• Bulletin of the Korean Chemical Society
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• 제35권8호
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• pp.2494-2504
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• 2014

P38 mitogen activated protein (MAP) kinase is an important anti-inflammatory drug target, which can be activated by responding to various stimuli such as stress and immune response. Based on the conformation of the conserved DFG loop (in or out), binding inhibitors are termed as type-I and II. Type-I inhibitors are ATP competitive, whereas type-II inhibitors bind in DFG-out conformation of allosteric pocket. It remains unclear that how these allosteric inhibitors stabilize the DFG-out conformation and interact. Organosilicon compounds provide unusual opportunity to enhance potency and diversity of drug molecules due to their low toxicity. However, very few examples have been reported to utilize this property. In this regard, we performed docking of an inhibitor (BIRB) and its silicon analog (Si-BIRB) in an allosteric binding pocket of p38. Further, molecular dynamics (MD) simulations were performed to study the dynamic behavior of the simulated complexes. The difference in the biological activity and mechanism of action of the simulated inhibitors could be explained based on the molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy per residue decomposition. MM/GBSA showed that biological activities were related with calculated binding free energy of inhibitors. Analyses of the per-residue decomposed energy indicated that van der Waals and non-polar interactions were predominant in the ligand-protein interactions. Further, crucial residues identified for hydrogen bond, salt bridge and hydrophobic interactions were Tyr35, Lys53, Glu71, Leu74, Leu75, Ile84, Met109, Leu167, Asp168 and Phe169. Our results indicate that stronger hydrophobic interaction of Si-BIRB with the binding site residues could be responsible for its greater binding affinity compared with BIRB.

• Journal of Ecology and Environment
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• 제40권2호
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• pp.89-106
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• 2016

Many plant species have two modes of reproduction: sexual and asexual. Both modes of reproduction have often been viewed as adaptations to temporally or spatially variable environments. The plant should adjust partitioning to match changes in the estimated success of the two reproductive modes. Perennial plants showed that favorable habitats in soil nutrients or water content tend to promote clonal growth over sexual reproduction. In contrast, under high light-quantity conditions, clonal plants tend to allocate more biomass to sexual reproduction and less to clonal propagation. On the other hand, plants with chasmogamous and cleistogamous flowers provides with a greater tendency of the opportunity to ensure some seed set in any stressful environmental conditions such as low light, low soil nutrients, or low soil moisture. It is considered that vegetative reproduction has high competitive ability and is the major means to expand established population of perennial plants, whereas cleistogamous reproduction is insurance to persist in stressful sites due to being strong. Chasmogamous reproduction mainly enhances established and new population. Therefore, the functions of sexual and asexual propagules of perennial or annual plants differ from each other. These traits of propagule thus determine its success at a particular region of any environmental gradients. Eventually, if environmental resources or stress levels change in either space or time, species composition will probably also change. The reason based on which the plants differ with respect to favored reproduction modes in each environmental condition, may be involved in their specific realized niche.

• Genomics & Informatics
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• 제8권1호
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• pp.41-49
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• 2010

Statins are competitive inhibitors of hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase and used most frequently to reduce plasma cholesterol levels and to decrease cardiovascular events. However, statins also have been reported to have undesirable side effects such as myotoxicity and hepatotoxicity associated with their intrinsic efficacy mechanisms. Clinical studies recurrently reported that statin therapy elevated the level of liver enzymes such as ALT and AST in patients suggesting possible liver toxicity due to statins. This observation has been drawn great attention since statins are the most prescribed drugs and statin-therapy was extended to a larger number of high-risk patients. Here we employed rat primary hepatocytes and microarray technique to understand underlying mechanism responsible for statin-induced liver toxicity on cell level. We isolated genes whose expressions were commonly modulated by statin treatments and examined their biological functions. It is of interest that those genes have function related to response to stress in particular immunity and defense in cells. Our study provided the basic information on cellular mechanism of statin-induced cytotoxicity and may serve for finding indicator genes of statin -induced toxicity in rat primary hepatocytes.

