• Title/Summary/Keyword: VE Model

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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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    • v.47 no.5
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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.

CD4+CD25+ Regulatory T Cells Selectively Diminish Systemic Autoreactivity in Arthritic K/BxN Mice

  • Kang, Sang Mee;Jang, Eunkyeong;Paik, Doo-Jin;Jang, Young-Ju;Youn, Jeehee
    • Molecules and Cells
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    • v.25 no.1
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    • pp.64-69
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    • 2008
  • Although the arthritis symptoms observed in the K/BxN model have been shown to be dependent on the functions of T and B cells specific to the self antigen glucose-6-phosphate isomerase, less is known about the in vivo roles of $CD4^{+}CD25^{+}$ regulatory T($T_{reg}$) cells in the pathology of K/BxN mice. We determined the quantitative and functional characteristics of the $T_{reg}$ cells in K/BxN mice. These mice contained a higher percentage of $Foxp3^+\;T_{reg}$ cells among the $CD4^+$ T cells than their BxN littermates. These $T_{reg}$ cells were anergic and efficiently suppressed the proliferation of $na\ddot{i}ve$ $CD4^+$ T cells and cytokine production by effector $CD4^+$ T cells in vitro. Antibody-mediated depletion of $CD25^+$ cells caused K/BxN mice to develop multi-organ inflammation and autoantibody production, while the symptoms of arthritis were not affected. These results demonstrate that despite the inability of the $T_{reg}$ cells to suppress arthritis development, they play a critical role protecting the arthritic mice from systemic expansion of autoimmunity.

Efficient Estimation of the Mean for Populations with a Linear Trend : An Extension of Systematic Sampling (선형추세를 갖는 모집단에 대한 효율적인 모평균 추정 : 계통추출의 확장)

  • 김혁주;석은양
    • The Korean Journal of Applied Statistics
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    • v.13 no.2
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    • pp.457-476
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    • 2000
  • In this study, we have proposed a sampling method and an estimation method for efficiently estimating the mean of a population which has a linear trend. These methods involve drawing a sample by the so-called "centered balanced systematic sampling", which is an extension of systematic sampling, and then estimating the population mean with an adjusted estimator, not with the sample mean itself. We used the concept of interpolation in determining the adjusted estimator.\Ve compared the efficiency of the proposed estimator with those of the estimators from existing methods, under the expected mean square error criterion based on the infinite superpopulation model introduced by Cochran(1946). The proposed method is for use in the case when the sample size n(2 5) is an odd number and k(the reciprocal of the sampling fraction) is an even number. A good result was also obtained in an example using computer simulation. simulation.

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Blockade of Trigeminal Glutamate Recycling Produces Anti-allodynic Effects in Rats with Inflammatory and Neuropathic Pain

  • Yang, Kui-Ye;Lee, Min-Kyung;Park, Min-Kyoung;Son, Jo-Young;Ju, Jin-Sook;Ahn, Dong-Kuk
    • International Journal of Oral Biology
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    • v.42 no.3
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    • pp.129-135
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    • 2017
  • The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-$1{\beta}$-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-$1{\beta}$ (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-${\beta}$-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-$1{\beta}$-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-$1{\beta}$ or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in na?ve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

Numerical Simulation on the Spreading and Heat Transfer of Ex-Vessel Core Melt in a Channel (전산해석을 이용한 원자로 노심 용융물의 노외 거동 및 열전달 특성 분석)

  • Ye, In-Soo;Ryu, Chang-Kook;Ha, Kwang-Soon;Song, Jin-Ho
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.35 no.4
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    • pp.425-429
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    • 2011
  • In the unlikely of nuclear reactor meltdown, the leaked core melt or corium must be contained in a device called core-catcher so that the corium can be cooled and stabilized. The ex-vessel behavior of corium involves complex physical and chemical mechanisms of flow propagation, heat transfer, and reactions with sacrificial substrates. In this study, the detailed characteristics of corium flow and heat transfer were investigated by using a commercial CFD code for VULCANO VE-U7 test reported in the literature. The volume-of-fluid (VOF) model was used to predict the interfacial surface formation of corium and the surrounding air, and the discrete ordinate model was adopted to calculate radiation between corium and the surroundings. It was found that cooling via radiation through the top surface of corium had a dominant effect on the temperature and viscosity profiles at the front of the corium flow.

