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Objective: In the largest avascular low-nutrient intervertebral disc, resident cells would utilize autophagy, a stress-response survival mechanism by self-digestion and recycling wastes. Our goal was to elucidate the involvement of autophagy in disc homeostasis through RNA interference of autophagy-related gene 5 (Atg5). Design: In vitro, small interfering RNAs (siRNAs) targeting autophagy-essential Atg5 were transfected into rat disc cells. Cell viability with levels of autophagy including Atg5 expression, apoptosis, and senescence was assessed under serum starvation and/or pro-inflammatory interleukin-1 beta (IL-1β) stimulation. In vivo, time-course autophagic flux was monitored following Alexa Fluor® 555-labeled Atg5-siRNA injection into rat tail discs. Furthermore, 24-h temporary static compression-induced disruption of Atg5 siRNA-injected discs was observed by radiography, histomorphology, and immunofluorescence. Results: In disc cells, three different Atg5 siRNAs consistently suppressed autophagy with Atg5 protein knockdown (mean 44.4% [95% confidence interval: −51.7, −37.1], 51.5% [−80.5, −22.5], 62.3% [−96.6, −28.2]). Then, Atg5 knockdown reduced cell viability through apoptosis and senescence not in serum-supplemented medium (93.6% [−0.8, 21.4]) but in serum-deprived medium (66.4% [−29.8, −8.6]) further with IL-1β (44.5% [−36.9, −23.5]). In disc tissues, immunofluorescence detected intradiscal signals for the labeled siRNA even at 56-d post-injection. Immunoblotting found 56-d autophagy suppression with prolonged Atg5 knockdown (33.2% [−52.8, −5.3]). With compression, Atg5 siRNA-injected discs presented radiographic height loss ([−43.9, −0.8]), histological damage ([−5.5, −0.2]), and immunofluorescent apoptosis ([2.2, 22.2]) and senescence ([4.1, 19.9]) induction compared to control siRNA-injected discs at 56 d. Conclusions: This loss-of-function study suggests Atg5-dependent autophagy-mediated anti-apoptosis and anti-senescence. Autophagy could be a molecular therapeutic target for degenerative disc disease.

High-throughput large-droplet sorting is demonstrated by an array of sequentially addressable dielectrophoretic sources., Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (

Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. Although STSS is mainly caused by Streptococcus pyogenes, group G streptococcus identified as S. dysgalactiae subsp. equisimilis (SDSE) causing STSS has also been reported; however, no study has analyzed >100 isolates of SDSE causing STSS. Therefore, we characterized the emm genotype of 173 SDSE isolates obtained from STSS patients in Japan during 2014–2016 and performed antimicrobial susceptibility testing using the broth microdilution method and emm gene typing. The predominant emm genotype was found to be stG6792, followed by stG485, stG245, stG10, stG6, and stG2078. These six genotypes constituted more than 75% of the STSS isolates. The proportion of each emm genotype in STSS isolates correlated with that in invasive isolates previously reported. We found that 16.2% of the isolates showed clindamycin resistance. The proportion of clindamycin-resistant SDSE isolates was significantly higher than that of S. pyogenes isolates. Thus, while treating STSS caused by SDSE, it is necessary to consider the possibility of clindamycin resistance and to ensure judicious use of the drug.

Severe adverse events (SAE) and late hematological malignancies have been reported after PBSC donation. No prospective data on incidence and risk factors have been available for family donors so far. The Japan Society for Hematopoietic Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory registration system. It defined standards for donor eligibility and asked harvest centers to report any SAE immediately. All donors were examined at day 30 and were to be contacted once each year for a period of 5 years. Acute SAEs within day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were reported from 39/1708 donors (2.3%). The incidence of acute SAEs was significantly higher among donors not matching the JSHCT standards (P=0.0023). Late hematological malignancies in PBSC donors were not different compared with a retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion, acute and late SAEs do occur in PBSC donors at relatively low frequency but risk factors can be defined.

