• 제목/요약/키워드: 3-D Mechanism

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Expression of TIMP1, TIMP2 Genes by Ionizing Radiation (이온화 방사선에 의한 TIMP1, TIMP2 유전자 발현 측정)

  • Park Kun-Koo;Jin Jung Sun;Park Ki Yong;Lee Yun Hee;Kim Sang Yoon;Noh Young Ju;Ahn Seung Do;Kim Jong Hoon;Choi Eun Kyung;Chang Hyesook
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.171-180
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    • 2001
  • Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.

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Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

  • Jang, Choon-Gon;Kang, Moon-Kyu;Cho, Jae-Han;Lee, Sun-Bok;Kim, Hyun-Taek;Park, Soon-Kwon;Lee, Jin-Woo;Park, Seong-Kyu;Hong, Moo-Chang;Shin, Min-Kyu;Shim, In-Sup;Bae , Hyun-Su
    • Archives of Pharmacal Research
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    • v.27 no.10
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    • pp.1065-1072
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    • 2004
  • Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

Crop Injury (Growth Inhibition) Induced by Herbicides and Remedy to Reduce It (제초제(除草劑) 약해발생(藥害發生) 양상(樣相)과 경감대책(輕減對策))

  • Kim, K.U.
    • Korean Journal of Weed Science
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    • v.12 no.3
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    • pp.261-270
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    • 1992
  • Many herbicides that are applied at the soil before weed emergence inhibit plant growth soon after weed germination occurs. Plant growth has been known as an irreversible increase in size as a result of the processes of cell divison and cell enlargement. Herbicides can influence primary growth in which most new plant tissues emerges from meristmatic region by affecting either or both of these processes. Herbicides which have sites of action during interphase($G_1$, S, $G_2$) of cell cycle and cause a subsequent reduction in the observed frequency of mitotic figures can be classified as an inhibitor of mitotic entry. Those herbicides that affect the mitotic sequence(mitosis) by influencing the development of the spindle apparatus or by influencing new cell plate formation should be classified as causing disruption of the mitotic sequence. Sulfonylureas, imidazolinones, chloroacetamides and some others inhibit plant growth by inhibiting the entry of cell into mitosis. The carbamate herbicides asulam, carbetamide, chlorpropham and propham etc. reported to disrupt the mitotic sequence, especially affecting on spindle function, and the dinitroaniline herbicides trifluralin, nitralin, pendimethalin, dinitramine and oryzalin etc. reported to disrupt the mitotic sequence, particularly causing disappearence of microtubles from treated cells due to inhibition of polymerization process. An inhibition of cell enlargement can be made by membrane demage, metabolic changes within cells, or changes in processes necessary for cell yielding. Several herbicides such as diallate, triallate, alachlor, metolachlor and EPTC etc. reported to inhibit cell enlargement, while 2, 4-D has been known to disrupt cell enlargement. One potential danger inherent in the use of soil acting herbicides is that build-up of residues could occur from year to year. In practice, the sort of build-up that would be disastrous is unikely to occur for substances applied at the correct soil concentration. Crop injury caused by soil applied herbicides can be minimized by (1) following the guidance of safe use of herbicides, particularly correct dose at correct time in right crop, (2) by use of safeners which protect crops against injury without protecting any weed ; interactions between herbicides and safeners(antagonists) at target sites do occur probably from the following mechanisms (1) competition for binding site, (2) circumvention of the target site, and (3) compensation of target site, and another mechanism of safener action can be explained by enhancement of glutathione and glutathione related enzyme activity as shown in the protection of rice from pretilachlor injury by safener fenclorim, (3) development of herbicide resistant crops ; development of herbicide-resistant weed biotypes can be explained by either gene pool theory or selection theory which are two most accepted explanations, and on this basis it is likely to develop herbicide-resistant crops of commercial use. Carry-over problems do occur following repeated use of the same herbicide in an extended period of monocropping, and by errors in initial application which lead to accidental and irregular overdosing, and by climatic influence on rates of loss. These problems are usually related to the marked sensitivity of the particular crops to the specific herbicide residues, e.g. wheat/pronamide, barley/napropamid, sugarbeet/ chlorsulfuron, quinclorac/tomato. Relatively-short-residual product, succeeding culture of insensitive crop to specific herbicide, and greater reliance on postemergence herbicide treatments should be alternatives for farmer practices to prevent these problems.

