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.     

Systematic packaging design tools integrating functional and environmental consequences on product life cycle: Case studies on laundry detergent and milk

This study presents systematic packaging design tools integrating functional and environmental consequences on product life cycle. To design packaging for sustainability, the trade-offs between functional and environmental aspects of packaging throughout the product life cycle should be considered. However, it is difficult for packaging designers to understand the overall trade-offs because the extent of the design consequences on the entire life cycle of packaging and its contents is unclear. We developed two tools for packaging design: the Life Cycle Association Matrix (LCAM) and the Function Network Diagram (FND). The following three steps, based on literature reviews and interviews with industrial experts, were applied. Firstly, we listed the product functions and design variables related to the functions as the attributes allocated to the product life cycle. Secondly, the attributes were connected appropriately based on causal relationships. Lastly, we identified the factors to support decision making in the packaging design procedure. As a result, the LCAM depicts the design consequences on the life cycle, and the FND determines the stakeholders affected by the design consequences. Two case studies were demonstrated to analyze the trade-offs by using our tools. In the case studies, a liquid laundry detergent bottle and a milk carton were redesigned. The tools identified the design consequences and stakeholders affected by the redesign of the usability and protective function for the detergent and milk cases, respectively. The results showed the significance of understanding the design consequences on the product life cycle by integrating the functional and environmental aspects.     

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.     

Principled analytic classifier for positive-unlabeled learning via weighted integral probability metric

Machine Learning - We consider the problem of learning a binary classifier from only positive and unlabeled observations (called PU learning). Recent studies in PU learning have shown superior...     

Cover Image,Volume 69, Issue 3

The cover image is based on the Mini‐Review Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications by Takeshi Endo et al., https://doi.org/10.1002/pi.5952 . Cover image © Takeshi Endo Images.

     

Glycoconjugated polymer 6. Synthesis of poly[styrene-<Emphasis Type="Italic">block</Emphasis>-(styrene-<Emphasis Type="Italic">graft</Emphasis>-amylose)] via potato phosphorylase-catalyzed polymerization

Summary The potato phosphorylase-catalyzed polymerization of α-D-glucose-1-phosphate (G-1-P) onto poly[styrene-block-(4-vinylbenzyl maltohexaoside)] (1) was performed at the molar ratios of [G-l-P]₀ and [maltohexaose]₀ of 35, 80, and 250. The product was found to be soluble in dimethyl sulfoxide, which was a good solvent for amylose, and showed the complex-formation with iodine, indicating that the product was assignable to poly[styrene-block-(styrene-graft-amylose)] (2). The quantitative analysis of the liberated phosphoric acid gave the average degree of polymerization o f the glucose unit (n) as 27, 5 1, and 180 for 2-I, 2-II, and 2-III, respectively. Received: 29 November 2002/Accepted: 22 December 2002 Correspondence to Toyoji Kakuchi     

Active sites of Cu-ZSM-5 for the decomposition of acrylonitrile

The catalytic decomposition of acrylonitrile (AN) over Cu-ZSM-5 prepared with various Cu loadings was investigated. AN conversion, during which the nitrogen atoms in AN were mainly converted to N₂, increased as Cu loading increased. N₂ selectivities as high as 90–95% were attained. X-ray diffraction measurements (XRD) and temperature-programmed reduction by H₂ (H₂-TPR) showed the existence of bulk CuO in Cu-ZSM-5 with a Cu loading of 6.4 wt% and the existence of highly dispersed CuO in Cu-ZSM-5 with a Cu loading of 3.3 wt%. Electron spin resonance measurements revealed that Cu-ZSM-5 contains three forms of isolated Cu²⁺ ions (square-planar, square-pyramidal, and distorted square-pyramidal). The H₂-TPR results suggested that in Cu-ZSM-5 with a Cu loading of 2.9 wt% and below, Cu⁺ existed even after oxidizing pretreatment. The activity of AN decomposition over Cu/SiO₂ suggested that CuO could form N₂, but, independent of the CuO dispersion, nitrogen oxides (NO_x) were formed above 350 °C. Cu⁺ and the square-pyramidal and distorted square-pyramidal forms of Cu²⁺ showed low activity for AN decomposition. Temperature-programmed desorption of NH₃ suggested that N₂ formation from NH₃ proceeded on Cu²⁺, resulting in the formation of Cu⁺. The Cu⁺ ions were oxidized to Cu²⁺ at around 300 °C. Thus, high N₂ selectivity over Cu-ZSM-5 with a wide range of temperature was probably attained by the reaction over the square-planar Cu²⁺, which can be reversibly reduced and oxidized.     

A cathode readout gas sampling calorimeter with conductive plastic tubes

We constructed and tested a prototype gas sampling electromagnetic calorimeter of the Pb-proportional tube sandwich type. The calorimeter uses conductive plastic tubes and cathode pad readout with a tower structure which resulted in reasonable energy and spatial resolutions for electrons in the momentum range 0.5–4.0 GeV/c; $\text{σ}{}_{\mathrm{E}}\text{E =}\text{21\%}\text{(E(}\text{GeV}\text{)}\text{)}{}^{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{, σ}{}_{\mathrm{x}}\text{= 6}\text{mm}\text{(at 3 GeV}$/c). This paper describes the test and the performance studied under various conditions.     

[110]-surface strained-SOI CMOS devices

We have newly developed [110]-surface strained-silicon-on-insulator (SOI) n- and p-MOSFETs on [110]-surface relaxed-SiGe-on-insulator substrates with the Ge content of 25%, fabricated by applying the Ge condensation technique to SiGe layers grown on [110]-surface SOI wafers. We have demonstrated that the electron and the hole mobility enhancement of [110]-surface strained-SOI devices amounts to 23% and 50%, respectively, against the mobilities of [110]-surface unstrained MOSFETs. As a result, the electron and the hole mobility ratios of [110]-surface strained-SOI MOSFETs to the universal mobility of (100)-surface bulk-MOSFETs increase up to 81% and 203%, respectively. Therefore, the current drive imbalance between n- and p-MOS can be reduced. Moreover, both the electron and the hole mobilities of the [110]-surface strained-SOIs strongly depend on the drain current flow direction, which is qualitatively explained by the anisotropic effective mass characteristics of the carriers on a [110]-surface Si. As a result, the [110]-surface strained-SOI technology with optimization of the current flow directions of n- and p-MOS is promising for realizing higher speed scaled CMOS.