A theoretical study on the relationship between pressure rise and the Damköhler number of end-gas auto-ignition in spark-ignited engines

The pressure rise caused by end-gas auto-ignition in spark-ignited engines is discussed using numerical simulation and theoretical approaches. The main objective of this study is to explain the mechanism by which the end-gas expansion during auto-ignition suppresses the pressure rise in spark-ignited engines, and theoretically to demonstrate using asymptotic analysis that the pressure rise depends on the Damköhler number. A one-dimensional direct numerical simulation (DNS) of end-gas auto-ignition is performed, and the modelling assumptions for it are discussed based on the DNS results. The Damköhler number, defined as the acoustic time scale and the characteristic time scale of the chemical reaction, is introduced in the modelling. The end-gas auto-ignition model is solved numerically, and it is shown that the pressure rise increases with the Damköhler number. Additionally, it is shown that the tendency of the pressure rise is due to the balance between the propagation rate of the expansion wave generated in the end gas and the reaction rate at auto-ignition, which varies with the Damköhler number. To derive the analytical solution of the relationship between the pressure rise and Damköhler number, the end-gas auto-ignition model is simplified based on the numerical results. The simplified model for end-gas auto-ignition is then solved using Newton’s method, and the analytical solution of the pressure rise is derived.</p

DataSheet1_Simulation of the crosstalk between glucose and acetaminophen metabolism in a liver zonation model.pdf

The liver metabolizes a variety of substances that sometimes interact and regulate each other. The modeling of a single cell or a single metabolic pathway does not represent the complexity of the organ, including metabolic zonation (heterogeneity of functions) along with liver sinusoids. Here, we integrated multiple metabolic pathways into a single numerical liver zonation model, including drug and glucose metabolism. The model simulated the time-course of metabolite concentrations by the combination of dynamic simulation and metabolic flux analysis and successfully reproduced metabolic zonation and localized hepatotoxicity induced by acetaminophen (APAP). Drug metabolism was affected by nutritional status as the glucuronidation reaction rate changed. Moreover, sensitivity analysis suggested that the reported metabolic characteristics of obese adults and healthy infants in glucose metabolism could be associated with the metabolic features of those in drug metabolism. High activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate phosphatase in obese adults led to increased APAP oxidation by cytochrome P450 2E1. In contrast, the high activity of glycogen synthase and low activities of PEPCK and glycogen phosphorylase in healthy infants led to low glucuronidation and high sulfation rates of APAP. In summary, this model showed the effects of glucose metabolism on drug metabolism by integrating multiple pathways into a single liver metabolic zonation model.</p

Direct Synthesis of Cup-Stacked Carbon Nanofiber Microspheres by the Catalytic Pyrolysis of Poly(ethylene glycol)

Uniformly sized microspheres tangled with cup-stacked carbon nanofibers (CSCNFs) were directly synthesized by the pyrolysis of poly­(ethylene glycol) (PEG) with a nickel catalyst. A PEG/Ni membrane was prepared on a silicon wafer surface by heating it to 750 °C at a heating rate of 15 °C min^–1. The wafer was heated to a temperature of 400 °C and was held at that temperature for 1 h before raising the temperature to 750 °C for 10 min to form the CSCNF microspheres. The final CSCNF microspheres and the intermediates were evaluated using scanning electron microscopy, transmission electron microscopy, X-ray diffractometry, and Raman spectroscopy to elucidate the growth mechanism. Furthermore, the CSCNF microspheres were successfully dispersed and maintained their spherical shape in an aqueous solution containing 0.5% Nafion. The CSCNF microspheres have the potential to work as a sophisticated carrier with high adsorption and fast electron-transfer exchange properties based on the graphene edges of the nanofiber surface

Effects of administration of nitrazepam and flumazenil on tail suspension test (TST) immobility time.

<p>Nitrazepam (1 mg/kg) causes a significant increase in immobility time in the TST, which was blocked by flumazenil (10 mg/kg) in both the <i>Usp46</i> mutant (MT) and in the <i>Usp46</i> KO mice (KO). In the wild-type mice (WT), no significant effects were observed with either single administration of nitrazepam, or co-administration of nitrazepam and flumazenil. Data are expressed as mean + S.E.M. for 5–6 mice in each group. *<i>P</i><0.05, **<i>P</i><0.01 (two-way ANOVA with Bonferroni’s test).</p

Effects of nitrazepam administration on tail suspension test (TST) immobility time.

