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.     

Interferometric method for preventing mode-hopping in tunable external-cavity semiconductor lasers

A problem in frequency-tuning of external-cavity lasers is mode-hopping between neighbouring external-cavity modes. We demonstrate a new interferometric method for monitoring mode-hoping and an automatic control circuit for a 1.3 ?m grating external-cavity laser that maintains single-mode operation when the lasing frequency is tuned.     

Wide-span optical frequency comb generator for accurate opticalfrequency difference measurement

An optical frequency comb (OFC) generator was realized for accurate optical frequency difference measurement of 1.5 μm wavelength semiconductor lasers by using a high frequency LiNbO₃ electrooptic phase modulator which was installed in a Fabry-Perot cavity. It was confirmed that the span of the OFC was wider than 4 THz. By using semiconductor lasers whose spectrum linewidths were narrowed to 1 kHz and a sensitive optical balanced-mixer-receiver for measuring beat signal between the sideband of the comb and the laser, we demonstrated a frequency difference measurement up to 0.5 THz with a signal-to-noise ratio higher than 61 dB, and a heterodyne optical phase locking with a heterodyne frequency of 0.5 THz in which the residual phase error variance was less than 0.01 rad². The maximum measurable frequency difference, which was defined as the sideband frequency with the signal-to-noise ratio of 0 dB, was estimated to be 4 THz     

Modulation characteristic of waveguide-type optical frequency combgenerator

We report the modulation characteristics of a waveguide-type optical frequency comb generator (WG-OFCG) with the advantages of compactness, high modulation index and low driving power. The characteristics of the optical frequency comb (OFC) generated when the modulation index exceeds 2π are discussed. The power of the modulation sidebands was measured by the optical heterodyne method with an external-cavity laser as a local oscillator. The dependence of the modulation index of the WG-OFCG on the modulation frequency up to 40 GHz was measured. The generation span of the OFC at the modulation frequency detuned from an integer multiple of the free spectral range (FSR) is discussed     

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.     

Thermal response in thermal energy storage material around heat transfer tubes: effect of additives on heat transfer rates

The effects of carbon-fiber chips and carbon brushes as additives on the thermal conductivity enhancement of phase change materials (PCMs) using in latent heat thermal energy storage are investigated experimentally and numerically by considering the wall effect of the additives. The carbon-fiber chips are effective for improving the heat transfer rate in PCMs. However, the thermal resistance near the heat transfer surface is higher than that for the carbon brushes. As a result, the overall heat transfer rate for the fiber chips is lower than that for the carbon brushes. Consequently, the carbon brushes are superior to the fiber chips for the thermal conductivity enhancement under the present experimental conditions. The carbon brushes are moreover applied to the packed beds of particles to overcome their low thermal conductivity in chemical heat pump/storage. The carbon brushes essentially improve the heat transfer characteristics in the packed beds, though the thermal resistance is observed because the particles obstruct contact between the fibers and the heat transfer surfaces.     

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.     

Limit of optical-frequency comb generation due to materialdispersion

The limit of optical frequency comb (OFC) generation (i.e., the limit of frequency difference measurement) due to the material dispersion in the EO crystal is experimentally studied. By using a modified monolithic OFC generator, we observed the OFC spectrum, and confirmed that the envelope of the OFC around 780 nm extended to a span as wide as 16 nm (or 7.6 THz) reaching the limit of the OFC generation. We also proposed a method of stabilizing the Fabry-Perot cavity for the monolithic OFC generator