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Zika Virus Proteins NS2A and NS4A Are Major Antagonists that Reduce IFN-β Promoter Activity Induced by the MDA5/RIG-I Signaling Pathway

  • Ngan, Nguyen Thi Thuy;Kim, Seong-Jun;Lee, Jeong Yoon;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.29 no.10
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    • pp.1665-1674
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    • 2019
  • Zika virus (ZIKV) is a mosquito-transmitted, emerging Flavivirus that causes Guillain-$Barr{\acute{e}}$ syndrome and microcephaly in adults and fetuses, respectively. Since ZIKV was first isolated in 1947, severe outbreaks have occurred at various places worldwide, including Yap Island in 2007, French Polynesia in 2013, and Brazil in 2015. Although incidences of ZIKV infection and dissemination have drastically increased, the mechanisms underlying the pathogenesis of ZIKV have not been sufficiently studied. In addition, despite extensive research, the exact roles of individual ZIKV genes in the viral evasion of the host innate immune responses remain elusive. Besides, it is still possible that more than one ZIKV-encoded protein may negatively affect type I interferon (IFN) induction. Hence, in this study, we aimed to determine the modulations of the IFN promoter activity, induced by the MDA5/RIG-I signaling pathway, by over-expressing individual ZIKV genes. Our results show that two nonstructural proteins, NS2A and NS4A, significantly down-regulated the promoter activity of IFN-${\beta}$ by inhibiting multiple signaling molecules involved in the activation of IFN-${\beta}$. Interestingly, while NS2A suppressed both full-length and constitutively active RIG-I, NS4A had inhibitory activity only on full-length RIG-I. In addition, while NS2A inhibited all forms of IRF3 (full-length, regulatory domain-deficient, and constitutively active), NS4A could not inhibit constitutively active IRF3-5D. Taken together, our results showed that NS2A and NS4A play major roles as antagonists of MDA5/RIG-I-mediated IFN-${\beta}$ induction and more importantly, these two viral proteins seem to inhibit induction of the type I IFN responses in differential mechanisms. We believe this study expands our understanding regarding the mechanisms via which ZIKV controls the innate immune responses in cells and may pave the way to development of ZIKV-specific therapeutics.

Area/free-surface relationship in the river cross-section (하천 횡단면에서 면적-수위 관계)

  • Hwang, Seung-Yong
    • Proceedings of the Korea Water Resources Association Conference
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    • 2019.05a
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    • pp.258-258
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    • 2019
  • 계산 격자에 기반하여 천수 흐름을 모의할 때, 그 격자에 담긴 물의 양을 정확하게 파악할 필요가 있다. 예를 들어, 초기조건으로 수위가 부여된다면 계산격자의 기하 특성에 맞추어 흐름 변수인 수심이나 흐름 단면적으로 바꾸어야하기 때문이다. 필요에 따라서는 모의 결과를 수위로 보이거나 격자 속 수심을 계산에 사용할 수도 있으므로 그 역변환도 고려되어야 한다. 2차원의 삼각형 계산격자에 대해서는 물의 부피와 수위 관계(volume/free-surface relationship)가 이미 정확(exact)하게 구명되어 있다(Hwang, 2017, J. KWRA). 그런데 1차원 문제의 횡단면에서 흐름 단면적과 수위의 관계(area/free-surface relationship)는 수위로부터 면적 환산에 대해서는 정확하나 그 역변환은 그렇지 않다. 매 시간 단계에서 갱신된 흐름 단면적으로부터 수위를 환산하기 위해 미리 작성된 면적-수위 자료를 이용한 선형 보간이 적용된다(Goodell, 2011, The RAS Solution). 이때, 환산 정확도는 자료의 해상도에 의존된다. 다행히 하천 횡단면 대부분을 채워 흐르는 홍수모의에서는 이 문제가 그리 심각하지는 않다. 심지어 수위가 복단면 저수로 턱에 걸쳐있어 흐름단면적이 급변하는 경우에도 환산 수위의 정확도는 크게 훼손되지 않는다. 그러나 미미한 환산 오차일지라도 그로 인해 수위가 저수로 턱을 넘거나 그보다 작을 수 있다. 이 경우, 홍수터의 잠김여부에 따라 수면폭(top width)이 실제 계산 결과에 비해 크게 달라질 수밖에 없다. 수면폭 오차는 그것을 이용하여 결정되는 수리 수심(hydraulic depth)이나 평균 하상고(mean bed level)의 산정에도 전파된다. 이 연구에서는 하천 횡단면에서 수위와 흐름 단면적 사이의 환산 정확도를 크게 높일 수 있는 기법을 제시하였다. 먼저 하천 횡단면에서 주어진 수위에 대해 흐름 단면적을 산정할 수 있는 알고리듬을 보였다. 또한, 횡단면에서 수위와 흐름 단면적의 관계가 단조 증가 함수(monotonically increasing function)임에 착안하여 그 역변환에 대해 해 찾기(root finding) 방법의 하나인 Brent 기법을 적용하였다. 이 기법은 주어진 구간에서 도함수가 알려져 있지 않은 경우에 대해서도 효과적으로 해를 찾을 수 있는 것으로 알려져 있다(Press et al., 2002, Numerical Recipes in C, 2nd Ed.). 내성천 하류 수계의 333개 단면에서 수면폭에 대한 상대 오차를 살펴보면, 선형 보간에 의한 기존 방법으로는 면적-수위 자료의 수가 1,000개가 되어도 그 최대치가 1% 이내에 들지 않은 반면, 이 연구에서 제시한 기법으로 면적-수위 자료 없이도 1% 이내로 줄어드는 것을 확인하였다. 다만, 반복 계산에 의한 계산 시간의 증대를 피할 수 없다. 미리 작성된 면적-수위 자료를 이용하면 계산 비용을 줄일 수 있으며, 약 35개의 구간으로 나누었을 때 비용 대비오차가 적절하였다. 이 연구는 한국건설기술연구원(주요사업 과제번호: 20190116-001)의 지원에 의한 것이다.

