• 제목/요약/키워드: Target-sensitivity

검색결과 615건 처리시간 0.025초

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

  • Yoo, Hee Min;Park, Jong Ho;Kim, Jae Yeon;Chung, Chin Ha
    • Molecules and Cells
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    • 제45권6호
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    • pp.425-434
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    • 2022
  • The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

A Study on Implementation of a Disaster Crisis Alert System based on National Disaster Management System

  • Hyong-Seop, Shim
    • 한국컴퓨터정보학회논문지
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    • 제28권1호
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    • pp.55-63
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    • 2023
  • 본 논문에서는 재난 위기경보 발령을 하기 위해 상황판단 기준을 자동분석하는 재난위기경보관리시스템의 기능 및 서비스와 국가재난관리정보시스템(NDMS) 체계에서 운영하기 위한 방안을 제안한다. 재난 발생시 위험수준에 따라 위기경보(관심-주의-경계-심각)를 발령하고 있다. 위기경보 수준을 자동분석 판단하기 위해 첫째, 데이터 수집, 위기경보 수준 분석, 위기경보 수준 판단, 공간규모별(시도, 시군구) 위기경보 등급을 표출하는 재난위기경보관리시스템을 구현하였다. 위기경보 수준 판단은 지능형 위기경보 수준(지역민감도, 위험수준, 위기경보 등급 판단)과 위기관리 매뉴얼의 위기경보 기준(시도 단위 기준 표준 설정)을 적용하여 두 가지 방식으로 분석하여 표출한다. 둘째, 국가재난정보관리시스템내에서 운영할 수 있도록 재난안전데이터 공유 플랫폼의 데이터 연동과 위기경보 데이터를 공동활용하기 위해 표준 메타데이터(구성항목 정의), 상황정보 연계(대상 정의), 데이터 제공을 위한 openAPI 표준을 제시한다.

한국 물리치료사 국가 면허시험 합격 여부의 예측요인 탐색 (Exploring the Predictive Factors of Passing the Korean Physical Therapist Licensing Examination)

  • 김소현;조성현
    • 대한통합의학회지
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    • 제10권3호
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    • pp.107-117
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    • 2022
  • Purpose : The purpose of this study was to establish a model of the predictive factors for success or failure of examinees undertaking the Korean physical therapist licensing examination (KPTLE). Additionally, we assessed the pass/fail cut-off point. Methods : We analyzed the results of 10,881 examinees who undertook the KPTLE, using data provided by the Korea Health Personnel Licensing Examination Institute. The target variable was the test result (pass or fail), and the input variables were: sex, age, test subject, and total score. Frequency analysis, chi-square test, descriptive statistics, independent t-test, correlation analysis, binary logistic regression, and receiver operating characteristic (ROC) curve analyses were performed on the data. Results : Sex and age were not significant predictors of attaining a pass (p>.05). The test subjects with the highest probability of passing were, in order, medical regulation (MR) (Odds ratio (OR)=2.91, p<.001), foundations of physical therapy (FPT) (OR=2.86, p<.001), diagnosis and evaluation for physical therapy (DEPT) (OR=2.74, p<.001), physical therapy intervention (PTI) (OR=2.66, p<.001), and practical examination (PE) (OR=1.24, p<.001). The cut-off points for each subject were: FPT, 32.50; DEPT, 29.50; PTI, 44.50; MR, 14.50; and PE, 50.50. The total score (TS) was 164.50. The sensitivity, specificity, and the classification accuracy of the prediction model was 99 %, 98 %, and 99 %, respectively, indicating high accuracy. Area under the curve (AUC) values for each subject were: FPT, .958; DEPT, .968; PTI, .984; MR, .885; PE, .962; and TS, .998, indicating a high degree of fit. Conclusion : In our study, the predictive factors for passing KPTLE were identified, and the optimal cut-off point was calculated for each subject. Logistic regression was adequate to explain the predictive model. These results will provide universities and examinees with useful information for predicting their success or failure in the KPTLE.

