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AimsCalcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.Methods and resultsAn aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.ConclusionSortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.

The development of dentition begins in the embryonic oral cavity and progresses in the branchial arches and alveolar bone. Continuous cellular and molecular crosstalk occurs during crown formation, after which the tooth germ begins to migrate apically through the alveolar process into the oral cavity. It eventually comes in contact with its antagonist in the contralateral jaw to establish functional occlusion. Any defect in either step can result in delayed tooth development, the spectrum of which varies from a congenitally missing tooth to an impacted tooth (infraocclusion) with an eruption problem, both of which can impair oral function.Congenitally missing teeth or eruption problems may result from genetic mutations. Several different mutations have been identified, each causing a distinct phenotype. Thus, it is imperative that medical providers understand the fundamentals of these genetic principles that govern such dental diseases.In this review, we focus on several diseases, including congenitally missing teeth and tooth eruption problems. We review these diseases with aspect to their association with a particular syndrome, as well as independently in a non-syndromic capacity. We also review previously identified genetic mutations and discuss the possible mechanisms that cause individual phenotypes by analyzing previous investigations. We also discuss future prospects of how genetic diagnosis and precision medicine could impact the clinical environment in the field of dentistry.Present study has been carried out in accordance with The Code of Ethics of the World Medical Association and approved by Institutional Review Board of Osaka University Graduate School of Dentistry.

Patients with congenital craniofacial anomalies often require orthodontic treatment to correct malocclusion. Numerous case reports about craniofacial anomalies have been published, but for many syndromic diseases the pathology of malocclusion and/or solutions for it remain elusive. In this study, we investigated craniofacial features as well as orthodontic treatment outcomes of patients with glucose transporter 1 deficiency syndrome (GLUT1-DS), which is an autosomal dominant genetic disease. Cross sectional study was performed using 9 GLUT1-DS patients, aged from 8 to 49 years old. All of the participants underwent intraoral and radiographic examinations. Lateral cephalogram measurement was performed for investigating possible craniofacial features in GLUT1-DS patients. Most of them showed skeletal discrepancy with large overjet. Some patients had a history of trauma to their maxillary incisor(s). In order to correct the patients’ malocclusion, we employed conventional orthodontic appliances and obtained good treatment outcomes. Based on these results, we summarized features associated with the deficiency of GLUT1-DS and also showed the benefit of correcting the malocclusion using conventional orthodontic procedures. Through this report, we showed the craniofacial characteristics and malocclusion of the GLUT1-DS patient which could be treated with conventional orthodontic approach.

Extracellular vesicles (EVs) play a critical role in intercellular communication by transferring microRNAs, lipids, and proteins to neighboring cells. Sortilin, a sorting receptor that directs target proteins to the secretory or endocytic compartments of cells, is found in both EVs and cells. In many human diseases, including cancer and cardiovascular disorders, sortilin expression levels are atypically high. To elucidate the relationship between cardiovascular disease, particularly vascular calcification, and sortilin expression levels, we explored the trafficking of sortilin in both the intracellular and extracellular milieu. We previously demonstrated that sortilin promotes vascular calcification via its trafficking of tissue-nonspecific alkaline phosphatase to EVs. Although recent reports have noted that sortilin is regulated by multiple post-translational modifications, the precise mechanisms of sortilin trafficking still need to be determined. Here, we show that sortilin forms homodimers with an intermolecular disulfide bond at the cysteine 783 (Cys783) residue, and because Cys783 can be palmitoylated, it could be shared via palmitoylation and an intermolecular disulfide bond. Formation of this intermolecular disulfide bond leads to trafficking of sortilin to EVs by preventing palmitoylation, which further promotes sortilin trafficking to the Golgi apparatus. Moreover, we found that sortilin-derived propeptide decreased sortilin homodimers within EVs. In conclusion, sortilin is transported to EVs via the formation of homodimers with an intermolecular disulfide bond, which is endogenously regulated by its own propeptide. Therefore, we propose that inhibiting dimerization of sortilin acts as a new therapeutic strategy for the treatment of EV-associated diseases, including vascular calcification and cancer.

