• Title/Summary/Keyword: Agent Model

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Antitumor Responses of Adoptively-Transferred Tumor-Specific T-Cell Cultures in a Murine Lymphoma Model

  • Kim, Hee-Sue;Lee, Hee-Gu;Lim, Jong-Seok;Lee, Ki-Young;Kim, Jae-Wha;Chung, Kyeong-Soo;Choe, Yong-Kyung;Choe, In-Seong;Chung, Tai-Wha;Kim, Kil-Hyoun
    • BMB Reports
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    • v.28 no.6
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    • pp.556-561
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    • 1995
  • The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.

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Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells

  • Katagiri, Wataru;Kawai, Takamasa;Osugi, Masashi;Sugimura-Wakayama, Yukiko;Sakaguchi, Kohei;Kojima, Taku;Kobayashi, Tadaharu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.39
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    • pp.8.1-8.8
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    • 2017
  • Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

Framework for Designing Explanatory Style of Interactive Agents (상호작용형 에이전트의 설명 양식을 디자인하기 위한 프레임워크 개발)

  • Oh, Se-Jin;Woo, Woon-Tack
    • Journal of the Institute of Electronics Engineers of Korea CI
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    • v.45 no.5
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    • pp.63-73
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    • 2008
  • Recent years have seen an explosion of interest in interactive agents motivating human learners to engage in edutainment systems which are designed to be entertaining and educational at the same time. Especially, work on socio-emotional processes has focus on understanding of human's social behavior in training and entertainment a applications. In contrast with work on social emotion, where research groups have developed detailed models of emotional processes, models of personality have emphasized shallow surface behavior. Here, we build on computational appraisal models of emotion to better characterize dispositional differences in how people come to understand social situations. Known as explanatory style, this dispositional factor plays a key role in social interactions and certain socio-emotional disorders, such as depression. Building on appraisal and attribution theories, we model key conceptual variables underlying the explanatory style, and enable agents to exhibit different explanatory tendencies with respect to their personalities. Furthermore, we developed an interactive AR agent based on our framework and applied it into an interactive teaming system that allows participants to explore individual differences in the explanation of social events, with the goal of encouraging the development of perspective laking and emotion-regulatory skills.

A Personal Digital Library on a Distributed Mobile Multiagents Platform (분산 모바일 멀티에이전트 플랫폼을 이용한 사용자 기반 디지털 라이브러리 구축)

  • Cho Young Im
    • Journal of KIISE:Software and Applications
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    • v.31 no.12
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    • pp.1637-1648
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    • 2004
  • When digital libraries are developed by the traditional client/sever system using a single agent on the distributed environment, several problems occur. First, as the search method is one dimensional, the search results have little relationship to each other. Second, the results do not reflect the user's preference. Third, whenever a client connects to the server, users have to receive the certification. Therefore, the retrieval of documents is less efficient causing dissatisfaction with the system. I propose a new platform of mobile multiagents for a personal digital library to overcome these problems. To develop this new platform I combine the existing DECAF multiagents platform with the Voyager mobile ORB and propose a new negotiation algorithm and scheduling algorithm. Although there has been some research for a personal digital library, I believe there have been few studies on their integration and systemization. For searches of related information, the proposed platform could increase the relationship of search results by subdividing the related documents, which are classified by a supervised neural network. For the user's preference, as some modular clients are applied to a neural network, the search results are optimized. By combining a mobile and multiagents platform a new mobile, multiagents platform is developed in order to decrease a network burden. Furthermore, a new negotiation algorithm and a scheduling algorithm are activated for the effectiveness of PDS. The results of the simulation demonstrate that as the number of servers and agents are increased, the search time for PDS decreases while the degree of the user's satisfaction is four times greater than with the C/S model.

Repurposing Auranofin, an Anti-Rheumatic Gold Compound, to Treat Acne Vulgaris by Targeting the NLRP3 Inflammasome