• 한국기계가공학회지
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• 제15권2호
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• pp.66-71
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• 2016

For the manual transmission gearbox used in the automotive industry, gear meshing transmission error is the main source of noise known as gear whine, and radiated gear whine noise plays an important role in the whole gearbox. Therefore, in order to keep competitive in the automotive market, the NVH performance of transmission gearboxes is increasingly important for automotive manufacturers when a new product is developed. In this paper, in order to achieve an optimized tooth contact pattern, gear tooth modification is applied to make up for the deformation of the teeth owing to load. A five-speed MT gearbox is firstly modeled in RomaxDesign software and the prediction of transmission error under the loaded torques is studied and compared. From the simulation, the transmission error and maximum contact stress are also simulated and compared after tooth modification of the loaded torques. Finally, the simulation results are used to optimize the whole gearbox design and the final gearbox prototype is testified to obtain NVH performance in a semi-anechoic room.

• 마이크로전자및패키징학회지
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• 제6권2호
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• pp.13-21
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• 1999

Flip chip assembly directly on organic boards offers miniaturization of package size as well as reduction in interconnection distances resulting in a high performance and cost-competitive Packaging method. This paper describes the investigation of alternative low cost flip-chip mounting processes using electroless Ni/Au bump and anisotropic conductive adhesives/films as an interconnection material on organic boards such as FR-4. As bumps for flip chip, electroless Ni/Au plating was performed and characterized in mechanical and metallurgical point of view. Effect of annealing on Ni bump characteristics informed that the formation of crystalline nickel with $Ni_3$P precipitation above $300^{\circ}C$ causes an increase of hardness and an increase of the intrinsic stress resulting in a reliability limitation. As an interconnection material, modified ACFs composed of nickel conductive fillers for electrical conductor and non-conductive inorganic fillers for modification of film properties such as coefficient of thermal expansion(CTE) and tensile strength were formulated for improved electrical and mechanical properties of ACF interconnection. The thermal fatigue life of ACA/F flip chip on organic board limited by the thermal expansion mismatch between the chip and the board could be increased by a modified ACA/F. Three ACF materials with different CTE values were prepared and bonded between Si chip and FR-4 board for the thermal strain measurement using moire interferometry. The thermal strain of ACF interconnection layer induced by temperature excursion of $80^{\circ}C$ was decreased with decreasing CTEs of ACF materials.

• 한국구조물진단유지관리공학회 논문집
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• 제14권2호
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• pp.97-105
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• 2010

시공단계에 따른 강상판교의 변위를 측정하였고, 이 결과와 비교하기 위하여 3차원 구조해석을 수행하였다. 검증된 모델을 사용하여 대블럭 시공법에 의한 시공단계에 따른 3차원 구조해석을 수행하여 다음과 같은 결론을 얻었다. 1. 설계에 사용된 Grid 해석과 3차원 해석에 의한 결과를 비교하면, Grid 해석의 결과는 곡선교의 변위를 모사하는데 한계가 있었으며, 두 가지 해석방법에 의한 변위의 차이는 약 10~20%정도였다. 2. 가설중에 일어날 수 있는 최대 처짐은 완료된 상태의 처짐에 비하여 1.7배까지 크게 발생하였다. 3. 시공단계 해석 결과, 블록시공법에 의하여 시공되는 교량의 거동은 전체 구조물이 일체로 되어 한 번에 거치되는 교량과는 다른 결과가 도출되며, 중간의 가설과정에서는 설계시 고려된 응답보다 더 큰 결과가 도출되고 있으므로, 설계시 시공단계를 고려한 해석을 통하여 합리적인 구조설계가 이루어져야 한다.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.559-569
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• 2021

As one of the major types of lung cancer, non-small cell lung cancer (NSCLC) accounts for the majority of cancer-related deaths worldwide. Treatments for NSCLC includes surgery, chemotherapy, and targeted therapy. Among the targeted therapies, resistance to inhibitors of the epidermal growth factor receptor (EGFR) is common and remains a problem to be solved. MET (hepatocyte growth factor receptor) amplification is one of the major causes of EGFR-tyrosine kinase inhibitor (TKI) resistance. Therefore, there exists a need to find new and more efficacious therapies. Deoxypodophyllotoxin (DPT) extracted from Anthriscus sylvestris roots exhibits various pharmacological activities including anti-inflammation and anti-cancer effects. In this study we sought to determine the anti-cancer effects of DPT on HCC827GR cells, which are resistant to gefitinib (EGFR-TKI) due to regulation of EGFR and MET and their related signaling pathways. To identify the direct binding of DPT to EGFR and MET, we performed pull-down, ATP-binding, and kinase assays. DPT exhibited competitive binding with ATP against the network kinases EGFR and MET and reduced their activities. Also, DPT suppressed the expression of p-EGFR and p-MET as well as their downstreat proteins p-ErbB3, p-AKT, and p-ERK. The treatment of HCC827GR cells with DPT induced high ROS generation that led to endoplasmic-reticulum stress. Accordingly, loss of mitochondrial membrane potential and apoptosis by multi-caspase activation were observed. In conclusion, these results demonstrate the apoptotic effects of DPT on HCC827GR cells and signify the potential of DPT to serve as an adjuvant anti-cancer drug by simultaneously inhibiting EGFR and MET.

