A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.

Science.gov (United States)

Crossland, Hannah; Timmons, James A; Atherton, Philip J

2017-12-01

Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1-mediated myotube hypertrophy in vitro Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (-64 ± 5% vs. IGF-1; P IGF-1; P IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro. -Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes. © The Author(s).

Phosphoinositide 3-kinase/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.

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Lim, Jeong A; Woo, Joo Hong; Kim, Hye Sun

2008-09-01

In this study, it was found that undifferentiated myoblasts were more vulnerable to menadione-induced oxidative stress than differentiated myotubes. Cell death occurred with a relatively low concentration of menadione in myoblasts compared to myotubes. With the same concentration of menadione, the Bcl-2/Bax ratio decreased and nuclei containing condensed chromatin were observed in myoblasts to a greater extent than in myotubes. However, myotubes became increasingly susceptible to menadione when phosphoinositide 3-kinase (PI3-K) was blocked by pre-incubation with LY294002, a PI3-K inhibitor. Actually, PI3-K activity was reduced by menadione in myoblasts but not in myotubes. In addition, the phosphorylation of Akt, a downstream effector of PI3-K, was inhibited in myoblasts by menadione but increased in myotubes. Both LY294002 and API-2, an Akt inhibitor, decreased the Bcl-2/Bax ratio in menadione-exposed myotubes. These results suggest that the differential activity of PI3-K/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.

Reduced TCA Flux in Diabetic Myotubes: Determined by Single Defects?

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Gaster, Michael

2012-01-01

The diabetic phenotype is complex, requiring elucidation of key initiating defects. Diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux but at present it is unclear in which part of the TCA cycle the defect is localised. In order to localise the defect we studied ATP production in isolated mitochondria from substrates entering the TCA cycle at various points. ATP production was measured by luminescence with or without concomitant ATP utilisation by hexokinase in mitochondria isolated from myotubes established from eight lean and eight type 2 diabetic subjects. The ATP production of investigated substrate combinations was significantly reduced in mitochondria isolated from type 2 diabetic subjects compared to lean. However, when ATP synthesis rates at different substrate combinations were normalized to the corresponding individual pyruvate-malate rate, there was no significant difference between groups. These results show that the primary reduced TCA cycle flux in diabetic myotubes is not explained by defects in specific part of the TCA cycle but rather results from a general downregulation of the TCA cycle.

Effect of Excess Gravitational Force on Cultured Myotubes in Vitro

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Shigehiro Hashimoto

2013-06-01

Full Text Available An effect of an excess gravitational force on cultured myoblasts has been studied in an experimental system with centrifugal force in vitro. Mouse myoblasts (C2C12 were seeded on a culture dish of 35 mm diameter, and cultured in the Dulbecco's Modified Eagle's Medium until the sub-confluent condition. To apply the excess gravitational force on the cultured cells, the dish was set in a conventional centrifugal machine. Constant gravitational force was applied to the cultured cells for three hours. Variations were made on the gravitational force (6 G, 10 G, 100 G, 500 G, and 800 G with control of the rotational speed of the rotator in the centrifugal machine. Morphology of the cells was observed with a phasecontrast microscope for eight days. The experimental results show that the myotube thickens day by day after the exposure to the excess gravitational force field. The results also show that the higher excess gravitational force thickens myotubes. The microscopic study shows that myotubes thicken with fusion each other.

C2C12 myotubes inhibit the proliferation and differentiation of 3T3-L1 preadipocytes by reducing the expression of glucocorticoid receptor gene

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Chu, Weiwei; Wei, Wei; Yu, Shigang; Han, Haiyin; Shi, Xiaoli [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Sun, Wenxing [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); College of Public Health, Nantong University, Nantong 226019 (China); Gao, Ying [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Zhang, Lifan [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Chen, Jie, E-mail: jiechen@njau.edu.cn [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China)

2016-03-25

Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1 preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3-L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes. - Highlights: • C2C12 myotubes inhibited proliferation and differentiation of 3T3-L1 preadipocytes. • C2C12 myotubes arrested cell cycle of 3T3-L1 preadipocytes. • C2C12 myotubes induced apoptosis of 3T3-L1 preadipocytes. • C2C12 inhibit 3T3-L1 cells by reducing the expression of glucocorticoid receptor gene.

Effect of diisopropylfluorophosphate on synaptic transmission and acetylcholine sensitivity in neuroblastoma-myotube co-culture

International Nuclear Information System (INIS)

Adler, M.; Chang, F.C.T.; Foster, R.E.; Glenn, J.F.; Mark, G.; Maxwell, D.

1986-01-01

The authors investigate the effects of the irreversible organophosphorous cholinesterase inhibitor, DFP, on clonal G8-1 myotubes co-cultured with ACh- secreting NG108-15 neuroblastoma x glioma hybrid cells. The enzyme activity is shown, plotted as a function of time in culture. The enzyme activity remained low over four days. At the end of this time, the cultures were nearly confluent with myoblasts but contained less than 2% multinucleated myotubes. The AChE activity increased gradually after horse serum was added to the growth medium to promote myotube formation, reaching a maximum of 1.1 nmole. C 14 ACh/min/mg protein on the 15th day

Production and release of acylcarnitines by primary myotubes reflect the differences in fasting fat oxidation of the donors.

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Wolf, Magnus; Chen, Shili; Zhao, Xinjie; Scheler, Mika; Irmler, Martin; Staiger, Harald; Beckers, Johannes; de Angelis, Martin Hrabé; Fritsche, Andreas; Häring, Hans-Ulrich; Schleicher, Erwin D; Xu, Guowang; Lehmann, Rainer; Weigert, Cora

2013-06-01

Acylcarnitines are biomarkers of incomplete β-oxidation and mitochondrial lipid overload but indicate also high rates of mitochondrial fatty acid oxidation. It is unknown whether the production of acylcarnitines in primary human myotubes obtained from lean, metabolically healthy subjects reflects the fat oxidation in vivo. Our objective was to quantify the acylcarnitine production in myotubes obtained from subjects with low and high fasting respiratory quotient (RQ). Fasting RQ was determined by indirect calorimetry. Muscle biopsies from the vastus lateralis muscle were taken from 6 subjects with low fasting RQ (mean 0.79 ± 0.03) and 6 with high fasting RQ (0.90 ± 0.03), and satellite cells were isolated, cultured, and differentiated to myotubes. Myotubes were cultivated with 125 μM (13)C-labeled palmitate for 30 minutes and 4 and 24 hours. Quantitative profiling of 42 intracellular and 31 extracellular acylcarnitines was performed by stable isotope dilution-based metabolomics analysis by liquid chromatography coupled to mass spectrometry. Myotubes from donors with high fasting RQ produced and released significant higher amounts of medium-chain acylcarnitines. High (13)C8 and (13)C10 acylcarnitine levels in the extracellular compartment correlated with high fasting RQ. The decreased expression of medium-chain acyl-coenzyme A dehydrogenase (MCAD) in these myotubes can explain the higher rate of incomplete fatty acid oxidation. A lower intracellular [(13)C]acetylcarnitine to carnitine and lower intracellular (13)C16/(13)C18 acylcarnitine to carnitine ratio indicate reduced fatty acid oxidation capacity in these myotubes. Mitochondrial DNA content was not different. Acylcarnitine production and release from primary human myotubes of donors with high fasting RQ indicate a reduced fatty acid oxidation capacity and a higher rate of incomplete fatty acid oxidation. Thus, quantitative profiling of acylcarnitine production in human myotubes can be a suitable tool to

The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes.

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Rom, Oren; Kaisari, Sharon; Aizenbud, Dror; Reznick, Abraham Z

2013-12-01

The toxic aldehydes acetaldehyde and acrolein were previously suggested to damage skeletal muscle. Several conditions in which exposure to acetaldehyde and acrolein is increased were associated with muscle wasting and dysfunction. These include alcoholic myopathy, renal failure, oxidative stress, and inflammation. A main exogenous source of both acetaldehyde and acrolein is cigarette smoking, which was previously associated with increased muscle catabolism. Recently, we have shown that exposure of skeletal myotubes to cigarette smoke stimulated muscle catabolism via increased oxidative stress, activation of p38 MAPK, and upregulation of muscle-specific E3 ubiquitin ligases. In this study, we aimed to investigate the effects of acetaldehyde and acrolein on catabolism of skeletal muscle. Skeletal myotubes differentiated from the C2 myoblast cell line were exposed to acetaldehyde or acrolein and their effects on signaling pathways related to muscle catabolism were studied. Exposure of myotubes to acetaldehyde did not promote muscle catabolism. However, exposure to acrolein caused increased generation of free radicals, activation of p38 MAPK, upregulation of the muscle-specific E3 ligases atrogin-1 and MuRF1, degradation of myosin heavy chain, and atrophy of myotubes. Inhibition of p38 MAPK by SB203580 abolished acrolein-induced muscle catabolism. Our findings demonstrate that acrolein but not acetaldehyde activates a signaling cascade resulting in muscle catabolism in skeletal myotubes. Although within the limitations of an in vitro study, these findings indicate that acrolein may promote muscle wasting in conditions of increased exposure to this aldehyde. Copyright © 2013 Elsevier Inc. All rights reserved.

