In order to evaluate the mechanical properties of a (Gd,Y,Er)BaCuO low porosity single-grain bulk sample fabricated by the infiltration growth technique, tensile tests of specimens cut from the bulk sample were carried out. Relationship between the tensile strength and porosity was investigated for the specimens. Tensile strength increases with decreasing the porosity, which is due to the increase of net cross-sectional area and reduction of defects where the stress concentration occurs. Tensile strength of the (Gd,Y,Er)BaCuO bulk sample is comparable to those of other low porosity single-grain bulk materials, (Gd,Dy)BaCuO fabricated by the infiltration growth technique and DyBaCuO fabricated by the melt-processing in O 2 atmosphere. Solidified liquid phase regions and segregated secondary phase particles are observed for the low tensile strength specimens.

High-density MgB2 bulks with superior mechanical and superconducting properties were fabricated using spark plasma sintering (SPS). The sharp superconducting transition at 37.5 K proved high quality of the superconductors. Critical current density significantly exceeded that of conventionally sintered bulks. Flux pinning diagrams indicated dominance of grain boundary pinning, with peak position at 0.2. SPS bulks showed improved mechanical properties with 8-times higher bending strength compared to dense hot isostatic pressed bulks. Trapped field was measured at 14 K and 20 K, 1 mm above the bulk's surface, with applied pulse field up to 2 T. A local overheating together with a complex trapped field formation in the MgB2 bulks during pulse-field magnetization were studied to elucidate limitations of Pulse Field Magnetization.

Mechanical properties of a DyBaCuO single-grain superconducting bulk material obtained through the melt-processing in 100% O 2 atmosphere were evaluated through tensile tests for the specimens cut from the bulk material. DyBaCuO bulk materials melt-processed in 50 and 75% O 2 atmosphere were also evaluated for comparison. The porosity was decreased with increasing the O 2 pressure in the melt-processing, and few pores were observed for the bulk material melt-processed in 100% O 2 atmosphere. The tensile test specimens were glued to metal rods, and the metal rods were connected to the universal joints for loading. The tensile strength was improved with decreasing the porosity. The tensile strength values obtained in this study were lower than bending strength values reported elsewhere. Flow-like patterns formed by the crack propagations were observed on the fracture surfaces of the tensile test specimens. Through the observations on the fracture surfaces, differences in the fracture mechanisms between the porous and the low porosity bulk materials are discussed.

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for cancer therapy. Anti-miR oligonucleotides are often used for the functional inhibition of miRNAs; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody–anti-miR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry anti-miR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then the complexes were introduced into the recipient cells. We also found that anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal miRNAs.

In order to investigate the mechanical properties of a (Gd,Y)BaCuO large single-grain bulk material, bending tests were carried out at room temperature for the specimens cut from the bulk material. A precursor, which consisted of three regions with different Gd and Y contents, was used for the fabrication of the large single-grain bulk material in order to overcome the undesirable nucleation apart from the seed crystal. The precursor was prepared such that Y content increased with increase in the distance from the center, where the seed crystal was placed, to decrease the peritectic decomposition temperature. Two types of bending test specimens were cut from the bulk material—the specimens that included the interface between two regions with different Gd and Y contents and the specimens that did not include the interface. Although the bending strength data of the specimens that did not include the interface scattered widely in comparison with the specimens that included the interface, the average bending strength values of these specimens were similar to each other. This result demonstrates that the interface does not cause the deterioration of the mechanical properties of the whole bulk material.

Overexpression of HER2 in breast cancer is correlated with poor prognosis. HER2-targeted drugs, such as trastuzumab and lapatinib, have been successful to treat HER2-positive breast cancers, however, the acquisition of the drug resistance of the cells is recognized. Here we suggest the novel molecular targets to cure HER2-positive breast cancers. The oncogenic roles of Rac1, a Rho family small GTPase, in a variety of cancers have been demonstrated. For example, the elevated expression or hyperactivation of Rac1 is frequently observed in human cancers, correlating with their aggressiveness and poor prognosis. In breast cancers, upregulation of Rac1 GEF (GTP exchange factor) and downregulation of Rac1 GAP (GTPase activating protein) have been reported. Moreover, activation of Rac1 contributed to trastuzumab resistance, which poses a serious problem during chemotherapy. In the present study, we first investigated in detail in which subtypes of breast cancers mRNA expression of Rac1 is correlated with their poor prognosis. Using the METABRIC database, we found that high mRNA expression of Rac1 significantly correlated with the poor prognosis of HER2-positive breast cancer (p=0.0012, High: n=49, Low: n=171). On the other hands, other three types (basal, claudin-low, or luminal-B type) did not show significant correlation between the expression levels of Rac1 mRNA and their prognosis (p=0.15, High: n=97, Low: n=102; p=0.052, High: n=110, Low: n=89; p=0.17, High: n=70, Low: n=391; respectively). In luminal-A type breast cancer, low mRNA expression of Rac1 significantly correlated with poor prognosis (p=0.0046, High: n=492, Low: n=187). We next investigated the molecular mechanism underlying Rac1 activation in HER2-positive breast cancer cells, SKBR-3 cells. We found that Cullin-3 (CUL3, a subunit of a RING ubiquitin E3 ligase complex) and its adaptor protein KCTD10 are essential for Rac1 activation. Mechanistically, CUL3/KCTD10 ubiquitinate RhoB, a Rho family small GTPase that suppresses the activation of Rac1, leading to the degradation RhoB. We also found that HER2 signaling is essential for the activation of Rac1. Conclusions: This study reveals that the novel molecular axis CUL3/KCTD10/RhoB regulates the Rac1 activation in HER2-positive breast cancer cells. The interference of CUL3/KCTD10 complex formation may be a new strategy to the treatment of HER2- and Rac1-positive breast cancers. Citation Format: Murakami A, Maekawa M, Kusakabe E, Yamasawa H, Aoki R, Komatsu S, Taguchi K, Nishiyama K, Yamashita M, Sugimori W, Kawai K, Nakayama J, Araki N, Semba K, Taguchi T, Kamei Y, Takada Y, Higashiyama S. Novel mechanisms of Rac1 activation by the Cullin-3/KCTD10 ubiquitin E3 complex in HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-05-02.