Buried void layer formation in silicon substrates was achieved by hydrogen ion implantation followed by 940-nm infrared laser rapid heating. P-type silicon substrates coated with 100-nm-thick thermally grown SiO2 layers were implanted with hydrogen atoms at 5x10 15 and 3x10 16 cm -2 at 60 keV. Structural investigation with analysis of optical reflectivity spectra revealed that 3x10 16 cm -2 implantation caused a void layer with a void ratio of 0.04 at a depth of 250 nm close to the position of hydrogen peak concentration. Laser irradiation at 4.2x10 4 W/cm 2 increased the void ratio to 0.12. No void layer was observed at ion implantation stage for sample with 5x10 15 cm -2 -hydrogen atoms. Laser irradiation at 4.9x10 4 W/cm 2 formed a void layer with a void ratio of 0.013 at a depth of 255 nm.

The Ortho-to-Para abundance ratio (OPR) of cometary molecules is considered to be one of primordial characters of comeary ices, which has information concerning their formation. In order to determine the OPR of cometary ammonia (NH3), high-dispersion spectra in the optical wavelength region have been the most powerful tool, since NH2 is a photo-dissociation product of NH3 ,a nd NH 2 has a strong electronic transition in the optical region. Here we present an improved procedure to derive the OPR of NH2 (OPR of NH3 is derived from that of NH2) from the high-dispersion spectra of NH2 in comets. We consider (1) the contamination of NH2 lines by the C2 Swan-band lines, (2) the influence by the telluric absorption lines, and (3) multiple measurements of OPR from different vibronic bands of NH2 in the optical region, to achieve a more accurate determination of OPRs than that in previous studies. We applied the new method to the spectrum of comet C/2001 Q4 (NEAT) for which the OPR of NH2 was determined in the previous study. The derived OPR of NH2 is 3.23 ˙ 0.03, and this is more accurate than before. The OPR of NH3 is estimated to be 1.12 ˙ 0.02, which corresponds to a nuclear spin temperature (Tspin )o f 30 +2 � 1 K. The Tspin value of NH3 is basically consistent with the temperature inferred from the mixing ratio of CO with respect to H2O found in the same comet.

Various fast and efficient computation techniques for a power converter simulation have been researched. According to the conventional methods, a single step size for a whole circuit is selected for the numerical integration. A real-power electronic system, however, is multirate in that its currents and voltages nonuniformly vary spatially and temporally, and its subcircuits have different transient rates. A simulation that selected an appropriate step size for each subcircuit independently would, therefore, be more efficient. Several multirate analysis techniques have already been proposed; this paper proposes a new method that divides the whole circuit into subcircuits by applying an explicit integration formula to series inductors and/or parallel capacitors, and then integrates subcircuits by applying an implicit formula with independent integration step sizes. As analysis examples, this method is applied to an ac-dc converter, a benchmark test circuit, and a dc-link inverter control system. The proposed method's effectiveness at reducing computational steps and CPU times is investigated, and its performance and efficiency are validated.

Comet 73P/Schwasmann–Wachmann 3 (hereafter SW3) is known as a split comet, and its fragments are the best targets to investigate the homogeneity of a cometary nucleus. We conducted optical low-dispersion spectroscopic observations of the brightest fragments, B and C, of comet SW3 with the NAYUTA telescope in 2006 early May, in the vicinity of the closest approach to Earth on 2006 May 12, UT. We report on the chemical compositions of these fragments. Both fragments are similar to each other in composition, and are significantly depleted in C2 compared with other comets.

