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result(s) for
"Ha, Taehun"
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Combined inhibition of Bcl-2 family members and YAP induces synthetic lethality in metastatic gastric cancer with RASA1 and NF2 deficiency
by
Kim, Dae-Yong
,
An, Hyeok-Won
,
Seok, Sang Hyeok
in
Animal models
,
Bcl-2 protein
,
Bcl-x protein
2023
Background
Targetable molecular drivers of gastric cancer (GC) metastasis remain largely unidentified, leading to limited targeted therapy options for advanced GC. We aimed to identify molecular drivers for metastasis and devise corresponding therapeutic strategies.
Methods
We performed an unbiased in vivo genome-wide CRISPR/Cas9 knockout (KO) screening in peritoneal dissemination using genetically engineered GC mouse models. Candidate genes were validated through in vivo transplantation assays using KO cells. We analyzed target expression patterns in GC clinical samples using immunohistochemistry. The functional contributions of target genes were studied through knockdown, KO, and overexpression approaches in tumorsphere and organoid assays. Small chemical inhibitors against Bcl-2 members and YAP were tested in vitro and in vivo
.
Results
We identified
Nf2
and
Rasa1
as metastasis-suppressing genes through the screening. Clinically,
RASA1
mutations along with low
NF2
expression define a distinct molecular subtype of metastatic GC exhibiting aggressive traits. NF2 and RASA1 deficiency increased in vivo metastasis and in vitro tumorsphere formation by synergistically amplifying Wnt and YAP signaling in cancer stem cells (CSCs). NF2 deficiency enhanced Bcl-2-mediated Wnt signaling, conferring resistance to YAP inhibition in CSCs. This resistance was counteracted via synthetic lethality achieved by simultaneous inhibition of YAP and Bcl-2. RASA1 deficiency amplified the Wnt pathway via Bcl-xL, contributing to cancer stemness.
RASA1
mutation created vulnerability to Bcl-xL inhibition, but the additional NF2 deletion conferred resistance to Bcl-xL inhibition due to YAP activation. The combined inhibition of Bcl-xL and YAP synergistically suppressed cancer stemness and in vivo metastasis in RASA1 and NF2 co-deficiency.
Conclusion
Our research unveils the intricate interplay between YAP and Bcl-2 family members, which can lead to synthetic lethality, offering a potential strategy to overcome drug resistance. Importantly, our findings support a personalized medicine approach where combined therapy targeting YAP and Bcl-2, tailored to NF2 and RASA1 status, could effectively manage metastatic GC.
Journal Article
Development of Driver Fuel Economy Index for Real Road Fuel Economy
by
Choi Seonwoo
,
Choi Hoimyung
,
Lee, Yoonwoo
in
Charge density
,
Combustion temperature
,
Compression ratio
2019
Although a 5-cycle testing was adopted to address the gap between the reported fuel economy from certification tests and fuel economy during real-world driving, the gap still remains and is difficult to be resolved without the consideration of the fuel consumption influencing parameters such as driver’s behavior, driving pattern and road condition. In this study, two types of driver fuel economy indices, the MAW (Moving Average Window) Power Ratio Index and the Constant Driving Index are newly defined to invent the index which can reflect the real-road conditions and simulate the real-world fuel economy. Both indices are defined as the ratio of actual driving to ideal (constant speed) driving in common but the former is based on the engine output and the latter is based on the work. Two types of indices are verified with 5-cycle testing results on chassis dynamometer. According to the verification, the MAW Power Ratio Index with window size of 60 seconds shows the highest correlation with the certified fuel economy and is the reasonable starting point of index for reflecting the real-road conditions.