In order to investigate the mechanical properties and fracture mechanisms of (Gd,Dy)BaCuO dense bulk material fabricated by the infiltration growth technique, tensile tests were carried out for specimens cut from the as-grown bulk material. The average tensile strength value of the (Gd,Dy)BaCuO dense bulk material fabricated by the infiltration growth technique was 44 MPa, which is superior to that of a porous bulk material fabricated through melt-processing in a 50% O2 atmosphere (37 MPa), and comparable to that of a dense bulk material fabricated through melt-processing in 100% O2 (45 MPa) that have been reported elsewhere. Through the observations of the flow-like patterns formed by the crack propagations on the fracture surfaces, the fatal crack initiation site was identified. One extraordinarily large pore, segregated secondary phase particles and some inclusion that mainly consists of Pt were observed around the crack initiation site on the fracture surfaces of the (Gd,Dy)BaCuO dense bulk material.

In order to investigate the fracture strength properties of a (Gd,Y)BaCuO large single-grain bulk with 90 mm in diameter, bending tests were carried out at liquid nitrogen temperature 77 K for the specimens cut from the bulk sample. The large single-grain bulk was fabricated by RE compositional gradient technique to overcome the problem of undesirable nucleation apart from the seed crystal. One precursor that consisted of some regions with different Gd and Y contents was used for the fabrication. Bending tests for the plain and the V-notched specimens were carried out to evaluate the fracture strength and fracture toughness, respectively. The fracture strength values of the specimens that included the interface between two regions with different Gd and Y contents were not lower than those of the specimens that did not include the interface, which is similar to the bending test results at room temperature. The fracture strength values at 77 K were higher than those at room temperature.

In order to investigate the effects of SPS pressure on the mechanical properties of MgB2 bulk, MgB2 bulk samples were processed by SPS under different pressures. Mechanical properties of these bulk samples were evaluated at room temperature through the bending tests for specimens cut from the bulk samples. Stress-strain behaviours of these bulk samples were almost linear until the fracture. No significant difference was observed for the Young's modulus values among the bulk samples. The average bending strength values of these bulk samples were also similar to each other. However, the bending strength data of the samples processed under higher pressure scattered widely in comparison with those of the sample processed under lower pressure. The bending strength values were related with the pore sizes observed on the tensile side fracture surfaces.

We synthesized phosphorothioated 2'-OMe RNAs containing PXA residues at the 5'-end of the strands (PXA-ORNs) for sequence-selective inhibition of gene expression of GFP in HeLa cells stably expressing GFP. The inhibitory efficiency is evaluated by measuring the fluorescent intensity of the expressed GFP. Cell-based assay revealed that under UV irradiation, PXAORNs greatly inhibit the gene expression of GFP (by as much as 60%).

