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This paper discusses the impact of pump-phase noise in the χ (2) -based optical parametric amplification process on the phase-conjugated idler. We show that the dispersive fiber propagation of the phase-conjugated idler causes the optically enhanced pump-phase noise (OEPN) effect including a group-velocity jitter. The signal penalty caused by the OEPN in the mid-link optical phase conjugation systems was quantified analytically and proved by numerical simulations. We also experimentally evaluated the OEPN with an optical parametric phase conjugator using periodically poled LiNbO 3 waveguides. With a 96-Gbaud probabilistically constellation-shaped 64QAM signal, the experimental results were in good agreement with the analytically derived penalty in a standard single-mode fiber link up to 800 km.

A sensitive analytical technique was developed for determining a 10 -7 level low 236 U/ 238 U ratio using multicollector inductively coupled plasma mass spectrometry. This analytical technique can determine the subnanogram amount of uranium in safeguards environmental samples. To increase the sensitivity of the 236 U/ 238 U ratio, (1) the feed solution was concentrated to one-tenth of that in the conventional method and (2) data acquisition was started from the beginning of the solution uptake until all of the solution was exhausted. All signal intensities were recorded. This technique was applied to the IRMM-184 uranium isotopic standard solution with a 1.2410 × 10 -7 236 U/ 238 U ratio. The IRMM-184 uranium solution (0.2 mL of 1 ng g -1 uranium) was prepared, and the 236 U/ 238 U ratios were determined using our new data collection method. The 236 U/ 238 U ratios were in agreement with the certified value within the uncertainty ( k = 2) evaluated using the Guide to the Expression of Uncertainty in Measurement (GUM) workbench. The uncertainties obtained with this new technique (32% on average) were revised to be 10 times smaller than those obtained with the conventional method using 0.1 ng g -1 IRMM-184. The tailing effect from the 238 U intense peak was determined using 10 times higher concentrations of NBL CRM U0002 uranium isotopic standard solution (10 ng g -1 uranium) to improve its uncertainty. Approximately 1-2% of the uncertainties of 236 U/ 238 U could be further reduced using this improved correction factor.

Wideband signal amplification and optical signal processing with a high gain using an optical parametric amplifier based on a periodically poled LiNbO 3 (PPLN) waveguide is attractive for constructing wideband optical fiber networks. We experimentally investigate the transfer characteristics of the phase noise of a pump laser in χ (2) -based optical parametric amplification and wavelength conversion on the basis of second-harmonic-generation and differential-frequency-generation processes. We also evaluate the effect of the transferred phase noise on signal quality in dispersion-unmanaged digital coherent fiber transmission systems. We show that the phase noise is transferred only to the wavelength-converted idler and does not affect the amplified signal even by using a pump laser with a MHz-order linewidth. We also show that the phase noise transferred to the idler light can have a similar impact on signal quality as equalization-enhanced phase noise (EEPN) in digital coherent transmission. The signal penalty including EEPN was evaluated with several pump lasers and at symbol rates of 32, 64, and 96 Gbaud. We also propose a method of using correlated pump lights between a wavelength converter pair to cancel out the transfer of phase noise.

We present computationally-efficient implementation techniques of multiple-input multiple-output (MIMO) frequency-domain equalization (FDE) that deals with a modal dispersion effect underlying in long-haul mode-division-multiplexed (MDM) signal transmission. Computational complexity reduction comes from twofold approaches: the first is out-of-band-exclusive (OBE) FDE for removing redundant computations in MIMO-FDE processing by taking a practical signal bandwidth occupation into account. A second appoarch, referred to as overlapping-reduced (OR) FDE, further reduces the complexity by modifying an overlapping ratio in the overlap-and-save FDE method to below 0.5. We show that OBE-FDE reduces complexity for processing with a larger number of spatial channels compared with the conventional FDE, and that the overlapping ratio is minimized up to 0.25 by the OR-FDE approach. Also shown is an experimental demonstration using the results of three-mode MDM transmission with different inter-mode coupling scenarios, verifying that the complexity is decreased by up to 37 % with negligible deterioration in signal performance by using the proposed method.

Phase-sensitive amplifiers (PSAs) via the optical parametric amplification (OPA) process are capable of near-noiseless amplification, which can improve the performance of optical communications systems. OPA based on periodically poled lithium niobate (PPLN) waveguides is a proven means to implement a PSA with low additional nonlinear effects, such as frequency chirp, stimulated Brillouin scattering, and parametric crosstalk due to unwanted nonlinear interactions among pump and other signal waves. However, fiber compatibility is a challenge because optical coupling loss between a fiber and PPLN waveguide limits essential performance such as the gain and noise figure (NF), which makes PSAs still far from being practical. In this work, we developed a PPLN-waveguide-based pump-combiner-integrated OPA module with fiber input and output ports. With our recent development and optimization of the OPA module, we demonstrated high-performance phase-sensitive amplification with a gain of over 30 dB and an NF of 1.0 dB. In addition, we observed a 3-dB gain bandwidth of over 65 nm and flat NF characteristics in that wavelength band. The high conversion efficiency and high damage resistance of the PPLN waveguide, obtained by employing direct bonding and dry etching techniques, provide a high parametric gain. The low-loss coupling for the signal and pump between the fiber and a spot-size-converter-integrated PPLN waveguide through the dichroic beam combiner improve not only the gain but also the NF of the amplifier. Using the PSA as a preamplifier, the low-noise characteristics were confirmed by the sensitivity improvement provided by the low NF value.

