• Title/Summary/Keyword: ASOS

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Drug Discovery Perspectives of Antisense Oligonucleotides

  • Yeonjoon Kim
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.241-252
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    • 2023
  • The era of innovative RNA therapies using antisense oligonucleotides (ASOs), siRNAs, and mRNAs is beginning. Since the emergence of the concept of ASOs in 1978, it took more than 20 years before they were developed into drugs for commercial use. Nine ASO drugs have been approved to date. However, they target only rare genetic diseases, and the number of chemistries and mechanisms of action of ASOs are limited. Nevertheless, ASOs are accepted as a powerful modality for next-generation medicines as they can theoretically target all disease-related RNAs, including (undruggable) protein-coding RNAs and non-coding RNAs. In addition, ASOs can not only downregulate but also upregulate gene expression through diverse mechanisms of action. This review summarizes the achievements in medicinal chemistry that enabled the translation of the ASO concept into real drugs, the molecular mechanisms of action of ASOs, the structure-activity relationship of ASO-protein binding, and the pharmacology, pharmacokinetics, and toxicology of ASOs. In addition, it discusses recent advances in medicinal chemistry in improving the therapeutic potential of ASOs by reducing their toxicity and enhancing their cellular uptake.

A Highly Effective and Long-Lasting Inhibition of miRNAs with PNA-Based Antisense Oligonucleotides

  • Oh, Su Young;Ju, YeongSoon;Park, Heekyung
    • Molecules and Cells
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    • v.28 no.4
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    • pp.341-345
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    • 2009
  • MiRNAs are non-coding RNAs that play a role in the regulation of major processes. The inhibition of miRNAs using antisense oligonucleotides (ASOs) is a unique and effective technique for the characterization and subsequent therapeutic targeting of miRNA function. Recent advances in ASO chemistry have been used to increase both the resistance to nucleases and the target affinity and specificity of these ASOs. Peptide nucleic acids (PNAs) are artificial oligonucleotides constructed on a peptide-like backbone. PNAs have a stronger affinity and greater specificity to DNA or RNA than natural nucleic acids and are resistant to nucleases, which is an essential characteristic for a miRNA inhibitor that will be exposed to serum and cellular nucleases. For increasing cell penetration, PNAs were conjugated with cell penetrating peptides (CPPs) at N-terminal. Among the tested CPPs, Tat-modified peptide-conjugated PNAs have most effective function for miRNA inhibition. PNA-based ASO was more effective miRNA inhibitor than other DNA-based ASOs and did not show cytotoxicity at concentration up to 1,000 nM. The effects of PNA-based ASOs were shown to persist for 9 days. Also, PNA-based ASOs showed considerable stability at storage temperature. These results suggest that PNA-based ASOs are more effective ASOs of miRNA than DNA-based ASOs and PNA-based ASO technology, compared with other technologies used to inhibit miRNA activity can be an effective tool for investigating miRNA functions.

Calculation of Soil Moisture and Evapotranspiration for KLDAS(Korea Land Data Assimilation System) using Hydrometeorological Data Set (수문기상 데이터 세트를 이용한 KLDAS(Korea Land Data Assimilation System)의 토양수분·증발산량 산출)

  • PARK, Gwang-Ha;LEE, Kyung-Tae;KYE, Chang-Woo;YU, Wan-Sik;HWANG, Eui-Ho;KANG, Do-Hyuk
    • Journal of the Korean Association of Geographic Information Studies
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    • v.24 no.4
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    • pp.65-81
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    • 2021
  • In this study, soil moisture and evapotranspiration were calculated throughout South Korea using the Korea Land Data Assimilation System(KLDAS) of the Korea-Land Surface Information System(K-LIS) built on the basis of the Land Information System (LIS). The hydrometeorological data sets used to drive K-LIS and build KLDAS are MERRA-2(Modern-Era Retrospective analysis for Research and Applications, version 2) GDAS(Global Data Assimilation System) and ASOS(Automated Synoptic Observing System) data. Since ASOS is a point-based observation, it was converted into grid data with a spatial resolution of 0.125° for the application of KLDAS(ASOS-S, ASOS-Spatial). After comparing the hydrometeorological data sets applied to KLDAS against the ground-based observation, the mean of R2 ASOS-S, MERRA-2, and GDAS were analyzed as temperature(0.994, 0.967, 0.975), pressure(0.995, 0.940, 0.942), humidity (0.993, 0.895, 0.915), and rainfall(0.897, 0.682, 0.695), respectively. For the hydrologic output comparisons, the mean of R2 was ASOS-S(0.493), MERRA-2(0.56) and GDAS (0.488) in soil moisture, and the mean of R2 was analyzed as ASOS-S(0.473), MERRA-2(0.43) and GDAS(0.615) in evapotranspiration. MERRA-2 and GDAS are quality-controlled data sets using multiple satellite and ground observation data, whereas ASOS-S is grid data using observation data from 103 points. Therefore, it is concluded that the accuracy is lowered due to the error from the distance difference between the observation data. If the more ASOS observation are secured and applied in the future, the less error due to the gridding will be expected with the increased accuracy.