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Angiopoietin-1 and -2 and vascular endothelial growth factor expression in ovarian grafts after cryopreservation using two methods

  • Cho, In Ae;Lee, Yeon Jee;Lee, Hee Jung;Choi, In Young;Shin, Jeong Kyu;Lee, Soon Ae;Lee, Jong Hak;Choi, Won Jun
    • Clinical and Experimental Reproductive Medicine
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    • v.45 no.3
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    • pp.143-148
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    • 2018
  • Objective: The favored method of preserving fertility in young female cancer survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing hypoxia until angiogenesis takes place is essential for the survival of transplanted ovarian tissue. The aim of this study was to investigate the role of angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two methods. Methods: Ovarian tissues harvested from ICR mice were divided into three groups: group I (control), no cryopreservation; group II, vitrification in EFS (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from ovarian tissue 1 week following cryopreservation and again 2 weeks after autotransplantation. We used reverse transcriptase-polymerase chain reaction to quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. Results: Angpt-1 and Angpt-2 expression decreased after cryopreservation in groups II and III. After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue showed different trends. Angpt-1 expression in groups II and III was lower than in group I, but Angpt-2 in groups II and III showed no significant difference from group I. The vitrified ovarian tissues had higher expression of VEGF and Angpt-2 than the slow-frozen ovarian tissues, but the difference was not statistically significant. Conclusion: Our results indicate that Angpt-2 may play an important role in ovarian tissue transplantation after cryopreservation although further studies are needed to understand its exact function.

Turbine Blading Performance Evaluation Using Geometry Scanning and Flowfield Prediction Tools