We propose a novel phase recovery scheme designed for coherent space division multiplexing (SDM) systems with independently-operated asynchronous light sources. The proposed scheme is based on the approach of the extended Kalman filter and is referred to as multiple-input multiple-output carrier phase recovery (MIMO-CPR). In the minimum mean squared error (MMSE) sense, it simultaneously and optimally obtains estimates of the multiple phase errors arising from phase-unlocked asynchronous light sources. To ensure the scheme's application for SDM fibers with a time-varying property, we also describe a modification to incorporate a MIMO equalization scheme and analyze the computational complexity. The performance of the proposed MIMO-CPR scheme is investigated through numerical simulation, which shows that it has a tolerance for the sum linewidth symbol duration product of up to 3.4 × 10 -4 , 1.0 × 10 -4 and 2.2 × 10 -5 for QPSK, 16QAM, and 64QAM signals, respectively, if 1-dB optical signal-to-noise ratio (OSNR) penalty is allowable to achieve BER of 10 -3 . Transmission experimental results using three spatial modes in a 51-km-long few-mode fiber (FMF) also verify the applicability of the MIMO-CPR scheme to carrier-asynchronous coherent SDM-MIMO systems.

We experimentally demonstrate an ultra-low-noise pre-amplification using a non-degenerate phase-sensitive amplifier (ND-PSA) with an optically dispersion-unmanaged link. Chromatic dispersion (CD) compensation is required for phase-sensitive amplification after fiber transmission. In the conventional transmitter configuration for ND-PSAs in which phase-conjugated light (idler light) is optically generated, it is necessary to optically compensate for the CD, for example, by using dispersion-compensating fibers. In this work, we propose an ND-PSA scheme using a digitally generated idler and CD pre-equalization by means of digital signal processing. We conduct an unrepeated transmission over a 200-km single-mode fiber with a 10-Gbaud 64QAM signal using the periodically poled LiNbO 3 -based PSA. The experimental results demonstrate that the proposed ND-PSA scheme provides a low-noise pre-amplification that outperforms the EDFA without optical CD compensation.

The treatment of skeletal deep bite does not remain stable. The patient was a Japanese woman aged 16 years and 10 months. Her chief complaint was maxillary protrusion. The degree of overjet was + 10.5 mm and overbite was + 5.0 mm; the intermolar relationship was Angle Class II. An excessive curve of Spee was observed in the mandibular arch. A hypodivergent skeletal pattern was indicated by a small mandibular plane angle and gonial angle. The maxillary incisors were proclined and the mandibular incisors were retroclined. Based on the above findings, the patient was diagnosed with Angle Class II maxillary protrusion and deep bite with hypodivergency. Both maxillary first premolars were extracted and orthodontic treatment was performed using multi-bracket appliances. A proper overbite was achieved by 5.0 mm intrusion of the mandibular incisors. The maxillary incisors were retracted by 11.2 mm and a proper overjet was achieved. Good treatment results were obtained without apical root resorption. After 2 years of retention, the occlusion has been well maintained. This report may constitute a remarkable suggestion for treatment of an unstable deep bite., (Copyright © 2019 CEO. Published by Elsevier Masson SAS. All rights reserved.)

Simple high-speed optical transmission technologies are desired for use in intra-and inter-datacenter networks. In this study, we demonstrate simple single-carrier intensity-modulated direct-detection (IMDD) transmissions at a net data rate of 400 Gbps (516.7 Gbps gross) over 20 km with a compact transmitter subassembly. The subassembly consists of a 2:1 analog multiplexer (AMUX) and an InP Mach-Zehnder modulator (MZM) placed close to each other and connected via wires. We employed 162-Gbaud single-carrier probabilistically shaped pulsed amplitude modulation (PS-PAM). The baseband signals with a bandwidth of around 81 GHz to drive the MZM were generated by a super-digital-to-analog converter (super-DAC) consisting of two sub-DACs and the AMUX. Digital nonlinear pre-distortion enabled us to transmit the signals with normalized generalized mutual information (NGMI) larger than the threshold of a soft-decision forward error correction (SD-FEC) code of 0.857. Truncation of the PS-PAM symbol distribution further enhanced performance. To the best of our knowledge, this is the first net-400-Gbps single-carrier IMDD transmission using a compact transmitter subassembly.

Background: Osteoclasts play a critical role in bone resorption due to orthodontic tooth movement (OTM). In OTM, a force is exerted on the tooth, creating compression of the periodontal ligament (PDL) on one side of the tooth, and tension on the other side. In response to these mechanical stresses, the balance of receptor activator of nuclear-factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) shifts to stimulate osteoclastogenesis. However, the mechanism of OPG expression in PDL cells under different mechanical stresses remains unclear. We hypothesized that compression and tension induce different microRNA (miRNA) expression profiles, which account for the difference in OPG expression in PDL cells. To study miRNA expression profiles resulting from OTM, compression force (2 g/cm 2 ) or tension force (15% elongation) was applied to immortalized human PDL (HPL) cells for 24 h, and miRNA extracted. The miRNA expression in each sample was analyzed using a human miRNA microarray, and the changes of miRNA expression were confirmed by real-time RT-PCR. In addition, miR-3198 mimic and inhibitor were transfected into HPL cells, and OPG expression and production assessed., Results: We found that certain miRNAs were expressed differentially under compression and tension. For instance, we observed that miR-572, - 663, - 575, - 3679-5p, UL70-3p, and - 3198 were upregulated only by compression. Real-time RT-PCR confirmed that compression induced miR-3198 expression, but tension reduced it, in HPL cells. Consistent with previous reports, OPG expression was reduced by compression and induced by tension, though RANKL was induced by both compression and tension. OPG expression was upregulated by miR-3198 inhibitor, and was reduced by miR-3198 mimic, in HPL cells. We observed that miR-3198 inhibitor rescued the compression-mediated downregulation of OPG. On the other hand, miR-3198 mimic reduced OPG expression under tension. However, RANKL expression was not affected by miR-3198 inhibitor or mimic., Conclusions: We conclude that miR-3198 is upregulated by compression and is downregulated by tension, suggesting that miR-3198 downregulates OPG expression in response to mechanical stress.

