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.     

Isolation of antimicrobial agent from the marine algae Cystoseira hakodatensis

Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL^?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria.     

Effect of Moving Speed of Charged Metallic Spherical Electrode on Electrostatic Discharge

In this investigation, the nature of the electrostatic discharge (ESD) that occurs when a charged object moves toward a stationary grounded object is experimentally clarified. The spark lengths, discharge currents, and induced voltages in a magnetic probe were measured when a charged metallic spherical electrode connected to a 422 pF capacitor approached a stationary grounded object, which was the current target, for different moving speeds of the charged metallic spherical electrode in a range of 1 mm/s to 100 mm/s. The charge voltages of the capacitor were +6.5 kV and +10 kV. Based on the results, the average gap length shortened with the speed of the spherical electrode. The average peak values of the discharge current and the induced voltage were likely to increase with the speed of the spherical electrode. The average rise times of the discharge current and the induced voltage were likely to drop with the speed of the spherical electrode. The relation between the spark length and the discharge current due to the ESD can be explained qualitatively by using an equation derived from the spark resistance formula proposed by Rompe and Weizel.     

An analysis of shielding against DC magnetic fields generated by electric railways. Evaluation of effective permeability of fine structure

This paper describes an effective analysis of magnetic shielding based on homogenization. The analyses become time‐consuming if the problems include the magnetic substances having fine structure. The homogenization of the structure makes it possible to analyze effectively the magnetic fields. The authors introduce a method to estimate the effective permeability of the homogenized substance. This method can be applied to any periodic structure made of magnetic substance. The magnetic shielding effects by the structures against direct‐current (DC) fields generated by electric railways are analyzed by using the present method. As a result, it is found that the overhead way and the protective fence near the railway work as a magnetic shield, whose effects can be improved by appropriate arrangement of those constructions. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 160(4): 7–15, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20310     

High Gd Concentration GaGdN Grown at Low Temperatures

GaGdN layers were grown at temperatures below 300°C by radio-frequency plasma-assisted molecular beam epitaxy on sapphire substrates. GaGdN samples with high Gd concentration as high as 12.5% were obtained by lowering the growth temperature. X-ray diffraction results showed no obvious secondary phase, which means that the phase separation can be suppressed by the growth at low temperatures. All samples, including those grown at room temperature, showed ferromagnetic characteristics. Photoluminescence emission was observed, though spectra exhibit broad and sharp luminescence bands related to many kinds of defects. It is suggested that electrons coming from defects, especially, nitrogen vacancy, stabilize ferromagnetism, and that the carrier-induced ferromagnetism occurs in the low-temperature-growth GaGdN.     

Investigation into the therapeutic efficacy of continuous isoproterenol inhalation in relation to respiratory infections in asthmatic children

In our Department, continuous isoproterenol inhalation therapy has been conducted on status asthmatics over the last 10 years. In the present study, we investigated whether there are any differences in the therapeutic efficacy of continuous inhalation of isoproterenol in the presence or absence of respiratory infections which may induce or aggravate asthma attacks. The treatment period was significantly longer in patients with pneumonia. Further prolongation of the treatment period was noted in patients with atelectasis. However, there were no apparent differences in therapeutic efficacy according to age or the severity of attacks. These findings suggest that continuous inhalation of isoproterenol is very effective for status asthmatics if respiratory infections are thoroughly controlled.     

An IR study on ion-specific and solvent-specific swelling of poly(N-vinyl-2-pyrrolidone) gel

Swelling degrees of poly(N-vinyl-2-pyrrolidone) (PVP) gel were measured in aqueous salt solutions and in water/organic solvent mixtures to find marked ion- and solvent-specificities. In order to investigate any correlation of those specificities with hydration or solvation of PVP, IR spectra band of the CO group was monitored by means of ATR method both for PVP gel and the relevant solution systems. Dependence of the peak frequency on the swelling ratio suggested that hydration of PVP carbonyl group in deswollen gel systems is different from that in the corresponding solution systems. In the solution systems, PVP carbonyl band showed a high-wavenumber shift for deswollen systems, which can be well correlated with changes in water proton charge through ionic hydration and with Gutmann's acceptor number of organic solvents. In the deswollen gel systems, the CO band showed a low-wavenumber shift, suggesting a strong hydration or doubly hydrated state. This unexpected behavior was interpreted by assuming an intermolecular hydrogen bond of two carbonyl groups intermediated by water molecules.     

Authorship and citation patterns in Management Science in comparison with operational research

The authorship and citation patterns in the journal titled Management Science (MS) are analysed. The purpose of the analysis is to examine the competitive relation of MS with OR (operational research or operations research). The analysis is focused on the use of mathematical methods, because MS entered the management research area by using mathematical methods developed by OR and because the use of mathematical methods in real management is facing difficulties. The relationship of MS with information systems (IS) and organisation research (Org) is analysed in regard to the competition of MS with OR. The analysis reveals the intermediate character of MS; that is, MS is less prone to mathematical methods and is more inclined towards IS and Org than OR is. This revised version was published online in June 2006 with corrections to the Cover Date.     

STRUCTURE FORMATION OF COATED FILMS WITH DISPERSED PIGMENTS DURING DRYING

In the drying of coated films with dispersed pigments, such as floppy disks, the structure of the film is formed during the drying process and depends on the drying condition. It is important to understand the structure formation during drying for the design of the dryer and die better quality of the product. We measured die drying characteristics of the film and determined the structure of dried film experimentally. A qualitative model for the structure formation during drying of the coated film is suggested.     

Scientific Screening of Raw Diamond for an Ultraprecision Cutting Tool with High Durability

The wide scattering in tool life of natural mono-crystalline diamond tools is considered to depend on intrinsic crystalline defects due to nitrogen impurities in raw diamond. In this paper, the correlation was investigated between the amounts and types of the impurity evaluated by infrared absorption (IRA) and the crater wear and chipping resistances. As a result, diamonds including less total amount of impurity show larger wear resistance and that with larger amount of B2-aggregates show larger chipping resistance. This suggests that the inspection by IRA can be a useful method for screening of raw diamond for highly durable cutting tools.