Journal Article
A Comparative Field Monitoring of Column Shortenings in Tall Buildings Using Wireless and Wired Sensor Network Systems
2016
A comparative field measurement for column shortening of tall buildings is presented in this study, with a focus on the reliability and stability of a wireless sensor network. A wireless sensor network was used for monitoring the column shortenings of a 58-story building under construction. The wireless sensor network, which was composed of sensor and master nodes, employed the ultra-high-frequency band and CDMA communication methods. To evaluate the reliability and stability of the wireless sensor network system, the column shortenings were also measured using a conventional wired monitoring system. Two vibration wire gauges were installed in each of the selected 7 columns and 3 walls. Measurements for selected columns and walls were collected for 270 days after casting of the concrete. The results measured by the wireless sensor network were compared with the results of the conventional method. The strains and column shortenings measured using both methods showed good agreement for all members. It was verified that the column shortenings of tall buildings could be monitored using the wireless sensor network system with its reliability and stability.
Journal Article
A Case Study on the Rehabilitation of a Fire-Damaged Structure
2016
This paper presents a case study on the rehabilitation of a fire-damaged structure and describes the results of a site investigation and tests, leading to a plan for the rehabilitation of the structure. The fire took place in the main control room of a thermal power plant and lasted about three hours until it was finally extinguished. To set up a rehabilitation plan for the damaged structure, a visual inspection of the damaged condition was first carried out, which was followed by analysis and on-site material tests indicating the degree of neutralization progress in the remaining structure. Specimens of damaged concrete and reinforcing bars were sampled and tested for their residual strengths. As a conclusion, two methods of rehabilitation were suggested considering the current condition of the structure and the sequence of construction.
Journal Article
Investigation on the liquid water droplet instability in a simulated flow channel of PEM fuel cell
2008
To investigate the characteristics of water droplets on the gas diffusion layer from both top-view and side-view of the flow channel, a rig test apparatus was designed and fabricated with prism attached plate. This experimental device was used to simulate the growth of a single liquid water droplet and its transport process with various air flow velocity and channel height. Not only dry condition but also fully humidified condition was also simulated by using a water absorbing sponge. The detachment height of the water droplet with dry and wet conditions was measured and analyzed. It was found that the droplet tends towards becoming unstable by decreased channel height, increased flow velocity or making a gas diffusion layer (GDL) dryer. Also, peculiar behavior of the water droplet in the channel was presented like attachment to hydrophilic wall or sudden breaking of droplet in case of fully hydrated condition. The simplified force balance model matches with experimental data as well.
Journal Article
Experimental verification of optimized NOX reduction strategies in a decrepit Euro-3 diesel engine retrofitted with a cooled EGR system
2016
Vehicle-produced NOx is among emissions that deteriorate human health and the environment. To regulate the NOx emissions from transport, especially from diesel-powered vehicles, various standards have been established globally, and regulations are becoming more stringent across the world. Considerable NOx from diesel vehicles are due to the compression ignition characteristics of engines. Accordingly, to meet the national and global standards, manifold advanced aftertreatment technologies, such as EGR, SCR and LNT, have been developed and widely adopted since introduction of the Euro-4 standards in 2006. In Korea, current allowable NOx standards have been greatly reinforced to one fourth of the permissible level in 2004 and one sixth in 2000. However, the percentage of diesel vehicles in Korea more than 10 years old, manufactured prior to Euro-4, is still significant, accounting for 29% of passenger vehicles, 32% of buses, and 45% of trucks in total registration. Against this backdrop, tremendous efforts are required to improve air quality, especially in metropolitan areas. Of all technical options currently available, installing a cooler to typical EGR systems is considered as a more efficient way for superannuated diesel vehicles to meet the Euro-4 than installing a SCR or LNT in terms of technical acceptability and costeffectiveness. In this study, NOx characteristics of a decrepit Euro-3 diesel engine are thoroughly analyzed before and after the installation of the EGR coolers with different cooling capacities. By applying real time control of EGR rate and exhaust backpressure in calibration procedures, optimized NOx reduction strategies are established.
