• Title/Summary/Keyword: Interaction Mechanism

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평행식 진동탄환 암거 천공기의 연구 (IV)(V)-실기 설계 제작 및 보장실험-Development of Balanced-Type Oscillating Mole Drainer(IV)(V)

  • 김용환;이승규;서상용
    • Journal of Biosystems Engineering
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    • v.2 no.1
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    • pp.7-24
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    • 1977
  • This paper is the forth and fifth one of the study on balanced type oscillating mole drainer. In the light of the results from previous reports about the model tests, some design criteria were established and a prototype machine was set up for experimental purpose. Motion characteristics and functionof the each parts of the machine were checked and analyzed. After that, performance tests of the prototype machine were carried out in thefield. Obtained results are summarized as follows ; 1. Ten centimeter of the bullet diameter was determined so as to be able to attach it to the tractors with capacity of 30 PS to 40 PS. 2. To maintain the balance between the moments of the front shank and rear shank, the oscillating amplitude of the rear bullet was determined to be larger than that of the front bullet. At the same time , the oscillating direction of the rear bullet was designed with the inclines of ten to thirty degrees. 3. An octagonal dynamo transduced was developed for measuring the compressive force of the upper link is measuring the draft force of the machine. Acceptable linear relationship between forces and strain responses from O.D.T. was obtained. 4. Analysing the balancing mechanism of the acting part of the machine , it was found that the total draft force of the machine was equal to the difference between the sum of the draft force produced from the right and left side bending moments of the lower drawber and the compressive force on the upper link. 5. There are acceptable linear relationship between the strain and twisting moment by driving shaft, and between strain and shank moment. Above results enable us to carry out the field experiment with prototype machine. 6. When the test machine was used in the field, it was possible to reduce the oscillating acceleration by forty percent in average as compared it with the single bullet mole drainer. 7. When the test machine was used under the oscillating condition, the dratt torce was reduced by 27 percent to 59 percent as compared it with the test machine under non-oscillating condition, while the draft force was increased by 7 percent to 20 percent as compared it with the mole drainer having oscillating single bullet. The reasoning behind this fact was considered as the resistance force due to the rear shank and bullet. 8. As the amplitude and frequency of the bullet were increased, the torque was increased accordingly. This tendency could be varied with the various characteristics of the given soils. And the larger frequency and amplitute, the more increasing oscil\ulcornerlating power but decreasing draft brce were needed, and draft force was increased as the velocity was increased.9. When the amplitude of the rear bullet was designed to be larger than that of the front bullet, the minimum value of the moment was lowered and oscillating acceleration was reduced. And when the oscillating direction of the rear bullet was declined back\ulcornerwards, oscillating acceleration was increased along with the increasing angle of decli\ulcornernation. When the test machine was operated in high speed, the difference between maximum moments and minimum ones became narrow. This varying magnitude of moments appeared on the moment oscillogram seems to be correlated to the oscillating acceleration and draft force. 10. From the analysis of variance, it was found that those factors such as frequency, amplitude, and operating velocity significantly affected in the oscillating acceleration, the draft resistance, the torque, the moment, and the total power required. And interaction between frequency and amplitude affected in the oscillating acceleration. 11. Within the given situation of this study, the most preferable operating conditions of the test machine were 7 Hz in oscillating frequency, 0.54 m/sec in operating velocity, and 39.1 mm in oscillating amplitude of front and rear bullets. However, it is necessary to select the proper frequency and magnitude of oscillation depending on the soil properties of the field in which the mole drainer is practiced by use of a bal1nced type oscillating mole drainer. 12. It is recommended that a comparative study of the mole drainers would be performed in the near future using two separate balanced oscillating bullet with the one which is operated by oscillating the movable bullet in a single cylinder or other balanced type which may be single oscillating bullet with spring, damper or balancing weight, and that of thing. To expand the applicability of the balanced type oscillating mole drainer in practical use, it is suggested to develop a new mechanism which perform mole drain with vinyl pipe or filling material such as rice hull.

