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TAK-448 and TAK-683, investigational agents with potential utility in the treatment of prostate cancer, are potent low molecular weight metastin receptor agonists consisting of nine amino acids. Monoclonal antibodies (mAbs) against these agents were developed to facilitate their evaluation in preclinical studies. Six mAbs were obtained from four immunogens. Three mAbs recognized the C-terminal of TAK-683 and TAK-448, two recognized the N-terminal of TAK-683, and one recognized the N-terminal of TAK-448. Using various combinations of these six mAbs, sandwich ELISAs for TAK-448 and TAK-683 were developed. These assays were highly sensitive, specific, and accurate. The detection limit for TAK-448 and TAK-683 was 3 and 5 pg/mL, respectively, and there was no interference from rat plasma, rat metastin, or analogs of TAK-448/TAK-683. Recovery achieved ≤±10% with intra-/inter-day assay precision coefficient of variation10%. The assay demonstrated high stability and sample pre-treatment was not required. Each assay detected the dose-dependent concentration of TAK-448 and TAK-683 in blood 24h after a single intravenous administration of 0.1 and 1mg/kg doses. In conclusion, sensitive sandwich ELISAs were developed to detect the small peptides TAK-448 and TAK-683. The novel assays reliably quantified these nonapeptides in rat plasma, and thus will be useful for preclinical studies of these agents. This methodology may be applicable to the development of similar assays for other short peptides.

Recently, manufacturing techniques of small-scale products have been improved. As a result, precise measurement is required of small inside diameters, for example, of engine nozzles. However, an in situ measurement and measurement system for small-sized products has yet to be fully established. In this research, a contactless technique to measure small inside diameters is proposed. This new method uses tandem low-coherence interferometry and an optical fiber cut at an angle of 45°. This optical fiber is up to 30 μm in diameter and is used as a probe. Our objective is to measure holes as small as 50-μm inside diameter with an accuracy of 100 nm. In the present paper, we report on the measurement principle, calculate the measurement uncertainty and show that experimental measurements can be obtained of small-size holes up to 300-μm inside diameter with an accuracy of 100 nm.

We develop a new method for high-resolution and contactless distance measurement based on self frequency beats of optical frequency combs. We use two optical frequency comb lasers with Rb-stabilized repetition frequencies for doing accurate distance measurement. The repetition frequencies of the optical frequency combs are different, thus parts of the high frequencies such as several gigahertz of self beats are beat-downed to several megahertz without an RF frequency oscillator. The phases of the beat signals of several megahertz frequencies are measured by a lock-in amplifier with a high resolution and high sensitivity. The new method is applied to distance measurement for objects which have rough-surface in the distance range of several-meters.

Metastin/kisspeptin is an amidated peptide with 54 amino acid residues isolated from human placental tissues as a ligand of the orphan G-protein-coupled receptor KISS1R that is expressed throughout the central nervous system and in a variety of endocrine and gonadal tissues. Compared to the full-length metastin protein, the N-terminal truncated peptide metastin(45-54) has 3-10 times higher receptor affinity and enhanced ability to increase intracellular calcium concentration which is essential for activation of protein kinases involved in intracellular signaling in a number of pathways that affect reproduction and cell migration. However, metastin(45-54) is rapidly inactivated in serum. In this study, we designed and synthesized a number of metastin(45-54) analogs and evaluated their agonistic activity and trypsin resistance. Among analogs with substitutions of arginine at position 53, N(ω)(-)methylarginine analog 8 showed 3-fold more potent agonistic activity compared with metastin(45-54). Furthermore, analog 8 was shown to resist trypsin cleavage between positions 53 and 54. This substitution may be useful in the development of other Arg-containing peptides for which the avoidance of cleavage is desired.

A Shack-Hartmann type laser wavefront senor was developed for achieving electron density distributions over an arc channel in an extinguishing phase by only a single measurement with high temporal and spatial resolutions. The sensor was applied to pulsed arcs in 3-mm air gap between rod-to-rod tungsten electrodes with a diameter of 1mm. Electron densities in the arc discharges with currents of several tens of amperes were lower around the gap centre than near the anode and cathode. The behaviour of the electron densities was consistent with the intensity of emission light from arc discharges.

This paper reports the characteristics of planar contactless power transfer systems, which are classified into the following types: single-phase primary and single-phase secondary system (SS system), three-phase primary and single-phase secondary system (TS system), and three-phase primary and three-phase secondary system (TT system). The SS system is used in conventional contactless power transfer. On the other hand, in the last few years, the TS system has been studied more. As a novel system, the TT system is here proposed. The characteristics of all three systems are measured by using a common experimental prototype made of printed circuit board. The comparison confirms that the TT system has higher efficiency and can output uniform power independent of the secondary position, as compared to the other systems.