  • Zachos, Pavlos K.;Pappa, Maria;Kalfas, Anestis I.;Mansour, Gabriel;Tsiafis, Ioannis;Pilidis, Pericles;Ohyama, Hiroharu;Watanabe, Eiichiro
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2008.03a
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    • pp.89-96
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    • 2008
  • This paper investigates the effect of blade deformation, caused by manufacturing inaccuracies, on the performance of a 2-stage axial steam turbine. A high fidelity 3D coordinate Measurement Machine has been employed to obtain the exact geometrical model of the blades. A Streamline Curvature solver was used to predict the overall performance of the turbine. During the manufacturing process of the casts and of the blades themselves, several types of errors can occur which lead to a different geometry from that envisaged by the designer. The main objective of this study is to investigate the effect of those errors on the performance of a 2-stage experimental axial steam turbine. A high fidelity measurement of the actual geometry of both stator and rotor blades has been carried out, using a 3D Coordinate Measurement Machine. The cross sections of the blades obtained by the measurement were compared with those produced by the design process to evaluate the change in blade inlet/exit angles. In addition, the geometrical deviations from the initial design have been subjected to a statistical study in order to locate the nature of the error. The actual(measured) model has been used as input into a Streamline Curvature solver to evaluate its performance. Finally, a comparison with the performance plots of the original geometry has been carried out. A measurable change of efficiency as well as in the total power delivered by the turbine was found. This suggests that the accumulated error caused during the manufacturing procedure plays a significant role in the overall performance of the machine by making it less efficient by more than 1%. Reverse engineering techniques are proposed to predict and alleviate these errors leading thereby to a final design of each stage with improved performance.

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Broadband Processing of Conventional Marine Seismic Data Through Source and Receiver Deghosting in Frequency-Ray Parameter Domain (주파수-파선변수 영역에서 음원 및 수신기 고스트 제거를 통한 전통적인 해양 탄성파 자료의 광대역 자료처리)

  • Kim, Su-min;Koo, Nam-Hyung;Lee, Ho-Young
    • Geophysics and Geophysical Exploration
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    • v.19 no.4
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    • pp.220-227
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    • 2016
  • Marine seismic data have not only primary signals from subsurface but also ghost signals reflected from the sea surface. The ghost decreases temporal resolution of seismic data because it attenuates specific frequency components. For eliminating the ghost signals effectively, the exact ghost delaytimes and reflection coefficients are required. Because of undulation of the sea surface and vertical movements of airguns and streamers, the ghost delaytime varies spatially and randomly while acquiring seismic data. The reflection coefficient is a function of frequency, incidence angle of plane-wave and the sea state. In order to estimate the proper ghost delaytimes considering these characteristics, we compared the ghost delaytimes estimated with L-1 norm, L-2 norm and kurtosis of the deghosted trace and its autocorrelation on synthetic data. L-1 norm of autocorrelation showed a minimal error and the reflection coefficient was calculated using Kirchhoff approximation equation which can handle the effect of wave height. We applied the estimated ghost delaytimes and the calculated reflection coefficients to remove the source and receiver ghost effects. By removing ghost signals, we reconstructed the frequency components attenuated near the notch frequency and produced the migrated stack section with enhanced temporal resolution.

The Clinical Study of Tongue Change in Diabetes Mellitus Patients as Oriental Diagnostic Method (糖尿환자의 27例의 舌診에 關한 臨床 硏究)

  • Seo, Gan-soo;Kim, Dong-woung
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.12 no.2
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    • pp.212-221
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    • 1999
  • Tongue examination is the most unique and important diagnostic method of oriental medicine. It reveals patients condition and give some information about direction of therapy and background of disease as well as produces clue of duration of disease changing that grasps it from outside. The aims of this study show that results of tongue examination is related to somewhat special pattern. we study 27 patients(age of means: 63.01 years old, male: 14, female: 13) who come to Wonkwang University Oriental-Medicine Hospital at Chonju with diabetes mellitus or diabetes mellitus complications. Tongue colors of this study result in pale-red 8 cases, pale 6 cases, red 6 cases, crimson 5 cases, blue-green-purple 2 cases and tongue fur of this study result in white-fur 16 cases, yellow-fur 7 cases, black-fur 1 case, none-fur 3 cases. And the condition of tongue fur with grimy and thin result in thin-white-fur 12 cases, white-grimy-fur 4 cases, thin-yellow-fur 5 cases, grimy-yellow-fur 2 cases, black-fur 1 case. Means level of fasting glucose during 7 days was $223.24{\pm}32.l7mg/dl$ and postprandial 2hours was $286.37{\pm}24.54mg/dl$ There were no changes in tongue body and tongue color but changes occur in tongue fur with 9cases in this period. 5 cases of patient make a difference between FBS(fasting blood glucose) and postprandial blood glucose level more than l00mg/dl (2 cases of patient with thin-white-fur gradually turned to slight-yellow-fur. There were no changes in 2 cases of patient with crimson-none-fur and pale-white-fur. 1 case of patient with slimy-yellow-fur turned to black fur.) 11 cases of patient had lesser than $10\%$ hemoglobin $A_lC$ and tongue color of these patient were pale-red 5cases, pale 2 cases, red 2 cases, crimson 2 cases. 16 cases of patient had more than $10\%$ Hemoglobin $A_1C$ and tongue color of these patients were pale-red 3 cases, pale 4 cases, red 4 cases, crimson 3 cases, blue 2 cases. This result shows that quantity of Hemoglobin $A_1C$ make a somewhat role in tongue color. The above results show that tongue color, fur color, condition and change of fur in diabetes mellitus patients is various in pale-red, pale, crimson, none-fur. So it is difficult to give an exact diagnosis on pathology of diabetes mellitus only with tongue examination because there are a little matches between blood glucose level, prevalence-period, short-term blood glucose regulation and tongue and fur colors.

