Description and classification for facilitating interoperability of heterogeneous data/events/services in the Internet of Things

Yim, H.J.,Seo, D.,Jung, H.,Back, M.K.,Kim, I.,Lee, K.C. Elsevier Science Publishers 2017 Neurocomputing Vol.256 No.-

<P>The Internet of Things (loT) refers to an infrastructure that integrates things over standard wired/wireless networks and allows them to exchange information with each other. The loT is a very complex heterogeneous network, enabling seamless integration of these things is a huge challenge. A publish/subscribe method of integration can be formulated to solve the problems of interconnecting billions of heterogeneous things. In our work, an IoT framework that uses an abstraction layer that decouples an application from the service calls and network interfaces is required to send and receive messages on a particular thing. This paper provides definitions and classifications for heterogeneous data/events/services according to the properties of the things in order to integrate them into a framework for description. Based on these definitions and classifications, heterogeneous data/events/services in the loT were integrated via topic description through the Data Distribution Service (DDS) middleware standard for real-time publish/subscribe. This paper also concludes with general remarks and a discussion of future work. (C) 2017 Elsevier B.V. All rights reserved.</P>

Structural dynamics of keyword networks: Liquid crystal display and plasma display panel cases

Yang, H.,Jung, W.S. Elsevier Science Publishers 2016 Journal of Engineering and Technology Management Vol.40 No.-

<P>This study focuses on understanding scientific evolution by using keyword co-occurrence networks, where keywords appearing in a scientific article are linked with a weight equal to the number of co-occurrences. To characterize structural changes of the network, we examine distributions of sums of weights by node over time. In particular, a change of power-law behavior is utilized to explore scientific evolution, such as emerging scientific paradigms and advancing normal science. As an illustration of the method used, the development of Liquid Crystal Displays (LCDs) and Plasma Display Panels (PDPs) is tracked. We detect two-tiered power-law distributions in the initial stage of scientific growth in both technologies due to differences in research intensity between two groups. The groups of keywords more likely to attract researchers' interest than others are incrementally developed until the mid-2000s to overtake those prior. Finally, we can capture a merging point of the dichotomous structure of PDPs but LCDs maintain the structural separation throughout the adjustment area. We expect that this structural investigation of keyword co-occurrence networks provides an indicator to diagnose the research evolution in that field. (C) 2016 Published by Elsevier B.V.</P>

Ethanol-induced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice

Kim, S.J.,Lee, J.W.,Jung, Y.S.,Kwon, D.Y.,Park, H.K.,Ryu, C.S.,Kim, S.K.,Oh, G.T.,Kim, Y.C. Elsevier Science Publishers 2009 Journal of hepatology Vol.50 No.6

Background/Aims: Oxidative stress via generation of reactive oxygen species is suggested to be the major mechanism of alcohol-induced liver injury. We investigated the effects of glutathione peroxidase-1 and catalase double deficiency (Gpx-1<SUP>-/-</SUP>/Cat<SUP>-/-</SUP>) on liver injury and changes in the sulfur amino acid metabolism induced by binge ethanol administration. Methods: Ethanol (5g/kg) was administered orally to the wild-type and the Gpx-1<SUP>-/-</SUP>/Cat<SUP>-/-</SUP> mice every 12h for a total of three doses. Mice were sacrificed 6h after the final dose. Results: The Gpx-1/Cat deficiency alone increased malondialdehyde levels in liver significantly. Hepatic methionine adenosyltransferase (MAT) activity and S-adenosylmethionine levels were decreased, however, glutathione contents were not changed. Ethanol administration to the Gpx-1<SUP>-/-</SUP>/Cat<SUP>-/-</SUP> mice increased the elevation of serum alanine aminotransferase activity, plasma homocysteine levels, hepatic fat accumulation and lipid peroxidation compared with the wild-type animals challenged with ethanol. Also the reduction of MAT activity and S-adenosylmethionine levels was enhanced, but MATI/III expression was increased significantly. Conclusions: The results indicate that Gpx-1 and Cat have critical roles in the protection of liver against binge ethanol exposure. Augmentation of ethanol-induced oxidative stress may be responsible for the impairment of the transsulfuration reactions and the aggravation of acute liver injury in the Gpx-1<SUP>-/-</SUP>/Cat<SUP>-/-</SUP> mice.

Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): In vitro and in vivo studies

Kim, E.M.,Jeong, H.J.,Park, I.K.,Cho, C.S.,Moon, H.B.,Yu, D.Y.,Bom, H.S.,Sohn, M.H.,Oh, I.J. Elsevier Science Publishers 2005 Journal of controlled release Vol.108 No.2

The asialoglycoprotein receptor (ASGP-R) on the hepatocyte membrane is a specific targeting marker for gene and drug delivery. Polyethylenimine (PEI) is a polycationic nonviral vector that is used for gene transfer. We have synthesized galactosylated polyethylenimine-graft-poly(ethylene glycol) (GPP) for performing gene delivery to the hepatocytes. The present study reports on the in vitro and in vivo data that was achieved in hepatoma bearing transgenic mice. The cytotoxicity was decreased with the increasing PEG content. The particle size of the complex was increased with the increasing PEG at an N/P ratio of 3.0, while the zeta potentials were decreased. The <SUP>99m</SUP>Tc labeled complexes were transfected into HepG2 and HeLa cells, while the GFP reporter genes were mainly expressed in the HepG2 cells. The in vivo data was achieved in ALB/c-Ha-ras transgenic mice. <SUP>99m</SUP>Tc labeled GPP<SUB>50</SUB>/DNA was injected into the mice via the tail vein, and the gamma images were acquired at 5, 15 and 30 min. The <SUP>99m</SUP>Tc labeled complexes were mainly localized in the heart and liver, and they were excreted through the kidneys. The GFP gene was mainly expressed in the proliferating cells at the tumor periphery. This result was confirmed by PCNA staining. The GPP<SUB>50</SUB>/DNA complexes were bound to ASGP-R of the proliferating hepatocytes in vitro and in vivo. The present results demonstrate the feasibility of nonviral gene transfer using galactosylated PEI-PEG in vivo.

Nonstructural 5A protein activates β-catenin signaling cascades: Implication of hepatitis C virus-induced liver pathogenesis

Park, C.Y.,Choi, S.H.,Kang, S.M.,Kang, J.I.,Ahn, B.Y.,Kim, H.,Jung, G.,Choi, K.Y.,Hwang, S.B. Elsevier Science Publishers 2009 Journal of hepatology Vol.51 No.5

Background/Aims: The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) has been implicated in HCV-induced liver pathogenesis. Wnt/β-catenin signaling has also been involved in tumorigenesis. To elucidate the molecular mechanism of HCV pathogenesis, we examined the potential effects of HCV NS5A protein on Wnt/β-catenin signal transduction cascades. Methods: The effects of NS5A protein on β-catenin signaling cascades in hepatic cells were investigated by luciferase reporter gene assay, confocal microscopy, immunoprecipitation assay, and immunoblot analysis. Results: β-Catenin-mediated transcriptional activity is elevated by NS5A protein, in the context of HCV replication, and by infection of cell culture-produced HCV. NS5A protein directly interacts with endogenous β-catenin and colocalizes with β-catenin in the cytoplasm. NS5A protein inactivates glycogen synthase kinase 3β and increases subsequent accumulation of β-catenin in HepG2 cells. β-Catenin was also accumulated in HCV patients' liver tissues. In addition, the accumulation of β-catenin in HCV replicon cells requires both activation of phosphatidylinositol 3-kinase and inactivation of GSK3β. Conclusions: NS5A activates β-catenin signaling cascades through increasing the stability of β-catenin. This modulation is accomplished by the protein interplay between viral and cellular signaling transducer. These data suggest that NS5A protein may directly be involved in Wnt/β-catenin-mediated liver pathogenesis.

