• 제목/요약/키워드: N ligand

검색결과 560건 처리시간 0.025초

골수유래줄기세포에서 분화된 골유사세포에서 ${\beta}-TCP$와 rhBMP-2의 골형성 효과에 관한 연구 (THE EFFECTS OF ${\beta}-TCP$/rhBMP-2 ON BONE FORMATION IN OSTEOBLAST-LIKE CELLS INDUCED FROM BONE MARROW-DERIVED MESENCHYMAL STEM CELLS)

  • 최용수;황경균;이재선;박창주;심광섭
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제34권4호
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    • pp.419-427
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    • 2008
  • The present study aimed to investigate the osteogenic potentials of differentiated osteoblast-like cells (DOCs) induced from bone marrow-derived mesenchymal stem cells (MSCs) on ${\beta}-tricalcium$ phosphate (${\beta}-TCP$) with recombinant human bone morphogenetic protein (rhBMP-2) in vitro. Osteoblast differentiation was induced in confluent cultures by adding 100 nM dexamethasone, 10 mM ${\beta}$-glycerophosphate, 50 mM L-ascorbic acid. The Alizarin red S staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were perfomed to examine the mRNA expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), receptor activator for nuclear factor ${\kappa}B$ ligand (RANKL), runt-related transcription factor 2 (RUNX2), collagen-Ⅰ (COL-Ⅰ). There were no significant differences in the osteogenic potentials of DOCs induced from MSCs on ${\beta}-TCP(+/-)$. According to the incubation period, there were significant increasing of Alizadin red S staining in the induction 3 weeks. The mRNA expression of ALP, RUNX2, and RANKL were higher in DOCs/${\beta}-TCP(-)$ than DOCs/${\beta}-TCP(+)$. According to rhBMP-2 concentrations, the mRNA expression of BSP was significantly increased in DOCs/${\beta}-TCP(+)$ compared to that of DOCs/${\beta}-TCP(-)$ on rhBMP 10 ng/ml. Our study presented the ${\beta}-TCP$ will have the possibility that calcium phosphate directly affect the osteoblastic differentiation of the bone marrowderived MSCs.

Acetonitrile에서의 Mg-EBT$^-$ 착물에 관한 연구 (Studies of Magnesium-Eriochrome Black T Complex in Acetonitrile)

  • 박두원;최원형;이흥락
    • 대한화학회지
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    • 제17권4호
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    • pp.256-261
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    • 1973
  • Mg(II)과 Eriochrome Black T가 Acetonitrile용액속에서 반응하여 만든 착물을 일정한 이온의 세기와 일정한 수소이온농도에서 분광광도법으로 연구했다. 유리전극과 Ag/0.1 M $AgNO_3$기준전극쌍을 써서 Acetonitrile 용액속에서 측정한 pH 값은 표준완충용액으로 검정했으며 그 결과는 다음과 같다. Picric acid$-10^{-3}M$ tetramethylammonium picrate 완충용액에 있어서는 은기준전극에 대한 유리 전극의 $25^{\circ}C$에서의 전위는 $E_{glass}=716+59.1logA_{H+}[mv]$이고, 1,3-Diphenylguanidine$-3{\times}10^{-3}M $1,3-diphenylguanidine perchlorate 완충용액에서는 $E_{glass}=1,193+59.1 logA_{H+}[mv]$이다. 리간드 Eriochrome Black T의 산해리지수$ pK_{H,EBT-}$는 9.1이었으며, 반응 $H_mEBT^{(3-m)-} + Mg^{2+} {\leftrightarrow}MgEBT^{-} + mH^{+}$ 으로 생성된 착물 $MgEBT^{-}$의 조건안정도상수를 log-ratio method으로 구하니 m이 2일때는 $logK_{MgEBT^-} + 3.97$이고, m이 1일 때는 $logK_{MgEBT^-} + 5.02$이었다. 착물의 조성은 수용액에서 Schwarzenbach씨 등이 구한 결과와 같이 비수용매 Acetonitrile속에서도 한 종류의 착물 $MgEBT^{-}$만이 생성됨을 알 수 있었다.

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Expression of peroxisome proliferator activated receptor gamma in the neuronal cells and modulation of their differentiation by PPAR gamma agonists

  • Hong, Jin-Tae
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.14-40
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    • 2002
  • 15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

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Gintonin influences the morphology and motility of adult brain neurons via LPA receptors

  • Kim, Do-Geun;Kim, Hyeon-Joong;Choi, Sun-Hye;Nam, Sung Min;Kim, Hyoung-Chun;Rhim, Hyewhon;Cho, Ik-Hyun;Rhee, Man Hee;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • 제45권3호
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    • pp.401-407
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    • 2021
  • Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain. Materials and methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment. Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425. Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration.

