Optimal stress signaling by Hypoxia Inducible Factor 2 (HIF-2) during low oxygen states or hypoxia requires coupled actions of a specific coactivator/lysine acetyltransferase, Creb binding protein (CBP), and a specific deacetylase, Sirtuin 1 (SIRT1). We recently reported that acetylation of HIF-2 by CBP also requires a specific acetyl CoA generator, acetate-dependent acetyl CoA synthetase 2 (ACSS2). In this study, we demonstrate that ACSS2/HIF-2 signaling is active not only during hypoxia, but also during glucose deprivation. Acetate levels increase during stress and coincide with maximal HIF-2α acetylation and CBP/HIF-2α complex formation. Exogenous acetate induces HIF-2α acetylation, CBP/HIF-2α complex formation, and HIF-2 signaling. ACSS2 and HIF-2 are required for maximal colony formation, proliferation, migration, and invasion during stress. Acetate also stimulates flank tumor growth and metastasis in mice in an ACSS2 and HIF-2 dependent manner. Thus, ACSS2/CBP/SIRT1/HIF-2 signaling links nutrient sensing and stress signaling with cancer growth and progression in mammals.

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Electrical discharge machining has emerged as one of the most accepted non-traditional machining methods that have the capability of attaining complex shapes and better feature size in difficult-to-machine materials. In this article, an advanced review of conventional electrical discharge machining and micro–electrical discharge machining of difficult-to-machine materials, such as nickel and its alloys, titanium alloys, stainless steel (SUS 304) and advanced ceramics, has been presented. The review begins with an introduction to the conventional electrical discharge machining and micro–electrical discharge machining processes, followed by classifications and a brief discussion on different aspects of micro-manufacturing methods. The current research trends and developments, research gaps and challenges of the conventional electrical discharge machining and micro–electrical discharge machining of nickel and its alloys, titanium alloys (Ti6Al4V), stainless steel and advanced ceramics are also discussed in depth. A brief note on future research trends, based on the available literature, has been included in the last section.

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In recent years, Wire-Electrical Discharge Machining (WEDM) has gained popularity in industry due to its capability to generate complicated shapes in exotic materials, irrespective of their hardness. Conventional machining of Nimonic C-263 super alloy is an extremely difficult and costly process due to its high hardness and tool wear rate. The present research work investigates the influence of the WEDM process parameters on different performance measures during machining of Nimonic C-263 super alloy.Mathematical model for all four important performance measures, namely, cutting rate, surface roughness, spark gap and wire wear ratio, was developed and the responses were used for studying the inter-relationship between performance measures and process parameters. The optimal settings of operating conditions were predicted using desirability function. The effectiveness of multi-cut strategy was also investigated in the paper.