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Kurokawa, Manabu,Kim, Jiyeon,Geradts, Joseph,Matsuura, Kenkyo,Liu, Liu,Ran, Xu,Xia, Wenle,Ribar, Thomas J.,Henao, Ricardo,Dewhirst, Mark W.,Kim, Wun-Jae,Lucas, Joseph E.,Wang, Shaomeng,Spector, Neil L AAAS 2013 Science signaling Vol.6 No.274
<P><B>Breaking Down to Build Resistance</B></P><P>Chemotherapeutic resistance often arises because of the rewiring of signaling pathways in cancer cells. Kurokawa <I>et al.</I> found that the ubiquitin E3 ligase MDM2 triggered the breakdown of another ubiquitin E3 ligase, HUWE1. In breast cancer cells that died when exposed to the HER2 (human epidermal growth factor receptor 2) EGFR (epidermal growth factor receptor) tyrosine kinase inhibitor lapatinib, MDM2 was degraded, which enabled HUWE1 to trigger the degradation of a prosurvival protein and promote assembly and activation of a protein complex required for the execution of cell death. However, MDM2 degradation did not occur in lapatinib-resistant breast cancer cells, and thus, the abundance of HUWE1 was decreased, promoting cell survival. In a mouse xenograft model, an inhibitor of MDM2 reduced the growth of tumors generated from lapatinib-resistant breast cancer cells. Thus, MDM2 could be targeted to circumvent resistance to lapatinib in breast cancers.</P>
Kurokawa, Kenji,Hamamoto, Hiroshi,Matsuo, Miki,Nishida, Satoshi,Yamane, Noriko,Lee, Bok Luel,Murakami, Kazuhisa,Maki, Hideki,Sekimizu, Kazuhisa American Society for Microbiology 2009 Antimicrobial Agents and Chemotherapy Vol.53 No.9
<B>ABSTRACT</B><P>The availability of a silkworm larva infection model to evaluate the therapeutic effectiveness of antibiotics was examined. The 50% effective doses (ED50) of d-cycloserine against the <I>Staphylococcus aureus ddlA</I> mutant-mediated killing of larvae were remarkably lower than those against the parental strain-mediated killing of larvae. Changes in MICs and ED50 of other antibiotics were negligible, suggesting that these alterations are d-cycloserine selective. Therefore, this model is useful for selecting desired compounds based on their therapeutic effectiveness during antibiotic development.</P>
Dynamic Characteristics of DC-DC Converters Using Digital Filters
Kurokawa, Fujio,Okamatsu, Masashi,Ishibashi, Taku,Nishida, Yasuyuki The Korean Institute of Power Electronics 2009 JOURNAL OF POWER ELECTRONICS Vol.9 No.3
This paper presents the dynamic characteristics of buck and buck-boost dc-dc converters with digital filters. At first, the PID, the minimum phase FIR filter and the IIR filter controls are discussed in the buck dc-dc converter. Comparisons of the dynamic characteristics between the buck and buck-boost converters are then discussed. As a result, it is clarified that the superior dynamic characteristics are realized in the IIR filter method. In the buck converter, the undershoot is less than 2% and the transient time is less than 0.4ms. On the other hand, in the buck-boost converter, the undershoot is about 3%. However, the transient time is approximately over 4ms because the output capacitance is too large to suppress the output voltage ripple in this type of converter.