Gold Nanoparticle and Polymerase Chain Reaction (PCR)-Based Colorimetric Assay for the Identification of Campylobacter spp. in Chicken Carcass

  • Seung-Hwan Hong;Kun-Ho Seo;Sung Ho Yoon;Soo-Ki Kim;Jungwhan Chon
    • 한국축산식품학회지
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    • 제43권1호
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    • pp.73-84
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    • 2023
  • Campylobacteriosis is a common cause of gastrointestinal disease. In this study, we suggest a general strategy of applying gold nanoparticles (AuNPs) in colorimetric biosensors to detect Campylobacter in chicken carcass. Polymerase chain reaction (PCR) was utilized for the amplification of the target genes, and the thiolated PCR products were collected. Following the blending of colloid AuNPs with PCR products, the thiol bound to the surface of AuNPs, forming AuNP-PCR products. The PCR products had a sufficient negative charge, which enabled AuNPs to maintain a dispersed formation under electrostatic repulsion. This platform presented a color change as AuNPs aggregate. It did not need additional time and optimization of pH for PCR amplicons to adhere to the AuNPs. The specificity of AuNPs of modified primer pairs for mapA from Campylobacter jejuni and ceuE from Campylobacter coli was activated perfectly (C. jejuni, p-value: 0.0085; C. coli, p-value: 0.0239) when compared to Salmonella Enteritidis and Escherichia coli as non-Campylobacter species. Likewise, C. jejuni was successfully detected from artificially contaminated chicken carcass samples. According to the sensitivity test, at least 15 ng/μL of Campylobacter PCR products or 1×103 CFU/mL of cells in the broth was needed for the detection using the optical method.

Tackling range uncertainty in proton therapy: Development and evaluation of a new multi-slit prompt-gamma camera (MSPGC) system

  • Youngmo Ku;Sehoon Choi;Jaeho Cho;Sehyun Jang;Jong Hwi Jeong;Sung Hun Kim;Sungkoo Cho;Chan Hyeong Kim
    • Nuclear Engineering and Technology
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    • 제55권9호
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    • pp.3140-3149
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    • 2023
  • In theory, the sharp dose falloff at the distal end of a proton beam allows for high conformal dose to the target. However, conformity has not been fully achieved in practice, primarily due to beam range uncertainty, which is approximately 4% and varies slightly across institutions. To address this issue, we developed a new range verification system prototype: a multi-slit prompt-gamma camera (MSPGC). This system features high prompt-gamma detection sensitivity, an advanced range estimation algorithm, and a precise camera positioning system. We evaluated the range measurement precision of the prototype for single spot beams with varying energies, proton quantities, and positions, as well as for spot-scanning proton beams in a simulated SSPT treatment using a phantom. Our results demonstrated high accuracy (<0.4 mm) in range measurement for the tested beam energies and positions. Measurement precision increased significantly with the number of protons, achieving 1% precision with 5 × 108 protons. For spot-scanning proton beams, the prototype ensured more than 5 × 108 protons per spot with a 7 mm or larger spot aggregation, achieving 1% range measurement precision. Based on these findings, we anticipate that the clinical application of the new prototype will reduce range uncertainty (currently approximately 4%) to 1% or less.

A Trend Analysis of Floral Products and Services Using Big Data of Social Networking Services

  • Park, Sin Young;Oh, Wook
    • 인간식물환경학회지
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    • 제22권5호
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    • pp.455-466
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    • 2019
  • This study was carried out to analyze trends in floral products and services through the big data analysis of various social networking services (SNSs) and then to provide objective marketing directions for the floricultural industry. To analyze the big data of SNSs, we used four analytical methods: Cotton Trend (Social Matrix), Naver Big Data Lab, Instagram Big Data Analysis, and YouTube Big Data Analysis. The results of the big data analysis showed that SNS users paid positive attention to flower one-day classes that can satisfy their needs for direct experiences. Consumers of floral products and services had their favorite designs in mind and purchased floral products very actively. The demand for flower items such as bouquets, wreaths, flower baskets, large bouquets, orchids, flower boxes, wedding bouquets, and potted plants was very high, and cut flowers such as roses, tulips, and freesia were most popular as of June 1, 2019. By gender of consumers, females (68%) purchased more flower products through SNSs than males (32%). Consumers preferred mobile devices (90%) for online access compared to personal computers (PCs; 10%) and frequently searched flower-related words from February to May for the past three years from 2016 to 2018. In the aspect of design, they preferred natural style to formal style. In conclusion, future marketing activities in the floricultural industry need to be focused on social networks based on the results of big data analysis of popular SNSs. Florists need to provide consumers with the floricultural products and services that meet the trends and to blend them with their own sensitivity. It is also needed to select SNS media suitable for each gender and age group and to apply effective marketing methods to each target.

Hypoxia-inducible factor 1α inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells

  • Masanobu Tsubaki;Tomoya Takeda;Takuya Matsuda;Akihiro Kimura;Remi Tanaka;Sakiko Nagayoshi;Tadafumi Hoshida;Kazufumi Tanabe;Shozo Nishida
    • 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.

