanical properties of materials extruded at 350 and 450℃.An increase in the extrusion temperature causes a decrease in the amount of strain energy accumulated in the material during extrusion,because of promoted activation of pyramidalslip and dynamic *** reduced strain energy weakens the DRX behavior during extrusion,which eventually results in a decrease in the area fraction of recrystallized grains of the extruded *** material extruded at 450℃has coarser grains and a stronger basal fiber texture than that extruded at 350℃.As the extrusion temperature increases from 350 to 450℃,the tensile yield strength(TYS)of the extruded material increases from 191.8 to 201.5 MPa,whereas its compressive yield strength(CYS)decreases from 122.5 to 111.0 MPa;consequently,its tension-compression yield stress ratio(CYS/TYS)decreases from 0.64 to *** increase in the TYS is attributed mainly to the stronger texture hardening and strain hardening effects of the extruded material,and the decrease in the CYS is attributed to the reduced twinning stress resulting from grain coarsening and texture *** microstructural and textural evolutions of the materials during extrusion and the deformation and hardening mechanisms of the extruded materials are discussed in detail.

关键词： Mg-Al-Zn alloy Extrusion Dynamic recrystallization Microstructure Yield asymmetry

Underlying mechanisms of variation in yield asymmetry and strain hardening behavior of extruded pure Mg with Gd addition

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Journal of Magnesium and Alloys 2023年第6期11卷 2165-2181页

作者： Gyo Myeong Lee sung hyuk Park School of Materials Science and Engineering Kyungpook National UniversityDaegu 41566Republic of Korea

Effects of Gd addition on the strain hardening behavior and yield asymmetry of pure Mg are investigated by subjecting extruded pure Mg,Mg–5Gd,and Mg–15Gd(all in wt%)to tension and compression tests along the extrusion direction(ED).As the amount of Gd added to pure Mg increases,the basal texture tilts toward the ED and the distribution of c-axes of grains becomes *** tension,the strain hardening rates of all the materials decrease until ***,under compression,the strain hardening rate increases in the early stage of deformation in pure Mg and Mg–5Gd,whereas it continuously decreases in Mg–*** Mg exhibits considerably high tension-compression yield asymmetry,with a compressive yield strength(CYS)to tensile yield strength(TYS)ratio of *** contrast,Mg–5Gd exhibits excellent yield symmetry with CYS/TYS of 0.9 and Mg–15Gd exhibits reversed yield asymmetry with CYS/TYS of *** mechanisms of these drastically different Gd-addition-induced deformation behaviors of the materials are discussed in terms of the crystallographic distribution of grains and the relative activation stresses of basal slip,prismatic slip,pyramidal slip,and{10–12}twinning under tension and compression.

关键词： Pure Mg Gd addition Texture Yield asymmetry Activation stress

Laser‑Induced and MOF‑Derived Metal Oxide/Carbon Composite for Synergistically Improved Ethanol Sensing at Room temperature

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Nano-Micro Letters 2024年第6期16卷 210-220页

作者： Hyeongtae Lim Hyeokjin kwon Hongki Kang Jae Eun Jang hyuk‑Jun kwon Department of Electrical Engineering and Computer Science DGISTDaegu 42988South Korea Convergence Research Advanced Centre for Olfaction DGISTDaegu 42988South Korea

Advancements in sensor technology have significantly enhanced atmospheric ***,metal oxide and carbon(MO_(x)/C)hybrids have gained attention for their exceptional sensitivity and room-temperature sensing ***,previous methods of synthesizing MO_(x)/C composites suffer from problems,including inhomogeneity,aggregation,and challenges in ***,we introduce a refined method that employs a metal–organic framework(MOF)as a precursor combined with direct laser *** inherent structure of MOFs ensures a uniform distribution of metal ions and organic linkers,yielding homogeneous MO_(x)/C *** laser processing facilitates precise micropatterning(<2μm,comparable to typical photolithography)of the MO_(x)/C *** optimized MOF-derived MO_(x)/C sensor rapidly detected ethanol gas even at room temperature(105 and 18 s for response and recovery,respectively),with a broad range of sensing performance from 170 to 3,400 ppm and a high response value of up to 3,500%.Additionally,this sensor exhibited enhanced stability and thermal resilience compared to previous MOF-based *** research opens up promising avenues for practical applications in MOF-derived sensing devices.

关键词： Metal-organic frameworks Metal oxide Carbon composite Laser Gas sensor

Effects of initial texture on deformation behavior during cold rolling and static recrystallization during subsequent annealing of AZ31 alloy

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Journal of Materials Science & Technology 2021年第7期66卷 139-149页

作者： Sang Won Lee Gukin Han Tea-sung Jun sung hyuk Park School of Materials Science and Engineering.Kyungpook National University Daegu 41566Republic of Korea Department of Mechanical Engineering Incheon National UniversityIncheon 22012Republic of Korea

This study demonstrates that the initial texture of Mg alloy significantly affects the microstructure developed during cold rolling and the recrystallization behavior during subsequent annealing. In a sample with a texture oriented toward the normal direction(ND sample), thick and large-sized shear bands are intensively formed during cold rolling and the deformation is strongly localized along these bands. In contrast,in a sample with a texture oriented toward the transverse direction(TD sample), many {10-12} twins are formed at the early stage of cold rolling, and then, numerous small-sized shear bands are formed in these twins. Results of nanoindentation tests reveal that the cold-rolled ND sample has internal strain energy that is substantially concentrated along the shear bands, whereas the cold-rolled TD sample has a large amount of internal strain energy that is homogeneously distributed throughout the material;this latter behavior is strongly related to the extensive {10-12} twinning and the resultant microstructural variations in the TD sample. During subsequent annealing, recrystallization occurs locally along the shear bands in the ND sample, which leads to the formation of a bimodal grain structure comprising fine recrystallized grains and coarse unrecrystallized grains. In contrast, during subsequent annealing of the TD sample, static recrystallization occurs homogeneously throughout the material, which results in the formation of a uniform grain structure that mostly comprises equiaxed recrystallized grains.

关键词： Magnesium alloy Cold rolling Initial texture Twinning Static recrystallization

Improved continuous precipitation kinetics and tensile properties of extruded AZ80 alloy through {10-12} twin formation

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Journal of Magnesium and Alloys 2023年第9期11卷 3323-3337页

作者： Hyun Ji Kim Sumi Jo sung hyuk Park Department of Materials Science and Metallurgical Engineering Kyungpook National UniversityDaegu 41566the Republic of Korea

This study investigates the effect of{10-12}deformation twins on the continuous precipitation behavior of an extruded Mg-8.0Al-0.5Zn-0.2Mn(AZ80)alloy during *** extruded AZ80 alloy is compressed along the transverse direction to introduce{10-12}twins,followed by an aging treatment at 300℃.The extruded material exhibits a twin-free microstructure with low internal strain energy,whereas the pre-twinned material possesses abundant{10-12}twins and has high internal strain *** aging results reveal that the peak-aging time of the pre-twinned material(1 h)is one-eighth of that of the extruded material(8 h).Although Mg_(17)Al_(12)continuous precipitates(CPs)are observed in both the peak-aged materials,these CPs are much smaller and more densely distributed in the pre-twinned material despite the significantly shorter aging *** CPs size in the peak-aged materials increases in the following order:twinned region in the pre-twinned material(0.47μm)

关键词： AZ80 alloy {10-12}twin Aging Continuous precipitation Tensile properties