DNA sequences capable of forming triplexes induce DNA double-strand breaks that have attracted attention in genome editing technologies (e.g., CRISPR/Cas9 system, TALEN, and ZFN). Therefore, novel functional tools that stabilize triplex DNA structures must be further investigated to spark renewed interest. In this study, we investigated the unique character of cationic comb-type copolymers for the selective stabilization of triplex DNA. The melting temperature (Tm) of triplex DNA increased from 24.5 to 73.0 °C (ΔTm = 48.5 °C) by the addition of poly(allylamine)-graft-dextran (PAA-g-Dex) under physiological conditions (at pH 7.0), while PAA-g-Dex did not stabilize but rather destabilized the DNA duplex. On the other hand, poly(l-lysine)-graft-dextran (PLL-g-Dex) stabilized both the duplex and triplex structures at pH 7.0. Thermodynamic parameters evaluated by isothermal titration calorimetry (ITC) revealed that the binding constant (Ka) for the intermolecular triplex formation in the presence of PAA-g-Dex was 1.1 × 109 M-1 at 25 °C which is more than 10 times larger than that in the presence of PLL-g-Dex (8.6 × 107 M-1). Stabilizing activity and selectivity of cationic copolymers toward DNA assemblies were successfully controlled by selecting appropriate backbone structures of the copolymer. Various functional molecules that stabilize DNA duplexes have been developed and used in biological research. However, there are few cationic polymers that stabilize triplex DNA selectively. This study indicates that PAA-g-Dex has great potential to regulate the biological activities of triplex DNA.

In order to understand the mechanical properties of EuBa2Cu3Oy “EuBaCuO” superconducting bulk material, 3- and 4-point bending tests were carried out at room and liquid nitrogen temperature (77.3 K) for specimens cut from a EuBaCuO single-grain bulk material. The Young’s modulus evaluated through the 3- point bending test and that through the 4-point bending test were similar to each other. On the other hand, the 3-point bending strength was higher than the 4-point bending strength, which is due to the smaller maximum bending moment area of the specimen in the 3-point bending test. The Young’s modulus at liquid nitrogen temperature was higher than that at room temperature (RT), which is due to the decrease of the interatomic distance by cooling. The bending strength at 77 K was also higher than that at RT. These mechanical property data of the EuBaCuO bulk material were comparable to those of other REBa2Cu3Oy “REBaCuO” bulk materials (RE: rare-earth elements).

MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs). miRNA is an essential component of RISC for modulation of gene expression. Therefore, the release of miRNA from RISC is considered as effective method for inhibition of RISC activity. In this study, the releasing profiles of miRNA from RISC, using anti-miRNA oligonucleotides, are revealed.

MicroRNAs (miRNAs) regulate gene expression by forming RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets. MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of miRNA from RISC is considered as an effective method for the inhibition of miRNA functions. In our previous study, we reported that anti-miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe) RNA, could induce the release of miRNA from RISC. However, the mechanisms underlying the miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-cancer drugs, are still unclear. In this study, we investigated the relationship between the miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC50) using conventional chemically modified AMOs. We demonstrated that the miRNA-releasing effects of AMOs are directly proportional to the IC50 values, and AMOs, which have an ability to promote the release of miRNA from RISC, can effectively inhibit RISC activity in living cells.

A new concept of an electromagnetic torque converter for hybrid electric vehicles is proposed. The electromagnetic torque converter, which is an electric system comprised of a set of double rotors and a stator, works as a high-efficiency transmission in the driving conditions of low gear ratio including a vehicle moving-off and as a starting device for an internal combustion engine. Moreover, it can be used for an electric vehicle driving as well as for a regenerative braking. In this concept, a high-efficiency drivetrain system for hybrid electric vehicles is constructed by replacing a fluid-type torque converter with the electromagnetic torque converter in the automatic transmission of a conventional vehicle. In this paper, we present the newly developed electromagnetic torque converter with a compact structure that enables mounting on a vehicle, and we evaluate its transmission efficiency by experiment. Furthermore, using the experimental results and finite element analysis of the electric machine, we clarify the system loss of the electromagnetic torque converter.

In the present paper, we introduce a drivetrain system using an electromagnetic coupling for hybrid electric vehicles, and propose a new control concept of vibration torque interception. The electromagnetic coupling is an electric machine that is composed of a pair of rotors, and electromagnetic torque acts mutually between the rotors. In the drivetrain system, the electromagnetic coupling works as a torque transmission device with a rotational-speed-converting function. We demonstrate that, by using this control, the electromagnetic coupling also works as a damping device that intercepts the vibration torque of the internal combustion engine, while transmitting the smooth torque to its drive line. Using a model of a two-inertia resonance system, a control system is designed such that a transfer function representing input-to-output torque is shaped in the frequency domain. Experimental results obtained using an electromagnetic coupling demonstrate the effectiveness of the proposed concept.

Mechanical properties of a high packing ratio MgB2 bulk sample processed by spark plasma sintering (SPS) were evaluated at 77 K through bending tests for specimens cut from the bulk sample. The effects of the packing ratio and temperature on the fracture strength of MgB2 bulk are discussed. The fracture strength at 77 K of the MgB2 bulk processed by SPS was higher than that at room temperature. The packing ratio of the MgB2 bulk processed by SPS was higher than those of other MgB2 bulks processed by sintering under the ambient pressure and hot isostatic pressing. The fracture strength was improved by increasing the packing ratio. The fracture strength at a very low temperature was estimated from the bending test results at 77 K and room temperature. The fracture strength at 20 K of the MgB2 bulk processed by SPS was estimated to be around 425 MPa.