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The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation.

Aims/Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease. Materials and Methods We assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of, Incidence of renal composite outcome and changes in logarithmic value of the albumin‐to‐creatinine ratio and estimated glomerular filtration rate.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2018-12-08, 資料番号: PA1920026000

In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue. TRPV4 gene knockout also suppressed epithelial repair in mouse cornea, although it did not seem to directly modulate migration of epithelium. In a co-culture experiment, TRPV4-introduced KO trigeminal ganglion upregulated nerve growth factor (NGF) in cultured corneal epithelial cells, but ganglion with a control vector did not. TRPV4 gene introduction into a damaged V1 nerve rescues the impairment of epithelial healing in association with partial recovery of the stem/progenitor cell markers and upregulation of cell proliferation and of NGF expression in the peripheral/limbal epithelium. Gene transfer of TRPV4 did not accelerate the regeneration of nerve fibers. Sensory nerve TRPV4 is critical to maintain stemness of peripheral/limbal basal cells, and is one of the major mechanisms of homeostasis maintenance of corneal epithelium.

Maternal–fetal transport of calcium (Ca2+) is important for bone mineralization in fetal development. Insufficient Ca2+ transport causes transient neonatal hyperparathyroidism (TNHP). Transient receptor potential cation channel, subfamily V, member 6 (TRPV6), has been found to play an important role in the active transport of Ca2+ through the placenta. Recently, TRPV6 gene was found to be the gene responsible for TNHP with severe skeletal undermineralization. To date, only seven cases of TNHP caused by TRPV6 recessive mutations have been reported. We present a case of TNHP caused by TRPV6 gene mutations. A female newborn was hospitalized because of respiratory distress. Marked undermineralization of the skeleton was observed in X-ray imaging. Laboratory examination revealed markedly high PTH and absence of hypercalcemia along with vitamin D deficiency. Her twin brother presented with almost no symptoms. Maternal laboratory findings indicated normocalcemia, but vitamin D deficiency with a high PTH level for the lactation period was observed. We initially diagnosed the patient as having secondary hyperparathyroidism because of maternal vitamin D deficiency. Nevertheless, the reasons underlying the discordant clinical manifestations between the twin siblings remained unclear. Our analysis of TRPV6 gene clarified that the patient had compound heterozygote mutations, which were reported previously (p.Ile223Thr and p.Gly428Arg). Pathologic mutations in TRPV6 gene were not detected in the other sibling. The clinical symptoms in the patient were transient: they resolved during infancy. TNHP caused by TRPV6 gene mutations is a unique disease in terms of its transient pathology in utero and relief after birth.

The stratum corneum (SC), the outermost epidermal layer, consists of nonviable anuclear keratinocytes, called corneocytes, which function as a protective barrier. The exact modes of cell death executed by keratinocytes of the upper stratum granulosum (SG1 cells) remain largely unknown. Here, using intravital imaging combined with intracellular Ca(2+)- and pH-responsive fluorescent probes, we aimed to dissect the SG1 death process in vivo. We found that SG1 cell death was preceded by prolonged (∼60 min) Ca(2+) elevation and rapid induction of intracellular acidification. Once such intracellular ionic changes were initiated, they became sustained, irreversibly committing the SG1 cells to corneocyte conversion. Time-lapse imaging of isolated murine SG1 cells revealed that intracellular acidification was essential for the degradation of keratohyalin granules and nuclear DNA, phenomena specific to SC corneocyte formation. Furthermore, intravital imaging showed that the number of SG1 cells exhibiting Ca(2+) elevation and the timing of intracellular acidification were both tightly regulated by the transient receptor potential cation channel V3. The functional activity of this protein was confirmed in isolated SG1 cells using whole-cell patch-clamp analysis. These findings provide a theoretical framework for improved understanding of the unique molecular mechanisms underlying keratinocyte-specific death mode, namely corneoptosis.

Mechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress during muscle formation remain unclear. Here, we investigate the role of the mechano-sensitive ion channel Piezo1 during myogenic progression. Direct manipulation of Piezo1 in muscle stem cells alters their myogenic progression. Indeed, Piezo1 knockdown suppresses myoblast fusion leading to smaller myotubes. Such event is accompanied by significant downregulation of the fusogenic protein Myomaker. In parallel, while Piezo1 knockdown also lowers Ca2+ influx in response to stretch, Piezo1 activation increases Ca2+ influx in response to stretch and enhances myoblasts fusion. We believe these findings may help understand molecular defects present in some muscle diseases. Altogether our study shows that Piezo1 is essential for terminal muscle differentiation acting on myoblast fusion, suggesting that Piezo1 deregulation may have implications in muscle aging and degenerative diseases including muscular dystrophies.

We built a machine learning model (ML model) which input the number of daily infection cases and the other information related to COVID-19 over the past 24 days in each of 17 provinces in South Korea, and output the total increase in the number of infection cases in each of 17 provinces over the coming 24 days. We employ a combination of XGBoost and MultiOutputRegressor as machine learning model (ML model). For each province, we conduct a binary classification whether our ML model can classify provinces where total infection cases over the coming 24 days is more than 100. The result is Sensitivity = 3/3 = 100%, Specificity = 11/14 = 78.6%, False Positive Rate = 3/11 = 21.4%, Accuracy = 14/17 = 82.4%. Sensitivity = 100% means that we did not overlook the three provinces where the number of COVID-19 infection cases increased by more than100. In addition, as for the provinces where the actual number of new COVID-19 infection cases is less than 100, the ratio (Specificity) that our ML model can correctly estimate was 78.6%, which is relatively high. From the above all, it is demonstrated that there is a sufficient possibility that our ML model can support the following four points. (1) Promotion of behavior modification of residents in dangerous areas, (2) Assistance for decision to resume economic activities in each province, (3) Assistance in determining infectious disease control measures in each province, (4) Search for factors that are highly correlated with the future increase in the number of COVID-19 infection cases.

Optical coherence tomography (OCT) scanning is useful in detecting various retinal diseases. However, there are not enough ophthalmologists who can diagnose retinal OCT images in much of the world. To provide OCT screening inexpensively and extensively, an automated diagnosis system is indispensable. Although many machine learning techniques have been presented for assisting ophthalmologists in diagnosing retinal OCT images, there is no technique that can diagnose independently without relying on an ophthalmologist, i.e., there is no technique that does not overlook any anomaly, including unlearned diseases. As long as there is a risk of overlooking a disease with a technique, ophthalmologists must double-check even those images that the technique classifies as normal. Here, we show that our deep-learning-based binary classifier (normal or abnormal) achieved a perfect classification on 108,308 two-dimensional retinal OCT images, i.e., true positive rate = 1.000000 and true negative rate = 1.000000; hence, the area under the ROC curve = 1.0000000. Although the test set included three types of diseases, two of these were not used for training. However, all test images were correctly classified. Furthermore, we demonstrated that our scheme was able to cope with differences in patient race. No conventional approach has achieved the above performances. Our work has a sufficient possibility of raising automated diagnosis techniques for retinal OCT images from "assistant for ophthalmologists" to "independent diagnosis system without ophthalmologists".

FK506 (tacrolimus) is an immunosuppressant widely used as an ointment in the treatment of atopic dermatitis. However, local application of FK506 can evoke burning sensations in atopic dermatitis patients, and its mechanisms are unknown. In this study, we found that FK506 activates transient receptor potential ankyrin 1 (TRPA1) channels. In Ca2+-imaging experiments, increases in intracellular Ca2+ concentrations ([Ca2+]i) by FK506 were observed in HEK293T cells expressing hTRPA1 or hTRPM8. FK506-induced currents were observed in HEK293T cells expressing hTRPA1 or mTRPA1, but less or not at all in cells expressing hTRPV1 or hTRPM8 using a patch-clamp technique. FK506 also evoked single-channel opening of hTRPA1 in an inside-out configuration. FK506-induced [Ca2+]i increases were also observed in TRPA1-expressing mouse primary sensory neurons. Furthermore, injection of FK506 evoked licking or biting behaviors and these behaviors were almost abolished in TRPA1 knockout mice. These results indicate that FK506 might cause pain sensations through TRPA1 activation.