The estrogen-related receptor γ modulator, GSK5182, inhibits osteoclast differentiation and accelerates osteoclast apoptosis

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Lee, Dong-Kyo;Jin, Xian;Che, Xiangguo;Choi, Je-Yong
    • BMB Reports
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    • 제54권5호
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    • pp.266-271
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    • 2021
  • Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

Immunostimulatory activity of hydrolyzed and fermented Platycodon grandiflorum extract occurs via the MAPK and NF-κB signaling pathway in RAW 264.7 cells

  • Jae In, Jung;Hyun Sook, Lee;So Mi, Kim;Soyeon, Kim;Jihoon, Lim;Moonjea, Woo;Eun Ji, Kim
    • Nutrition Research and Practice
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    • 제16권6호
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    • pp.685-699
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    • 2022
  • BACKGROUND/OBJECTIVES: Platycodon grandiflorum (PG) has long been known as a medicinal herb effective in various diseases, including bronchitis and asthma, but is still more widely used for food. Fermentation methods are being applied to increase the pharmacological composition of PG extracts and commercialize them with high added value. This study examines the hydrolyzed and fermented PG extract (HFPGE) fermented with Lactobacillus casei in RAW 264.7 cells, and investigates the effect of amplifying the immune and the probable molecular mechanism. MATERIALS/METHODS: HFPGE's total phenolic, flavonoid, saponin, and platycodin D contents were analyzed by colorimetric analysis or high-performance liquid chromatography. Cell viability was measured by the MTT assay. Phagocytic activity was analyzed by a phagocytosis assay kit, nitric oxide (NO) production by a Griess reagent system, and cytokines by enzyme-linked immunosorbent assay kits. The mRNA expressions of inducible nitric oxide synthase (iNOS) and cytokines were analyzed by reverse transcription-polymerase chain reaction, whereas MAPK and nuclear factor (NF)-κB activation were analyzed by Western blots. RESULTS: Compared to PGE, HFPGE was determined to contain 13.76 times and 6.69 times higher contents of crude saponin and platycodin D, respectively. HFPGE promoted cell proliferation and phagocytosis in RAW 264.7 cells and regulated the NO production and iNOS expression. Treatment with HFPGE also resulted in increased production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-X-C motif chemokine ligand10, granulocyte-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-1, and the mRNA expressions of these cytokines. HFPGE also resulted in significantly increasing the phosphorylation of NF-κB p65, extracellular signal-regulated kinase, and c-Jun N-terminal kinase. CONCLUSIONS: Taken together, our results imply that fermentation and hydrolysis result in the extraction of more active ingredients of PG. Furthermore, we determined that HFPGE exerts immunostimulatory activity via the MAPK and NF-κB signaling pathways.

Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROS-dependent inactivation of the PI3K/Akt signaling pathway

  • Park, Cheol;Choi, Eun Ok;Hwangbo, Hyun;Lee, Hyesook;Jeong, Jin-Woo;Han, Min Ho;Moon, Sung-Kwon;Yun, Seok Joong;Kim, Wun-Jae;Kim, Gi-Young;Hwang, Hye-Jin;Choi, Yung Hyun
    • Nutrition Research and Practice
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    • 제16권3호
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    • pp.330-343
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    • 2022
  • BACKGROUND/OBJECTIVES: Zanthoxylum schinifolium is traditionally used as a spice for cooking in East Asian countries. This study was undertaken to evaluate the anti-proliferative potential of ethanol extracts of Z. schinifolium leaves (EEZS) against human bladder cancer T24 cells. MATERIALS/METHODS: Subsequent to measuring the cytotoxicity of EEZS, the anti-cancer activity was measured by assessing apoptosis induction, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). In addition, we determined the underlying mechanism of EEZS-induced apoptosis through various assays, including Western blot analysis. RESULTS: EEZS treatment concentration-dependently inhibited T24 cell survival, which is associated with apoptosis induction. Exposure to EEZS induced the expression of Fas and Fas-ligand, activated caspases, and subsequently resulted to cleavage of poly (ADP-ribose) polymerase. EEZS also enhanced the expression of cytochrome c in the cytoplasm by suppressing MMP, following increase in the ratio of Bax:Bcl-2 expression and truncation of Bid. However, EEZS-mediated growth inhibition and apoptosis were significantly diminished by a pan-caspase inhibitor. Moreover, EEZS inhibited activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and the apoptosis-inducing potential of EEZS was promoted in the presence of PI3K/Akt inhibitor. In addition, EEZS enhanced the production of ROS, whereas N-acetyl cysteine (NAC), a ROS scavenger, markedly suppressed growth inhibition and inactivation of the PI3K/Akt signaling pathway induced by EEZS. Furthermore, NAC significantly attenuated the EEZS-induced apoptosis and reduction of cell viability. CONCLUSIONS: Taken together, our results indicate that exposure to EEZS exhibits anti-cancer activity in T24 bladder cancer cells through ROS-dependent induction of apoptosis and inactivation of the PI3K/Akt signaling pathway.

