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>

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.

Local BMP-7 release from a PLGA scaffolding-matrix for the repair of osteochondral defects in rabbits

Jung, M.R.,Shim, I.K.,Chung, H.J.,Lee, H.R.,Park, Y.J.,Lee, M.C.,Yang, Y.I.,Do, S.H.,Lee, S.J. Elsevier Science Publishers 2012 Journal of controlled release Vol.162 No.3

The use of tissue engineering to repair large osteochondral defects has been impeded by the limited regenerative capacity of cartilage. Herein, we describe the local release of bone morphogenetic protein 7 (BMP-7) to stimulate the bone marrow-derived progenitors to repair osteochondral defects. BMP-7-releasing poly(d,l-lactide-co-glycolide) (PLGA) matrix was specially designed to retain the dual-function of local BMP-7 release and progenitor-scaffolding with its defect-fitting architecture. To optimize the release kinetics during the repair period, BMP-7/PLGA film was cast on the surface of a cylindrical PLGA matrix. The matrix demonstrated a release profile of BMP-7 in a sustained manner over 28days, maintaining its biological activity. The cylindrical PLGA matrices loaded with BMP-7 were implanted into the osteochondral defects (2mm in diameter, 3mm in depth) in rabbit knees. Histological observations revealed that neo-cartilage generation was completed in a well-integrated morphology with its surrounding normal cartilage and subchondral bone at 12weeks post-implantation. Partial degradation of the PLGA matrix during the repair period guided neo-cartilage formation, which verified the effective scaffolding function of the matrix. Regenerated cartilage in BMP-7-treated defects stained positive for type II collagen and glycosaminoglycan (GAG). Adjacent BMP-7-untreated defects were also repaired with cartilage regeneration, suggesting the effect of local BMP-7 release in the synovial fluid. The BMP-7-unloaded PLGA matrix demonstrated guided cartilage regeneration to a certain extent, whereas the adjacent defects without the matrix revealed only fibrous tissue infiltration. These results indicated that a strategy employing the combined functions of local BMP-7 release and the cell scaffolding of a PLGA matrix might be a potential modality for osteochondral repair.

A combined theoretical and in vitro modeling approach for predicting the magnetic capture and retention of magnetic nanoparticles in vivo

David, A.E.,Cole, A.J.,Chertok, B.,Park, Y.S.,Yang, V.C. Elsevier Science Publishers 2011 Journal of controlled release Vol.152 No.1

Magnetic nanoparticles (MNP) continue to draw considerable attention as potential diagnostic and therapeutic tools in the fight against cancer. Although many interacting forces present themselves during magnetic targeting of MNP to tumors, most theoretical considerations of this process ignore all except for the magnetic and drag forces. Our validation of a simple in vitro model against in vivo data, and subsequent reproduction of the in vitro results with a theoretical model indicated that these two forces do indeed dominate the magnetic capture of MNP. However, because nanoparticles can be subject to aggregation, and large MNP experience an increased magnetic force, the effects of surface forces on MNP stability cannot be ignored. We accounted for the aggregating surface forces simply by measuring the size of MNP retained from flow by magnetic fields, and utilized this size in the mathematical model. This presumably accounted for all particle-particle interactions, including those between magnetic dipoles. Thus, our ''corrected'' mathematical model provided a reasonable estimate of not only fractional MNP retention, but also predicted the regions of accumulation in a simulated capillary. Furthermore, the model was also utilized to calculate the effects of MNP size and spatial location, relative to the magnet, on targeting of MNPs to tumors. This combination of an in vitro model with a theoretical model could potentially assist with parametric evaluations of magnetic targeting, and enable rapid enhancement and optimization of magnetic targeting methodologies.

