Young-Il Kim

A cluster validation index for GK cluster analysis based on relative degree of sharing

In this paper, the problem of traditional validity indices when applied to the Gustafson-Kessel (GK) clustering are reviewed. A new cluster validity index for the GK algorithm is proposed. This validity index is defined as the average value of the relative degrees of sharing of all possible pairs of fuzzy clusters in the system. It computes the overlap of each pair of fuzzy clusters by considering the degree of sharing of each data point in the overlap. The optimal number of clusters is obtained by minimizing the validity index. Experiments in which the proposed validity index and several traditional validity indices were applied to 6 data sets highlight the superior qualities of the proposed index. The results indicate that the proposed validity index is very reliable.

A genetic screen for modifiers of Drosophila caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes

BackgroundCaspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of Dcp-1 gain-of-function (GF) animals by screening promoter element- inserted Drosophila melanogaster lines (EP lines).ResultsWe screened ~15,000 EP lines and identified 72 Dcp-1-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by Dcp-1 GF. Paradoxically, we found that over-expression of full-length Dcp-1 induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation.ConclusionsWe identified a number of Dcp-1 modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that Dcp-1 and autophagy-related genes influence each other will aid future investigations of the complicated relationships between apoptosis and autophagy.

Communication-efficient hardware acceleration for fast functional simulation

This paper presents new technology that accelerates system verification. Traditional methods for verifying functional designs are based on logic simulation, which becomes more time-consuming as design complexity increases. To accelerate functional simulation, hardware acceleration is used to offload calculation-intensive tasks from the software simulator. Hardware accelerated simulation dramatically reduces the simulation time. However, the communication overhead between the software simulator and hardware accelerator is becoming a new critical bottleneck. We reduce the communication overhead by exploiting burst data transfer and parallelism, which are obtained by splitting testbench and moving a part of testbench into hardware accelerator. Our experiments demonstrated that the proposed method reduces the communication overhead by a factor of about 40 compared to conventional hardware accelerated simulation while maintaining the cycle accuracy and compatibility with the original testbench.

TAK1 regulates autophagic cell death by suppressing the phosphorylation of p70 S6 kinase 1

There is growing interest in identifying regulators of autophagy. The molecular mechanism underlying transforming growth factor-β activated kinase 1 (TAK1)-induced autophagy is poorly understood. We found that TAK1 inhibits p70 S6 kinase1 (S6K1) phosphorylation by interfering interaction of raptor with S6K1, thus inducing autophagy. The factors that determine whether autophagy is cytoprotective or cytotoxic have not been fully elucidated. In Drosophila, TAK1 overexpression leads to an impaired eye phenotype despite inhibition of apoptosis, indicating that the phenotype was mainly due to autophagy. Also, TAK1 overexpression increases lactate dehydrogenase (LDH) level in mammalian cells. When treated with autophagy inhibitors, the level of TAK1-induced cytotoxicity or cell death was significantly attenuated, indicating that TAK1 induces cytotoxic autophagic cell death. This study provides the first in vitro and in vivo evidence of TAK1-induced autophagy and we believe that our findings significantly contribute to the understanding of the mechanisms underlying the induction of autophagy.

TPartition: testbench partitioning for hardware-accelerated functional verification

This hybrid dynamic simulation scheme implements part of the simulator in software running on a processor and maps the rest onto a programmable hardware accelerator. An algorithm for hardware synthesis of behavioral testbenches enables better partitions, resulting in lower communication costs between the two components. TPartition improves the performance of hardware accelerated simulation without a designers remodeling effort and without losing compatibility with the original testbench.

Systematic functional coverage metric synthesis from hierarchical temporal event relation graph

Functional coverage is a technique for checking the completeness of test vectors in HDL simulation. Temporal events are used to monitor the sequence of events in the specification. In this paper, automatic generation of temporal events for functional coverage is proposed. The HiTER is the graph where nodes represent basic temporal properties or subgraph and edges represent time-shift value between two nodes. Hierarchical temporal events are generated by traversing HiTER such that invalid, or irrelevant properties are eliminated. Concurrent edge groups make it possible to generate more comprehensive temporal properties and hierarchical structure makes it easy to describe large design by combining multiple subgraphs. Automatically generated temporal events describe almost all the possible temporal properties of the design under verification.

Nucleolar GTPase NOG-1 Regulates Development, Fat Storage, and Longevity through Insulin/IGF Signaling in C. elegans

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

Mouse adaptation of influenza B virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets

To investigate the molecular changes that allow influenza B viruses to adapt to new mammalian hosts, influenza B/Florida/04/2006 was serially passaged in BALB/c mice until highly virulent. The viral factors underlying this transition were then investigated in mice and ferrets. Five viruses, including the wild-type virus (P0), three intermediate viruses (P5, P9, and P12), and a lethal mouse-adapted virus (P17 (MA)), harbored one to five amino acid substitutions in the hemagglutinin, M, NP, and PA segments suggesting that these mutations enhance virulence. The P17 (MA) virus replicated significantly more efficiently than the P0 virus both in vitro and in vivo (Pu2009<u20090.0001), and was highly virulent (MLD50: 105.25TCID50) while the P0, P5, and P9 viruses did not kill any infected mice (MLD50u2009>u2009106.0TCID50). Furthermore, the P17 (MA) virus grew to greater titers in the ferret upper respiratory tract compared with the P0 and intermediate viruses, and only the P17 (MA) virus was transmissible between ferrets via both direct and aerosol contact. To our knowledge, this is the first study to demonstrate ferret-to-ferret transmission of influenza B virus and to delineate factors that may affect its transmission.

Complementary Dual Detectors for Effective Classification

In this paper we introduce a method of using a pair of complementary negative detectors. When both self and non-self antigens are given, we can build a pair of complementary negative detectors using self and non-self antigens respectively and augment the results given by the detectors. When self or non-self antigens change over time, antibodies of a negative detector that gives a false positive error for the change, are used to fill the holes of the other negative detector giving a false negative error. They try to adapt to the change in complementary ways.

Rapid acquisition of polymorphic virulence markers during adaptation of highly pathogenic avian influenza H5N8 virus in the mouse

Emergence of a highly pathogenic avian influenza (HPAI) H5N8 virus in Asia and its spread to Europe and North America has caused great concern for human health. Although the H5N8 virus has been only moderately pathogenic to mammalian hosts, virulence can still increase. We evaluated the pathogenic potential of several H5N8 strains via the mouse-adaptation method. Two H5N8 viruses were sequentially passaged in BALB/c mice and plaque-purified from lung samples. The viruses rapidly obtained high virulence (MLD50, up to 0.5 log10u2009PFU/mL) within 5 passages. Sequence analysis revealed the acquisition of several virulence markers, including the novel marker P708S in PB1 gene. Combinations of markers synergistically enhanced viral replication and polymerase activity in human cell lines and virulence and multiorgan dissemination in mice. These results suggest that H5N8 viruses can rapidly acquire virulence markers in mammalian hosts; thus, rapid spread as well as repeated viral introduction into the hosts may significantly increase the risk of human infection and elevate pandemic potential.