Numerical and experimental methods were employed to assess the individual and collective dosimetry of mice used in a bioassay on the exposure to pulsed radiofrequency energy at 900 MHz in the Ferris-wheel exposure system (Utteridge et al., Radiat. Res. 158, 357-364, 2002). Twin-well calorimetry was employed to measure the whole-body specific absorption rate (SAR) of mice for three body masses (23 g, 32 g and 36 g) to determine the lifetime exposure history of the mice used in the bioassay. Calorimetric measurements showed about 95% exposure efficiency and lifetime average whole-body SARs of 0.21, 0.86, 1.7 and 3.4 W kg(-1) for the four exposure groups. A larger statistical variation in SAR was observed in the smallest mice because they had the largest variation in posture inside the plastic restrainers. Infrared thermography provided SAR distributions over the sagittal plane of mouse cadavers. Thermograms typically showed SAR peaks in the abdomen, neck and head. The peak local SAR at these locations, determined by thermometric measurements, showed peak-to-average SAR ratios below 6:1, with typical values around 3:1. Results indicate that the Ferris wheel fulfills the requirement of providing a robust exposure setup, allowing uniform collective lifetime exposure of mice.

For more size reduction of the high temperature superconducting coplanar waveguide (CPW) bandpass filter (BPF), we introduce the design method of the meanderline quarter-wavelength resonator BPF. The admittance and impedance inverters (J- and K-inverters) are realized by using interdigital gaps and meanderline short stubs. Also, we estimate the slope parameter of the meanderline resonator by using EM-simulator. In order to control the attenuation poles, we adjust the meanderline intervals and shapes of the cross-coupling section, so that we can design the frequency and number of the attenuation poles. The size of the 6-pole CPW quarter-wavelength resonator with two attenuation poles (center frequency = 2 GHz) was 3.5 /spl times/ 8 mm.

Background: Formaldehyde (FA) is well documented as a cause of occupational asthma. Recently, attention has been paid to FA as an allergen and a pollutant that enhances allergic sensitization. We have investigated the prevalence of FA-specific IgE in asthmatic children and the correlation between IgE sensitization to FA and the severity of asthma. Methods: One hundred and fifty-five children were investigated, 122 of them asthmatic and 33 nonallergic. Specific IgE against FA was measured by CAP RAST. In addition, the patients answered a questionnaire, containing questions on clinical features of their asthma, their living conditions, and symptoms of mucosal irritation. Results: Of all the subjects assessed, FA-specific IgE was detected in only two asthmatics, and their IgE levels of FA were low (0.42 and 0.46 UA/ml). One of the two patients with FA-specific IgE had severe asthma and frequent symptoms of mucosal irritation, but the other had mild asthma and only rare symptoms of mucosal irritation. Conclusions: The prevalence of IgE sensitization to FA appears very low in Japanese children, whether or not they have asthma. Therefore, it appears likely that FA is not one of the major allergens causing childhood asthma.

The design and performance of a LiNbO/sub 3/ optical modulator and switch, which employ superconducting circuits, have been studied. Based on a novel design method of the booster circuit using superconducting coplanar waveguide transmission lines, we designed a voltage amplifier with center frequency of 10 GHz, bandwidth of 5 MHz, and the voltage gain of 33 dB using an electromagnetic wave simulator. We also designed a high speed optical switch combining optical directional coupler and Mach-Zehnder interferometer. A preliminary experiment with YBCO electrode on MgO substrate flip-chip-bonded on LiNbO/sub 3/ optical waveguide has been made.

Secondary ion mass spectrometry (SIMS) provides very sensitive chemical and elemental information. Nanoscale SIMS analysis is, however, very difficult to carry out by conventional methods, mainly because of the primary beam diameter and vibrations. In our work, we used the latest technology for focused ion beam (FIB) formation, which realizes nanoscale beam diameter. Our detection system (Mattauch–Herzog type mass-analyzer and 120-channel parallel detector) realizes highly sensitive parallel-mass-detection with parallel counting units. In order to minimize the influence of vibrations, the sample was mounted on the end cap of FIB column directly. Under this condition, the ion induced secondary electron image of a vacuum-evaporated Au film on a carbon plate was obtained without the influence of vibrations. The beam profile and a secondary ion image of the IC pattern was obtained using same geometry. The lateral resolution was estimated to be 30 nm at worst. As a result, simultaneous multi-elemental measurements on nanoscale dimension became possible.

