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To investigate the wear resistance characteristics of micro-sized ceramic beads, wear tests reflecting real milling conditions were performed on yttrium-stabilized zirconia beads with diameters of approximately 100 μm. And a novel method for monitoring of wear state is proposed to obtain the wear rate of micro-sized beads using the change in size of beads with time. A vertical bead mill was employed to simulate the milling environment of the beads. The size change of the ceramic beads as a function of milling time was monitored using a particle size analyzer and plotted to determine their wear rate. The wear rate of each ceramic bead was derived from the slope obtained through linear regression analysis: 0.0215 μm/h, 0.0058 μm/h, and 0.0075 μm/h for Beads #1, #2, and #3, respectively. The Vickers hardness, phase fraction, and grain size of the ceramic beads were analyzed and compared to find out the cause of the difference in the wear rate. Vickers hardness was measured in the central, intermediate, and outer regions of the cross-sections of the ceramic beads. The wear rate of the ceramic beads was largely dependent on the hardness of the outer region, rather than those of the central and intermediate regions. Bead #2, which had the lowest wear rate, exhibited the highest hardness of 1371 HV (measured in the outer region). Bead #2 had more tetragonal phase and smaller grain sizes than those of Beads #1 and #3. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: We have performed virtual screening of a chemical database of 508,143 commercially available chemicals to search for new methionyl-tRNA synthetase (MetRS) inhibitors. In this study, potent lead compounds with a novel skeleton, including compound 27 with IC50 =237nM, were successfully identified as Escherichia coli MetRS inhibitors. [Copyright &y& Elsevier]

Abstract: Skeletal muscle recovery from disuse atrophy requires the recruitment of insulin signaling for muscle growth, which is driven by protein synthesis. Dietary fish oil, which is rich in long-chain n−3 polyunsaturated fatty acids, is known to enhance insulin signaling and protein metabolism. Therefore, this study was performed to evaluate whether dietary fish oil facilitates muscle recovery during remobilization after disuse atrophy. Ten days of immobilization, followed by 3 or 13 days of remobilization, were applied to the hindlimbs of rats fed corn oil [corn oil diet group as control (CO)] or fish oil [fish oil diet group (FO)] as source of dietary fat. The immobilization-induced reductions in soleus muscle weight and myosin heavy-chain content were significantly restored by 3 days of remobilization in CO. However, in FO, these muscle recovery measurements did not significantly change until 13 days of remobilization. At 3 days of remobilization, both groups had significant elevations in p70 ribosomal S6 kinase (p70s6k) activation and at a greater extent in CO than in FO. The activation of Akt was also increased on Day 3, but it was not significant in FO. Throughout the remobilization period, levels of prostaglandin F2α (PGF2α) and cyclooxygenase-2 mRNA were significantly augmented. However, FO had a lesser increase in PGF2α than CO until Day 13. These findings indicate that dietary fish oil inhibits the early stage of soleus muscle recovery after disuse atrophy by suppressing the activation of Akt–p70s6k signaling and PGF2α synthesis. [ABSTRACT FROM AUTHOR]

High-quality alumina (Al 2 O 3) coating has an extensive demand in the fields of optoelectronics, solar cells, and corrosion/impurity resistant coatings and cutting tools. The quality of alumina coating depends on its hardness and transparency. To obtain hard and highly transparent alumina coating, which is also a widely used ceramic material, a novel, aerosol deposition approach is presented in which the starting powder, used to fabricate Al 2 O 3 ceramic coatings, is composed of angular and spherical Al 2 O 3 particles. Films fabricated using angular:spherical Al 2 O 3 particle mixtures with ratios of 10:0, 7:3, 5:5, 3:7, and 0:10, showed significant variation in surface roughness and microstructure. The dramatic morphology modulation of the 3:7 angular:spherical Al 2 O 3 mixture film, resulting from the superposition hammering effect caused by the aerosol mixture, improved transmittance (84.7%) and hardness (13.6 GPa). Previous studies used high-energy approaches to optimize Al 2 O 3 film properties. This dual-particle approach, however, produces Al 2 O 3 film with excellent transmittance and hardness while achieving a fast coating speed (32 mm2 × μm/min) without additional thermal treatment. Our proposed approach provides a novel and energy efficient method to produce transparent Al 2 O 3 films with superior durability. [ABSTRACT FROM AUTHOR]

Abstract: We explored the association between the degree of adherence to recommendations and diabetes management in Korean adults who had type 2 diabetes for an average of 8 years. Subjects who met five or more lifestyle recommendations showed significantly lower blood lipid parameters and glycated hemoglobin than those who did not. [Copyright &y& Elsevier]

JX-594 is a targeted and granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing oncolytic poxvirus designed to selectively replicate in and destroy cancer cells through viral oncolysis and tumor-specific immunity. In order to study the mechanisms-of-action (MOA) of JX-594 in humans, a mechanistic proof-of-concept clinical trial was performed at a low dose equivalent to ≤10% of the maximum-tolerated dose (MTD) in other clinical trials. Ten patients with previously treated stage IV melanoma were enrolled. Tumors were injected weekly for up to nine total treatments. Blood samples and tumor biopsies were analyzed for evidence of transgene activity, virus replication, and immune stimulation. The β-galactosidase (β-gal) transgene was expressed in all patients as evidenced by antibody induction. Six patients had significant induction of GM-CSF-responsive white blood cell (WBC) subsets such as neutrophils (25-300% increase). JX-594 replication and subsequent shedding into blood was detectable in five patients after cycles 1-9. Tumor biopsies demonstrated JX-594 replication, perivascular lymphocytic infiltration, and diffuse tumor necrosis. Mild flu-like symptoms were the most common adverse events. In sum, JX-594 replication, oncolysis, and expression of both transgenes were demonstrated; replication was still evident after multiple cycles. These findings have implications for further clinical development of JX-594 and other transgene-armed oncolytic viruses. [ABSTRACT FROM AUTHOR]