A novel internal diameter measurement method based on a low-coherence tandem scheme is firstly demonstrated. From operational analysis, it is understood that a low-coherence tandem scheme can be served for internal diameter evaluation by using a combination of a transmission grating and a ring gauge instead of a classical Michelson interferometer to store and transmit the internal diameter information. As a result of the experiment, in the present experimental environment, diameter measurement of several millimetres with a relative standard uncertainty of several micrometres was performed. Taken together, these results suggest that the present measurement method is expected to be used as a powerful remote internal diameter calibration tool for next-generation calibration network systems.

FASN is a multifunctional enzyme that catalyzes de novo biosynthesis of long-chain saturated fatty acid, and alteration of this enzyme may affect economic traits including fatty acid composition. Sequencing the coding sequence (CDS) of the FASN gene has so far been done only partially for dairy cattle. In this study, the CDS of the FASN gene of eight Holstein cattle was sequenced to detect nucleotide polymorphisms. We could identify 13 single nucleotide polymorphisms (SNPs) of which five were non-synonymous mutations (H1390Y, I1856L, T1950A, W1955R and T2264A). The association between these SNPs and economic traits was analyzed using 198 Holstein dams. Genotypes of H1390Y corresponded to those of the I1856L in the group, suggesting these SNPs were linked. Furthermore, the T1950A was suggestively linked with the W1955R. The association study revealed that T1950A/W1955R had an effect on milk fat content and the C14 Index. This will help to understand the complex association between the FASN gene and economic traits.

This paper studies the model for the three-phase contactless power transfer system. A phase winding in the three-phase contactless power transformer has the magnetic couplings with all of the other phase windings. Moreover, the magnetic couplings depend on the displacement of the secondary armature with respect to the primary armature. The equivalent model of the three-phase system with the complicated mutual inductances due to such magnetic couplings is presented. The model is transformed into the single-phase model that is similar to the model for the conventional system. The simplified model allows the easy consideration of the operation of the three-phase system. By using the model, the resonant capacitances for the three-phase system are available. The model is confirmed to successfully simulate the performance of the actual system. In addition, the experimental and theoretical results confirm that the three-phase system has the stable performance of the power transfer independently of the displacement of the secondary.

By a series of positional cloning, we successfully narrowed down the AM candidate region to approximately 1.2 Mbp on GGA2q including 7 functional genes. Subsequently, we identified WWP1 gene as the most likely AM candidate by sequence comparison. The amino acid sequence around the candidate mutation was highly conserved among tetrapods, suggesting that WWP1 is the causative gene of chicken muscular dystrophy. Transfection of mutated WWP1 gene into C₂C₁₂ myoblasts disrupted muscle differentiation process. The abnormal muscle differentiation is a characteristic of chicken muscular dystrophy, so we could demonstrate a part of phenotype of the disease. Furthermore, western blotting revealed that accumulation of caveolin-3 protein is limited in damaged muscle of muscular dystrophic chicken, suggesting caveolin-3 may be associated with the pathological change of the disease. We could conclude that WWP1 gene is the responsible one for chicken muscular dystrophy from these results, but the mechanism leading the onset should be clarified in the future. The information will contribute to the study of chicken muscular dystrophy and the corresponding human dystrophies.

To know electron densities in low current arcs, Shack-Hartmann type laser wavefront sensor was developed, improved in terms of measurement accuracy, and applied to atmospheric arcs with a peak current of 0.8kA. An electron density in pre-extinguishing phase was 5×1023m-3 at gap centre when an instantaneous current decreased to 0.1kA.

In measurements of impulse voltages by Pockels sensors, oscillatory components have been observed in the tail parts of the optical signals. In this paper, oscillatory components of Bi4Ge3O12 (BGO) Pockels crystals of various shapes are investigated. The tested BGO crystals are rectangular solids, a cylindrical solid, and a tapered quadratic solid. The oscillatory components are derived from the light outputs and the frequency analysis is performed. The oscillation frequency of the rectangular crystals is lower than the theoretical value and that of a cylinder is the same as that of circumscribed rectangular solid. In the case of the tapered BGO crystal, it is possible to reduce the oscillatory components by distributing piezoelectric vibration over a broad frequency bandwidth. © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

The boost motor driver with electric double layer capacitors (EDLCs) was proposed. This driver was proved to be able to stably boost the dc-link voltage and reduce peak input power without degrading the motor-drive performance. In this paper, an EDLC charge strategy to operate the charge circuit implemented in the driver is presented. The strategy has three modes of operation: the initial charge mode, the driving charge mode, and the regenerative charge mode. In the initial charge mode, the charge circuit operates in order to charge the EDLCs before a motor drive. In contrast, the driving charge mode is operated in order to charge the EDLCs while a motor is driven. The charge circuit in the regenerative charge mode suppresses the increase in the dc-link voltage in regenerative braking. The experimental results confirm that the charge circuit can well perform in accordance with this charge strategy. Moreover, the comparison with the results of a conventional driver proves that the drive performance of the proposed driver does not degrade during the charge operation. Finally, the proposed driver is confirmed to be able to perform well without decreasing the EDLC voltage in extended duration drive.

