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.     

A comparative study of DPSK and OOK WDM transmission over transoceanic distances and their performance degradations due to nonlinear phase noise

We have compared experimentally the transmission performance of return-to-zero differential phase-shift keying (RZ-DPSK) with RZ-ON-OFF keying (OOK), nonreturn-to-zero differential phase-shift keying (NRZ-DPSK), and NRZ-OOK for 100/spl times/10-Gb/s transmission with a spectral efficiency of 0.22 b/s/Hz over transoceanic distances. The Q degradation of the RZ-DPSK after transmission over 9180 km was 3 dB greater than that of RZ-OOK. The experimental results clearly showed the major cause of degradation for DPSK is not cross-phase modulation but self-phase modulation. The calculated nonlinear phase noise, i.e., the Gordon-Mollenauer effect, agreed with the experimental results. A distributed-Raman-amplifier assisted erbium-doped-fiber-amplified transmission line acted well in reducing the nonlinear phase noise.     

Solution intercalation of polystyrene and the comparison with poly(ethyl methacrylate)

Polystyrene nanocomposites have been prepared via solution intercalation method. Combination of wide-angle X-ray diffraction and thermogravimetric analysis is used to study the effect of solvents on the morphology of the nanocomposites as a function of the amount of residual solvent. d-Spacing of the polystyrene nanocomposites has a minimum value when the residual solvent concentration is between 2 and 4 wt%. Different interaction level between the solvent molecules and polymer chains is considered to be the reason for this special d-spacing change behavior. By comparing the solution intercalation of polystyrene and poly(ethyl methacrylate) from different solvents, it is concluded that the interactions between polymer-surfactant, solvent-surfactant, and polymer-solvent play important role for the solution intercalation of polymers.     

Suppression control method for torque vibration of three-phase HB-type stepping motor utilizing feedforward control

This paper proposes a method to reduce the vibration of the three-phase HB-type stepping motor with cogging torque by the feedforward compensation control. The compensation signal to suppress the vibration of the motor frame is obtained by the repetitive controller installing an online Fourier transformer and utilizing an acceleration sensor attached to the motor frame or an acoustic sensor such as a microphone placed close to the frame. The sensor is used only for the acquisition of the feedforward compensation data. The feedforward compensation signal at an arbitrary operating point is derived from the amplitude and phase data of the frequency components and the operating point data. Compensation data obtained by the repetitive controller is applied to the operating point changed by reference frequency and load condition in steady state. The compensation signal for the new operating point will be generated from compensation data utilizing polynomial equation approximation and linear interpolation method. The effectiveness of this proposed method is confirmed by the experimental results.     

Digitally tunable optical filters using arrayed-waveguide grating(AWG) multiplexers and optical switches

Two novel configurations for digitally tunable optical filters based on arrayed-waveguide grating (AWG) multiplexers are described in detail with emphasis on the connection of the AWG multiplexer and optical switches. Performance comparisons show that conventional configurations are disadvantaged by the switch size required and loss imbalance among the optical frequency-division-multiplexed (FDM) channels; the proposed configurations require only O(√(N)) switch elements to select one of N FDM channels, and the loss imbalance is lower by up to 75% in decibel     

Tuning-current splitting network for three-section DBR lasers

A simple current-splitting network for DBR-laser frequency tuning is proposed that distributes a single control current among two tuning sections and can adjust the current distribution without yielding impedance mismatching. The nonlinear characteristics of the tuning sections realise the non-proportional current splitting suitable for continuous tuning; 470 GHz (3.8 nm) tuning range is achieved     

Continuous hydrolysis of olive oil by lipase in microporous hydrophobic membrane bioreactor

Continuous hydrolysis of olive oil byCandida cylindracea’s lipase was studied in a microporous hydrophobic membrane bioreactor. Olive oil and buffer solution, fed continuously through two compartments partitioned by membrane, caused reaction at the interface of lipase-adsorbed membrane and buffer solution. Fatty acid was obtained in a single phase without being mixed with components of other phases. At all mean residence times, countercurrent flow mode was superior to cocurrent one. The lipase was adsorbed onto the membrane, and its adsorption was suggested to be partially specific from the experiments with enzymes having various levels of purity. The percent hydrolysis depended hyperbolically on the interfacial enzyme concentration. The hydrolysis seemed to be limited by diffusion of fat or fatty acid through the micropores of the membrane at higher interfacial enzyme concentrations. The lipase was stabilized significantly by glycerol added to the buffer solution. Satisfactory performance of the membrane bioreactor was obtained in a longterm continuous operation which lasted for 24 days by feeding buffer-glycerol (18.0%) solution over the adsorbed lipase. The operational half-life of the adsorbed enzyme was 15 days at 40 C.     

Stability,cure properties,and applicability as one part adhesives of systems of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisepoxide

Heterogeneous curable compositions of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisphenol A diglycidyl ether (BADG) systems were prepared by merely mixing these components at room temperature. Stability at room temperature and cure properties at high temperature of the compositions were investigated for evaluating their applicability as one part adhesive. It was found that the systems containing Mg were generally more stable than those containing Ca. Similarly, at 150°C the Ca-containing systems showed generally shorter gelation time than the Mg-containing ones, due to the fact that the Ca salt dissolves more rapidly and enters into the addition reaction with the anhydride, leading to the faster appearance of the catalytic activities of the Ca carboxylate group. Among the various combinations of components, the metal salt–succinic anhydride (SA)–BADG systems were stable at room temperature for more than 6 months and rapidly cured at high temperature, showing excellent adhesive properties. This result indicates that the SA-containing systems should be of interest in applications to one part adhesives.