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Production of $PGE_2$ and $H_2O_2$ from Alveolar Macrophage Stimulated by Silica (유리규산에 의하여 자극된 폐포 대식세포의 $H_2O_2$$PGE_2$ 생성)

  • Lee, Seong-Beom;Choi, Moon-Ju;Park, Won-Sang;Lee, Jung-Yong;Chae, Gue-Tae;Kim, Sang-Ho;Kim, Choo-Soung
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.5
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    • pp.513-520
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    • 1994
  • Background: The pathogenesis of silicosis has been focused on the interaction between alveolar macrophages and silica particle. Although fibrosis in silicosis has been studied extensively, the mechanism is still not fully understood. There is increasing evidence that monokines and arachidonic acid metabolites macrophage are involved in pathogenesis of silicosis. Recently, it was reported that prostaglandin E2 produced from macrophage counteracts the stimulatory effects of other monokines on fibroblast proliferation or collagen production. Until now, it was remained uncertain by which mechanism silica particle may activate alveolar macrophage to an enhanced release of prostaglandin E2. Methods: In order to investigate the relationship between the activity of alveolar macrophage and the production of $PGE_2$ from activated alveolar macrophage, the authors measured hydrogen peroxide and $PGE_2$ from alveolar macrophages activated by silica in vitro and from alveolar macrophages in the silicotic nodules from rat. Experimental silicosis was induced by intratracheal infusion of silica($SiO_2$) suspended in saline(50 mg/ml) in Sprague-Dawley rats. Results: produced by 1) The silicotic nodules with fibrosis were seen from the sections of rat lung at 60 days after intratracheal injection with 50 mg aqueous suspension of silica(Fig. 1). 2) In vitro, silica caused the dose dependent increase of hydrogen peroxide(p<0.05, Fig. 2A) and $PGE_2$(p>0.05, Fig. 2B) release from alveolar macrophages. Alveolar macrophages from rat with silicotic nodules released more hydrogen peroxide and $PGE_2$ than those of control group(p<0.05, Fig. 3). Conclusion: These results suggest that silica particle could activate macrophage directly and enhanced the release of $PGE_2$ and hydrogen peroxide from the alveolar macrophage.

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Interaction of Sodium Selenite on Neurotoxicity Induced by Methylmercuric Chloride (유기수은의 신경독성에 대한 셀레늄의 보상작용)

  • Park, J.S.;Lee, H.M.;Chung, Y.;Shin, D.C.;Roh, J.H.;Moon, Y.H.
    • Journal of Preventive Medicine and Public Health
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    • v.25 no.1 s.37
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    • pp.13-25
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    • 1992
  • This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular $Ca^{2+}$concentration of the neuron. Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride($25{\mu}M,\;50{\mu}M,\;100{\mu}M$) and sodium selenite($200{\mu}M$) on free intrasynaptosomal $Ca^{2+}$ concentration were studied using the fluorescent $Ca^{2+}$ indicator fura -2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succlnic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular $Ca^{2+}$ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal $Ca^{2+}$ concentration were measured with fura-2 in vitro. The results were summarized as follows ; 1. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of $CH_3HgCl$ only. 2. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of $CH_3HgCl$ only. Particularly pretreatment of $Na_2SeO_3$ significantly more compared to the administration of $CH_3HgCl$ only. The concentration of adenosine-5'-triphosphate in $Na_2SeO_3$ treatment groups revealed a favourable effect compared to the administration of $CH_3HgCl$ only. 3. Intracellular $Ca^{2+}$ concentration in administration of $CH_3HgCl$ only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time interval more decreased significantly intracellular $Ca^{2+}$ concentration compared to the administration of $CH_3HgCl$ only. 4. Free intrasynaptosomal $Ca^{2+}$ concentration in the combined administration of $CH_3HgCl$ and $Na_2SeO_3$ was decreased ($24%{\sim}40%$) significantly more than the administration of $CH_3HgCl$ only. From the above results, the specific dosage of $Na_2SeO_3$ decreased increment of intracellular $Ca^{2+}$ concentration induced by administration of $CH_3HgCl$. These findings suggest the protective mechanism of $Na_2SeO_3$ on the neurotoxicity of $CH_3HgCl$.

