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...     

Serotype-specific amplification of Rickettsia tsutsugamushi DNA by nested polymerase chain reaction

Polymerase chain reaction (PCR) with nested primer pairs was used to diagnose scrub typhus and identify the Rickettsia tsutsugamushi serotype. The primer pairs used for PCR were designed on the basis of the nucleotide sequence of the gene that encodes the 56-kDa antigen. Serotype-specific primers were used in the second PCR amplification. Five serovariants, the Gilliam, Karp, Kato, Kawasaki, and Kuroki strains of R. tsutsugamushi, were identified by nested PCR. In addition, the serotype identified by PCR with DNA from blood clots was the same as that of the strain isolated from five patients with scrub typhus. These findings indicate that this method is useful for diagnosis and identification of the rickettsial serotype in infected patients.     

Monitoring of human enteric viruses and coliform bacteria in waters after urban flood in Jakarta, Indonesia.

Floodwaters in Kampung Melayu village, Jakarta, Indonesia, as well as river water and consumable water (including groundwater and tap water) samples in flooded and non-flooded areas, were quantitatively analysed to assess occurrence of viruses and total coliforms and E. coli as bacterial indicators after flooding event. High numbers of enterovirus, hepatitis A virus, norovirus (G1, G2) and adenovirus were detected at high concentration in floodwaters and waters sampled from Ciliwung River which runs across metropolitan Jakarta and is used widely for agriculture and domestic purposes by poor residents. One out of three groundwater wells in the flooded area was contaminated with all viruses tested while no viruses were found in groundwater samples in non-flooded areas and tap water samples. The results revealed that human enteric viruses, especially hepatitis A virus and adenovirus, were prevalent in Jakarta, Indonesia. This study suggested that flooding posed a higher risk of viral infection to the people through contamination of drinking water sources or direct contact with floodwaters.     

A stochastic realization algorithm via block LQ decomposition in Hilbert space

A stochastic realization problem of a stationary stochastic process is re-visited, and a new stochastically balanced realization algorithm is derived in a Hilbert space generated by second-order stationary processes. The present algorithm computes a stochastically balanced realization by means of the singular value decomposition of a weighted block Hankel matrix derived by a “block LQ decomposition”. Extension to a stochastic subspace identification method explains how the proposed abstract algorithm is implemented in system identification.     

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.     

Galvanic cell measurements on supersaturated activities of oxygen in Fe-Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) melts

Using a mullite (3Al₂O₃ · 2SiO₂)-tube and ZrO₂-9 mol pct MgO-plug type solid electrolyte galvanic cells, the activities of supersaturated oxygen in Fe-0.0017 to 0.41 mass pct Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) alloys were measured as a function of total Al or M contents at 1873 K in an alumina crucible. Based on these results, the effects of alloying elements on the supersaturated oxygen activity with respect to alumina precipitation were studied. In the Fe-Al-M (M=C, Te, Mn, Cr, and Si) alloys, the supersaturated oxygen activities for a given Al level approach the equilibrium values with increasing contents of alloying elements. However, the oxygen activities for a given Al level are still supersaturated in the Fe-Al-M (M=Ti, Zr, and Ce) alloys even in the presence of considerable amounts of the alloying elements.     

Transmit permission control on spread ALOHA packets in LEOsatellite systems

A transmit permission control method for improving the throughput characteristics of a low Earth orbit (LEO) satellite communication system employing spread-slotted ALOHA multiple-access scheme is proposed. Both nonfading and fading satellite links are considered. The basic idea of the proposed scheme is to decrease the level of interference at each satellite and, hence, to increase the probability of packet success, by prohibiting the packet transmission from the users with relatively high propagation loss to their connecting satellites. It is shown that the method has the ability to improve the throughput performance in heavy traffic loads and the peak value of the throughput, significantly. It is also shown that the average delay performance of the system employing the proposed scheme is superior to that of the conventional system at heavy traffic loads