Regulation of nonmuscle myosin II during 3-methylcholanthrene induced dedifferentiation of C2C12 myotubes

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Dey, Sumit K.; Saha, Shekhar; Das, Provas; Das, Mahua R.; Jana, Siddhartha S., E-mail: bcssj@iacs.res.in

2014-08-01

3-Methylcholanthrene (3MC) induces tumor formation at the site of injection in the hind leg of mice within 110 days. Recent reports reveal that the transformation of normal muscle cells to atypical cells is one of the causes for tumor formation, however the molecular mechanism behind this process is not well understood. Here, we show in an in vitro study that 3MC induces fragmentation of multinucleate myotubes into viable mononucleates. These mononucleates form colonies when they are seeded into soft agar, indicative of cellular transformation. Immunoblot analysis reveals that phosphorylation of myosin regulatory light chain (RLC{sub 20}) is 5.6±0.5 fold reduced in 3MC treated myotubes in comparison to vehicle treated myotubes during the fragmentation of myotubes. In contrast, levels of myogenic factors such as MyoD, Myogenin and cell cycle regulators such as Cyclin D, Cyclin E1 remain unchanged as assessed by real-time PCR array and reverse transcriptase PCR analysis, respectively. Interestingly, addition of the myosin light chain kinase inhibitor, ML-7, enhances the fragmentation, whereas phosphatase inhibitor perturbs the 3MC induced fragmentation of myotubes. These results suggest that decrease in RLC{sub 20} phosphorylation may be associated with the fragmentation step of dedifferentiation. - Highlights: • 3-Methylcholanthrene induces fragmentation of C2C12-myotubes. • Dedifferentiation can be divided into two steps – fragmentation and proliferation. • Fragmentation is associated with rearrangement of nonmuscle myosin II. • Genes associated with differentiation and proliferation are not altered during fragmentation. • Phosphorylation of myosin regulatory light chain is reduced during fragmentation.

An Assessment of Myotube Morphology, Matrix Deformation, and Myogenic mRNA Expression in Custom-Built and Commercially Available Engineered Muscle Chamber Configurations

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Julia M. Jones

2018-05-01

Full Text Available There are several three-dimensional (3D skeletal muscle (SkM tissue engineered models reported in the literature. 3D SkM tissue engineering (TE aims to recapitulate the structure and function of native (in vivo tissue, within an in vitro environment. This requires the differentiation of myoblasts into aligned multinucleated myotubes surrounded by a biologically representative extracellular matrix (ECM. In the present work, a new commercially available 3D SkM TE culture chamber manufactured from polyether ether ketone (PEEK that facilitates suitable development of these myotubes is presented. To assess the outcomes of the myotubes within these constructs, morphological, gene expression, and ECM remodeling parameters were compared against a previously published custom-built model. No significant differences were observed in the morphological and gene expression measures between the newly introduced and the established construct configuration, suggesting biological reproducibility irrespective of manufacturing process. However, TE SkM fabricated using the commercially available PEEK chambers displayed reduced variability in both construct attachment and matrix deformation, likely due to increased reproducibility within the manufacturing process. The mechanical differences between systems may also have contributed to such differences, however, investigation of these variables was beyond the scope of the investigation. Though more expensive than the custom-built models, these PEEK chambers are also suitable for multiple use after autoclaving. As such this would support its use over the previously published handmade culture chamber system, particularly when seeking to develop higher-throughput systems or when experimental cost is not a factor.

Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

International Nuclear Information System (INIS)

Rovetta, Francesca; Stacchiotti, Alessandra; Faggi, Fiorella; Catalani, Simona; Apostoli, Pietro; Fanzani, Alessandro; Aleo, Maria Francesca

2013-01-01

Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl 2 doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl 2 doses for prolonged time points. Furthermore, CoCl 2 treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes

Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

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Kim CH

2016-05-01

Full Text Available Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged

Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

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Rovetta, Francesca [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Stacchiotti, Alessandra [Institute of Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, Brescia I-25123 (Italy); Faggi, Fiorella [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Catalani, Simona; Apostoli, Pietro [Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia I-25123 (Italy); Fanzani, Alessandro, E-mail: fanzani@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Aleo, Maria Francesca, E-mail: aleo@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy)

2013-09-01

Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl{sub 2} doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl{sub 2} doses for prolonged time points. Furthermore, CoCl{sub 2} treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes.

Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

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Nielsen Niels

2010-02-01

Full Text Available Abstract Background Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. Methods Differentiated mouse myotube cultures (C2C12 were exposed to 5 mM creatine monohydrate (CMH for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional 1H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH2 oxidation after 24 h pre-incubation with CMH. Results The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the

Injectable Anisotropic Nanocomposite Hydrogels Direct in Situ Growth and Alignment of Myotubes

International Nuclear Information System (INIS)

De France, Kevin J.; Yager, Kevin G.; Chan, Katelyn J. W.; Corbett, Brandon; Cranston, Emily D.; Hoare, Todd

2017-01-01

Here, while injectable in situ cross-linking hydrogels have attracted increasing attention as minimally invasive tissue scaffolds and controlled delivery systems, their inherently disorganized and isotropic network structure limits their utility in engineering oriented biological tissues. Traditional methods to prepare anisotropic hydrogels are not easily translatable to injectable systems given the need for external equipment to direct anisotropic gel fabrication and/or the required use of temperatures or solvents incompatible with biological systems. Herein, we report a new class of injectable nanocomposite hydrogels based on hydrazone cross-linked poly(oligoethylene glycol methacrylate) and magnetically aligned cellulose nanocrystals (CNCs) capable of encapsulating skeletal muscle myoblasts and promoting their differentiation into highly oriented myotubes in situ. CNC alignment occurs on the same time scale as network gelation and remains fixed after the removal of the magnetic field, enabling concurrent CNC orientation and hydrogel injection. The aligned hydrogels show mechanical and swelling profiles that can be rationally modulated by the degree of CNC alignment and can direct myotube alignment both in two- and three-dimensions following coinjection of the myoblasts with the gel precursor components. As such, these hydrogels represent a critical advancement in anisotropic biomimetic scaffolds that can be generated noninvasively in vivo following simple injection.

Novel in vitro platform to investigate myotube atrophy.

Science.gov (United States)

Oelkrug, Christopher; Horn, Katharina; Makert, Gustavo R; Schubert, Andreas

2015-04-01

The electrical current exclusion (ECE) principle provides an alternative to common methods of cell diameter measurement and especially in atrophy and cancer associated cachexia research. C2C12 myoblasts were differentiated into myotubes and treated with 100 μM dexamethasone to induce atrophy in vitro. Subsequently, they were incubated for 24 h with media containing different concentrations of curcumin and/or branched-chain amino acids (BCAAs) in order to counteract atrophy. After treatment with curcumin, an increase in cell diameter was detectable; the highest increase with 13.9 ± 0.4% was seen with 10 μM curcumin. The combination of curcumin and BCAAs showed an increase of 13.4 ± 1.2 %. Cell diameter measurement via the ECE showed that curcumin, and curcumin in combination with BCAAs, were able to restore atrophic C2C12 myotubes. Therefore, the application of ECE in muscle atrophy and also cancer-associated cachexia research allows rapid screening of novel compounds in order to test their efficacy in vitro. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Reduced TCA Flux in Diabetic Myotubes

DEFF Research Database (Denmark)

Gaster, Michael

2012-01-01

The diabetic phenotype is complex, requiring elucidation of key initiating defects. Diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux but at present it is unclear in which part of the TCA cycle the defect is localised. In order to localise the defect we studied ATP p...... production of investigated substrate combinations was significantly reduced in mitochondria isolated from type 2 diabetic subjects compared to lean. However, when ATP synthesis rates at different substrate combinations were normalized to the corresponding individual pyruvate-malate rate...

Mitochondrial mass is inversely correlated to complete lipid oxidation in human myotubes

DEFF Research Database (Denmark)

Gaster, Michael

2011-01-01

Exercise increases while physical inactivity decrease mitochondrial content and oxidative capacity of skeletal muscles in vivo. It is unknown whether mitochondrial mass and substrate oxidation are related in non-contracting skeletal muscle. Mitochondrial mass, ATP, ADP, AMP, glucose and lipid......, basal glucose oxidation and incomplete lipid oxidation were significantly increased while complete lipid oxidation was lower. Mitochondrial mass was not correlated to glucose oxidation or incomplete lipid oxidation in human myotubes but inversely correlated to complete lipid oxidation. Thus within...... a stable energetic background, an increased mitochondrial mass in human myotubes was not positive correlated to an increased substrate oxidation as expected from skeletal muscles in vivo but surprisingly with a reduced complete lipid oxidation....

Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

Science.gov (United States)

Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu; Khademhosseini, Ali

2014-10-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.

Melatonin modulates rat myotube-acetylcholine receptors by inhibiting calmodulin.

