RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease.     

Construction of a diabody (small recombinant bispecific antibody) using a refolding system

Diabodies are the recombinant bispecific antibodies (BsAbs),constructed from heterogeneous single-chain antibodies. Usually,diabodies have been prepared from bacterial periplasmic fractionusing a co-expression vector (i.e. genes encoding two chainswere tandemly located under the same promoter). Some diabodies,however, cannot be expressed as a soluble material owing toinclusion body formation, which limits the utilization of diabodiesin various fields. Here we report an improved method for theconstruction of diabodies using a refolding system. As a model,a bispecific diabody binding to adenocarcinoma-associated antigenMUC1 and to CD3 on T cells was studied. One chain consistedof a VH specific for MUC1 linked to a VL specific for CD3 witha short polypeptide linker (GGGGS). The second was composedof a VL specific for MUC1 linked to a VH specific for CD3. Thetwo hetero scFvs were independently obtained from intracellularinsoluble fractions of Escherichia coli, purified, mixed stoichiometrically(at an equivalent molar ratio of 1:1) and refolded. The refoldedtwo hetero scFv has a hetero-dimeric structure, with completespecificity for both target cells [i.e. MUC1 positive cellsand CD3 positive lymphokine-activated killer cells with a Tcell phenotype (T-LAK)]. Evaluation of the in vitro efficacyof T-LAK with the diabody by growth inhibition assay of cancercells demonstrated maximum growth inhibition of cancer cellsto reach ~98% at an effector:target ratio (E:T ratio) of 10,almost identical with that with anti-MUC1xanti-CD3 chemicallysynthesized BsAbs (c-BsAbs). This is the first report of theconstruction of a diabody using a refolding system.     

Corner Separations around a NACA65 Blade in a Decelerating Flow （Experi- mental Investigations by Five-Hole Probe and PIV）

In order to examine the fundamental characteristics of corner separation in a decelerating cascade flow,the experimental apparatus was made and separations around a NACA65 blade in a decelerating channel flow were examined.Two-dimensional calculations show that the NACA65 cascade flow that has 45 deg.of turning,1.24 of solidity and 17 deg.of stagger angle is equivalent to the channel flow that has 14 deg.of stagger angle in terms of pitchwise blade force.Experimental investigation by five-hole probe shows that the accumulations of low energy fluid can be seen around the corner part and the overturning flow due to the secondary flow exists.And,as the periodicity of the blade wake in a pitchwise direction is comparably good,the wake of this channel flow is similar to the wake of the cascade flow for two pitch portion.PIV measurement results shows that a vortex pattern can be seen in the momentary streamline on the suction surface of the blade and in the averaged streamline on the perpendicular to both the suction surface and the endwall.     

Fracture strength estimation of SiC block for IS process

The Japan Atomic Energy Agency has been conducting R&D on thermochemical water-splitting Iodine–Sulfur (IS) process for hydrogen production to meet massive demand in the future hydrogen economy. A concept of sulfuric acid decomposer was developed featuring a heat exchanger block made of SiC. Recent activity has focused on the reliability assessment of SiC block. Although knowing the strength of SiC block is important for the reliability assessment, it is difficult to evaluate a large-scale ceramics structure without destructive test. In this study, a novel approach for strength estimation of SiC structure was proposed. Since accurate strength estimation of individual ceramics structure is difficult, a prediction method of minimum strength in the structure of the same design was proposed based on effective volume theory and optimized Weibull modulus. Optimum value of the Weibull modulus was determined for estimating the lowest strength. The strength estimation line was developed by using the determined modulus. The validity of the line was verified by destructive test of SiC block model, which is small-scale model of the SiC block. The fracture strength of small-scale model satisfied the predicted strength.     

Experimental study on heat transfer and pressure drop in mercury flow system for spallation neutron source

In the design of MW-class spallation target system, using mercury to produce practical neutron applications, keeping the highest level of safety is vitally important. To establish the safety of spallation target system, it is essential to understand the thermal hydraulic properties of mercury. Through thermal hydraulic experiments using a mercury experimental loop, which flows at the rate of 1.2 m³/hr maximum, the following facts were experimentally confirmed. The wall friction factor was relatively larger than the Blasius correlation due to the effects of wall roughness. The heat transfer coefficients agreed well with the Subbotin correlation. Furthermore, for validation of the design analysis code, thermal hydraulic analyses were conducted by using the STAR-CD code under the same conditions as the experiments. Analytical results showed good agreement with the experimental results, using optimized turbulent Prandtl number and mesh size.     