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Formation Process and Its Mechanism of the Sancheong Anorthosite Complex, Korea (산청 회장암복합체의 형성과정과 그 메커니즘)

  • Kang, Ji-Hoon;Lee, Deok-Seon
    • Economic and Environmental Geology
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    • v.48 no.6
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    • pp.431-449
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    • 2015
  • The study area is located in the western part of the Precambrian stock type of Sancheong anorthosite complex, the Jirisan province of the Yeongnam massif, in the southern part of the Korean Peninsula. We perform a detailed field geological investigation on the Sancheong anorthosite complex, and report the characteristics of lithofacies, occurrences, foliations, and research formation process and its mechanism of the Sancheong anorthosite complex. The Sancheong anorthosite complex is classified into massive and foliation types of Sancheong anorthosite (SA), Fe-Ti ore body (FTO), and mafic granulite (MG). Foliations are developed in the Sancheong anorthosite complex except the massif type of SA. The foliation type of SA, FTO, MG foliations are magmatic foliations which were formed in a not fully congealed state of SA from a result of the flow of FTO and MG melts and the kinematic interaction of SA blocks, and were continuously produced in the comagmatic differentiation. The Sancheong anorthosite complex is formed as the following sequence: the massive type of SA (a primary fractional crystallization of parental magmas under high pressure)${\rightarrow}$ the foliation type of SA [a secondary fractional crystallization of the plagioclase-rich crystal mushes (anorthositic magmas) primarily differentiated from parental magmas under low pressure]${\rightarrow}$the FTO (an injection by filter pressing of the residual mafic magmas in the last differentiation stage of anorthositic magmas into the not fully congealed SA)${\rightarrow}$the MG (a solidification of the finally residual mafic magmas). It indicates that the massive and foliation types of SA, the FTO, and the MG were not formed from the intrusion and differentiation of magmas which were different from each other in genesis and age but from the multiple fractionation and polybaric crystallization of the coeval and cogenetic magma.

Study of the Sludge Formation Mechanism in Advanced Packaging Process and Prevention Method for the Sludge (어드밴스드 패키징 공정에서 발생할 수 있는 슬러지의 인자 확인 및 형성 방지법의 제안)

  • Jiwon Kim;Suk Jekal;Ha-Yeong Kim;Min Sang Kim;Dong Hyun Kim;Chan-Gyo Kim;Yeon-Ryong Chu;Neunghi Lee;Chang-Min Yoon
    • Journal of the Korea Organic Resources Recycling Association
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    • v.31 no.1
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    • pp.35-45
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    • 2023
  • In this study, the sludge formation in the wastewater drain from the advanced packaging process mechanisms are revealed as well as the key factors, materials, and sludge prevention methods using surfactant. Compared with that of conventional packaging process, advanced packaging process employ similar process to the semiconductor fabrication process, and thus many processes may generate wastewater. In specific, a large amount of wastewater may generate during the carrier wafer bonding, photo, development, and carrier wafer debonding processes. In order to identify the key factors for the formation of sludge during the advanced packaging process, six types of chemicals including bonding glue, HMDS, photoresist (PR), PR developer, debonding cleaner, and water are utilized and mixing evaluation is assessed. As a result, it is confirmed that the black solid sludge is formed, which is originated by the sludge seed formation by hydrolysis/dehydration reaction of HMDS and sludge growth via hydrophobic-hydrophobic binding with sludge seed and PR. For the sludge prevention investigation, three surfactants of CTAB, PEG, and shampoo are mixed with the key materials of sludge, and it is confirmed that the sludge formations are successfully suppressed. The underlying mechanism behind the sludge formation is that the carbon tails of the surfactant bind to PR with hydrophobic-hydrophobic interaction and inhibit the reaction with HMDS-based slurry seeds to prevent the sludge formation. In this regard, it is expected that various problems like clogging in drains and pipes during the advanced packaging process may effectively solve by the injection of surfactants into the drains.

A Folksonomy Ranking Framework: A Semantic Graph-based Approach (폭소노미 사이트를 위한 랭킹 프레임워크 설계: 시맨틱 그래프기반 접근)

