• BMB Reports
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• 제56권2호
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• pp.78-83
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• 2023

Chronic myeloid leukemia (CML) has a markedly improved prognosis with the use of breakpoint cluster region-abelson 1 (BCR-ABL1) tyrosine kinase inhibitors (BCR-ABL1 TKIs). However, approximately 40% of patients are resistant or intolerant to BCR-ABL1 TKIs. Hypoxia-inducible factor 1α (HIF-1α) is a hypoxia response factor that has been reported to be highly expressed in CML patients, making it a therapeutic target for BCR-ABL1 TKI-sensitive CML and BCR-ABL1 TKI-resistant CML. In this study, we examined whether HIF-1α inhibitors induce cell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death in BCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrations while the cell sensitivity was not affected with imatinib or dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition, echinomycin and PX-478 inhibited the c-Jun N-terminal kinase (JNK), Akt, and extracellular-regulated protein kinase 1/2 (ERK1/2) activation via suppression of BCR-ABL1 and Met expression in BCR-ABL1 sensitive and resistant CML cells. Moreover, treatment with HIF-1α siRNA induced cell death by inhibiting BCR-ABL1 and Met expression and activation of JNK, Akt, and ERK1/2 in BCR-ABL1 TKIs sensitive and resistant CML cells. These results indicated that HIF-1α regulates BCR-ABL and Met expression and is involved in cell survival in CML cells, suggesting that HIF-1α inhibitors induce cell death in BCR-ABL1 TKIs sensitive and resistant CML cells and therefore HIF-1α inhibitors are potential candidates for CML treatment.

• BMB Reports
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• 제29권3호
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• pp.241-247
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• 1996

The Philadelphia (Ph) chromosome is the single most intensively studied chromosome alteration characterizing a human malignancy. The specific genetic alteration of chronic myelogenous leukemia (CML) is the formation of the BCR/abl fusion gene in leukemic cells. The presence of the BCR/abl gene has important diagnostic and prognostic implications in CML. The detection of BCR/abl transcripts by reverse transcriptase based polymerase chain reaction (RT-PCR) was investigated in patients with CML in whom the Ph chromosome abnormality was documented by cytogenetic analysis. In a total of 68 CML patient cases, the Ph chromosome was found in 53 cases (77.9%) by cytogenetic analysis. On the other hand, sixty two cases (91.2%) were detected to have BCR/abl gene rearrangement Of these, b3a2 was 44 cases (64.7%) and b2a2 was 17 cases (25,0%). There was one case with both b3a2 and b2a2 (1.5%). Of the fifteen cases of Ph chromosome negative by cytogenetic anlaysis, the BCR/abl gene was observed in nine cases, The results of BCR/abl fusion gene confirmed by the direct sequencing method correlated well with PCR analysis, The amplified PCR products were detected by $1{\times}10^{-5}$ dilutions. In conclusion, PCR technique is sensitive, rapid and relatively simple for a laboratory test in detecting the BCR/abl fusion gene with CML regardless of the result of cytogenetic analysis.

• BMB Reports
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• 제53권10호
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• 마이크로전자및패키징학회지
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• 제21권2호
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• pp.37-41
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• 2014

차세대 전자 소자 기술에서 전력전달은 소자의 전력을 낮추고 발열로 인한 문제 해결을 위해서 매우 중요한 기술로 대두되고 있다. 본 연구에서는 직사각형 ABL 전력 범프를 이용한, Cu-to-Cu 플립 칩 본딩 공정의 신뢰성 문제에 대해 살펴보았다. 다이 내 범프 높이 차이는 전기도금 후 CMP 공정을 진행했을 경우 약 $0.3{\sim}0.5{\mu}m$ 이었고, CMP 공정을 진행하지 않았을 경우는 약 $1.1{\sim}1.4{\mu}m$으로 나타났다. 또한 면적이 큰 ABL 전력 범프가 입출력 범프 보다 높이가 높게 나타났다. 다이 내 범프 높이 차이로 인해 플립 칩 본딩 공정 시 misalignment 문제가 발생하였고, 이는 본딩 quality 에도 영향을 미쳤다. Cu-to-Cu 플립 칩 공정을 위해선 다이 내 범프 높이 균일도와 Cu 범프의 평탄도 조절이 매우 중요한 요소라 하겠다.

• Wind and Structures
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• 제34권5호
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• pp.395-405
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• 2022

Tornado-induced damages to high-rise buildings and low-rise buildings are quite different in nature. Tornado losses to high-rise buildings are generally associated with building envelope failures while tornado-induced damages to low-rise buildings are usually associated with structural or large component failures such as complete collapses, or roofs being torn off. While studies of tornado-induced structural damages tend to focus mainly on low-rise residential buildings, transmission towers, or nuclear power plants, the current rapid expansion of city centers and development of large-scale building complexes increases the risk of tornadoes impacting tall buildings. It is, therefore, important to determine how tornado-induced load affects tall buildings compared with those based on synoptic boundary layer winds. The present study applies an experimentally simulated tornado wind field to the Commonwealth Advisory Aeronautical Research Council (CAARC) building and estimates and compares its pressure coefficient effects against the Atmospheric Boundary Layer (ABL) flow field. Simulations are performed at the Wind Engineering, Energy and Environment (WindEEE) Dome which is capable of generating both ABL and tornadic winds. A model of the CAARC building at a scale of 1:200 for both ABL and tornado flows was built and equipped with pressure taps. Mean and peak surface pressures for TLV flow are reported and compared with the ABL induced wind for different time-averaging. By following a compatible definition of the pressure coefficients for TLV and ABL fields, the resulting TLV pressure field presents a similar trend to the ABL case. Also, the results show that, for the high-rise building model, the mean and 3-sec peak pressures are larger for the ABL case compared to the TLV case. These results provide a way forward for the code implementation of tornado-induced pressures on high-rise buildings.

