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ABSTRACT: The Earth Simulator (ES) is an SMP cluster system. There are two types of parallel programming models available on the ES. One is a flat programming model, in which a parallel program is implemented by MPI interfaces only, both within an SMP node and among nodes. The other is a hybrid programming model, in which a parallel program is written by using thread programming within an SMP node and MPI programming among nodes simultaneously. It is generally known that it is difficult to obtain the same high level of performance using the hybrid programming model as can be achieved with the flat programming model.In this paper, we have evaluated scalability of the code for direct numerical simulation of the Navier–Stokes equations on the ES. The hybrid programming model achieves the sustained performance of 346.9 Gflop/s, while the flat programming model achieves 296.4 Gflop/s with 16 PNs of the ES for a DNS problem size of 2563. For small scale problems, however, the hybrid programming model is not as efficient because of microtasking overhead. It is shown that there is an advantage for the hybrid programming model on the ES for the larger size problems.
Parallel Computing. 01/2004;
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ABSTRACT: In the previous study (Chem. Eur. J., 7, 176 (2001)) we demonstrated that the comb-type polycationic copolymer (PLL-g-Dex) which is composed of poly (L-lysine) backbone and dextran graft chains expedited the DNA strand exchange reaction. In this study, fluorescence resonance energy transfer (FRET) was employed to explore the copolymer-mediated DNA strand exchange with higher time-resolution. To initiate strand exchange reaction the duplex prepared from 3'-fluorescein isothiocyanate (FITC)--and 5'-carboxytetramethylrhodamine(TAMRA)-labeled complementary DNAs was added to its non-labeled complementary single strand. DNA strand exchange was monitored by observing the recovery of the FITC quenching. More than 20,000 times increase in strand exchange rate at 37 degrees C by the copolymer was estimated. To investigate the accelerating mechanisms of the copolymer, the same reactions but at various ionic strenghts were studied. With increasing ionic strengths the strand exchange rate in the absence of the copolymer increased, suggesting that ionic repulsion among DNAs is unfavorable for the strand exchange to occur. Hence, alleviation of the electrostatic repulsion through interpolyelectrolyte complex formation is probably a role of the copolymer for accelerating the strand exchange reaction.
Nucleic acids research. Supplement (2001). 02/2001;
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ABSTRACT: We have focused on proteineus ligand conjugate with oligonucleotides (ODNs) as a cell-specific delivery vector for peptide nucleic acids (PNAs). Asialofetuin (AF), a hepatocyte-specific proteineus ligand, was conjugated with ODNs that served as binding sites for PNAs. Succinimidyl-transe-4(N-maleimidylmethyl)-cyclohexane-1-carboxylate (SMCC) modified AF was coupled with 5'-thiolated oligodeoxynucleotide (HS-ODN). The resulting conjugate held PNAs with sequence-specific manner. The PNA/DNA conjugate complex has resistance against nucleases in serum. The efficient release of PNA from the complex was observed when the complex was made in contact with a target nucleotide. PNA uptake to hepatocytes was greatly enhanced when hepatocytes was incubated with PNA/conjugate complex. Free AF thoroughly inhibited PNA uptake with the conjugate, evidencing asialoglycoprotein receptor (ASGP-R) mediated endocytosis to be a major-route for the cellular uptake.
Nucleic acids research. Supplement (2001). 02/2001;
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ABSTRACT: The accelerating effect of cationic substances on the DNA strand exchange reaction between a 20 bp DNA duplex and its complementary single strand was studied. A polycationic comb-type copolymer, that consists of a poly(L-lysine) backbone and a dextran graft chain (PLL-g-Dex) and known to stabilize triplex DNA, expedites the strand exchange reaction under physiological relevant conditions. Electrostatically a small excess of the copolymer let to a 300-1500-fold increase in the DNA strand exchange while large excess of spermine or cetyltrimethylammonium bromide, a cationic detergent known to promote markedly hybridization of complementary DNA strands, shows only a slight effect. The efficacy of the copolymer was not affected by a 10 mM Mg2+ concentration. Notably the copolymer promotes the strand exchange reaction while it stabilizes double-stranded DNA. The stabilization of strand exchange intermediates consisting of the parent duplex and the single strand by the copolymer is believed to be responsible for the observed acceleration behavior.