Journal Article
Experimental verification of optimized NO X reduction strategies in a decrepit Euro-3 diesel engine retrofitted with a cooled EGR system
2016
Vehicle-produced NOx is among emissions that deteriorate human health and the environment. To regulate the NOx emissions from transport, especially from diesel-powered vehicles, various standards have been established globally, and regulations are becoming more stringent across the world. Considerable NOx from diesel vehicles are due to the compression ignition characteristics of engines. Accordingly, to meet the national and global standards, manifold advanced aftertreatment technologies, such as EGR, SCR and LNT, have been developed and widely adopted since introduction of the Euro-4 standards in 2006. In Korea, current allowable NOx standards have been greatly reinforced to one fourth of the permissible level in 2004 and one sixth in 2000. However, the percentage of diesel vehicles in Korea more than 10 years old, manufactured prior to Euro-4, is still significant, accounting for 29% of passenger vehicles, 32% of buses, and 45% of trucks in total registration. Against this backdrop, tremendous efforts are required to improve air quality, especially in metropolitan areas. Of all technical options currently available, installing a cooler to typical EGR systems is considered as a more efficient way for superannuated diesel vehicles to meet the Euro-4 than installing a SCR or LNT in terms of technical acceptability and costeffectiveness. In this study, NOx characteristics of a decrepit Euro-3 diesel engine are thoroughly analyzed before and after the installation of the EGR coolers with different cooling capacities. By applying real time control of EGR rate and exhaust backpressure in calibration procedures, optimized NOx reduction strategies are established. KCI Citation Count: 0
Journal Article
Experimental verification of optimized NO sub(X) reduction strategies in a decrepit Euro-3 diesel engine retrofitted with a cooled EGR system
2016
Vehicle-produced NOx is among emissions that deteriorate human health and the environment. To regulate the NOx emissions from transport, especially from diesel-powered vehicles, various standards have been established globally, and regulations are becoming more stringent across the world. Considerable NOx from diesel vehicles are due to the compression ignition characteristics of engines. Accordingly, to meet the national and global standards, manifold advanced aftertreatment technologies, such as EGR, SCR and LNT, have been developed and widely adopted since introduction of the Euro-4 standards in 2006. In Korea, current allowable NOx standards have been greatly reinforced to one fourth of the permissible level in 2004 and one sixth in 2000. However, the percentage of diesel vehicles in Korea more than 10 years old, manufactured prior to Euro-4, is still significant, accounting for 29% of passenger vehicles, 32% of buses, and 45% of trucks in total registration. Against this backdrop, tremendous efforts are required to improve air quality, especially in metropolitan areas. Of all technical options currently available, installing a cooler to typical EGR systems is considered as a more efficient way for superannuated diesel vehicles to meet the Euro-4 than installing a SCR or LNT in terms of technical acceptability and costeffectiveness. In this study, NOx characteristics of a decrepit Euro-3 diesel engine are thoroughly analyzed before and after the installation of the EGR coolers with different cooling capacities. By applying real time control of EGR rate and exhaust backpressure in calibration procedures, optimized NOx reduction strategies are established.
Journal Article
Effective Capacity of Diagonal Strut for Shear Strength of Reinforced Concrete Beams without Shear Reinforcement
2012
The appropriate evaluation of the effective capacity of a concrete strut is an important factor in the analysis and design of concrete members using the strut-and-tie model. Current design codes for the strut-and-tie model introduce this factor using the effective compressive strength of concrete in a strut or nodal zone. This study considers that the mechanism of diagonal cracking reduces the width of a concrete strut and hence causes a reduction in the capacity of the concrete strut. Based on this approach, models for predicting the diagonal cracking strength and ultimate shear strength of simply supported beams without shear reinforcement are proposed, with the concrete strength, shear span-depth ratio (a/h), and longitudinal reinforcement ratio as the primary parameters. The predicted values are compared with proven test data from various published experiments and codes of practice to show the validity of the proposed models. [PUBLICATION ABSTRACT]
Journal Article