Physical Time-Varying Transfer Functions as Generic Low-Overhead Power-SCA Countermeasure

Mathematically-secure cryptographic algorithms leak significant side channel information through their power supplies when implemented on a physical platform. These side channel leakages can be exploited by an attacker to extract the secret key of an embedded device. The existing state-of-the-art countermeasures mainly focus on the power balancing, gate-level masking, or signal-to-noise (SNR) reduction using noise injection and signature attenuation, all of which suffer either from the limitations of high power/area overheads, performance degradation or are not synthesizable. In this article, we propose a generic low-overhead digital-friendly power SCA countermeasure utilizing physical Time-Varying Transfer Functions (TVTF) by randomly shuffling distributed switched capacitors to significantly obfuscate the traces in the time domain. System-level simulation results of the TVTF-AES implemented in TSMC 65nm CMOS technology show > 4000x MTD improvement over the unprotected implementation with nearly 1.25x power and 1.2x area overheads, and without any performance degradation

Complete reversal of epithelial to mesenchymal transition requires inhibition of both ZEB expression and the Rho pathway

<p>Abstract</p> <p>Background</p> <p>Epithelial to Mesenchymal Transition (EMT) induced by Transforming Growth Factor-β (TGF-β) is an important cellular event in organogenesis, cancer, and organ fibrosis. The process to reverse EMT is not well established. Our purpose is to define signaling pathways and transcription factors that maintain the TGF-β-induced mesenchymal state.</p> <p>Results</p> <p>Inhibitors of five kinases implicated in EMT, TGF-β Type I receptor kinase (TβRI), p38 mitogen-activated protein kinase (p38 MAPK), MAP kinase kinase/extracellular signal-regulated kinase activator kinase (MEK1), c-Jun NH-terminal kinase (JNK), and Rho kinase (ROCK), were evaluated for reversal of the mesenchymal state induced in renal tubular epithelial cells. Single agents did not fully reverse EMT as determined by cellular morphology and gene expression. However, exposure to the TβRI inhibitor SB431542, combined with the ROCK inhibitor Y27632, eliminated detectable actin stress fibers and mesenchymal gene expression while restoring epithelial E-cadherin and Kidney-specific cadherin (Ksp-cadherin) expression. A second combination, the TβRI inhibitor SB431542 together with the p38 MAPK inhibitor SB203580, was partially effective in reversing EMT. Furthermore, JNK inhibitor SP600125 inhibits the effectiveness of the TβRI inhibitor SB431542 to reverse EMT. To explore the molecular basis underlying EMT reversal, we also targeted the transcriptional repressors ZEB1 and ZEB2/SIP1. Decreasing ZEB1 and ZEB2 expression in mouse mammary gland cells with shRNAs was sufficient to up-regulate expression of epithelial proteins such as E-cadherin and to re-establish epithelial features. However, complete restoration of cortical F-actin required incubation with the ROCK inhibitor Y27632 in combination with ZEB1/2 knockdown.</p> <p>Conclusions</p> <p>We demonstrate that reversal of EMT requires re-establishing both epithelial transcription and structural components by sustained and independent signaling through TβRI and ROCK. These findings indicate that combination small molecule therapy targeting multiple kinases may be necessary to reverse disease conditions.</p