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CFD ANALYSIS OF TURBULENT JET BEHAVIOR INDUCED BY A STEAM JET DISCHARGED THROUGH A VERTICAL UPWARD SINGLE HOLE IN A SUBCOOLED WATER POOL

  • Kang, Hyung-Seok;Song, Chul-Hwa
    • Nuclear Engineering and Technology
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    • v.42 no.4
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    • pp.382-393
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    • 2010
  • Thermal mixing by steam jets in a pool is dominantly influenced by a turbulent water jet generated by the condensing steam jets, and the proper prediction of this turbulent jet behavior is critical for the pool mixing analysis. A turbulent jet flow induced by a steam jet discharged through a vertical upward single hole into a subcooled water pool was subjected to computational fluid dynamics (CFD) analysis. Based on the small-scale test data derived under a horizontal steam discharging condition, this analysis was performed to validate a CFD method of analysis previously developed for condensing jet-induced pool mixing phenomena. In previous validation work, the CFD results and the test data for a limited range of radial and axial directions were compared in terms of profiles of the turbulent jet velocity and temperature. Furthermore, the behavior of the turbulent jet induced by the steam jet through a horizontal single hole in a subcooled water pool failed to show the exact axisymmetric flow pattern with regards to an overall pool mixing, whereas the CFD analysis was done with an axisymmetric grid model. Therefore, another new small-scale test was conducted under a vertical upward steam discharging condition. The purpose of this test was to generate the velocity and temperature profiles of the turbulent jet by expanding the measurement ranges from the jet center to a location at about 5% of $U_m$ and 10 cm to 30 cm from the exit of the discharge nozzle. The results of the new CFD analysis show that the recommended CFD model of the high turbulent intensity of 40% for the turbulent jet and the fine mesh grid model can accurately predict the test results within an error rate of about 10%. In this work, the turbulent jet model, which is used to simply predict the temperature and velocity profiles along the axial and radial directions by means of the empirical correlations and Tollmien's theory was improved on the basis of the new test data. The results validate the CFD model of analysis. Furthermore, the turbulent jet model developed in this study can be used to analyze pool thermal mixing when an ellipsoidal steam jet is discharged under a high steam mass flux in a subcooled water pool.

Modified Empirical Formula of Dynamic Amplification Factor for Wind Turbine Installation Vessel (해상풍력발전기 설치선박의 수정 동적증폭계수 추정식)

  • Ma, Kuk-Yeol;Park, Joo-Shin;Lee, Dong-Hun;Seo, Jung-Kwan
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.27 no.6
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    • pp.846-855
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    • 2021
  • Eco-friendly and renewable energy sources are actively being researched in recent times, and of shore wind power generation requires advanced design technologies in terms of increasing the capacities of wind turbines and enlarging wind turbine installation vessels (WTIVs). The WTIV ensures that the hull is situated at a height that is not affected by waves. The most important part of the WTIV is the leg structure, which must respond dynamically according to the wave, current, and wind loads. In particular, the wave load is composed of irregular waves, and it is important to know the exact dynamic response. The dynamic response analysis uses a single degree of freedom (SDOF) method, which is a simplified approach, but it is limited owing to the consideration of random waves. Therefore, in industrial practice, the time-domain analysis of random waves is based on the multi degree of freedom (MDOF) method. Although the MDOF method provides high-precision results, its data convergence is sensitive and difficult to apply owing to design complexity. Therefore, a dynamic amplification factor (DAF) estimation formula is developed in this study to express the dynamic response characteristics of random waves through time-domain analysis based on different variables. It is confirmed that the calculation time can be shortened and accuracy enhanced compared to existing MDOF methods. The developed formula will be used in the initial design of WTIVs and similar structures.

