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.     

Anti‐Sway Crane Control Considering Wind Disturbance and Container Mass

A method for estimating the sway angle using an observer has already been proposed. The state observer estimates the sway angle accurately and must use the detected sway angle value. However, the estimated sway angle has an error owing to rope length error, friction force, and wind. Moreover, the container mass cannot be determined, and therefore the observer parameter is not suitable. We already proposed robust antisway control for overcoming rope length error without adding a new sensor. Further, we designed a friction disturbance observer to cancel out the influence of the friction force. In this paper, we first propose a container mass estimation method when a crane system performs rolling up control. The observer parameter can be selected using the estimated mass value. Second, in crane parallel shift control, we propose a robust antisway control even when there is a wind disturbance. We design a wind disturbance observer and propose a wind disturbance estimator to separate the friction observer output from the wind disturbance observer output. We confirm through experiments that the proposed method can reduce vibration.     

Cover Picture: UV‐Light‐Induced Swelling and Visible‐Light‐Induced Shrinking of a TiO2‐Containing Redox Gel (Adv. Mater. 9/2007)

Polyacrylate gels containing Ag⁺ and TiO₂ nanoparticles are shown to swell under UV light and shrink under visible light in water. In work reported by Tetsu Tatsuma and co‐workers on p. 1249, the TiO₂ absorbs UV light and reduces the Ag⁺, whereas the deposited Ag absorbs visible light and dissolves itself. These redox reactions change the interactions between the polymer chains and eventually the volume of the gel, as shown on the cover.     

Phase diagrams calculated for Fe-rich Fe-Si-Co and Fe-Si-Al ordering alloy systems

Theoretical analysis based on the calculation of phase diagrams was employed for Fe-Si-Co and Fe-Si-Al ordering systems to clarify the necessity for the occurrence of phase separation in Fe-base ternary ordering systems. The free energy of Fe-base ternary ordering alloys where B2 and D0₃ ordered structures are formed is evaluated statistically using a pairwise interaction approximation up to second nearest neighbours, taking into account not only the atomic interaction but also the magnetic interaction, based on the Bragg-Williams-Gorsky model. The calculated phase diagrams are consistent with the experimentally obtained ones. The phase diagram calculation in this work is useful to predict the equilibrium states of the ternary ordering systems. The phase separation in ordering alloys is caused by the contribution of excess free energies due to ordering. The influences of ferromagnetism on the two-phase regions are also demonstrated.     

Tunable laser for sensing atmospheric transmission in the infrared region of 11 ∼ 16 µm

We succeeded in observing the continuously tunable, pulsed InSb SFR (Spin-Flip Raman) laser emission in the infrared region of 11～16µm (11.4～16.3µm) from only one InSb device, merely by adjusting the pumping wavelength (11 lines from the infrared NH₃ laser) and the applied magnetic field (0～80 kGauss).     

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.     

Effect of rapid sample cooling on efficiency of multiple impurity-atom doping

Shallow and efficient doping of wide band-gap semiconductors has remained one of yet unresolved problems to date. A possible solution to this problem is doping with complexes of a few impurity atoms at a quasi-equilibrium state, which is introduced by controlled cooling of a sample after doping. In this work, (1) we first define a global and quasi-equilibria of our interest based on a simple thermodynamic model for a doped crystal, and then (2) we discuss how the cooling rate affects the probability of impurity-complex formation at a quasi-equilibrium as defined. Our main message is that one should design impurity complexes as small in size as possible which have as large a binding energy as possible. This is a required condition for complex designs when it is difficult to tune the cooling rate.