α-tocopherol affects the urinary and biliary excretion of 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman, γ-tocopherol metabolite, in rats

In this study, we investigated a change in the excretory content of 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman (γ-CEHC), a γ-tocopherol (γ-Toc) metabolite, in rat urine and bile by using a new high-performance liquid chromatography-elelectrochemical detection (HPLC-ECD) method. In this determination, CEHC [α- and γ-CEHC, where α-CEHC-2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychioman] in the biological specimens were treated with 3 N methanolic HCl to hydrolyze conjugates and to promote esterification. The methylated samples were extracted by n-hexane/water (1∶2). The analyses of the methyl esters of α-CEHC and γ-CEHC were performed by an HPLC-ECD using an ODS-3 column at 35°C. The mobile phase was acetonitrile/water (45∶55, vol/vol) containing 50 mM sodium perchlorate. After rat urine and bile samples, respectively, were methylated as described above, methylated biliary metabolites were identified by liquid chromatography mass spectrometry as methyl esters of γ-CEHC. Furthermore, we examined the differences in the excretion of γ-CEHC between rat urine and bile after an oral administration of γ-Toc or α- +γ-Toc by the above HPLC method. In the γ-Toc group, each vitamin E-deficient rat was given 0.5 mL of a stripped corn oil preparation containing 10 mg of γ-Toc. In the α- +γ-Toc group, the rat was given 10 mg of α-Toc and 10 mg of γ-Toc. The content of γ-CEHC in rat urine from the α- +γ-Toc group was increased more in comparison to the γ-Toc group at 18–36 h after oral administration. Moreover, the content of γ-CEHC in rat bile in the α- +γ-Toc group was increased more in comparison to the γ-Toc group at 6–18 h after oral administration. Therefore, we have suggested that γ-CEHC was shifted mainly to urinary excretion after γ-CEHC had been excreted into the bile. Furthermore, we assume that α-Toc may affect the metabolism of γ-Toc to γ-CEHC in the body.     

Addition effects of aluminum and in situ formation of alumina in MoSi2

Phase composition change and mechanical properties at room temperature of MoSi₂ materials with the addition of aluminum were investigated. An explanation was given to the appearance of Mo₅Si₃ when hot pressing MoSi₂ raw powder containing oxygen. The mechanical properties including Vickers hardness, bending strength and fracture toughness were improved with the addition of aluminum up to the limit content needed for absorbing the oxygen in MoSi₂ raw powder. More aluminum addition than the limit content (in this study it is 5 wt %) will result in the formation of Mo(Si ,Al)₂ and Si. The in situ formed Al₂O₃ could act as a crack pinning element. However, because the thermal expansion coefficients of Al₂O₃ and MoSi₂ are near and there is a strong bonding between them, the toughening effect by such in situ formed small Al₂O₃ particles (less than 2 m) is limited.     

Ultrahigh strength of nanocrystalline iron-based alloys produced by high-pressure torsion

Microstructural evolution of an Fe–18.1%Ni–34.9%Co–9.3%Ti (in at.%) in processing by high-pressure torsion (HPT) was investigated by electron backscatter diffraction. After 10 turns of HPT straining at room temperature with a rotation speed of 1 rpm under a pressure of 6 GPa, the alloy was composed of body-centered cubic-structured grains with sizes of 20–50 nm having high density crystal defects inside the grains. The mechanism of this significant grain refinement was discussed in relation to the stress-induced martensitic transformation and transgranular shear near ideal strength. The actual shear stress of the nanocrystalline iron-based alloy was estimated to be 1.37 GPa and as high as 38% of the ideal shear stress, which is similar to Gum Metal exhibiting deformation without dislocation activity. It is inferred from these results that the dislocation motion can be suppressed up to ultrahigh stress level near ideal strength by the formation of nano-sized grains.     

Correlation Analysis for Simultaneously Controlling Reliability and Validity

The purpose of the present study is to propose a procedure for correlation analysis of several (especially two) sets of variables, which includes canonical correlation analysis, principal component analysis, and multiple regression analysis as a special case. The proposed method derives components from each set of variables which maximize the weighted geometric mean of two types of indicators: one is the contribution rate of the components for their original variables, the other is the squared correlation between the components. In terms of the test theory, the former are indicators of reliability and the latter are indicators of concurrent validity. Through the numerical examples applying this method to the data of two Japanese language personality inventory, the method is shown to be particularly useful when determining the weights for test items.

