Optimization of dynamic shear force measurement for fiber wobbling method

Fiber wobbling method can be used to study nanotribological properties of a head disk interface. It can measure 1 nN shear force at a high shear rate. In this study, an optical system for the shear force measurement was optimized considering the spherical aberration of a sphere lens and the saturation of the position sensitive detector, and the minimum shear force detection limit of sub-nano-newton has been achieved.     

Digital-signal-waveform improvement on VLSI packaging including inductances

As the digital signal frequency in printed circuit boards (PCBs) increases, waveform distortion, or the signal integrity (SI) problem, is getting more and more serious. The reason the SI problem is becoming serious is that wires or traces need to be regarded as transmission lines which are sensitive to electric noise. In order to overcome this problem, we have proposed a novel methodology called a segmental transmission line (STL), and have shown its effectiveness using computer simulations and fundamental prototypes. However, in the STL design, the combinatorial explosion problem occurs. To solve this problem, a genetic algorithm (GA) was used to design the STL. In this article, we apply the STL to a bus system that includes inductances, which come from the very-large-scale integration (VLSI) packaging. We evaluated the STL in simulation experiments as well as actual experiments using prototypes, and obtained a maximum improvement ratio of 1.53 in the actual experiment.     

Aneurysm of the membranous ventricular septum with ventricular septal defect, mitral and tricuspid insufficiency

Bile acids are known to promote colon carcinogenesis. However, there is one study showing that ursodeoxycholic acid (UDCA) supplemented in the diet at the concentration of 0.4% prevented azoxymethane-induced rat colon tumorigenesis. The aim of our study was to explore the inhibitory effect of a much smaller dose of UDCA on colon carcinogenesis in rats. One hundred 7-week-old F344 rats were given 2 mg of N-methylnitrosourea 3 times a week for 3 weeks by intrarectal instillation, and were fed a 0% (control), 0.4% or 0.08% UDCA-supplemented diet for the next 27 weeks. All the rats were killed and examined for tumor development at week 30. The tumor incidence and number were significantly lower and smaller, respectively, in the UDCA-fed rats than in the control rats: 40% and 36% vs. 68%; 0.5 +/- 0.1 (mean +/- SEM) and 0.4 +/- 0.1 vs. 1.0 +/- 0.2. All the tumors were located in the distal half of the colon and were plaque-shaped or polypoid, being well-differentiated adenocarcinomas restricted to the mucosa or submucosa. Bile acids in the feces and the blood obtained at weeks 20 and 30, respectively, were analyzed by HPLC. A significant increase of UDCA was confirmed in both the feces and the blood of the UDCA-fed rats compared with the control rats. The results suggest that the continuous feeding of a small dose of UDCA may prevent colon carcinogenesis.     

Expression of Bcl-2 family of proteins in fresh myeloma cells

Members of the Bcl-2 family of proteins, Bcl-2, Bcl-X(L), Bcl-Xs and Bax, are considered to play important roles in the regulation of apoptosis and drug resistance. To understand the significance of these proteins in fresh human myeloma cells, expression of Bcl-2 family of proteins was analyzed by Western blotting in 17 cases with multiple myeloma (MM) and three cases with plasma cell leukemia (PCL). Bcl-2 and Bcl-X(L) were found in 12 and nine samples, respectively. All PCL cases showed co-expression of Bcl-2 and Bcl-X(L). Analysis of MM cases showed that Bcl-2 was preferentially expressed in samples from cases with early clinical stage while Bcl-X(L) tended to be expressed in samples from cases at advanced clinical stage. Bcl-X(L) was significantly expressed in tumor cells from cases with extramedullar lesions. There was no correlation between the expression levels of Bcl-2 or Bcl-X(L) and preceding chemotherapy. Expression of Bax was found in only one patient who had pleural effusion caused by invasion of myeloma cells and a high serum LDH level. Survival analysis revealed that there was no statistical significance in expression of Bcl-2 or Bcl-X(L) although Bcl-X(L) tended to be expressed in cases with poor prognosis. These findings indicate that expression of Bcl-2 family of proteins is heterogeneously regulated in fresh myeloma cells. Expression of Bcl-X(L) and Bcl-2 may correlate with extramedullar invasion and early stage of the disease, respectively. Absence of Bax in myeloma cells may contribute to low sensitivity of myeloma cells to anti-cancer agents since Bax is reported to mediate cytotoxicity of some anti-cancer drugs.     

GH and GnRH analog treatment in children who enter puberty at short stature

It is well known that height at the onset of puberty is closely related to final height. To improve final height of short children who enter puberty at short stature, twenty-one short boys and six short girls were treated with a combination of GH and GnRH analog. The boys started the combination treatment at a mean age of 12.0 years when their mean height was 128.5 cm (-2.74 SD) and the girls at a mean age of 10.68 years when their mean height was 126.4 cm (-2.23 SD). The boys discontinued GnRH at a mean age of 16.88 years after a mean treatment period of 4.89 years when their height was 153.7 cm (-2.75 SD), and the girls at a mean age of 13.89 years after a mean treatment period of 3.20 years when their height was 143.3 cm (-1.94 SD). Bone age maturation significantly decelerated during the combination treatment. Bone age rarely exceeded 14 years in boys and did not exceed 13 years in girls. Bone age maturation during combination treatment decelerated after bone age 12 years in boys and 10.5 years in girls. On average, bone age matured at a mean rate of 0.48 years a year in boys and 0.56 years a year in girls during the combination treatment. During the combination treatment, height velocity did not decelerate rapidly and remained at 3-5 cm/year for a longer duration because of the bone age deceleration, although a definite pubertal growth spurt was not observed. As a consequence, the mean projected height SDS for bone age increased 1.50 (+/- 0.76) SD in boys and 1.24 (+/- 0.49) SD during the combination treatment. Although most of the patients have not yet reached their final height, combined GnRH analog and GH treatment should increase the pubertal height gain and the adult height in short children who enter puberty early for height, when the post-GST growth is taken into account. The combination treatment seems more effective in boys than in girls. This improvement is attributed to the lengthening of the treatment period by slower bone maturation and maintained growth velocity.     