High-Resolution Flow Simulations Around a Steep Mountainous Island in Korea Using a CFD Model with One-way Nested Grid System

  • Mun, Da-Som;Kim, Jae-Jin
    • Korean Journal of Remote Sensing
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    • v.36 no.4
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    • pp.557-571
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    • 2020
  • High-resolution flows around a steep mountainous island (Ulleungdo) in Korea were simulated by a computational fluid dynamics (CFD) model. To cover entire Ulleungdo and to resolve the topography around the Ulleungdo automatic synoptic observing system (ASOS) with high resolution, one-way nested grid system with large (60 m), and small (20 m) grid sizes was applied in the CFD model simulations. We conducted the numerical simulations for 16 inflow directions, and, for each inflow direction, we considered six different wind velocities(5, 10, 15, 20, 25, and 30 m s-1) at the reference height (1,000 m). The effects of topography on surface wind observations were well reflected in the observed wind roses for the period of January 01, 2012 ~ December 31, 2016 at the Ulleungdo ASOS and marine buoy. Wind roses at the Ulleungdo ASOS was reproduced based on the CFD simulations. The changes in surface winds at the Ulleungdo ASOS caused by surrounding topography were relatively well simulated by the CFD model. The simulated wind-rose indicated that south-southwesterly and northeasterly were the dominant wind directions, which were also observed at the Ulleungdo ASOS. We investigated the flow characteristics around the Ulleungdo ASOS for northwesterly, south-southwesterly, and northeasterly winds in detail.

Assessment of Observation Environments of Automated Synoptic Observing Systems Using GIS and WMO Meteorological Observation Guidelines (GIS와 WMO 기상 관측 환경 기준을 이용한 종관기상관측소 관측환경평가)

  • Kang, Jung-Eun;Kim, Jae-Jin
    • Korean Journal of Remote Sensing
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    • v.36 no.5_1
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    • pp.693-706
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    • 2020
  • For ten meteorological observatories running an automated synoptic observing system (ASOS), we classified the observation environments into five classes based on the World Meteorological Organization (WMO) classification guidelines. Obstacles (such as topography and buildings) and land-cover types were the main factors in evaluating the observation environments for the sunshine duration, air-temperature, and surface wind. We used the digital maps of topography, buildings, and land-cover types. The observation environment of the sunshine duration was most affected by the surrounding buildings when the solar altitude angle was low around the sunrise and sunset. The air-temperature observation environment was determined based on not only the solar altitude angle but the distance between the heat/water source and ASOS. There was no water source around the ASOSs considered in this study. Heat sources located near some ASOSs were not large enough to affect the observation environment. We evaluated the surface wind observation environment based on the roughness length around the ASOS and the distance between surrounding buildings and the ASOS. Most ASOSs lay at a higher altitude than the surroundings and the roughness lengths around the ASOSs were small enough to satisfy the condition for the best level.

Analyzing fractal features in rainfall using high-resolution ASOS data (고해상도 ASOS 자료를 이용한 강우의 프랙털 특성 분석)