Dynamic metabolic changes occur in the liver during the transition between fasting and feeding. Here we show that transient ER stress responses in the liver following feeding terminated by Sdf2l1 are essential for normal glucose and lipid homeostasis. Sdf2l1 regulates ERAD through interaction with a trafficking protein, TMED10. Suppression of Sdf2l1 expression in the liver results in insulin resistance and increases triglyceride content with sustained ER stress. In obese and diabetic mice, Sdf2l1 is downregulated due to decreased levels of nuclear XBP-1s, whereas restoration of Sdf2l1 expression ameliorates glucose intolerance and fatty liver with decreased ER stress. In diabetic patients, insufficient induction of Sdf2l1 correlates with progression of insulin resistance and steatohepatitis. Therefore, failure to build an ER stress response in the liver may be a causal factor in obesity-related diabetes and nonalcoholic steatohepatitis, for which Sdf2l1 could serve as a therapeutic target and sensitive biomarker., Endoplasmic reticulum (ER) stress has been proposed to play a role in metabolic diseases. Here, Sasako and colleagues identify stromal cell-derived factor 2 like 1 (Sdf2l1) as a regulator of the ER stress response to feeding in the liver, and suggest that its downregulation may promote diabetes and hepatic steatosis in humans.

Objective: Extracellular vesicles (EVs) play a critical role in intercellular communication by transferring microRNAs, lipids and proteins to neighboring cells. Sortilin, a sorting receptor that directs target proteins to the secretary or endocytic compartments of cells, is found in both EVs and cells. In many diseases, including cardiovascular calcification and cancer, sortilin expression levels are atypically high. We previously demonstrated that sortilin promotes vascular calcification via its trafficking of tissue-nonspecific alkaline phosphatase to EVs. Therefore, suppressing trafficking of sortilin to EVs may act as a novel therapy against EV-associated diseases. However, the precise mechanisms of sortilin trafficking remain to be determined. In this study, we hypothesized that dimerization of sortilin regulates its trafficking to EVs. Approach and Results: We found that sortilin forms a homodimer with an intermolecular disulfide bond (IDB) at Cysteine783 (Cys783) residue. Palmitoylation and the IDB formation compete for Cys783. Formation of the IDB led to trafficking of sortilin to EVs by preventing palmitoylation, which further promoted sortilin trafficking to the Golgi apparatus. Moreover, addition of sortilin-derived propeptide decreased sortilin homodimers within EVs, suggesting that the propeptide binding suppresses sortilin trafficking to EVs through prevention of its dimerization. We also found that soluble sortilin secreted by cells overexpressing full-length sortilin forms homodimers with IDBs using various commercially available antibodies against sortilin, thus providing an opportunity for diagnosis of EV-associated diseases by detection of sortilin homodimers in patients. Conclusions: Sortilin is transported to EVs via the formation of homodimers with an IDB, which is endogenously regulated by its own propeptide. Therefore, inhibiting sortilin dimerization may provide a novel therapy against EV-associated diseases, including cardiovascular calcification and cancer. In addition, soluble sortilin homodimer with IDBs could be detected and used as a novel diagnostic biomarker for EV-associated diseases.