Introduction: The purpose of this study was to examine growth-promoting effects of myo-inositol nutritional supplementation on the mandible in experimental animals., Methods: Mice were fed on diets that contained various concentration of myo-inositol for 3 to 12 weeks. The length of the mandible, maxilla, and femur were measured on μCT images. The mandible and tibia were examined histologically and immunohistochemically. The effects of myo-inositol on cell proliferation and chondrocytic differentiation were examined using ATDC5 cells., Results: Myo-inositol supplementation had no effects on body weight, length, and maxilla and femur lengths. However, the length of mandible and the thickness of the mandibular condylar cartilage (MCC) were increased by myo-inositol supplement. Microarray analysis revealed that Pik3cd was highly expressed in MCC as compared to that in the cartilage of the tibial growth plate, which was confirmed by real-time RT-PCR and immunohistochemistry. ATDC5 cells also highly expressed Pik3CD. Myoinositol induced increases in cell proliferation and chondrocytic differentiation in ATDC5 cells. The addition of a PIK3CD inhibitor blocked the induction of cell proliferation by myo-inositol in ATDC5 cells., Conclusions: Nutritional supplementation with myo-inositol in growing mice augmented mandibular endochondral growth without any systemic effects. The specific promotion of mandibular growth by myoinositol is primarily dependent on the specific intensive expression of PIK3CD in the MCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Osteoclastic bone resorption enables orthodontic tooth movement (OTM) in orthodontic treatment. Previously, we demonstrated that local epigallocatechin gallate (EGCG) injection successfully slowed the rate of OTM; however, repeat injections were required. In the present study, we produced a liquid form of EGCG-modified gelatin (EGCG-GL) and examined the properties of EGCG-GL with respect to prolonging EGCG release, NF-E2-related factor 2 (Nrf2) activation, osteoclastogenesis inhibition, bone destruction, and OTM. We found EGCG-GL both prolonged the release of EGCG and induced the expression of antioxidant enzyme genes, such as heme oxygenase 1 (Hmox1) and glutamate-cysteine ligase (Gclc), in the mouse macrophage cell line, RAW264.7. EGCG-GL attenuated intracellular reactive oxygen species (ROS) levels were induced by the receptor activator of nuclear factor-kB ligand (RANKL) and inhibited RANKL-mediated osteoclastogenesis in vitro. An animal model of bone destruction, induced by repeat Lipopolysaccharide (LPS)-injections into the calvaria of male BALB/c mice, revealed that a single injection of EGCG-GL on day-1 could successfully inhibit LPS-mediated bone destruction. Additionally, experimental OTM of maxillary first molars in male mice was attenuated by a single EGCG-GL injection on day-1. In conclusion, EGCG-GL prolongs the release of EGCG and inhibits osteoclastogenesis via the attenuation of intracellular ROS signaling through the increased expression of antioxidant enzymes. These results indicate EGCG-GL would be a beneficial therapeutic approach both in destructive bone disease and in controlling alveolar bone metabolism.

Acquired open bite mainly occurs after adolescence and is caused by a pathological or biological process. We herein report the case of an 18-year and 10-month-old Japanese woman. Her chief complaint was difficulty with mastication. Only distal cusps of first molars and second molars had contact. An angle class II molar relationship and extreme mesially inclined mandibular first molars were observed. The degree of overjet was +6.1mm and overbite was -2.0mm. There were no symptoms or abnormal findings in temporomandibular joints by radiography and magnetic resonance imaging. A skeletal class II jaw relationship was indicated. Therefore, the patient was diagnosed with a skeletal class II acquired open bite malocclusion accompanied with extreme mesial inclination of mandibular first molars. Orthodontic treatment with extraction of maxillary first premolars was performed. After stabilizing the maxillary dental arch, mandibular molars were uprighted and intruded by class III elastics. After treatment, overjet was +3.0mm and overbite was +2.3mm. Occlusal cusp-fossa relationships were established and canine relationships were class I. The lower occlusal plane and mandible were rotated counterclockwise, which helped to achieve proper overbite. After 2 years of retention, occlusion was well maintained., (Copyright © 2018 CEO. Published by Elsevier Masson SAS. All rights reserved.)

We propose and demonstrate a hybrid cladding-pumped multicore erbium-doped fiber amplifier (EDFA) and distributed Raman amplification for space division multiplexing transmission systems. The cladding-pumped multicore EDFA is used to efficiently amplify signals in multiple cores simultaneously, while Raman pumping is used to control loss in each core individually. We construct an in-line amplified 7-core transmission line, and show that distributed Raman amplification can compensate loss variation between cores. Furthermore, we transmit 46 WDM PDM-16QAM signals over a long distance of greater than 1000 km and demonstrate good transmission performance.