Flow cytometry (FC) is widely utilized in the diagnosis of lymphoma and the light chain ratio (LCR) is especially useful in the diagnosis of B-cell malignancy. In this study we analysed, retrospectively, the predictive value of the LCR in the diagnosis of B-cell lymphoma in 105 consecutive patients with persistent lymph node enlargement or extranodal masses who underwent biopsy. We used a receiver-operating characteristic curve to establish a LCR threshold value of 2.0. The specificity, sensitivity, positive and negative predictive values were 92.3%, 73.1%, 90% and 77%, respectively. We concluded that determination of LCR is a useful adjunct to pathological diagnosis.

We presented optical and near-infrared multi-band linear polarimetry of the highly reddened Type Ia SN~2014J appeared in M82. SN~2014J exhibits large polarization at shorter wavelengths, e.g., $4.8$\% in $B$ band, and the polarization decreases rapidly at longer wavelengths, with the position angle of the polarization remaining at approximately $40^{\circ}$ over the observed wavelength range. These polarimetric properties suggest that the observed polarization is likely to be caused predominantly by the interstellar dust within M82. Further analysis shows that the polarization peaks at a wavelengths much shorter than those obtained for the Galactic dust. The wavelength dependence of the polarization can be better described by an inverse power law rather than by Serkowski law for Galactic interstellar polarization. These suggests that the nature of the dust in M82 may be different from that in our Galaxy, with polarizing dust grains having a mean radius of $, 8 pages, 4 figures, accepted for publication in ApJ Letters

A new design theory is presented of the high-T/sub c/ superconducting broadband booster circuit for a LiNbO/sub 3/ optical modulator. Based on this theory we studied the gain and bandwidth characteristics of the modulator using a transmission line model. We also designed the practical booster circuit using an electromagnetic wave simulator and demonstrated the optical modulator with broadband and high voltage gain as expected from the theory.

The aim of this study was to evaluate whether cisplatin sensitivity relates to patient's prognosis in oesophageal squamous cell carcinoma and to find a useful chemosensitivity molecular marker. 59 oesophageal squamous cell carcinoma (SCC) patients received cisplatin 30 mg/m 2 /week treatment of two to five cycles, followed by oesophagectomy. We analysed retrospectively whether the histological effect was related to patient's prognosis. Furthermore, to evaluate the relationship between the effect of preoperative cisplatin treatment and p53 and cyclin D1 expression, we investigated p53 and cyclin D1 expression in pretreatment biopsy samples using an immunohistochemical analysis and compared the results with the histological effect to cisplatin in the resected oesophagus. The cases that showed immunohistochemical p53 staining in the pretreatment biopsy samples were resistant to cisplatin ( P =0.032). However, there was no relationship between cyclin D1 expression and histological effect ( P =0.230). Nevertheless, combined analysis of p53 and cyclin D1 can predict histological effect ( P =0.032). The prognosis of cisplatin-sensitive cases was significantly better than that of cisplatin-resistant cases ( P =0.041). Cox's multivariate analysis revealed that the histological effect was an independent prognostic factor. In contrast, p53 protein accumulation and cyclin D1 were not. Histological response after neoadjuvant cisplatin treatment is a prognostic factor for oesophageal SCC and cisplatin chemotherapy may be selected according to the findings of p53 and cyclin D1 expression.

In the LHD (Large-scale Helical Device) system of National Institute far Fusion Science (NIFS), Toki, Gifu, Japan, the experiments using superconducting magnets with total stored energy of roughly 1.6 GJ are carried out. The LHD consists of nine coils those are fed by large-scale DC power supply. The superconducting bus-lines are connecting the power supply and coils with a length of about 50 m and a current capacity of 32 kA (rated current). As this bus-line has thick stabilizing barking metal (high purity Al), a resistive voltage generated at small normal-transitioned region is very small. Meanwhile, the inductive voltage noise induced by the external magnetic field or its own magnetic field is large because the length of the bus-line is large. Besides, the voltage detection leads cannot be attached directly just outside the conductors because of the thick thermal insulation and the care for electrical insulation. Therefore, it is difficult to decide the state of the superconducting bus-line only by the voltage signals, So, the authors proposed to introduce the Fuzzy theorem calculating the "dangerous rate" of the bus-line. In this system, not only the voltage signals of the bus-line but also the transport current and the liquid helium flow-rate in the bus-line are taken into consideration. The experimental result shows that the state of the bus-lines is well expressed by the "dangerous rate", and the bus-line has enough operation margin.