Charge-pumping boost driver (CPBD) with electric double-layer capacitors (EDLCs) was proposed by the author. CPBD has advantages over conventional drivers. However, CPBD comprises a charge circuit, including an inductor to charge the EDLCs, which increases size and cost of CPBD. This problem led to the proposal of noncharge-circuit charge-pumping boost driver (NCPBD) with EDLCs. NCPBD can be realized in a smaller and more reasonable configuration than CPBD because NCPBD does not comprise the charge circuit. In this paper, an EDLCs charge method, exciting-axis voltage vibration method (EVVM), is proposed for NCPBD. EVVM enables NCPBD eliminating the charge circuit to charge the EDLCs. Additionally, EVVM can work even in a motor standstill and in a constant speed drive. The charge performance by EVVM is experimentally confirmed to be sufficiently well. Additionally, the drive performance during the charge operation is proved not to degrade. From the experimental results, the charge characteristics of EVVM are reported. Then, these charge characteristics introduce a charge strategy. Finally, the charge experiment adopting the strategy confirms that EVVM enables NCPBD to drive the motor without decreasing the EDLCs voltage in an acceleration and deceleration drive.

A novel etch chemistry, C4H9F was evaluated for highly selective patterning of SiN using both organic and SiOx masks for line/space and cylindrical geometries. Patterning of 80 nm of SiN using 65 nm of the organic planarization layer (OPL) mask with a C4H9F:O2:CF4 admixture yielded line edge roughness (LER) and line width roughness (LWR) values of 1.9 and 2.8 nm on sub-25 nm critical dimension (CD) SiN lines at 50 nm pitch, with >50 nm mask retention up to 40% overetch values. The LER and LWR values were 60% and 66% lower than features patterned using a CF4:CHF3 admixture, which also exhibited complete OPL mask loss and nitride erosion of 27 nm even at the endpointed etch condition. Using 20 nm of SiOx as a mask and removing CF4 from the chemistry admixture, LER and LWR values of 2.7 and 3.3 nm were achieved with nearly full SiOx retention for features of identical dimensions. At smaller mask pitches (21 and 24 nm) formed by directed self-assembly of high-χ block copolymers, the highly selective nature of C4H9F to organic masks facilitated SiN pattern transfer where CF4 based admixtures failed, achieving line CDs of ∼12 nm with LWR and LER of 1.6 and 2.2 nm. Applied to alternate geometry, hole patterning in SiN at ∼30 nm CD and 60 nm pitch was demonstrated. A subsequent image reversal process yielded pillars by filling the hole pattern with OPL and etching back the surrounding SiN layer, reaffirming the extremely high selectivity of C4H9F to organic masks.A novel etch chemistry, C4H9F was evaluated for highly selective patterning of SiN using both organic and SiOx masks for line/space and cylindrical geometries. Patterning of 80 nm of SiN using 65 nm of the organic planarization layer (OPL) mask with a C4H9F:O2:CF4 admixture yielded line edge roughness (LER) and line width roughness (LWR) values of 1.9 and 2.8 nm on sub-25 nm critical dimension (CD) SiN lines at 50 nm pitch, with >50 nm mask retention up to 40% overetch values. The LER and LWR values were 60% and 66% lower than features patterned using a CF4:CHF3 admixture, which also exhibited complete OPL mask loss and nitride erosion of 27 nm even at the endpointed etch condition. Using 20 nm of SiOx as a mask and removing CF4 from the chemistry admixture, LER and LWR values of 2.7 and 3.3 nm were achieved with nearly full SiOx retention for features of identical dimensions. At smaller mask pitches (21 and 24 nm) formed by directed self-assembly of high-χ block copolymers, the highly selective nature of...