Bone destructive diseases are common worldwide and are caused by dysregulation of osteoclast formation and activation. During osteoclastogenesis, reactive oxygen species (ROS) play a role in the intracellular signalling triggered by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Previously, we demonstrated that induction of antioxidant enzymes by Nrf2 activation using Nrf2-gene transfer, an ETGE-peptide or polyphenols, successfully ameliorated RANKL-dependent osteoclastogenesis. Dimethyl fumarate (DMF) has been shown to activate Nrf2 signalling and has been lately used in clinical trials for neurodegenerative diseases. In this study, we hypothesized that Nrf2 activation by DMF would inhibit osteoclastogenesis and bone destruction via attenuation of intracellular ROS signalling through antioxidant mechanisms. RAW 264.7 cells were used as osteoclast progenitor cells. We found that DMF induced Nrf2 translocation to the nucleus, augmented Nrf2 promoter-luciferase reporter activity and increased antioxidant enzyme expression. Using flow cytometry, we found that DMF attenuated RANKL-mediated intracellular ROS generation, which resulted in the inhibition of RANKL-mediated osteoclastogenesis. Local DMF injection into the calvaria of male BALB/c mice resulted in attenuated bone destruction in lipopolysaccharide-treated mice. In conclusion, we demonstrated in a preclinical setting that DMF inhibited RANKL-mediated osteoclastogenesis and bone destruction via induction of Nrf2-mediated transcription of antioxidant genes and consequent decrease in intracellular ROS levels. Our results suggest that DMF may be a promising inhibitor of bone destruction in diseases like periodontitis, rheumatoid arthritis and osteoporosis., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Introduction: The purpose of this study was to investigate whether a local unilateral IGF-1 injection into the mandibular condylar cavity can induce unilateral endochondral mandibular growth without any systemic adverse effects., Methods: Seventy-five 3-week-old male Jcl:ICR mice were used in this study. The mice were divided into 2 groups: control group (n = 22) and IGF-1 group (n = 53). In the IGF-1 group, human IGF-1 was injected into the right mandibular condylar cavity, and phosphate-buffered saline solution was injected into the left cavity, 3 times per week for 10 weeks., Results: There was no significant difference in body weight, serum human IGF-1 concentration, and soft tissue thickness of the cheeks including the masseter muscles between the 2 groups. Unilateral IGF-1 injection induced a lateral shift of the mandible to the contralateral side, and microcomputed tomogtraphy analysis showed that unilateral IGF-1 injection induced endochondral growth in the condyle. Col2, Ihh, and Runx2 were extensively upregulated by the local unilateral IGF-1 injection in real-time reverse transcription polymerase chain reaction analysis. Proliferation marker KI67, IGF-1 signaling molecule AKT1, and chondrogenic differentiation marker Col2 were strongly expressed in the IGF-1 injected condyle by immunohistochemistry. Vital labeling showed that the distance between the labels was increased in the IGF-1 injection group compared with that of the control group., Conclusions: The results verified in this study indicated that local unilateral IGF-1 injection into the mandibular condylar cavity successfully induced unilateral endochondral mandibular growth in mice without any systemic adverse effects. Thus, local unilateral IGF-1 injection into the mandibular condylar cavity could be a useful alternative for mandibular asymmetry therapy during the growth period. However, additional experimental and clinical studies will be necessary to prove the real effect of this new therapy., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Mandibular condylar cartilage (MCC) exhibits dual roles both articular cartilage and growth center. Of many growth factors, TGF-β has been implicated in the growth of articular cartilage including MCC. Recently, Asporin, decoy to TGF-β, was discovered and it blocks TGF-β signaling. Asporin is expressed in a variety of tissues including osteoarthritic articular cartilage, though there was no report of Asporin expression in MCC. In the present study, we investigated the temporal and spatial expression of Asporin in MCC. Gene expression profile of MCC and epiphyseal cartilage in tibia of 5 weeks old ICR mice were firstly compared with microarray analysis using the laser capture microdissected samples. Variance of gene expression was further confirmed by real-time RT-PCR and immunohistochemical staining at 1,3,10, and 20 weeks old. TGF-β and its signaling molecule, phosphorylated Smad-2/3 (p-Smad2/3), were also examined by immunohistochemical staining. Microarray analysis revealed that Asporin was highly expressed in MCC. Real-time RT-PCR analysis confirmed that the fibrous layer of MCC exhibited stable higher Asporin expression at any time points as compared to epiphyseal cartilage. This was also observed in immunohistochemical staining. Deeper layer in MCC augmented Asporin expression with age. Whereas, TGF-β was stably highly observed in the layer. The fibrous layer of MCC exhibited weak staining of p-Smad2/3, though the proliferating layer of MCC was strongly stained as compared to epiphyseal cartilage of tibia at early time point. Consistent with the increase of Asporin expression in the deeper layer of MCC, the intensity of p-Smad-2/3 staining was decreased with age. In conclusion, we discovered that Asporin was stably expressed at the fibrous layer of MCC, which makes it possible to manage both articular cartilage and growth center at the same time.

Periodontitis, an inflammatory disease that affects the tissues surrounding the teeth, is a common disease worldwide. It is caused by a dysregulation of the host inflammatory response to bacterial infection, which leads to soft and hard tissue destruction. In particular, it is the excessive inflammation in response to bacterial plaque that leads to the release of reactive oxygen species (ROS) from neutrophils, which, then play a critical role in the destruction of periodontal tissue. Generally, ROS produced from immune cells exhibit an anti-bacterial effect and play a role in host defense and immune regulation. Excessive ROS, however, can exert cytotoxic effects, cause oxidative damage to proteins, and DNA, can interfere with cell growth and cell cycle progression, and induce apoptosis of gingival fibroblasts. Collectively, these effects enable ROS to directly induce periodontal tissue damage. Some ROS also act as intracellular signaling molecules during osteoclastogenesis, and can thus also play an indirect role in bone destruction. Cells have several protective mechanisms to manage such oxidative stress, most of which involve production of cytoprotective enzymes that scavenge ROS. These enzymes are transcriptionally regulated via NRF2, Sirtuin, and FOXO. Some reports indicate an association between periodontitis and these cytoprotective enzymes' regulatory axes, with superoxide dismutase (SOD) the most extensively investigated. In this review article, we discuss the role of oxidative stress in the tissue destruction manifest in periodontitis, and the mechanisms that protect against this oxidative stress.

