Role of Mitochondria in the Mechanism(s) of Action of Metformin

Metformin is a drug from the biguanide family that is used for decades as the first-line therapeutic choice for the treatment of type 2 diabetes. Despite its worldwide democratization, owing to its clinical efficacy, high safety profile and cheap cost, the exact mechanism(s) of action of this anti-hyperglycemic molecule with pleiotropic properties still remains to be fully elucidated. The concept that metformin would exert some of its actions though modulation of the mitochondrial bioenergetics was initially forged in the 50s but undeniably revived at the beginning of the twenty-first century when it was shown to induce a weak but specific inhibition of the mitochondrial respiratory-chain complex 1. Furthermore, metformin has been reported to reduce generation of reactive oxygen species at the complex 1 and to prevent mitochondrial-mediated apoptosis, suggesting that it can protect against oxidative stress-induced cell death. Nevertheless, despite some recent progress and the demonstration of its key role in the inhibition of hepatic gluconeogenesis, the exact nature of the mitochondrial interaction between the drug and the complex 1 is still poorly characterized. Recent studies reported that metformin may also have anti-neoplastic properties by inhibiting cancer cell growth and proliferation, at least partly through its mitochondrial action. As such, many trials are currently conducted for exploring the repositioning of metformin as a potential drug for cancer therapy. In this mini-review, we discuss both historical and more recent findings on the central role played by the interaction between metformin and the mitochondria in its cellular mechanism of action

Finite Element Method

International audienceIn this chapter, we demonstrate a general formulation of the Finite Element Method allowing to calculate the diffraction efficiencies from the electromagnetic field diffracted by arbitrarily shaped gratings embedded in a multilayered stack lightened by a plane wave of arbitrary incidence and polarization angle. It relies on a rigorous treatment of the plane wave sources problem through an equivalent radiation problem with localized sources. Bloch conditions and a new Adaptative Perfectly Matched Layer have been implemented in order to truncate the computational domain. We derive this formulation for both mono-dimensional gratings in TE/TM polarization cases (2D or scalar case) and for the most general bidimensional or crossed gratings (3D or vector case). The main advantage of this formulation is its complete generality with respect to the studied geometries and the material properties. Its principle remains independent of both the number of diffractive elements by period and number of stack layers. The flexibility of our approach makes it a handy and powerful tool for the study of metamaterials, finite size photonic crystals, periodic plasmonic structures..

Transmission enhancement through square coaxial apertures arrays in metallic film: when leaky modes filter infrared light

We consider arrays of square coaxial apertures in a gold layer and study their diffractive behavior in the far infrared region. These structures exhibit a resonant transmission enhancement that is used to design tunable bandpass filters. We provide a study of their spectral features and show by a modal analysis that the resonance peak is due to the excitation of leaky modes of the open photonic structure. Fourier transform infrared (FTIR) spectrophotometry transmission measurements of samples deposited on Si substrate show good agreement with numerical results and demonstrate angular tolerance up to 30 degrees of the fabricated filters.Comment: 4 pages, 3 figure

The Model of Reading: Modelling principles, Definitions, Schema, Alignments

This technical report introduces the data model developed to address the systematic collection and use of reading experiences in READ-IT project. The model of reading presented in this document is meant to inform the development of the READ-IT database and tools. This document describes the methodological approach and design principles adopted in the development of the model of reading. Furthermore, this technical report describes the content of the first version of the data model of the reading experience, including a preliminary analysis of the alignments between READ-IT model of reading with CIDOC-CRM, FRBRoo, FoaF and Schema.org

The Model of Reading : Modelling principles, Definitions, Schema, Alignments

READ-IT Model of Reading -V2Executive Summary This technical report introduces the data model developed to address the systematic collection and use of reading experiences in READ-IT project. The model of reading presented in this document is meant to inform the development of the READ-IT database and tools. This document describes the methodological approach and design principles adopted in the development of the model of reading. Furthermore, this technical report describes the content of the first version of the data model of the reading experience, including a preliminary analysis of the alignments between READ-IT model of reading with CIDOC-CRM, FRBRoo, FoaF and Schema.org

Resonant metamaterial absorbers for infrared spectral filtering: quasimodal analysis, design, fabrication and characterization

We present a modal analysis of metal-insulator-metal (MIM) based metamaterials in the far infrared region. These structures can be used as resonant reflection bandcut spectral filters that are independent of the polarization and direction of incidence because of the excitation of quasimodes (modes associated with a complex frequency) leading to quasi-total absorption. We fabricated large area samples made of chromium nanorod gratings on top of Si/Cr layers deposited on silicon substrate and measurements by Fourier Transform spectrophotometry show good agreement with finite element simulations. A quasimodal expansion method is developed to obtain a reduced order model that fits very well full wave simulations and that highlights excitation conditions of the modes.Comment: 8 pages, 7 figure