Chemistry 02/2001; 7(1):176-80. · 5.93 Impact Factor
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ABSTRACT: Cell modulators such as colchicine (CO), cytochalasin B (CY) and taxol (TX) loaded nanoparticles coated with carbohydrate-carrying polymers, as hepatocyte-specific targeting material using galactose ligands as recognition signals to asialoglycoprotein receptors were prepared by the diafiltration method. Effects of cell modulators from their loaded nanoparticles on morphology of hepatocytes were studied. Receptor-mediated endocytosis of the nanoparticles were examined by fluorescence and confocal laser microscopy. It was found that the shapes of most hepatocytes were changed for the CY-loaded, TX-loaded, or CO-loaded nanoparticles whereas their shapes were not changed in comparison with control when CY, TX, or CO were mixed with the nanoparticles. From the fluorescence and confocal laser microscopic studies, it is suggested that the nanoparticles coated with sugar-carrying polymers were internalized by the hepatocytes through the receptor-mediated mechanism.
Biomaterials 02/2001; 22(1):45-51. · 7.40 Impact Factor
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ABSTRACT: The accelerating effect of cationic substances on DNA strand exchange reaction between 20 bp DNA duplex and its complementary single strand was studied. A comb-type polycationic copolymer which is composed of poly (L-lysine) backbone and dextran graft chain (PLL-g-Dex) and known to stabilize triplex DNA expedites the strand exchange reaction under physiological relevant conditions. Electrostatically small excess of the copolymer increased DNA strand exchange rate by 300-fold while large excess of spermine or cethyltrimethylammonium bromide, cationic detergent known to promote markedly hybridization of complementary DNA strands, showed slight effect. It should be noted that the copolymer promotes the strand exchange reaction while it stabilizes double stranded DNA.
Nucleic Acids Symposium Series 02/2000;
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ABSTRACT: Polycation comb-type copolymer that is composed of polylysine backbone and dextran side chains (PLL-g-Dex) has previously been shown to stabilize duplex and triplex DNAs quite effectively. In this study, we have conjugated PLL-g-Dex with oligonucleotides (ODN) aiming to increase the triplex stabilizing efficiency of the copolymer. Here we have demonstrated that the copolymer-TFO conjugates selectively stabilize triplex DNA. Also its potential to form triplex DNA was found to be greater than PLL-g-Dex/ODN mixture.
Nucleic Acids Symposium Series 02/2000;
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ABSTRACT: The dendriTIc graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) main chain and grafts of arabinogalactan (AG) were prepared as a liver cell-specific DNA carrier. The copolymers were successfully prepared by reductive amination reaction between a reductive end of AG and epsilon-amino groups of PLL using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated by ultrafiltration from unreacted AG and characterized by 1H NMR and gel permeation chromatography equipped with a multiangle laser light scattering detector (GPC-MALLS). The binding and internalization of DNA to hepatoma cells, HepG2, were considerably enhanced by complexing DNA with PAX copolymers. The interactions between PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the presence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the PAX copolymers may provide a new research tool for cell-specific gene delivery and eventually enhance gene-therapy technology.
Preparative Biochemistry & Biotechnology 12/1999; 29(4):353-70. · 0.47 Impact Factor
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ABSTRACT: Nanoparticles bearing carbohydrate chains on the surface can be prepared by the simple diafiltration method. The nanoparticles prepared by the present method displayed high yield, no-aggregation formation, small size, narrow size distribution, and one-step procedure. Also, the high density carbohydrate chains on the particles can be recognized by liver cells.
Biomaterials 03/1997; 18(4):323-6. · 7.40 Impact Factor
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ABSTRACT: A novel method of preparing nanoparticles bearing high density carbohydrate chains on their surface is described. Carbohydrate-bearing nanoparticles of poly(lactic acid) or polystyrene were prepared by the solvent evaporation method using a carbohydrate-carrying polystyrene derivative which served as both an emulsifier and a surface coating. The diameter of the obtained nanoparticles ranged from 80 to 300 nm depending on the concentration of the polystyrene derivative. As the concentration of the polystyrene derivatives increased the nanoparticle diameter decreased, indicating that the polystyrene derivatives worked as an emulsifier. The obtained particles were specifically aggregated by carbohydrate-specific lectin, showing that the polystyrene derivative was retained on the particle surfaces and expressed carbohydrate residues. The density of carbohydrates on the particle surfaces was determined to be 3-5 molecules per square nanometre. The particles prepared by the present method were stably dispersed and hardly aggregated in aqueous media during storage and centrifugal treatment compared with the post-coated particles that were prepared by adsorbing polystyrene particles with the polystyrene derivative. In vitro study with isolated rat hepatocytes revealed that surface carbohydrate chains were recognized by hepatocytes.