지반 불확실성을 고려한 연직배수재 배치간격의 확률론적 해석과 결정 (Probabilistic Analysis and Design of the Spacing of Prefabricated Vertical Drains Considering Uncertainties in Geotechnical Property)

  • 김방식;김병일
    • 한국지반공학회논문집
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    • 제23권4호
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    • pp.125-132
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    • 2007
  • 본 연구에서는 표준압밀, 방사형 일정변형속도 압밀, 로우셀압밀, 복합통수능 및 교란영역시험을 수행하여 연직배수공법의 신뢰성 설계를 위한 파라미터를 산정하였다. 또한 방사형 압밀이론에 대한 민감도 해석, 결정론적 해석 및 확률론적 해석이 수행되었다. 시험 결과를 이용한 방사형 압밀이론의 확률론적 해석 결과와 결정론적 해석 결과를 비교, 분석 하였으며, 그로부터 배수재 배치간격은 확률론적 방법보다 결정론적 방법에서 더 넓게 산정됨을 제시하였다. 이는 결정론적 해석에서는 지반 불확실성을 고려하지 못하였기 때문이다. 두 방법을 이용하여 산정된 배치간격간의 차이는 목표 압밀도에 도달할 수 있는 확률과 수평압밀계수의 변동계수에 영향을 받는 것으로 나타났다.

실내모형시험과 수치해석을 통한 SVE의 효율성 평가 (Evaluation of Efficiency of SVE from Lab-scale Model Tests and Numerical Analysis)

  • 석희준;서민우;고경석
    • 대한토목학회논문집
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    • 제28권1B호
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    • pp.137-147
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    • 2008
  • SVE 공법은 휘발성 유기물로 오염된 불포화대의 정화 공법으로 널리 적용되어 왔다. 본 연구에서는 SVE 적용시 오염물 제거 기작을 관찰하기 위해 모형조 시험을 수행하였으며, 이로부터 SVE의 주요 특징인 tailing 현상, 즉 후반부로 갈수록 제거 속도가 급격히 느려지는 꼬리 효과를 확인하였다. 본 연구에서는 액상 막에서의 확산 제약 현상을 고려할 수 있는 수치 모델을 적용하였으며, 모형조 시험 결과와 구축된 수치 모델링을 통해 SVE의 전형적인 특징이 꼬리 현상을 적절하게 모사할 수 있었다. 또한 4가지 변수에 대한 민감도 분석을 수행하여, 총토양농도의 백분율은 액상확산계수가 클수록, 가스상 확산계수가 클수록, 실제확산경로가 짧을수록, 물포화도가 작을수록 빠르게 감소함을 확인하였다.

A Field Deployable Real-Time Loop-Mediated Isothermal Amplification Targeting Five Copy nrdB Gene for the Detection of 'Candidatus Liberibacter asiaticus' in Citrus

  • Tirumalareddy Danda;Jong-Won Park;Kimberly L. Timmons;Mamoudou Setamou;Eliezer S. Louzada;Madhurababu Kunta
    • The Plant Pathology Journal
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    • 제39권4호
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    • pp.309-318
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    • 2023
  • Huanglongbing (HLB) is one of the most destructive diseases in citrus, which imperils the sustainability of citriculture worldwide. The presumed causal agent of HLB, 'Candidatus Liberibacter asiaticus' (CLas) is a non-culturable phloem-limited α-proteobacterium transmitted by Asian citrus psyllids (ACP, Diaphorina citri Kuwayama). A widely adopted method for HLB diagnosis is based on quantitative real-time polymerase chain reaction (qPCR). Although HLB diagnostic qPCR provides high sensitivity and good reproducibility, it is limited by time-consuming DNA preparation from plant tissue or ACP and the requirement of proper lab instruments including a thermal cycler to conduct qPCR. In an attempt to develop a quick assay that can be deployed in the field for CLas detection, we developed a real-time loop-mediated isothermal amplification (rt-LAMP) assay by targeting the CLas five copy nrdB gene. The rt-LAMP assay using various plant sample types and psyllids successfully detected the nrdB target as low as ~2.6 Log10 copies. Although the rt-LAMP assay was less sensitive than laboratory-based qPCR (detection limit ~10 copies), the data obtained with citrus leaf and bark and ACP showed that the rt-LAMP assay has >96% CLas detection rate, compared to that of laboratory-based qPCR. However, the CLas detection rate in fibrous roots was significantly decreased compared to qPCR due to low CLas titer in some root DNA sample. We also demonstrated that the rt-LAMP assay can be used with a crude leaf DNA extract which is fully deployable in the field for quick and reliable HLB screening.