  • Kang, Hyoungseok;Paik, Kyungrock
    • Proceedings of the Korea Water Resources Association Conference
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    • 2017.05a
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    • pp.171-171
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    • 2017
  • 강우의 시간분포는 다양한 시간규모에 걸쳐 프랙털 또는 멀티프랙털 특성을 가지고 있음이 알려졌다. 기존의 연구는 주로 시간단위 이상의 프랙털 특성에 관한 것이었다. 실제로 극한 홍수를 가져오는 집중호우는 짧은 시간 규모에서 발생함에도, 이것에 대해서는 관측 자료가 제한되어 극소수의 실험적 연구만 가능했다. 본 연구에서는 기상청에서 제공한 고해상도(1분 단위) ASOS(Automated Synoptic Observation System) 자료를 이용하여, 강우 사상 안에서의 프랙털 특성을 분석해보았다. 대부분의 사상에서 단일 멱함수보다는 2개의 멱함수로 나누어지는 것이 밝혀졌으며, 나뉘는 시간 규모(T*)는 $3{\times}10$ 분으로 파악되었다. 이 시간 규모는 한 단위의 집중호우를 가져올 수 있는 구름크기의 물리적 상한과 관련이 있는 것으로 보인다. T*보다 작은 시간 규모에서의 멱함수 지수는 그 이후의 값보다 대체로 작은 것으로 나타났다. 이는 호우가 집중되는 기간의 변동성이, 강수가 물리적 한계에 도달한 이후보다 훨씬 작기 때문으로 보인다. 구체적인 멱함수의 지수는 강수의 발생과정과도 관련이 있을 것으로 추정된다.

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Estimation of seasonal rainfall based on multiple regression analysis using ASOS data of Korea Meteorological Administration (기상청 ASOS 자료를 활용한 다중회귀분석 기반의 계절 강수량 예측)

  • Kim, Chul-gyum;Lee, Jeongwoo;Lee, Jeong Eun;Kim, Nam-won;Kim, Hyeonjun
    • Proceedings of the Korea Water Resources Association Conference
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    • 2019.05a
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    • pp.310-310
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    • 2019
  • 본 연구에서는 기상청 ASOS(종관기상관측장비) 자료와 통계적 기반의 다중회귀분석모형을 이용하여 경안천 유역에 대한 봄철 강수량(3~5월 누적강수량)의 예측성을 평가하였다. 예측대상기간은 2006~2018년이며 예측인자로서 전국 96개 지점의 ASOS 자료 중 35개 기상요소에 대한 월 자료를 활용하였다. 전망기간(1~12개월)에 따라 강수량 기준 최소 1개월에서 최대 24개월까지의 지체시간을 고려하여 1~24개월 선행 ASOS 기상자료와 강수량 사이의 상관성을 분석하였다. 예측대상년도를 기준으로 과거 40년간의 자료를 이용하여 상관성 분석을 수행하였으며, 상관성이 높은 상위 30개 기상인자를 조합하여 다중회귀분석모형의 예측인자(독립변수)로 활용하였다. 예측대상년도와 전망기간에 따라 최적의 예측인자를 조합하고, 교차검증을 통하여 각각 4,000개의 다중회귀모형을 도출하여 예측범위를 산출하였다. 다중회귀모형에 의한 예측범위를 분석한 결과, 2013년 자료까지는 예측범위가 관측값을 잘 포함하고 예측값의 평균이나 중간값이 관측값과 유사하게 나타난 반면, 2014년부터는 전망기간에 따라 관측값과 예측범위의 차이가 크게 나타나는 경우도 있었다. 예측치의 중간값을 기준으로 3분위(평년 이상, 평년 수준, 평년 이하) 적중률을 분석하면, 2006~2013년에 대해서는 58.3%인 반면, 2014~2018년에 대해서는 11.2% 수준으로 나타났다.

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Effects of Differential Heating by Land-Use types on flow and air temperature in an urban area (토지 피복별 차등 가열이 도시 지역의 흐름과 기온에 미치는 영향)

  • Park, Soo-Jin;Choi, So-Hee;Kang, Jung-Eun;Kim, Dong-Ju;Moon, Da-Som;Choi, Wonsik;Kim, Jae-Jin;Lee, Young-Gon
    • Korean Journal of Remote Sensing
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    • v.32 no.6
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    • pp.603-616
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    • 2016
  • In this study, the effects of differential heating by land-use types on flow and air temperature at an Seoul Automated Synoptic Observing Systems (ASOS) located at Songwol-dong, Jongno-gu, Seoul was analyzed. For this, a computation fluid dynamics (CFD) model was coupled to the local data assimilation and prediction system (LDAPS) for reflecting the local meteorological characteristics at the boundaries of the CFD model domain. Time variation of temperatures on solid surfaces was calculated using observation data at El-Oued, Algeria of which latitude is similar to that of the target area. Considering land-use type and shadow, surface temperatures were prescribed in the LDAPS-CFD coupled model. The LDAPS overestimated wind speeds and underestimated air temperature compared to the observations. However, a coupled LDAPS-CFD model relatively well reproduced the observed wind speeds and air temperature, considering complicated flows and surface temperatures in the urban area. In the morning when the easterly was dominant around the target area, both the LDAPS and coupled LDAPS-CFD model underestimated the observed temperatures at the Seoul ASOS. This is because the Kyunghee Palace located at the upwind region was composed of green area and its surface temperature was relatively low. However, in the afternoon when the southeasterly was dominant, the LDAPS still underestimated, on the while, the coupled LDAPS-CFD model well reproduced the observed temperatures at the Seoul ASOS by considering the building-surface heating.