Development of 28?GHz and 77?GHz, Mega-Watt Gyrotrons for Fusion Devices

A 28 GHz 1 MW with TE_8,3 cavity for GAMMA10 tandem mirror and a 77 GHz 1.5 MW gyrotron with TE_18,6 for Large Helical Device (LHD) have been developed to upgrade their Electron Cyclotron Heating (ECH) systems. In the 28 GHz gyrotron, the maximum power of 1.05 MW was obtained, which is in agreement with its design target value. And the high efficiency of 40% without collector potential depression (CPD) was obtained with 0.8 MW. In the first and second 77 GHz gyrotrons, 0.8 MW 3.6 sec., 0.3 MW 60 sec operations have been achieved, but several issues due to the stray RF and velocity dispersion have been found, too. In consideration of these, the design improvement was performed to aim at 1.5 MW in the third tube. In the short pulse test, the maximum output power of 1.6 MW and the maximum total efficiency of 49.4% with CPD were obtained. In the long pulse test, the pulse length extended to 5 sec with 1 MW, 1800 sec with 0.1 MW, 1.6 sec with 1.5 MW. Total injection power of 3.1 MW to LHD plasma has been achieved. It is shown that the electron beam pitch factor ?? decreases with increasing of beam current, comparing with the experimental and calculation results.     

Automatic spin measurements for pitched Baseballs via consumer-grade high-speed cameras

Controlling the spin of a ball is important in a variety of sports, especially baseball. For an athlete to properly train, it is necessary to know spin information immediately after throwing or hitting a baseball. This paper presents a fully automatic and marker-free technique to measure both the spin rate and spin axis of a pitched baseball using a consumer-grade high-speed camera. After tracking a ball from the high-speed video, our technique measures spin rate by detecting periods in which similar ball images appear, and then estimates spin axis by performing rigid registration that considers three-dimensional rotation. By separating the spin rate measurement and spin axis estimation processes, we achieve reasonable computational efficiency and robustness for small blurred baseball images extracted from video. We evaluated the accuracy of our presented technique by using synthesized videos. To illustrate the feasibility of our technique, we applied it to a variety of breaking ball pitches captured under normal outdoor lighting conditions.     

Magnetic properties of PLD‐fabricated ND‐Fe‐B film magnets and their applications to millimeter‐size motors

We succeeded in depositing 200‐ to 300‐µm‐thick Nd‐Fe‐B film magnets with (BH)_max of approximately 55 kJ/m³ on Fe substrates by the PLD method. In addition, we confirmed that a millimeter‐size motor, which was prepared from the obtained film, rotates at 15,160 rpm under a no‐load test. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 159(2): 1–6, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20215     

Development of ultra-fine-grain binderless cBN tool for precision cutting of ferrous materials

A new cutting tool was developed from ultra-fine-grain (<100 nm), binderless cubic boron nitride (cBN) material fabricated by transforming hexagonal boron nitride to cBN by means of sintering under an ultra-high pressure of 10 GPa at 1800 °C. The cutting edges of the newly developed cBN tool can be made as sharp as those of single-crystal diamond tools. In this experiment, cBN and single-crystal diamond tools of the same shape were compared by precision cutting tests using stainless steel specimens and steel specimens coated with an electroless Ni-P layer. The surface roughness (R_z) of specimen surfaces cut with the cBN tool by means of planing was approximately 100 nm for both the Ni-P-coated steel and stainless steel specimens. Though similar R_z values were obtained for Ni-P layers cut by the cBN and diamond tools, an R_z value exceeding 2000 nm was obtained for stainless steel cut by the diamond tool. High-precision surfaces with R_z values of 50–100 nm were obtained for stainless steel specimens cut with the cBN tool under high-speed milling (942 m/min) conditions. These results indicate that the newly developed cBN tool is useful for the ultra-precision or precision cutting of ferrous materials.