자궁세포 성장에 미치는 항에스트로젠제의 작용기전 (Action Mechanism of Antiestrogens on Uterine Growth in Immature Rats)

  • 이중빈;윤미정;김창미;홍사석;유경자
    • 대한약리학회지
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    • 제26권2호
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    • pp.167-176
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    • 1990
  • 비스테로이드성 항에스트로젠제는 표적기관에서 estrogen 수용체와 상경적으로 결합하므로써 estrogen의 작용을 억제하는 것으로 알려져 있다. 비스테로이드성 항에스트로젠제는 대체로 triphenylethylene계로서 tamoxifen, clomiphene, LYl17018등이 있으며 표적기관에서 estrogen의 작용을 억제하기 때문에 estrogen과 관련된 질환을 치료하는데 이용되어 오고 있다. 본 연구에서는 생후 21-23일된 미성숙 흰쥐를 재료로 항에스트로젠제중 tamoxifen과 LY117018이 자궁세포 성장에 어떠한 영향을 미치며 어떠한 기전으로 estrogen의 작용을 길항하는지를 규명하고자, 항에스트로젠제가 estrogen작용의 중요 지포에 미치는 영향을 비교 관찰하여 다음과 같은 결과를 얻었다. Tamoxifen과 LY117018은 자궁세포에서 estrogen의 영향이 없는 경우에는 estrogen agonist로, estrogen작용하에서는 estrogen antagonist로서 작용하였다. Estrogen 작용의 여러 가지 지표에 대해 tamoxifen이 LY117018보다 agonistic effect는 더 컸으나, antagonistic effect는 LY117018이 더 큰 것으로 나타났다. Estrogen 수용체에 대한 결합능은 LY117018이 estradiol보다는 약간 낮았으나 용량에 비례하여 estrogen 수용체와 결합하였다. 그러나 tamoxifen은 estrogen 수용체에 대한 결합이 아주 낮았다. Estrogen 수용체에 대한 binding affinity는 estradiol(100%), LY117018(77%), tamoxifen(6.3%) 순으로 나타났다. 항에스트로젠제의 생체내 투여는 estrogen 존재 유무에 따라 estrogen 수용체 농도에 agonist 또는 antagonist로 작용하였다. 항에스트로젠제의 단독투여는 progesterone 수용체 생성을 증가시키나, estrogen에 의하여 유도된 progesterone 수용체 생성을 억제하였다. 이상의 결과로 보아, tamoxifen과 LY117018은 estrogen유무에 따라 흰쥐 자궁세포에서 estrogen antagonist로서 뿐만 아니라 agonist로서도 작용함을 알 수 있다. 그러나 estrogen수용체와의 결합능력이 아주 낮은 tamoxifen은, 용량에 비례하여 estrogen수용체에 결합하므로써 작용하는 LY117018과는 다른 기전으로 작용하는 것으로 생각된다.

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한국과 캐나다 대학생들의 콩가공식품에 대한 수응도 및 소비실태 비교 연구 (A Comparative Study on the Acceptability and the Consumption Attitude for Soy Foods between Korean and Canadian University Students)

