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.     

The World robot summit disaster robotics category – achievements of the 2018 preliminary competition

The World Robot Summit is a robot Olympics and aims to be held in a different country every four years from 2020. The concept of the Plant Disaster Prevention challenge is daily inspections, checks, and emergency response in industrial plants, and in this competition, robots must carry out these types of missions in a mock-up plant. The concept of the Tunnel Disaster Response and Recovery challenge is emergency response to tunnel disasters, and is a simulation competition whereby teams compete to show their ability to deal with disasters, by collecting information and removing debris. The Standard Disaster Robotics challenge assesses, in the form of a contest, the standard performance levels of a robot that are necessary for disaster prevention and emergency response. The World Robot Summit Preliminary Competition was held at Tokyo Big Sight in October 2018, and 36 teams participated in the Disaster Robotics Category. UGVs and UAVs contended the merits of new technology for solving complex problems, using core technologies such as mobility, sensing, recognition, performing operations, human interface, autonomous intelligence etc., as well as system integration and implementation of strategies for completing missions, gaining high-level results.     

Real-Time Duplex Applications of Loop-Mediated AMPlification (LAMP) by Assimilating Probes

Isothermal nucleic-acid amplification methods such as Loop-Mediated isothermal AMPlification (LAMP) are increasingly appealing alternatives to PCR for use in portable diagnostic system due to the low cost, weight, and power requirements of the instrumentation. As such, interest in developing new probes and other functionality based on the LAMP reaction has been intense. Here, we report on the development of duplexed LAMP assays for pathogen detection using spectrally unique Assimilating Probes. As proof of principle, we used a reaction for Salmonella enterica as a model coupled with a reaction for λ-phage DNA as an internal control, as well as a duplexed assay to sub-type specific quarantine strains of the bacterial wilt pathogen Ralstonia solanacearum. Detection limits for bacterial DNA analyzed in individual reactions was less than 100 genomic equivalents in all cases, and increased by one to two orders of magnitude when reactions were coupled in duplexed formats. Even so, due to the more robust activity of newly available strand-displacing polymerases, the duplexed assays reported here were more powerful than analogous individual reactions reported only a few years ago, and represent a significant advance for incorporation of internal controls to validate assay results in the field.     

Changes in the gaseous H2S barrier properties of damaged silicate coated nylon 6 films

The damage imposed on SiO _x deposited nylon 6 films as a result of abrasion with a cotton cloth and Gelboflex testing was examined by evaluating the rate at which copper plates, which were enveloped by the damaged films, were corroded by H₂S. Abrasion with a cotton cloth caused some micro-cracking of the SiO _x layer and the permeation rate of H₂S approached that of the uncoated nylon 6 film. Damage to the SiO _x layer by twisting and crushing progressed gradually with the number of Gelboflex test cycles and correspondingly the corrosion rate of the copper plates increased. Comparison of the corrosion rates of the copper plates kept in the pouches made of various commercial films with those obtained for the damaged SiO _x deposited nylon 6 films showed a clear relationship between the H₂ permeation rate of the films and the corrosion rate of the copper plates by H₂S.     

A low-resistance self-aligned T-shaped gate for high-performancesub-0.1-μm CMOS

This paper describes the high performance of T-shaped-gate CMOS devices with effective channel lengths in the sub-0.1-μm region. These devices were fabricated by using selective W growth, which allows low-resistance gates smaller than 0.1 μm to be made without requiring fine lithography alignment. We used counter-doping to scale down the threshold voltage while still maintaining acceptable short-channel effects. This approach allowed us to make ring oscillators with a gate-delay time as short as 21 ps at 2 V with a gate length of 0.15 μm. Furthermore, we experimentally show that the high circuit speed of a sub-0.1-μm gate length CMOS device is mainly due to the PMOS device performance, especially in terms of its drivability     

Wortmannin enhances CPP32-like activity during neuronal differentiation of P19 embryonal carcinoma cells induced by retinoic acid

P19 EC cells undergoes apoptosis during neuronal differentiation induced by retinoic acid. Two CPP32-like proteases, CPP32 and Mch-3, are expressed in untreated and retinoic acid-treated P19 EC cells. CPP32-like activity is remarkably increased in apoptosis during neuronal differentiation of P19 EC cells. Inhibition of CPP32-like proteases prevents apoptosis, suggesting that activation of CPP32-like proteases play central roles in the apoptosis during neuronal differentiation of P19 EC cells. Wortmannin, PI-3K inhibitor, enhances the CPP32-like activity of the retinoic acid-treated P19 EC cells. PI-3K may be involved in the apoptosis during neuronal differentiation as negative regulator.     

Surgical treatment for primary cardiac malignant lymphoma

A 60-year-old woman who complained of palpitation was diagnosed as ventricular tachycardia on electrocardiography and admitted to our hospital. The ultrasonic cardiography showed cardiac tumor in right ventricle and right atrium. Due to the obstruction of the right ventricle inflow by the tumor, we immediately performed resection of cardiac tumor and repair of right ventricle wall under cardiopulmonary bypass. The tumor was diagnosed as malignant lymphoma by pathological examination for surgical specimen of tumor. After operation her general condition was good, but residual cardiac lymphoma developed large size. We performed radiation therapy for cardiac lymphoma. Therefore the lymphoma was reduced to minimum size. Six months after operation metastatic malignant lymphoma appeared at whole body. So we performed chemotherapy for reduction of systemic malignant lymphoma. At first the chemotherapy was very effective. But metastasis spread rapidly and effectiveness of chemotherapy reduced. Thirteen months after operation she died for respiratory distress, probably due to metastatic brain tumor.