     

Preparation of Polyacetylenes via Organometallic C-C Coupling Reactions

Summary Dehalogenative polycondensation of 1,2-dibromoethylene, trans-1,2-dichloroethylene, and cis-1,2-dichloroethylene with a Ni(0) complex gave a black polymer whose IR spectrum essentially agreed with that of trans-polyacetylene. Suzuki-Miyaura coupling between 1,2-dibromoethylene and vinylene diboronic compounds was applied to synthesis of -conjugated polymers.     

Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells

In the treatment of breakpoint cluster region-Abelson (BCR-ABL)-positive chronic myeloid leukemia (CML) using BCR-ABL inhibitors, the appearance of a gatekeeper mutation (T315I) in BCR-ABL is a serious issue. Therefore, the development of novel drugs that overcome acquired resistance to BCR-ABL inhibitors by CML cells is required. We previously demonstrated that a bis-pyridinium fullerene derivative (BPF) induced apoptosis in human chronic myeloid leukemia (CML)-derived K562 cells partially through the generation of reactive oxygen species (ROS). We herein show that BPF enhanced the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase (MEK-ERK) pathway in a ROS-independent manner. BPF-induced apoptosis was attenuated by trametinib, suggesting the functional involvement of the MEK-ERK pathway in apoptosis in K562 cells. In addition, the constitutive activation of the MEK-ERK pathway by the enforced expression of the BRAFV600E mutant significantly increased the sensitivity of K562 cells to BPF. These results confirmed for the first time that BPF induces apoptosis in K562 cells through dual pathways—ROS production and the activation of the MEK-ERK pathway. Furthermore, BPF induced cell death in transformed Ba/F3 cells expressing not only BCR-ABL but also T315I mutant through the activation of the MEK-ERK pathway. These results indicate that BPF is as an effective CML drug that overcomes resistance to BCR-ABL inhibitors.     

Corrosion Behavior of Single-Crystal Alumina in Argon, Air, and Water Vapor Atmospheres at 1700-2000°C

The results for the corrosion of alumina single crystals at 1700-2000°C in argon, argon/water vapor, air, and air/water vapor for 10 h are reported. There were no obvious weight and volume changes after corrosion. White spots were observed on the surfaces of the specimens after corrosion tests. The initial temperature for the appearance of these white spots was 1800°C for argon and air, 1900°C for argon/water vapor, and 2000°C for air/water vapor. These white spots were likely formed by internal impurities, which diffused outward to the surface and coalesced at high temperatures. There was no evidence of corrosion damage inside the specimens. The flexural strength of the specimens was clearly enhanced after the corrosion tests and showed no evident relation to the corrosion conditions. This increase in strength after corrosion was likely due to the healing of surface machining flaws. The surface flaw healing temperature for alumina crystals was higher than 1400°C.     

YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development

Trastuzumab-emtansine (T-DM1) is a therapeutic agent molecularly targeting human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and it is especially effective for MBC with resistance to trastuzumab. Although several reports have described T-DM1 resistance, few have examined the mechanism underlying T-DM1 resistance after the development of acquired resistance to trastuzumab. We previously reported that YES1, a member of the Src family, plays an important role in acquired resistance to trastuzumab in HER2-amplified breast cancer cells. We newly established a trastuzumab/T-DM1-dual-resistant cell line and analyzed the resistance mechanisms in this cell line. At first, the T-DM1 effectively inhibited the YES1-amplified trastuzumab-resistant cell line, but resistance to T-DM1 gradually developed. YES1 amplification was further enhanced after acquired resistance to T-DM1 became apparent, and the knockdown of the YES1 or the administration of the Src inhibitor dasatinib restored sensitivity to T-DM1. Our results indicate that YES1 is also strongly associated with T-DM1 resistance after the development of acquired resistance to trastuzumab, and the continuous inhibition of YES1 is important for overcoming resistance to T-DM1.     

A radio frequency identification implanted in a tooth can communicate with the outside world.

A radio frequency identification (RFID) transponder covering the 13.56 MHz band was adapted to minimize its volume so that it could be placed in the pulp chamber of an endodontically treated human tooth. The minimized transponder had a maximum communication distance of 30 mm. In an animal experiment, the transponder was fixed in the cavity of a mandibular canine of a dog. An RFID reader positioned close to the dog's face could communicate with the transponder in the dog's tooth. In certain cases, the system is applicable for the personal identification procedures for hospitalized patients instead of an identification wristband.