Isotope ratio analysis of individual uranium-plutonium (U-Pu) mixed oxide particles contained within environmental samples taken from nuclear facilities is proving to be increasingly important in the field of nuclear safeguards. However, isobaric interferences, such as 238 U with 238 Pu and 241 Am with 241 Pu, make it difficult to determine plutonium isotope ratios in mass spectrometric measurements. In the present study, the isotope ratios of 238 Pu/ 239 Pu, 240 Pu/ 239 Pu, 241 Pu/ 239 Pu, and 242 Pu/ 239 Pu were measured for individual Pu and U-Pu mixed oxide particles by a combination of alpha spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). As a consequence, we were able to determine the 240 Pu/ 239 Pu, 241 Pu/ 239 Pu, and 242 Pu/ 239 Pu isotope ratios with ICP-MS after particle dissolution and chemical separation of plutonium with UTEVA resins. Furthermore, 238 Pu/ 239 Pu isotope ratios were able to be calculated by using both the 238 Pu/( 239 Pu+ 240 Pu) activity ratios that had been measured through alpha spectrometry and the 240 Pu/ 239 Pu isotope ratios determined through ICP-MS. Therefore, the combined use of alpha spectrometry and ICP-MS is useful in determining plutonium isotope ratios, including 238 Pu/ 239 Pu, in individual U-Pu mixed oxide particles., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We propose a novel simple space division multiplexing (SDM) node which is rearrangeble nonblocking, and effectively utilizes enhanced network resources through SDM. The proposed node can reduce a number of ports of wavelength selective switches (WSSs) and a number of WSS modules by modifying conventional multi-stage switches and employing integrated multiple arrayed WSSs. We experimentally actualized the newly proposed node, and demonstrate wavelength, core, and direction switching functions based on 127-Gbps Dual Polarization Quadrature Phase Shift Keying (DP-QPSK) signals. We also confirm the feasibility of the proposed SDM node through SDM transmission experiments using a 40-km multicore fiber and a multicore amplifier.

Reactive oxygen species (ROS) play a role in intracellular signaling during osteoclastogenesis. We previously reported that transcriptional factor nuclear factor E2-related factor 2 (Nrf2) was exported from the nucleus to the cytoplasm by receptor activator of nuclear factor-κB ligand (RANKL), and that Nrf2 negatively regulated osteoclastogenesis via antioxidant enzyme up-regulation. Knockout mice of BTB and CNC homology 1 (Bach1)-the competitor for Nrf2 in transcriptional regulation-was known to attenuate RANKL-mediated osteoclastogenesis, although the mechanism remains unclear. Therefore, we hypothesized that RANKL could be involved in the nuclear translocation of Bach1, which would attenuate Nrf2-mediated antioxidant enzymes, thereby augmenting intracellular ROS signaling in osteoclasts. RANKL induced Bach1 nuclear import and Nrf2 nuclear export. Induction of Bach1 nuclear export increased Nrf2 nuclear import, augmented antioxidant enzyme expression, and, thus, diminished RANKL-mediated osteoclastogenesis via attenuated intracellular ROS signaling. Finally, an in vivo mouse bone destruction model clearly demonstrated that induction of Bach1 nuclear export inhibited bone destruction. In this study, we report that RANKL favors osteoclastogenesis via attenuation of Nrf2-mediated antioxidant enzyme expression by competing with Bach1 nuclear accumulation. Of importance, induction of Bach1 nuclear export activates Nrf2-dependent antioxidant enzyme expression, thereby attenuating osteoclastogenesis. Bach1 nuclear export might be a therapeutic target for such bone destructive diseases as rheumatoid arthritis, osteoporosis, and periodontitis.-Kanzaki, H., Shinohara, F., Itohiya, K., Yamaguchi, Y., Katsumata, Y., Matsuzawa, M., Fukaya, S., Miyamoto, Y., Wada, S., Nakamura, Y. RANKL induces Bach1 nuclear import and attenuates Nrf2-mediated antioxidant enzymes, thereby augmenting intracellular reactive oxygen species signaling and osteoclastogenesis in mice., (© FASEB.)

Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases.

It has been reported that reactive oxygen species (ROS), such as hydrogen peroxide and superoxide, take part in osteoclast differentiation as intra-cellular signaling molecules. The current assumed signaling cascade from RANK to ROS production is RANK, TRAF6, Rac1, and then Nox. The target molecules of ROS in RANKL signaling remain unclear; however, several reports support the theory that NF-κB signaling could be the crucial downstream signaling molecule of RANKL-mediated ROS signaling. Furthermore, ROS exert cytotoxic effects such as peroxidation of lipids and phospholipids and oxidative damage to proteins and DNA. Therefore, cells have several protective mechanisms against oxidative stressors that mainly induce cytoprotective enzymes and ROS scavenging. Three well-known mechanisms regulate cytoprotective enzymes including Nrf2-, FOXO-, and sirtuin-dependent mechanisms. Several reports have indicated a crosslink between FOXO- and sirtuin-dependent regulatory mechanisms. The agonists against the regulatory mechanisms are reported to induce these cytoprotective enzymes successfully. Some of them inhibit osteoclast differentiation and bone destruction via attenuation of intracellular ROS signaling. In this review article, we discuss the above topics and summarize the current information available on the relationship between cytoprotective enzymes and osteoclastogenesis., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

