Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.     

Mass transfer in polycrystalline ytterbium monosilicate under oxygen potential gradients at high temperatures

Mass transfer in polycrystalline Yb₂SiO₅ wafers with precise composition control was evaluated and analyzed by oxygen permeation experiments at high temperatures using an oxygen tracer. Oxygen permeation proceeded due to mutual grain boundary diffusion of oxide ions and Yb ions without synergistic effects such as acceleration or suppression. The oxygen shielding properties of Yb₂SiO₅ were compared with those of the other line compounds such as Yb₂Si₂O₇ and Al₂O₃ based on the determined mass transfer parameters. It was found that the more preferentially an oxide ion diffuses in the grain boundary compared to the interior of the grain, the greater the effect of suppressing the movement of the oxide ion by applying an oxygen potential gradient becomes.     

Applications of analytical electron microscopy to guide the design of boron carbide

Compositional analysis of boron carbide on nanometer length scales to examine or interpret atomic mechanisms, for example, solid-state amorphization or grain-boundary segregation, is challenging. This work reviews advancements in high-resolution microanalysis to characterize multiple generations of boron carbide. First, ζ-factor microanalysis will be introduced as a powerful (scanning) transmission electron microscopy ((S)TEM) analytical framework to accurately characterize boron carbide. Three case studies involving the application of ζ-factor microanalysis will then be presented: (1) accurate stoichiometry determination of B-doped boron carbide using ζ-factor microanalysis and electron energy loss spectroscopy, (2) normalized quantification of silicon grain-boundary segregation in Si-doped boron carbide, and (3) calibration of a scanning electron microscope X-ray energy-dispersive spectroscopy (XEDS) system to measure compositional homogeneity differences of B/Si-doped arc-melted boron carbides in the as-melted and annealed conditions. Overall, the improvement and application of advanced analytical tools have helped better understand processing–microstructure–property relationships and successfully manufacture high-performance ceramics.     

Size-dependent separation of graphene oxide by deformation of packed-gel in a chromatographic column

ABSTRACT

A deformable gel-packed chromatographic column was used to separate as-synthesized graphite oxide with different sizes. The synthesized gel (56 µm) was deformed by pressure of the fluid flow and the gaps in the gels showed a range of sizes. A suspension of graphene oxide (0.1 g/L, 10 mL) was injected, and graphene oxide in the elution had a size at 0.56 μm and 0.14 μm, whereas in half upper and bottom domain of the gel layer graphene oxide had a size at 33 µm and 2.9 µm, respectively, demonstrating that graphene oxide suspension was separated by size through gel layer.     

Principled analytic classifier for positive-unlabeled learning via weighted integral probability metric

Machine Learning - We consider the problem of learning a binary classifier from only positive and unlabeled observations (called PU learning). Recent studies in PU learning have shown superior...     

Study on estimating electric potential in space between parallel electrodes

We have been studying on estimating distribution of permittivity between measurement electrodes using capacitance and electric potential. Two arc electrodes were separated by long distance and there electrodes were surrounded by additional electrodes respectively. In past research work, we carried out numerical electric analysis for calculating the capacitance and electric potential using Finite Element Method (FEM) and compared with experimental and numerical results. The capacitance values were almost agreed with experimental and numerical results. However, the electric potential values were different between experimental and numerical results in conventional studies. In this paper, we proposed an equivalent circuit including the stray capacity and measurement method for capacitance, the electric potential in space between long distance electrodes was estimated.     

Main‐chain smectic liquid crystalline polymer exhibiting unusually high thermal conductivity in an isotropic composite

The thermal conductivity (TC) of an isotropic composite comprising of a main‐chain smectic liquid crystalline PB‐10 polyester and 50‐μm‐sized roughly spherical magnesium oxide (MgO) particles is investigated. The increase in the composite TC with higher MgO fractions is steeper than that expected by Bruggeman's theory for the TC of a polydomain PB‐10 polyester (0.52 W m^?1 K^?1). When the filler content is larger than 30 vol %, the composite TC approaches a value that can be explained only if the polyester functions as a matrix with 1.0 W m^?1 K^?1, which is five times as high as those of isotropic common polymers (0.2 W m^?1 K^?1). Such an unusually high TC for a polymer matrix is attributed to some polymer lamellae that lie parallel to the particle surface and are stacked toward neighboring particles, thus creating effective heat paths between the particles and a continuous thermal network in a composite. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 39896.     

Lightning occurrence data observed with lightning location systems of electric power companies in Japan: 2009–2013

Nine electric power companies in Japan have been collecting lightning data with lightning location systems. Five years of the lightning data (2009–2013) are summarized and analyzed in this paper. The recent annual number of lightning flashes of which the current is more than 10 kA in Japan is around 1 million. The variations of lightning occurrence characteristics by areas, seasons, and so on, are clarified. Meteorological conditions that may affect lightning occurrence are also discussed. Furthermore, we show that there is a clear correlation between the number of lightning strikes and the outage rate of transmission lines. © 2016 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.