A Study on Predictive Modeling of Public Data: Survival of Fried Chicken Restaurants in Seoul (서울 치킨집 폐업 예측 모형 개발 연구)

  • Bang, Junah;Son, Kwangmin;Lee, So Jung Ashley;Lee, Hyeongeun;Jo, Subin
    • The Journal of Bigdata
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    • v.3 no.2
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    • pp.35-49
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    • 2018
  • It seems unrealistic to say that fried chicken, often known as the American soul food, has one of the biggest markets in South Korea. Yet, South Korea owns more numbers of fried chicken restaurants than those of McDonald's franchise globally[4]. Needless to say not all these fast-food commerce survive in such small country. In this study, we propose a predictive model that could potentially help one's decision whilst deciding to open a store. We've extracted all fried chicken restaurants registered at the Korean Ministry of the Interior and Safety, then collected a number of features that seem relevant to a store's closure. After comparing the results of different algorithms, we conclude that in order to best predict a store's survival is FDA(Flexible Discriminant Analysis). While Neural Network showed the highest prediction rate, FDA showed better balanced performance considering sensitivity and specificity.

A Causality Analysis of the Prices between Imported Fisheries and Domestic Fisheries in Distribution Channel (수입 수산물과 국내산 수산물의 가격간 유통단계별 인과성 분석 : 명태, 갈치, 조기 냉동품을 대상으로)

  • Cha, Young-Gi;Kim, Ki-Soo
    • The Journal of Fisheries Business Administration
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    • v.40 no.2
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    • pp.105-126
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    • 2009
  • This study applies the cointegration theory to analyse the causality of the prices between imported fisheries and domestic fisheries in distribution channel. We've focused on the prices of import, wholesale and retail about the frozen Alaska pollack, hairtail and croaker which take up high portion and are popular among most of the consumers. In process of analysis, the unit root test was adopted to find the stability of time series data prior to the cointegration test. If the time series data was found as stable one in unit root test, we should analyse the VAR model. If unstable, the cointegratioin test was adopeted to find the long-run equilibrium relationship between the data. When the long-run equilibrium relationship was found among the price of the import, wholesale and retail price, the VECM model was adoped. If not, the differenced VAR model was adopted. The main findings of this study could be summarized as follows ; First, according to the result of the analysis on VAR model, time series data of frozen Alaska pollack was found as stable and has causality relationship and close effect was existing among the import, wholesale and retail price. Second, the data of frozen hairtail was found as an unstable one in unit root test and the result of cointegration test showed the long-run equilibrium relationship at lag 1. From the results of VECM model, we could find that the coefficient of error correction is effective, and the sign is negative(-). It means that the existence of adjustment tendency to long-run equilibrium after a short-run deviation. But the short-run causality of the prices were not found except the price of wholesale. Third, according to the results of differenced VAR model, data from frozen croaker did not have the stability and long-run equilibrium. Moreover, it was found that the import price has a weak causality on the retail price. Because of having difficulties in collecting data, the result of this paper could not explain the relationship among the prices of import, wholesale and retail perfectly. However, it more or less contributed to a long-lasted debate on the direction of causality of price-setting in academic research and provided a useful guide for the policy makers in charge of the price-setting of fisheries products as well.

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Beneficial Effects of Herbal Mixture (JAUN-1) on 0.1% Iodoacetamide-induced Gastritis Rat Model (0.1% Iodoacetamide에 의해 유도된 흰쥐 위염 모델에서 한약처방(JAUN-1)의 유익한 효능규명)