We experimentally demonstrated the simultaneous nonlinearity mitigation of PDM-16QAM WDM signals using complementary-spectrally-inverted optical phase conjugation (CSI-OPC). We achieved reserved-band-less, guard-band-less, and polarization independent OPC based on periodically poled LiNbO 3 waveguides. By employing the CSI-OPC, 2.325-THz-band (93 × 25 GHz) complementary spectral inversion was achieved while retaining the original WDM bandwidth. A Q 2 -factor improvement of over 0.4 dB and a 5120 km transmission with a Q 2 -factor above the FEC limit were confirmed using a 10-channel WDM transmission at the signal band center and signal band edge. We then demonstrated the mitigation of the nonlinear impairments in a 3840 km long-haul WDM signal transmission for all 92-channel 180-Gbit/s PDM-16QAM quasi-Nyquist-WDM signals.

Carpal tunnel syndrome (CTS) is a common peripheral entrapment neuropathy of the median nerve at wrist level, and is thought to be caused by compression of the median nerve in the carpal tunnel. There is no standard quantitative reference for the diagnosis of CTS. Grey-scale sonography and sonoelastography (SEL) have been used as diagnostic tools. The most commonly agreed findings in grey-scale sonography for the diagnosis of CTS is enlargement of the median nerve cross-sectional area (CSA). Several authors have assessed additional parameters. "Delta CSA" is the difference between the proximal median nerve CSA at the pronator quadratus and the maximal CSA within the carpal tunnel. The "CSA ratio" is the ratio of CSA in the carpal tunnel to the CSA at the mid forearm. These additional parameters showed better diagnostic accuracy than CSA measurement alone. Recently, a number of studies have investigated the elasticity of the median nerve using SEL, and have shown that this also has diagnostic value, as it was significantly stiffer in CTS patients compared to healthy volunteers. In this review, we summarize the usefulness of grey-scale sonography and SEL in diagnosing CTS.

Age of individual uranium-plutonium (U/Pu) mixed particles with various U/Pu atomic ratios (1-70) were determined by inductively coupled plasma mass spectrometry. Micron-sized particles were prepared from U and Pu certified reference materials. The Pu reference was stored for 4-6 years since the last purification (July 14, 2008). The Pu purification age was obtained from the (241)Am/(241)Pu ratio which was calculated from the product of three measured ratios of Pu and Am isotopes in the eluted fractions. These ratios were measured by a high-resolution inductively coupled plasma mass spectrometer equipped with a desolvation system. Femto-gram to pico-gram quantities of Am, U, and Pu in a sample solution were sequentially separated on a small anion-exchange column. The (241)Am/(241)Pu ratio was accurately determined by spiking pure (243)Am into the sample solution. The average determined age for the particles for the five independent U/Pu ratios was in good agreement with the expected age with high accuracy (difference age 0.27 years) and high precision (standard deviation 0.44 years). The described analytical technique can serve as an effective tool for nuclear safeguards and environmental radiochemistry. Figure Young (4-6 y) Pu purification age of individual U/Pu mixed micron-sized reference particles for the five independent U/Pu ratios (1-70) were determined with 0.27±0.44 y difference from the expected age. Sub pico-gram quantities of Am, U and Pu were sequentially separated a small column, and their isotope ratios were accurately measured using an ICP-MS by applying the (243)Am spiking technique to the analysis and correcting the impurity and the contaminations.

Uranium, thorium, lead, and the lanthanides were automatically and sequentially separated with a single anion-exchange column. This separation was achieved using eluents consisting of a simple and highly pure acid mixture of HCl, HNO3, acetic acid, and HF. The elements of interest were separated from the major constituents, which included alkaline metal elements, alkaline earth metal elements, and iron. This simple and automatic system is driven with pressurized nitrogen gas and controlled using a computer program. An optimized separation was accomplished under the following conditions: a 50 mm long and 2 mm diameter column, 11 μm diameter anion-exchange resin, and a 35 μL min(-1) flow rate. Using this system, 50 ng of varied elements in a 100 μL feed solution were perfectly separated within 5 h with >400 decontamination factors and >95% yield. In order to evaluate the performance of this system, a reference powdered rock sample was separated using this system. Abundances of objective elements, including 0.23 ng of lutetium, were accurately determined without corrections of chemical recovery yield or subtraction of the process blank. This separation technique saves time and effort for chemical processing, and is useful for ultra-trace quantitative and isotopic analyses of elements in small environmental samples.

Unlabelled: This case report describes the importance of preventing more excessive transverse dental compensation during orthodontic treatment for a patient with severe transverse skeletal discrepancy., Summary: The patient, a 33-years-old Japanese woman, had severe transverse skeletal discrepancy involving the maxilla and mandible. In addition, she had an extreme transverse dental compensation of the posterior teeth in mandibular arch (i.e. excessive lingual inclination of mandibular molars)., Aim: Therefore, the main treatment objectives were to prevent more excessive transverse dental compensation by orthodontic treatment and improve the occlusal function., Method: We chose non-surgical orthodontic treatment. Because this patient did not think that the esthetic improvement with surgery would be worth the risk., Result: The orthodontic treatment resulted in sufficient elimination of the transverse dental compensation and movement of the teeth into their proper position where basal bone firmly support them. Anterior crossbite was corrected with remaining buccal crossbite, facial profile was improved and functional occlusion was obtained. At 2 years 2 months after the orthodontic treatment, the facial profile and occlusion remained favorable., Conclusion: This report would become an alternative to ideal treatment for a case with transverse skeletal discrepancy.

