• 제목/요약/키워드: Mechanistic model

검색결과 178건 처리시간 0.026초

지하 처분장에서의 방사성폐기물 고화체의 용출 및 용해에 대한 수학적 모형 분석 (Mathematical Modeling for Leaching and dissolution of Solidified Radioactive Waste in a Geologic Reposiory)

  • Kim, Chang-Lak;Park, Kwang-Sub;Cho, Chan-Hee;Kim, Jhinwung;Suh, In-Suk
    • Nuclear Engineering and Technology
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    • 제20권2호
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    • pp.120-131
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    • 1988
  • 지중매몰된 방사성핵종들이 지하수계를 통해 이동을 하는 Source를 수학적으로 표시하는 Source Term 모형이 필요하다. 물질전달식 또는 측정식에 근거한 여러 Source Term 모형을 비교 분석하였다. 일반적으로 용출 또는 용해에는 (1) 화학반응, (2) 확산 등에 의한 물질이동의 두 가지 작용이 관여한다. 화학반응은 고화체가 지하수에 노출된 후 초기의 짧은 기간 동안에만 용해율을 조절한다. 외부로의 물질전달율이 지하 처분장에서 방사성폐기물 고화체로부터의 장기간에 걸친 핵종유출율을 조절하는 역할을 한다. 물질전단 이론을 적용 할 때는, 필요로 하는 물질이동 현상을 기술할 수 있는 식을 선택해야 한다. 적절히 사용했을 경우, 물질전달 이론에 입각한 Source Term 모형은 핵종유출율의 신뢰할 만한 예측을 위한 귀중한 도구이다.

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Non-Ionic Surfactants Antagonize Toxicity of Potential Phenolic Endocrine-Disrupting Chemicals, Including Triclosan in Caenorhabditis elegans

  • Alfhili, Mohammad A.;Yoon, Dong Suk;Faten, Taki A.;Francis, Jocelyn A.;Cha, Dong Seok;Zhang, Baohong;Pan, Xiaoping;Lee, Myon-Hee
    • Molecules and Cells
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    • 제41권12호
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    • pp.1052-1060
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    • 2018
  • Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.

Integrative Omics Reveals Metabolic and Transcriptomic Alteration of Nonalcoholic Fatty Liver Disease in Catalase Knockout Mice

  • Na, Jinhyuk;Choi, Soo An;Khan, Adnan;Huh, Joo Young;Piao, Lingjuan;Hwang, Inah;Ha, Hunjoo;Park, Youngja H
    • Biomolecules & Therapeutics
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    • 제27권2호
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    • pp.134-144
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    • 2019
  • The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

A novel mechanism of Korean Red Ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

  • Min, Ji-Hyun;Cho, Hui-Jin;Yi, Young-Su
    • Journal of Ginseng Research
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    • 제46권5호
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    • pp.675-682
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    • 2022
  • Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

물-공기 수평 성층류 유동조건에서 액적이탈 현상에 대한 실험연구 (Experimental Investigation on the Droplet Entrainment in the Air-Water Horizontal Stratified Flow)

  • 배병건;윤병조;김경두;배병언
    • 에너지공학
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    • 제24권1호
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    • pp.114-122
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    • 2015
  • 수평 성층류 2상 유동에서 기체의 속도가 액체의 속도보다 상대적으로 큰 고유속 유동조건에서는 불규칙한 파형들이 생성되고 이때 상 경계면에서는 액적이탈이 발생한다. 한국원자력연구원(KAERI)에서는 이러한 상 경계면에서의 액적이탈 현상을 기구학적으로 예측하기 위하여 전단력, 표면장력, 그리고 중력 항으로 구성되는 새로운 액적이탈 모델을 제시하였다. 그러나 이 액적이탈 모델 내부에는 아직 결정되지 않은 모델 계수가 존재한다. 모델 계수를 결정하기 위해서는 두 상 사이의 계면파 특성과 관련되는 물리변수들에 대한 실험데이터의 확보가 필요하다. 주요 물리변수들에는 파의 기울기, 파의 빗변길이, 파의 속도, 파의 주파수, 그리고 파장이 있다. 본 연구에서는 계면파 특성과 관련된 주요 물리변수들을 측정하기 위하여 폭 40 mm, 높이 50 mm, 길이 4.2 m의 수평사각유로에서 가시화실험을 수행하였다. 실험은 1기압의 물-공기 성층류 유동에서 액적이탈이 발생되는 조건에서 수행되었다. 본 실험에서 계면 형상을 2차원적으로 가시화하고 계면파에서 국소적인 물속도 분포를 측정하기 위하여 유로 측면에서 PIV기법을 적용하였다. 추가적으로, 가시화실험을 통해 획득한 계면 이미지로부터 측정된 계면 높이를 검증하기 위하여 평행 와이어 전도도 센서를 개발하였다. 가시화방법과 센서를 통해 측정된 수위를 비교한 결과, 두 가지 방법론에 의해 측정된 수위결과가 잘 일치함을 확인하였다. 최종적으로 개발된 측정기법을 적용하여 액적이탈 조건에서 계면파 특성과 관련된 주요 물리변수들을 측정하였다.

