182 research outputs found

    Evidence for the singlet-dimer ground state in an S = 1 antiferromag netic bond alternating chain

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    Susceptibility, ESR and magnetization measurements have been performed on si ngle crystals of an S=1 bond alternating chain compound: [Ni(333-tet)(\mu-NO _2)](ClO_4) (333-tet = N,N'-bis(3-aminopropyl)propane-1,3-diamine) and the c ompound doped with a small amount of Zn. We observed an anomalous angular de pendence in the Zn-doped sample. These behaviors are well explained by the m odel based on the VBS picture for the singlet-dimer phase. The picture impli es that the free spins of S=1 with a positive single-ion anisotropy are indu ced at the edges of the chains without forming the singlet-dimer.Comment: RevTeX, 14pages (preprint.sty) with 5figures, submitted to Phys. R ev. Let

    A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

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    BACKGROUND: Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown the elevated expression levels of TfR on cancer cells compared with normal cells. The elevated expression levels of this receptor in malignancies, which is the accessible extracellular protein, can be a fascinating target for the treatment of cancer. We have recently designed novel type of immunotoxin, termed "hybrid peptide", which is chemically synthesized and is composed of target-binding peptide and lytic peptide containing cationic-rich amino acids components that disintegrates the cell membrane for the cancer cell killing. The lytic peptide is newly designed to induce rapid killing of cancer cells due to conformational change. In this study, we designed TfR binding peptide connected with this novel lytic peptide and assessed the cytotoxic activity in vitro and in vivo. METHODS: In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed. RESULTS: The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC(50 )values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC(50 )values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively kill these cells and induce approximately 80% apoptotic cell death but not in normal cells. The intravenous administration of TfR-lytic peptide in the athymic mice model significantly inhibited tumor progression. CONCLUSIONS: TfR-lytic peptide might provide a potent and selective anticancer therapy for patients

    Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent

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    <p>Abstract</p> <p>Background</p> <p>Despite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.</p> <p>Methods</p> <p>We focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.</p> <p>Results</p> <p>It was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer cell lines <it>in vitro</it>. In contrast, Antp-TPR peptide did not affect the viability of normal cells. Moreover, analysis <it>in vivo </it>revealed that Antp-TPR peptide displayed a significant antitumor activity in a xenograft model of human pancreatic cancer in mice.</p> <p>Conclusion</p> <p>These results indicate that Antp-TPR peptide would provide a potent and selective anticancer therapy to cancer patients.</p

    Rat limbal epithelial side population cells exhibit a distinct expression of stem cell markers that are lacking in side population cells from the central cornea

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    AbstractThe side population (SP) phenotype is shared by stem cells in various tissues and species. Here we demonstrate SP cells with Hoechst dye efflux were surprisingly collected from the epithelia of both the rat limbus and central cornea, unlike in human and rabbit eyes. Our results show that rat limbal SP cells have a significantly higher expression of the stem cell markers ABCG2, nestin, and notch 1, compared to central corneal SP cells. Immunohistochemistry also revealed that ABCG2 and the epithelial stem/progenitor cell marker p63 were expressed only in basal limbal epithelial cells. These results demonstrate that ABCG2 expression is closely linked to the stem cell phenotype of SP cells

    ASTE CO(3-2) Mapping toward the Whole Optical Disk of M 83: Properties of Inter-arm GMAs

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    We present a new on-the-fly (OTF) mapping of CO(J=3-2) line emission with the Atacama Submillimeter Telescope Experiment (ASTE) toward the 8' x 8' (or 10.5 x 10.5 kpc at the distance of 4.5 Mpc) region of the nearby barred spiral galaxy M 83 at an effective resolution of 25''. Due to its very high sensitivity, our CO(J=3-2) map can depict not only spiral arm structures but also spur-like substructures extended in inter-arm regions. This spur-like substructures in CO(J=3-2) emission are well coincident with the distribution of massive star forming regions traced by Halpha luminosity and Spitzer/IRAC 8 um emission. We have identified 54 CO(J=3-2) clumps as Giant Molecular-cloud Associations (GMAs) employing the CLUMPFIND algorithm, and have obtained their sizes, velocity dispersions, virial masses, and CO luminosity masses. We found that the virial parameter alpha, which is defined as the ratio of the virial mass to the CO luminosity mass, is almost unity for GMAs in spiral arms, whereas there exist some GMAs whose alpha are 3 -- 10 in the inter-arm region. We found that GMAs with higher α\alpha tend not to be associated with massive star forming regions, while other virialized GMAs are. Since alpha mainly depends on velocity dispersion of the GMA, we suppose the onset of star formation in these unvirialized GMAs with higher alpha are suppressed by an increase in internal velocity dispersions of Giant Molecular Clouds within these GMAs due to shear motion.Comment: 42 pages, 16 figures, ApJ in press, version with high resolution figures is available via http://www.nro.nao.ac.jp/~kmuraoka/m83paper/m83aste-otf.pd

    Thalidomide Prevents the Progression of Peritoneal Fibrosis in Mice

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    Thalidomide is clinically recognized as a therapeutic agent for multiple myeloma and has been known to exert anti-angiogenic actions. Recent studies have suggested the involvement of angiogenesis in the progression of peritoneal fibrosis. The present study investigated the effects of thalidomide on the development of peritoneal fibrosis induced by injection of chlorhexidine gluconate (CG) into the mouse peritoneal cavity every other day for 3 weeks. Thalidomide was given orally every day. Peritoneal tissues were dissected out 21 days after CG injection. Expression of CD31 (as a marker of endothelial cells), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), α-smooth muscle actin (as a marker of myofibroblasts), type III collagen and transforming growth factor (TGF)-β was examined using immunohistochemistry. CG group showed thickening of the submesothelial zone and increased numbers of vessels and myofibroblasts. Large numbers of VEGF-, PCNA-, and TGF-β-positive cells were observed in the submesothelial area. Thalidomide treatment significantly ameliorated submesothelial thickening and angiogenesis, and decreased numbers of PCNA- and VEGF-expressing cells, myofibroblasts, and TGF-β-positive cells. Moreover, thalidomide attenuated peritoneal permeability for creatinine, compared to the CG group. Our results indicate the potential utility of thalidomide for preventing peritoneal fibrosis

    Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study

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    Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI

    Enhanced boiling surface with hydrophobic circle spots evaporator of looped thermosiphon

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    Heat transfer characteristic of a closed two-phase thermosiphon with enhanced boiling surface is studied and compared with that of a copper mirror surface. Two-phase cooling improves heat transfer coefficient (HTC) a lot compared to singlephase liquid cooling. The evaporator surfaces coated with a pattern of hydrophobic circle spots (non-electroplating, 0.5 2 mm in diameter and 1.5 3 mm in pitch) achieve very high heat transfer coefficient and lower the incipience temperature overshoot using water as the working fluid. Sub-atmospheric boiling on the hydrophobic spot-coated surface shows a much better heat transfer performance. Tests with heat loads (30 W to 260 W) revealed the optimum thermosiphon performance. Hydrophobic circle spots coated surface with diameter 1 mm, pitch 1.5 mm achieves the maximum heat transfer enhancement with the boiling thermal resistance as low as 0.03 K/W.Papers presented at the 13th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Portoroz, Slovenia on 17-19 July 2017 .International centre for heat and mass transfer.American society of thermal and fluids engineers
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