In recent years, synthetic fiber ropes have attracted much attention because of their potential to increase the load capacity, reduce the size, and lighten the weight of tendon-driven mechanisms. However, the mechanical characteristics of synthetic fiber ropes in a dynamic loading situation remain an open problem because of their visco-elasto-plasticity. This letter focuses on modeling synthetic fiber ropes, and the frequency response of a long-distance cable-pulley system for a tendon-driven robot. We show that a synthetic fiber rope can be modeled by Flory's model, and that it can be reduced to a conventional four-element model with sufficient preloading. After empirically acquiring the parameters of the four-element model for four different synthetic fiber ropes, each frequency response of a long-distance cable-pulley servo system was measured and compared to the analytical results based on the model, as well as the results of a stainless wire rope. Consequently, we show that synthetic fiber ropes achieved comparable bandwidth to that of the stainless wire rope. The damping of synthetic fiber ropes was found to suppress the servo system gain. This is useful for joint control of a tendon-driven robot with a relatively large amount of inertia, such as a long-reach robot arm.

The relationship between the propagation directions of ultrasonic wave and the direction of the principal axis of anisotropy in uni-directional CFRP with straight fiber is well known. However, the behavior of ultrasonic wave in CFRP with curved fibers is not clarified in details. In this paper, numerical analyses using the finite difference method were conducted to visualize the behavior of ultrasonic waves in CFRP with concentrically curved fibers. Numerical simulation results showed the energy of quasi-longitudinal ultrasonic wave curved along the fiber direction. In order to confirm the analytical result, CFRP specimen with curved fibers were prepared by utilizing 3D-printer and the behavior of ultrasonic propagation was observed by using Laser ultrasonic system. The observed results confirmed the analytical results that the ultrasonic wave curved along carbon fibers.

Hypotonic solutions can cause painful sensations in nasal and ocular mucosa through molecular mechanisms that are not entirely understood. We clarified the ability of human TRPA1 (hTRPA1) to respond to physical stimulus, and evaluated the response of hTRPA1 to cell swelling under hypotonic conditions. Using a Ca2+-imaging method, we found that modulation of AITC-induced hTRPA1 activity occurred under hypotonic conditions. Moreover, cell swelling in hypotonic conditions evoked single-channel activation of hTRPA1 in a cell-attached mode when the patch pipette was attached after cell swelling under hypotonic conditions, but not before swelling. Single-channel currents activated by cell swelling were also inhibited by a known hTRPA1 blocker. Since pre-application of thapsigargin or pretreatment with the calcium chelator BAPTA did not affect the single-channel activation induced by cell swelling, changes in intracellular calcium concentrations are likely not related to hTRPA1 activation induced by physical stimuli.

Acoustic Emission Testing (AT) is one of the major non-destructive testing methods used for severity evaluation of structures. Amplitude distributions of AE signals are characterized by b-value and the value is mainly used for the severity evaluation of concrete structures until now. The value is assumed to be independent with propagation distance between acoustic emission sources to AE sensors. We evaluate the influence of the wide frequency band encountered in the fracture behavior of glass fiber reinforced plastic (GFRP) on the b-value analysis. In tensile tests, the b-value was determined from an acoustic emission (AE) source generated near a centered hole in a specimen of GFRP. At 15 mm from the hole, the b-value analysis indicated a decreasing trend with increasing tensile stress. At a propagation length of 45 mm, farthest from the hole, a small number of AE signals were received. The attenuation is more rapid for high-frequency AE signals. Thus, the amplitude distribution bandwidth is wide and the b-value changes. This change in b-value for GFRPs is investigated by analyzing the spectral components of the AE signals. For a single-frequency AE source, the b-value is unchanged with propagation length. In contrast, multiple-frequency AE sources produce changes in b-value proportional to the fraction of each spectral component in the received signal. This is due to the frequency dependence of the attenuation with propagation length. From these results, the b-value analysis cannot be applied to considering frequency dependence of AE attenuation.