중엽세포의 체적 및 표면적과 콩잎의 광합성 능력간 관계 (Leaf Photosynthesis as Influenced by Mesophyll Cell Volume and Surface Area in Chamber-Grown Soybean (Glycine max) Leaves)

  • Jin Il, Yun;S. Elwynn, Taylor
    • 한국작물학회지
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    • 제33권4호
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    • pp.353-359
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    • 1988
  • 두께가 서로 다른 $C_3$ 식물의 잎은 단위엽면적당 광합성 능력에 있어서도 차이가 나는 바 잎의 내부구조와 기체교환 사이의 관계를 바탕으로 그 원인을 구명하였다. 광합성의 2대 제한요인으로 기체확산과 생화학적 과정의 상대적인 중요도를 결정하기 위해 중엽세포의 표면은 기체확산 저항의, 그리고 세포의 체적은 탄소고정 능력의 지표로 가정하였다. 즉 세포의 표면적이 증가하면 이산화탄소의 액상확산 저항이 감소하며 체적이 증대되면 carboxylation, oxygenation, 그리고 dark respiration 반응속도가 증가한다고 간주하였다. 이러한 개념을 함축하는 광합성 모형을 작성하고 이 가설의 검증을 위해 대두 품종 Amsoy잎을 이용한 실험을 수행하였다. 생장조절실내에서 200, 400, 600$\mu$mol photons m$^{-2}$ s$^{-1}$ PAR을 공급하여 서로 다른 두께의 잎을 준비하였으며 제3 및 4본엽에 대해 1,000 $\mu$mol photons m$^{-2}$ s$^{-1}$ PAR 및 28 기온 환경하에서 이산화탄소 흡수속도를 측정한 결과 세포의 체적과 표면적의 영향을 동시에 고려한 광합성 모형이 세포 표면적만을 고려한 경우 보다 실측치에 가까운 예측치를 산출하였다. 이로 미루어 세포의 표면적과 체적은 잎의 두께 및 그에 따른 광합성 능력의 예측에 적절한 변수로 간주된다.

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Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways

  • Kwon, Yujin;Cho, Su-Yeon;Kwon, Jaeyoung;Hwang, Min;Hwang, Hoseong;Kang, Yoon Jin;Lee, Hyeon-Seong;Kim, Jiyoon;Kim, Won Kyu
    • BMB Reports
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    • 제55권6호
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    • pp.275-280
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    • 2022
  • The treatment of atopic dermatitis (AD) is challenging due to its complex etiology. From epidermal disruption to chronic inflammation, various cells and inflammatory pathways contribute to the progression of AD. As with immunosuppressants, general inhibition of inflammatory pathways can be effective, but this approach is not suitable for long-term treatment due to its side effects. This study aimed to identify a plant extract (PE) with anti-inflammatory effects on multiple cell types involved in AD development and provide relevant mechanistic evidence. Degranulation was measured in RBL-2H3 cells to screen 30 PEs native to South Korea. To investigate the anti-inflammatory effects of Parasenecio auriculatus var. matsumurana Nakai extract (PAE) in AD, production of cytokines and nitric oxide, activation status of FcεRI and TLR4 signaling, cell-cell junction, and cell viability were evaluated using qRT-PCR, western blotting, confocal microscopy, Griess system, and an MTT assay in RBL-2H3, HEK293, RAW264.7, and HaCaT cells. For in vivo experiments, a DNCBinduced AD mouse model was constructed, and hematoxylin and eosin, periodic acid-Schiff, toluidine blue, and F4/80-staining were performed. The chemical constituents of PAE were analyzed by HPLC-MS. By measuring the anti-degranulation effects of 30 PEs in RBL-2H3 cells, we found that Paeonia lactiflora Pall., PA, and Rehmannia glutinosa (Gaertn.) Libosch. ex Steud. show an inhibitory activity of more than 50%. Of these, PAE most dramatically and consistently suppressed cytokine expression, including IL-4, IL-9, IL-13, and TNF-α. PAE potently inhibited FcεRI signaling, which mechanistically supports its basophil-stabilizing effects, and PAE downregulated cytokines and NO production in macrophages via perturbation of toll-like receptor signaling. Moreover, PAE suppressed cytokine production in keratinocytes and upregulated the expression of tight junction molecules ZO-1 and occludin. In a DNCB-induced AD mouse model, the topical application of PAE significantly improved atopic index scores, immune cell infiltration, cytokine expression, abnormal activation of signaling molecules in FcεRI and TLR signaling, and damaged skin structure compared with dexamethasone. The anti-inflammatory effect of PAE was mainly due to integerrimine. Our findings suggest that PAE could potently inhibit multi-inflammatory cells involved in AD development, synergistically block the propagation of inflammatory responses, and thus alleviate AD symptoms.

