• 한국콘텐츠학회논문지
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• 제17권4호
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• pp.541-549
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• 2017

본 연구에서는 정액연구 지원방식에 대한 정량평가 방법을 연구하고, 효율적인 평가방법을 확립하기 위한 모델을 만들었다. 첫째, 기존의 평가 시스템을 분석하여 몇 가지 문제점과 과제를 발견했다. 둘째, 정액연구 지원방식에 대한 정량평가 방법을 제안하고, 20만개 이상의 데이터와 모델을 이용하여 시뮬레이션하였다. 셋째, 제안된 모델을 시험하여 최적의 모델을 찾았다. 그리고 이러한 결과에 따라 몇 가지 정책적 시사점을 제시하였다.

• Molecules and Cells
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• 제44권7호
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• pp.500-516
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• 2021

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.

• Mass Spectrometry Letters
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• 제2권3호
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• pp.69-72
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• 2011

Defective synthesis of the steroid hormones by the adrenal cortex has profound effects on human development and homeostasis. Due to the time-consuming chromatography procedure combined with mass spectrometry, the matrix-assisted laser desorption ionization method coupled to the linear ion-trap tandem mass spectrometry (MALDI-LTQ-MS/MS) was developed for quantitative analysis of 10 adrenal steroids in human serum. Although MALDI-MS can be introduced for its applicability as a high-throughput screening method, it has a limitation on reproducibility within and between samples, which renders poor reproducibility for quantification. For quantitative MALDI-MS/MS analysis, the stable-isotope labeled internal standards were used and the conditions of crystallization were tested. The precision and accuracy were 3.1~35.5% and 83.8~138.5%, respectively, when a mixture of 10 mg/mL ${\alpha}$-cyano-4-hydroxycinnamic acid in 0.2% TFA of 70% acetonitrile was used as the MALDI matrix. The limit of quantification ranged from 5 to 340 ng/mL, and the linearity as a correlation coefficient was higher than 0.988 for all analytes in the calibration range. Clinical applications include quantitative analyses of patients with congenital adrenal hyperplasia. The devised MALDI-MS/MS technique could be successfully applied to diagnosis of clinical samples.

• Communications for Statistical Applications and Methods
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• 제27권6호
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• pp.701-714
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• 2020

Quantitative high throughput screening (qHTS) assays are used to assess toxicity for many chemicals in a short period by collectively analyzing them at several concentrations. Data are routinely analyzed using nonlinear regression models; however, we propose a new method to analyze qHTS data using a nonlinear mixed effects model. qHTS data are generated by repeating the same experiment several times for each chemical; therefor, they can be viewed as if they are repeated measures data and hence analyzed using a nonlinear mixed effects model which accounts for both intra- and inter-individual variabilities. Furthermore, we apply a one-step approach incorporating robust estimation methods to estimate fixed effect parameters and the variance-covariance structure since outliers or influential observations are not uncommon in qHTS data. The toxicity of chemicals from a qHTS assay is classified based on the significance of a parameter related to the efficacy of the chemicals using the proposed method. We evaluate the performance of the proposed method in terms of power and false discovery rate using simulation studies comparing with one existing method. The proposed method is illustrated using a dataset obtained from the National Toxicology Program.

• 한국환경성돌연변이발암원학회지
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• 제21권2호
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• pp.113-117
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• 2001

The screening of various molecular descriptors for predicting carcinogenic, mutagenic and teratogenic activities of chlorinated aliphatic compounds as drinking water disinfection byproducts (DBPs) has been investigated for the application of quantitative structure-activity relationships (QSAR). The present work embodies the study of relationship between molecular descriptors and toxicity parameters of the genotoxicity endpoints for the screening of relevant molecular descriptors. The toxicity Indices for 29 compounds constituting the testing set were computed by the PASS program and active values were chosen. We investigate feasibility of screening descriptors and of their applications among different genotoxic endpoints. The correlation to teratogenicity of all 29 compounds was significantly improved when the same analysis was done with 20 alkanes only without alkene compounds. The HOMO (highest occupied molecular orbital) energy and number of Cl parameters were dominantly contributed.

• Journal of mucopolysaccharidosis and rare diseases
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• 제3권1호
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• pp.9-13
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• 2017

Tandem mass spectrometry and other new technologies for the multiplex and quantitative analysis of dried blood spots have emerged as powerful techniques for the early screening and assessment of newborns for lysosomal storage diseases (LSDs). Screening newborns for these diseases is important, since treatment options, including enzyme replacement therapy or hematopoietic transplantation, are available for some LSDs, such as infant-onset Pompe disease, Fabry disease, some types of mucopolysaccharidoses (MPSs), and Krabbe disease. For these diseases, early initiation of treatment, before symptoms worsen, often leads to better clinical outcomes. Several problems, however, are associated with newborn screening for LSDs, including the development of accurate test methods to reduce low false-positive rates and treatment guidelines for late-onset or mild disease variants, the high costs associated with multiplex assays, and ethical issues. In this review, we discuss the history, current status, and ethical problems associated with the newborn screening for LSDs, including MPSs.

