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The effect of calcium consumption in the prevention of type 2 diabetes mellitus (T2DM) remains controversial, and depends on food calcium sources. This prospective study aimed to evaluate the association between calcium-rich food consumption and T2DM incidence among Korean adults. We analyzed the data of 8574 adults aged 40&ndash, 69 years, without a history of T2DM, cardiovascular disease, and cancer at the baseline from the Korean Genome and Epidemiology Study. The consumption of calcium-rich foods was assessed using a validated semi-quantitative food frequency questionnaire. T2DM-related data were collected using biennial questionnaires, health examinations, and clinical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. In the multivariate-adjusted model, yogurt intake was inversely associated with T2DM risk (HR: 0.73, 95% CI: 0.61&ndash, 0.88 in the fourth quartile as compared to the first quartile). However, the intakes of other calcium-rich foods, including milk and anchovies, were not significantly associated with T2DM risk. Yogurt may provide protective effects against T2DM in Korean adults, owing to the beneficial effects of probiotics. Further prospective large-scale cohort studies should be conducted to validate these findings.

Developing and mature chondrocytes constantly interact with and remodel the surrounding extracellular matrix (ECM). Recent research indicates that integrin-ECM interaction is differentially regulated during cartilage formation (chondrogenesis). Integrin signaling is also a key source of the catabolic reactions responsible for joint destruction in both rheumatoid arthritis and osteoarthritis. However, we do not understand how chondrocytes dynamically regulate integrin signaling in such an ECM-rich environment. Here, we found that developing chondrocytes express integrin-β-like 1 (Itgbl1) at specific stages, inhibiting integrin signaling and promoting chondrogenesis. Unlike cytosolic integrin inhibitors, ITGBL1 is secreted and physically interacts with integrins to down-regulate activity. We observed that Itgbl1 expression was strongly reduced in the damaged articular cartilage of patients with osteoarthritis (OA). Ectopic expression of Itgbl1 protected joint cartilage against OA development in the destabilization of the medial meniscus-induced OA mouse model. Our results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders and suggest the potential therapeutic utility of targeting ITGBL1 to modulate integrin signaling in human disease.

Background and Purpose 3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models. Experimental Approach The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes in vitro and an in vivo mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining. Key Results 3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis via NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models. Conclusions and Implications 3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.

The Baekdong and Gwangcheon areas are located within the Hongseong collision belt of South Korea, and the discovery of late Permian–Triassic eclogites has confirmed this belt as an extension of the Qinling–Dabie–Sulu collision belt in China. The Qinling–Dabie–Sulu belt records a middle Paleozoic continental collision in addition to the late Permian–Triassic collision of the North and South China cratons. In this paper, we present evidence for middle Paleozoic igneous and metamorphic events in the Baekdong and Gwangcheon areas. Metabasites and meta-basaltic andesites in the Baekdong area originated in an arc tectonic setting at ca. 470–437 Ma, and underwent an intermediate-P/T metamorphism (6.2–8.2 kbar, 620–700 °C) at ca. 418–405 Ma. The meta-basaltic andesite in the Gwangcheon area underwent a high-pressure granulite facies metamorphism (close to the eclogite facies) at ca. 392–381 Ma. P–T values of 15.7–19.9 kbar and 860–890 °C were obtained for the peak metamorphism using conventional geothermobarometry, and conditions of 16–17 kbar and 870–920 °C were estimated by thermodynamic pseudosection analysis using the Perplex X program. Together with the late Permian–Triassic eclogites previously reported from the Hongseong area, these middle Paleozoic igneous activities that were related to subduction and metamorphism indicate that the Hongseong area underwent collision in the middle Paleozoic (418–381 Ma), in addition to the late Permian–Triassic collision, as recorded in the Qinling–Dabie–Sulu belt in China.

