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.     

Very low threshold graded-indexseparate-confinement-heterostructure strained InGaAsPsingle-quantum-well lasers

A low threshold current density of ~100 A/cm² has been obtained at 1.55 μm using a graded-index separate-confinement-heterostructure strained InGaAsP single-quantum-well laser. The design of the laser structure is based on results calculated from the viewpoint of effective carrier injection into the well     

Preparation of Laminin-apatite-polymer Composites Using Metastable Calcium Phosphate Solutions

A synthetic polymer with a laminin-apatite composite layer on its surface would be useful as a percutaneous device. The preparation of such a composite was attempted in the present study using poly（ ethylene terephthalate ） （PET） and polyethylene （PE） as the synthetic polymer. PET and PE plates and those pretreated with an oxygen plasma were alternately dipped in calcium and phosphate ion solutions, and then immersed in a metastable calcium phosphate solution supplemented with laminin （ LCP solution ）. The PET and PE plates pretreated with an oxygen plasma formed a uniform and continuous layer of a laminin-apatite composite on their surfaces. In contrast, the PET and PE plates that had not been pretreated with an oxygen plasma did not form a continuous layer of a laminin-apatite composite on their surfaces. The hydrophilic functional groups on the PET and PE surfaces introduced by the plasma treatment were responsible for the successful laminin-apatite coruposite coating.     

Molecular cloning of human class IV alcohol dehydrogenase cDNA

A cDNA encoding a new type of alcohol dehydrogenase was cloned from a human stomach cDNA library. PCR amplification of 5'-stretch human stomach lambda gt11 library, using degenerate inosine-containing oligonucleotide probes compatible with peptide sequences of human sigma-ADH, resulted in a single product. Subsequently, internal non-degenerate primers were constructed according to the sequences occurring in the product. By PCR with combinations of these new primers and lambda gt11 forward and reverse primers, fragments of the cDNA containing its 5' and 3' ends were amplified. The full length cDNA sequence has 1125 nucleotides with a 72% similarity to those of human class I ADH. The polypeptide sequence, predicted from the cDNA, corresponds to 373 amino acids with a high degree of similarity (96%) to fragments of sigma-ADH previously reported. Northern hybridization analysis with the specific probe for the mRNA of this protein showed that it is expressed in the human stomach but not in the liver. These data indicate that the cDNA we cloned is that of human class IV ADH.     

Electrochemically induced asymmetrical etching in InAlAs/InGaAs heterostructures for MODFET gate-groove fabrication

We have achieved a self-controlled asymmetrical etching in metalorganic chemical vapor deposition-grown InAlAs/InGaAs heterostructures, which can be suitable for fabricating modulation-doped field-effect transistors (MODFETs) with gate-groove profiles for improved performance. The technology is based on electrochemical etching phenomena, which can be effectively controlled by using different surface metals for ohmic electrodes. When surface metals of Pt and Ni are deposited on the source and the drain, respectively, the higher electrode potential of Pt results in slower etching on the source side than on the drain side. Thus, asymmetry of gate grooves can be formed by wet-chemical etching with citric-acid-based etchant. This represents a new possibility to conduct “recess engineering” for InAlAs/InGaAs MODFETs.     

Stabilization of inter-area and/or oscillatory modes in large-scale power system by voltage impedance power system (VIPS) apparatus based on decentralized control scheme

New technologies such as power electronics have made it possible to change continuously the impedance of a power system not only to control power flow but also to enhance stability. A power system incorporating a variable impedance apparatus such as a variable series capacitor (VSrC) and high-speed phase shifter (HSPS) is called VIPS (Variable Impedance Power System) by the authors. This paper proposes a novel control method of VIPS apparatus such as VSrC and HSPS installed at an interconnecting point for stabilizing inter-area unstable and/or oscillatory modes. The proposed design method of the control system is a kind of hierarchical decentralized control method of a large-scale power system based on a Lyapunov function. Under the proposed control scheme, each subsystem can be stabilized independently by local controllers such as AVR, speed governor and PSS, and then the whole interconnected system can be stabilized by VIPS apparatus taking into account interactions between subsystems. The effectiveness and robustness of the VIPS apparatus control are shown by numerical examples with model systems including a large-scale power system.     

The relation between luminous properties and oxygen content inZnS:TbOF thin-film electroluminescent devices fabricated byradio-frequency magnetron sputtering method

The purpose of this paper is to study the relationship between the oxygen concentration and brightness degradation in ZnS:TbOF green thin-film electroluminescent (EL) devices. The characteristics including crystallinity, optical, and electrical properties were discussed. The brightness-voltage (B-V) measurement results shelved that with higher oxygen-content in ZnS:TbOF phosphor layer, lower brightness was measured. It was consistent with the poor crystallinity, worse photoluminescent intensity, and easier to get moisture in the oxygen-rich (O/Tb>1) phosphor film. Furthermore, deep level transient spectroscopy (DLTS) measurements identified that when the O/Tb ratio was greater than 1, the oxygen-related deep hole traps E_H1 and/or E_H2 could be detected in the ZnS:TbOF phosphor layer. These E _H1 and/or E_H2 traps were believed to be the main killers for the brightness of the device since they capture most of the holes from the generated electron-hole pairs. This evidence strongly supports that the modified energy transfer model is more dominant than direct impact excitation during the luminescent process     

Practical method for generation expansion planning based on dynamic programming

This paper presents an efficient method which provides the optimal generation mix and the optimal generation construction process. The approximation method in which the dynamic programming technique and gradient method are combined is applied to determine the optimal generation mix with hydropower generation technologies. The successive approximations dynamic programming (SADP) technique, which is very suitable for high-dimensional multistage decision process problems, is used for obtaining the optimal generation construction process. The effectiveness and feasibility of the developed technique are demonstrated on a practical power system model which has five types of generation technologies including a hydropower generation technology.