• Title/Summary/Keyword: Infiltration model

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In vivo multiplex gene targeting with Streptococcus pyogens and Campylobacter jejuni Cas9 for pancreatic cancer modeling in wild-type animal

  • Chang, Yoo Jin;Bae, Jihyeon;Zhao, Yang;Lee, Geonseong;Han, Jeongpil;Lee, Yoon Hoo;Koo, Ok Jae;Seo, Sunmin;Choi, Yang-Kyu;Yeom, Su Cheong
    • Journal of Veterinary Science
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    • v.21 no.2
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    • pp.26.1-26.14
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    • 2020
  • Pancreatic ductal adenocarcinoma is a lethal cancer type that is associated with multiple gene mutations in somatic cells. Genetically engineered mouse is hardly applicable for developing a pancreatic cancer model, and the xenograft model poses a limitation in the reflection of early stage pancreatic cancer. Thus, in vivo somatic cell gene engineering with clustered regularly interspaced short palindromic repeats is drawing increasing attention for generating an animal model of pancreatic cancer. In this study, we selected Kras, Trp53, Ink4a, Smad4, and Brca2 as target genes, and applied Campylobacter jejuni Cas9 (CjCas9) and Streptococcus pyogens Cas9 (SpCas9) for developing pancreatic cancer using adeno associated virus (AAV) transduction. After confirming multifocal and diffuse transduction of AAV2, we generated SpCas9 overexpression mice, which exhibited high double-strand DNA breakage (DSB) in target genes and pancreatic intraepithelial neoplasia (PanIN) lesions with two AAV transductions; however, wild-type (WT) mice with three AAV transductions did not develop PanIN. Furthermore, small-sized Cjcas9 was applied to WT mice with two AAV system, which, in addition, developed high extensive DSB and PanIN lesions. Histological changes and expression of cancer markers such as Ki67, cytokeratin, Mucin5a, alpha smooth muscle actin in duct and islet cells were observed. In addition, the study revealed several findings such as 1) multiple DSB potential of AAV-CjCas9, 2) peri-ductal lymphocyte infiltration, 3) multi-focal cancer marker expression, and 4) requirement of > 12 months for initiation of PanIN in AAV mediated targeting. In this study, we present a useful tool for in vivo cancer modeling that would be applicable for other disease models as well.

Prediction of Hydrodynamic Behavior of Unsaturated Ground Due to Hydrogen Gas Leakage in a Low-depth Underground Hydrogen Storage Facility (저심도 지중 수소저장시설에서의 수소가스 누출에 따른 불포화 지반의 수리-역학적 거동 예측 연구)

  • Go, Gyu-Hyun;Jeon, Jun-Seo;Kim, YoungSeok;Kim, Hee Won;Choi, Hyun-Jun
    • Journal of the Korean Geotechnical Society
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    • v.38 no.11
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    • pp.107-118
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    • 2022
  • The social need for stable hydrogen storage technologies that respond to the increasing demand for hydrogen energy is increasing. Among them, underground hydrogen storage is recognized as the most economical and reasonable storage method because of its vast hydrogen storage capacity. In Korea, low-depth hydrogen storage using artificial protective structures is being considered. Further, establishing corresponding safety standards and ground stability evaluation is becoming essential. This study evaluated the hydro-mechanical behavior of the ground during a hydrogen gas leak from a low-depth underground hydrogen storage facility through the HM coupled analysis model. The predictive reliability of the simulation model was verified through benchmark experiments. A parameter study was performed using a metamodel to analyze the sensitivity of factors affecting the surface uplift caused by the upward infiltration of high-pressure hydrogen gas. Accordingly, it was confirmed that the elastic modulus of the ground was the largest. The simulation results are considered to be valuable primary data for evaluating the complex analysis of hydrogen gas explosions as well as hydrogen gas leaks in the future.

Estimation of Water Quality Variation in Sewer Network using MOUSE TRAP Model (MOUSE TRAP 모델을 이용한 하수관거내 수질변화 예측)

  • Yang, Hae Jin;Jun, Hang Bae;Son, Dae Ik
    • Journal of Korean Society of Water and Wastewater
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    • v.23 no.6
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    • pp.743-752
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    • 2009
  • One of the major problems associated with operation of domestic sewer lines involves hydraulic problems such as insufficient conveyance capacity, exceeding maximum velocity, and deficiency of minimum velocity. It has also been pointed out that influent concentration lower than design concentration of pollutants, which is mainly caused by unidentified inflow and infiltration, degrades the operational efficiency of many sewage treatment plants (STPs). A computer-added analysis method supporting a coupled simulation of sewage quality and quantity is essentially required to evaluate the status of existing STPs and to improve their efficiency by a proper sewer rehabilitation work. In this study, dynamic water quality simulations were conducted using MOUSE TRAP to investigate the principal parameters that governs the changes of BOD, ${NH_4}^+$, and ${PO_4}^{3-}$3- concentrations within the sewer networks based on data acquired through on-site and laboratory measurements. The BOD, ${NH_4}^+$ and ${PO_4}^{3-}$3- concentrations estimated by MOUSE TRAP was lower than theoretical pollution loads because of sedimentation and decomposition in the sewer. The results revealed that sedimentation is a most important factor than other biological reactions in decreasing pollutant load in the sewers of C-city. The sensitivity analysis of parameters pertaining to water quality changes indicated that the effect of the BOD decay rate, the initial DO concentration, the half-saturation coefficient of dissolved BOD, and the initial sediment depth is marginal. However, the influence of settling rate and temperature is relatively high because sedimentation and precipitation, rather than biological degradation, are dominant processes that affect water quality in the study sewer systems.