Maternal–fetal calcium (Ca2+) transport in the placenta plays a critical role in maintaining fetal bone mineralization. Mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6) have been identified as causative mutations of transient neonatal hyperparathyroidism due to insufficient maternal–fetal Ca2+ transport in the placenta. In this study, we found two novel mutations in subjects that have transient neonatal hyperparathyroidism. TRPV6 carrying the mutation p.Arg390His that localizes to the outer edge of the first transmembrane domain (S1) showed impaired trafficking to the plasma membrane, whereas TRPV6 having the mutation p.Gly291Ser in the sixth ankyrin repeat (AR) domain had channel properties that were comparable those of WT channels, although the increases in steady-state intracellular Ca2+ concentration could have led to Ca2+ overload and subsequent death of cells expressing this mutant channel. These results indicate that the AR6 domain contributes to TRPV6-mediated maintenance of intracellular Ca2+ concentrations, and that this region could play a novel role in regulating the activity of TRPV6 Ca2+-selective channels.

Masking is a direct behavioral response to environmental changes and plays an important role in the temporal distribution of activity. However, the mechanisms responsible for masking remain unclear. Here we identify thermosensors and a possible neural circuit regulating temperature-dependent masking behavior in mice. Analysis of mice lacking thermosensitive transient receptor potential (TRP) channels (Trpv1/3/4 and Trpm2/8) reveals that temperature-dependent masking is impaired in Trpm2- and Trpm8-null mice. Several brain regions are activated during temperature-dependent masking, including the preoptic area (POA), known as the thermoregulatory center, the suprachiasmatic nucleus (SCN), which is the primary circadian pacemaker, the paraventricular nucleus of the thalamus (PVT), and the nucleus accumbens (NAc). The POA, SCN, PVT are interconnected, and the PVT sends dense projections to the NAc, a key brain region involved in wheel-running activity. Partial chemical lesion of the PVT attenuates masking, suggesting the involvement of the PVT in temperature-dependent masking behavior.

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2020-09-09, 資料番号: PA2120053000

The present study deals with electrical resistance changes in woven-fabric CFRP during loading. Four kinds of plain weave woven-fabric CFRP laminated specimens are prepared and subjected to cyclic tensile loading that does not cause any damages, and the electrical resistance changes of the specimens are measured experimentally by the four-probe method. As a result, the present study shows that the electrical resistance of a specimen comprised of six ±45° plies decreases remarkably with increasing number of loading cycles. The decrease is caused by shear plastic deformation of ±45° plies. The thickness shrinkage caused by shear plastic deformation increases the number of fiber contacts, and this decreases the interlaminar contact resistance between the plies. For a single ±45° ply, the same electrical resistance decrease caused by the shear plastic deformation is observed, and the magnitude of the decrease is smaller than that of the six-ply laminate tested. This is because the effect of interlaminar conta...

The placenta is required to transport calcium (Ca2+) from mother to fetus during fetal bone mineralization. In an attempt to clarify the molecular basis of Ca2+ entry for this transport, we identified TRPM6 as a candidate for apical Ca2+ entry pathway. TRPM6 mRNA increased during the last 4 days of pregnancy, coinciding with fetal bone mineralization in mice. TRPM6 mRNA and protein was localized in the trophoblasts in labyrinth where the maternal–fetal Ca2+ transport occurs. In patch-clamp recordings, we observed TRPM6/TRPM7-like currents in mouse trophoblasts after starting fetal bone mineralization but not before mineralization. Plasma membrane Ca2+ permeability was significantly increased in TRPM6/TRPM7 expressed HEK293 cells under physiological Mg2+ and ATP concentration but not in TRPM6 or TRPM7 homomer-expressing cells. These results suggest that TRPM6 is functionally expressed in mouse placental trophoblasts, implicating in maternal–fetal Ca2+ transport likely with TRPM7, which might enable to sustain fetal bone mineralization.

This paper presents an eddy current testing method to detect in-plane fiber waviness in cross-ply carbon fiber reinforced plastic (CFRP) laminates. We propose a method which has high sensitivity to presence of in-plane waviness and can select layers to be inspected. The probe was used to detect artificially induced in-plane waviness in cross-ply CFRP laminates. It was observed that obtained signal has extreme value at the edges and vertex of the waviness, which implies the possibility of precise identification of waviness location. Detectability of subsurface waviness was investigated using 20 layer cross-ply laminate with in-plane waviness at different depths. Experimental results showed that in-plane waviness 18 layers away from the surface could be detected. The minimum misalignment angle of the detected waviness was 7.4°. The effectiveness of the probe and physical background of the obtained signals were verified by finite element method analyses.