Comparisons of 1-Hour-Averaged Surface Temperatures from High-Resolution Reanalysis Data and Surface Observations (고해상도 재분석자료와 관측소 1시간 평균 지상 온도 비교)

  • Song, Hyunggyu;Youn, Daeok
    • Journal of the Korean earth science society
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    • v.41 no.2
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    • pp.95-110
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    • 2020
  • Comparisons between two different surface temperatures from high-resolution ECMWF ReAnalysis 5 (ERA5) and Automated Synoptic Observing System (ASOS) observations were performed to investigate the reliability of the new reanalysis data over South Korea. As ERA5 has been recently produced and provided to the public, it will be highly used in various research fields. The analysis period in this study is limited to 1999-2018 because regularly recorded hourly data have been provided for 61 ASOS stations since 1999. Topographic characteristics of the 61 ASOS locations are classified as inland, coastal, and mountain based on Digital Elevation Model (DEM) data. The spatial distributions of whole period time-averaged temperatures for ASOS and ERA5 were similar without significant differences in their values. Scatter plots between ASOS and ERA5 for three different periods of yearlong, summer, and winter confirmed the characteristics of seasonal variability, also shown in the time-series of monthly error probability density functions (PDFs). Statistical indices NMB, RMSE, R, and IOA were adopted to quantify the temperature differences, which showed no significant differences in all indices, as R and IOA were all close to 0.99. In particular, the daily mean temperature differences based on 1-hour-averaged temperature had a smaller error than the classical daily mean temperature differences, showing a higher correlation between the two data. To check if the complex topography inside one ERA5 grid cell is related to the temperature differences, the kurtosis and skewness values of 90-m DEM PDFs in a ERA5 grid cell were compared to the one-year period amplitude among those of the power spectrum in the time-series of monthly temperature error PDFs at each station, showing positive correlations. The results account for the topographic effect as one of the largest possible drivers of the difference between ASOS and ERA5.

Development of Observational Environment Evaluation Model for Sunshine Duration at ASOSs Located in Urban Areas (도시지역 유인관측소 일조 관측환경 평가 모델 개발)

  • Kim, Do-Yong;Kim, Do-Hyoung;Kim, Jae-Jin
    • Atmosphere
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    • v.23 no.3
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    • pp.275-282
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    • 2013
  • In this study, the numerical model was developed to evaluate the observational environment of sunshine duration and, for evaluating the accuracy and utility of the model, it was verified against the observational data measured at Dae-gu Automated Synoptic Observing System (ASOS) located in an urban area. Three-dimensional topography and building configuration as the surface input data of the model were constructed using a Geographic Information System (GIS) data. First, the accuracy of the computing planetary positions suggested by Paul Schlyter was verified against the data provided by Korea Astronomy and Space Science Institute (KASI) and the results showed that the numerical model predicted the Sun's position (the solar azimuth and altitude angles) quite precisely. Then, this model was applied to reproduce the sunshine duration at the Dae-gu ASOS. The observed and calculated sunshine durations were similar to each other. However, the observed and calculated sunrise (sunset) times were delayed (curtailed), compared to those provided by KASI that considered just the ASOS's position information such as latitude, longitude, and elevation height but did not consider the building and topography information. Further investigation showed that this was caused by not only the topographic characteristic (higher in the east and lower in the west) but also the buildings located in the southeast near the sunrise and the southwest near the sunset. It was found that higher building resolution increased the accuracy of the model. It was concluded that, for the accurate evaluation of the sunshine duration, detailed building and topography information around the observing sites was required and the numerical model developed in this study was successful to predict and/or the sunshine duration of the ASOS located in an urban area.