Screening and isolation of a natural dopamine D₁ receptor antagonist using cell-based assays

Yu, S.,Park, J.S.,Paredes, V.,Song, M.C.,Baek, N.I.,Lee, S.I.,Lim, J.S.,Cho, N.Y.,Yoon, J.,Baek, K. Elsevier Science Publishers 2010 Journal of biotechnology Vol.145 No.3

To develop a cell-based assay to screen for human dopamine D<SUB>1</SUB> receptor agonists or antagonists from medicinal plant extracts, a stable Chinese hamster ovary (CHO) cell line (CHO-D1R) expressing the human dopamine D<SUB>1</SUB> receptor was established using an expression vector containing a scaffold attachment region (SAR) element. CHO-D1R cells showed specific binding to [<SUP>3</SUP>H]-SCH23390 with high affinity (K<SUB>d</SUB>=1.47+/-0.17nM) and dose-dependent responses for the dopamine-mediated stimulation of cAMP concentrations (EC<SUB>50</SUB>=20.6+/-1.44nM). The screening of medicinal plant extracts using cell-based cAMP assays revealed that an extract of Gleditsia sinensis Lam., which is known to be rich in saponin, had strong antagonist activity for the D<SUB>1</SUB> receptor. From the activity-guided fractionation and chemical structural analysis of the G. sinensis extract, a compound called gleditsioside F was isolated and was identified to have antagonist activity for the D<SUB>1</SUB> receptor. Gleditsioside F showed very effective D<SUB>1</SUB> antagonist activity by inhibiting ligand binding to the D<SUB>1</SUB> receptor as well as by inhibiting dopamine-mediated increases in cAMP concentration.

Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: Implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration

Won, M.,Park, K.A.,Byun, H.S.,Kim, Y.R.,Choi, B.L.,Hong, J.H.,Park, J.,Seok, J.H.,Lee, Y.H.,Cho, C.H.,Song, I.S.,Kim, Y.K.,Shen, H.M.,Hur, G.M. Elsevier Science Publishers 2009 Journal of hepatology Vol.51 No.1

Background/Aims: Based on the observation of biphasic induction of SGK1 expression in the regenerating liver, we investigated the role of SGK1 in the regulation of MEK/ERK signaling pathway which plays a crucial role in regulating growth and survival signaling. Methods: To determine the role of SGK1 in the activation of MEK/ERK signaling cascade, we infected primary hepatocytes with recombinant adenoviral vector encoding SGK1, and assessed its effect on the MEK/ERK signaling pathway. Results: Partial hepatectomy resulted in the biphasic transcriptional induction of SGK1 in regenerating liver tissues. Infection of primary hepatocytes with an adenoviral vector encoding SGK1 enhanced the ERK phosphorylation under serum-starved conditions and this was blocked by the expression of kinase-dead SGK1. SGK1 was found to physically interact with ERK½ as well as MEK½. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser<SUP>29</SUP> in a serum-dependent manner. Replacement of Ser<SUP>29</SUP> to aspartic acid, which mimics the phosphorylation of Ser<SUP>29</SUP>, enhanced the ERK2 activity as well as the MEK/ERK complexes formation. Conclusions: SGK1 expression during liver regeneration is a part of a signaling pathway that is necessary for enhancing ERK signaling activation through modulating the MEK/ERK complex formation.

High antiangiogenic and low anticoagulant efficacy of orally active low molecular weight heparin derivatives

Park, J.W.,Jeon, O.C.,Kim, S.K.,Al-Hilal, T.A.,Jin, S.J.,Moon, H.T.,Yang, V.C.,Kim, S.Y.,Byun, Y. Elsevier Science Publishers 2010 Journal of controlled release Vol.148 No.3

Heparin, an anticoagulant that is widely used clinically, is also known to bind to several kinds of proteins through electrostatic interactions because of its polyanionic character. These interactions are mediated by the physicochemical properties of heparin such as sequence composition, sulfation patterns, charge distribution, overall charge density, and molecular size. Although this electrostatic character mediates its binding to many proteins related with tumor progression, thereby providing its antiangiogenic property, the administration of heparin for treating cancer is limited in clinical applications due to several drawbacks, such as its low oral absorption, unsatisfactory therapeutic effects, and strong anticoagulant activity which induces hemorrhaging. Here, we evaluated novel, orally active, low molecular weight heparin (LMWH) derivatives (LHD) conjugated with deoxycholic acid (DOCA) that show reduced anticoagulant activity and enhanced antiangiogenic activity. The chemical conjugate of LMWH and DOCA was synthesized by conjugating the amine group of N-deoxycholylethylamine (EtDOCA) with the carboxylic groups of heparin at various DOCA conjugation ratios. The LMWH-DOCA conjugate series (LHD1, LHD1.5, LHD2, and LHD4) were further formulated with poloxamer 407 as a solubilizer for oral administration. An in vitro endothelial tubular formation and in vivo Matrigel plug assay were performed to verify the antiangiogenic potential of LHD. Finally, we evaluated tumor growth inhibition of oral LHD administration in a SCC7 model as well as in A549 human cancer cell lines in a mouse xenograft model. Increasing DOCA conjugation ratios showed decreased anticoagulant activity, eventually to zero. LHD could block angiogenesis in the tubular formation assay and the Matrigel plug assay. In particular, oral administration of LHD4, which has 4 molecules of DOCA per mole of LMWH, inhibited tumor growth in SCC7 mice model as well as A549 mice xenograft model. LHD4 was orally absorbable, showed minimal anticoagulant activity and inhibits tumor growth via antiangiogenesis. These findings demonstrate the therapeutic potential of LHD4 as a new oral anti-cancer drug.

