Distribution of Forces in Gravitationally Clustered Systems

We have studied the distribution of forces in gravitational systems through numerical experiments. Data were taken from an N-body simulation in an expanding universe. Before clustering, the distribution of random forces was represented as a Holtsmark distribution; the nearest-neighbor distribution is also shown as a comparison. The analytical and simulation distributions are in good agreement. When clustering becomes strong, the simulation result showed that the contribution of the forces acting on each galaxy, which is generated from all other galaxies, is almost entirely due to the gravitational attraction of its nearest neighbor. This implies that nearest-neighbor galactic encounters may play the main role in the dynamics of galaxy clustering.Comment: 8 pages, 4 Postscript figures, LaTeX fil

Gravothermal Expansion in an NN-Body System

This paper describes the numerical evolution of an $N$-body system with a slight ``temperature inversion''; i.e. the maximum velocity dispersion occurs not at the centre but further out. Fluid models predict that the core of such a system expands on a time-scale of thousands of central relaxation times, and here this behaviour is qualitatively confirmed for an $N$-body system of over 3000 bodies. With certain qualifications, this demonstrates the existence in N-body systems of one of the fundamental mechanisms which, in fluid models, drive the gravothermal oscillations discovered by Bettwieser & Sugimoto.Comment: 25pp and 12 figures (available from [email protected]), te

Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition

Idiopathic pulmonary fibrosis (IPF) is the most common and most deadly form of interstitial lung disease. Osteopontin (OPN), a matricellular protein with proinflammatory and profibrotic properties, plays a major role in several fibrotic diseases, including IPF; OPN is highly upregulated in patients' lung samples. In this study, we knocked down OPN in a bleomycin (BLM)-induced pulmonary fibrosis (PF) mouse model using small interfering RNA (siRNA) to determine whether the use of OPN siRNA is an effective therapeutic strategy for IPF. We found that fibrosing areas were significantly smaller in specimens from OPN siRNA-treated mice. The number of alveolar macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid was also reduced in OPN siRNA-treated mice. Regarding the expression of epithelial-mesenchymal transition (EMT)-related proteins, the administration of OPN-siRNA to BLM-treated mice upregulated E-cadherin expression and downregulated vimentin expression. Moreover, in vitro, we incubated the human alveolar adenocarcinoma cell line A549 with transforming growth factor (TGF)-beta 1 and subsequently transfected the cells with OPN siRNA. We found a significant upregulation of Col1A1, fibronectin, and vimentin after TGF-beta 1 stimulation in A549 cells. In contrast, a downregulation of Col1A1, fibronectin, and vimentin mRNA levels was observed in TGF-beta 1-stimulated OPN knockdown A549 cells. Therefore, the downregulation of OPN effectively reduced pulmonary fibrotic and EMT changes both in vitro and in vivo. Altogether, our results indicate that OPN siRNA exerts a protective effect on BLM-induced PF in mice. Our results provide a basis for the development of novel targeted therapeutic strategies for IPF

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1 beta-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1 beta-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints

Applicability of the Movement Assessment Battery for Children-Second Edition (MABC-2) for Japanese Children Aged 3–6 Years: A Preliminary Investigation Emphasizing Internal Consistency and Factorial Validity

This study investigated the applicability of the Movement Assessment Battery for Children – Second Edition (MABC-2) for 3- to 6-year-old Japanese children, particularly addressing its internal consistency and factorial validity. The MABC-2 test set for 3- to 6-year-old children was administered to 252 children. Differences between Japanese children and those of the original normative sample (i.e. United Kingdom children) were investigated along with sex differences. The Japanese children aged 3–6 years were found to have higher Manual Dexterity and Balance component scores than children of the normative sample. Girls scored higher than boys on the Balance component. Results of several analyses showed good internal consistency of the MABC-2. Confirmatory factor analysis revealed that a theoretical three-component model of the MABC-2 was not fitted to Japanese children aged 3–6 years. Instead, a new three-component model was postulated and discussed. The new three-component model of the MABC-2, with Manual Dexterity, Static Balance and Ball Skills, and Dynamic Balance, has high factorial validity in Japanese children aged 3–6 years

Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans

Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYPs) and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6β-position to form α-muricholic acid (MCA) and ursodeoxycholic acid (UDCA) to form β-MCA. However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known. Comparison of several Cyp-null mouse lines revealed that α-MCA and β-MCA were not detected in the liver samples from Cyp2c-cluster null (Cyp2c-null) mice. Global bile acid analysis further revealed the absence of MCAs and their conjugated derivatives, and high concentrations of CDCA and UDCA in Cyp2c-null mouse cecum and feces. Analysis of recombinant CYPs revealed that α-MCA and β-MCA were produced by oxidation of CDCA and UDCA by Cyp2c70, respectively. CYP2C9-humanized mice have similar bile acid metabolites as the Cyp2c-null mice, indicating that human CYP2C9 does not oxidize CDCA and UDCA, thus explaining the species differences in production of MCA. Because humans do not produce MCA, they lack tauro-β-MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis

DYNAMICAL EVOLUTIONOF SELF-GRAVITATING SYSTEMS

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