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.     

Direct Observation of Pure Cu and Cu-Ag Anode Passivation in H2SO4-CuSO4 Aqueous Solution by Channel Flow Double Electrode and Optical Microscopy

Metallurgical and Materials Transactions B - The dissolution and passivation of pure Cu and Cu-5 wt pct Ag anodes in H2SO4-CuSO4 electrolyte were investigated by a direct...     

Upflow anaerobic sludge blanket (UASB) treatment of supernatant of cow manure by thermal pre-treatment.

Upflow anaerobic sludge blanket (UASB) methane fermentation treatment of cow manure that was subjected to screw pressing, thermal treatment and subsequent solid-liquid separation was studied. Conducting batch scale tests at temperatures between 140 and 180 degrees C, the optimal temperature for sludge settling and the color suppression was found to be between 160-170 degrees C. UASB treatment was carried out with a supernatant obtained from the thermal treatment at the optimal conditions (170 degrees C for 30 minutes) and polymer-dosed solid-liquid separation. In the UASB treatment with a COD(Cr) loading of 11.7 kg/m3/d and water temperature of 32.2 degrees C, the COD(Cr) level dropped from 16,360 mg/L in raw water to 3,940 mg/L in treated water (COD(Cr), removal rate of 75.9%), and the methane production rate per COD(Cr) was 0.187 Nm3/kg. Using wastewater thermal-treated at the optimal conditions, also a methane fermentation treatment with a continuously stirred tank reactor (CSTR) was conducted (COD(Cr) in raw water: 38,000 mg/L, hydraulic retention time (HRT): 20 days, 35 degrees C). At the COD(Cr) loading of 1.9 kg/m3/d, the methane production rate per COD(Cr), was 0.153 Nm3/kg. This result shows that UASB treatment using thermal pre-treatment provides a COD(Cr), loading of four times or more and a methane production rate of 1.3 times higher than the CSTR treatment.     

High-gain hybrid amplifier consisting of cascaded fluoride-based TDFA and silica-based EDFA in 1458-1540 nm wavelength region

A hybrid optical fibre amplifier is described that consists of a fluoride-based thulium-doped fibre amplifier and a silica-based erbium-doped fibre amplifier connected in a cascade. The amplifier has a gain of more than 25 dB and a noise figure of less than 9 dB over a wide wavelength region of 1458-1540 nm.     

High-resolution long-array thermal ink jet printhead fabricated by anisotropic wet etching and deep Si RIE

This paper describes the fabrication and characterization of a thermal ink jet (TIJ) printhead suitable for high speed and high-quality printing. The printhead has been fabricated by dicing the bonded wafer, which consists of a bubble generating heater plate and a Si channel plate. The Si channel plate consists of an ink chamber and an ink inlet formed by KOH etching, and a nozzle formed by inductively couple plasma reactive ion etching (ICP RIE). The nozzle formed by RIE has squeezed structures, which contribute to high-energy efficiency of drop ejector and, therefore, successful ejection of small ink drop. The nozzle also has a dome-like structure called channel pit, which contributes to high jetting frequency and high-energy efficiency. These two wafers are directly bonded using electrostatic bonding of full-cured polyimide to Si. The adhesive-less bonding provided an ideal shaped small nozzle orifice. Use of the same material (Si substrate) in heater plate and channel plate enables the fabrication of high precision long printhead because no displacement and delamination occur, which are caused by the difference in thermal expansion coefficient between the plates. With these technologies, we have fabricated a 1" long printhead with 832 nozzles having 800 dots per inch (dpi) resolution and a 4 pl. ink drop volume.     

Driving voltage reduction in a two-phase CCD by suppression ofpotential pockets in inter-electrode gaps

This study reports an optimum design for a two-phase charge-coupled device (CCD) and limitations on its driving voltage reduction. The two-phase CCD to be used as a horizontal-CCD (H-CCD) in a CCD image sensor requires low-voltage and high-speed operation. Reducing the driving voltage, however, may induce potential pockets in the channel under the inter-electrode gaps which results in a fatal decrease in charge-transfer efficiency. In this case it is necessary to optimize the CCD design to be free of pocket generation. For this requirement, we conducted two-dimensional (2-D) device simulations for the two-phase CCD, whose potential barriers are formed by boron ion-implantation. Our simulations indicated that the edge position of the potential barrier region and the dose of boron-ion implantation would be important parameters for controlling the size of potential pockets. At an optimum edge position and a boron dose, the minimum driving voltage appears to be reducible to 1.1 V. Characteristics of potential pockets and methods of their suppression are also discussed