application/pdf, Welding in the World. 2015, 59 (4), P.589-595

Background: The rodent salivary gland is not fully developed at birth and the cellular definitive differentiation takes place postnatally. However, little is known about its molecular mechanism. Results: Here we provide the loss-of-function genetic evidence that Runx signaling affects postnatal development of the submandibular gland (SMG). Core binding factor b (Cbfb) is a cotranscription factor which forms a heterodimer with Runx proteins. Cbfb was specifically expressed in the duct epithelium, specifically in the SMG. Epithelial Cbfb deficiency resulted in decrease in the size of the SMG and in the saliva secretion on postnatal day 35. The Cbfb mutant SMG specifically exhibited involution of the granular convoluted tubules (GCT), with a down-regulated expression of its marker genes, such as Klk1, Ngf, and Egf. The induction of GCT is under the control of androgens, and the Cbfb mutant SMG demonstrated down-regulated expression of Crisp3, an androgen-dependent transcript. Because the circulating testosterone or tissue dihydrotestosterone levels were not affected in the Cbfb mutants, it appears that Runx/Cbfb signaling regulate androgen receptor pathway, but does not affect the circulating testosterone levels or the enzymatic conversion to DHT. Conclusions: Runx signaling is important in the postnatal development of androgen-dependent GCT in the SMG. Developmental Dynamics 000:000–000, 2014. V C 2014 Wiley Periodicals, Inc.

Due to the rapid improvement of digital cameras, especially the pixel resolution, digital image correlation (DIC) has been introduced to measure the deformation and strain of structures. Using digital cameras for the DIC technique is an easy and fast method for obtaining structural information, represented as all the pixel points in a photo. Because a wide range of structural deformation can be obtained with high accuracy, this method has the potential to be very useful. Currently, DIC can execute a measurement with high accuracy only when the out-of-plane displacement is small. When the out-of-plane displacement is large, the deformation causes the measurement error. Therefore, a stereo imaging method using two digital cameras is proposed in this study. The proposed method can measure not only in-plane deformation but also out-of-plane deformation with high accuracy without calibration of the errors caused by the out-of-plane displacement. In this paper, the measurement accuracy of the proposed method fo...

Displacement during welding provides important information to understand the mechanisms of welding deformation and residual stress. In particular, if welding deformation can be measured sequentially and the displacement distribution over full field can be measured such as the results obtained by finite element analysis, they can be valuable information. Therefore, in this study, a 3-dimensional (3D) deformation (in-plane and out-of-plane deformation) measurement method is developed using a digital camera, which requires no special equipment. This method is a non-contact method and it can sequentially measure over the entire photographed image. Furthermore, since image analysis is based on the technique of image matching, the method is applicable even when measuring deformation is large. In addition, since it is possible to use all pixels as measuring points, the number of available measuring points at one time is the same as the number of effective pixels of the camera. This is currently more than 15 mill...

Recent progress in gene-editing technology has provided a strong impact for improved our understanding of molecular functions in living organisms. Here we describe our method to generate transgene-overexpressing mouse models, which method involves the use of tissue-specific promoters for analyzing a certain molecule (s) in special tissues. The protocol described in this chapter uses the Col2a1 promoter-enhancer, which is known for driving specific and strong transgene expression in cartilage and is based on several of our studies showing a positive role of the connective tissue growth factor (CCN2) in cartilage-bone development and maintenance of articular cartilage. These mice show strongly accelerated endochondral ossification resulting in enhanced bone elongation, as well as resistance to age-related articular degeneration. This protocol also describes how to analyze the molecular mechanisms of these phenomena by use of chondrocytes isolated from CCN2-overexpressing cartilage.

Recent progress in gene-editing technology has provided a strong impact for improved our understanding of molecular functions in living organisms. Here we describe our method to generate transgene-overexpressing mouse models, which method involves the use of tissue-specific promoters for analyzing a certain molecule (s) in special tissues. The protocol described in this chapter uses the Col2a1 promoter-enhancer, which is known for driving specific and strong transgene expression in cartilage and is based on several of our studies showing a positive role of the connective tissue growth factor (CCN2) in cartilage-bone development and maintenance of articular cartilage. These mice show strongly accelerated endochondral ossification resulting in enhanced bone elongation, as well as resistance to age-related articular degeneration. This protocol also describes how to analyze the molecular mechanisms of these phenomena by use of chondrocytes isolated from CCN2-overexpressing cartilage.