A 70-year-old woman was seen at the hospital because of an egg-sized mass at dorsal side of contralateral upper limb. There was previous history of undergoing a radical mastectomy for left breast cancer in the lower median quadrant 18 years before admission. The histological type was papillotubular adenocarcinoma (T2b N1b M0, Stage II) and she had remained free of disease except for left arm edema. After admission the mass was originally considered a malignant tumor derived from soft tissue because of its long interval after the initial surgery and rareness of recurrence of breast cancer on the site. A histological examination on the resected tumor revealed that it was rare distant recurrence of breast cancer and no other recurrence signs were detected by further clinical examination. Late phase recurrence of breast cancer occurs mainly at local skin or lymph nodes, but rarely at distant subcutaneous tissue. We report an uncommon case of late phase recurrence of breast cancer. It is worth while paying much attention to longer and more precise follow-up observation on bresat cancer patients.

The design and performance of a LiNbO/sub 3/ optical modulator employing low-loss superconducting electrodes as a transmission line for a traveling-wave signal have been studied. In the case of velocity matching between signal and optical waves using a shielding plane on top of a coplanar waveguide electrode, numerical calculations of the attenuation constants of superconducting transmission lines indicate that the performance of the optical modulator can be much superior to that using normal metals, with respect to the figure-of-merit of bandwidth/driving voltage in the case of extended coupling lengths. Microwave operation of a velocity-matched traveling-wave-type optical modulator with superconductor electrodes has been confirmed at low temperatures down to 4.2 K in the frequency range between DC and 26.5 GHz.

The performance of a LiNbO/sub 3/ optical modulator employing superconducting electrodes as a transmission line for a traveling-wave signal has been studied theoretically as well as experimentally. In the case of velocity matching between signal and optical waves using a shielding plane on top of a coplanar waveguide, numerical calculations of the attenuation constants of both superconducting and normal-conducting transmission lines indicate that the performance of the optical modulator can be far superior to that using normal-metals with respect to the figure of merit of bandwidth/driving-voltage. Microwave operation of a velocity-matched traveling-wave-type optical modulator with superconductor electrodes (NbN) has been successfully demonstrated. In the frequency range between dc and 26.5 [GHz] it is shown that the obtained modulation depth is in good agreement with the theoretically expected one.

In the LHD (Large-scale Helical Device) system, superconducting coils are fed by superconducting bus-lines. For sound operation of the LHD, a reliable quench detection system of the superconducting bus-lines is essential. The first difficulty for the quench detection is the lack of the voltage monitoring leads closely running along the conductors. The conductors of the bus-lines are covered by thick thermal insulation pipe. Taking care for the electrical insulation, no voltage lead is inserted inside the pipe. Therefore, one has to locate the voltage leads outside the pipe. This situation will bring heavy voltage noise induced by the stray magnetic field. So, the authors have proposed a voltage detection system which utilizes a noise cancellation technique. In this system, the difference of the voltage of the plus polarity lead and that of the minus one is monitored. The magnetically induced noises of both leads almost cancel each other in the monitoring voltage. All the voltage signals are converted to digital ones using 16-bit A/D converters, and processed digitally. These digitized voltage signals and other signals, like the current and liquid He, levels are input to PCs. The PCs carry out the fuzzy computation and calculate the "dangerous rate" which stands for the state of the superconducting bus-lines. To obtain further fine adjustment to minimize the noise voltage, a digital differentiation technique is also introduced. Experiments of the proposed fuzzy SC-bus monitoring system were carried out in May 1998, with the LHD system of NIFS, Told, Gifu, Japan. These experimental results are shown in this paper.