Science.gov (United States)

de Almeida-Paula, Lidiana Duarte; Costa-Lotufo, Leticia V; Silva Ferreira, Zulma; Monteiro, Amanda Elisa G; Isoldi, Mauro Cesar; Godinho, Rosely O; Markus, Regina P

2005-11-21

Melatonin, the pineal gland hormone, modulates alpha-bungarotoxin sensitive nicotinic acetylcholine receptors in sympathetic nerve terminals, cerebellum and chick retina imposing a diurnal variation in functional responses [Markus, R.P., Zago, W.M., Carneiro, R.C., 1996. Melatonin modulation of presynaptic nicotinic acetylcholine receptors in the rat vas deferens. J. Pharmacol. Exp. Ther. 279, 18-22; Markus, R.P., Santos, J.M., Zago, W., Reno, L.A., 2003. Melatonin nocturnal surge modulates nicotinic receptors and nicotine-induced [3HI] glutamate release in rat cerebellum slices. J. Pharmacol. Exp. Ther. 305, 525-530; Sampaio, L.F.S., Hamassaki-Britto, D.E., Markus, R.P., 2005. Influence of melatonin on the development of functional nicotinic acetylcholine receptors in cultured chick retinal cells. Braz. J. Med. Biol. Res. 38, 603-613]. Here we show that in rat myotubes forskolin and melatonin reduced the number of nicotinic acetylcholine receptors expressed in plasma membrane. In addition, these cells expressed melatonin MT1 receptors, which are known to be coupled to G(i)-protein. However, the pharmacological profile of melatonin analogs regarding the reduction in cyclic AMP accumulation and number of nicotinic acetylcholine receptors did not point to a mechanism mediated by activation of G(i)-protein coupled receptors. On the other hand, calmidazolium, a classical inhibitor of calmodulin, reduced in a similar manner both effects. Considering that one isoform of adenylyl cyclase present in rat myotubes is regulated by Ca2+/calmodulin, we propose that melatonin modulates the number of nicotinic acetylcholine receptors via reduction in cyclic AMP accumulation.

Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

DEFF Research Database (Denmark)

Nehlin, Jan O; Just, Marlene; Rustan, Arild C

2011-01-01

Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the prolif......Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating...... that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength....

GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with TGN

DEFF Research Database (Denmark)

Ralston, E; Ploug, Thorkil

1996-01-01

of the constitutive endosomal-lysosomal pathway. To address this question, we have investigated the localization of the endogenous GLUT4 in non-stimulated skeletal myotubes from the cell line C2, by immunofluorescence and immunoelectron microscopy. We have used a panel of antibodies to markers of the Golgi complex...... and in vesicles just beyond, i.e. in the structures that constitute the trans-Golgi network (TGN). In myotubes treated with brefeldin A, the immunofluorescence pattern of GLUT4 is modified, but it differs from both Golgi complex markers and TGN38. Instead, it resembles the pattern of the transferrin receptor...... to the GLUT4-containing tubulo-vesicular elements. In brefeldin A-treated cells, a network of tubules of approximately 70 nm diameter, studded with varicosities, stains for both GLUT4 and transferrin receptor, suggesting that brefeldin A has caused fusion of the transferrin receptor and GLUT4-containing...

Effect of curcumin Extract on Ttranslocation of Glut 4 in C2C12 Myotubes

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J Zavarreza

2013-06-01

Full Text Available Introduction: Curcumin is a major phenolic compound of Curcuma longa, which has long been used in traditional Indian medicine. Recently, curcumin has been reported to have antihyperglycemic activity in animal models. However, the molecular basis of this action has not been adequatedly described. In the present study the antihyperglycemic effect of curcumin was examined using C2C12 myoblast cells. Methods: The effects of curcumin were investigated in C2C12 myotubes by treating the cells with 40 µM of curcumin for 1.5 h. C2C12 myotubes were homogenized and the subcellular fractionation was prepared using ultracentrifugation; Then protein assay was performed using Bradford method and Glut4 determination was done using SDS-PAGE. Moreover, western immunoblotting techniques were exerted for semi-quantitative measurement. Data analysis was performed via gene tools software of Gel documentation and SPSS. An ANOVA test was used to compare three groups together. Results: Comparison of Glut4 levels in C2C12 myotubes showed that myotubes which were exposed to1.5 hours of 40 µM curcunin had higher Glut4 percentages in both cytosolic and membrane fractions and Glut4 percentages were significant with a confidence interval (CI of 95% ( P<0.05 . Conclusion: The study results showed that curcumin can strongly induce the increase of Glut4 translocation in differentiated C2C12 cells, indicating its possible regulatory role in the glucose metabolism of skeletal muscle cells

Apoptosis in differentiating C2C12 muscle cells selectively targets Bcl-2-deficient myotubes

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Schoneich, Christian; Dremina, Elena; Galeva, Nadezhda; Sharov, Victor

2014-01-01

Muscle cell apoptosis accompanies normal muscle development and regeneration, as well as degenerative diseases and aging. C2C12 murine myoblast cells represent a common model to study muscle differentiation. Though it was already shown that myogenic differentiation of C2C12 cells is accompanied by enhanced apoptosis in a fraction of cells, either the cell population sensitive to apoptosis or regulatory mechanisms for the apoptotic response are unclear so far. In the current study we characterize apoptotic phenotypes of different types of C2C12 cells at all stages of differentiation, and report here that myotubes of differentiated C2C12 cells with low levels of anti-apoptotic Bcl-2 expression are particularly vulnerable to apoptosis even though they are displaying low levels of pro-apoptotic proteins Bax, Bak and Bad. In contrast, reserve cells exhibit higher levels of Bcl-2 and high resistance to apoptosis. The transfection of proliferating myoblasts with Bcl-2 prior to differentiation did not protect against spontaneous apoptosis accompanying differentiation of C2C12 cell but led to Bcl-2 overexpression in myotubes and to significant protection from apoptotic cell loss caused by exposure to hydrogen peroxide. Overall, our data advocate for a Bcl-2-dependent mechanism of apoptosis in differentiated muscle cells. However, downstream processes for spontaneous and hydrogen peroxide induced apoptosis are not completely similar. Apoptosis in differentiating myoblasts and myotubes is regulated not through interaction of Bcl-2 with pro-apoptotic Bcl-2 family proteins such as Bax, Bak, and Bad. PMID:24129924

Novel in vitro platform to investigate myotube atrophy

OpenAIRE

Oelkrug, Christopher; Horn, Katharina; Makert, Gustavo R.; Schubert, Andreas

2015-01-01

The electrical current exclusion (ECE) principle provides an alternative to common methods of cell diameter measurement and especially in atrophy and cancer associated cachexia research. C2C12 myoblasts were differentiated into myotubes and treated with 100 μM dexamethasone to induce atrophy in vitro. Subsequently, they were incubated for 24 h with media containing different concentrations of curcumin and/or branched-chain amino acids (BCAAs) in order to counteract atrophy. After treatment wi...

Partly ordered synthesis and degradation of glycogen in cultured rat myotubes

DEFF Research Database (Denmark)

Elsner, Peter; Quistorff, Bjørn; Hansen, Gert H

2001-01-01

The following questions concerning glycogen synthesis and degradation were examined in cultured rat myotubes. 1) Is synthesis and degradation of the individual glycogen molecule a strictly ordered process, with the last glucosyl unit incorporated into the molecule being the first to be released...

Liver X receptor antagonist reduces lipid formation and increases glucose metabolism in myotubes from lean, obese and type 2 diabetic individuals

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Kase, E T; Thoresen, G H; Westerlund, S

2007-01-01

AIMS/HYPOTHESIS: Liver X receptors (LXRs) play important roles in lipid and carbohydrate metabolism. The purpose of the present study was to evaluate effects of the endogenous LXR agonist 22-R-hydroxycholesterol (22-R-HC) and its stereoisomer 22-S-hydroxycholesterol (22-S-HC), in comparison...... with the synthetic agonist T0901317 on lipid and glucose metabolism in human skeletal muscle cells (myotubes). METHODS: Myotubes established from lean and obese control volunteers and from obese type 2 diabetic volunteers were treated with LXR ligands for 4 days. Lipid and glucose metabolisms were studied...... with labelled precursors, and gene expression was analysed using real-time PCR. RESULTS: Treatment with T0901317 increased lipogenesis (de novo lipid synthesis) and lipid accumulation in myotubes, this increase being more pronounced in myotubes from type 2 diabetic volunteers than from lean volunteers...

L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy.

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Mobley, Christopher Brooks; Fox, Carlton D; Ferguson, Brian S; Amin, Rajesh H; Dalbo, Vincent J; Baier, Shawn; Rathmacher, John A; Wilson, Jacob M; Roberts, Michael D

2014-01-01

The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy in vivo.

The primary defect in glycogen synthase activity is not based on increased glycogen synthase kinase-3a activity in diabetic myotubes

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Gaster, Michael; Brusgaard, Klaus; Handberg, Aa.

2004-01-01

The mechanism responsible for the diminished activation of glycogen synthase (GS) in diabetic myotubes remains unclear, but may involve increased activity and/or expression of glycogen synthase kinase-3 (GSK-3). In myotubes established from type 2 diabetic and healthy control subjects we determined...

Long-chain Acyl-CoA is not increased in Myotubes established from Type 2 Diabetic Subjects

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Just, Malene; Faergeman, Nils J; Knudsen, Jens

2006-01-01

Accumulation of intramuscular long-chain acyl-CoA esters (LCACoA) has previously in animal and human models been suggested to play an important role in lipid induced insulin resistance. The aim of this study was to examine whether myotubes established from type 2 diabetic (T2D) subjects and lean...... controls express differences in long-chain acyl-CoA esters (LCACoA) precultured under physiological conditions and during chronic exposure to palmitate (PA) and oleic acids (OA) with/without acute insulin stimulation. No significant differences were found between diabetic and control myotubes, neither...