A three-dimensional (3D) deformation (in plane and out of plane deformations) measurement method is developed using digital cameras, which require no special equipment. This method is a non-contact method, and it can sequentially measure over the entire photographed image. Furthermore, since image analysis is based on the technique of image matching, the method is applicable even when the deformation to be measured is large. In addition, since it is possible to use all pixels as measuring points, the number of available measuring points at one time is the same as the number of effective pixels of the camera. In this study, the proposed method is applied to the sequential measurement of displacement under strong lighting levels in arc welding. Through the comparison of the results measured by a 3D shape measurement system (LAT-3D) using a laser displacement gauge and digital caliper, the quantitative validity of the proposed method is also verified.

The technique that can measure the transient welding deformation directly is very important for investigating the mechanism of welding deformation. In this study, an in-situ displacement measurement method using digital camera is self developed. This system is non-contact type and it does not need any complicated optical systems but it can measure the in situ displacement over the full field high accuracy using digital image correlation technique. Therefore, it is considered to be useful and easy to apply to practical problems. The number of measuring points that can be obtained at a time is more than 10 million. It is the same as the available pixels of the digital camera. Furthermore, since the active light source is not necessary in this system, the influence of the fluctuation of the atmosphere caused by the high temperature area is small. In this study, the detail of the proposed system is given and it is applied to the transient in-plane deformation problem under very high brightness lightened by we...

In temper bead welding, hardness is one of the key criteria to evaluate the tempering effect. A neural network-based method for hardness prediction in the heat affected zone (HAZ) of low-alloy steel has been investigated in the present study to evaluate the tempering effect in temper bead welding. The new hardness prediction system was constructed by using a neural network based on the experimentally obtained hardness database. On the basis of the thermal cycles numerically obtained by FEM, hardness distribution in HAZ of low alloy steel welded with temper bead welding method was calculated. The predicted hardness was in good accordance with the experimental results. It follows that our new prediction system is effective for estimating the tempering effect in HAZ during temper bead welding and hence enables us to assess the effectiveness of temper bead welding.

A new thermal cycle tempering parameter (TCTP) to characterize the tempering effect during multi-pass thermal cycles has been proposed by extending the Larson-Miller parameter (LMP) to non-isothermal heat treatment. Experimental results revealed that the hardness in synthetic HAZ of low-alloy steel subjected to multi-pass tempering thermal cycles has a good linear relationship with the TCTP. The new hardness prediction system was constructed by using a neural network taking into consideration of the tempering effect during multi-pass welding, estimated by using the TCTP. Based on the thermal cycles numerically obtained by FEM and the experimentally obtained hardness database, the hardness distribution in HAZ of low-alloy steel welded with temper bead welding method was calculated. The predicted hardness was in good accordance with the experimental results. It follows that our new prediction system is effective for estimating the tempering effect in HAZ during multi-pass welding and hence enables us to assess the effectiveness of temper bead welding.

SummaryInsulin receptor substrate (Irs) mediates metabolic actions of insulin. Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis. The PI3K activity associated with Irs2 began to increase during fasting, reached its peak immediately after refeeding, and decreased rapidly thereafter. By contrast, the PI3K activity associated with Irs1 began to increase a few hours after refeeding and reached its peak thereafter. The data indicate that Irs2 mainly functions during fasting and immediately after refeeding, and Irs1 functions primarily after refeeding. In fact, liver-specific Irs1-knockout mice failed to exhibit insulin resistance during fasting, but showed insulin resistance after refeeding; conversely, liver-specific Irs2-knockout mice displayed insulin resistance during fasting but not after refeeding. We propose the concept of the existence of a dynamic relay between Irs1 and Irs2 in hepatic insulin signaling during fasting and feeding.