A self consistent method for evaluating the complex conductivities of high Tc superconducting Y-Ba-Cu-O(YBCO) thin films has been studied using the coplanar waveguide resonator technique. In order to evaluate the magnetic penetration depth precisely, we measured the temperature dependence of the resonant frequency and compared it with the numerical results self consistently. In the present experiments the observed temperature dependence of the complex conductivities is shown to be able to distinguish the effects of the weaklink from the intrinsic property of the grain of an epitaxial thin film and demonstrate the weakly coupled grain model of YBCO thin films.

Aerosol-size distributions of218Po were determined for the accelerator tunnel air sampled during machine operation and for the basement air of a concrete building, where the number and the size distribution of non-radioactive aerosols are greatly different from each other. The218Po distributions depended very much on the size distributions of ambient non-radioactive aerosols, and could be well explained by an attachment model of218Po to ambient non-radioactive aerosols.

Apolipoprotein A-I (apo A-I) stimulates human placental lactogen (hPL) release via protein kinase C (PKC)-dependent pathways. Since PKC has been shown to activate the MAP kinase cascade in other cell types, we examined the effect of two inhibitors of the MAP kinase cascade on apo A-I-induced hPL secretion and the effect of apo A-I on MAP kinase activity in human trophoblast cells. Apigenin (10 μM) and PD98059 (100 μM) inhibited apo A-I-induced hPL release by 94 and 73%, respectively. Moreover, apo A-I activated MAP kinase in a time- and dose-dependent manner. Activation of PKC by phorbol myristate acetate (PMA) stimulated MAP kinase activity, and down-regulation of PKC completely prevented apo A-I-stimulation of MAP kinase activity. Taken together, these results strongly suggest that activation of MAP kinase is involved in the intracellular mechanism of apo A-I-induced hPL release.

The human surface Ag CD38 is a 46-kDa type II transmembrane glycoprotein, and its expression is dependent on the cell differentiation and activation of lymphocytes. Our previous work in human myeloid cells showed that ligation of CD38 with mAbs (HB-7 and T-16; IgG1 subclass) not only induced protein-tyrosine phosphorylation but also potentiated superoxide generation stimulated by G protein-coupled receptors. In the present study we analyzed the mechanisms of action of the agonistic mAbs. HB-7-induced tyrosine phosphorylation could be still observed in human myeloid cells expressing CD38 mutants, of which cytoplasmic and transmembrane domains had been deleted or replaced by those of another type II glycoprotein (PC-1). Moreover, N-linked glycosylation on the cell surface CD38 was not required for the HB-7-induced cell signaling. The profile of tyrosine-phosphorylated proteins by HB-7 was exactly the same as that induced by cross-linking of FcgammaII receptors (FcgammaRII/CD32), and FcgammaRII itself was tyrosine phosphorylated in the two stimulated cells. The HB-7-induced tyrosine phosphorylation was completely abolished after masking of FcgammaRII with its mAb. Finally, F(ab')2 of HB-7 failed to mimic the actions of the whole form of mAb. These results indicate that anti-CD38 mAb-induced tyrosine phosphorylation and its associated cell response are entirely mediated through the FcgammaRII-induced signaling pathway, possibly resulting from stimulation of the cell surface human FcgammaRII with the mouse Fc region (IgG1 subclass) of CD38-ligated mAbs.

Microwave characteristics of a LiNbO/sub 3/ optical modulator employing a superconductor electrode (Nb) as a transmission line of a traveling signal has been studied experimentally in the temperature range from 300 K to 4.2 K. In the frequency range between dc and 26.5 GHz it is shown that the obtained modulation depth is in good agreement with the theoretically expected one. The present results demonstrate the possible applications of superconducting electrodes to high performance LiNbO/sub 3/ optical modulators.