The performance of low-k nitride spacer etch processes for fin-field effect transistor device fabrication was investigated using C4H9F based and CH3F based plasma gas chemistries. C4H9F showed a larger process window of O2 gas flow rate to obtain infinite etch selectivities of blanket SiN/SiO and SiN/poly-Si than CH3F. The etch selectivity increased in both gases with the reduction of duty cycle in synchronously pulsed plasmas. Low-k spacer formation using a 60-nm gate pitch testsite was demonstrated resulting in the minimized fin recess of 4.7 nm using C4H9F-O2-He plasma at a duty cycle of 30%. This was 2.2 times smaller than that by the CH3F-He plasma. Fifty percent extended etch time resulted in a fin recess of 5.1 nm, suggesting self-limiting behavior using C4H9F-O2-He plasma chemistry. Gap structure analysis on the blanket films suggested that the selective deposition of fluorocarbon, which enhances the selectivity, is driven by plasma assisted deposition in case of the C4H9F-O2-He plasma. These unique characteristics of C4H9F can facilitate innovative plasma etch processes for nitride-based materials patterning in a wide range of applications.The performance of low-k nitride spacer etch processes for fin-field effect transistor device fabrication was investigated using C4H9F based and CH3F based plasma gas chemistries. C4H9F showed a larger process window of O2 gas flow rate to obtain infinite etch selectivities of blanket SiN/SiO and SiN/poly-Si than CH3F. The etch selectivity increased in both gases with the reduction of duty cycle in synchronously pulsed plasmas. Low-k spacer formation using a 60-nm gate pitch testsite was demonstrated resulting in the minimized fin recess of 4.7 nm using C4H9F-O2-He plasma at a duty cycle of 30%. This was 2.2 times smaller than that by the CH3F-He plasma. Fifty percent extended etch time resulted in a fin recess of 5.1 nm, suggesting self-limiting behavior using C4H9F-O2-He plasma chemistry. Gap structure analysis on the blanket films suggested that the selective deposition of fluorocarbon, which enhances the selectivity, is driven by plasma assisted deposition in case of the C4H9F-O2-He plasma. These uniq...

We propose a novel absolute measurement method for precisely measuring the internal distance between two points, using a tandem low-coherence interferometer. In this method, a beam splitter is positioned between two plane mirrors, the locations of which are accurately determined at the nanometre level using tandem low-coherence interferometry. Using a He–Ne laser interferometer as a reference length standard, an internal distance of up to 100 mm was measured remotely, with a measurement uncertainty of 178 nm (k = 2).

The WW domain containing E3 ubiquitin protein ligase 1 (WWP1), which plays an important role in ubiquitin-proteasome pathway to degrade unneeded or damaged proteins, was recently identified as the responsible for chicken muscular dystrophy. Despite intensive studies on oncogenic characters, the role of WWP1 to muscular diseases has not yet been fully understood. Previously, we transfected either of wild and mutated types of WWP1 gene into C2C12 mouse myoblasts to monitor the expression pattern of muscle-differentiation markers, so that excessive WWP1 expression enhanced the expression of the myosin heavy chain (MyHC) Ia gene but lowered the expression of the MyHC IIb gene, while mutated WWP1 gene transfected into myoblasts was distinct from these cases in that the MyHC gene or genes expression inhibited the normal myoblast differentiation. However, the mechanism for the mutation to inhibit muscle differentiation remains elucidated. The current study attempted to suppress the WWP1 expression by RNAi technique and to observe its effect on C2C12 cells. The effect of WWP1 suppression was clearly different from that of the R441Q missense mutation in the WWP1 gene. The WWP1 suppression reduced the proliferation rate of C2C12 myoblasts, while clear difference was not observed in the proliferation rate by the transfection of the mutated WWP1 gene into the cells. Our RT-PCR analysis indicated that the reduction of the WWP1 expression is the specific effect mediated by RNAi and that the reduction of proliferation rate observed in this study is largely attributed to the suppression of the WWP1 expression. These data indicated that the mutation responsible for chicken muscular dystrophy does not eliminate the enzymatic activity and provides some new function for the gene.

粉体挙動に大きな影響を与える粒子形状を離散要素法（DEM）シミュレーションに取り込むために，転がり摩擦に着目し，球形要素を用いて経済的に粒子形状の効果を表現する方法を提案した．まず，傾斜部を持つ平板上を転動する多角柱の挙動から転がり摩擦係数が粒子形状に関する係数と回転速度の関数で与えられることを明らかにし，円柱要素を用いたDEMシミュレーションにより多角柱の挙動を再現した．また，この粒子形状と転がり摩擦係数の関係を任意の物質へ適用する換算法を明らかにした．つづいて，輪郭フーリエ変換を用いて不規則形状粒子の形状の等価多角形数を求め，転がり摩擦係数を得た．傾斜樋上における不規則形状粒子群の流動挙動の実験およびシミュレーションの結果は良好な一致を示し，提案した形状表現法およびその形状から求める粒子群の等価転がり摩擦係数の信頼性を確認した．