Amino acids and insulin act additively to regulate components of the ubiquitin-proteasome pathway in C2C12 myotubes

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Lomax Michael A

2007-03-01

Full Text Available Abstract Background The ubiquitin-proteasome system is the predominant pathway for myofibrillar proteolysis but a previous study in C2C12 myotubes only observed alterations in lysosome-dependent proteolysis in response to complete starvation of amino acids or leucine from the media. Here, we determined the interaction between insulin and amino acids in the regulation of myotube proteolysis Results Incubation of C2C12 myotubes with 0.2 × physiological amino acids concentration (0.2 × PC AA, relative to 1.0 × PC AA, significantly increased total proteolysis and the expression of 14-kDa E2 ubiquitin conjugating enzyme (p Conclusion In a C2C12 myotube model of myofibrillar protein turnover, amino acid limitation increases proteolysis in a ubiquitin-proteasome-dependent manner. Increasing amino acids or leucine alone, act additively with insulin to down regulate proteolysis and expression of components of ubiquitin-proteasome pathway. The effects of amino acids on proteolysis but not insulin and leucine, are blocked by inhibition of the mTOR signalling pathway.

Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

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Soo-Yeon Lee

2018-01-01

Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Formation and characterisation of neuromuscular junctions between hiPSC derived motoneurons and myotubes

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M. Demestre

2015-09-01

Full Text Available Striated skeletal muscle cells from humans represent a valuable source for in vitro studies of the motoric system as well as for pathophysiological investigations in the clinical settings. Myoblasts can readily be grown from human muscle tissue. However, if muscle tissue is unavailable, myogenic cells can be generated from human induced pluripotent stem cells (hiPSCs preferably without genetic engineering. Our study aimed to optimize the generation of hiPSCs derived myogenic cells by employing selection of CD34 positive cells and followed by distinct, stepwise culture conditions. Following the expansion of CD34 positive single cells under myogenic cell culture conditions, serum deprived myoblast-like cells finally fused and formed multinucleated striated myotubes that expressed a set of key markers for muscle differentiation. In addition, these myotubes contracted upon electrical stimulation, responded to acetylcholine (Ach and were able to generate action potentials. Finally, we co-cultured motoneurons and myotubes generated from identical hiPSCs cell lines. We could observe the early aggregation of acetylcholine receptors in muscle cells of immature co-cultures. At later stages, we identified and characterised mature neuromuscular junctions (NMJs. In summary, we describe here the successful generation of an iPS cell derived functional cellular system consisting of two distinct communicating cells types. This in vitro co-culture system could therefore contribute to research on diseases in which the motoneurons and the NMJ are predominantly affected, such as in amyotrophic lateral sclerosis or spinal muscular atrophy.

Acute myotube protein synthesis regulation by IL-6-related cytokines.

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Gao, Song; Durstine, J Larry; Koh, Ho-Jin; Carver, Wayne E; Frizzell, Norma; Carson, James A

2017-11-01

IL-6 and leukemia inhibitory factor (LIF), members of the IL-6 family of cytokines, play recognized paradoxical roles in skeletal muscle mass regulation, being associated with both growth and atrophy. Overload or muscle contractions can induce a transient increase in muscle IL-6 and LIF expression, which has a regulatory role in muscle hypertrophy. However, the cellular mechanisms involved in this regulation have not been completely identified. The induction of mammalian target of rapamycin complex 1 (mTORC1)-dependent myofiber protein synthesis is an established regulator of muscle hypertrophy, but the involvement of the IL-6 family of cytokines in this process is poorly understood. Therefore, we investigated the acute effects of IL-6 and LIF administration on mTORC1 signaling and protein synthesis in C2C12 myotubes. The role of glycoprotein 130 (gp130) receptor and downstream signaling pathways, including phosphoinositide 3-kinase (PI3K)-Akt-mTORC1 and signal transducer and activator of transcription 3 (STAT3)-suppressor of cytokine signaling 3 (SOCS3), was investigated by administration of specific siRNA or pharmaceutical inhibitors. Acute administration of IL-6 and LIF induced protein synthesis, which was accompanied by STAT3 activation, Akt-mTORC1 activation, and increased SOCS3 expression. This induction of protein synthesis was blocked by both gp130 siRNA knockdown and Akt inhibition. Interestingly, STAT3 inhibition or Akt downstream mTORC1 signaling inhibition did not fully block the IL-6 or LIF induction of protein synthesis. SOCS3 siRNA knockdown increased basal protein synthesis and extended the duration of the protein synthesis induction by IL-6 and LIF. These results demonstrate that either IL-6 or LIF can activate gp130-Akt signaling axis, which induces protein synthesis via mTORC1-independent mechanisms in cultured myotubes. However, IL-6- or LIF-induced SOCS3 negatively regulates the activation of myotube protein synthesis. Copyright © 2017 the

Primary skeletal muscle cells cultured on gelatin bead microcarriers develop structural and biochemical features characteristic of adult skeletal muscle.

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Kubis, Hans-Peter; Scheibe, Renate J; Decker, Brigitte; Hufendiek, Karsten; Hanke, Nina; Gros, Gerolf; Meissner, Joachim D

2016-04-01

A primary skeletal muscle cell culture, in which myoblasts derived from newborn rabbit hindlimb muscles grow on gelatin bead microcarriers in suspension and differentiate into myotubes, has been established previously. In the course of differentiation and beginning spontaneous contractions, these multinucleated myotubes do not detach from their support. Here, we describe the development of the primary myotubes with respect to their ultrastructural differentiation. Scanning electron microscopy reveals that myotubes not only grow around the surface of one carrier bead but also attach themselves to neighboring carriers, forming bridges between carriers. Transmission electron microscopy demonstrates highly ordered myofibrils, T-tubules, and sarcoplasmic reticulum. The functionality of the contractile apparatus is evidenced by contractile activity that occurs spontaneously or can be elicited by electrostimulation. Creatine kinase activity increases steadily until day 20 of culture. Regarding the expression of isoforms of myosin heavy chains (MHC), we could demonstrate that from day 16 on, no non-adult MHC isoform mRNAs are present. Instead, on day 28 the myotubes express predominantly adult fast MHCIId/x mRNA and protein. This MHC pattern resembles that of fast muscles of adult rabbits. In contrast, primary myotubes grown on matrigel-covered culture dishes express substantial amounts of non-adult MHC protein even on day 21. To conclude, primary myotubes grown on microcarriers in their later stages exhibit many features of adult skeletal muscle and characteristics of fast type II fibers. Thus, the culture represents an excellent model of adult fast skeletal muscle, for example, when investigating molecular mechanisms of fast-to-slow fiber-type transformation. © 2015 International Federation for Cell Biology.

Metabolic effects of physiological levels of caffeine in myotubes.

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Schnuck, Jamie K; Gould, Lacey M; Parry, Hailey A; Johnson, Michele A; Gannon, Nicholas P; Sunderland, Kyle L; Vaughan, Roger A

2018-02-01

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.

Astragalus Polysaccharide Improves Palmitate-Induced Insulin Resistance by Inhibiting PTP1B and NF-κB in C2C12 Myotubes

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Yong Li

2012-06-01

Full Text Available We investigated the effects of Astragalus polysaccharide (APS on palmitate-induced insulin resistance in C2C12 skeletal muscle myotubes. Palmitate-reduced glucose uptake was restored by APS. APS prevented palmitate-induced C2C12 myotubes from impaired insulin signaling by inhibiting Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 and increasing Ser473 phosphorylation of Akt. Moreover, the increases in protein-tyrosine phosphatase-1B (PTP1B protein level and NF-κB activation associated with palmitate treatment were also prevented by APS. However the treatment with APS didn’t change AMP-activated protein kinase (AMPK activation in palmitate-induced myotubes. The results of the present study suggest that Astragalus polysaccharide inhibits palmitate-induced insulin resistance in C2C12 myotubes by inhibiting expression of PTP1B and regulating NF-κB but not AMPK pathway.

A Novel Protocol for Directed Differentiation of C9orf72-Associated Human Induced Pluripotent Stem Cells Into Contractile Skeletal Myotubes.

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Swartz, Elliot W; Baek, Jaeyun; Pribadi, Mochtar; Wojta, Kevin J; Almeida, Sandra; Karydas, Anna; Gao, Fen-Biao; Miller, Bruce L; Coppola, Giovanni

2016-11-01

: Induced pluripotent stem cells (iPSCs) offer an unlimited resource of cells to be used for the study of underlying molecular biology of disease, therapeutic drug screening, and transplant-based regenerative medicine. However, methods for the directed differentiation of skeletal muscle for these purposes remain scarce and incomplete. Here, we present a novel, small molecule-based protocol for the generation of multinucleated skeletal myotubes using eight independent iPSC lines. Through combinatorial inhibition of phosphoinositide 3-kinase (PI3K) and glycogen synthase kinase 3β (GSK3β) with addition of bone morphogenic protein 4 (BMP4) and fibroblast growth factor 2 (FGF2), we report up to 64% conversion of iPSCs into the myogenic program by day 36 as indicated by MYOG + cell populations. These cells began to exhibit spontaneous contractions as early as 34 days in vitro in the presence of a serum-free medium formulation. We used this protocol to obtain iPSC-derived muscle cells from frontotemporal dementia (FTD) patients harboring C9orf72 hexanucleotide repeat expansions (rGGGGCC), sporadic FTD, and unaffected controls. iPSCs derived from rGGGGCC carriers contained RNA foci but did not vary in differentiation efficiency when compared to unaffected controls nor display mislocalized TDP-43 after as many as 120 days in vitro. This study presents a rapid, efficient, and transgene-free method for generating multinucleated skeletal myotubes from iPSCs and a resource for further modeling the role of skeletal muscle in amyotrophic lateral sclerosis and other motor neuron diseases. Protocols to produce skeletal myotubes for disease modeling or therapy are scarce and incomplete. The present study efficiently generates functional skeletal myotubes from human induced pluripotent stem cells using a small molecule-based approach. Using this strategy, terminal myogenic induction of up to 64% in 36 days and spontaneously contractile myotubes within 34 days were achieved

IGF-1 prevents simvastatin-induced myotoxicity in C2C12 myotubes.

