Youngjoo Kim

MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2)

MicroRNAs (miRNAs) constitute a class of small noncoding RNAs that play important roles in a variety of biological processes including development, apoptosis, proliferation, and differentiation. Here we show that the expression of miR-199a and miR-199a*(miR-199a/a*), which are processed from the same precursor, is confined to fibroblast cells among cultured cell lines. The fibroblast-specific expression pattern correlated well with methylation patterns: gene loci on chromosome 1 and 19 were fully methylated in all examined cell lines but unmethylated in fibroblasts. Transfection of miR-199a and/or -199a* mimetics into several cancer cell lines caused prominent apoptosis with miR-199a* being more pro-apoptotic. The mechanism underlying apoptosis induced by miR-199a was caspase-dependent, whereas a caspase-independent pathway was involved in apoptosis induced by miR-199a* in A549 cells. By employing microarray and immunoblotting analyses, we identified the MET proto-oncogene as a target of miR-199a*. Studies with a luciferase reporter fused to the 3′-untranslated region of the MET gene demonstrated miR-199a*-mediated down-regulation of luciferase activity through a binding site of miR-199a*. Interestingly, extracellular signal-regulated kinase 2 (ERK2) was also down-regulated by miR-199a*. Coordinated down-regulation of both MET and its downstream effector ERK2 by miR-199a* may be effective in inhibiting not only cell proliferation but also motility and invasive capabilities of tumor cells.

A protein interaction network associated with asthma.

Identifying candidate genes related to complex diseases or traits and mapping their relationships require a system-level analysis at a cellular scale. The objective of the present study is to systematically analyze the complex effects of interrelated genes and provide a framework for revealing their relationships in association with a specific disease (asthma in this case). We observed that protein-protein interaction (PPI) networks associated with asthma have a power-law connectivity distribution as many other biological networks have. The hub nodes and skeleton substructure of the result network are consistent with the prior knowledge about asthma pathways, and also suggest unknown candidate target genes associated with asthma, including GNB2L1, BRCA1, CBL, and VAV1. In particular, GNB2L1 appears to play a very important role in the asthma network through frequent interactions with key proteins in cellular signaling. This network-based approach represents an alternative method for analyzing the complex effects of candidate genes associated with complex diseases and suggesting a list of gene drug targets. The full list of genes and the analysis details are available in the following online supplementary materials: http://biosoft.kaist.ac.kr:8080/resources/asthma_ppi.

An optimal operating policy for the production system with rework

Rework, the transformation of defective products generated during production period into serviceable ones, is an important issue in reverse logistics. This paper studies a production inventory system with rework where a stationary demand is satisfied either by production setup with new raw materials or by rework setup with defective items coming from production process. Through the formulation of mathematical models, we find simultaneously the optimal number of production and rework setups in a cycle, their sequence, and the economic production quantity of each setup. Numerical examples are solved to illustrate the validity of the solution procedure proposed.

SSL-Based Lightweight Security of IP-Based Wireless Sensor Networks

IP-based wireless sensor networks (IP-WSN) are popularly recognized as a global sensor networks infrastructure by combining IPv6 technology with wireless sensor networks (WSN). However, IP-WSN, currently, does not provide security because it is commonly recognized that it is a big burden for IP-WSN to adapt Internets dominant security protocol. We suggest a security protocol for IP-WSN based on Secure Sockets Layer (SSL). We have developed IP-WSN sensor node hardware with 16-bit MSP430 MCU including 116 KB Flash and 8 KB RAM, and implemented IP-WSN software stack and lightweight SSL components. The resource consumption is around 64 KB of Flash and 7 KB of RAM when it is used that ECC for key-exchange and authentication, RC4 for data encryption, and MD5 for hashing. And it takes total 2 s for a full SSL handshake and a 127 bytes packet transfer. It can make IP-WSN secure and be used for the public and private services such as military observation, healthcare, and home-network.

UPnP-ZigBee internetworking architecture mirroring a multi-hop ZigBee network topology

In this paper, we present a UPnP-ZigBee internetworking architecture. Different from traditional internetworking architectures which focus on integrating either wired networks or single-hop wireless networks into UPnP networks, integrating ZigBee with UPnP is more difficult because ZigBee nodes communicate over multi-hop wireless network, and further their short addresses can be changed due to mobility of ZigBee nodes. To cope with it, we combine UPnP-ZigBee gateway with ZigBee network topology monitoring functions. A UPnP-ZigBee gateway mirrors ZigBee network topology; therefore, it creates, terminates, and updates virtual UPnP proxies according to ZigBee topology changes. Thus, the proposed internetworking architecture dynamically and automatically integrates ZigBee devices into the UPnP network and provides seamless internetworking between a multi-hop ZigBee network and the UPnP network. We have demonstrated the proposed architecture by implementing both the UPnP-ZigBee gateway and network monitoring functions and integrating them together. By conducting experiments on physical testbed, we have shown that the proposed architecture provides dynamic integration and seamless internetworking.