The brain mechanism regulating gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release is sexually differentiated in rodents. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) have been suggested to be sexually dimorphic and involved in the GnRH/LH surge generation. The present study aimed to determine the significance of neonatal testicular androgen to defeminize AVPV kisspeptin expression and the GnRH/LH surge-generating system. To this end, we tested whether neonatal castration feminizes AVPV kisspeptin neurons and the LH surge-generating system in male rats and whether neonatal estradiol benzoate (EB) treatment suppresses the kisspeptin expression and the LH surge in female rats. Immunohistochemistry, in situ hybridization, and quantitative real-time RT-PCR were performed to investigate kisspeptin and Kiss1 mRNA expressions. Male rats were castrated immediately after birth, and females were treated with EB on postnatal Day 5. Neonatal castration caused an increase in AVPV kisspeptin expression at peptide and mRNA levels in the genetically male rats, and the animals showed surge-like LH release in the presence of the preovulatory level of estradiol (E2) at adulthood. On the other hand, neonatal EB treatment decreased the number of AVPV kisspeptin neurons and caused an absence of E2-induced LH surge in female rats. Semiquantitative RT-PCR analysis showed that neonatal steroidal manipulation affects Kiss1 expression but does not significantly affect gene expressions of neuropeptides (neurotensin and galanin) and enzymes or transporter for neurotransmitters (gamma-aminobutyric acid, glutamate, and dopamine) in the AVPV, suggesting that the manipulation specifically affects Kiss1 expressions. Taken together, our present results provide physiological evidence that neonatal testicular androgen causes the reduction of AVPV kisspeptin expression and failure of LH surge in genetically male rats. Thus, it is plausible that perinatal testicular androgen causes defeminization of the AVPV kisspeptin system, resulting in the loss of the surge system in male rats.

Prolactin-releasing peptide (PrRP) was isolated as an endogenous ligand of the orphan G-protein coupled receptor hGR3. PrRP has been shown to be involved in the regulation of food intake, stress responses, prolactin secretion and release, blood pressure, and the opioid system. Here we report that PrRP and its receptor, GPR10, were found in the mouse substantia nigra pars compacta (SNpc), the main location of dopaminergic (DA) neurons of the nigrostriatal system. We generated PrRP knockout (KO) mice, and then treated PrRP KO mice and their wild type (WT) littermates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neuron toxin that selectively damages DA neurons in the SNpc. We found that PrRP KO mice were resistant to MPTP-induced lesions of the nigrostriatal system. These effects were further confirmed by the intracerebroventricular injection of P2L-1C, a monoclonal antibody against PrRP into mice. Taken together, our data established a critical role of PrRP in MPTP intoxication in mice.

Kisspeptin, a peptide encoded by the Kiss1 gene, has been considered as a potential candidate for a factor triggering the onset of puberty, and its expression in the hypothalamus was found to increase during peripubertal period in rodent models. The present study aimed to clarify the oestrogenic regulation of peripubertal changes in Kiss1 mRNA expression in the anteroventral periventricular nucleus (AVPV) and hypothalamic arcuate nucleus (ARC), and to determine which population of kisspeptin neurones shows a change in kisspeptin expression parallel to that in luteinising hormone (LH) pulses at the peripubertal period. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry revealed an apparent increase in the ARC Kiss1 mRNA expression and kisspeptin immunoreactivity around the time of vaginal opening in intact female rats. The AVPV Kiss1 mRNA levels also increased at day 26, but decreased at day 31, and then increased at day 36/41. In ovariectomised (OVX) rats, ARC Kiss1 mRNA expression did not show peripubertal changes and was kept at a high level throughout peripubertal periods. Apparent LH pulses were found in these prepubertal OVX rats. Oestradiol replacement suppressed ARC Kiss1 mRNA expression in OVX prepubertal rats, but not in adults. Similarly, LH pulses were suppressed by oestradiol in the prepubertal period (days 21 and 26), but regular pulses were found in adulthood. The present study suggests that a pubertal increase of Kiss1/kisspeptin expression both in the ARC and AVPV is involved in the onset of puberty. These results also suggest that both LH pulses and ARC Kiss1 expression are more negatively regulated by oestrogen in prepubertal female rats compared to adult rats.

A fiber-based frequency comb has been developed to measure the frequency of a 633-nm iodine-stabilized laser at the National Metrology Institute of Japan (NMIJ). The measured frequency was consistent with the previous results measured with a Ti:sapphire-based comb. The NMIJ comb was shipped to Australia for the validation of the measurement capability of the National Measurement Institute, Australia (NMIA) and NMIJ combs using a common microwave reference and a common optical frequency. Consequently, the frequency consistency of the two combs was approximately 8 times10-17. Furthermore, we demonstrate that an absolute mode number of the comb can easily and clearly be determined by using the two combs.

The supply used in servo systems tends to have a high voltage in order to reduce loss and improve the response of motor drives. We propose a new boost motor driver that comprises EDLCs. The proposed driver has a simple structure, wherein the EDLCs are connected in series to the supply, and comprises a charge circuit to charge the EDLCs. The proposed driver has three advantages over conventional boost drivers. The first advantage is that the driver can easily attain the stable boost voltage. The second advantage is that the driver can reduce input power peaks. In a servo system, the input power peaks become greater than the rated power in order to accelerate the motor rapidly. This implies that the equipments that supply power to servo systems must have sufficient power capacity to satisfy the power peaks. The proposed driver can suppress the increase of the power capacity of supply facilities. The third advantage is that the driver can store almost all of the regenerative energy. Conventional drivers have a braking resistor to suppress the increase in the DC link voltage. This causes a considerable reduction in the efficiency. The proposed driver is more efficient than conventional drivers. In this study, the experimental results confirmed the effectiveness of the proposed driver and showed that the drive performance of the proposed driver is the same as that of a conventional driver. Furthermore, it was confirmed that the results of the simulation of a model of the EDLC module, whose capacitance is dependent on the frequency, correspond well with the experimental results.

The WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is classified into one of ubiquitin ligases which play an important role in ubiquitin-proteasome pathway. Previously, we identified the WWP1 gene as a candidate gene of chicken muscular dystrophy by linkage analysis and sequence comparison. However, the mechanism causing pathological changes and underlaying gene function remains elucidated. In the present study, we analyzed the WWP1 gene expression in various muscles and tissues of normal chickens, and compared with those from muscular dystrophic chickens. Two mRNA isoforms were detected in all tissues examined and revealed almost equal expression level. The WWP1 expression of dystrophic chickens was decreased in almost all skeletal muscles including unaffected muscles. These data indicate that there might not be a causal relationship between the alteration of WWP1 expression level and the severity of muscular dystrophy.

The administration of Hange-shashin-to is effective in preventing diarrhea caused by irinotecan hydrochloride (CPT-11)when they are coadministered but a high incidence of constipation has been reported when CPT-11 is used in combination with anti-diarrhea drugs.As many aspects of the occurrence of constipation with the combined use of Hange-shashin-to and CPT-11 were unclear,we decided to clarify the occurrence of constipation and its relationship with the CPT-11 dosage.To do this,we retrospectively compared two treatment groups in which Hange-shashin-to had been coadministered with CPT11 at 60 mg/m2 and 48 mg/m2,respectively.The incidence of constipation was significantly higher in the group treated with CPT-11 at 60 mg/m2 and Hange-shashin-to than that treated with CPT-11 at 48 mg/m2.These results indicate that the occurrence of constipation in such combined use is correlated not only with the CPT-11 dose but also Hange-shashin-to activity.The results also suggest that interaction between Hange-shashin-to and CPT-11 is strongly associated with the occurrence of constipation.

Practical length standards are remotely measured using a tandem low coherence interferometer through an optical fiber network for communication of about 20 km length between Tsukuba City and Tsuchiura City in Japan. The reference low-coherence interferometer is installed at the National Institute of Advanced Industrial Science and Technology (AIST) and the measurement interferometer with a gauge block of 100 mm nominal length is installed at a calibration laboratory in Tsuchiura City. The optical fibers work as a common path for the tandem interferometric system. Interference fringes are generated when the optical path difference between the reference and measurement interferometers is equal, and thus the gauge block is measured within a standard uncertainty of 46 nm remotely.

The refractive index of air is accurately measured using a vacuum cell and a tandem low-coherence interferometer with a communication optical fiber of 30 km length with standard uncertainties of 0.20 ppm for the phase refractive index and 0.29 ppm for the group refractive index. Experimental results are compared with the value calculated from the equation for the refractive index of air using data obtained from measurements of the surrounding air, with a standard uncertainty of 0.22 ppm, and the difference between the average values is within 0.1 ppm. This method is applicable to the in situ high-precision measurement of optical length.

We report a method for optimizing the amplification of femtosecond optical pulses by using dispersion management. The amount of dispersion provided to the seed optical pulse of an erbium-doped fiber (EBF) has an optimal region that enhances the output power of an amplifier. The power enhancement is accompanied by spectral broadening, which originates from adiabatic narrowing in the erbium-doped fiber. The amplified optical pulses can be used to generate an octave-spanning optical frequency comb (OFC) by employing a highly nonlinear fiber (HNLF).

Line profiles of a rovibrational transition of 13C acetylene have been measured for various pressures in the near infrared region. In order to accomplish high precision in frequency, we have employed a diode-laser, the frequency of which is locked to an optical comb. By tuning the comb frequency we have achieved a continuous frequency tuning over 2 GHz for the measurement of Doppler broadened line profiles spread over 2 GHz. In addition we have stabilized the incident power of the laser on the sample cell by adjusting the gain of a fiber amplifier via a feed-back loop. Observed profile data have been analyzed by the generalized Voigt function to determine the Gaussian width precisely: at the present we realized a precision of 10 - 3 . The zero pressure line center position was determined with a precision of 10 - 9 .