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Bonifacio, Annalisa; Sanvee, Gerda M; Brecht, Karin; Kratschmar, Denise V; Odermatt, Alex; Bouitbir, Jamal; Krähenbühl, Stephan

2017-05-01

Statins are generally well tolerated, but treatment with these drugs may be associated with myopathy. The mechanisms of statin-associated myopathy are not completely understood. Statins inhibit AKT phosphorylation by an unclear mechanism, whereas insulin-like growth factor (IGF-1) activates the IGF-1/AKT signaling pathway and promotes muscle growth. The aims of the study were to investigate mechanisms of impaired AKT phosphorylation by simvastatin and to assess effects of IGF-1 on simvastatin-induced myotoxicity in C2C12 myotubes. C2C12 mouse myotubes were exposed to 10 μM simvastatin and/or 10 ng/mL IGF-1 for 18 h. Simvastatin inhibited the IGF-1/AKT signaling pathway, resulting in increased breakdown of myofibrillar proteins, impaired protein synthesis and increased apoptosis. Simvastatin inhibited AKT S473 phosphorylation, indicating reduced activity of mTORC2. In addition, simvastatin impaired stimulation of AKT T308 phosphorylation by IGF-1, indicating reduced activation of the IGF-1R/PI3K pathway by IGF-1. Nevertheless, simvastatin-induced myotoxicity could be at least partially prevented by IGF-1. The protective effects of IGF-1 were mediated by activation of the IGF-1R/AKT signaling cascade. Treatment with IGF-1 also suppressed muscle atrophy markers, restored protein synthesis and inhibited apoptosis. These results were confirmed by normalization of myotube morphology and protein content of C2C12 cells exposed to simvastatin and treated with IGF-1. In conclusion, impaired activity of AKT can be explained by reduced function of mTORC2 and of the IGF-1R/PI3K pathway. IGF-1 can prevent simvastatin-associated cytotoxicity and metabolic effects on C2C12 cells. The study gives insight into mechanisms of simvastatin-associated myotoxicity and provides potential targets for therapeutic intervention.

BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes.

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Xu, Qi; Luo, Jiao; Wu, Ning; Zhang, Renshuai; Shi, Dayong

2018-01-01

Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B. Molecular docking study and analysis of small- molecule interaction with PTP1B all showed BPN inhibited PTP1B activity via binding to the catalytic site through hydrogen bonds. We then found that BPN permeated into C2C12 myotubes, on the one hand, activated insulin signaling in an insulin-independent manner in C2C12 cells; on the other hand, ameliorated palmitate-induced insulin resistance through augmenting insulin sensitivity. Moreover, our studies also showed that PTP1B inhibition by BPN increased glucose uptake in normal and insulin-resistant C2C12 myotubes through glucose transporter 4 (GLUT4) translocation. Taken together, BPN activates insulin signaling and alleviates insulin resistance and represents a potential candidate for further development as an antidiabetic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Reduced TCA flux in diabetic myotubes: A governing influence on the diabetic phenotype?

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Gaster, Michael

2009-10-02

The diabetic phenotype is complex, requiring elucidation of key initiating defects. It is unknown whether the reduced tricarboxylic acid cycle (TCA) flux in skeletal muscle of obese and obese type 2 diabetic (T2D) subjects is of primary origin. Acetate oxidation (measurement of TCA-flux) was significantly reduced in primary myotube cultures established from T2D versus lean subjects. Acetate oxidation was acutely stimulated by insulin and respiratory uncoupling. Inhibition of TCA flux in lean myotubes by malonate was followed by a measured decline in; acetate oxidation, complete palmitate oxidation, lipid uptake, glycogen synthesis, ATP content and increased glucose uptake, while glucose oxidation was unaffected. Acute TCA inhibition did not induce insulin resistance. Thus the reduced TCA cycle flux in T2D skeletal muscle may be of primary origin. The diabetic phenotype of increased basal glucose uptake and glucose oxidation, the reduced complete lipid oxidation and increased respiratory quotient, are likely to be adaptive responses to the reduced TCA cycle flux.

Halofuginone inhibits Smad3 phosphorylation via the PI3K/Akt and MAPK/ERK pathways in muscle cells: Effect on myotube fusion

International Nuclear Information System (INIS)

Roffe, Suzy; Hagai, Yosey; Pines, Mark; Halevy, Orna

2010-01-01

Halofuginone, a novel inhibitor of Smad3 phosphorylation, has been shown to inhibit muscle fibrosis and to improve cardiac and skeletal muscle functions in the mdx mouse model of Duchenne muscular dystrophy. Here, we demonstrate that halofuginone promotes the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) family members in a C2 muscle cell line and in primary myoblasts derived from wild-type and mdx mice diaphragms. Halofuginone enhanced the association of phosphorylated Akt and MAPK/extracellular signal-regulated protein kinase (ERK) with the non-phosphorylated form of Smad3, accompanied by a reduction in Smad3 phosphorylation levels. This reduction was reversed by inhibitors of the phosphoinositide 3'-kinase/Akt (PI3K/Akt) and MAPK/ERK pathways, suggesting their specific role in mediating halofuginone's inhibitory effect on Smad3 phosphorylation. Halofuginone enhanced Akt, MAPK/ERK and p38 MAPK phosphorylation and inhibited Smad3 phosphorylation in myotubes, all of which are crucial for myotube fusion. In addition, halofuginone increased the association Akt and MAPK/ERK with Smad3. As a consequence, halofuginone promoted myotube fusion, as reflected by an increased percentage of C2 and mdx myotubes containing high numbers of nuclei, and this was reversed by specific inhibitors of the PI3K and MAPK/ERK pathways. Together, the data suggest a role, either direct or via inhibition of Smad3 phosphorylation, for Akt or MAPK/ERK in halofuginone-enhanced myotube fusion, a feature which is crucial to improving muscle function in muscular dystrophies.

Halofuginone inhibits Smad3 phosphorylation via the PI3K/Akt and MAPK/ERK pathways in muscle cells: Effect on myotube fusion

Energy Technology Data Exchange (ETDEWEB)

Roffe, Suzy [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Hagai, Yosey [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel); Institute of Animal Sciences, Volcani Center, Bet Dagan 50250 (Israel); Pines, Mark [Institute of Animal Sciences, Volcani Center, Bet Dagan 50250 (Israel); Halevy, Orna, E-mail: halevyo@agri.huji.ac.il [Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100 (Israel)

2010-04-01

Halofuginone, a novel inhibitor of Smad3 phosphorylation, has been shown to inhibit muscle fibrosis and to improve cardiac and skeletal muscle functions in the mdx mouse model of Duchenne muscular dystrophy. Here, we demonstrate that halofuginone promotes the phosphorylation of Akt and mitogen-activated protein kinase (MAPK) family members in a C2 muscle cell line and in primary myoblasts derived from wild-type and mdx mice diaphragms. Halofuginone enhanced the association of phosphorylated Akt and MAPK/extracellular signal-regulated protein kinase (ERK) with the non-phosphorylated form of Smad3, accompanied by a reduction in Smad3 phosphorylation levels. This reduction was reversed by inhibitors of the phosphoinositide 3'-kinase/Akt (PI3K/Akt) and MAPK/ERK pathways, suggesting their specific role in mediating halofuginone's inhibitory effect on Smad3 phosphorylation. Halofuginone enhanced Akt, MAPK/ERK and p38 MAPK phosphorylation and inhibited Smad3 phosphorylation in myotubes, all of which are crucial for myotube fusion. In addition, halofuginone increased the association Akt and MAPK/ERK with Smad3. As a consequence, halofuginone promoted myotube fusion, as reflected by an increased percentage of C2 and mdx myotubes containing high numbers of nuclei, and this was reversed by specific inhibitors of the PI3K and MAPK/ERK pathways. Together, the data suggest a role, either direct or via inhibition of Smad3 phosphorylation, for Akt or MAPK/ERK in halofuginone-enhanced myotube fusion, a feature which is crucial to improving muscle function in muscular dystrophies.

Kinetics of lactate and pyruvate transport in cultured rat myotubes

DEFF Research Database (Denmark)

von Grumbckow, Lena; Elsner, Peter; Hellsten, Ylva

1999-01-01

, respectively. Furthermore, it was observed that the two monocarboxylate transporter isoforms present in mature skeletal muscles, MCT1 and MCT4 (formerly called MCT3 (M.C. Wilson, V.N. Jackson, C. Heddle, N.T. Price, H. Pilegaard, C. Juel, A. Bonen, I. Montgomery, O.F. Hutter, A.P. Halestrap, Lactic acid efflux...... from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3, J. Biol. Chem. 273 (1998) 15920-15926)), were also expressed in primary culture of myotubes....

Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes

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Chunzi Liang

2014-01-01

Full Text Available Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB, a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM, alanine (0.5 mM, valine (0.5 mM, EX527 (SIRT1 inhibitor, 25 μM, and Compound C (AMPK inhibitor, 25 μM alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

The dynamic of lipid oxidation in human myotubes

DEFF Research Database (Denmark)

Gaster, Michael

2009-01-01

Both endogenous and exogenous lipid levels may be regulators of total lipid oxidation in skeletal muscles. We studied the dynamics of lipid oxidation in human myotubes established from healthy, lean subjects exposed to acutely and chronically increased palmitate concentrations. The intramyocellular...... triacylglycerol content increased with chronic palmitate exposure. Both, ectopically increased intracellular and extracellular lipid levels were simultaneously oxidized and could partly suppress each other's oxidation. Overall, the highest acute palmitate treatments stimulated fatty acid oxidation whilst...... the highest chronic treatments decreased total lipid oxidation. Intracellular lipids showed a more complete oxidation than exogenous lipids. Endogenous lipids reduced insulin-mediated glucose oxidation. Thus, both endogenous and exogenous lipid concentrations regulated each other's oxidation and total lipid...

Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations

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Fraser, D. A.; Hessvik, N. P.; Nikolić, N.; Aas, V.; Hanssen, K. F.; Bøhn, S. K.; Thoresen, G. H.; Rustan, A. C.

2011-01-01

The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measu...

Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

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Hughes, M A; Downs, R M; Webb, G W; Crocker, C L; Kinsey, S T; Baumgarner, Bradley L

2017-04-01

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

Effects of inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate induced insulin resistance in L6 myotubes.

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Agnieszka Mikłosz

Full Text Available BACKGROUND: The objective of this study was to examine the effects of short (2 h and prolonged (18 h inhibition of serine palmitoyltransferase (SPT and sphingosine kinase 1 (SphK1 on palmitate (PA induced insulin resistance in L6 myotubes. METHODS: L6 myotubes were treated simultaneously with either PA and myriocin (SPT inhibitor or PA and Ski II (SphK1inhibitor for different time periods (2 h and 18 h. Insulin stimulated glucose uptake was measured using radioactive isotope. Expression of insulin signaling proteins was determined using Western blot analyses. Intracellular sphingolipids content [sphinganine (SFA, ceramide (CER, sphingosine (SFO, sphingosine-1-phosphate (S1P] were estimated by HPLC. RESULTS: Our results revealed that both short and prolonged time of inhibition of SPT by myriocin was sufficient to prevent ceramide accumulation and simultaneously reverse palmitate induced inhibition of insulin-stimulated glucose transport. In contrast, prolonged inhibition of SphK1 intensified the effect of PA on insulin-stimulated glucose uptake and attenuated further the activity of insulin signaling proteins (pGSK3β/GSK3β ratio in L6 myotubes. These effects were related to the accumulation of sphingosine in palmitate treated myotubes. CONCLUSION: Myriocin is more effective in restoration of palmitate induced insulin resistance in L6 myocytes, despite of the time of SPT inhibition, comparing to SKII (a specific SphK1 inhibitor. Observed changes in insulin signaling proteins were related to the content of specific sphingolipids, namely to the reduction of ceramide. Interestingly, inactivation of SphK1 augmented the effect of PA induced insulin resistance in L6 myotubes, which was associated with further inhibition of insulin stimulated PKB and GSK3β phosphorylation, glucose uptake and the accumulation of sphingosine.

Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

NARCIS (Netherlands)

Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M

Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance.

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Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun; Jakobsen, Marianne Antonius; Brusgaard, Klaus; Tan, Qihua; Gaster, Michael

2014-09-05

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls. Glucose transport in myotubes was comparable in patients with PCOS vs. controls and was unchanged by testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that testosterone treatment of myotubes increases the aromatase and androgen receptor gene expression without affecting insulin sensitivity and if testosterone is implicated in muscular insulin resistance in PCOS, this is by and indirect mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

DEFF Research Database (Denmark)

Young, Jette Feveile; Larsen, Lotte Bach; Malmendal, Anders

2010-01-01

Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat......-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating...... the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. METHODS: Differentiated mouse myotube cultures (C2C12) were exposed to 5 mM creatine monohydrate (CMH) for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension...

NMR-Based Metabonomic Investigation of Heat Stress in Myotubes Reveals a Time-Dependent Change in the Metabolites

DEFF Research Database (Denmark)

Straadt, Ida K; Young, Jette F; Bross, Peter

2010-01-01

NMR-based metabonomics was applied to elucidate the time-dependent stress responses in mouse myotubes after heat exposure of either 42 or 45 degrees C for 1 h. Principal component analysis (PCA) revealed that the gradual time-dependent changes in metabolites contributing to the clustering...... and separation of the control samples from the different time points after heat stress primarily are in the metabolites glucose, leucine, lysine, phenylalanine, creatine, glutamine, and acetate. In addition, PC scores revealed a maximum change in metabolite composition 4 h after the stress exposure; thereafter......, samples returned toward control samples, however, without reaching the control samples even 10 h after stress. The results also indicate that the myotubes efficiently regulate the pH level by release of lactate to the culture medium at a heat stress level of 42 degrees C, which is a temperature level...

Serum Amyloid A Induces Toll-Like Receptor 2-Dependent Inflammatory Cytokine Expression and Atrophy in C2C12 Skeletal Muscle Myotubes.

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Passey, Samantha L; Bozinovski, Steven; Vlahos, Ross; Anderson, Gary P; Hansen, Michelle J

2016-01-01

Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of muscle mass.

Characterization of thyroid hormone effects on Na-K pump and membrane potential of cultured rat skeletal myotubes

International Nuclear Information System (INIS)

Brodie, C.; Sampson, S.R.

1988-01-01

The purpose of this study was to characterize the effects of thyroid hormone on the Na-K pump and resting membrane potential (EM) of rat skeletal myotubes in culture. Myotubes were obtained from fetal (19-21 day) or neonatal rats (1-2 day) by serial trypsinization and maintained in culture for up to 10 days. Cells were treated with T4 or T3 on day 6 or 7, and measurements were made of EM, [ 3 H]ouabain binding, and ouabain-sensitive 86 Rb uptake at various times thereafter. Hormone treatment increased the values of all three variables within 24 h, plateau levels being attained by 48-72 h. Cycloheximide and actinomycin D totally blocked the effects of thyroid hormone when added together to the cells, thus suggesting that protein synthesis is necessary for the effects of these hormones. Scatchard analysis showed that the new receptors have lower ouabain affinity than those in control. Blockade of spontaneously occurring action potentials with tetrodotoxin, which blocks voltage-dependent Na channels, or Na/H antiporter with amiloride, abolished the hormone effects seen after 24 h and significantly reduced those obtained after 48 h of hormone treatment. The results demonstrate that thyroid hormone-induced increased amount and activity of the electrogenic Na-K pump in cultured myotubes occurs, at least in part, in response to an initial effect to increase Na influx. Moreover, the findings are consistent with the concept that the Na-K pump plays an important role in regulation of EM in this preparation

Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

Energy Technology Data Exchange (ETDEWEB)

Eom, Young Woo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Lee, Jong Eun; Yang, Mal Sook; Jang, In Keun; Kim, Hyo Eun; Lee, Doo Hoon; Kim, Young Jin [Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Park, Won Jin [Dr. Park' s Aesthetic Clinic, Seoul (Korea, Republic of); Kong, Jee Hyun; Shim, Kwang Yong [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In, E-mail: oncochem@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@unitel.co.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

2011-04-29

Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

International Nuclear Information System (INIS)

Eom, Young Woo; Lee, Jong Eun; Yang, Mal Sook; Jang, In Keun; Kim, Hyo Eun; Lee, Doo Hoon; Kim, Young Jin; Park, Won Jin; Kong, Jee Hyun; Shim, Kwang Yong; Lee, Jong In; Kim, Hyun Soo

2011-01-01

Highlights: → hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. → Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. → hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

Activation of estrogen response elements is mediated both via estrogen and muscle contractions in rat skeletal muscle myotubes

DEFF Research Database (Denmark)

Wiik, A.; Hellsten, Ylva; Berthelson, P.

2009-01-01

is ER independent. The muscle contraction-induced transactivation of ERE and increase in ERbeta mRNA were instead found to be MAP kinase (MAPK) dependent. This study demonstrates for the first time that muscle contractions have a similar functional effect as estrogen in skeletal muscle myotubes, causing......The aim of the present study was to investigate the activation of estrogen response elements (EREs) by estrogen and muscle contractions in rat myotubes in culture and to assess whether the activation is dependent on the estrogen receptors (ERs). In addition, the effect of estrogen and contraction...... on the mRNA levels of ERalpha and ERbeta was studied to determine the functional consequence of the transactivation. Myoblasts were isolated from rat skeletal muscle and transfected with a vector consisting of sequences of EREs coupled to the gene for luciferase. The transfected myoblasts were...