The concentration of polyacrylate (PA) used as a scale inhibitor was potentiometrically determined with a solid state copper ion-selective electrode after addition of Cu2+ as a probe. While the conventional methods monitor only the total concentration of PA, the proposed method measures the free, “effective” concentration of PA in equilibrium with species like Ca2+ and CaCO3. The slope of a potential response to PA was −40 mV decade−1 and the limit of detection was 10−6.3 M (= mol dm−3) at a probe concentration of 10−6 M. The system could be used to control the PA concentration just enough to prevent the scale formation in various circulating water systems.

We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration.

The Finite Element Method (FEM) is a powerful tool to predict welding residual stresses and distortions. However, it is impossible to analyse the hot cracking with a simple thermal-elastic-plastic FEM code, since the conventional FEM models only volumetric behaviour. Based on the interface element proposed for the cracking propagation problem, a three-dimensional FEM with a temperature dependent interface element has been developed. The proposed method is applied to the analysis of the pear-shaped bead cracking under narrow gap welding as one example of hot cracking in welding. Both the pear-shaped bead cracking and the surface cracking along the welding line can be simulated using the proposed method. Also, it is found that the heat input, the groove width, and the constraint under the solidification are the essential causes of the pear-shaped bead cracking.

Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules that play roles in organization of a variety of cell-cell junctions in cooperation with or independently of cadherins. Four nectins have been identified. Five nectin-like molecules, which have domain structures similar to those of nectins, have been identified, and we characterized here nectin-like molecule-2 (Necl-2)/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1. Necl-2 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-1/TSLL1/SynCAM3 and nectin-3. Necl-2 was widely expressed in rat tissues examined. Necl-2 localized at the basolateral plasma membrane in epithelial cells of the mouse gall bladder, but not at specialized cell-cell junctions, such as tight junctions, adherens junctions, and desmosomes. Nectins bind afadin, whereas Necl-2 did not bind afadin but bound Pals2, a membrane-associated guanylate kinase family member known to bind Lin-7, implicated in the proper localization of the Let-23 protein in Caenorhabditis elegans, the homologue of mammalian epidermal growth factor receptor. These results indicate the unique localization of Necl-2 and its possible involvement in localization of a transmembrane protein(s) through Pals2.

Malignant transformation of cells causes disruption of cell-cell adhesion, enhancement of cell motility, and invasion into surrounding tissues. Nectins have both homophilic and heterophilic cell-cell adhesion activities and organize adherens junctions in cooperation with cadherins. We examined here whether Tage4, which was originally identified to be a gene overexpressed in colon carcinoma and has a domain structure similar to those of nectins, is involved in cell adhesion and/or migration. Tage4 heterophilically trans-interacted with nectin-3, but not homophilically with Tage4. Expression of Tage4 was markedly elevated in NIH3T3 cells transformed by an oncogenic Ki-Ras (V12Ras-NIH3T3 cells) as compared with that of wild-type NIH3T3 cells. trans-Interaction of Tage4 with nectin-3 enhanced motility of V12Ras-NIH3T3 cells. Tage4 did not bind afadin, a nectin- and actin filament-binding protein that connects nectins to the actin cytoskeleton and cadherins through catenins. Thus, Tage4 heterophilically trans-interacts with nectin-3 and regulates cell migration. Tage4 is tentatively re-named here nectin-like molecule-5 (necl-5) on the basis of its function and domain structure similar to those of nectins.

In this study, a spectroscopic method is applied to measure two-dimensional (2D) distributions of flame temperatures during regenerative combustion of natural gas with highly preheated air in a test furnace of industrial size. By using a CCD camera fitted with an optical bandpass filter, the 2D distributions of the continuum emission from soot particles in premix and diffusion flames are measured at two different wavelengths. Subsequently, the temperature is determined on the basis of the two-color 2D thermometry, in which the ratio of the 2D emission intensity distributions is converted into the 2D temperature distribution with much higher spatial resolution in comparison with those obtainable by thermocouples. The emission profiles of NO radiation also were measured and the results are discussed in conjunction with difference in the temperature profiles of the flames.