This study investigated the similarity law of ultrasonic propagation in CFRP with concentrically curved fibers. The similarity law was formulated by introducing a new dimensionless number D. Additionally, the similarity law for a two-dimensionally propagating bulk wave was mathematically proven using the governing equation. A numerical simulation was conducted to visually demonstrate how this similarity law is held in CFRP with concentrically curved fibers. The simulation results revealed that the wavefronts of waves generated at different points had geometrically similar shapes when the D values for each wavefront were identical. The experimental visualization of ultrasonic propagation through a CFRP plate with concentrically curved fibers was also conducted, and the results revealed that the similarity law held in actual CFRP material specimens.

Purpose: Calcium entry channels in the plasma membrane are thought to play a major role in maintaining cellular Ca2+ levels, crucial for growth and survival of normal and cancer cells. The calcium-selective channel TRPV6 is expressed in prostate, breast, and other cancer cells. Its expression coincides with cancer progression, suggesting that it drives cancer cell growth. However, no specific inhibitors for TRPV6 have been identified thus far. Methods: To develop specific TRPV6 inhibitors, we synthesized molecules based on the lead compound TH-1177, reported to inhibit calcium entry channels in prostate cancer cells in vitro and in vivo. Results: We found that one of our compounds (#03) selectively inhibited TRPV6 over five times better than TRPV5, whereas TH-1177 and the other synthesized compounds preferentially inhibited TRPV5. The IC50 value for growth inhibition by blocking endogenous Ca2+ entry channels in the LNCaP human prostate cancer cell line was 0.44 ± 0.07 μM compared to TH-1177 (50 ± 0.4 μM). Conclusions: These results suggest that compound #03 is a relatively selective and potent inhibitor for TRPV6 and that it is an interesting lead compound for the treatment of prostate cancer and other cancers of epithelial origin.

Transient neonatal hyperparathyroidism (TNHP) is etiologically a heterogeneous condition. One of the etiologies is an insufficient maternal-fetal calcium transport through the placenta. We report six subjects with homozygous and/or compound-heterozygous mutations in the gene encoding the transient receptor potential cation channel, subfamily V, member 6 (TRPV6), an epithelial Ca2+-selective channel associated with this condition. Exome sequencing on two neonates with skeletal findings consistent with neonatal hyperparathyroidism identified homozygous frameshift mutations before the first transmembrane domain in a subject born to first-cousins parents of Pakistani descent as well as compound-heterozygous mutations (a combination of a frameshift mutation and an intronic mutation that alters mRNA splicing) in an individual born to a non-consanguineous couple of African descent. Subsequently, targeted mutation analysis of TRPV6 performed on four other individuals (born to non-consanguineous Japanese parents) with similar X-rays findings identified compound-heterozygous mutations. The skeletal findings improved or resolved in most subjects during the first few months of life. We identified three missense variants (at the outer edges of the second and third transmembrane domains) that alter the localization of the TRPV6: one recurrent variant at the S2-S3 loop and two recurrent variants (in the fourth ankyrin repeat domain) that impair TRPV6 stability. Compound heterozygous loss-of-function mutations for the pathogenic frameshift allele and the allele with an intronic c.607+5G>A mutation resulted in the most severe phenotype. These results suggest that TNHP is an autosomal-recessive disease caused by TRPV6 mutations that affect maternal-fetal calcium transport.

Transient receptor potential ankyrin 1 (TRPA1) protein is a nonselective cation channel. Although many studies suggest that TRPA1 is involved in inflammatory and neuropathic pain, its mechanism remains unclear. Here we identify an alternative splice variant of the mouse Trpa1 gene. TRPA1a (full-length) and TRPA1b (splice variant) physically interact with each other and TRPA1b increases the expression of TRPA1a in the plasma membrane. TRPA1a and TRPA1b co-expression significantly increases current density in response to different agonists without affecting their single-channel conductance. Exogenous overexpression of Trpa1b gene in wild-type and TRPA1KO DRG neurons also increases TRPA1a-mediated AITC responses. Moreover, expression levels of Trpa1a and Trpa1b mRNAs change dynamically in two pain models (complete Freund’s adjuvant-induced inflammatory pain and partial sciatic nerve ligation-induced neuropathic pain models). These results suggest that TRPA1 may be regulated through alternative splicing under these pathological conditions., TRPA1 is a transient receptor potential channel family member and is involved in the detection of nociceptive stimuli. Zhou et al. identify an alternative splice variant of TRPA1, which increases TRPA1 plasma expression and channel function, and enhances pain-like behaviour in mice.