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The Effect of Au Addition on the Hardening Mechanism in Ag-25wt% Pd-15wt% Cu (Ag-25wt% Pd-15wt% Cu 3원합금(元合金) 및 Au 첨가합금(添加合金)의 시효경화특성(時效京華特性))

  • Bea, B.J.;Lee, H.S.;Lee, K.D.
    • Journal of Technologic Dentistry
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    • v.20 no.1
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    • pp.37-49
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    • 1998
  • The specimens used were Ag-25 Pd-15 Cu ternary alloy and Au addition alloy. These alloys were melted and casted by induction electric furnace and centrifugal casting machine in Ar atmosphere. These specimens were solution treated for 2hr at $800^{\circ}C$ and were then quenched into iced water, and aged at $350{\sim}550^{\circ}C$ Age- hardening characteristics of the small Au-containing Ag-Pd-Cu dental alloys were investigated by means of hardness testing. X-ray diffraction and electron microscope observations, electrical resistance, ergy dispersed spectra and electron probe microanalysis. Principal results are as follows : Hardening occured in two stages, i.e., stage I in low temperature and stage II in high temperature regions, during continuous aging. The case of hardening in stage I was due to the formation of the $L1_0$ type face-centered tetragonal PdCu-ordered phase in the grain interior and hardening in stage I was affected by the Cu concentration. In stage II, decomposition of the ${\alpha}$ solid solution to a PdCu ordered phase($L1_0$ type) and an Ag-rich ${\alpha}2$ phase occurred and a discontinuous precipitation occurred at the grain boundary. From the electron microscope study, it was conclued that the cause of age-hardening in this alloy is the precipitation of the PdCu ordered phase, which has AuCu I type face-centered tetragonal structure. Precipetation procedure was ${\alpha}{\to}{\alpha}+{\alpha}_2+PdCu {\to}{\alpha}_1+{\alpha}_2+PdCu$ at Pd/Cu = 1.7 Ag-Pd-Cu alloy is more effective dental alloy as ageing treatment and is suitable to isothermal ageing at $450^{\circ}C$.

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Estimating Carrying Capacity of Lake Shihwa for Water Quality Management (수질관리를 위한 시화호의 환경용량 산정)

  • Kim, Hyung-Chul;Choi, Woo-Jeung;Lee, Won-Chan;Koo, Jun-Ho;Lee, Pil-Yong;Park, Sung-Eun;Hong, Seok-Jin;Jang, Ju-Hyoung
    • Journal of Environmental Science International
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    • v.16 no.5
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    • pp.571-581
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    • 2007
  • The mechanism of water pollution in Lake Shihwa, one of highly eutrophicated artificial lakes in Korea, has been studied using a numerical 3D physical-biochemical coupled model. In this study, the model was applied to estimate the contribution of land-based pollutant load to water quality of heavily polluted Lake Shihwa. The chemical oxygen demand(COD) was adopted as an index of the lake water quality, and the spatial distribution of an average COD concentration during the summer from 1999 to 2000 was simulated by the model. The simulated COD showed a good agreement with the observed data. According to reproducibility of COD, the high-est levels between 8 and 9 mg/L were shown at the inner site of the lake with inflow of many rivers and ditches, while the lowest was found to be about 5 mg/L at the southwestern site near to dike gate. In the pre-diction of water quality of Lake Shihwa, COD showed still higher levels than 3 mg/L in case of reduction of 95% for land-based pollutant load. This suggests that the curtailment of land-based pollutant load is not only sufficient but the improvement of sediment quality or the increase of seawater exchange should be considered together to improve a water quality in Lake Shihwa.

${\gamma}{\delta}$ T Cells in the Peripheral Blood of Pulmonary Tuberculosis (폐결핵환자의 말초혈액에서의 ${\gamma}{\delta}$ T 림프구에 관한 연구)

  • Shim, Tae-Sun;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.239-247
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    • 1994
  • Background: T cell mediated immunity is important in the defense mechanism of tuberculosis. Since ${\gamma}{\delta}$ T cell receptor was found to react with 65 kD heat shock protein of M.tuberculosis, there have been some reports on the role of ${\gamma}{\delta}$ T cells in the defense against M.tuberculosis. But until now, the role of the ${\gamma}{\delta}$ T cells in tuberculosis is not clear. Methods: We therefore measured the percentage of ${\gamma}{\delta}$ T cells of peripheral blood by flowcytometry before and after stimulation with Con-A, PPD and H37Ra lysate and compared between tuberculosis patients and healthy controls. Results: ${\gamma}{\delta}$ T cells of pheripheral blood in pulmonary tuberculosis patients was $7.5{\pm}5.2%$, showing no difference compared with healthy control($10.0{\pm}4.8%$). But IL-2R(+) ${\gamma}{\delta}$ T cells were higher in tuberculosis compared with healthy control($4.8{\pm}5.1%$ vs. $1.8{\pm}2.8%$). After stimulation with PPD or Con-A, the percentage of ${\gamma}{\delta}$ T cells showed no significant change, but IL-2R(+) ${\gamma}{\delta}$ T cells increased significantly in both tuberculosis($17.9{\pm}13.4%,\;57.6{\pm}20.2%$ respectively) and healthy control group($11.5{\pm}9.1%,\;80.8{\pm}9.3%$). After stimulation with H37Ra lysate, percentage of ${\gamma}{\delta}$ T cells showed increasing tendency in healthy control group, but it was not statistically significant. Conclusion: In this study, we could not demonstrate the role of ${\gamma}{\delta}$ T cells in the peripheral blood of pulmonary tuberculosis. It is suggested that further studies will be needed in the regional sites of M.tuberculosis infection.