Biomaterials 11/1994; 15(13):1035-42. · 7.40 Impact Factor
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ABSTRACT: The density effect of carbohydrate-ligands on nanometer-order particles (nanoparticles) upon cellular binding and internalization was investigated. Poly(vinylbenzyl-beta-D-lactonamide) (PVLA), a beta-galactose-carrying styrene homopolymer, was employed as a model ligand for the asialoglycoprotein receptors on hepatocytes. In order to control the surface ligand densities on the particles, PVLA was mixed with poly(vinylbenzyl-D-gluconamide) (PVGA), a PVLA analog without beta-galactose, and their mixtures were used as surface coatings. The particles with low ligand densities associated more with hepatocytes than high ligand density particles. The surface density of the ligand considerably influenced the cellular distribution. Most of the particles bearing high densities of ligands were found inside the cells, whereas particles with low ligand densities were found on the plasma membrane surface of the hepatocytes. These results were indicative of high densities of ligands on the surface requiring hepatocytes to internalize the particles promptly by receptor-mediated endocytosis, while low densities of ligands on the surface was not sufficient to internalize, but allowed particles to bind on the cell surface. These findings enabled us to regulate cellular distributions of particles by controlling ligand density on the surface.
Journal of Biomaterials Science Polymer Edition 02/1994; 6(5):463-79. · 1.69 Impact Factor
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ABSTRACT: Biodegradable nanoparticles, which contain the sites for both polynucleotide adsorption and targeting ligand on their surfaces, were prepared as a novel carrier for genetic materials. The nanoparticles were obtained from poly(D,L-lactic acid) and poly(L-lysine)-graft-polysaccharide copolymers by using either a solvent evaporation method or a diafiltration method. The size of the particles prepared by the diafiltration method was controlled by varying the initial concentration of the graft copolymer. Nanoparticles as small as 60 nm in diameter were successfully obtained from the graft copolymers with high polysaccharide contents but not from the poly(L-lysine) homopolymer. Polysaccharide moieties on the surface of the nanoparticles were found to interact specifically with a particular lectin as verified by the aggregation assay. The polynucleotide adsorption capacity of the nanoparticles was increased with increasing polysaccharide contents in the graft copolymers, suggesting that the adsorption conformation of poly(L-lysine) moiety in the graft copolymer on the nanoparticle surface is different from that in poly(L-lysine) homopolymer. Moreover, the nanoparticles from the graft copolymer exhibited resistance against self-aggregation and nonspecific adsorption of serum proteins, presumably due to the polymer brush effect and/or exclusion effect from the polysaccharide graft chains. These results suggest that the nanoparticles prepared from poly(L-lysine)-graft-polysaccharide copolymer and poly(D,L-lactic acid) can serve as a good DNA carrier in vivo.
Bioconjugate Chemistry 8(5):735-42. · 4.93 Impact Factor
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ABSTRACT: There are many reports in the literature of a spectral difference between the triboluminescence (TL) spectrum and the solid-state photoluminescence (PL) spectrum of the same compound. Numerous reasons have been suggested for this difference including pressure-induced changes to Franck-Condon factors during the lifetime of the TL light emission; self-absorption of the TL emission and fracture-induced symmetry changes perturbing the local field of the TL emitting species. However, in a number of cases, the luminescent spectra were recorded on different equipment with different spectral responses, with the resolution of either luminescent spectrum rarely quoted. To avoid artificial spectral differences, care must be taken to account for the response of each equipment over the wavelength range studied, as well as any resolution difference. We have therefore measured the TL and solid-state PL spectra of sixteen TL compounds on the same spectrometer at an identical resolution. Furthermore, the solid-state photoluminescent lifetime has been determined for all samples and the implication that these values have for observing pressure-induced (Franck-Condon) luminescent spectral changes discussed. Finally, in all cases where a significant difference was observed between TL and PL spectra, either self-absorption of the TL emission or fracture-induced perturbations of the local field have been evoked to explain the difference.
Journal of Luminescence.
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ABSTRACT: High quality indium tin oxide (ITO) films of thickness 80±20 nm grown by laser irradiation of the glass substrates during pulsed laser deposition are reported. Films were deposited from a 5 wt.% SnO2-doped In2O3 target at substrate temperatures (Ts) ranging from room temperature (RT) to 400°C and oxygen pressure (PO2) of 1.3 Pa. The energy of the laser beam focused unto the middle of the glass substrate during coatings was about 70 mJ cm−2. The structural, electrical and optical properties of the laser-irradiated and the nonirradiated parts of the ITO films were studied as a function of Ts. Crystalline films with 〈1 1 1〉 preferred orientation and crystal sizes⪢200 nm were obtained at all Ts. At RT, the resistivity of the laser-irradiated part of one film was 1.2×10−4 Ω cm compared with 2.3×10−4 Ω cm for a nonirradiated part. At 300°C, a low resistivity value of 8.5×10−5 Ω cm was achieved for both the laser-irradiated and the nonirradiated parts of the ITO film. The achievement of low resistivity resulted from the high carrier concentration ∼1.2×1021 cm−3 and the high Hall mobility (40–57) cm2 V−1 s−1. The films also exhibited high optical transmittance (∼90%) to visible light.