  • Park, Hyun-Jung;Rho, Sang-Kyu
    • Asia pacific journal of information systems
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    • v.21 no.2
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    • pp.89-116
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    • 2011
  • In collaborative tagging systems such as Delicious.com and Flickr.com, users assign keywords or tags to their uploaded resources, such as bookmarks and pictures, for their future use or sharing purposes. The collection of resources and tags generated by a user is called a personomy, and the collection of all personomies constitutes the folksonomy. The most significant need of the folksonomy users Is to efficiently find useful resources or experts on specific topics. An excellent ranking algorithm would assign higher ranking to more useful resources or experts. What resources are considered useful In a folksonomic system? Does a standard superior to frequency or freshness exist? The resource recommended by more users with mere expertise should be worthy of attention. This ranking paradigm can be implemented through a graph-based ranking algorithm. Two well-known representatives of such a paradigm are Page Rank by Google and HITS(Hypertext Induced Topic Selection) by Kleinberg. Both Page Rank and HITS assign a higher evaluation score to pages linked to more higher-scored pages. HITS differs from PageRank in that it utilizes two kinds of scores: authority and hub scores. The ranking objects of these pages are limited to Web pages, whereas the ranking objects of a folksonomic system are somewhat heterogeneous(i.e., users, resources, and tags). Therefore, uniform application of the voting notion of PageRank and HITS based on the links to a folksonomy would be unreasonable, In a folksonomic system, each link corresponding to a property can have an opposite direction, depending on whether the property is an active or a passive voice. The current research stems from the Idea that a graph-based ranking algorithm could be applied to the folksonomic system using the concept of mutual Interactions between entitles, rather than the voting notion of PageRank or HITS. The concept of mutual interactions, proposed for ranking the Semantic Web resources, enables the calculation of importance scores of various resources unaffected by link directions. The weights of a property representing the mutual interaction between classes are assigned depending on the relative significance of the property to the resource importance of each class. This class-oriented approach is based on the fact that, in the Semantic Web, there are many heterogeneous classes; thus, applying a different appraisal standard for each class is more reasonable. This is similar to the evaluation method of humans, where different items are assigned specific weights, which are then summed up to determine the weighted average. We can check for missing properties more easily with this approach than with other predicate-oriented approaches. A user of a tagging system usually assigns more than one tags to the same resource, and there can be more than one tags with the same subjectivity and objectivity. In the case that many users assign similar tags to the same resource, grading the users differently depending on the assignment order becomes necessary. This idea comes from the studies in psychology wherein expertise involves the ability to select the most relevant information for achieving a goal. An expert should be someone who not only has a large collection of documents annotated with a particular tag, but also tends to add documents of high quality to his/her collections. Such documents are identified by the number, as well as the expertise, of users who have the same documents in their collections. In other words, there is a relationship of mutual reinforcement between the expertise of a user and the quality of a document. In addition, there is a need to rank entities related more closely to a certain entity. Considering the property of social media that ensures the popularity of a topic is temporary, recent data should have more weight than old data. We propose a comprehensive folksonomy ranking framework in which all these considerations are dealt with and that can be easily customized to each folksonomy site for ranking purposes. To examine the validity of our ranking algorithm and show the mechanism of adjusting property, time, and expertise weights, we first use a dataset designed for analyzing the effect of each ranking factor independently. We then show the ranking results of a real folksonomy site, with the ranking factors combined. Because the ground truth of a given dataset is not known when it comes to ranking, we inject simulated data whose ranking results can be predicted into the real dataset and compare the ranking results of our algorithm with that of a previous HITS-based algorithm. Our semantic ranking algorithm based on the concept of mutual interaction seems to be preferable to the HITS-based algorithm as a flexible folksonomy ranking framework. Some concrete points of difference are as follows. First, with the time concept applied to the property weights, our algorithm shows superior performance in lowering the scores of older data and raising the scores of newer data. Second, applying the time concept to the expertise weights, as well as to the property weights, our algorithm controls the conflicting influence of expertise weights and enhances overall consistency of time-valued ranking. The expertise weights of the previous study can act as an obstacle to the time-valued ranking because the number of followers increases as time goes on. Third, many new properties and classes can be included in our framework. The previous HITS-based algorithm, based on the voting notion, loses ground in the situation where the domain consists of more than two classes, or where other important properties, such as "sent through twitter" or "registered as a friend," are added to the domain. Forth, there is a big difference in the calculation time and memory use between the two kinds of algorithms. While the matrix multiplication of two matrices, has to be executed twice for the previous HITS-based algorithm, this is unnecessary with our algorithm. In our ranking framework, various folksonomy ranking policies can be expressed with the ranking factors combined and our approach can work, even if the folksonomy site is not implemented with Semantic Web languages. Above all, the time weight proposed in this paper will be applicable to various domains, including social media, where time value is considered important.