  • Yang, Gabsik;Lee, Seon Joo;Kang, Han Chang;Cho, Yong-Yeon;Lee, Hye Suk;Zouboulis, Christos C.;Han, Sin-Hee;Ma, Kyung-Ho;Jang, Jae-Ki;Lee, Joo Young
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.437-442
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    • 2020
  • Activation of the NLRP3 inflammasome is critical for host defense as well as the progression of inflammatory diseases through the production of the proinflammatory cytokine IL-1β, which is cleaved by active caspase-1. It has been reported that overactivation of the NLRP3 inflammasome contributes to the development and pathology of acne vulgaris. Therefore, inhibiting activation of the NLRP3 inflammasome may provide a new therapeutic strategy for acne vulgaris. In this study, we investigated whether auranofin, an anti-rheumatoid arthritis agent, inhibited NLRP3 inflammasome activation, thereby effectively treating acne vulgaris. Auranofin suppressed NLRP3 inflammasome activation induced by Propionibacterium acnes, reducing the production of IL-1β in primary mouse macrophages and human sebocytes. In a P. acnes-induced acne mouse model, injection of P. acnes into the ears of mice induced acne symptoms such as redness, swelling, and neutrophil infiltration. Topical application of auranofin (0.5 or 1%) to mouse ears significantly reduced the inflammatory symptoms of acne vulgaris induced by P. acnes injection. Topical application of auranofin led to the downregulation of the NLRP3 inflammasome activated by P. acnes in mouse ear skin. These results show that auranofin inhibits the NLRP3 inflammasome, the activation of which is associated with acne symptoms. The results further suggest that topical application of auranofin could be a new therapeutic strategy for treating acne vulgaris by targeting the NLRP3 inflammasome.

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy (Adriamycin 유발 신병증에서 중간엽 줄기세포의 완화 효과)

  • Kang, Hee-Gyung;Park, So-Yeon;Ha, Il-Soo;Cheong, Hae-Il;Choi, Yong
    • Childhood Kidney Diseases
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    • v.14 no.1
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    • pp.32-41
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    • 2010
  • Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

Effects of Cyclophosphamide on Immunological Memory in Mice (Cyclophosphamide가 마우스의 면역기억에 미치는 영향)

  • Park, Young-Min;Park, Yoon-Kyu;Ahn, Woo-Sup;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.22 no.2
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    • pp.175-184
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    • 1987
  • The use of alkylating agent cyclophosphamide(CY), a widely used antitumor drug is well known as a potent immunosuppressant and has been used as a probe for investigating the functional capabilities of lymphocyte subsets of both T and B cells that play an important role in the regulation of the immune response. The present study was undertaken in an effort to assess the effects of CY on immunological memory in murine model. CY, given as a single dose of CY(250mg/kg) before sensitization with sheep red blood cells(SRBC) enhanced the primary response of Arthus and delayed-type hypersensitivity(DTH), as measured by footpad swelling reaction, but suppressed their tertiary DTH response. The similar CY pretreatment enhanced both the primary and tertiary hemagglutinin(HA) responses to SRBC, and the tertiary antibody response against polyvinylpyrroridone(PVP), a thymus-independent antigen but not the primary response against PVP. CY, given as a single dose of 250mg/kg 2 days before the primary immunization and two doses of 100mg/kg 2 days before the secondary and tertiary immunization, markedly suppressed the tertiary DTH and HA responses to SRBC. However, CY, given as small multiple daily doses(10mg/kg) over 4 days before sensitization but not after sensitization, enhanced the secondary HA response to SRBC. Contact sensitivity to dinitrofluorobenzene(DNFB) was suppressed by the drug, given either as a single large dose(300mg/kg) or as multiple dose(10mg/kg) administered 2 days before, together with or after DNFB sensitization. This suppression was more pronounced and more significant when CY was given as multiple dose. However, the enhancement of the secondary contact sensitivity to DNFB by CY was not clear-cut. The splenectomy appears to increase the enhancing effect of CY on contact sensitivity. These results suggest that CY selectively influences the immune response depending on the time of the drug administration relative to immunization and that the secondary or tertiary immune response involve memory cells with different susceptibilities to CY. Moreover, these results suggest that multiple low doses may sesectivley inhibit suppressor T cell proliferation involving DTH, HA or contact sensitivity without effecting helper T cells, but high doses presumably inhibit helper T cells and suppressor T cells with effecting B cells.

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Effect of Transglutaminase, Acorn, and Mungbean Powder on Quality Characteristics of Low-fat/salt Pork Model Sausages (Transglutaminase와 도토리 및 녹두 가루 첨가가 저지방/저염 돈육 모델소시지의 품질에 미치는 영향)

  • Lee, Hong-Chul;Chin, Koo-Bok
    • Food Science of Animal Resources
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    • v.29 no.3
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    • pp.374-381
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    • 2009
  • Low-fat pork sausages (LFPS) were prepared with 1% transglutaminase (TG) and 0.5% sodium caseinate (SC), and with or without different type of hydrocolloids (0.3%; acorn, AC or mungbean, MB) to evaluate the effects of these ingredients on the physicochemical and textural properties of LFPS with reduced salt. pH, moisture content (%) and lightness of low-fat/salt pork sausages (LFSPS) were affected by the addition of TG combined with SC (TG-SC) and acorn or mungbean powders affected the lightness and yellowness of LFSPS. However, cooking yield of LFSPS decreased, while textural properties were increased with the addition of TG-SC combination, which did not affect expressible moisture contents (%) of LFSPS. Both AC and MB tended to improve the cooking yield and water holding capacity of LFSPS, especially, MB rather than AC. However, these had no effect on the textural properties of LFSPS, except for textural chewiness. These results indicated that AC and MB powders could be used as a water binding agent in TG-SC combination of LFSPS.

