Linear-time algorithms for the subpath kernel

The subpath kernel is a useful positive definite kernel, which takes arbitrary rooted trees as input, no matter whether they are ordered or unordered, We first show that the subpath kernel can exhibit excellent classification performance in combination with SVM through an intensive experiment. Secondly, we develop a theory of irreducible trees, and then, using it as a rigid mathematical basis, reconstruct a bottom-up linear-time algorithm for the subtree kernel, which is a correction of an algorithm well-known in the literature. Thirdly, we show a novel top-down algorithm, with which we can realize a linear-time parallel-computing algorithm to compute the subpath kernel

Monoclonal antibodies to human laminin alpha 4 chain globular domain inhibit tumor cell adhesion and migration on laminins 411 and 421, and binding of alpha 6 beta 1 integrin and MCAM to alpha 4-laminins

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分泌型白血球プロテアーゼインヒビターによる歯肉上皮細胞のPorphyromonas gingivalis感染制御

Secretory leukocyte protease inhibitor (SLPI) has been recognized as not only a protease inhibitor but also an important defense component in mucosal secretory fluids. To elucidate the functional role in innate immunity in gingival crevices, the SLPI production from a gingival epithelial cell line, GE1, with or without the stimulation of Porphyromonas gingivalis lyophilized whole cells (Pg-WC) and the lipopolysaccharides (Pg-LPS), and the inhibitory effect on P. gingivalis proteases were investigated. The unstimulated GE1 cells showed low levels of SLPI mRNA expression, which was augmented by the stimulation with Pg-LPS as well as Pg-WC. The augmentation of SLPI mRNA expression in GE1 cells was accompanied by the inductions of IL-6, TNF-α and IL-1β mRNA expressions. Although IL-6 could induce macrophages to produce SLPI, the kinetics analyses suggested that the augmentation of SLPI production in GE1 cells could not be a second response to the IL-6 induced by the stimulant, but a direct response by the P. gingivalis antigens. Further experiments using rSLPI indicated that SLPI showed a direct inhibitory effect on the P. gingivalis protease of Lys-gingipain. Thus, it was suggested that gingival epithelial cells could be a substantial producer of SLPI that functions inhibitory to the pathogenic P. gingivalis protease in gingival crevices. It was also suggested that the SLPI production could increase in response to P. gingivalis through the stimulation with its pathogenic constituents

Phase Diagram of Pressure-Induced Superconductivity in EuFe2As2 Probed by High-Pressure Resistivity up to 3.2 GPa

We have constructed a pressure$-$temperature ($P-T$) phase diagram of $P$-induced superconductivity in EuFe$_2$As$_2$ single crystals, via resistivity ($\rho$) measurements up to 3.2 GPa. As hydrostatic pressure is applied, an antiferromagnetic (AF) transition attributed to the FeAs layers at $T_\mathrm{0}$ shifts to lower temperatures, and the corresponding resistive anomaly becomes undetectable for $P$ $\ge$ 2.5 GPa. This suggests that the critical pressure $P_\mathrm{c}$ where $T_\mathrm{0}$ becomes zero is about 2.5 GPa. We have found that the AF order of the Eu$^{2+}$ moments survives up to 3.2 GPa without significant changes in the AF ordering temperature $T_\mathrm{N}$. The superconducting (SC) ground state with a sharp transition to zero resistivity at $T_\mathrm{c}$ $\sim$ 30 K, indicative of bulk superconductivity, emerges in a pressure range from $P_\mathrm{c}$ $\sim$ 2.5 GPa to $\sim$ 3.0 GPa. At pressures close to but outside the SC phase, the $\rho(T)$ curve shows a partial SC transition (i.e., zero resistivity is not attained) followed by a reentrant-like hump at approximately $T_\mathrm{N}$ with decreasing temperature. When nonhydrostatic pressure with a uniaxial-like strain component is applied using a solid pressure medium, the partial superconductivity is continuously observed in a wide pressure range from 1.1 GPa to 3.2 GPa.Comment: 7 pages, 6 figures, accepted for publication in Physical Review B, selected as "Editors' Suggestion

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation and Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. GO-Y022-induced tumor cell death was further enhanced by 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Combination treatment of GO-Y022 and 2DG results in reduced L-lactate production and Treg generation in gastric tumor cells. Overall, GO-Y022-treatment with restricted glucose metabolism inhibits gastric tumor cell survival and promotes anti-tumor immunity

Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-α used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4–8, 12–16, and 20–24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12–16 and 20–24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12–16 and in five patients (50%) at weeks 20–24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics

A novel high-throughput (HTP) cloning strategy for site-directed designed chimeragenesis and mutation using the Gateway cloning system

There is an increasing demand for easy, high-throughput (HTP) methods for protein engineering to support advances in the development of structural biology, bioinformatics and drug design. Here, we describe an N- and C-terminal cloning method utilizing Gateway cloning technology that we have adopted for chimeric and mutant genes production as well as domain shuffling. This method involves only three steps: PCR, in vitro recombination and transformation. All three processes consist of simple handling, mixing and incubation steps. We have characterized this novel HTP method on 96 targets with >90% success. Here, we also discuss an N- and C-terminal cloning method for domain shuffling and a combination of mutation and chimeragenesis with two types of plasmid vectors

A Novel Monoclonal Antibody to Human Laminin alpha 5 Chain Strongly Inhibits Integrin-Mediated Cell Adhesion and Migration on Laminins 511 and 521

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