• BMB Reports
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• 제57권6호
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• pp.293-298
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• 2024

Microtubule acetylation has been shown to regulate actin filament dynamics by modulating signaling pathways that control actin organization, although the precise mechanisms remain unknown. In this study, we found that the downregulation of microtubule acetylation via the disruption ATAT1 (which encodes α-tubulin N-acetyltransferase 1) inhibited the expression of RhoA, a small GTPase involved in regulating the organization of actin filaments and the formation of stress fibers. Analysis of RHOA promoter and chromatin immunoprecipitation assays revealed that C/EBPβ is a major regulator of RHOA expression. Interestingly, the majority of C/EBPβ in ATAT1 knockout (KO) cells was found in the nucleus as a 27-kDa fragment (referred to as C/EBPβ^p27) lacking the N-terminus of C/EBPβ. Overexpression of a gene encoding a C/EBPβ^p27-mimicking protein via an N-terminal deletion in C/EBPβ led to competitive binding with wild-type C/EBPβ at the C/EBPβ binding site in the RHOA promoter, resulting in a significant decrease of RHOA expression. We also found that cathepsin L (CTSL), which is overexpressed in ATAT1 KO cells, is responsible for C/EBPβ^p27 formation in the nucleus. Treatment with a CTSL inhibitor led to the restoration of RHOA expression by downregulation of C/EBPβ^p27 and the invasive ability of ATAT1 KO MDA-MB-231 breast cancer cells. Collectively, our findings suggest that the downregulation of microtubule acetylation associated with ATAT1 deficiency suppresses RHOA expression by forming C/EBPβ^p27 in the nucleus through CTSL. We propose that CTSL and C/EBPβ^p27 may represent a novel therapeutic target for breast cancer treatment.

• 대한물리의학회지
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• 제9권1호
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• pp.45-53
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• 2014

PURPOSE: In this study, we tried to find out what kind of exercise was more effective in sleep disorder by comparing melatonin in blood after applying low intensity with high intensity exercise to sleep disordered rats induced by experiment. METHODS: We used male Sprague-Dawley rats which were 8weeks old and weighted 300g. They were supplied with water and food without any restriction. We kept the room temperature at $25^{\circ}C$ and controld the length of day and night in 12 hours blocks, respectively. We divided the rats 60 into 2 groups. To one group we applied low intensity exercise, and to the other we applied high intensity exercise for 15minutes per day over a period of 4 weeks. We extracted the blood from abdominal aorta before, after exercise, moved into EDTA tube, performed centrifugation. We decanted the serum $200{\mu}l$ from the blood into microcentrifuge tube by samples and moved into polypropylene culture tubes with micro pipette. We split enzyme solution $50{\mu}l$ into the tubes with melatonin direct kits and make them react at $37^{\circ}C$ for 2 hours. We split assay buffer $50{\mu}l$ into each tube and mixed melatonin tracer $50{\mu}l$ and melatonin antiserum $50{\mu}l$, respectively. After we made them react in room temperature, we decanted the superficial layer with a centrifuge and measured the activity for 1 minute by competitive method with ${\gamma}$-counter equipment. We draw a standard curve through logit-log graph with CPM(counts per minute) and counted the melatonin by B/B0. We conducted independent t-test to examine the homogeneous of melatonin value of before low-intensity and high-intensity exercise. We performed paired t-test to compare before and after low-intensity and high-intensity exercise, respectively. We carried out independent t-test to compare melatonin value after low-intensity and high-intensity exercise. Significance level was .05. RESULTS: The results were as follows; firstly melatonin was more increased in the group who was exposed to high intensity exercise when we compared before to after high and low intensity exercise, respectively. Secondly, high intensity exercise was more effective than low intensity exercise when we compared the two. CONCLUSION: In conclusion, secretion of melatonin which is the material of sleep improvement could be promoted by high intensity exercise. Low intensity exercise acted as a stress rather than improving sleep and had a negative effect on the secretion of melatonin because the melatonin was affected by stress.