Adsorption Features of Lead Ion on Waste Undaria pinnatifida (폐기된 해조류를 이용한 납 이온의 흡착 특성)

  • Seo Myung-Soon;Kim Dong-Su
    • Resources Recycling
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    • v.13 no.4
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    • pp.23-31
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    • 2004
  • Basic studies have been conducted regarding the attempt of the utilization of waste Undaria pinnatifida as an adsorbent for the adsorption treatment of lead-containing wastewater. Undaria pinnatifida was found to be chiefly composed of hyo-carbonaceous compounds and have a fairly high specific surface area, which suggesting the possibility of its application as a Potential adsorbent. The electrokinetic Potential of Undaria pinnatifida particles was observed to be negatively highest at around pH 8 and the fact that its electrokinetic potentials are negative at the whole pH range supported it might be an efficient adsorbent especially for cationic adsorbates. Under the experimental conditions, $Pb^{2+}$ was found to mostly adsorb onto Undaria pinnatifida within a few minutes and reach the equilibrium in adsorption within ca. 30 minutes. The adsorption of $Pb^{2+}$ was exothermic and explained well by e Freundlich model. Acidic pretreatment of Undaria pinnatifida enhanced its adsorption capacity for $Pb^{2+}$ , however, the reverse was observed for alkaline pretreatment. The formation of organometallic complex between $Pb^{2+}$ and some functional groups on the surface of Undaria pinnatifida was considered to be one of the main drives for adsorption. Finally the adsorbability of$ Pb^{2+}$ was examined to be rather affected by several solution features such as the coexistence of other adsorbate, the variation of ionic strength, and the concentration of complexing agent.

The Effects of Co-cultivation Medium and Culture Conditions on Rice Transformation Efficiency (공동배양과정의 배지조성과 배양조건이 벼 형질전환효율에 미치는 영향)

  • Kim, Yul-Ho;Park, Hyang-Mi;Choi, Man-Soo;Yun, Hong-Tai;Choi, Im-Soo;Shin, Dong-Bum;Kim, Chung-Kon;Lee, Jang-Yong
    • Korean Journal of Breeding Science
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    • v.41 no.3
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    • pp.252-260
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    • 2009
  • Rice is the most important cereal crop not only in supplying the basic staple food for more than half of the world's population but also as a model plant for functional genomic studies of monocotyledons. Although rice transformation method using A. tumefaciens has already been widely used to generate transgenic plants, the transformation rate is still low in most Korean elite cultivars. We made several modifications of the standard protocol especially in the co-cultivation step to improve the efficiency of the rice transformation. The co-culture medium was modified by the addition of three antioxidant compounds (10.5 mg/L L-cysteine, 1 mM sodium thiosulfate, 1 mM dithiothreitol) and of Agrobacterium growth-inhibiting agent (5 mg/L silver nitrate). Co-cultivation temperature ($23.5^{\circ}C$ for 1 day, $26.5^{\circ}C$ for 6 days) and duration (7 days) were also changed. The plasmid of pMJC-GB-GUS carrying the GUS reporter gene and the bar gene as the selectable marker was used to evaluate the efficiency of the transformation. After co-cultivation, a high level of GUS gene expression was observed in calli treated with the modified method. It is likely that those newly added compounds helped to minimize the damage due to oxidative bursts during plant cell-Agrobacterium interaction and to prevent necrosis of rice cells. And the transformation rate under the modified method was also remarkably increased approximately 8-fold in Heungnambyeo and 2-fold in Ilmibyeo as compared to the corresponding standard method. Furthermore, we could produce the transgenic plants stably from Ilpumbyeo which is a high-quality rice but its transformation rate is extremely low. Transformation and the copy number of transgenes were confirmed by PCR, bar strip and Southern blot analysis. The improved method would attribute reducing the effort and the time required to produce a large number of transgenic rice plants.