Objective Hypoxia-inducible factor 2α (HIF-2α), encoded by Epas1 , causes osteoarthritic cartilage destruction by regulating the expression of matrix-degrading enzymes. We undertook this study to explore the role of nicotinamide phosphoribosyltransferase (NAMPT or visfatin) in HIF-2α-mediated osteoarthritic cartilage destruction. Methods The expression of HIF-2α, NAMPT and matrix-degrading enzymes was determined at the mRNA and protein levels in human osteoarthritis (OA) cartilage, mouse experimental OA cartilage and primary cultured mouse chondrocytes. Experimental OA in mice was induced by destabilisation of the medial meniscus (DMM) surgery or intra-articular injection of Ad- Epas1 or Ad- Nampt in wild-type, Epas1 +/− , Epas1 fl/fl ; Col2a1-Cre and Col2a1-Nampt transgenic (TG) mice. Primary cultured mouse chondrocytes were treated with recombinant NAMPT protein or were infected with adenoviruses. Results We found that the Nampt gene is a direct target of HIF-2α in articular chondrocytes and OA cartilage. NAMPT protein, in turn, increased mRNA levels and activities of MMP3, MMP12 and MMP13 in chondrocytes, an action that was necessary for HIF-2α-induced expression of catabolic enzymes. Gain-of-function studies (intra-articular injection of Ad- Nampt; Col2a1-Nampt TG mice) and loss-of-function studies (intra-articular injection of the NAMPT inhibitor FK866) demonstrated that NAMPT is an essential catabolic regulator of osteoarthritic cartilage destruction caused by HIF-2α or DMM surgery. Conclusions Our findings indicate that NAMPT, whose corresponding gene is a direct target of HIF-2α, plays an essential catabolic role in OA pathogenesis and acts as a crucial mediator of osteoarthritic cartilage destruction caused by HIF-2α or DMM surgery.

We have shown that cytokine-like 1 (Cytl1) is a novel autocrine regulatory factor that regulates chondrogenesis of mouse mesenchymal cells (Kim, J. S., Ryoo, Z. Y., and Chun, J. S. (2007) J. Biol. Chem. 282, 29359-29367). In this previous work, we found that Cytl1 expression was very low in mesenchymal cells, increased dramatically during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. Moreover, exogenous addition or ectopic expression of Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells. In the current study, we generated a Cytl1 knock-out (Cytl1(-/-)) mouse to investigate the in vivo role of Cytl1. Deletion of the Cytl1 gene did not affect chondrogenesis or cartilage development. Cytl1(-/-) mice also showed normal endochondral ossification and long bone development. Additionally, ultrastructural features of articular cartilage, such as matrix organization and chondrocyte morphology, were similar in wild-type and Cytl1(-/-) mice. However, Cytl1(-/-) mice were more sensitive to osteoarthritic (OA) cartilage destruction. Compared with wild-type littermates, Cytl1(-/-) mice showed more severe OA cartilage destruction upon destabilization of the medial meniscus of mouse knee joints. In addition, expression levels of Cytl1 were markedly decreased in OA cartilage of humans and experimental mice. Taken together, our results suggest that, rather than regulating cartilage and bone development, Cytl1 is required for the maintenance of cartilage homeostasis, and loss of Cytl1 function is associated with experimental OA cartilage destruction in mice.

Summary Osteoarthritis (OA), primarily characterized by cartilage degeneration, is caused by an imbalance between anabolic and catabolic factors. Here, we investigated the role of zinc (Zn 2+ ) homeostasis, Zn 2+ transporters, and Zn 2+ -dependent transcription factors in OA pathogenesis. Among Zn 2+ transporters, the Zn 2+ importer ZIP8 was specifically upregulated in OA cartilage of humans and mice, resulting in increased levels of intracellular Zn 2+ in chondrocytes. ZIP8-mediated Zn 2+ influx upregulated the expression of matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, and ADAMTS5) in chondrocytes. Ectopic expression of ZIP8 in mouse cartilage tissue caused OA cartilage destruction, whereas Zip8 knockout suppressed surgically induced OA pathogenesis, with concomitant modulation of Zn 2+ influx and matrix-degrading enzymes. Furthermore, MTF1 was identified as an essential transcription factor in mediating Zn 2+ /ZIP8-induced catabolic factor expression, and genetic modulation of Mtf1 in mice altered OA pathogenesis. We propose that the zinc-ZIP8-MTF1 axis is an essential catabolic regulator of OA pathogenesis.

Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1–4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte- and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption. © 2012 American Society for Bone and Mineral Research.

In a distributed system, the synchronization of tasks executed in different nodes is necessary. Therefore, we propose a method of synchronization of tasks in a distributed system using FlexRay. FlexRay is expected to become a dominant protocol in automotive systems. It supports a clock synchronization mechanism. We present two methods for synchronization of tasks using a clock synchronized by FlexRay. One is a synchronization method for the start point of tasks. The other is a synchronization method for specific points in the task. We implement the proposed method as an experiment.

Nowadays, electronic control units (ECUs) have more and more importance on the value of modern automobiles. This trend is causing the complexity of the overall systems to increase and make the development cycles longer. In order to address these problems, strategies to reuse software and a growing emphasis to develop hardware/software co-simulation schemes are gathering strength. The software reuse allows modular design aspects to be promoted and helps in limiting the development efforts needed. The hardware/software co-simulation enables early validation, easy robustness evaluation of the system and reduces the overall development cycles. This article proposes the development and adoption of software reusable blocks that can be in the hardware and/or software domains. The proposed blocks contain the common characteristics of several communication protocols. In this paper, we develop the CAN communication protocol by using the proposed softwarepsilas reusable common blocks and added block that has some protocol specialized characteristics and compare the simulation results with real CAN signals from 16-bit embedded system for ECUs.

Human-robot interaction technology, used to command a robot or to acquire information from a robot, is defined as the communication method between humans and the robot. Human-robot interaction consists of the input facility, environment display, intuitive command and reaction, and the architecture of the interface program. This research focuses on the framework of the interface program that contains the controls, communication architecture and robot mark-up languages. The application that builds the intelligent user interface uses the functions: plug-and-play for robot peripherals; self-diagnosis; and multimodal sensor fusion. This research proposes the robotpsilas architecture to make the decision based on the robotpsilas level of autonomy. Our intelligent user interface system consists of ultrasonic, position sensitive detector (PSD), and DC motors. We verify operation of the intelligent user interface for the human-robot interaction through evaluating a scenario: the remote control of the mobile robotpsilas navigation in an environment containing obstacles.

The gateway system is an essential component for network-to-network communication using different protocols inside a distributed system. Since reliability is an important aspect in an automotive system, here we propose a method for improving the reliability of the gateway system by using OSEK/VDX and duplication scheme. Three factors were considered for improving the reliability of the gateway. First, a high priority message must be processed first. Second, the gateway should not transmit messages to erroneous nodes that cannot receive messages by checking the accessibility of the destination node. Third, a sub-gateway should be used alternately with the main gateway when the main gateway cannot operate correctly. In this study, we developed a CAN and FlexRay gateway embedded system and applied the proposed method to this system.

Developing and validating a distributed system requires great cost, time, and effort than a centralized system because the systems are inherently concurrent, asynchronous, and nondeterministic. For this reason, accurate simulation function is significantly important for developing the distributed system. In particular, it finds applications in the automobile embedded system industry, which requires short time-to-market. If the simulation function is able to simulate the hardware characteristics of the distributed system, the accuracy of the simulator increases. We develop a 16-bit embedded system for an electronic control unit (ECU) in an automobile system and a block for modeling and simulating for distributed system with considering of hardware characteristics, especially caused by network characteristics. In this paper, consequence of simulation with real-value in the 16-bit embedded system is compared.