Analysis of Fire Suppression Efficiency for Intermittent Water Spray Pattern by Fire Dynamics Simulator (FDS를 이용한 교번식 미분무방식의 소화 성능 분석)

  • Jee, Moon-Hak;Lee, Byung-Kon
    • Fire Science and Engineering
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    • v.22 no.3
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    • pp.216-220
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    • 2008
  • Water mist fire suppression system utilizes the fire suppression features such as cooling of fire source, dilution of ambient oxygen, and shielding of radiation heat with the evaporation of microscopic water droplets. The momentum of water mist is relatively lower than that of larger water droplet and the infiltration of water mist to the fire source is not effective. Contribution of evaporated water vapor is liable to decline to limited portion of fire source due to its light weight and sparse density. On the other hand, the cycling water mist pattern is expected to improve the penetration force of water mist as well as the air expelling capability with the stratified spray characteristics. At this paper, we present the analyzed fire suppression capability of intermittent water spray pattern by use of FDS which is computational fire dynamics fire model. We expect this analysis can support the basic concept to the development of the prototype of water mist nozzle.

Suppressive Effect of CYTG on Collagen Induced Arthritis(CIA) in DBA1/J Mice (CYTG 처방이 콜라겐 유발 관절염 모델에 미치는 효과)

  • Choi, Sung-Wook;Kim, Yong-Chan;Kim, Kyoung-Shin;Kim, Byoung-Soo;Lim, Jong-Soon;Kang, Jung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.62-69
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    • 2007
  • To evaluate effect of CYTG on inhibiting the occurrence of arthritis, we performed the experiments including production of inflammatory cytokine and immunoglobulin in collagen arthritis model. The results were obtained as fellows. CYTG group showed inhibitory effect on arthritis incidence than control group for four weeks. Arthritis index of CYTG group reduced compared with control group. In CYTG group, production of cytokines which show suppressive effect on inflammation(IL-2, COX-2) was increased and which promotes inflammation(IL-10) was decreases in spleen. In CYTG group, production of immunoglobulin (IgG-RF) was reduced compared with control, and rate of CD3+CD69+T cell is lower in lymph node and CD4+CD25+ T cell is higher in lymph node and spleen. And synovial infiltration in the knee were observed in the controls (PBS-treated mice), whereas CYTG-treated mice exhibited significantly reduced histologic evidence of destruction and inflammation. So, the histopathological scoring average of CYTG group was 2.5 compared with control group(CIA mice) 4.5. It was thought that our data express high effect via immune system specially through the controling the inflammatory cytokines and immunoglobulins. CYTG could be usefully applied for the prevention and treatment of RA, and also is expected to be clinically helpful on the treatment of RA through modification.

Development of Simplified Computer Program for the Design of Size and Culvert Outlet in Detention Pond (저류지의 규모 및 방류암거의 설계를 위한 간편프로그램 개발)

  • Lee, Jae Joon;Ahn, Jae Chan;Kim, Byung Il
    • Journal of Korea Water Resources Association
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    • v.47 no.7
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    • pp.587-598
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    • 2014
  • Recently runoff reduction facilities such as detention ponds were rarely used and limited primarily to cases. A specific installation criteria and method of design for runoff reduction facilities is insignificant in our country. Also it has difficult problems with quantification. A detention pond being installed at outfalls and generalized in our country is adopted as basic form with infiltration facilities because quantification index for runoff reduction facilities have not been developed. A processing of detention pond design has to determinate storage volume and outlet form is very complex and wasting human resources and time in the planning step. In this study, we have been unified FFC11-SimPOND being able to simply calculate size with simplified design method of culvert outlet and made a computing model (SimPOND-CO) for practical users.

