Carbon nanofiber assisted micro electro discharge machining of reaction-bonded silicon carbide

Carbon nanofiber assisted micro electro discharge machining was proposed and experiments were performed on reaction-bonded silicon carbide. The changes in electro discharging behavior, material removal rate, electrode wear ratio, electrode geometry, spark gap, surface finish, surface topography and surface damage with carbon nanofiber concentration were examined. It has been found that the addition of carbon nanofiber not only improves the electro discharge frequency, material removal rate, discharge gap, but also reduces the electrode wear and electrode tip concavity. Bidirectional material migrations between the electrode and the workpiece surface were detected, and the migration behavior was strongly suppressed by carbon nanofiber addition. Adhesion of carbon nanofibers to the workpiece surface occurs, which contributes to the improvement of electro discharge machinability. These findings provide possibility for high-efficiency precision manufacturing of microstructures on ultra-hard ceramic materials

Micro-RNA-1 is decreased by hypoxia and contributes to the development of pulmonary vascular remodeling via regulation of sphingosine kinase 1

Sphingosine kinase 1 (SphK1) upregulation is associated with pathologic pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), but the mechanisms controlling its expression are undefined. In this study, we sought to characterize the regulation of SphK1 expression by micro-RNAs (miRs). In silico analysis of the SphK1 3'-untranslated region identified several putative miR binding sites, with miR-1-3p (miR-1) being the most highly predicted target. Therefore we further investigated the role of miR-1 in modulating SphK1 expression and characterized its effects on the phenotype of pulmonary artery smooth muscle cells (PASMCs) and the development of experimental pulmonary hypertension in vivo. Our results demonstrate that miR-1 is downregulated by hypoxia in PASMCs and can directly inhibit SphK1 expression. Overexpression of miR-1 in human PASMCs inhibits basal and hypoxia-induced proliferation and migration. Human PASMCs isolated from PAH patients exhibit reduced miR-1 expression. We also demonstrate that miR-1 is downregulated in mouse lung tissues during experimental hypoxia-mediated pulmonary hypertension (HPH), consistent with upregulation of SphK1. Furthermore, administration of miR-1 mimics in vivo prevented the development of HPH in mice and attenuated induction of SphK1 in PASMCs. These data reveal the importance of miR-1 in regulating SphK1 expression during hypoxia in PASMCs. A pivotal role is played by miR-1 in pulmonary vascular remodeling, including PASMC proliferation and migration, and its overexpression protects from the development of HPH in vivo. These studies improve our understanding of the molecular mechanisms underlying the pathogenesis of pulmonary hypertension

MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase

Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3' UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling

Fabrication of deep micro-holes in reaction-bonded SiC by ultrasonic cavitation assisted micro-EDM

Ultrasonic vibration was applied to dielectric fluid by a probe-type vibrator to assist micro electrical discharge machining of deep micro-holes in ceramic materials. Changes of machined hole depth, hole geometry, surface topography, machining stability and tool material deposition under various machining conditions were investigated. Results show that ultrasonic vibration not only induces stirring effect, but also causes cloud cavitation effect which is helpful for removing debris and preventing tool material deposition on machined surface. The machining characteristics are strongly affected by the vibration amplitude, and the best machining performance is obtained when carbon nanofibers are added into the vibrated dielectric fluid. As test pieces, micro-holes having 10 μm level diameters and high aspect ratios (420) were successfully fabricated on reaction-bonded silicon carbide in a few minutes. The hybrid EDM process combining ultrasonic cavitation and carbon nanofiber addition is demonstrated to be useful for fabricating microstructures on hard brittle ceramic materials

Effect of Different Dielectric Fluids on Micro EDM of Low Conductivity Ceramic Material RB-SiC

The machining characteristics of reaction bonded silicon carbide (RB-SiC) in micro electrical discharge machining process were studied by using EDM oil, deionized water, and graphite fiber mixed EDM oil as the dielectric fluids. The process performances were measured in terms of material removal rate, surface roughness and surface topography. The effect of deionized water on SUS 304 also was tried and compared with that on RB-SiC. It was found that when graphite fiber mixed EDM oil was used, higher material removal rate, better surface finish and smoother surface topography were obtained compared to that pure EDM oil and deionized water on RB-SiC. Deionized water could produce better form accuracy, however, electrolytic corrosion occurred and small pits were formed around the machining area of RB-SiC. In contrast, electrolytic corrosion was insignificant for SUS 304

Molecular and Cellular Mechanisms of Aging in Hematopoietic Stem Cells and Their Niches

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of HSC aging. In addition, we discuss the potential mechanisms by which HSC aging is regulated