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.     

Robust vector control of induction motors using full-order observer in consideration of core loss

This paper proposes a method for designing a robust full-order observer for vector-controlled induction motors taking core loss into account. Although conventional research focuses on parameter identification, global stability of the identification remains questionable. Therefore, robustness against some parameters is required. This paper describes the design of a robust full-order observer which takes core loss into account, using both the gain-scheduled H/sub /spl infin// control and the linear matrix inequality technique. This design always results in a stable controller. The robustness of the proposed method against variations of resistances is evaluated by experiments.     

Supermedia-enhanced Internet-based telerobotics

This paper introduces new planning and control methods for supermedia-enhanced real-time telerobotic operations via the Internet. Supermedia is the collection of video, audio, haptic information, temperature, and other sensory feedback. However, when the communication medium used, such as the Internet, introduces random communication time delay, several challenges and difficulties arise. Most importantly, random communication delay causes instability, loss of transparency, and desynchronization in real-time closed-loop telerobotic systems. Due to the complexity and diversity of such systems, the first challenge is to develop a general and efficient modeling and analysis tool. This paper proposes the use of Petri net modeling to capture the concurrency and complexity of Internet-based teleoperation. Combined with the event-based planning and control method, it also provides an efficient analysis and design tool to study the stability, transparency, and synchronization of such systems. In addition, the concepts of event transparency and event synchronization are introduced and analyzed. This modeling and control method has been applied to the design of several supermedia-enhanced Internet-based telerobotic systems, including the bilateral control of mobile robots and mobile manipulators. These systems have been experimentally implemented in three sites test bed consisting of robotic laboratories in the USA, Hong Kong, and Japan. The experimental results have verified the theoretical development and further demonstrated the stability, event transparency, and event synchronization of the systems.     

Efficiency of repeated batch penicillin fermentation using two fermentors. Computer simulation and optimisation

Repeated batch operation using two fermentors (RBTF) to penicillin fermentation was demonstrated by computer simulation to improve productivity. Three operation modes were compared: chemostat, repeated batch operation using a single fermentor (RBSF) and RBTF; in each case account was made of the lag period before growth. The simulated fermentor performances were assessed on the basis of the penicillin productivity and concentration; the simulation was based on published batch fermentation data. It was shown that RBTF was superior to RBSF and chemostat. The advantage of RBTF increased as the lag period became greater.     

Differentiation of Arthroderma spp. by random amplification of polymorphic DNA (RAPD) and Southern hybridization

To develop the molecular differentiation analysis of dermatophytes, we carried out RAPD and Southern hybridization analyses using genomic DNAs of six Arthroderma species, including A. fulvum, A. grubyi, A. gypseum, A. incurvatum, A. otae and A. racemosum. The RAPD analysis gave different band patterns specific to each of the six Arthroderma fungi. However, minor differences in the banding patterns were observed between the strains of plus (+) and minus (-) mating types of A. gypseum, A. fulvum and A. incurvatum. Southern blot analysis using a probe (1S) obtained from A. grubyi DNA gave specific bands only in the DNA samples of A. grubyi and A. incurvatum. On the other hand, Southern blot analysis using a probe (C3) obtained from A. otae DNA gave specific bands in all six Arthroderma species examined, and the size of the bands were specific to each species. These findings indicate that RAPD and Southern hybridization analyses are useful in the differentiation of these Arthroderma species.     

Immunohistochemical demonstration of 3,2''-dimethyl-4-aminobiphenyl DNA adduct formation in various organs of Syrian golden hamsters

We attempted to purify endogenous growth factors of chick embryonal retinal pigment epithelial cells from bovine neural retina. Ammonium sulfate precipitation, gel filtration, and anion exchange column chromatography were used. Though only partially purification, bovine retinal extract had two effects, growth and transformation, on chick embryonal pigment epithelial cells. We think that these purified factors may be novel from the estimation of their molecular weight by gel filtration.