• 한국토양비료학회지
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• 제39권5호
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• pp.321-327
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• 2006

농업환경지표가 OECD 회원국간의 농업환경 비교와 이를 통한 농업환경 개선과 농업정책 수립에 대한 권고의 수단으로만 작용을 하지만 이것이 향후 통상 무역과 연계될 것은 추측 가능한 사실이다. OECD 농업환경지표를 우리나라에 그대로 적용했을 때 얻어진 지표 값이 우리나라의 농업환경을 사실대로 반영하지 못한다면 우리가 받을 피해는 미래에도 작용할 것이므로 이에 대한 새로운 제안을 통해 우리나라에 적합한 지표를 설정해야 한다. OECD에 의해 제안된 농업용수 사용 강도 지표는 논이나 밭에서 이용되거나 배수 유출되는 물의 특성을 모두 반영한 방법이 아니므로 몬순 기후지대에 속하는 한국에 적당하지 않다. 특히, 여름철 집중호우시기에 년 강우량의 2/3가 내리는 강우 특성은 이를 담수해 저장하는 능력을 가진 농경지의 수자원 보유능과 기타의 농업적 특성을 고려한 계산방법으로 농업용수를 산정해야 한다. 논의 경우 강우가 내리거나 관개가 되었을 때 담수나 침투를 통해 물을 지하로 배수해 지하수를 형성하거나 지표의 배수로나 하천을 통해 강이나 저수지로 상당량의 물을 흘려보내 다시 이용할 수 있도록 해준다. 즉, 농업용수로 계산되어 있는 물의 상당량은 다른 농경지나 생활용수 또는 공업용수나 하천 유지용수로 다시 이용된다. 따라서, 물 사용강도에 이용되는 농업용수는 농경지에서 소모되지 않고 지하수로 흘러 들어가거나 하천으로 유입되는 배출수를 고려하여 계산하는 것이 합리적이다. 이렇게 계산하면 22.9%(2001년)로 OECD 계산방법으로 얻어진 47%보다 24.1%가 낮아진다. 합리적인 농업용수 스트레스 지표를 산출하기 위해서는 각 나라마다 다른 나라와 강을 공유하고 있는지의 여부와 농업을 위한 주 취수원이 무엇인지를 살펴보아 그 나라에 적합한 스트레스 지표를 산출하도록 유도하는 것이 바람직할 것이다. 그러나, 실제 물에 대한 스트레스는 강우량, 수계별 수자원 부존량, 사용가능량, 농업용수 총공급수량, 환경 유지용수를 위한 기준 갈수량 확보 가능성, 농업용수 관리현황 및 저수율 분석, 수계별 농업용수 사용 가능량 및 기상 등이 복잡하게 작용할 것이므로 이 모든 인자들을 포함한 지표를 만들기는 쉬운 일이 아니다. 따라서, 우리나라는 OECD의 스트레스 지표와는 달리 환경 위해성 판단이 필요 없고, 계산이 복잡하지 않으며 우리의 환경에 적합하도록 주 취수원인 농업용 저수지의 저수율로 농업용수 스트레스 지표를 산정 했다. 농업용수 사용 기술적 효율지표는 작물의 재배 생리특성 및 이용특성과 지역마다 차이가 나는 기후의 특성을 반영하지 않은 계산의 결과이다. 그러므로 이러한 특성들을 반영하는 기술적 물 이용효율 지표를 만들기 위해서는 각 지역 또는 나라마다 작물별로 기준이 되는 물 소요량을 산정한 후 그 소요량에 대한 공급된 양의 비율로 WUTE를 결정하는 것이 합리적이다. 지역별, 작물별 특성을 포함해야 하는 농업용수 사용 경제적 효율 지표는 소비된 물을 분모로 삼아 계산에 이용하는 대신에 농업용수 사용 기술적 효율에서 제안한 각 지역 또는 나라마다 작물별로 기준이 되는 물 소요량을 산정한 후 그 소요량에 대한 공급된 양의 비율을 계산식의 분모에 적용하고, 벼의 경우는 생산물의 가격 대신에 지하수가 되는 양과 하천수가 되는 양에 대한 경제적 평가에 더해 논에 많은 양의 물이 관개됨으로서 발생하는 수변 생태계에 의한 환경유지 기능과 온도와 습도가 높은 한국의 기후 특성에서 전체 에너지 밸런스를 유지하는데 기여하는 관개수의 가치에 대한 평가와 더불어 생산물의 가격을 포함하는 것이 합리적일 것이다.