Reliability issues and modeling of Flash and post-Flash memory (Invited Paper)

Flash memory, in particular NAND, has been an enabling technology for portable applications for the last two decades. The strength of Flash is its excellent scaling capability, allowing an ever increasing density at a decreasing cost and maintained reliability. However, the geometrical scaling of the cell exacerbates charge loss and fluctuation effects. On the other hand, new post-Flash memory technologies are being proposed, with different storage concepts and reliability physics. This review discusses the major reliability issues for Flash, with emphasis on the physical mechanisms and modeling. The reliability of charge trap and resistive memories, such as phase change and resistive switching memories, is addressed.     

Magnetic resonance butterfly coils: Design and application for hyperpolarized C studies

Hyperpolarized ¹³C magnetic resonance spectroscopy in pig models enables cardiac metabolism assessment and provides a powerful tool for heart physiology studies, although the low molar concentration of derivate metabolites gives rise to technological limitations in terms of data quality. The design of dedicated coils capable of providing large field of view with high Signal-to-Noise Ratio (SNR) data is of fundamental importance.     

Potential Mechanisms Linking Atherosclerosis and Increased Cardiovascular Risk in COPD: Focus On Sirtuins

The development of atherosclerosis is a multi-step process, at least in part controlled by the vascular endothelium function. Observations in humans and experimental models of atherosclerosis have identified monocyte recruitment as an early event in atherogenesis. Chronic inflammation is associated with ageing and its related diseases (e.g., atherosclerosis and chronic obstructive pulmonary disease). Recently it has been discovered that Sirtuins (NAD⁺-dependent deacetylases) represent a pivotal regulator of longevity and health. They appear to have a prominent role in vascular biology and regulate aspects of age-dependent atherosclerosis. Many studies demonstrate that SIRT1 exhibits anti-inflammatory properties in vitro (e.g., fatty acid-induced inflammation), in vivo (e.g., atherosclerosis, sustainment of normal immune function in knock-out mice) and in clinical studies (e.g., patients with chronic obstructive pulmonary disease). Because of a significant reduction of SIRT1 in rodent lungs exposed to cigarette smoke and in lungs of patients with chronic obstructive pulmonary disease (COPD), activation of SIRT1 may be a potential target for chronic obstructive pulmonary disease therapy. We review the inflammatory mechanisms involved in COPD-CVD coexistence and the potential role of SIRT1 in the regulation of these systems.     

Dynamical Behavior in a DPCM System with an Order 2 Predictor. Case of a Constant Input

This paper deals with a differential pulse code modulation (DPCM) transmission system. It includes an encoder which uses a coupling between a transversal predictor and a nonlinear quantizer. This paper studies, from a dynamical point of view, an order 2 DPCM system modeled via a noninvertible two-dimensional map. Chaotic phenomena can be observed; depending on the kind of application, it can be interesting to avoid chaos or to use it. In both cases, it is necessary to understand the mechanisms which give rise to it. For that, the usual tools of chaotic dynamics are used (bifurcation structures, critical and invariant manifolds).     

Target Hopping as a Useful Tool for the Identification of Novel EphA2 Protein–Protein Antagonists

Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and the G‐protein‐coupled receptor TGR5, has been recently described as an antagonist of the EphA2 receptor, a key member of the ephrin signalling system involved in tumour growth. Given the ability of LCA to recognize FXR, TGR5, and EphA2 receptors, we hypothesized that the structural requirements for a small molecule to bind each of these receptors might be similar. We therefore selected a set of commercially available FXR or TGR5 ligands and tested them for their ability to inhibit EphA2 by targeting the EphA2‐ephrin‐A1 interface. Among the selected compounds, the stilbene carboxylic acid GW4064 was identified as an effective antagonist of EphA2, being able to block EphA2 activation in prostate carcinoma cells, in the micromolar range. This finding proposes the “target hopping” approach as a new effective strategy to discover new protein–protein interaction inhibitors.     

The Fight against the Influenza A Virus H1N1: Synthesis,Molecular Modeling,and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors

The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA–PB1 inhibitors.