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Phosphorus and Nitrogen Reduction from Animal Wastewater with MAP Process (축산폐수에서 질소$\cdot$인의 추출을 위한 MAP공정 개발)

  • Oh I. H.;Lee J. H.;Jeung D. S.;Jo J. W.
    • Journal of Animal Environmental Science
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    • v.11 no.3
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    • pp.207-214
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    • 2005
  • To reduce phosphorus and nitrogen from the swine wastewater, magnesium chloride $(MgCl_2)$ was used as a reaction material for both soluble phosphorus (SP) and ammonia-nitrogen (AN). The initial value of SP content were $471mg/\ell$ far aeration test and $515 mg/\ell$ for NaOH addition test, but treatment of $MgCl_2$ reduced SP value to $5mg/\ell$ and $4mg/\ell$. The removal efficiency of $MgCl_2$ for SP showed $99\%$ in both treatment, and the removal efficiency of $MgCl_2$ for AN showed $15\%$ with treatment of aeration and $18\%$ with NaOH. All the experiments were done in a low temperature of 6 to $8^{\circ}C$, suggesting that this methods are possibly able to apply to a cold weather conditions. Moreover, the struvite crystal structure was identified by electronic microscope, implying that $MgCl_2$ is an effective material for removal of SP from swine wastewater In addition to the increased removal rate of the AN in wastewater, both $MgCl_2$ and $KH_2PO_4$ were added. The SP value was reduced by $99\%$ with 2g addition of the phosphate. The SP removal rate by 4g addition of the phosphate was increased only as $15-19\%$, but the quantity of removed SP was higher than that of 2g addition test. The value of AN was not reduced as expected by adding $KH_2PO_4$. The AN removal rate were low as $18\%$ and $15\%$ like as the level of the former test with $MgCl_2$ alone. Therefore, it is needed to examine closely the reaction mechanism f3r reducing both SP and AN simultaneously.

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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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Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

  • Li, Yuwen;Piao, Longzhen;Yang, Keum-Jin;Shin, Sang-Hee;Shin, Eul-Soon;Park, Kyung-Ah;Byun, Hee-Sun;Won, Min-Ho;Choi, Byung-Lyul;Lee, Hyun-Ji;Kim, Young-Rae;Hong, Jang-Hee;Hur, Gang-Min;Kim, Jeong-Lan;Cho, Jae-Youl;Seok, Jeong-Ho;Park, Jong-Sun
    • Toxicological Research
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    • v.24 no.3
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    • pp.175-182
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    • 2008
  • DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be $2^{nd}$ upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

Data Mining Approaches for DDoS Attack Detection (분산 서비스거부 공격 탐지를 위한 데이터 마이닝 기법)

  • Kim, Mi-Hui;Na, Hyun-Jung;Chae, Ki-Joon;Bang, Hyo-Chan;Na, Jung-Chan
    • Journal of KIISE:Information Networking
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    • v.32 no.3
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    • pp.279-290
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    • 2005
  • Recently, as the serious damage caused by DDoS attacks increases, the rapid detection and the proper response mechanisms are urgent. However, existing security mechanisms do not effectively defend against these attacks, or the defense capability of some mechanisms is only limited to specific DDoS attacks. In this paper, we propose a detection architecture against DDoS attack using data mining technology that can classify the latest types of DDoS attack, and can detect the modification of existing attacks as well as the novel attacks. This architecture consists of a Misuse Detection Module modeling to classify the existing attacks, and an Anomaly Detection Module modeling to detect the novel attacks. And it utilizes the off-line generated models in order to detect the DDoS attack using the real-time traffic. We gathered the NetFlow data generated at an access router of our network in order to model the real network traffic and test it. The NetFlow provides the useful flow-based statistical information without tremendous preprocessing. Also, we mounted the well-known DDoS attack tools to gather the attack traffic. And then, our experimental results show that our approach can provide the outstanding performance against existing attacks, and provide the possibility of detection against the novel attack.