  • Han, Kyung-Ju;Koo, Sung-Tae;Hwang, Hye-Suk;Kim, Yu-Sung;Lee, Ji-Eun;Ko, Mi-Mi;Jung, Bong-Yeon;Choi, Sun-Mi
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.6
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    • pp.1549-1554
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    • 2007
  • To verify the effects of JAUN-1, which is a water-extracted herbal mixture, on gastroenteric disorders induced by 0.1 percent of iodoacetamide (IA) in rats. We divided four groups, $Na{\"{\i}}ve$ + Distilled Water (DW), 0.1% IA + DW, 0.1% IA + Proton pump inhibitor (Lansoprazole, 5 mg/kg) and 0.1% IA + Herbal mixture (JAUN-1, 50mg/kg) and performed following experimental methods to confirm its advantageous effects against ulcerogenic stomach in rats induced by 0.1% IA; cell cytotoxicity, analysis of lesions score, Hematoxylin & Eosin (H&E) stain, RT-PCR for ${\beta}-actin$, COX-1 and COX-2 and evaluation of intestinal prokinetic activity. No cytotoxicity was elucidated at the concentration of 1, 5, 10, 50, 100, $500\;{\mu}g/ml$ and 1mg/ml JAUN-1 through MTT Assay using by human stomach epithelial AGS cells, respectively. In addition, the JAUN-1 treated group and the lansoprazole treated group significantly decreased in lesions score compared to the DW treated group in the gastritis induced rat model, and results of immunohistochemistry by H&E staining showed that histological recovery in Proton Pump Inhibitor (PPI) and JAUN-1 treated groups rather than the DW administrated group. Another outcome was that ${\beta}-actin$ relative COX-2 expression level was significantly promoted in the DW treated group while ${\beta}-actin$ relative COX-1 expression level was no meaningful change in this rat model. Finally, intestinal prokinetic activity was recovered from low level of prokinetic activity due to 0.1% IA induced gastritis to the similar level of Normal group. These results suggested that JAUN-1 may have beneficial effects against 0.1% IA-induced gastritis rat model through decreasing lesions score, histological recovery, ${\beta}-actin$ relative COX-1, 2 expression level and prokinetic activity.

BUILDING INFORMATION MODELING (BIM)-BASED DESIGN OF ENERGY EFFICIENT BUILDINGS

  • Cho, Chung-Suk;Chen, Don;Woo, Sungkwon
    • Journal of KIBIM
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    • v.2 no.1
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    • pp.1-6
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    • 2012
  • With the increased awareness of energy consumption as well as the environmental impact of building operations, architects, designers and planners are required to place more consideration on sustainability and energy performance of the building. To ensure most of those considerations are reflected in the building performance, critical design decisions should be made by key stakeholders early during the design development stage. The application of BIM during building energy simulations has profoundly improved the energy analysis process and thus this approach has gained momentum. However, despite rapid advances in BIM-based processes, the question still remains how ordinary building stakeholders can perform energy performance analysis, which has previously been conducted predominantly by professionals, to maximize energy efficient building performance. To address this issue, we identified two leading building performance analysis software programs, Energy Plus and IES (IES ), and compared their effectiveness and suitability as BIM-based energy simulation tools. To facilitate this study, we examined a case study on Building Performance Model (BPM) of a single story building with one door, multiple windows on each wall, a slab and a roof. We focused particularly on building energy performance by differing building orientation and window sizes and compared how effectively these two software programs analyzed the performance. We also looked at typical decision-making processes implementing building energy simulation program during the early design stages in the U.S. Finally, conclusions were drawn as to how to conduct BIM-based building energy performance evaluations more efficiently. Suggestions for further avenues of research are also made.

Evaluation of inelastic performance of moment resisting steel frames designed by resizing algorithms (재분배 기법 적용에 따른 모멘트 저항골조의 비선형 특성 평가)

  • Seo, Ji Hyun;Kwon, Bong kwon;Park, Hyo Seon
    • Journal of Korean Society of Steel Construction
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    • v.18 no.3
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    • pp.361-371
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    • 2006
  • In recent years, to overcome drawbacks related to the aplicati on of classical structural optimization algorithms, various drift design methods based on factores of member displacement participation factors have been developed to size members if they satisfy stiffness criteria. In particular, a resizing algorithm based on dynamic displacement participation factors from the response spectrum analysis has been applied in the drift design of steel structures subjec ted to seismic lateral forces. In this aproach, active members are selected for displacement control based on the displacement participation fa ve members may be taken out and added to the active members for the drift control. The resizing algorithm can be practically and effectively applied to drift design of high-rise buildings however, the inelastic behavior o f the resizing algorithm has not ben evaluated yet. To develop the resizing algorithm considering the performance of nonlinearity as well a s elastic stifness, the evaluation model of resizing algorithm s is developed and aplied to the examples of moment-resisting steel frame, which is one of the simplest structural systems. The inelastic behavior of moment-resisting steel frame designed by the resizing algorithm is also discussed.