Near net shape machining by Micro-EDM and Micro-WEDM

Near net shape is a concept that is widely used in the recent years to address the issues of sustainability and resource optimization in the manufacturing sector. Near net shape (NNS) processes are the processes that require least or no post-processing to manufacture a product. Electro-discharge machining (EDM) is a non-conventional machining process that uses spark erosion principle for machining conductivematerial. If the tool in the EDMis a flexible metallic wire, then the process is termed as wire EDM. Further to this, when the discharge energy, tool and wire diameter, and the machined features are in micron domain, the machining technique is termed μEDM or μWEDM. In μEDM/μWEDM, the resultant structure does not require any post-processing to attain the final dimensional accuracy and surface finish; therefore, these processes can be considered as NNS processes. In this chapter, different applications of μEDM and μWEDM have been discussed as NNS process

Dysregulation of valvular interstitial cell let-7c, miR-17, miR-20a, and miR-30d in naturally occurring canine myxomatous mitral valve disease

Canine myxomatous mitral valve disease (MMVD) resembles the early stages of myxomatous pathology seen in human non-syndromic mitral valve prolapse, a common valvular heart disease in the adult human population. Canine MMVD is seen in older subjects, suggesting age-related epigenetic dysregulation leading to derangements in valvular cell populations and matrix synthesis or degradation. We hypothesized that valvular interstitial cells (VICs) undergo disease-relevant changes in miRNA expression. In primary VIC lines from diseased and control valves, miRNA expression was profiled using RT-qPCR and next generation sequencing. VICs from diseased valves showed phenotypic changes consistent with myofibroblastic differentiation (vimentinlow+, a-SMAhigh+), increases in senescence markers (p21, SA-b-gal), and decreased cell viability and proliferation potential. RT-qPCR and miRNA sequencing analyses both showed significant (p<0.05) downregulation of let-7c, miR-17, miR-20a, and miR-30d in VICs from diseased valves compared to controls. Decreased let-7c, miR-17, and miR-20a may contribute to myofibroblastic differentiation in addition to cell senescence, and decreased miR-30d may disinhibit cell apoptosis. These data support the hypothesis that epigenetic dysregulation plays an important role in age-related canine MMVD