Tumor-homing multifunctional nanoparticles for cancer theragnosis: Simultaneous diagnosis, drug delivery, and therapeutic monitoring

Kim, K.,Kim, J.H.,Park, H.,Kim, Y.S.,Park, K.,Nam, H.,Lee, S.,Park, J.H.,Park, R.W.,Kim, I.S.,Choi, K.,Kim, S.Y.,Park, K.,Kwon, I.C. Elsevier Science Publishers 2010 Journal of controlled release Vol.146 No.2

Theragnostic multifunctional nanoparticles hold great promise in simultaneous diagnosis of disease, targeted drug delivery with minimal toxicity, and monitoring of treatment. One of the current challenges in cancer treatment is enhancing the tumor-specific targeting of both imaging probes and anticancer agents. Herein, we report tumor-homing chitosan-based nanoparticles (CNPs) that simultaneously execute cancer diagnosis and therapy (cancer theragnosis). These CNPs are unique for their three distinctive characteristics, such as stability in serum, deformability, and rapid uptake by tumor cells. These properties are critical in increasing their tumor targeting specificity and reducing their nonspecific uptake by normal tissues. To develop these CNPs into novel theragnostic nanoparticles, we labeled them with Cy5.5, a near-infrared fluorescent (NIRF) dye, for imaging and also loaded them with paclitaxel (PTX-CNPs), an anticancer drug, for cancer treatment. Cy5.5 labeled PTX-CNPs exhibited significantly increased tumor-homing ability with low nonspecific uptake by other tissues in SCC7 tumor-bearing mice. Theragnostic nanoparticles, Cy5.5 labeled PTX-CNPs, are highly useful for simultaneous diagnosis of early-stage cancer and drug delivery.

Pegylated poly-l-arginine derivatives of chitosan for effective delivery of siRNA

Noh, S.M.,Park, M.O.,Shim, G.,Han, S.E.,Lee, H.Y.,Huh, J.H.,Kim, M.S.,Choi, J.J.,Kim, K.,Kwon, I.C.,Kim, J.S.,Baek, K.H.,Oh, Y.K. Elsevier Science Publishers 2010 Journal of controlled release Vol.145 No.2

For delivery of siRNA, chitosan (CS) was derivatized with poly-l-arginine (PLR) and polyethylene glycol (PEG). The formation of polyplexes with siRNA was confirmed by gel retardation. The PLR-grafted CS formed nanosized particles with siRNA. PLR-grafted CS showed higher cellular delivery efficiency of siRNA than did CS, pegylated CS, PLR, or pegylated PLR. The extent of reduction in the expression of fluorescent proteins was highest following treatment of the cells using PLR derivatives of CS in complexes with specific siRNAs. Cell viability was greater in populations treated with pegylated CS-PLR than in those treated with PLR. Hemolysis of erythrocytes was reduced upon conjugation of PLR with CS. The delivery of siRNAs via pegylated CS-PLR revealed little dependence on serum. Molecular imaging techniques revealed that the intratumoral administration of red fluorescent protein-specific siRNA in complexes with pegylated CS-PLR significantly silenced the expression of red fluorescent proteins in tumor tissues in vivo. These results indicate that pegylated CS-PLR might be useful for in vivo delivery of therapeutic siRNAs.