Heparin affinity high-performance liquid chromatography as an alternative to bioassay of CS23 mutein of recombinant human basic fibroblast growth factor

We investigated whether a chemical assay by high-performance liquid chromatography (HPLC) as an alternative to the complicated and time-consuming bioassay for CS23 mutein of recombinant human basic fibroblast growth factor (rhbFGF-CS23) using the fetal bovine heart endothelial cell line ATCC CRL 1395. Physically, chemically or enzymatically denatured rhbFGF-CS23 was subjected to heparin affinity (HA)-HPLC and the bioassay. Good agreement was observed between the results obtained by these two methods. Moreover, HA-HPLC gave much more reproducible results (RSD = 1.9%, n = 6) than the bioassay (RSD = 7.4%, n = 18). HA-HPLC is therefore a simple, accurate and reproducible alternative to the bioassay for quality control and stability studies for rhbFGF-CS23 preparations. HA-HPLC is also considered to be applicable to assays for FGFs which have heparin affinity and biological activity similar to those of the CS23 mutein.     

Cerebral angioplasty in a patient with vascular dementia

A mechanical computerized three-dimensional scanner with a resolution of 1 micron was used to assess loss of enamel caused by orthodontic bonding and debonding. A total of 2646 measurements was performed on six human premolars. The results showed an average loss of enamel of 7.4 microns. The range was between 1 and 52 microns, which may account for discrepancies with earlier studies that measured only a few points per tooth surface.     

Sensitive Label-Free Immunoassay by Colorimetric Plasmonic Biosensors Using Silver Nanodome Arrays

The sensitive direct detection of biomolecules is demonstrated by a colorimetric plasmonic biosensor utilizing the surface colors of plasmonic metasurfaces named Ag nanodome arrays. The Ag nanodome arrays consist of polystyrene bead monolayers coated with Ag thin films whose surface colors are optimized by changing the size of the polystyrene beads. The bulk refractive index sensitivity of colorimetric detection evaluated using the hue angle is 590° RIU⁻¹ (RIU: refractive index unit). For selected geometry, the refractive index resolution (5.0 × 10⁻⁵ RIU) obtained by colorimetric detection surpasses that of spectroscopic detection evaluated via the dip wavelength in the reflection spectrum. The numerical simulations predict an enhanced sensing performance when the hue angle of the surface colors of the Ag nanodome arrays changes from 300° to 200°, corresponding to changes in the dip wavelength from 570 to 600 nm in the reflection spectra. Furthermore, the detection sensitivity of the biomolecules is characterized using a direct IgG immunoassay format. The detection limit of the IgG concentration is as low as 134 pM using simple colorimetric detection. The feasibility of sensitive label-free immunoassays using a colorimetric plasmonic biosensor is expected to accelerate the development of highly sensitive and reliable smartphone-based plasmonic biosensors.     

Estimation of the surface velocity of debris flow with computer-based spatial filtering

A computer-based spatial-filtering velocimeter to measure the surface velocity of natural debris flow is described. This is a simple and interesting technique implemented with a spatial filter constructed as a software program that processes the video image of debris flow instead of a hardware implementation. The surface velocity of the debris flow at the Mt. Yakedake Volcano, Japan, was estimated by this computer-based spatial-filtering method, and the results were compared with those obtained by a hardware-based spatial-filtering method. Computer-based spatial filtering has the important advantage of a capability for tuning the spatial-filter parameters to the target flow.     

Scalability of hybrid programming for a CFD code on the Earth Simulator

The Earth Simulator (ES) is an SMP cluster system. There are two types of parallel programming models available on the ES. One is a flat programming model, in which a parallel program is implemented by MPI interfaces only, both within an SMP node and among nodes. The other is a hybrid programming model, in which a parallel program is written by using thread programming within an SMP node and MPI programming among nodes simultaneously. It is generally known that it is difficult to obtain the same high level of performance using the hybrid programming model as can be achieved with the flat programming model.

In this paper, we have evaluated scalability of the code for direct numerical simulation of the Navier–Stokes equations on the ES. The hybrid programming model achieves the sustained performance of 346.9 Gflop/s, while the flat programming model achieves 296.4 Gflop/s with 16 PNs of the ES for a DNS problem size of 256³. For small scale problems, however, the hybrid programming model is not as efficient because of microtasking overhead. It is shown that there is an advantage for the hybrid programming model on the ES for the larger size problems.     

Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice

We previously demonstrated that repetitive administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. However, we have not evaluated in detail the effect of single or intermittent BDNF administration on glucose metabolism in a diabetic animal model. The objectives of this study were to examine the dose-response effect and dosing interval of BDNF administration in db/db mice and to evaluate the effect of intermittent BDNF administration on pancreatic function in db/db mice. We evaluated the dose-response effect of BDNF by single administration in db/db mice. First, single administration of BDNF greater than 70 mg/kg significantly reduced blood glucose concentration one day after administered, and the BDNF effect was maintained for 6 d. Next, the effects of BDNF administered twice a week at 4, 10, 25, and 62.5 mg/kg on blood glucose concentration, and the effects of BDNF administered once a week at 10, 20, 30, 50, and 70 mg/kg on blood glucose concentration were examined in db/db mice. In the intermittent treatment studies, BDNF dose-dependently ameliorated glucose metabolism by not only the twice-a-week administration but also the once-a-week administration. Lastly, because BDNF reduces the food intake of obese hyperphagic diabetic mice, the effects of BDNF administered once or twice a week on the blood glucose concentration and plasma and pancreatic insulin concentrations in db/db mice were compared with those of the vehicle under pair-fed conditions. Under pair-fed conditions, the intermittent administration of BDNF (25 mg/kg, twice a week, or 50 mg/kg, once a week) significantly reduced the blood glucose concentration and increased the plasma and pancreatic insulin concentrations compared with those in the pair-fed vehicle-treated db/db mice. This indicates that the prolonged hypoglycemic effect of BDNF is not simply due to the reduction of food intake. In conclusion, we demonstrated that the intermittent administration of BDNF ameliorates glucose metabolism and prevents pancreatic exhaustion in obese diabetic mice. These findings indicate that BDNF may have potential as a unique hypoglycemic agent for the treatment of diabetes at a fundamental level with good patient compliance.     

Analysis of mumps vaccine failure by means of avidity testing for mumps virus-specific immunoglobulin G

Rapid ventricular pacing (RVP) in dogs creates a well characterized model of dilated cardiomyopathy. Standard pacing protocols use RVP at 240-260 beats/min for 2-4 weeks, and result in high mortality rates if continued longer. The authors describe a modification of RVP that results in significant heart failure by 4 weeks, but can be continued for up to 10 weeks with low mortality. Nineteen mongrels underwent RVP at 215 beats/min for 10 weeks. Serial pressure-volume analysis and echocardiography were performed in this model to assess longitudinally changes in left ventricular (LV) function and volumes. The mortality rate was 10%. Significant progressive LV dysfunction with concomitant LV enlargement was observed throughout the pacing period. Finally, norepinephrine levels were elevated at the end of pacing, consistent with an activated sympathetic system. This modified RVP protocol permits long-term pacing with a low mortality rate and results in progressive heart failure throughout the pacing period. This model would be useful in the long-term evaluation of newer surgical and medical therapies of the failing heart.     

Creation of Titania Artificial Interfaces with Geometric Patterns by Using Microstereolithography and Aqueous Solution Techniques

Titania micropatterns with periodic arrangements were successfully formed on glass substrates for use with electromagnetic wave energy resonance and localizations in terahertz frequency ranges. Geometric arrangements of acrylic polygonal tablets with titania particle dispersions were fabricated by using micropatterning stereolithography. Moreover, periodically arranged full anatase‐phase titania tablets were created homogeneously through liquid‐phase crystal depositions of water solvent processes, using microtemplates fabricated by using the stereolithography system. The terahertz wave properties were measured and calculated by using a time‐domain spectroscopic system and finite‐difference time‐domain method.     

First-Principles Study on the Grain Boundary Embrittlement of Metals by Solute Segregation: Part II. Metal (Fe,Al, Cu)-Hydrogen (H) Systems

The microscopic mechanism of grain boundary (GB) embrittlement in metals by hydrogen segregation (trapping) has been not well understood for many years. From first-principles calculations, we show here that the calculated cohesive energy of bcc Fe Σ3(111) and fcc Al(Cu) Σ5(012) symmetrical tilt GBs can be significantly reduced if many hydrogen atoms segregate at the GBs. This indicates that the reduction of the cohesive energy of the GB may cause the hydrogen-induced GB embrittlement in Fe, Al, and Cu. Considering the “mobile” effect of hydrogen during fracture, especially for the Fe system, more hydrogen atoms coming from solid solution state can segregate on the gradually formed two fracture surfaces and reduce further the cohesive energy. We suggest a new idea about the upper and lower critical stresses observed in the constant-load test of hydrogen-induced delayed fracture in high-strength steels; the upper critical stress is determined by the amount (density) of “immobile” hydrogen atoms segregated at the GB before fracture, and the lower critical stress is determined by the total amount (density) of immobile and mobile hydrogen atoms, the latter of which segregate on the two fracture surfaces during fracture.     

Allixin, a phytoalexin produced by garlic, and its analogues as novel exogenous substances with neurotrophic activity

Effects of allixin, a phytoalexin of garlic, and its analogues were studied on the survival and morphology of primary cultured neurons from fetal rat brain. Addition of allixin (1-100 ng/ml) to medium significantly promoted the survival of neurons derived from various regions of brain and increased the number of branching points per axon in hippocampal neurons. Allixin, however, was cytotoxic at higher concentrations (>1 microg/ml). Among the analogues of allixin, 2,6-dimethyl-3-hydroxy-4H-pyran-4-one (DHP) possessed potent neurotrophic activity at concentrations over 10 ng/ml without any obvious cytotoxicity up to 10 microg/ml. DHP also retained the activity to promote axonal branching. These results indicate that DHP is a novel exogenous low molecular weight neurotrophic substance without apparent cytotoxicity. This compound may be a useful prototype leading chemical for developing therapeutic and/or prophylactic drugs for neurodegenerative disorders.