Effects of Ephedra sinica (ES) Extract on the Ovalbumin-Induced Allergid Asthma in Mice (마황 추출물 투여가 Ovalbumin으로 유발된 마우스 알레르기성 천식에 미치는 영향)

  • Jo, Eun-Hee;Jo, Il-Joo;Park, Seong-Ju;Jo, So-Hyun;Park, Min-Cheol
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.27 no.3
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    • pp.84-95
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    • 2014
  • Objective : Ephedra sinica (ES) has has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of ES on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline(PBS) intraperitoneally on day 1 and 15. mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 h after the last challenge. we examined the lung histology, airway hyper sensitivity, total inflammatory cell count in bronchoaveloar lavage fluid(BALF), Th2-associated cytokines production and IgE production. Results : ES potently inhibited the lung damage and the development of Penh. ES also reduced the number of BAL cells during OVA-induced allergic asthma. Furthermore, ES inhibited cytokines production such as IL-4, IL-13 productions, and IgE level of serum. Conclusion : These results suggest that ES may inhibit the production of IL-4, IL-13, IgE and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

Effects of Glycyrrhiza uralensis Fisch (GUF) Extract on the Ovalbumin-Induced Allergid Asthma in Mice (감초 추출물 투여가 Ovalbumin으로 유발된 마우스 알레르기성 천식에 미치는 영향)

  • Jo, Eun-Hee;Jo, Il-Joo;Park, Seong-Ju;Jo, So-Hyun;Park, Min-Cheol
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.27 no.3
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    • pp.96-105
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    • 2014
  • Objective : Glycyrrhiza uralensis Fisch (GUF) has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of GUF on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline (PBS) intraperitoneally on day 1 and 15. Mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 hrs after the last challenge. We examined total inflammatory cell number in bronchoaveloar lavage fluid (BALF), Th2-associated cytokine productions and lung histology. Results : GUF potently inhibited the development of airway hypersensitivity and also reduced the number of BAL cells during OVA-induced allergic asthma. GUF also inhibited cytokine productions such as IL-4, IL-13 in lung tissue. Furthermore, GUF treatment inhibited allergic airway inflammation. Conclusion : These results suggest that GUF may inhibit the production of IL-4, IL-13 and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

IL-4 and IL-5 Secretions Predominate in the Airways of Wistar Rats Exposed to Toluene Diisocyanate Vapor

  • Kouadio, Kouame;Zheng, Kui-Cheng;Toure, Abdoulaye Abba;Dosso, Mireille;Todoriki, Hidemi
    • Journal of Preventive Medicine and Public Health
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    • v.47 no.1
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    • pp.57-63
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    • 2014
  • Objectives: We established a Wistar rat model of asthma caused by toluene diisocyanate (TDI) exposure, and investigated the relationship between TDI exposure concentrations and respiratory hypersensitivity, airway inflammation, and cytokine secretions in animals, to better understand the mechanism of TDI induced occupational asthma. Methods: Wistar rats were exposed to two different concentrations of TDI vapor four hours a day for five consecutive days. Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the BAL fluid were analyzed. Lung histopathological examination was carried out to investigate the inflammatory status in the airways. Production of cytokines interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined with enzyme-linked immunosorbent assay kits. Results: The TDI-exposed rats exhibited greater airway hypersensitivity symptoms than the control rats. The BAL differential cell count and lung histopathological examination demonstrated that inflammation reactions were present in both the central and peripheral airways, characterized with marked infiltration of eosinophils in the TDI-exposed rats. The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the BAL fluid in vivo. Conclusions: These findings imply that TDI exposure concentrations may greatly affect the occurrence and extent of inflammatory events and that Th2 type cytokines may play an important role in the immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.

Paclitaxel Coating Inhibits Inflammation Surrounding Subcutaneously Implanted Expanded Polytetrafluoroethylene (ePTFE) Hemodialysis Grafts in Rabbit Model

  • Baek, In-Su;Lee, Yu-Ji;Park, Soo-Jin;Bai, Cheng Zhe;Park, Jong-Sang;Kim, Dae-Joong
    • Bulletin of the Korean Chemical Society
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    • v.31 no.2
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    • pp.281-285
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    • 2010
  • Hemodialysis vascular access dysfunction (HVAD) due to the aggressive development of venous neointimal hyperplasia remains a major complication for patients with synthetic arteriovenous grafts. Paclitaxel-coated expanded polytetrafluoroethylene (ePTFE) grafts effectively prevent neointimal hyperplasia and stenosis. However, perigraft inflammation or edema can be another complication of ePTFE grafts, preventing early cannulation. Three different types of ePTFE grafts, including grafts without paclitaxel coating (control group, n = 12), grafts with paclitaxel coating at a dose density of $0.61ug/mm^2$ (low concentration group, n = 12), and grafts with paclitaxel coating at a dose density of $1.15ug/mm^2$ (high concentration group, n = 12) were placed in the backs of 12 rabbits, simultaneously. Six rabbits were euthanized after one week and the remaining six were euthanized two weeks after implantation. Perigraft inflammation, graft wall inflammation, stromal cell proliferation, blood vessel formation, tissue necrosis and edema were analyzed for the grafts in each animal. Inflammation surrounding the paclitaxel-coated grafts was significantly reduced compared to the control group. Stromal cell layers were detected at the interface between the graft and the surrounding tissue in the control group, infiltrated into the graft interstices, and differentiated into myofibroblasts for graft healing. Paclitaxel-coated grafts inhibited stromal cell proliferation and infiltration into the graft wall. Tissue necrosis and edema were not detected in either of the paclitaxel-coated graft groups.