Viral genome DNA/lipoplexes elicit in situ oncolytic viral replication and potent antitumor efficacy via systemic delivery

Kwon, O.J.,Kang, E.,Kim, S.,Yun, C.O. Elsevier Science Publishers 2011 Journal of controlled release Vol.155 No.2

Modifying the viral genome to express potent and cancer-selective therapeutic genes has enhanced the role of adenoviruses (Ads) in cancer molecular therapeutics. However, the efficacy of Ad systemic delivery in vivo is limited by neutralizing antibodies, short blood circulation time, and high levels of nonspecific liver uptake resulting in hepatotoxicity. We therefore investigated the systemic delivery of tumor necrosis factor-related apoptosis-inducing ligand-expressing oncolytic Ad genome DNA (pmT-d19/stTR) via lipid envelopment as an alternative approach for cancer virotherapy in an orthotopic lung cancer model. Cationic liposomes (DOTAP/DOPE) were complexed with pmT-d19/stTR to generate pmT-d19/stTR+DOTAP/DOPE with the average diameter of which was 143.3+/-5.7nm at the optimal DNA:lipid ratio (1:6). Systemic administration of pmT-d19/stTR+DOTAP/DOPE elicited highly effective antitumor responses in vivo, with tumor volumes decreasing 94.5%, 90.5%, and 92.4% compared to phosphate buffered saline-, naked Ad (mT-d19/stTR)-, or pmT-d19/stTR-treated groups, respectively. Additionally, innate immune responses and Ad-specific neutralizing antibodies were significantly decreased in pmT-d19/stTR+DOTAP/DOPE-treated mice compared to those in the mT-d19/stTR-treated group. The biodistribution profile analyzed by quantitative-PCR and immunohistochemical analysis demonstrated that viral replication occurred preferentially in tumor tissues. Moreover, the viral genome tumor-to-liver ratio was significantly elevated in pmT-d19/stTR+DOTAP/DOPE-treated mice, which was 934- and 27-fold greater than the mT-d19/stTR- and pmT-d19/stTR-treated mice, respectively. These results demonstrate that systemic delivery of oncolytic viral genome DNA with liposomes is a powerful alternative to naked Ad, overcoming the limited clinical applicability of conventional Ads and enabling effective treatment of disseminated metastatic tumors.

Efficient skin permeation of soluble proteins via flexible and functional nano-carrier

Choi, W.I.,Lee, J.H.,Kim, J.Y.,Kim, J.C.,Kim, Y.H.,Tae, G. Elsevier Science Publishers 2012 Journal of controlled release Vol.157 No.2

In spite of several intrinsic and distinct advantages, a topical and transdermal administration of drugs has been limited mainly due to very low permeability of drugs across skin. Especially, it is generally regarded that hydrophilic macromolecules such as proteins, peptides, and vaccines cannot penetrate across skin. In this study, we demonstrated that chitosan-conjugated, Pluronic-based nano-carrier (nanogel) can act as an efficient delivery vehicle of hydrophilic proteins across human skin. The functional nano-carrier (<100nm in size), chemically-crosslinking Pluronic F 127 with chitosan conjugation, is flexible and soft with reservoir characteristics for biomacromolecules. The in-vitro permeation experiments through human cadaver skin revealed remarkable permeability of hydrophilic proteins of various sizes including FITC-BSA (67kDa) and FITC-Insulin (6kDa) by direct penetration of the nano-carrier across skin. The bioactivity post-permeation of proteins via the functional nano-carrier was also confirmed by delivering sz-galactosidase. Results presented in this paper suggest the use of chitosan-conjugated flexible nano-carrier as a novel platform for transcutaneous delivery of hydrophilic macromolecules and other drug-delivery applications.