• 한국군사과학기술학회지
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• 제12권1호
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• pp.51-59
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• 2009

This work describes the possibility of ABL(Airborne Laser) applications to the Korean missile defense. The missile defense system is the multilayered defense system that consists of shooters, sensors and BM/C4I. The ABL is the missile defense system of boost phase. It is placing a high energy, megawatt class chemical oxygen iodine laser and highly sophisticated beam control/fire control and battle management systems on a modified Boeing 747-400F aircraft to detect, track and destroy ballistic missiles in their boost phase of flight. This work analysis the ballistic missile's threat of North Korea and the flight trajectory for the SCUD missile that is cut-off by the ABL. From this analysis the possibility of the ABL applications to the Korean missile defense is presented.

• International Journal of Naval Architecture and Ocean Engineering
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• 제12권1호
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• pp.819-831
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• 2020

Wind load is one of the major design loads for the hull and mooring of offshore floating structures, especially due to much larger windage area above water than under water. By virtue of extreme design philosophy, fully turbulent flow assumption can be justified and the hydrodynamic characteristics of the flow remain almost constant which implies the wind load is less sensitive to the Reynolds number around the design wind speed than wind profile. In the perspective of meteorology, wind profile used for wind load estimation is a part of Atmospheric Boundary Layer (ABL), especially maritime ABL (MBL) and have been studied how to implement the profile without losing turbulence properties numerically by several researchers. In this study, the MBL is implemented using an open source CFD toolkit, OpenFOAM and extended to unstable ABL as well as neutral ABL referred to as NPD profile. The homogeneity of the wind profile along wind direction is examined, especially with NPD profile. The NPD profile was applied to a semi-submersible rig and estimated wind load was compared with the results from wind tunnel test.

• 한국식품영양과학회지
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• 제45권6호
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• pp.880-888
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• 2016

고추장 재료(잡곡, 죽염)와 종균을 이용하여 제조된 고추장은 일반적인 고추장에 비해 수분 함량, pH, 산도, 색도는 특별한 차이를 보이지 않았다. 모든 고추장 시료는 발효기간이 지남에 따라 수분 함량은 증가하고 pH는 감소하였으며, 산도, 아미노태 질소는 증가하였다. 잡곡과 죽염, 유산균이 들어간 혼합균주 스타터 고추장(MG-BS-ABL)은 6주간 발효되었을 때 아미노태 질소, 유리아미노산의 양이 다른 고추장에 비해 유의적으로 많은 것으로 나타났다(P<0.05). 또한, 관능평가에서 외관, 향기, 맛, 전반적인 기호도가 모두 다른 고추장에 비해 높은 점수를 나타내었다. 이상의 결과로 MG-BS-ABL군은 일반적인 고추장과 유사한 고추장의 품질 특성을 나타내었으며, 아미노태 질소, 유리아미노산의 함량이 높아 관능평가에서도 높은 점수를 얻은 것으로 생각된다. 이 결과는 아마도 기장에 함유된 높은 단백질의 함유량과 죽염의 미네랄 조성, Aspergillus oryzae, Bacillus subtilis와 Lactobacillus plantarum의 혼합균주 메주의 발효에 의한 것으로 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9961-9966
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• 2014

Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higher prevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence of m-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear. Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patients and 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examination and bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment were followed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year. Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higher proportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABL relative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBC counts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALL groups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations in both CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor in CML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associated more with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patients compared to M-bcr patients.

• 한국식품저장유통학회지
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• 제24권8호
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• pp.1188-1194
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• 2017

DSS로 대장염을 유도한 C57BL/6 마우스에게 잡곡(보리, 수수, 기장)과 죽염, 종균(AB, ABL)을 접종한 메주로 만든 고추장을 섭취시켰다. MG-AB와 MG-ABL을 섭취한 마우스는 control에 비교해 대장의 길이를 증가시키고, 무게/길이비율은 감소시켜 대장염의 염증반응을 억제시켰다. MG-ABL은 혈청에서 IL-6의 발현을 control과 MG-AB군에 비해 유의적으로 감소시켰고, apoptosis 관련 인자인 Bax와 Bcl-2의 발현을 조절하여 apoptosis를 유도하였다. 따라서 MG-ABL은 발효 시 첨가된 Lab. plantarum로 인해 대장조직의 손상을 억제하고 전염증성 사이토카인과 apoptosis 관련 인자를 조절하여 대장염을 억제하는 것으로 나타났다.