• Title/Summary/Keyword: Target-sensitivity

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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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    • v.45 no.6
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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
    • Journal of the Korea Society of Computer and Information
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    • v.28 no.1
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    • pp.55-63
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    • 2023
  • In this paper, we propose a function and service of the Disaster Crisis Alert Management System that automatically analyzes the situation judgment criteria to issue a disaster crisis alert and a plan to operate in the National Disaster Management System(NDMS). In the event of a disaster, a crisis alert(interest-caution-alert-serious) is issued according to the crisis alert level. In order to automatically analyze and determine the crisis alert level, first, data collection, crisis alert level analysis, crisis alert level judgment, and disaster crisis alert management system that expresses the crisis alert level by spatial scale(province, city, district) were implemented. The crisis alert level was analyzed and expressed in two ways by applying the intelligent crisis alert level(determination of regional sensitivity, risk level, and crisis alert level) and the crisis alert standard of the crisis management manual(province-level standard setting). Second, standard metadata, linkage of situation information of target) and API standards for data provision are presented to jointly utilize data linkage and crisis alert data of the disaster and safety data sharing platform so that it can be operated within the NDMS.

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

  • Kim, So-Hyun;Cho, Sung-Hyoun
    • Journal of The Korean Society of Integrative Medicine
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    • v.10 no.3
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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
    • Food Science of Animal Resources
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    • v.43 no.1
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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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    • v.55 no.9
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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
    • Journal of People, Plants, and Environment
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    • v.22 no.5
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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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    • 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.

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

  • Kim, Bang-Sig;Kim, Byung-Il
    • Journal of the Korean Geotechnical Society
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    • v.23 no.4
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    • pp.125-132
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    • 2007
  • The oedometer, radial CRS and Rowe cell tests, composite discharge capacity tests and smear effect tests are carried out to estimate the parameters for the reliability-based design of vertical drain method. Also the sensitivity analysis, the probabilistic and deterministic solutions of radial consolidation theory are presented. The result of probabilistic analysis was compared to that of deterministic analysis using the tested and estimated parameters. The results indicated that the drain spacing in the deterministic method is larger than that in the probabilistic method because the former does not consider the uncertainties in the geotechnical property. The divergence of two methods is dependent on the probability of achieving target degree of consolidation by a given time and the coefficient of variation (COV) of the coefficient of horizontal consolidation ($c_h$).

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

  • Suk, Heejun;Seo, Min Woo;Ko, Kyung-Seok
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.28 no.1B
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    • pp.137-147
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    • 2008
  • Soil Vapor Extraction (SVE) has been extensively used to remove volatile organic compounds (VOCs) from the vadoze zone. In order to investigate the removal mechanism during SVE operation, laboratory modeling experiments were carried out and tailing effect could be observed in later stage of the experiment. Tailing effect means that removal rate of contaminants gets significantly to decrease in later stage of SVE operation. Also, mathematical model simulating the tailing effect was used, which considers rate-limited diffusion in a water film during mass transfer among gas, liquid, and solid phases. Measurement data obtained through the experiment was used as input data of the numerical analyses. Sensitivity analysis was performed to examine the effect of each parameter on required time to reach final target concentration. Finally, it was found that the concentration in the soil phase decreased significantly with a liquid and gas diffusion coefficient larger, actual path length shorter, and water saturation smaller.

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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    • v.39 no.4
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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.