<p>Nitrazepam induces dose-dependent increases of TST immobility time in <i>Usp46</i> mutant mice (MT). Data are expressed as mean + S.E.M. for 6 mice in each group. ^##<i>P</i><0.01 compared with the wild-type mice for each dose; *<i>P</i><0.05, **<i>P</i><0.01 (two-way ANOVA with Bonferroni’s test).</p

Expression of <i>Usp46</i> mRNA in the brain analyzed by northern blot analysis.

<p>(A) Schematic diagram of cDNA and probes for <i>Usp46</i>. Probes A and B were used for the northern blot analysis. Black arrowhead indicates the <i>EcoR1</i> site. F514 and R1982 are a primer pair for PCR. (B) Northern blot from brain total RNA hybridized with the mouse <i>Usp46</i> cDNA probes A and B, labeled with [α-³²P] dCTP. The blot was hybridized with a cDNA probe for S18 as an internal control (the middle panel). The bottom panel shows a photograph of an RNA gel, indicating that equivalent amounts of total RNA were used in each lane. (C) Relative values of <i>Usp46</i> mRNA. PSL (Photo stimulated luminescence) was measured. Signals from the <i>Usp46</i> KO mice (KO) were not detected (N.D.). The differences between the wild-type mice (WT) and the heterozygotic mice (H) were significant (**<i>P</i><0.01, n = 6, Student’s <i>t</i>-test).</p

Generation of the <i>Usp46</i> KO mice.

<p>(A) Integration site of the pU-17 trap vector. The trap vector is inserted approximately 16 kbp downstream from exon 1. The trap vector contains a splice acceptor (SA), the β-galactosidase/neomycin-resistance fusion (β-geo) gene, a polyadeylation signal (pA) and pSP73 vector sequences <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039084#pone.0039084-Taniwaki1" target="_blank">[10]</a>. The white arrows (FP3, RP1, and SA6AS) indicate the primers used for genotyping. (B) Genotyping by the polymerase chain reaction. DNA fragments of 772 bp from the wild type allele and 1.4 kbp from the inserted allele were amplified by the primer pairs FP3-RP1 and FP3-SA6AS, respectively. (C) Immobility time in wild-type (WT) and <i>Usp46</i> KO mice (KO) in the tail suspension test (TST). The KO mice showed a significantly shorter immobility time than the WT mice in the TST. Data represent the mean + S.E.M. for 5–6 mice in each group. **<i>P</i><0.01 (Student’s <i>t-</i>test).</p

Effects of nitrazepam (1 mg/kg) and flumazenil (10 mg/kg) on general behaviors in OFT.

<p>Data are shown as the mean ± S.E.M. The number of animals is given in parentheses. **<i>P</i><0.01 compared with the saline-treated group in wild-type (WT) mice, *<i>P</i><0.05 compared with the saline-treated group in the <i>Usp46</i> KO mice (KO) (Tukey-Kramer post-hoc test).</p

Production of Cisplatin-Incorporating Hyaluronan Nanogels via Chelating Ligand–Metal Coordination

Hyaluronan (HA) is a promising drug carrier for cancer therapy because of its CD44 targeting ability, good biocompatibility, and biodegradability. In this study, cisplatin (CDDP)-incorporating HA nanogels were fabricated through a chelating ligand–metal coordination cross-linking reaction. We conjugated chelating ligands, iminodiacetic acid or malonic acid, to HA and used them as a precursor polymer. By mixing the ligand-conjugated HA with CDDP, cross-linking occurred via coordination of the ligands with the platinum in CDDP, resulting in the spontaneous formation of CDDP-loaded HA nanogels. The nanogels showed pH-responsive release of CDDP, because the stability of the ligand–platinum complex decreases in an acidic environment. Cell viability assays for MKN45P human gastric cancer cells and Met-5A human mesothelial cells revealed that the HA nanogels selectively inhibited the growth of gastric cancer cells. In vivo experiments using a mouse model of peritoneal dissemination of gastric cancer demonstrated that HA nanogels specifically localized in peritoneal nodules after the intraperitoneal administration. Moreover, penetration assays using multicellular tumor spheroids indicated that HA nanogels had a significantly higher ability to penetrate tumors than conventional, linear HA. These results suggest that chelating-ligand conjugated HA nanogels will be useful for targeted cancer therapy