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.     

Radiophotoluminescence phenomenon in copper-doped aluminoborosilicate glass

Radiophotoluminescence phenomena have been widely investigated on various types of materials for dosimetry applications. We report that an aluminoborosilicate glass containing 0.005 mol% copper exhibits intense photoluminescence in the visible region induced by X-ray and γ-ray irradiation. The luminescence is assigned to the 3d⁹4s¹ → 3d¹⁰ transition of Cu⁺. The proportionality of the intensity of the induced photoluminescence to the irradiation dose was confirmed up to 0.5 kGy using ⁶⁰Co γ-ray irradiation. Based on the spectroscopic results, a potential mechanism was proposed for the enhancement of the photoluminescence. The exposure to the ionizing radiation generates electron-hole pairs in the glass, and the electrons are subsequently captured by the Cu²⁺ ions, which are converted to Cu⁺ and emit the luminescence. For the glass containing 0.01 mol% copper, the pronounced enhancement of the photoluminescence was not observed because the reverse reaction, ie, the capture of the holes by the Cu⁺ ions, becomes prominent. The photoluminescence induced by the irradiation was stably observed for the glasses kept at room temperature and even for the glasses heat-treated at 150°C. However, the induced photoluminescence could be eliminated by the heat treatment at a temperature at 500°C, and the glass returned to the initial pre-irradiation state. The Cu-doped aluminoborosilicate glass is a potential candidate for use in dosimetry applications.     

An equation of state for 1,1-difluroethane (HFC 152a)

An equation of state for 1,1-difluoroethane (HFC 152a, CH₃CHF₂) has been developed on the basis of reliable experimental data including PVT, liquid C_p, and saturated-liquid-density data measured by our group. It is a non-dimensionalized virial equation whose functional form is the same as that originally developed for 1,1,1,2-tetrafluoroethane (HFC 134a) in our group. The effective range is for pressures up to 15 MPa, temperatures from 230 to 450 K, and densities to 1000 kg m⁻³. The equation represents reliable PVT measurements within ± 1% in pressure for the superheated vapour and supercritical fluid, while within ±0.5% in density for the compressed liquid. In addition, it should be noted that the equation represents the other essential thermodynamic properties including vapour pressures, saturated-liquid/ vapour densities, isobaric/isochoric specific heats and sound velocity in both the liquid and gaseous phase of HFC 152a.     

Subsurface structures in initial stage of FeSi2 growth studied by high-resolution Rutherford backscattering spectroscopy

The initial stage of iron silicide formation is investigated by high-resolution Rutherford backscattering spectroscopy. During the Fe deposition on Si(001) at 470 °C, the formation of FeSi₂ is confirmed by the surface peak analysis. Initially, FeSi₂ grows epitaxially so that one of the major crystallographic axes is parallel to the <111> axis of the Si substrate. With increasing Fe deposition, the deviation between the major crystallographic axis of the silicide region and Si<111> increases although the electron diffraction pattern is independent of the amount of Fe deposition. Therefore, the subsurface crystallographic structure of iron silicide is transformed from a cubic-like to a low-symmetry structure.     

Improvement of Mechanical Properties of Machinable Glass-Ceramics through Postmachining Heat Treatments

A mica-based machinable glass-ceramic has been converted to a glass-ceramic containing cordiertie and body-centered cubic chondrodite through heat treatment at temperatures higher than that used for the crystallization of mica. The machinability is lost, microhardness increases, and the thermal expansion coefficient decreases with the change of the crystalline phase from mica to cordierite and chondrodite.     

Bias-stress-induced increase in parasitic resistance of InP-based InAlAs/InGaAs HEMTs

The reliability of InP-based HEMTs is studied, focussing on how it is affected by the doped layer material and gate recess structure. Bias-and-temperature stress tests reveal that fluorine-induced donor passivation in the recess region, formed adjacent to the gate electrode, causes the source resistance (R_s) to increase at large drain bias voltages. The increase in R_s can be prevented by using InP or InAlP as the carrier supply layer material instead of InAlAs. On the other hand, the increase in the drain resistance (R_d) does not depend on the material of the carrier supply layer, which suggests that a mechanism different from that in the case of R_s should be considered. It is also found that a deep gate recess suppresses the increase in R_d after long-term stressing.     

When West meets East: Contributions of Eastern traditions to the future of psychotherapy.

Discusses 2 interrelated traditions as they are reflected in contemporary and traditional approaches to psychotherapy in Japan. One uses various meditational and self-focusing instructional sets whose common goal is to facilitate the slowing down, deepening, and clearer focusing of sensory and interpersonal awareness. The 2nd tradition focuses on physical self-regulation and autonomic self-control through exercises that foster enhanced voluntary control over physical states and processes. Eastern psychology offers a set of practices that help the individual overcome the inherent selfishness of his/her isolated experience. The goals of such work include recognition of gratitude to important people in the client's life, rediscovery of the joy of meaningful work, and the experience of a unifying cosmic consciousness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)