Enhanced cytosolic drug delivery using fully biodegradable poly(amino oxalate) particles

Seong, K.,Seo, H.,Ahn, W.,Yoo, D.,Cho, S.,Khang, G.,Lee, D. Elsevier Science Publishers 2011 Journal of controlled release Vol.152 No.2

Rapid endosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially proteins that are susceptible to lysosomal degradation. In this paper, we report poly(amino oxalate) (PAOX) as a new protein delivery system that is capable of disrupting endosomes and mediating cytosolic drug delivery. A cationic fully-biodegradable PAOX was synthesized from a one-step reaction of oxalyl chloride, cyclohexanedimethanol and piperazinediethanol. The incorporation of tertiary amine groups in the backbone of PAOX enhanced its hydrolytic nature, which results in a fast drug release. The studies of confocal fluorescence imaging using calcein and LysoTracker Red revealed that PAOX particles disrupted endosomes via ''proton sponge'' effects and mediated the cytosolic delivery of membrane-impermeable calcein. A protein delivery efficiency of PAOX particles was evaluated using catalase as a model protein. Catalase-loaded PAOX microparticles significantly inhibited hydrogen peroxide generation in Phorbol-12-myristate-13-acetate (PMA)-stimulated macrophages, in a dose-dependent manner. Given the excellent biocompatibility and physicochemical properties, we anticipate that PAOX is a promising cytosolic protein delivery system and is useful for the treatment of acute inflammatory diseases.

Facilitated intracellular delivery of peptide-guided nanoparticles in tumor tissues

Kim, J.H.,Bae, S.M.,Na, M.H.,Shin, H.,Yang, Y.J.,Min, K.H.,Choi, K.Y.,Kim, K.,Park, R.W.,Kwon, I.C.,Lee, B.H.,Hoffman, A.S.,Kim, I.S. Elsevier Science Publishers 2012 Journal of controlled release Vol.157 No.3

Macromolecular nanoparticles can extravasate and accumulate within tumor tissues via the passive targeting system, reflecting enhanced permeability and the retention effect. However, the unsatisfactory tumor therapeutic efficacy of the passive-targeting system, attributable to the retention of extravasated nanoparticles in the vicinity of tumor vessels, argues that a new system that facilitates intracellular delivery of nanoparticles within tumors is needed. Here, we developed hydrophobically modified glycol chitosan (HGC) nanoparticles conjugated with interleukin-4 receptor (IL-4R) binding peptides, termed I4R, and tested them in mice bearing IL-4R-positive tumors. These HGC-I4R nanoparticles exhibited enhanced IL-4R-dependent cellular uptake in tumors compared to nonconjugated nanoparticles, leading to better therapeutic and imaging efficacy. We conclude that I4R facilitates and enhances cellular uptake of nanoparticles in tumor tissues. This study suggests that the intracelluar uptake of nanoparticles in tumors is an essential factor to consider in designing nanoparticles for tumor-targeted drug delivery and imaging.

Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction

Jeong, J.H.,Yook, S.,Jung, Y.,Im, B.H.,Lee, M.,Ahn, C.H.,Lee, D.Y.,Byun, Y. Elsevier Science Publishers 2012 Journal of controlled release Vol.159 No.3

This study assessed whether the newly designed exendin-4 (Ex-4) gene with highly releasable characteristics could enhance the beta cell function, thereby attenuating the essential islet mass required to cure diabetes. We constructed a lentivirus system encoding for a highly releasable secretion signal peptide, the peptide linked Ex-4 (SP-Ex-4) gene. After the transduction of lentivirus encoding for SP-Ex-4 (LV-SP-Ex-4) gene into the islets, the therapeutic effects of Ex-4 secreted were evaluated by conducting glucose-stimulated insulin secretion and cytokine- or hypoxia-induced apoptosis. Additionally, the effect of reduced islet numbers for transplantation was evaluated via in vivo models. The transduction of LV-SP-Ex-4 gene did not affect the viability of islets. In diabetic animal models, 50 islets expressing Ex-4 were transplanted to cure the diabetic nude mice, whereas at least 150 untransduced islets had to be transplanted to cure the diabetic nude mice. When the transduced islets were transplanted into diabetic immunocompetent mice, the survival rate of the mice was 18.0+/-4.9days; however, when the untransduced islets were transplanted, they were rejected within 10.0+/-0.6days. Therefore, the highly releasable Ex-4 could enhance the beta cell function with slightly enhanced viability of transplanted islets, presenting as a potential technology for overcoming islet shortage.