The rodent salivary gland is not fully developed at birth and the cellular definitive differentiation takes place postnatally. However, little is known about its molecular mechanism.Here we provide the loss-of-function genetic evidence that Runx signaling affects postnatal development of the submandibular gland (SMG). Core binding factor β (Cbfb) is a cotranscription factor which forms a heterodimer with Runx proteins. Cbfb was specifically expressed in the duct epithelium, specifically in the SMG. Epithelial Cbfb deficiency resulted in decrease in the size of the SMG and in the saliva secretion on postnatal day 35. The Cbfb mutant SMG specifically exhibited involution of the granular convoluted tubules (GCT), with a down-regulated expression of its marker genes, such as Klk1, Ngf, and Egf. The induction of GCT is under the control of androgens, and the Cbfb mutant SMG demonstrated down-regulated expression of Crisp3, an androgen-dependent transcript. Because the circulating testosterone or tissue dihydrotestosterone levels were not affected in the Cbfb mutants, it appears that Runx/Cbfb signaling regulate androgen receptor pathway, but does not affect the circulating testosterone levels or the enzymatic conversion to DHT.Runx signaling is important in the postnatal development of androgen-dependent GCT in the SMG.

Laser-induced plasma spectroscopy (LIPS) was applied to direct multi-element analysis of chemical species in a hydrogen–air diffusion flame. The plasma was generated by focusing the second harmonic radiation from a Nd:YAG laser at a wavelength of 532 nm and the resulting plasma emission was detected by a multi-channel spectrometer. The spatial profiles obtained by LIPS measurements for the atomic emission intensities of hydrogen and oxygen, normalized by that of nitrogen, were in good agreement with those of numerical simulation. The present results show that LIPS has a high potential for the quantitative elemental analysis of chemical species in a flame.

To prevent primary water stress corrosion cracking (PWSCC), water jet peening (WJP) has been used on the welds of Ni-based alloys in pressurized water reactors (PWRs). Before WJP, the welds are machined and buffed in order to conduct a penetrant test (PT) to verify the weld qualities to access, and microstructure evolution takes place in the target area due to the severe plastic deformation. The compressive residual stresses induced by WJP might be unstable under elevated temperatures because of the high dislocation density in the compressive stress layer. Therefore, the stability of the compressive residual stresses caused by WJP was investigated during long-term operation by considering the microstructure evolution due to the working processes. The following conclusions were made: The compressive residual stresses were slightly relaxed in the surface layers of the thermally aged specimens. There were no differences in the magnitude of the relaxation based on temperature or time. The compressive residual stresses induced by WJP were confirmed to remain stable under elevated temperatures. The stress relaxation at the surface followed the Johnson–Mehl equation, which states that stress relaxation can occur due to the recovery of severe plastic strain, since the estimated activation energy agrees very well with the self-diffusion energy for Ni. By utilizing the additivity rule, it was indicated that stress relaxation due to recovery is completed during the startup process. It was proposed that the long-term stability of WJP under elevated temperatures must be assessed based on compressive stresses with respect to the yield stress. Thermal elastic–plastic creep analysis was performed to predict the effect of creep strain. After 100 yr of simulated continuous operation at 80% capacity, there was little change in the WJP compressive stresses under an actual operating temperature of 623 K. Therefore, the long-term stability of WJP during actual operation was analytically predicted.