We generated a 1-Tb/s single-carrier PDM-16QAM signal using a single optical modulator with external PDM emulation. To achieve the high symbol rate of 125 Gbaud, we used high-speed InP MUX-DAC modules, each consisting of six 2:1 MUXs and a 6-bit DAC in a single package, and an integrated optical modulator, which contains a generator of two orthogonal CSRZ pulse trains for spectrally efficient OTDM followed by IQ modulators for each tributary. The signal was received and demodulated without using any time-domain demultiplexing. Transmission over 80-km SSMF was demonstrated.

We report the design and fabrication of a compact multi-core fiber fan-in/fan-out using a grating coupler array on the SOI platform. The grating couplers are fully-etched, enabling the whole circuit to be fabricated in a single lithography and etching step. Thanks to the apodized design for the grating couplers and the introduction of an aluminum reflective mirror, a highest coupling efficiency of -3.8 dB with 3 dB coupling bandwidth of 48 nm and 1.5 dB bandwidth covering the whole C band, together with crosstalk lower than -32 dB are demonstrated.

Uranium and plutonium isotope ratios in individual uranium-plutonium (U-Pu) mixed particles with various U/Pu atomic ratios were analyzed without prior chemical separation by thermal ionization mass spectrometry (TIMS). Prior to measurement, micron-sized particles with U/Pu ratios of 1, 5, 10, 18, and 70 were produced from uranium and plutonium certified reference materials. In the TIMS analysis, the peaks of americium, plutonium, and uranium ion signals were successfully separated by continuously increasing the evaporation filament current. Consequently, the uranium and plutonium isotope ratios, except the (238)Pu/(239)Pu ratio, were successfully determined for the particles at all U/Pu ratios. This indicates that TIMS direct analysis allows for the measurement of individual U-Pu mixed particles without prior chemical separation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

It has been reported that reactive oxygen species (ROS) play a role as intracellular signaling molecules in RANKL stimulation. Previously we demonstrated that induction of cytoprotective enzyme expression by Nrf2-gene transfer successfully ameliorated RANKL-dependent osteoclastogenesis. In the present study, we hypothesized that Nrf2 activation by inhibiting ubiquitination and degradation of Nrf2 by ETGE-peptide would induce Nrf2-dependent cytoprotective enzyme expression, attenuate ROS signaling, and thereby inhibit RANKL-dependent osteoclastogenesis. ETGE-peptide containing a cell-permeable sequence (seven consecutive arginine; 7R-ETGE) was applied to a mouse macrophage cell-line RAW 264.7 cell or a primary macrophage culture. ETGE-peptide prevents Keap1 from binding to Nrf2. Nrf2 nuclear translocation and Nrf2-dependent cytoprotective enzyme induction was observed. The effects of 7R-ETGE on RANKL-dependent induction of intracellular ROS levels and osteoclastogenesis were examined. Finally, the protective effect of 7R-ETGE on RANKL-mediated bone destruction was investigated in mice. 7R-ETGE dose-dependently induced nuclear Nrf2, followed by the induction of cytoprotective enzyme expression at both the gene and protein level. 7R-ETGE inhibited upregulation of intracellular ROS levels by RANKL stimulation, and osteoclastogenesis was attenuated. Of particular interest was that local injection of 7R-ETGE ameliorated RANKL-mediated bone destruction. Local induction of nuclear Nrf2 by protein transduction is a potential novel therapeutic target for bone destruction diseases such as periodontitis and rheumatoid arthritis., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

An Auto Bias Control (ABC) technique for the IQ-modulator of a flexible optical QAM transmitter is described. This technique can support various optical QAM signal formats with Nyquist filtering and electronic dispersion pre-compensation. 16, 32 and 64-QAM signals (21 Gbaud) are successfully generated, and all bias voltages are held to their optimum value even when signal format is changed.

Phase-sensitive amplifiers (PSA) using periodically poled (PPLN) LiNbO₃ waveguides are promising as low-noise optical amplifiers. However, it is difficult to realize in-line operation for multi-level phase modulated signals using a PPLN based PSA with the conventional configuration. In this paper, we report a PPLN based in-line PSA that can regenerate quadrature phase shift keying (QPSK) signals. Multi-stage frequency mixing in a multiple quasi-phase matched LiNbO₃waveguide allows carrier phase recovery from a QPSK signal. Non-degenerate parametric amplification enables the phase-sensitive amplification of a QPSK signal. Amplitude and phase regeneration is examined utilizing gain saturation and phase squeezing capability.

Airborne radioactive particles released by the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident in 2011 were collected with a cascade low-pressure impactor at the Japan Atomic Energy Agency (JAEA) in Tokai, Japan, 114 km south of the FDNPP. Size-fractionated samples were collected twice, in the periods of March 17-April 1, 2011, and May 9-13, 2011. These size-fractionated samplings were carried out in the earliest days at a short distance from the FDNPP. Radioactivity of short-lived nuclides (several ten days of half-life) was determined as well as (134)Cs and (137)Cs. The elemental composition of size-fractionated samples was also measured. In the first collection, the activity median aerodynamic diameter (AMAD) of (129m)Te, (140)Ba, (134)Cs, (136)Cs and (137)Cs was 1.5-1.6 μm, while the diameter of (131)I was 0.45 μm. The diameters of (134)Cs and (137)Cs in the second collection were expressed as three peaks at <0.5 μm, 0.94 μm, and 7.8 μm. The (134)Cs/(137)Cs ratio of the first collection was 1.02 in total, but the ratio in the fine fractions was 0.91. A distribution map of (134)Cs/(137)Cs - (136)Cs/(137)Cs ratios was helpful in understanding the change of radioactive Cs composition. The Cs composition of size fractions <0.43 μm and the composition in the 1.1-2.1 μm range (including the AMAD of 1.5-1.6 μm) were similar to the calculated compositions of fuels in the reactors No. 1 and No. 3 at the FDNPP using the ORIGEN-II code. The Cs composition collected in May, 2011 was similar to the calculation results of reactor No. 2 fuel composition. The change of Cs composition implies that the radioactive Cs was released from the three reactors at the FDNPP via different processes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We demonstrate bidirectional transmission over 450 km of newly-developed dual-ring structured 12-core fiber with large effective area and low crosstalk. Inter-core crosstalk is suppressed by employing propagation-direction interleaving, and 409-Tb/s capacities are achieved for both directions.