Kurokawa, Kenji,Jung, Dong-Jun,An, Jang-Hyun,Fuchs, Katharina,Jeon, Yu-Jin,Kim, Na-Hyang,Li, Xuehua,Tateishi, Koichiro,Park, Ji Ae,Xia, Guoqing,Matsushita, Misao,Takahashi, Kazue,Park, Hee-Ju,Peschel, American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.43
<P>Serum antibodies and mannose-binding lectin (MBL) are important host defense factors for host adaptive and innate immunity, respectively. Antibodies and MBL also initiate the classical and lectin complement pathways, respectively, leading to opsonophagocytosis. We have shown previously that <I>Staphylococcus aureus</I> wall teichoic acid (WTA), a cell wall glycopolymer consisting of ribitol phosphate substituted with α- or β-<I>O-N</I>-acetyl-<SMALL>d</SMALL>-glucosamine (GlcNAc) and <SMALL>d</SMALL>-alanine, is recognized by MBL and serum anti-WTA IgG. However, the exact antigenic determinants to which anti-WTA antibodies or MBL bind have not been determined. To answer this question, several <I>S. aureus</I> mutants, such as α-GlcNAc glycosyltransferase-deficient <I>S. aureus</I> Δ<I>tarM</I>, β-GlcNAc glycosyltransferase-deficient Δ<I>tarS</I>, and Δ<I>tarMS</I> double mutant cells, were prepared from a laboratory and a community-associated methicillin-resistant <I>S. aureus</I> strain. Here, we describe the unexpected finding that β-GlcNAc WTA-deficient Δ<I>tarS</I> mutant cells (which have intact α-GlcNAc) escape from anti-WTA antibody-mediated opsonophagocytosis, whereas α-GlcNAc WTA-deficient Δ<I>tarM</I> mutant cells (which have intact β-GlcNAc) are efficiently engulfed by human leukocytes via anti-WTA IgG. Likewise, MBL binding in <I>S. aureus</I> cells was lost in the Δ<I>tarMS</I> double mutant but not in either single mutant. When we determined the serum concentrations of the anti-α- or anti-β-GlcNAc-specific WTA IgGs, anti-β-GlcNAc WTA-IgG was dominant in pooled human IgG fractions and in the intact sera of healthy adults and infants. These data demonstrate the importance of the WTA sugar conformation for human innate and adaptive immunity against <I>S. aureus</I> infection.</P>
Kurokawa, Kenji,Lee, Hanna,Roh, Kyung-Baeg,Asanuma, Miwako,Kim, Young Sook,Nakayama, Hiroshi,Shiratsuchi, Akiko,Choi, Youngnim,Takeuchi, Osamu,Kang, Hee Jung,Dohmae, Naoshi,Nakanishi, Yoshinobu,Akira, American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.13
<P>Some synthetic lipopeptides, in addition to native lipoproteins derived from both Gram-negative bacteria and mycoplasmas, are known to activate TLR2 (Toll-like receptor 2). However, the native lipoproteins inherent to Gram-positive bacteria, which function as TLR2 ligands, have not been characterized. Here, we have purified a native lipoprotein to homogeneity from Staphylococcus aureus to study as a native TLR2 ligand. The purified 33-kDa lipoprotein was capable of stimulating TLR2 and was identified as a triacylated SitC lipoprotein, which belongs to a family of ATP binding cluster (ABC) transporter substrate-binding proteins. Analyses of the SitC-mediated production of cytokine using mouse peritoneal macrophages revealed that the SitC protein (3 nm) induced the production of tumor necrosis factor-alpha and interleukin-6. Moreover, analysis of knock-out mice showed that SitC required TLR2 and MyD88, but not TLR1 or TLR6, for the induction of cytokines. In addition to the S. aureus SitC lipoprotein, we purified two other native ABC transporter substrate-binding lipoproteins from Bacillus subtilis and Micrococcus luteus, which were both shown to stimulate TLR2. These results demonstrate that S. aureus SitC lipoprotein is triacylated and that the ABC transporter substrate-binding lipoproteins of Gram-positive bacteria function as native ligands for TLR2.</P>
J-Groove Technique for Suppressing Various Anomalous Flow Phenomena in Turbomachines
Kurokawa, Junichi Korean Society for Fluid machinery 2011 International journal of fluid machinery and syste Vol.4 No.1
In operating a turbomachine at off-design conditions various instabilities caused by anomalous flow phenomena occur and sometimes lead to the damage of a turbomachine. In order to avoid these phenomena various devices characteristic to each phenomenon have been developed, however they make turbomachines large-sized and cause efficiency drop. The present author has developed a very simple and innovative device, termed "J-groove," of suppressing various anomalous flow phenomena commonly by controlling the angular momentum of the main flow. It has been revealed that J-groove makes an operation of a turbomachine stable in all flow range, causes little efficiency drop, and can be easily applied to an existing machine. Here is reviewed totally the results of suppressing various anomalous flow phenomena in turbomachines.
Flow Analysis in Positive Displacement Micro-Hydro Turbine and Development of Low Pulsation Turbine
Kurokawa, Junichi,Matsui, Jun,Choi, Young-Do Korean Society for Fluid machinery 2008 International journal of fluid machinery and syste Vol.1 No.1
In order to extract micro hydropower in the very low specific speed range, a Positive Displacement Turbine (PDT) was proposed and steady performance was determined experimentally. However, the suppression of large pressure pulsation is inevitable for practical application of PDT. The objective of the present study is to reveal the mechanism and the characteristics of pressure pulsation in PDT by use of CFD and to suppress the pressure pulsation. Unsteady CFD analysis has revealed that large pressure pulsation is caused by large variation of rotational speed of the following rotor, while the driving rotor, which is output rotor, keeps constant speed. Here is newly proposed a 4-lobe helical type rotor which can reduce the pressure pulsation drastically and the performance prediction of new PDT is determined.