Trpm7 is a divalent cation-permeable channel that has been reported to be involved in magnesium homeostasis as well as cellular adhesion and migration. We generated urothelium-specific Trpm7 knock-out (KO) mice to reveal the function of Trpm7 in vivo. A Trpm7 KO was induced by tamoxifen and was confirmed by genomic PCR and immunohistochemistry. By using patch clamp recordings in primary urothelial cells, we observed that Mg(2+)-inhibitable cation currents as well as acid-inducible currents were significantly smaller in Trpm7 KO urothelial cells than in cells from control mice. Assessment of voiding behavior indicated a significantly smaller voided volume in Trpm7 KO mice (mean voided volume 0.28 ± 0.08 g in KO mice and 0.36 ± 0.04 g in control mice, p < 0.05, n = 6-8). Histological analysis showed partial but substantial edema in the submucosal layer of Trpm7 KO mice, most likely due to inflammation. The expression of proinflammatory cytokines TNF-α and IL-1β was significantly higher in Trpm7 KO bladders than in controls. In transmission electron microscopic analysis, immature intercellular junctions were observed in Trpm7 KO urothelium but not in control mice. These results suggest that Trpm7 is involved in the formation of intercellular junctions in mouse urothelium. Immature intercellular junctions in Trpm7 knock-out mice might lead to a disruption of barrier function resulting in inflammation and hypersensitive bladder afferent nerves that may affect voiding behavior in vivo.

A non-destructive inspection method of carbon fibre reinforced polymer (CFRP) is self-sensing technology that uses carbon fibres as sensors. The technology applies electric current to composites and measures the electrical resistance change to detect damage. Although the technique detects damage precisely, it requires many electrodes on the CFRP surface. Time-domain reflectometry (TDR) has previously been proposed to detect damage over a wide area with a small number of electrodes and applied to detect fibre breakage in unidirectional CFRP ply specimens. In the present paper, experiments are conducted for a cross-ply CFRP laminate subjected to impact damage. Three impact loads are applied and the damage is inspected employing self-sensing TDR and a micro-strip line. Results show that the self-sensing TDR can be applied to laminated CFRP structures that have several fibre directions and when damage such as a delamination crack extends under or close to the micro-strip line.

This paper presents analytical solutions to eddy current distribution in carbon fiber-reinforced plastics induced by line current. Derived solutions show that eddy current distribution in unidirectional carbon fiber composite is dependent only on electrical conductivity in the drive current direction when the drive current is directed in the fiber direction or the transverse direction. Moreover, according to the derived analytical solution, skin depth of eddy current depends not only on frequency of drive current but on lift-off and width of the drive current unlike general expression of skin depth. Finally, we discuss improvement of sensitivity of eddy current conductivity sensor using analytical solutions. It is found that analytical solutions can clearly divide effects of magnetic field from drive current and that from eddy current. Sensitivity of eddy current sensor can be improved by 10 times placing pickup coil at region where the effect of magnetic field from eddy current is large.

Liquid composite molding (LCM) is a method to manufacture fiber-reinforced composites, where dry fabric reinforcement is impregnated with a resin in a molding apparatus. However, the inherent process variability changes resin flow patterns during mold filling, which in turn may cause void formation. We propose a method to reconstruct three-dimensional resin flow in LCM, without embedding sensors into the composite structure. Capacitance measured from pairs of electrodes on molding tools and the stochastic simulation of resin flow during an LCM process are integrated by a sequential data assimilation method based on the ensemble Kalman filter; then, three-dimensional resin flow and permeability distribution are estimated simultaneously. The applicability of this method is investigated by numerical experiments, characterized by different spatial distributions of permeability. We confirmed that changes in resin flow caused by spatial permeability variations could be captured and the spatial distribution of permeability could be estimated by the proposed method.