Nanofabrication of solid surface using probe oxidation

Surface-nanofabrication using probe oxidation is presented. Electrochemically generated oxide nano ridge structures can be fabricated using probes for atomic force microscopy. Moreover, removing the oxide ridge by hydrofluoric acid etching can also produce nanogroove structures. The relationship between the nanostructure shapes and fabrication conditions such as applied voltage and radius of curvature of the probe was investigated. The height of the oxide ridge can be controlled with sub-nanometer accuracy by the applied voltage and the width can be controlled by the tip radius. The depth and width of the groove can be controlled by adjusting the height and width of the ridge. Nanostructures with a very small height or depth (about 50 nm wide and < 1 nm high or deep) can be fabricated by our method. This is very useful for clarifying the nanotribology of micro- or nanomechanical devices.     

Mesoscopic-level Simulation of Dynamics and Interactions of Biological Molecules Using Monte Carlo Simulation

A mesoscopic-level method for clarifying living cell dynamics is described that uses Monte Carlo simulation of biological molecule interactions. The molecules are described as particles that take a random walk in 3-dimensional discrete space. Many kinds of molecules (including complex forms) are supported, so complex reactions with enzymes can be simulated. Also described is an field programmable gate array system with reconfigurable hardware that that will support complete modeling of an entire cell. Two-phase processing (migration and reaction) is used to simulate the complex reactions, so the method can be implemented in a limited amount of hardware. The migration and reaction circuits are deeply pipelined, resulting in high performance. Estimated performance is 30 times faster than with a 3.2-GHz Pentium 4 computer. This approach should make it possible to eventually simulate cell interactions involving one billion particles.

Embedded Human Periodontal Ligament Stem Cells Spheroids Enhance Cementogenic Differentiation via Plasminogen Activator Inhibitor 1

Spheroids reproduce the tissue structure that is found in vivo more accurately than classic two-dimensional (2D) monolayer cultures. We cultured human periodontal ligament stem cells (HPLSCs) as spheroids that were embedded in collagen gel to examine whether their cementogenic differentiation could be enhanced by treatment with recombinant human plasminogen activator inhibitor-1 (rhPAI-1). The upregulated expression of cementum protein 1 (CEMP1) and cementum attachment protein (CAP), established cementoblast markers, was observed in the 2D monolayer HPLSCs that were treated with rhPAI-1 for 3 weeks compared with that in the control and osteogenic-induction medium groups. In the embedded HPLSC spheroids, rhPAI-1 treatment induced interplay between the spheroids and collagenous extracellular matrix (ECM), indicating that disaggregated HPLSCs migrated and spread into the surrounding ECM 72 h after three-dimensional (3D) culture. Western blot and immunocytochemistry analyses showed that the CEMP1 expression levels were significantly upregulated in the rhPAI-1-treated embedded HPLSC spheroids compared with all the 2D monolayer HPLSCs groups and the 3D spheroid groups. Therefore, 3D collagen-embedded spheroid culture in combination with rhPAI-1 treatment may be useful for facilitating cementogenic differentiation of HPLSCs.     

A genetically encoded metallothionein tag enabling efficient protein detection by electron microscopy

The observation of biological materials by transmission electron microscopy (TEM) frequently requires the use of negative staining and/or immuno-gold labeling to visualize or identify the specimen, but these techniques are limited. In contrast, genetic labeling with green fluorescent protein (GFP) and its homologs have led to rapid advances in the observation of proteins of interest in cells by light microscopy (LM). These fluorescent tags allow for the visualization of dynamic processes in live cells without the use of secondary reagents. Here, we report the development of an artificial metalloprotein fusion protein expressed in Escherichia coli grown in Cd(2+)-containing medium that allows for efficient protein detection by TEM without additional staining steps. We linked the subunits of the bacterial 14-mer protein GroEL with three repeats of metallothionein (3MT). The 3MT-fused GroEL (GroEL-14(3MT)) was successfully expressed in E. coli, and the purified protein included 250 cadmium atoms per molecule on average. Cd(2+)-bound GroEL-14(3MT) was detected by TEM in the absence of negative staining on a carbon grid, and the particle densities of GroEL-14(3MT) were much greater than those of untagged GroEL in vitreous ice. Taken together, our data indicate that the 3MT tag provides a promising means of allowing the identification of oligomeric proteins isolated from cells in the absence of other detection techniques.     

Effects of swift heavy ion irradiation on the structure of Er2O3-doped CeO2

In order to simulate the effects of burnable poison doping on the fission fragment damage of UO₂ nuclear fuels, Er₂O₃-doped CeO₂ pellets were irradiated with 200 MeV Xe¹⁴⁺ ions. The irradiation effect was measured by means of X-ray diffraction (XRD). The expansion of lattice and the disordering of atomic arrangement due to the irradiation become more remarkable with increasing the concentration of the Er₂O₃ dopant.