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.     

Intramolecular triplet energy migration in poly(2-vinylnaphthalene) and poly(naphthylalkyl methacrylate)s in solid solution: Effects of side chain length

Summary The effect of side chain length on intramolecular triplet energy migration of naphthalene containing polymers was investigated by a delayed fluorescence (DF) spectroscopy for the solid solution of the polymers. The degree of triplet energy migration depends strongly on whether the chromophores are directly attached to the main chain or not.     

Transient analysis of an advanced static var compensator using quad-series voltage-source PAM inverters

This paper deals with an advanced static Var compensator (ASVC) using quad-series voltage-source PAM inverters. The ASVC consists of four three-phase voltage-source inverters with a common dc capacitor and four three-phase transformers, each primary winding of which is connected in series with each other. Each inverter outputs a square-wave voltage, while the synthesized output voltage of the ASVC has a 24-step wave shape. This results not only in a great reduction of harmonic currents and dc voltage ripples but also in fewer switching and snubbing losses. In this paper, transient analysis is performed with the focus on the response of reactive power and the resonance between the dc capacitor and ac reactors. Experimental results obtained from a small-rated laboratory model of 10 kVA are also shown to verify analytical results based on the p-q transformation. The analytical results help in the design of system parameters such as the capacity of the dc capacitor and feedback gains.     

Synthesis and applications of fluoroalkyl end-capped cooligomers having fullerene and mixed fullerenes in the main chain

Fluoroalkanoyl peroxides reacted with FULLERENES [fullerene (C₆₀) and commercially available fullerenes (Nanom Mix^TR and Nanom Black^TR)] and radical polymerizable comonomers such as acrylic acid, N,N-dimethylacrylamide, N-(1,1-dimethyl-3-oxobutyl)acrylamide, and acryloylmorpholine to afford fluoroalkyl end-capped cooligomers having FULLERENES in the main chain under very mild conditions. Fluoroalkyl end-capped Nanom Mix and Nanom Black cooligomers thus obtained were found to exhibit a similar solubility to that of the corresponding fluoroalkyl end-capped cooligomers having fullerene in the main chain. These fluorinated FULLERENES cooligomers were found to form the nanometer size-controlled self-assembled cooligomeric aggregates in aqueous solutions. These fluoroalkyl end-capped FULLERENES cooligomers were more effective for solubilizing fullerene, Nanom Mix and Nanom Black into water, compared to those of the corresponding fluoroalkyl end-capped homooligomers having no FULLERENES in the main chain. Fluoroalkyl end-capped fullerene- and Nanom Mix-acrylic acid cooligomers were found to exhibit fluorescence spectra related to fullerene and Nanom Mix in cooligomers, respectively, in aqueous solutions. Additionally, these fluorinated fullerene- and Nanom Mix-acrylic acid cooligomers were able to increase chemiluminescence intensity related to luminol, effectively, compared to the corresponding fluorinated acrylic acid homooligomers.     

Simulation with an improved plasma model utilized to design a new structure of microwave plasma discharge for chemical vapor deposition of diamond crystals

A new structure of microwave plasma for chemical vapor deposition of diamond crystal is proposed. The structure is designed numerically, for which an improved model given in our previous work [H. Yamada et al., J. Appl. Phys. 101 (2007), art. no. 063302.] is utilized. The experimental observations and numerical predictions agree well with each other. It is demonstrated experimentally that the proposed structure can achieve a growth rate larger than 50 μm/h over an area 1 in. in diameter.     

Protein modelling using a chimera reference protein derived from exons

Bovine pancreatic /S-trypsin (PDB ID-code: 1TPO) which is registeredin the Brookhaven Protein Data Bank (PDB) consists of four exons.The results of homology searches for each exon in the PDB showedthat homologous proteins were tonin (PDB ID-code: 1TON), ratmast cell protease (PDB ID-code: 3RP2_A), kaffikrein A (PDBID-code: 2PKA_B) and kallikrein A (2PKA_B) respectively. Thus,for the three-dimensional structure prediction of 1TPO, a chimeraprotein was constructed from the three proteins mentioned aboveand the 3-D structure prediction was performed using this chimerareference protein. The modelled structure of 1TPO was energeticallyoptimized by molecular mechanics and molecular dynamics simulationand was compared with its X-ray crystal structure registeredin the PDB. The root mean square deviations (r.m.s.d.) of mainchain atoms and the neighbouring active site (5 sphere fromHis57, AsplO2 and Serl95) between the modelled structure andthe X-ray structure were 1.66 and 0.94 respectively. Porcinepancreatic elastase (PDB ID-code: 3EST) which is registeredin the PDB was used as the reference protein and the modelledstructure from 3EST was also compared with the X-ray data. Ther.m.s.d. of main chain atoms and that of the active site were2.14 and 1.18 respectively. These results dearly support thepropriety of this method using the chimera reference protein.     

Preparation of TiB2 sintered compacts by hot pressing

A sintered compact of titanium diboride (TiB₂) was prepared by hot pressing of the synthesized TiB₂ powder, which was obtained by a solid-state reaction between TiN and amorphous boron. Densification of the sintered compact occurred at 20 MPa and 1800° C for 5 to 60 min with the aid of a reaction sintering, including the TiB₂ formation reaction between excess 20 at % amorphous boron in the as-synthesized powder (TiB₂ + 0.2B) and intentionally added 10 at % titanium metal. A homogeneous sintered compact of a single phase of TiB₂, which was prepared by hot pressing for 30 min from the starting powder composition [(TiB₂ + 0.2B) + 0.1 Ti], had a fine-grained microstructure composed of TiB₂ grains with diameters of 2 to 3 m. The bulk density was 4.47 g cm^–3, i.e. 98% of the theoretical density. The microhardness, transverse rupture strength and fracture toughness of the TiB₂ sintered compact were 2850 kg mm^–2, 48 kg mm^–2 and 2.4 MN m^–3/2, respectively. The thermal expansion coefficient increased with increasing temperature up to 400° C and had a constant value of 8.8 x 10^–6 deg^–1 above 500° C.