Structural capacitors are composite structures that function as energy storage capacitors. Parallel plate-type capacitors have the advantage of high voltage resistance, but are limited by low capacitance. An electric double-layer capacitor with a composite structure using a solid polymer electrolyte matrix with a glass fiber fabric separator has recently been developed. However, the solid polymer electrolyte caused the capacitor to possess high internal resistance. In the present study, a new design of supercapacitor using a form core sandwich with high water retention is proposed and experimentally investigated. Activated carbon sheets are used as electrodes on the form core sandwich to make a supercapacitor. Woven carbon fabric is used as lead wires of the supercapacitor. The resulting supercapacitor displays a low surface resistance of 810 Ωcm2 and high areal capacitance of 520 mF/cm2.

Carbon fiber reinforced polymer composites (CFRP) have been applied to aerospace and automobile structures. For many CFRP structures, mechanical metallic fasteners are usually adopted. For the fasteners used in internal structures such as a wing box, the damage to the CFRP structures around fastener holes is visually quite difficult to find. A simple method to find the damage around fastener holes is required. In this study a self-sensing time domain reflectometry (TDR) method is newly applied to detect bearing failure around the fastener holes of CFRP structures. A microstrip-line method is generally used to create a transmission line. When the transmission line is mounted near the metallic fasteners, they may affect the impedance of the transmission line. In this study, the effect of distance between the fasteners and the transmission line was numerically investigated using a finite difference time domain analysis method. After finding the appropriate distance, experiments were performed to detect the bearing failure around a fastener hole. The experiments showed the performance of the self-sensing TDR for detecting bearing failure.

The inhibitory responses of renal sympathetic nerve activity (RSNA) and heart rate (HR) to sustained hemorrhagic shock occurred in anesthetized rats, but have not yet been determined in mice. Here, we investigated the responses of RSNA and HR to hemorrhagic hypotension in anesthetized mice, with an emphasis on the molecule-based mechanism for roles of afferent vagal nerves.RSNA, HR, and mean systemic arterial pressure were continuously measured in male pentobarbital-anesthetized C57BL/6N mice. Hemorrhagic hypotension of 50 mmHg was evoked and maintained for 10 min.During hemorrhagic hypotension, RSNA initially increased and then sustainedly decreased, while HR progressively decreased. Vagotomy eliminated the second-phase sympathoinhibition and bradycardia, and carotid sinus denervation with vagotomy abolished the initial renal sympathoexcitation. The renal sympathoinihibition during hemorrhagic hypotension of 50 mmHg was eliminated in mice pretreated with a transient receptor potential vanilloid type 1 channel (TRPV1) inhibitor, capsazepine, and in TRPV1 knockout (TRPV1) mice, but not in TRPV4 knockout mice. The bradycardia response to hemorrhagic hypotension was also absent in TRPV1 mice and mice pretreated with capsazepine.Hemorrhagic hypotension in anesthetized mice causes biphasic responses of RSNA with an initial increase, followed by a sustained decrease, and a progressive decrease in HR. The initial sympathoexcitation is mediated by carotid sinus baroreceptors, while the later sympathoinhibition and bradycardia are mediated via the TRPV1 signals of vagal afferents.

近年，高機能，高性能な化学繊維の開発が盛んである．筆者らはこれらの化学繊維を用いたワイヤを高強度化学繊維ワイヤと呼び，金属ワイヤに代替してこれらの特性を活かしたロボットの実現を目指している．本報では，高強度化学繊維ワイヤが駆動系の周波数特性に与える影響を検証するために長軸間距離試験機を製作し，周波数特性試験を行った．また，ワイヤの粘弾性測定から長軸間距離試験機の伝達関数を求め，測定した周波数応答と比較しおおむね一致することを確認した．, Synthetic fiber ropes, which are lightweight and have high tensile strength and flexibility, have attracted attention as an alternative to stainless steel wire rope. This study clarifies various physical characteristics of synthetic fiber ropes to design a tendon-driven mechanism. This paper investigates a viscoelasticity model for Ultra High molecular weight Polyethylene (UHPE) rope and its dynamic property applied to a long distant antagonistic tendon-driven servo system. We confirm that UHPE can be modeled by four element model, and obtained its transfer function of a tendon-driven servo system. The validity of the transfer function was confirmed by a frequency response experiment. %This paper takes note of performance of synthetic fiber rope on tendon-driven servo system. %We estimated a viscoelasticity of a UHPE(Ultra High Molecular Weight Polyethylene) rope by four element model and using the viscoelasticity to obtained the transfer function of a tendon-driven servo system.

