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.     

Investigation into the therapeutic efficacy of continuous isoproterenol inhalation in relation to respiratory infections in asthmatic children

In our Department, continuous isoproterenol inhalation therapy has been conducted on status asthmatics over the last 10 years. In the present study, we investigated whether there are any differences in the therapeutic efficacy of continuous inhalation of isoproterenol in the presence or absence of respiratory infections which may induce or aggravate asthma attacks. The treatment period was significantly longer in patients with pneumonia. Further prolongation of the treatment period was noted in patients with atelectasis. However, there were no apparent differences in therapeutic efficacy according to age or the severity of attacks. These findings suggest that continuous inhalation of isoproterenol is very effective for status asthmatics if respiratory infections are thoroughly controlled.     

Scientific Screening of Raw Diamond for an Ultraprecision Cutting Tool with High Durability

The wide scattering in tool life of natural mono-crystalline diamond tools is considered to depend on intrinsic crystalline defects due to nitrogen impurities in raw diamond. In this paper, the correlation was investigated between the amounts and types of the impurity evaluated by infrared absorption (IRA) and the crater wear and chipping resistances. As a result, diamonds including less total amount of impurity show larger wear resistance and that with larger amount of B2-aggregates show larger chipping resistance. This suggests that the inspection by IRA can be a useful method for screening of raw diamond for highly durable cutting tools.     

Pseudo-binary system Bi2O3-TeO2 in air

The phase equilibria in the pseudo-binary system Bi₂O₃-TeO₂ at 600° 950° C in air were examined by solid-state reaction techniques and X-ray powder diffraction method. Four pseudo-binary compounds appeared, i.e., -Bi₂O₃ type solid solution having a compositional range of (1-x)Bi₂O₃·xTeO₂ wherex=0 0.4 a new compound Bi₆Te₂O₁₅ which has an orthorhombic cell of a=2.27(4) nm, b=1.06(1) nm and c = 0.539(8) nm, 2Bi₂O₃ · 3TeO₂, and an unidentified phase Bi₂O₃·2TeO₂. The formation of the phase Bi₆Te₂O₁₅, in which all the Te ions are hexavalent, was confirmed by the thermogravimetry and by the Mössbauer spectra. The liquidus curves for whole system were determined by DTA method.     

Static Coarse Grain Task Scheduling with Cache Optimization Using OpenMP

Effective use of cache memory is getting more important with increasing gap between the processor speed and memory access speed. Also, use of multigrain parallelism is getting more important to improve effective performance beyond the limitation of loop iteration level parallelism. Considering these factors, this paper proposes a coarse grain task static scheduling scheme considering cache optimization. The proposed scheme schedules coarse grain tasks to threads so that shared data among coarse grain tasks can be passed via cache after task and data decomposition considering cache size at compile time. It is implemented on OSCAR Fortran multigrain parallelizing compiler and evaluated on Sun Ultra80 four-processor SMP workstation using Swim and Tomcatv from the SPEC fp 95. As the results, the proposed scheme gives us 4.56 times speedup for Swim and 2.37 times on 4 processors for Tomcatv respectively against the Sun Forte HPC Ver. 6 update 1 loop parallelizing compiler.     

Phase Diagram of Hydrogen in Palladium

Hydrogen in palladium, Pd-H(D), is an interesting system because of the highly mobile hydrogen and the presence of a phase boundary below 100 K. Experimentally, however, the nature of this transition has not been established. Historically this transition around 55 to 100 K has been thought to be an order-disorder transition. Such a transition would produce a phase boundary with anomalies at specific hydrogen concentrations corresponding to the specific ordered structures. In order to check this phase boundary we have performed a detailed study of the hydrogen concentration dependence of the specific heat of PdH _x over the temperature range from below 0.5 K to above 100 K using PdH _x specimens with x up to 0.8753. The measured heat capacity has been analyzed as the sum of contributions due to the lattice specific heat of Pd, the electronic specific heat of PdH _x , and the excess contribution caused by hydrogenation of the specimen. The excess specific heat result shows a sharp peak which indicates a phase boundary with transition temperature T ₁=55 K to 85 K depending linearly on the hydrogen concentration from x=0.6572 to 0.8753. We do not observe anomalies at specific x values as would be expected for the specific ordered structures.     

EXPERIMENTAL STUDIES ON A NOVEL CHEMICAL HEAT PUMP DRYER USING A GAS-SOLID REACTION

The authors have been studying Chemical Heat Pumps (CHP) from the viewpoints of energy saving and environmental impact. The CHP can store thermal energy in the form of chemical energy by an endothermic reaction, and release it at various temperature levels during heat demand periods by exo/endothermic reactions. The authors have proposed in an earlier study a novel chemical heat pump (CHP) system for environmentally-friendly effective utilization of thermal energy in drying as a chemical heat pump dryer (CHPD). In this exploratory study, we test the effectiveness of operating the proposed CHPDs experimentally. Basic experiments on the CHPDs such as hot dry air production for convective drying are performed on lab-scale CHPD apparatuses using gas-solid reactions in calcium oxide/calcium hydroxide reactant beds. The proposed CHPDs are found to produce hot air by CHP operation for drying. The temperature levels of the produced hot air and the reaction rates/conversions are as good as in the case of hot water supply system using basically same CHP operation. The cold heat for air dehumidification is also found to be generated/recovered by the same CHPD system. The generated heat amounts can be increased by changing the operating conditions although the heat recovery must be enhanced for practical application of CHPDs.     

Isolation and characterization of a novel gene encoding alpha-L-arabinofuranosidase from Aspergillus oryzae

We cloned and characterized a novel gene (abfA) encoding alpha-L-arabinofuranosidase (alpha-L-AFase) from Aspergillus oryzae. One clone homologous to the alpha-L-AFase gene of Thermotoga maritima was found in an expressed sequence tag (EST) library of A. oryzae and a corresponding gene was isolated. Molecular analysis showed that the abfA gene carried six exons interrupted by five introns and had an open reading frame encoding 481 amino acid residues. The amino acid sequence similarity at active sites to the alpha-L-AFases from other organisms indicated that the alpha-L-AFase encoded by abfA was classified as a family 51 glycoside hydrolase. When the abfA was overexpressed in the homologous hyperexpression system of A. oryzae, a large amount of alpha-L-AFase was produced as intracellular protein. The apparent molecular mass of the purified enzyme was estimated to be 228,000 by gel filtration and that of its subunit as 55,000 by SDS-PAGE, suggesting that the enzyme is a tetramer. The enzyme hydrolyzed p-nitrophenyl-alpha-L-arabinofuranoside but not other p-nitrophenyl glycosides. These results demonstrated that the abfA gene encodes a functional alpha-L-AFase.     

Development of coincidence transmission electron microscope. III. Incorporation with gamma-type imaging energy filter

We have developed a new analytical transmission electron microscope (TEM), called coincidence TEM, which, in principle, enables observation of elemental mapping images at a high signal-to-noise ratio. We have previously reported the successful observation of an elemental mapping image of a specimen, but over a very long period of time (168 h). To solve this inefficiency, we installed a gamma-type imaging energy filter in the coincidence TEM to remove the no-loss electrons, which are mainly transmitted electrons. This has enabled the intensity of the background signals in the coincidence measurement to be markedly reduced. The coincidence TEM with a gamma-type imaging energy filter allows the coincidence image to be observed in 3 h, thus, the measurement time is shortened by two orders of magnitude. Moreover, the use of a silicon drift detector (SDD) will shorten the measurement time.