Proliferation and skeletal myotube formation capability of C2C12 and H9c2 cells on isotropic and anisotropic electrospun nanofibrous PHB scaffolds

International Nuclear Information System (INIS)

Ricotti, Leonardo; Genchi, Giada G; Menciassi, Arianna; Polini, Alessandro; Iandolo, Donata; Pisignano, Dario; Ciofani, Gianni; Mattoli, Virgilio; Vazão, Helena; Ferreira, Lino

2012-01-01

This study aims at investigating the behavior in terms of the proliferation and skeletal muscle differentiation capability of two myoblastic cell lines, C2C12 and H9c2, on both isotropic and anisotropic electrospun nanofibrous poly(hydroxybutyrate) (PHB) scaffolds, as well as on PHB films and polystyrene controls. After a careful characterization of the matrices in terms of surface morphology, surface roughness and mechanical properties, the proliferation rate and the capability of the two cell lines to form skeletal myotubes were evaluated. Genetic analyses were also performed in order to assess the differentiation level of the cells on the different substrates. We demonstrated that the aligned nanofibrous mesh decreases the proliferation activity and provides a higher differentiative stimulus. We also clarified how the nanofibrous substrate influences myotube formation, and quantified a series of myotube-related parameters for both C2C12 and H9c2 cells. (paper)

FA1 Induces Pro-Inflammatory and Anti-Adipogenic Pathways/Markers in Human Myotubes Established from Lean, Obese, and Type 2 Diabetic Subjects but Not Insulin Resistance

DEFF Research Database (Denmark)

Abdallah, Basem M; Beck-Nielsen, Henning; Gaster, Michael

2013-01-01

Aims: Delta like 1/fetal antigen 1 (Dlk1/FA1) is a protein secreted by hormone producing cells in adult human and mice that is known to inhibit adipogenesis. Recent studies demonstrated the role of Dlk1/FA1 in inducing insulin resistance in mice. To investigate the involvement of circulating Dlk1....../FA1 in insulin resistance and type 2 diabetes in human subjects, we studied the effects of chronic FA1 on the intermediary metabolism in myotubes established from lean, obese, and type 2 diabetic (T2D) subjects. Methods: Myotube cultures were established from lean and obese control subjects......, and obese T2D subjects and treated with soluble FA1 for 4 days supplemented with/without palmitate (PA). Lipid- and glucose metabolism were studied with labeled precursors while quantitative expression of genes was analyzed using real-time PCR. Results: Diabetic myotubes express significantly reduced...

Ndrg2 is a PGC-1α/ERRα target gene that controls protein synthesis and expression of contractile-type genes in C2C12 myotubes.

Science.gov (United States)

Foletta, Victoria C; Brown, Erin L; Cho, Yoshitake; Snow, Rod J; Kralli, Anastasia; Russell, Aaron P

2013-12-01

The stress-responsive, tumor suppressor N-myc downstream-regulated gene 2 (Ndrg2) is highly expressed in striated muscle. In response to anabolic and catabolic signals, Ndrg2 is suppressed and induced, respectively, in mouse C2C12 myotubes. However, little is known about the mechanisms regulating Ndrg2 expression in muscle, as well as the biological role for Ndrg2 in differentiated myotubes. Here, we show that Ndrg2 is a target of a peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and estrogen-related receptor alpha (ERRα) transcriptional program and is induced in response to endurance exercise, a physiological stress known also to increase PGC-1α/ERRα activity. Analyses of global gene and protein expression profiles in C2C12 myotubes with reduced levels of NDRG2, suggest that NDRG2 affects muscle growth, contractile properties, MAPK signaling, ion and vesicle transport and oxidative phosphorylation. Indeed, suppression of NDRG2 in myotubes increased protein synthesis and the expression of fast glycolytic myosin heavy chain isoforms, while reducing the expression of embryonic myosin Myh3, other contractile-associated genes and the MAPK p90 RSK1. Conversely, enhanced expression of NDRG2 reduced protein synthesis, and furthermore, partially blocked the increased protein synthesis rates elicited by a constitutively active form of ERRα. In contrast, suppressing or increasing levels of NDRG2 did not affect mRNA expression of genes involved in mitochondrial biogenesis that are regulated by PGC-1α or ERRα. This study shows that in C2C12 myotubes Ndrg2 is a novel PGC-1α/ERRα transcriptional target, which influences protein turnover and the regulation of genes involved in muscle contraction and function. © 2013 Elsevier B.V. All rights reserved.

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Science.gov (United States)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Intramolecular ex vivo Fluorescence Resonance Energy Transfer (FRET of Dihydropyridine Receptor (DHPR β1a Subunit Reveals Conformational Change Induced by RYR1 in Mouse Skeletal Myotubes.

Directory of Open Access Journals (Sweden)

Dipankar Bhattacharya

Full Text Available The dihydropyridine receptor (DHPR β1a subunit is essential for skeletal muscle excitation-contraction coupling, but the structural organization of β1a as part of the macromolecular DHPR-ryanodine receptor type I (RyR1 complex is still debatable. We used fluorescence resonance energy transfer (FRET to probe proximity relationships within the β1a subunit in cultured skeletal myotubes lacking or expressing RyR1. The fluorescein biarsenical reagent FlAsH was used as the FRET acceptor, which exhibits fluorescence upon binding to specific tetracysteine motifs, and enhanced cyan fluorescent protein (CFP was used as the FRET donor. Ten β1a reporter constructs were generated by inserting the CCPGCC FlAsH binding motif into five positions probing the five domains of β1a with either carboxyl or amino terminal fused CFP. FRET efficiency was largest when CCPGCC was positioned next to CFP, and significant intramolecular FRET was observed for all constructs suggesting that in situ the β1a subunit has a relatively compact conformation in which the carboxyl and amino termini are not extended. Comparison of the FRET efficiency in wild type to that in dyspedic (lacking RyR1 myotubes revealed that in only one construct (H458 CCPGCC β1a -CFP FRET efficiency was specifically altered by the presence of RyR1. The present study reveals that the C-terminal of the β1a subunit changes conformation in the presence of RyR1 consistent with an interaction between the C-terminal of β1a and RyR1 in resting myotubes.

CHARACTERIZATION OF P2-PURINOCEPTOR MEDIATED CYCLIC-AMP FORMATION IN MOUSE C2C12 MYOTUBES

NARCIS (Netherlands)

HENNING, RH; DUIN, M; DENHERTOG, A; NELEMANS, A

1 The formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and inositol(1,4,5)trisphosphate (Ins(1,4,5)P3), induced by ATP and other nucleotides was investigated in mouse C2Cl2 myotubes. 2 ATP (100 muM) and ATPgammaS (100 muM) caused a sustained increase in cyclic AMP content of the cells,

The basal kinetic parameters of glycogen synthase in human myotube cultures are not affected by chronic high insulin exposure

DEFF Research Database (Denmark)

Gaster, M; Schrøder, H D; Handberg, A

2001-01-01

results show that chronic exposure of human myotubes to high insulin with or without high glucose did not affect the basal kinetic parameters but abolished the reactivity of GS to acute insulin stimulation. We suggest that insulin induced insulin resistance of GS is caused by a failure of acute insulin......There is no consensus regarding the results from in vivo and in vitro studies on the impact of chronic high insulin and/or high glucose exposure on acute insulin stimulation of glycogen synthase (GS) kinetic parameters in human skeletal muscle. The aim of this study was to evaluate the kinetic...... parameters of glycogen synthase activity in human myotube cultures at conditions of chronic high insulin combined or not with high glucose exposure, before and after a subsequent acute insulin stimulation. Acute insulin stimulation significantly increased the fractional activity (FV(0.1)) of GS, increased...

Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

Energy Technology Data Exchange (ETDEWEB)

Yokokawa, Takumi [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Sato, Koji [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Iwanaka, Nobumasa [The Graduate School of Science and Engineering, Ritsumeikan University, Shiga (Japan); Honda, Hiroki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Higashida, Kazuhiko [Faculty of Sport Science, Waseda University, Saitama (Japan); Iemitsu, Motoyuki [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan); Hayashi, Tatsuya [Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto (Japan); Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Graduate School of Sport & Health Science, Ritsumeikan University, Shiga (Japan)

2015-07-17

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA.

Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes

International Nuclear Information System (INIS)

Yokokawa, Takumi; Sato, Koji; Iwanaka, Nobumasa; Honda, Hiroki; Higashida, Kazuhiko; Iemitsu, Motoyuki; Hayashi, Tatsuya; Hashimoto, Takeshi

2015-01-01

Exercise and caloric restriction (CR) have been reported to have anti-ageing, anti-obesity, and health-promoting effects. Both interventions increase the level of dehydroepiandrosterone (DHEA) in muscle and blood, suggesting that DHEA might partially mediate these effects. In addition, it is thought that either 5′-adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) mediates the beneficial effects of exercise and CR. However, the effects of DHEA on AMPK activity and PGC-1α expression remain unclear. Therefore, we explored whether DHEA in myotubes acts as an activator of AMPK and increases PGC-1α. DHEA exposure increased glucose uptake but not the phosphorylation levels of Akt and PKCζ/λ in C2C12 myotubes. In contrast, the phosphorylation levels of AMPK were elevated by DHEA exposure. Finally, we found that DHEA induced the expression of the genes PGC-1α and GLUT4. Our current results might reveal a previously unrecognized physiological role of DHEA; the activation of AMPK and the induction of PGC-1α by DHEA might mediate its anti-obesity and health-promoting effects in living organisms. - Highlights: • We assessed whether dehydroepiandrosterone (DHEA) activates AMPK and PGC-1α. • DHEA exposure increased glucose uptake in C2C12 myotubes. • The phosphorylation levels of AMPK were elevated by DHEA exposure. • DHEA induced the expression of the genes PGC-1α and GLUT4. • AMPK might mediate the anti-obesity and health-promoting effects of DHEA

Regulation of the sodium-potassium pump in cultured rat skeletal myotubes by intracellular sodium ions

International Nuclear Information System (INIS)

Brodie, C.; Sampson, S.R.