The Use of Pharmacogenomic Method for the Prediction of Antidepressant Responsiveness (약리 유전학적 방법을 이용한 항우울제 치료반응성의 예측)

  • Kim, Doh Kwan;Lim, Shinn-Won
    • Korean Journal of Biological Psychiatry
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    • v.9 no.1
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    • pp.25-33
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    • 2002
  • Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

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Investigation on Inhibitory Effect of ErmSF N-Terminal End Region Peptide on ErmSF Methyltansferase Activity In Vivo Through Development of Co-Expression System of Two Different Proteins in One Cell (서로 다른 두 단백질의 세포 내 동시 발현 체계의 개발을 통한 ErmSF에서 특이적으로 발견되는 N-Terminal End Region (NTER)을 포함하는 펩타이드의 생체내에서의 ErmSF 활성 억제 효과 검색)

  • Jin, Hyung-Jong
    • Korean Journal of Microbiology
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    • v.47 no.3
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    • pp.200-208
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    • 2011
  • Most problematic antibiotic resistance mechanism for MLS (macrolide-lincosamide-streptogramn B) antibiotics encountered in clinical practice is mono- or dimethylation of specific adenine residue at 2058 (E. coli coordinate) of 23S rRNA which is performed by Erm (erythromycin ribosome resistance) protein through which bacterial ribosomes reduce the affinity to the antibiotics and become resistant to them. ErmSF is one of the four gene products produced by Streptomyces fradiae to be resistant to its own antibiotic, tylosin. Unlike other Erm proteins, ErmSF harbors idiosyncratic long N-terminal end region (NTER) 25% of which is comprised of arginine well known to interact with RNA. Furthermore, NTER was found to be important because when it was truncated, most of the enzyme activity was lost. Based on these facts, capability of NTER peptide to inhibit the enzymatic activity of ErmSF was sought. For this, expression system for two different proteins to be expressed in one cell was developed. In this system, two plasmids, pET23b and pACYC184 have unique replication origins to be compatible with each other in a cell. And expression system harboring promoter, ribosome binding site and transcription termination signal is identical but disparate amount of protein could be expressed according to the copy number of each vector, 15 for pACYC and 40 for pET23b. Expression of NTER peptide in pET23b together with ErmSF in pACYC 184 in E. coli successfully gave more amounts of NTER than ErmSF but no inhibitory effects were observed suggesting that there should be dynamicity in interaction between ErmSF and rRNA rather than simple and fixed binding to each other in methylation of 23S rRNA by ErmSF.

Analysis of Global Gene Expression Profile of Human Adipose Tissue Derived Mesenchymal Stem Cell Cultured with Cancer Cells (암세포주와 공동 배양된 인간 지방 조직 유래 중간엽 줄기 세포의 유전자 발현 분석)

  • Kim, Jong-Myung;Yu, Ji-Min;Bae, Yong-Chan;Jung, Jin-Sup
    • Journal of Life Science
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    • v.21 no.5
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    • pp.631-646
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    • 2011
  • Mesenchymal stem cells (MSC) are multipotent and can be isolated from diverse human tissues including bone marrow, fat, placenta, dental pulp, synovium, tonsil, and the thymus. They function as regulators of tissue homeostasis. Because of their various advantages such as plasticity, easy isolation and manipulation, chemotaxis to cancer, and immune regulatory function, MSCs have been considered to be a potent cell source for regenerative medicine, cancer treatment and other cell based therapy such as GVHD. However, relating to its supportive feature for surrounding cell and tissue, it has been frequently reported that MSCs accelerate tumor growth by modulating cancer microenvironment through promoting angiogenesis, secreting growth factors, and suppressing anti-tumorigenic immune reaction. Thus, clinical application of MSCs has been limited. To understand the underlying mechanism which modulates MSCs to function as tumor supportive cells, we co-cultured human adipose tissue derived mesenchymal stem cells (ASC) with cancer cell lines H460 and U87MG. Then, expression data of ASCs co-cultured with cancer cells and cultured alone were obtained via microarray. Comparative expression analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and PANTHER (Protein ANalysis THrough Evolutionary Relationships) in divers aspects including biological process, molecular function, cellular component, protein class, disease, tissue expression, and signal pathway. We found that cancer cells alter the expression profile of MSCs to cancer associated fibroblast like cells by modulating its energy metabolism, stemness, cell structure components, and paracrine effect in a variety of levels. These findings will improve the clinical efficacy and safety of MSCs based cell therapy.

Insulin-like growth factor가 소장 점막 세포 증식에 미치는 영향

  • 윤정한
    • Proceedings of the Korean Nutrition Society Conference
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    • 1995.11b
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    • pp.11-34
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    • 1995
  • Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

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