Applied Surface Science.
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ABSTRACT: The polyionic interaction between DNA and polycations grafted with hydrophilic dextran side chains was evaluated. The comb-type copolymers, poly(L-lysine)-graft-dextran, were successfully prepared by employing a reductive amination reaction between epsilon-amino groups of poly(L-lysine) (PLL) and the reductive ends of dextran (Dex). A coupling efficacy on the order of 70% was obtained regardless of intrinsic philicities of the solvents used, either aqueous buffer or DMSO. The resulting graft copolymers, which varied in the degree of grafting and the length of hydrophilic side chains, formed a soluble complex with DNA. They also affected the melting behavior of double-stranded DNA (dsDNA) in different ways. Copolymers having a high degree of grafting thermally stabilized dsDNA without affecting its reversible transition between single-stranded and double-stranded forms. However, copolymers with a low degree of grafting or with a high degree of grafting of short dextran chains impeded the reversibility of this transition. Furthermore, highly grafted copolymers also accelerated the hybridization of DNA strands in a low-ionic strength medium. It is of particular note that these copolymers scarcely altered circular dichroismic signals of dsDNA even when the copolymers were added in excess. This suggested that the copolymer interacted with dsDNA without affecting its native structure or physicochemical properties. Finally, the copolymer even formed a stable complex with a short oligonucleotide (20 bases). We, therefore, concluded that, by regulating the degree of grafting and the molecular weight of grafted side chains, it would be possible to design novel different graft copolymers capable of acting as carriers of functional genes to target cells or tissue.
Bioconjugate Chemistry 9(2):292-9. · 4.93 Impact Factor
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ABSTRACT: DNA triplex formation has been studied as a potential strategy for regulation of gene expression. The triplex is, however, unstable under physiological conditions, so that an effective stabilizer for the triplex formation is needed. Here is shown a novel strategy to stabilize the triplex based on the molecular design of a comb-type polycation. Linear polycations, such as poly(L-lysine) and poly(L-arginine), thermally stabilize DNA duplexes (and triplexes). The complexes between DNA and the polycation are irreversible and are liable to precipitate out of aqueous media. The irreversibility and phase separating properties of the complex impede association of single-stranded (ss) DNAs in the complex to form duplexes and triplexes. A comb-type polycation consisting of a poly(L-lysine) backbone and grafted chains of hydrophilic polymers was prepared. The comb-type copolymers increased solubility of their complex with DNA and suppressed conformational changes of DNA. Thermal melting curve analyses revealed that the comb-type copolymer markedly stabilized DNA triplexes and did not disturb ssDNAs in forming duplexes and triplexes. Reversible and one-step melting/reassociation transitions of poly(dA).2poly(dT) triplex were shown in the pressure of the copolymers. The stabilizing effect of the copolymer was larger than that of spermine, a polyamine considered effective in stabilizing triplexes. These results indicated that molecular design of polycations with a comb-type structure is a novel strategy to create efficient triplex stabilizers. Such comb-type copolymer consisting of various types of polycation backbones and hydrophilic graft chains may have many applications in which specific and precise interactions of polynucleotides are involved.
Bioconjugate Chemistry 8(1):3-6. · 4.93 Impact Factor
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ABSTRACT: Various comb-type copolymer containing a polycation as a main chain was design to construct delivery systems of DNAs. The comb-type copolymers having cell-specific polysaccharides were proved to be useful to deliver DNA to the target cells in vivo. Of interest, the copolymers with abundant side chains of hydrophilic polymers are capable of stabilizing DNA triplex. Further, injectable nanoparticles for controlled releases of DNAs were fabricated from the copolymer and a biodegradable polymer.
Nucleosides & nucleotides 18(6-7):1681-2. · 1.13 Impact Factor
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ABSTRACT: Nanoparticles bearing carbohydrate chains on the surface can be prepared by the simple diafiltration method. The nanoparticles prepared by the present method displayed high yield, no-aggregation formation, small size, narrow size distribution, and one-step procedure. Also, the high density carbohydrate chains on the particles can be recognized by liver cells.
Biomaterials.