Abstract: Inorganic phosphate (Pi) plays a key role in diverse physiologic functions. In a previous study, we showed that high dietary Pi perturbs brain growth through Akt/ERK signaling in developing mice. However, no study has investigated the response of the brain to low dietary Pi. In this study, we addressed this question by studying the effects of low dietary Pi on the cerebrum of developing mice. Two-week-old weaned mice were fed with a low phosphate diet for 4 weeks. At the end of the study, their cerebrum was dissected and signals important for protein translation, apoptosis and cell cycle were examined. The low phosphate diet did not cause physiologically significant changes; it increased the protein expression of phosphatase and tensin homolog deleted on chromosome 10 but decreased Akt activity. In addition, expression of eukaryotic translation initiation factor binding protein coupled with increased complex formation of eukaryotic translation initiation factor 4E/eukaryotic translation initiation factor binding protein 1 was induced in the cerebrum by low phosphate, leading to reduced cap-dependent protein translation. Finally, low phosphate facilitated apoptosis and suppressed signals important for the cell cycle in the cerebrum of dual-luciferase reporter mice. In summary, our results showed that a low phosphate diet affects the brain by controlling protein translation, apoptosis and cell cycle in developing mice. Our results support the hypothesis that Pi works as a stimulus capable of increasing or decreasing several pivotal genes for normal development and suggest that regulation of Pi consumption is important in maintaining a healthy life. [Copyright &y& Elsevier]

Abstract: Objective: Genistein has been suggested to prevent insulin resistance and its related diseases. We investigated the effects of dietary genistein at different levels on hepatic lipid levels and mitochondrial functions in mice fed high-fat diets. Methods: C57BL/6J mice were randomly divided into four groups and fed a high-fat diet containing genistein at levels of 0%, 0.1%, 0.2%, and 0.4% (HF, HF + 0.1G, HF + 0.2G, and HF + 0.4G) for 12 wk. We measured lipid levels in the blood and liver. We also observed messenger RNA (mRNA) expression of genes encoding proteins related to lipid and energy metabolism and antioxidant defense system and mitochondrial enzyme activities in the liver. Results: The induction of fatty liver by HF was substantially decreased in the HF + 0.2G and HF + 0.4G groups. Peroxisome proliferator-activated receptorγ coactivator mRNA was increased by HF + 0.4G. Although genistein did not affect peroxisomal acyl-CoA oxidase mRNA expression, it increased medium-chain acyl-CoA dehydrogenase mRNA expression in a dose-dependent manner and HF + 0.2G increased uncoupling protein-2 mRNA expression two-fold relative to HF mice. Genistein decreased malondialdehyde levels and increased glutathione levels in liver homogenates, regardless of dose. The HF + 0.1G diet increased mitochondrial glutathione peroxidase activity and mitochondrial succinate dehydrogenase activity. Conclusions: Although genistein at higher levels decreased hepatic fat accumulation possibly by increasing fatty acid oxidation and uncoupling protein, low-dose genistein increased mitochondrial enzyme activities in mice with fatty liver and obesity induced by high-fat diets. [Copyright &y& Elsevier]

To understand the molecular mechanisms underlying alterations in the pathophysiologic status of dietary obesity, we examined hepatic genes differentially expressed in a long-term high-fat intake-induced obesity mouse model. C57BL/6J male mice were fed with two kinds of diets for 12 weeks; a low-fat diet (LFD), a high-fat diet (HFD; n=8), and the expression levels of ∼10,000 transcripts in liver tissues from the two groups were assessed using cDNA microarray analysis. Twelve-week feeding with the HFD resulted in significant increase in body weight, visceral fat accumulation and circulating cholesterol concentration, compared with the LFD group. The cDNA microarray analysis revealed marked differences in the expressions of 97 hepatic genes. These genes were categorized into seven groups:The expression of genes involved in fatty acid catabolism and ketone body synthesis, such as acyl–CoA oxidase1 (Acox1) and HMG–CoA lyase (Hmgcl), was significantly increased, and expression of genes involved in lipogenesis and cholesterol synthesis, such as acetyl–CoA synthetase2 (Acs2), fatty acid synthase (Fasn), and squalene epoxidase (Sqle), was drastically decreased in the HFD group. Interestingly, the genes implicated in defense and stress responses, such as glutathione S-transferases (GSTs) and heat shock proteins (Hsps), were also highly represented in the HFD group. Besides, a number of previously unappreciated regulatory molecules were changed by the HFD. These results revealed a transcriptional adaptation to long-term HFD and provided interesting information about the molecules involved in the development and maintenance of the obesity phenotype in vivo. [Copyright &y& Elsevier]