We experimentally test a previously reported lightning protection sheet (LPS) sensor to detect impacts within a short collision interval. The exact loading position is achieved using a two-step method. Our sensor sheet is flexible and can easily be attached to different shaped structures. Current flows in the sensor only during loading and our quick switching system identifies the real-time x, y coordinates of the loading position. Using this method multiple impacts can be detected when the time difference between two impacts is larger than 10 ms. The position of a single impact is estimated within 16 mm. This means that detailed inspection needs to be conducted only over a circular area with a radius about a few centimeters. Our method is ideally suited for aircraft components and it reduces costs and saves time as only small specific areas require inspection using ultrasonic or electrical resistance techniques.

The urothelium is a sensory structure that contributes to mechanosensation in the urinary bladder. Here, we provide evidence for a critical role for the Piezo1 channel, a newly identified mechanosensory molecule, in the mouse bladder urothelium. We performed a systematic analysis of the molecular and functional expression of Piezo1 channels in the urothelium. Immunofluorescence examination demonstrated abundant expression of Piezo1 in the mouse and human urothelium. Urothelial cells isolated from mice exhibited a Piezo1-dependent increase in cytosolic Ca(2+) concentrations in response to mechanical stretch stimuli, leading to potent ATP release; this response was suppressed in Piezo1-knockdown cells. In addition, Piezo1 and TRPV4 distinguished different intensities of mechanical stimulus. Moreover, GsMTx4, an inhibitor of stretch-activated channels, attenuated the Ca(2+) influx into urothelial cells and decreased ATP release from them upon stretch stimulation. These results suggest that Piezo1 senses extension of the bladder urothelium, leading to production of an ATP signal. Thus, inhibition of Piezo1 might provide a promising means of treating bladder dysfunction.

Transient receptor potential (TRP) channels play important roles in thermal, chemical, and mechanical sensation in various tissues. In this study, we investigated the differences in urothelial TRP channels between normal urothelial cells and bladder cancer cells. TRPV2 and TRPM7 expression levels and TRPV2 activator-induced intracellular Ca(2+) increases were significantly higher, whereas TRPV4 expression and TRPV4 activator-induced intracellular Ca(2+) increases were significantly lower in mouse bladder cancer (MBT-2) cells compared to normal mouse urothelial cells. The proliferation rate of MBT-2 cells overexpressing dominant-negative TRPV2 was significantly increased. In contrast, treatment with TRPV2 activators significantly decreased the proliferation rate. TRPM7-overexpressing MBT-2 cells proliferated more slowly, as compared to mock-transfected cells. Moreover, expression of dominant-negative TRPV2 significantly decreased plasma membrane Ca(2+) permeability of MBT-2 cells as compared to that in mock-transfected cells. Increases in the expression of TRPV2 mRNA, immunoreactivity, and TRPV2 activator-induced intracellular Ca(2+) were also observed in T24 human bladder cancer cells. These results suggested that TRPV2 and TRPM7 were functionally expressed in bladder cancer cells and served as negative regulators of bladder cancer cell proliferation, most likely to prevent excess mechanical stresses.

Self-sensing multifunctional composite has sensing function using electrical resistance changes. Carbon Fiber Reinforced Polymer (CFRP) composite is one of the self-sensing multifunctional composites. For the reliability of the self-sensing, electrical contact between the lead wire and the carbon fibers is the most important issue. The present study focuses on the effect of the cyclic loading of lower applied strain range than the fatigue damage level. As a result, the electrical contact resistance at the copper electrode increased with the increase of cycles. That means that the electrical change at the electrodes must be considered for the long-term self-sensing monitoring system. When a four-probe method is used to measure the electrical resistance, the contact resistance effect is minimized. Moreover, angle-ply laminates have plastic deformation caused by shear loading, and that causes electrical resistance decrease during the cyclic loading. Cross-ply laminates of CFRP composites have no electrical resistance increase without damage. Quasi-isotropic laminates of CFRP composites, however, have electrical resistance decrease with the increase of the number of cycles because of the plastic deformation of the angle-ply laminates.