• Genomics & Informatics
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• 제5권1호
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• pp.24-29
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• 2007

Computational virtual screening has become an essential platform of drug discovery for the efficient identification of active candidates. Moleculardocking, a key technology of receptor-centric virtual screening, is commonly used to predict the binding affinities of chemical compounds on target receptors. Despite the advancement and extensive application of these methods, substantial improvement is still required to increase their accuracy and time-efficiency. Here, we evaluate several advanced structure-based virtual screening approaches for elucidating the rank-order activity of chemical libraries, and the quantitative structureactivity relationship (QSAR). Our results show that the ensemble-average free energy estimation, including implicit solvation energy terms, significantly improves the hit enrichment of the virtual screening. We also demonstrate that the assignment of quantum mechanical-polarized (QM-polarized) partial charges to docked ligands contributes to the reproduction of the crystal pose of ligands in the docking and scoring procedure.

• 전력전자학회논문지
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• 제27권2호
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• pp.142-149
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• 2022

In increasing the safety and usage of lithium-ion battery packs, reducing the parameter deviation between cells, such as voltage and temperature within the battery pack, is important. In this study, we propose a screening method to reduce parameter deviation between cells in battery packs. Screening algorithms are constructed based on Fuzzy logic and quantitatively express the similarities between battery cells. Screening is applied by utilizing series resistance components after experiments of electrical characteristics that consider the operation status of battery packs. After screening, the standard deviation of series resistance components according to the similarity ranking is compared and analyzed, and their conformity are verified with the algorithm parameters.

• 통합자연과학논문집
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• 제9권1호
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• pp.72-79
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• 2016

Hexane, ethyl acetate and methanol extracts of whole plant of Boerhavia diffusa were screened for phytochemical and biological activities. Qualitative phytochemical screening via colorimetric method and the quantitative estimation of phenolic and flavonoid content were performed. Antioxidant assay using DPPH scavenging method was studied. Antimicrobial screening of plant extracts was done by cup diffusion technique. Cytotoxic activity of B. diffusa was studied by brine shrimp bioassay and anthelminthic activity was evaluated in vitro in Pheretima posthuma. This study revealed B. diffusa as a source of various phyto-constituents such as alkaloids, glycosides, saponins, tannins, carbohydrates, cardiac glycosides, flavonoids and terpenoids. Quantitative estimation of total phenol was found to be maximum in BEE i.e. $29.73{\pm}0.88$, BME $19.8{\pm}2.02$ and in BHE $9.15{\pm}0.304mgGAE/g$. Similarly, the total flavonoid content was found to be $17.44{\pm}0.75$ in BEE, $14.43{\pm}0.23$ in BHE and 3.678 mg QE/g in BME. Ethyl acetate extract showed its antibacterial activity against all tested pathogens except Escherichia coli whereas Staphylococcus aureus and Salmonella Typhi were resistant to methanol and hexane extract. The zone of inhibition (ZOI) of ethyl acetate extract against S. Typhi and B. cereus was found to be 18 mm and 14 mm respectively. The MIC value of BEE in S. Typhi was $3.125{\mu}g/ml$ and in B. cereus was $12.5{\mu}g/ml$. The preliminary screening of anticancer property of B. diffusa i.e. BSLT in methanol was found to be $165.19{\mu}g/ml$. B. diffusa was also found to contain anthelmintic property. The study helped in further exploration of medicinal properties of B. diffusa by phytochemical screening and biological activities paving the path for study and investigation in this plant.

• 한국산학기술학회논문지
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• 제17권8호
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• pp.379-388
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• 2016

현대 무기체계 제조를 위해 적용되는 수많은 생산 기술과 다양한 공정 환경으로 인해 다양한 결함이 무기체계 제조공정에 유입되고 있다. 이렇게 제조공정에 유입되는 결함 중 육안 검사, 기능 시험 등 기존 품질 관리 절차를 통해 검출할 수 있는 "명백결함(Patent Defect)"과 무기체계 복잡성과 제조공정의 복잡도로 기존 품질 관리 방식으로 검출이 제한되는 "잠재결함(Latent Defect)" 2가지 종류가 있다. 이러한 초기 결함 문제를 최소화하기 위해 무기체계 생산공정 중 유입된 결함요소를 환경부하(온도, 진동)를 활용하여 결함검출/제거/개선하기 위해 환경 부하 선별(ESS : Environmental Stress Screening) 시험을 수행해야 한다. 본 논문은 국내 무기체계 제조업체에서 정량적 환경 부하 선별 시험 설계의 어려움을 최소화하기 위해 MIL-HDBK-344(Environmental Stress Screening of Electronic Equipment)의 수학적 모델을 기반으로 정량적 환경 부하 선별시험 효과도 분석 및 프로파일 자동화 도구를 구현하였으며, 6가지(온도부하변수 3가지(온도범위/온도변화율/허용 잔류결함밀도), 진동부하변수 2가지(부하크기/허용 잔류결함밀도), 시험설계변수 1가지(허용 시험시간)) 시나리오를 통해 구현된 도구 유효성을 확인했다.