We demonstrated the simultaneous amplification of a coherent multi-carrier signal using a χ(2)-based non-degenerate phase sensitive amplifier (PSA). The signal-to-noise ratio (SNR), which is degraded by the additional amplified spontaneous emission (ASE) noise, can be recovered due to the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. Utilizing the second harmonic pumping of a χ(2)-based PSA enables us to observe the SNR recovery directly by comparing the SNR for the input with that for the PSA output. A 3-dB optical-SNR (OSNR) improvement was obtained as a result of the gain difference. We also achieved a 3-dB SNR improvement in the electric domain by reducing the signal-ASE beat noise. The receiver sensitivity for a 10 Gbit/s phase shift keying signal was clearly improved with the PSA.

ABC (Auto Bias Control) technique for QAM (Quadrature Amplitude Modulation) transmitter is demonstrated. 16-QAM (10G baud) is generated and controlled using a single IQ modulator and asymmetric bias dithering technique. Measured penalty is 0.3 dB., (© 2011 Optical Society of America)

A field trial of 100-Gbit/s Ethernet over an optical transport network (OTN) is conducted using a real-time digital coherent signal processor. Error free operation with the Q-margin of 3.2 dB is confirmed at a 100 Gbit/s Ethernet analyzer by concatenating a low-density parity-check code with a OTN framer forward error correction, after 80-ch WDM transmission through 6 spans x 70 km of dispersion shifted fiber without inline-dispersion compensation. Also, the recovery time of 12 msec is observed in an optical route switching experiment, which is achieved through fast chromatic dispersion estimation functionality.

Information on plutonium isotope ratios in individual particles is of great importance for nuclear safeguards, nuclear forensics and so on. Although secondary ion mass spectrometry (SIMS) is successfully utilized for the analysis of individual uranium particles, the isobaric interference of americium-241 to plutonium-241 makes difficult to obtain accurate isotope ratios in individual plutonium particles. In the present work, an analytical technique by a combination of chemical separation and inductively coupled plasma mass spectrometry (ICP-MS) is developed and applied to isotope ratio analysis of individual sub-micrometer plutonium particles. The ICP-MS results for individual plutonium particles prepared from a standard reference material (NBL SRM-947) indicate that the use of a desolvation system for sample introduction improves the precision of isotope ratios. In addition, the accuracy of the (241)Pu/(239)Pu isotope ratio is much improved, owing to the chemical separation of plutonium and americium. In conclusion, the performance of the proposed ICP-MS technique is sufficient for the analysis of individual plutonium particles., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Fluoride complexation of element 104, rutherfordium (Rf), produced in the 248Cm(18O,5n)261Rf reaction has been studied by anion-exchange chromatography on an atom-at-a-time scale. The anion-exchange chromatographic behavior of Rf was investigated in 1.9-13.9 M hydrofluoric acid together with those of the group-4 elements Zr and Hf produced in the 18O-induced reactions on Ge and Gd targets, respectively. It was found that the adsorption behavior of Rf on anion-exchange resin is quite different from those of Zr and Hf, suggesting the influence of relativistic effects on the fluoride complexation of Rf.

KRP-197, 4-(2-methylimidazol-l-yl)-2,2-diphenylbutyramide, is a newly synthesized antimuscarinic drug, developed for the treatment for overactive bladder. For evaluation of pharmacological characteristics of KRP-197, we investigated whether it influenced both prejunctional and postjunctional muscarinic receptors on the isolated human detrusor smooth muscles as compared with the effects of atropine, oxybutynin, and propiverine. Using the muscle bath technique, we investigated the effects of various antimuscarinic drugs on the contractions induced by carbachol, KCl, CaCl(2), and electrical field stimulation. Furthermore, using high-performance liquid chromatography with a microdialysis technique, we measured the acetylcholine release from the muscle strips during electrical field stimulation. The effects of various antimuscarinic drugs on acetylcholine releases were also evaluated. Pretreatment with various antimuscarinic drugs caused parallel shifts to the right in carbachol-induced concentration-response curves. The rank order of pA(2) values was KRP-197 > or = atropine > oxybutynin > propiverine. Atropine and KRP-197 did not cause significant inhibition of KCl- and CaCl(2)-induced contractions. All drugs caused concentration-dependent inhibitions in electrical field stimulation-induced contractions. Pretreatment with atropine and propiverine did not cause significant changes in electrical field stimulation-induced acetylcholine release. However, KRP-197, and oxybutynin caused significant decreases in acetylcholine release. The present study demonstrates that KRP-197 has an inhibitory effect on postjunctional muscarinic receptors as well as on prejunctional muscarinic receptors to modulate acetylcholine release in human detrusor smooth muscles. The findings suggest the usefulness of KRP-197 as a therapeutic drug for an overactive bladder with symptoms of frequency, urgency, and urge incontinence., (Copyright 2003 S. Karger AG, Basel)