The Study on Applicability of Manufactured Lead(II) Iodide Dosimeter for Dose Measurement in Brachytherapy (방사선근접치료 분야의 선량 측정을 위해 제조된 Lead(II) Iodide 선량계의 적용가능성 연구)

  • Yang, Seung-Woo;Han, Moo-Jae;Park, Sung-Kwang
    • Journal of the Korean Society of Radiology
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    • v.15 no.6
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    • pp.789-794
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    • 2021
  • Brachytherapy is a treatment in which radioactive isotopes are placed inside the body to intensively irradiate the tumor with radiation. Because brachytherapy uses a radioisotope source with a high dose rate, it is very important to know the exact location and dose of the source. However, in clinical practice, it is evaluated inaccurately with the naked eye through rulers and autoradiographs. Therefore, in this study, a dosimeter that can be used for brachytherapy was developed using a lead(II) iodide (PbI2) material, and the applicability was evaluated by analyzing the reproducibility, linearity, and PID items. As a result of reproducibility evaluation, the RSD value was 1.41%, satisfying the evaluation criteria of 1.5%. As a result of the linearity evaluation, the R2 value was 0.9993, which satisfies the evaluation criterion of 0.9990. As a result of PID evaluation, it showed only a difference of 0.06 cm compared with the theoretical value of the inverse square law of distance at the 50% dose reduction point. The dosimeter manufactured in this experiment shows results that satisfy the standard in all evaluations, so it is judged that the possibility of applying the dosimeter in the radiation brachytherapy area is sufficient.

Analyzing the Significance of T1 Slope minus Cervical Lordosis in Patients with Anterior Cervical Discectomy and Fusion Surgery

  • Lee, Ho Jin;You, Soon Tae;Sung, Jae Hoon;Kim, Il Sup;Hong, Jae Taek
    • Journal of Korean Neurosurgical Society
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    • v.64 no.6
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    • pp.913-921
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    • 2021
  • Objective : Accurate measurement of T1 slope (a component of T1s minus cervical lordosis [CL]) is often constrained by anatomical limitations. In this situation, efforts should be made to find the exact meaning of T1s-CL and whether there are any alternatives to it. Methods : We enrolled 117 patients who received two-level anterior cervical discectomy and fusion (ACDF). Occipital slope, C2 slope (C2s), C7 slope (C7s), T1, O-C2 angle (O-C2A), C2-7 angle (C2-7A), O-C7 angle (O-C7A), T1s-CL, C7-T1 angle (C7-T1A), and C2-7 sagittal vertical axis were measured. We determined 16° (T1s-CL) as the reference point for dividing subjects into the mismatch group and the balance group, and a comparative analysis was performed. Results : The mean value of C7-T1A was constantly maintained within 2.6° peri-operatively. In addition, C2s and T1s-CL showed the same absolute change (Δ|0.8|°). The mean values of T1s-CL of the mismatch and balance groups were 23.0° and 7.6°, respectively. The five factors with the largest differences between the two groups were as follows : C2s (Δ13.3°), T1s-CL (Δ15.4°), O-C2A (Δ8.7°), C2-7A (Δ14.7°), and segmental angle (Δ7.9°) before surgery. Only four factors showed statistically significant change between the two groups after ACDF : T1s-CL (Δ4.0° vs. Δ0.2°), C2s (Δ3.2° vs. Δ0.7°), O-C2A (Δ2.6° vs. Δ1.3°), C2-7A (Δ6.3° vs. Δ1.3°). A very strong correlation between T1s-CL and C2s was also found (r=|0.88-0.96|). Conclusion : C2s itself may be the essential key to represent T1s-CL. The amounts and directions of change of these two factors (T1s-CL and C2s) were also almost identical. The above phenomenon was re-confirmed once again through the correlation analysis.