AsiDesigner: exon-based siRNA design server considering alternative splicing

RNA interference (RNAi) with small interfering RNA (siRNA) has become a powerful tool in functional and medical genomic research through directed post-transcriptional gene silencing. In order to apply RNAi technique for eukaryotic organisms, where frequent alternative splicing results in diversification of mRNAs and finally of proteins, we need spliced mRNA isoform silencing to study the function of individual proteins. AsiDesigner is a web-based siRNA design software system, which provides siRNA design capability to account for alternative splicing for mRNA level gene silencing. It provides numerous novel functions including the designing of common siRNAs for the silencing of more than two mRNAs simultaneously, a scoring scheme to evaluate the performance of designed siRNAs by adopting currently known key design factors, a stepwise off-target searching with BLAST and FASTA algorithms and checking the folding secondary structure energy of siRNAs. To do this, we developed a novel algorithm to evaluate the common target region, where siRNAs can be designed to knockdown a specific mRNA isoform or more than two mRNA isoforms from a target gene simultaneously. The developed algorithm and the AsiDesigner were tested and validated as very effective throughout widely performed gene silencing experiments. It is expected that AsiDesigner will play an important role in functional genomics, drug discovery and other molecular biological research. AsiDesigner is freely accessible at http://sysbio.kribb.re.kr/AsiDesigner/.

Dual knockdown of p65 and p50 subunits of NF-kappaB by siRNA inhibits the induction of inflammatory cytokines and significantly enhance apoptosis in human primary synoviocytes treated with tumor necrosis factor-alpha.

In order to develop an anti-NF-κB siRNA as a novel class of anti-inflammatory drug, we have isolated a highly efficient siRNA targeting the p65 (RelA) subunit of NF-κB, hereafter named REL1096. To determine whether down-regulation of p65 by REL1096 can block the induction of inflammatory cytokines after treatment with tumor necrosis factor-alpha (TNF-α), human primary fibroblast-like synoviocytes were isolated from patients with rheumatoid arthritis. When treated with REL1096, the TNF-mediated induction of downstream target genes such as inflammatory cytokines, chemokines, and anti-apoptosis genes was drastically inhibited. To enhance the inhibitory effect of REL1096, cells were treated with siRNA targeting the p50 subunit of NF-κB together with REL1096. In addition to effective downregulation of inflammatory cytokines, knockdown of both p65 and p50 resulted in much more extensive apoptosis when compared to cells treated with either REL1096 or p50-siRNA alone. Thus, our results provide evidence for the potential use of siRNA targeting NF-κB as an effective means to treat rheumatoid arthritis. In addition to effective amelioration of synovial inflammation by downregulation of inflammatory cytokines, increased apoptosis by dual knockdown of p65 and p50 may prove advantageous in preventing invasiveness and destructiveness of hyperplastic synoviocytes.

A genome-wide scan for the Sasang constitution in a Korean family suggests significant linkage at chromosomes 8q11.22-23 and 11q22.1-3.

OBJECTIVESnWe aim to identify the genetic loci responsible for Sasang constitution type, which is important for effective personalized treatments in traditional Korean medicine.nnnSUBJECTSnForty (40) individuals in a Korean family were recruited for linkage analysis and 310 unrelated individuals for association analysis to confirm the linkage result.nnnOUTCOME MEASURESnGenome-wide linkage analysis was performed for the Korean family using the Affymetrix 500K arrays. MERLIN software was used for multipoint nonparametric linkage (NPL) analysis. The significant candidate regions in linkage analysis were also investigated with association analysis of independent 310 individuals.nnnRESULTSnLinkage analysis showed four significant peaks, 3q27.3, 8p11.21, 8q11.22-23, and 11q22.1-3, whose NPL Z scores are greater than 5.0. Among the significant loci, the 8q11.22-23 and 11q22.1-3 regions were supported by independent association analysis at the level of p < 0.05.nnnCONCLUSIONSnThe 8q11.22-23 and 11q22.1-3 regions were suggested as the candidate region for significant linkage to Sasang constitution.

SNP@Domain: a web resource of single nucleotide polymorphisms (SNPs) within protein domain structures and sequences

The single nucleotide polymorphisms (SNPs) in conserved protein regions have been thought to be strong candidates that alter protein functions. Thus, we have developed SNP@Domain, a web resource, to identify SNPs within human protein domains. We annotated SNPs from dbSNP with protein structure-based as well as sequence-based domains: (i) structure-based using SCOP and (ii) sequence-based using Pfam to avoid conflicts from two domain assignment methodologies. Users can investigate SNPs within protein domains with 2D and 3D maps. We expect this visual annotation of SNPs within protein domains will help scientists select and interpret SNPs associated with diseases. A web interface for the SNP@Domain is freely available at and from .

Industrial application of concolic testing approach: a case study on libexif by using CREST-BV and KLEE

As smartphones become popular, manufacturers such as Samsung Electronics are developing smartphones with rich functionality such as a camera and photo editing quickly, which accelerates the adoption of open source applications in the smartphone platforms. However, developers often do not know the detail of open source applications, because they did not develop the applications themselves. Thus, it is a challenging problem to test open source applications effectively in short time. This paper reports our experience of applying concolic testing technique to test libexif, an open source library to manipulate EXIF information in image files. We have demonstrated that concolic testing technique is effective and efficient at detecting bugs with modest effort in industrial setting. We also compare two concolic testing tools, CREST-BV and KLEE, in this testing project. Furthermore, we compare the concolic testing results with the analysis result of the Coverity Prevent static analyzer. We detected a memory access bug, a null pointer dereference bug, and four divide-by-zero bugs in libexif through concolic testing, none of which were detected by Coverity Prevent.