현장 계측자료를 이용한 아스팔트 포장체 온도 예측 연구 (A Study on the Temperature Prediction for Asphalt Pavement Using Field Monitoring Data)

  • 안덕순;박희문;엄병식;김제원
    • 대한토목학회논문집
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    • 제26권1D호
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    • pp.67-72
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    • 2006
  • 아스팔트 포장체내의 온도예측은 역학적-경험적 포장설계법에서 포장의 거동해석 및 공용성 예측시 매우 중요한 요소 중에 하나다. 본 연구에서는 현장 온도 계측자료를 이용하여 아스팔트 포장체의 시간별, 깊이별 온도예측에 관한 연구를 수행하였다. 이를 위해 전국의 대표 지점을 선정하여 깊이별로 온도계측 센서를 매설하고 주기적으로 대기, 포장표면 및 내부온도를 계측하였으며, 이 현장 자료를 이용하여 개발된 온도 예측 모델의 보정을 수행하였다. 보정된 온도예측 모델을 이용하여 포장체의 표면 및 중간깊이의 온도를 예측한 후에 현장 계측자료와 비교분석하였다. 본 연구의 결과, 온도예측 모델에 필요한 계수값 중 가을철의 경우 태양흡수율과 방사율(emissivity) 값이 다른 계절과 다르게 나타났다. 아스팔트 포장체 중간 깊이에서의 예측과 실측 온도차는 ${\pm}3^{\circ}C$내이며, 온도 예측 모델이 현장 온도를 정확히 예측할 수 있음을 입증하였다. 또한, 온도예측에 있어서 지역별 특성의 영향은 받지 않는 것으로 증명되었다.

Targeting the epitope spreader Pep19 by naïve human CD45RA+ regulatory T cells dictates a distinct suppressive T cell fate in a novel form of immunotherapy

  • Kim, Hyun-Joo;Cha, Gil Sun;Joo, Ji-Young;Lee, Juyoun;Kim, Sung-Jo;Lee, Jeongae;Park, So Youn;Choi, Jeomil
    • Journal of Periodontal and Implant Science
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    • 제47권5호
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    • pp.292-311
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    • 2017
  • Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

유해 무기질의 자연정화 : 지화학적 고찰 (NATURAL ATTENUATION OF HAZARDOUS INORGANIC COMPONENTS: GEOCHEMISTRY PROSPECTIVE)

  • Lee, Suk-Young;Lee, Chae-Young;Yun, Jun-Ki
    • 대한자원환경지질학회:학술대회논문집
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    • 대한자원환경지질학회 2002년도 제18차 공동학술강연회 자연저감고 지질학 (대한 자원 환경지질학회)
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    • pp.81-100
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    • 2002
  • While most of regulatory communities in abroad recognize ' 'natural attenuation " to include degradation, dispersion, dilution, sorption (including precipitation and transformation), and volatilization as governing Processes, regulators prefer "degradation" because this mechanism destroys the contaminant of concern. Unfortunately, true degradation only applies to organic contaminants and short- lived radionuclides, and leaves most metals and long-lived radionuclides. The natural attenuation Processes may reduce the potential risk Posed by site contaminants in three ways: (i)contaminants could be converted to a less toxic form througy destructive processes such as biodegradation or abiotic transformations; (ii) potential exposure levels may be reduced by lowering concentrations (dilution and dispersion); and (iii) contaminant mobility and bioavailability may be reduced by sorption to geomedia. In this review, authors will focus will focul on "sorption" among the natural attenuation processes of hazardous inorganic contaminants including radionuclides. Note though that sorption and transformation processes of inorganic contaminants in the natural setting could be influenced by biotic activities but our discussion would limit only to geochemical reactions involved in the natural attenuation. All of the geochemical reactions have been studied in-depth by numerous researchers for many years to understand "retardation" process of contaminants in the geomedia. The most common approach for estimating retardation is the determination of distrubution coefficiendts ($K_{d}$) of contaminants using parametric or mechanistic models. As typocally used in fate and contaminant transport calculations such as predictive models of the natural attenuation, the $K_{d}$ is defined as the ratio of the contaminant concentration in the surrounding aqueous solution when the system is at equilibrium. Unfortunately, generic or default $K_{d}$ values can result in significant error when used to predict contaminant migration rate and to select a site remediation alternative. Thus, to input the best $K_{d}$ value in the contaminant transport model, it is essential that important geochemical processes affecting the transport should be identified and understood. Precipitation/dissolution and adsorption/desorption are considered the most important geochemical processes affecting the interaction of inorganic and radionuclide contaminants with geomedia at the near and far field, respectively. Most of contaminants to be discussed in this presentation are relatively immobile, i.e., have very high $K_{d}$ values under natural geochemical environments. Unfortunately, the obvious containment in a source area may not be good enough to qualify as monitored natural attenuation site unless owner demonstrate the efficacy if institutional controls that were put in place to protect potential receptors. In this view, natural attenuation as a remedial alternative for some of sites contaminated by hazardous-inorganic components is regulatory and public acceptance issues rather than scientific issue.

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