• BMB Reports
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• v.56 no.2
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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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• v.29 no.3
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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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• v.53 no.10
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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.

• Journal of the Microelectronics and Packaging Society
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• v.21 no.2
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• pp.37-41
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• 2014

One of the important developments in next generation electronic devices is the technology for power delivery and heat dissipation. In this study, the Cu-to-Cu flip chip bonding process was evaluated using the square ABL power bumps and circular I/O bumps. The difference in bump height after Cu electroplating followed by CMP process was about $0.3{\sim}0.5{\mu}m$ and the bump height after Cu electroplating only was about $1.1{\sim}1.4{\mu}m$. Also, the height of ABL bumps was higher than I/O bumps. The degree of Cu bump planarization and Cu bump height uniformity within a die affected significantly on the misalignment and bonding quality of Cu-to-Cu flip chip bonding process. To utilize Cu-to-Cu flip chip bonding with ABL bumps, both bump planarization and within-die bump height control are required.

• Wind and Structures
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• v.34 no.5
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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.

• Journal of the Korea Institute of Military Science and Technology
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• v.12 no.1
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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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• v.12 no.1
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.880-888
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• 2016

Changes in quality characteristics of gochujang prepared with different ingredients (white rice, barley, sorghum and millet, bamboo salt) and meju starters were studied. The gochujang samples were fermented for 6 weeks at $40^{\circ}C$ and analyzed for changes in their physicochemical properties and sensory characteristics. Eight different gochujang samples were prepared: WR-SS-AB, WR-SS-ABL, WR-BS-AB, WR-BS-ABL, MG-SS-AB, MG-SS-ABL, MG-BS-AB, MG-BS-ABL (WR: white rice, MG: mixed grains, SS: solar salt, BS: bamboo salt, AB: Aspergillus oryzae/Bacillus subtilis starter meju, ABL: Aspergillus oryzae/Bacillus subtilis/Lactobacillus plantarum starter meju). There were significant differences between experimental groups in terms of moisture content, pH, acidity, and color value. All gochujang samples showed increased moisture contents and pH as well as increased acidity and amino-type nitrogen during fermentation. MG-BS-ABL showed the highest contents of amino-type nitrogen and free amino acids after 6 weeks of fermentation compared with other experiment groups. In addition, MG-BS-ABL showed the highest sensory analysis score, including appearance, flavor, taste, and overall acceptability after the fermentation of samples. Based on the results, MG-BS-ABL exhibited similar quality characteristics as general gochujang but showed the highest sensory scores and contents of amino-type nitrogen and free amino acids. These results might be due to the high protein contents of mixed grains and high mineral contents of bamboo salt and fermented products from mixed probiotic starters.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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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.

• Food Science and Preservation
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• v.24 no.8
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• pp.1188-1194
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• 2017

Gochujang, a traditional Korean food, is fermented by mixing red pepper powder, various grain, meju and salt. Changes in the kind of ingredients and fermentation method could increase health functionalities. In this study, in vivo anti-colitis effects of gochujang prepared with mixed grains, bamboo salt baked 3 times and meju starters on DSS-induced colitis in C57BL/6 mice were studied. We prepared gochujang prepared with mixed grains (MG), bamboo salt, and Aspergillus oryzae (A) and Baccillus subtilis (B) mixed starters (MG-AB) and gochujang prepared with MG, bamboo salt and A, B and Lactobacillus plantarum (L) mixed starters (MG-ABL). MG-AB and MG-ABL significantly increased body weight and colon length compared to the control (p<0.05). MG-ABL showed significantly decreased interleukin-6 (IL-6) expression in serum compared to the control and MG-AB group (p<0.05). MG-ABL also regulated mRNA and protein levels of pro-apoptotic Bcl-2-associated X protein (Bax) and anti-apoptotic B-cell lymphoma-2 (Bcl-2) in the mice colon tissue (p<0.05). Therefore, MG-ABL exhibited the increased anticolitis effects by inhibiting damage of colon tissue, probably by regulating a pro-inflammatory cytokine of IL-6 and regulated apoptosis related genes. These results indicated that gochujang changed with good ingredients and starters had colitis preventive effects and might be due to active compounds in mixed grain and bamboo salt, and produced by L during the fermentation of gochujang.