  • 안태현
    • 한국작물학회지
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    • 제51권5호
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    • pp.466-476
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    • 2006
  • 한국과 캐나다의 젊은 소비계층인 대학생들을 중심으로 콩에 대한 일반적 인지도, 콩가공식품에 대한 구매 및 소비행태, 수응도 등을 설문문항을 통하여 비교해 보았고, 콩가공식품의 소비시 지적되는 문제점을 알아보았다. 한국 대학생들이 캐나다 대학생들에 비해 콩식품에 대하여 더욱 긍정적인 생각과 올바른 지식을 가지고 있었고, 콩식품에 대한 정보를 얻는 방법으로는 한국 대학생들의 경우 주로 상업적 매체를 통하는 것으로 나타났던 반면, 캐나다 대학생들의 경우는 주로 가족이나 친구 등 인맥을 통하는 비율이 높게 나타났다. 소비행태에 있어서는, 한국의 경우 조사대상자 전체가 구매경험이 있는 것으로 조사되었으나 캐나다의 경우는 조사대상자의 55.4%만이 콩가공식품 구매경험이 있었으며, 친숙하게 느껴지는 콩가공식품, 구매경험이 있는 콩가공식품 그리고 구매빈도가 높은 콩가공식품 등에 대해서는 한국과 캐나다 모두 매우 유사한 경향을 보였는데 두유에 대한 인지도가 가장 높았으며 소비량도 많은 것으로 나타났고 다음으로 콩음료, 마가린 등의 순서로 나타났다. 본 연구결과, 콩가공식품을 포함한 콩식품은 단순한 동양의 전통식품만이 아니라 동서양의 식생활에 일반적인 식품으로 자리매김하고 있는 것으로 나타났다. 단지 콩 유입의 역사가 짧고 낙농업 위주의 식생활이 주를 이루고있는 캐나다에서는 콩식품에 대한 관심이 한국보다 적어 소비경험이 전혀 없는 대학생들이 많았고(44.6%)우유식품을 선호하는 학생들이 많았다. 반면, 한국의 경우는 다양한 콩 가공식품이 일반화되지 않아 두유나 콩음료 등 특정 콩가공식품에 대한 소비율만 높은 것으로 나타났다. 그러나 앞으로 캐나다의 콩가공식품의 소비는 더욱 늘어날 것으로 전망되며, 우리나라 또한 젊은 소비자들의 콩식품 소비 활성화를 위하여 다양한 기호와 욕구를 충족시킬 수 있는 제품개발이 지속적으로 이루어진다면 전통적인 콩식품 및 콩가공식품 소비는 더욱 늘어날 것으로 전망되어 진다.능력이 있었다. 그러므로 $(PPAR{\gamma})$의 활성에 있어 RXR heterodimer가 사람의 백혈병세포에 대한 조절 경로로서 존재하며, PTEN의 upregulation을 통해 백혈병을 조절하기 때문에 백혈병의 예방 및 치료 접근에 $(PPAR{\gamma})$와 RXR ligands가 중요한 역할을 할 것이다.제안 객체 모델에서는 객체의 상태에 따라 사용 가능한 행위가 결정되는 가상 환경을 위해 새로운 인터페이스로 컨텍스트 메뉴(context menu) 인터페이스와 동작 생성 모델을 제시한다. 정의하였다. 객체 모델에서 객체의 상태 정보와 행위 정보를 분석해 아바타가 할 수 있는 행위를 컨텍스트 메뉴로 제공하기 때문에 사용자는 가상 환경의 상태에 상관 없이 직관적으로 명령을 줄 수 있다. 또한 사용자는 기존의 2D 혹은 텍스트기반 스크립트 작성기법을 벗어나 사용자는 제안된 3D 인터페이스 기법을 통하여 실시간으로 아바타의 행위 스크립트를 작성 및 재생 할 수 있다. 본 논문에서 제시한 시스템은 기존의 아바타 중심적인 제어를 객체에 분산함으로써 효율적이고 직관적인 명령을 내릴 수 있고 또한 손쉬운 시나리오 생성을 가능하게 하였다. 본 연구에서는 제안 기법의 활용을 위해 프리젠테이션 도메인 환경의 시스템을 구축하고 아바타-객체 행위제어 및 스크립트 생성 기법을 적용하였다.S는 스크립트 언어를 사용하는 전문가 시스템[7]으로 선언적 룰(Declarative Rule)을 이용하여 지식을 표현 하고 추론을 수행하는 추론 엔진의 한 종류이다. JESS의 지식 표현 방식은 튜닝 원칙을 쉽게 표현하고 수용할 수 있는 구조를 가지고 있으며 작은 크기와 빠른 추론 성능을 가지기 때문에 실시간으로 처리 되는 어플리케이션 튜닝에 적합하다. 지식 기반 모률의 가장 큰 역할은 주어진 데이터베이스 시스템의 모델을 통하여 필요한 새로운 지식을 생성하고 저장하는 것이다.

Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • 대한핵의학회지
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    • 제18권2호
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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