Galanin-like peptide (GALP), a ligand for three types of galanin receptor, is reported to have a role in regulating luteinising hormone (LH) release in male rodents and primates, but its role in LH release in female rodents remains controversial. The present study was conducted to test whether GALP has a stimulatory role in regulating LH secretion in female rats. The effect of i.c.v. infusion of GALP (5 nmol) on pulsatile LH release was investigated in Wistar-Imamichi strain female rats, or lean and obese Zucker rats. In oestradiol-17beta (oestradiol)-primed ovariectomised (OVX) Wistar-Imamichi female rats, i.c.v. infusion of GALP caused a gradual increase in LH release for the first 1.5 h after the infusion followed by an increased LH pulse frequency during the next 1.5 h, resulting in a significant increase in the mean LH concentrations and baseline levels of LH pulses throughout the sampling period and in the frequency of LH pulses at the last half of the period compared to vehicle-treated controls. The stimulatory effect of GALP was oestrogen-dependent because the same GALP treatment did not affect LH release in OVX rats in the absence of oestradiol. In lean Zucker rats, LH pulses were found in oestradiol-primed OVX individuals and central GALP infusion increased mean LH concentrations in the last half of the period. By contrast, few LH pulses were found in oestradiol-primed OVX obese Zucker rats reportedly with lower hypothalamic GALP expression. Central GALP infusion caused an apparent but transient increase in LH release, resulting in the significant increase in all pulse parameters of LH pulses compared to vehicle-treated controls in the first half of the sampling period. These results suggest that hypothalamic GALP is likely involved in stimulating GnRH/LH release, and that the stimulatory effect of GALP on LH release is oestrogen-dependent in female rats.

Muscular dystrophies, a group of inherited diseases with the progressive weakness and degeneration of skeletal muscle, contain genetically variable diseases. Though chicken muscular dystrophy with abnormal muscle (AM) has long been known, the gene responsible has not yet been identified. In this study, a resource family for AM was established with 487 F2 individuals and 22 gene markers, including microsatellite and insertion–deletion markers, were developed. The haplotypes were analyzed with these markers for the candidate region of GGA2q described in a previous study. The candidate region was successfully narrowed down to approximately 1Mbp. The region included seven functional genes predicted as the most likely AM candidates.

The authors have demonstrated optical frequency synthesis using a fiber-based frequency comb system, referenced to an ultrastable microwave oscillator. The oscillator is based on a high Q-factor cryogenic sapphire resonator cooled with liquid helium. The 100-MHz signal synthesized from the 10.8-GHz oscillation frequency of the cryogenic sapphire oscillator (CSO) was used to stabilize the repetition frequency of the mode-locked fiber laser. When the synthesized optical frequency was compared with a rubidium two-photon stabilized laser at 778 nm, the measured fractional frequency stability was ~6 10-14 tau -12 for the averaging times tau between 1 and 100 s, and the best frequency stability was 3.0 10-15 for an averaging time of 1280 s

This paper proposes a boost-voltage motor driver with a low-capacitance charge-pump circuit. To deal with considerably changing boost-voltage, a voltage control method based on the space vector modulation technique is proposed. The experiments under repetitive acceleration and deceleration drive operation confirm that the driver can perform well. Furthermore, the proposed driver is verified to have higher drive efficiencies than the conventional driver.

The group refractive index of BK-7 glass material is accurately measured using a tandem low-coherence interferometer, which is composed of a Mychelson interferometer and a Fizeau interferometer, within a combined standard uncertainty of 8.4 ppm. The experimental results are compared with the value calculated from the conventional data base on the phase refractive index, within a difference of about 4.7 ppm. This new method is applicable to in situ measurement due to the principle of its common optical path.

An optical frequency measurement system based on an octave-spanning optical frequency comb generated by a chirped-mirror-dispersion-controlled mode-locked Ti:Al2O3 laser and a photonic-crystal fiber is developed. All of the modes of the octave-spanning optical frequency comb are frequency-stabilized to a microwave frequency standard, where the carrier-envelope offset frequency is phase-locked with self-referencing of the comb. We investigate the methods of controlling carrier-envelope offset frequency in a chirped-mirror-dispersion-controlled mode-locked laser. The rotation of a pair of chirped mirrors is useful for setting the bias of carrier-envelope offset frequency. Although our mode-locked laser has a low pulse-repetition frequency of 150 MHz, a high signal-to-noise ratio in beats results in the direct measurement of beat frequency with a laser to be measured using a frequency counter, and enables us to phase lock carrier-envelope offset frequency merely by using a mixer analogously without the need for a prescaler, with a servo bandwidth at approximately 500 kHz. The uncertainty of our optical frequency measurement system, besides the uncertainty of microwave reference frequency, is 4×10-14, and is limited by the uncertainty of the rf synthesizer used for phase locking and by that of the beat frequency measurement. Frequency measurements of an iodine-stabilized frequency-doubled Nd:YAG laser at 532 nm, an iodine-stabilized He–Ne laser at 633 nm and a rubidium two-photon-absorption stabilized extended-cavity laser diode at 778 nm are conducted. The results contributed to the revision of the practical realization of the metre adopted by the International Conference on Weights and Measures (CIPM) in 2001.

Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4-one-based non-peptide luteinizing hormone-releasing hormone (LHRH) receptor antagonists are described. Starting with the thienopyridin-4-one derivative 26d (T-98475) an optimization study was performed, which resulted in the identification of a highly potent and orally bioavailable LHRH receptor antagonist, 3-(N-benzyl-N-methylaminomethyl)-7-(2,6-difluorobenzyl)-4,7-dihydro-2-[4-(1-hydroxy-1-cyclopropanecarboxamido)phenyl]-5-isobutyryl-4-oxothieno[2,3-b]pyridine (33c). Compound 33c displayed subnanomolar in vitro activities for the human receptor and its oral administration caused effective suppression of the plasma LH levels in castrated male cynomolgus monkeys. Furthermore, SAR studies revealed that a hydroxyalkylamido moiety on the 2-phenyl ring is virtually equivalent to an alkylureido moiety, at least in this series of compounds.

Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges that are induced by positive feedback action of estrogen secreted by the mature ovarian follicles. The central mechanism of positive feedback action of estrogen on GnRH/LH secretion, however, is not fully understood yet. The present study examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Metastin had a profound stimulation on LHsecretionbyactingonthepreopticarea(POA),wheremost GnRH neurons projecting to the median eminence are located, because injection of metastin into the third ventricle or POA increased plasma LH concentrations in estrogen-primed ovariectomized rats. Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to be colocalized with estrogen receptors with some fibers in the preoptic area (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and POA, respectively. The blockade of local metastin action in the POA with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the ARC showed a marked increase and c-Fos expression in the early proestrus afternoon compared with the day of diestrus. Thus, metastin released in the POA is involved in inducing the preovulatory LH surge and regulating estrous cyclicity. (Endocrinology 146: 4431–4436, 2005)

Prolactin-releasing peptide (PrRP) is a novel peptide found in bovine hypothalamus as an endogenous ligand of an orphan G-protein-coupled receptor (hGR3). It is known that PrRP is widely distributed and plays roles in the central nervous system (CNS). In particular, PrRP acts as a neurotransmitter that mediates stress and activates the hypothalamo-pituitary-adrenal axis. On the other hand, only a few studies have so far been performed on PrRP in peripheral tissues. Among peripheral tissues, appreciable levels of PrRP are found only in the adrenal gland; however, the PrRP-producing cells in the adrenal gland have not been identified. In this study, we detected PrRP mRNA in the rat adrenal medulla. So, we tried to identify the PrRP-producing cells in primary culture cells of the adrenal medulla. We found immunopositive PrRP cells among the cultured cells from the adrenal gland, but not in the adrenal gland tissue, by means of immunocytochemistry. The PrRP immunopositive cells were double positive for tyrosine hydroxylase (TH) and for phenylethanolamine N-methyltransferase (PNMT), which indicates that PrRP may be produced in a part of the adrenaline cells in the adrenal gland. This is the first report that PrRP is produced in the adrenaline-containing cells of the adrenal gland.

We have established an ensemble of iodine-stabilized Nd:YAG lasers to verify the frequency reproducibility of the laser. The stability, repeatability and several systematic shifts of the laser frequency are investigated by heterodyne beating of the lasers. The frequency dispersion of the ensemble of lasers is evaluated to be 0.5 kHz (corresponding to a relative frequency uncertainty of 8 × 10−13). The absolute frequency of one of the lasers (named as Y3) is measured to be 563 260 223 507 897(58) Hz using a femtosecond optical comb, when the laser was stabilized on the a10 component of the R(56)32-0 transition of 127I2 for a cold-finger temperature of −10 °C. This group of lasers, including one transportable laser, forms an ensemble of optical frequency standards, which serves for many applications such as international comparisons, optical frequency measurements, frequency calibration services and high-resolution spectroscopy.

It is possible that a high-temperature superconducting (HTS) bulk linear synchronous motor (LSM) can be propelled contactlessly with no guidance and levitation control. Its design and dynamics simulation are based on very complicated analysis of HTS bulk. This paper proposes HTS bulk LSM applied to ropeless linear elevator analyzed numerically taking into account the electric field-current density (E-J) characteristic in finite-element methods. The LSM can be propelled following command motion pattern with proportional-integral-derivative control and producing stable guidance force without its control.

We have proposed a new linear synchronous motor (LSM) theory which is based on an idea of considering the pinning force as synchronizing one in using current-carrying-armature-winding instead of permanent magnets. We have carried out basic experiments on two-dimensional electromagnetic forces produced in HTS bulk within DC-magnetic-field. As a result, we found that HTS bulk magnet in a cooling case can be levitated and guided stably according to the flux conditions between bulk and DC magnet. HTS bulk LSM can produce propulsion, levitation and guidance forces from zero speed, and be used in many applications. This paper proposes HTS bulk LSM analyzed and designed taking into account E–J characteristic. The LSM can produce stable guidance force without control. The LSM propulsion and guidance motion can be simulated numerically only by a simple propulsion control, which is not only closed-loop control but also open-loop control.