Previously we showed that CCN family member 2/connective tissue growth factor (CCN2) promotes the proliferation, differentiation, and maturation of growth cartilage cells in vitro. To elucidate the specific role and molecular mechanism of CCN2 in cartilage development in vivo, in the present study we generated transgenic mice overexpressing CCN2 and analyzed them with respect to cartilage and bone development. Transgenic mice were generated expressing a ccn2/lacZ fusion gene in cartilage under the control of the 6 kb-Col2a1-enhancer/promoter. Changes in cartilage and bone development were analyzed histologically and immunohistologically and also by micro CT. Primary chondrocytes as well as limb bud mesenchymal cells were cultured and analyzed for changes in expression of cartilage-related genes, and non-transgenic chondrocytes were treated in culture with recombinant CCN2. Newborn transgenic mice showed extended length of their long bones, increased content of proteoglycans and collagen II accumulation. Micro-CT analysis of transgenic bones indicated increases in bone thickness and mineral density. Chondrocyte proliferation was enhanced in the transgenic cartilage. In in vitro short-term cultures of transgenic chondrocytes, the expression of col2a1, aggrecan and ccn2 genes was substantially enhanced; and in long-term cultures the expression levels of these genes were further enhanced. Also, in vitro chondrogenesis was strongly enhanced. IGF-I and IGF-II mRNA levels were elevated in transgenic chondrocytes, and treatment of non-transgenic chondrocytes with recombinant CCN2 stimulated the expression of these mRNA. The addition of CCN2 to non-transgenic chondrocytes induced the phosphorylation of IGFR, and ccn2-overexpressing chondrocytes showed enhanced phosphorylation of IGFR. Our data indicates that the observed effects of CCN2 may be mediated in part by CCN2-induced overexpression of IGF-I and IGF-II. These findings indicate that CCN2-overexpression in transgenic mice accelerated the endochondral ossification processes, resulting in increased length of their long bones. Our results also indicate the possible involvement of locally enhanced IGF-I or IGF-II in this extended bone growth.

A 3-dimensional deformation (in-plane and out-of-plane deformation) measurement method is developed using digital cameras, which require no special equipment. This method is a non-contact method and it can sequentially measure over the entire photographed image. Furthermore, since image analysis is based on the technique of image matching, the method is applicable even when measuring deformation is large. In addition, since it is possible to use all pixels as measuring points, the number of available measuring points at one time is the same as the number of effective pixels of the camera. In this study, proposed method is applied to the sequential measurement of displacement under the strong lighting levels in arc welding. Through the comparison of the results measured by a 3-dimensional shape measurement system (LAT-3D) using a laser displacement gauge and digital caliper, quantitative validity of the proposed method is also verified.

Heavy thick steel plate is used for pipes and also ship structures, and multi-pass welding is usually adopted for the welding. Because of the heavy thickness, residual stress plays an important role, particularly in crack propagation. Implicit Finite Element Method (FEM) is often used as a welding analysis method to examine the residual stress of the welded plate, but it is not easily applied to multi-pass welding problems with tens of thousands of degrees of freedom, because of the huge computational time and memory consumption. Alternatively, it is possible to simulate the residual stress in shorter time with lower memory consumption by using Idealized Explicit Finite Element Method developed by the authors. Moreover, the computational time can be shortened by using Idealized Explicit FEM using a Graphics Processing Unit (GPU). In this research, Idealized Explicit FEM parallelized using a GPU is applied to the analysis of the residual stresses of the multi-pass welding joint of a pipe structure made of heavy thick steel plate. As the result, the residual stress simulated by the Idealized Explicit FEM corresponds to the measured residual stress. Furthermore, it is found that the grouping method may affect to the residual stress distribution.

BACKGROUND:K-134 is a more potent antiplatelet drug with a selective inhibitory effect on phosphodiesterase 3 (PDE3) compared with its analogue, cilostazol. OBJECTIVES:This study was performed to compare the ameliorating effects of K-134 and cilostazol on brain damage in an experimental photothrombotic cerebral infarction model. METHODS AND RESULTS:We investigated the effects of oral preadministration of PDE3 inhibitors in a rat stroke model established by photothrombotic middle cerebral artery (MCA) occlusion. K-134 significantly prolonged MCA occlusion time at doses >10 mg/kg, and reduced cerebral infarct size at 30 mg/kg in the stroke model (n = 12, 87.5±5.6 vs. 126.8±7.5 mm(3), P