1989-01-01

The properties of the Na-K pump and some of the factors controlling its amount and function were studied in rat myotubes in culture. The number of Na-K pump sites was quantified by measuring the amount of [ 3 H]ouabain bound to whole-cell preparations. Activity of the pump was determined by measurement of ouabain-sensitive 86 Rb-uptake and component of membrane potential. Chronic treatment of myotubes with tetrodotoxin (TTX), which lowers [Na]i, decreased the number of Na-K pumps, the ouabain-sensitive 86Rb uptake, and the size of the electrogenic pump component of Em. In contrast, chronic treatment with either ouabain or veratridine, which increases [Na+]i, resulted in an elevated level of Na-K pump sites. This effect was blocked by inhibitors of protein synthesis. Neither rates of degradation nor affinity of pump sites in cells treated with TTX, veratridine, or ouabain differred from those in control cells. The number and activity of Na-K pump sites were unaffected by chronic elevation in [Ca]i or chronic depolarization. We conclude that alterations in the level in intracellular Na ions play the major role in regulation of Na-K pump synthesis in cultured mammalian skeletal muscle

Transciptional profiling of myotubes from patients with type 2 diabetes

DEFF Research Database (Denmark)

Frederiksen, CM; Højlund, K; Hansen, L

2008-01-01

AIMS/HYPOTHESIS: Microarray-based studies of skeletal muscle from patients with type 2 diabetes and high-risk individuals have demonstrated that insulin resistance and reduced mitochondrial biogenesis co-exist early in the pathogenesis of type 2 diabetes independently of hyperglycaemia and obesity....... It is unknown whether reduced mitochondrial biogenesis or other transcriptional alterations co-exist with impaired insulin responsiveness in primary human muscle cells from patients with type 2 diabetes. METHODS: Using cDNA microarray technology and global pathway analysis with the Gene Map Annotator...... and Pathway Profiler (GenMapp 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1), we examined transcript levels in myotubes established from obese patients with type 2 diabetes and matched obese healthy participants, who had been extensively metabolically characterised both in vivo and in vitro. We have...

Metabolic profiling of heat or anoxic stress in mouse C2C12 myotubes using multinuclear magnetic resonance spectroscopy

DEFF Research Database (Denmark)

Straadt, Ida K; Young, Jette F; Petersen, Bent O

2010-01-01

to anaerobic metabolism due to inhibition of the aerobic pathway in the mitochondria. Conversely, lower levels of unlabeled ((12)C) lactate were apparent at increasing severity of stress, which indicate that lactate is released from the myotubes to the medium. In conclusion, the metabolites identified......In the present study, the metabolic effects of heat and anoxic stress in myotubes from the mouse cell line C2C12 were investigated by using a combination of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy and enrichment with [(13)C]-glucose. Both the (13)C and the (1)H NMR...... spectra showed reduced levels of the amino acids alanine, glutamate, and aspartate after heat or anoxic stress. The decreases were smallest at 42 degrees C, larger at 45 degrees C, and most pronounced after anoxic conditions. In addition, in both the (1)H and the (31)P NMR spectra, decreases in the high...

Angiopoietin-like 4 mediates PPAR delta effect on lipoprotein lipase-dependent fatty acid uptake but not on beta-oxidation in myotubes.

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Marius R Robciuc

Full Text Available Peroxisome proliferator-activated receptor (PPAR delta is an important regulator of fatty acid (FA metabolism. Angiopoietin-like 4 (Angptl4, a multifunctional protein, is one of the major targets of PPAR delta in skeletal muscle cells. Here we investigated the regulation of Angptl4 and its role in mediating PPAR delta functions using human, rat and mouse myotubes. Expression of Angptl4 was upregulated during myotubes differentiation and by oleic acid, insulin and PPAR delta agonist GW501516. Treatment with GW501516 or Angptl4 overexpression inhibited both lipoprotein lipase (LPL activity and LPL-dependent uptake of FAs whereas uptake of BSA-bound FAs was not affected by either treatment. Activation of retinoic X receptor (RXR, PPAR delta functional partner, using bexarotene upregulated Angptl4 expression and inhibited LPL activity in a PPAR delta dependent fashion. Silencing of Angptl4 blocked the effect of GW501516 and bexarotene on LPL activity. Treatment with GW501516 but not Angptl4 overexpression significantly increased palmitate oxidation. Furthermore, Angptl4 overexpression did not affect the capacity of GW501516 to increase palmitate oxidation. Basal and insulin stimulated glucose uptake, glycogen synthesis and glucose oxidation were not significantly modulated by Angptl4 overexpression. Our findings suggest that FAs-PPARdelta/RXR-Angptl4 axis controls the LPL-dependent uptake of FAs in myotubes, whereas the effect of PPAR delta activation on beta-oxidation is independent of Angptl4.

Oxidative stress-induced metabolic changes in mouse C2C12 myotubes studied with high-resolution 13C, 1H, and 31P NMR spectroscopy

DEFF Research Database (Denmark)

Straadt, Ida K; Young, Jette F; Petersen, Bent O

2010-01-01

In this study, stress in relation to slaughter was investigated in a model system by the use of (13)C, (1)H, and (31)P nuclear magnetic resonance (NMR) spectroscopy for elucidating changes in the metabolites in C2C12 myotubes exposed to H(2)O(2)-induced stress. Oxidative stress resulted in lower...... to lower levels of the unlabeled ((12)C) lactate were identified in the (1)H spectra after stress exposure. These data indicate an increase in de novo synthesis of alanine, concomitant with a release of lactate from the myotubes to the medium at oxidative stress conditions. The changes in the metabolite...

Skeletal muscle myotubes of the severely obese exhibit altered ubiquitin-proteasome and autophagic/lysosomal proteolytic flux

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Bollinger, Lance M.; Powell, Jonathan J. S.; Houmard, Joseph A.; Witczak, Carol A.; Brault, Jeffrey J.

2015-01-01

Objective Whole-body protein metabolism is dysregulated with obesity. Our goal was to determine if activity and expression of major protein degradation pathways are compromised specifically in human skeletal muscle with obesity. Methods We utilized primary Human Skeletal Muscle cell (HSkM) cultures since cellular mechanisms can be studied absent of hormones and contractile activity that could independently influence metabolism. HSkM from 10 lean (BMI ≤ 26.0 kg/m2) and 8 severely obese (BMI ≥ 39.0) women were examined basally and when stimulated to atrophy (serum and amino acid starvation). Results HSkM from obese donors had a lower proportion of type I myosin heavy chain and slower flux through the autophagic/lysosomal pathway. During starvation, flux through the ubiquitin-proteasome system diverged according to obesity status, with a decrease in the lean and an increase in HSkM from obese subjects. HSkMC from the obese also displayed elevated proteasome activity despite no difference in proteasome content. Atrophy-related gene expression and myotube area were similar in myotubes derived from lean and obese individuals under basal and starved conditions. Conclusions Our data indicate that muscle cells of the lean and severely obese have innate differences in management of protein degradation, which may explain their metabolic differences. PMID:26010327

Triacylglycerol Accumulation is not primarily affected in Myotubes established from Type 2 Diabetic Subjects

DEFF Research Database (Denmark)

Gaster, Michael; Beck-Nielsen, Henning

2006-01-01

In the present study, we investigated triacylglycerol (TAG) accumulation, glucose and fatty acid (FA) uptake, and glycogen synthesis (GS) in human myotubes from healthy, lean, and obese subjects with and without type 2 diabetes (T2D), exposed to increasing palmitate (PA) and oleate (OA...... uptake (P0.05). These results indicate that (1) TAG accumulation is not primarily affected in skeletal muscle tissue of obese and T2D; (2) induced inhibition of oxidative phosphorylation is followed by TAG accumulation...... in skeletal muscle of obese and T2D subjects is adaptive....

Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations.

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Fraser, D A; Hessvik, N P; Nikolić, N; Aas, V; Hanssen, K F; Bøhn, S K; Thoresen, G H; Rustan, A C

2012-07-01

The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal.

INDUCTION OF NA+/K+-ATPASE ACTIVITY BY LONG-TERM STIMULATION OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN C2CL2 MYOTUBES

NARCIS (Netherlands)

HENNING, RH; NELEMANS, SA; VANDENAKKER, J; DENHERTOG, A

1 To investigate the role of long-term stimulation of nicotinic acety]choline receptors (AChRs) on the regulation of membrane potential, non-contracting C2C12 myotubes were stimulated for 1-4 days with carbachol (10 mu M) and membrane potentials were measured by the intracellular microelectrode

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

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Perry, Ben D; Rahnert, Jill A; Xie, Yang; Zheng, Bin; Woodworth-Hobbs, Myra E; Price, S Russ

2018-01-01

Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.

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Ben D Perry

Full Text Available Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4. Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides, palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242. Inflammatory indicators of TLR4 activation (IL-6 and TNFα and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle in part by induction of ER stress.

Differential regulation of iPLA2beta splice variants by in vitro ischemia in C2C12 myotubes

DEFF Research Database (Denmark)

Poulsen, K. A.; Kolko, M.; Lambert, I. H.

2006-01-01

In this study we investigated the activity, expression and regulation of iPLA2 during ischemia in mouse C2C12 myotubes. Here, we show that in vitro ischemia, i.e. oxygen deprivation and glucose starvation, induces an iPLA2 activity that is totally reversed by siRNA knock down of iPLA2£], indicating...... preferential activation of iPLA2£]. The activity of the native iPLA2£] tetramer has in humans been proposed to be negatively regulated by interactions with catalytic inactive splice variants of the full-length protein. These variants, characterized by the presence exon 9a, have however not been identified...... of this transcript would be a C-terminally truncated î50 kDa protein lacking the catalytic site. qPCR indicated that, while the total iPLA2£] mRNA level in C2C12 myotubes increased weakly within 1-2 hours of in vitro ischemia, the transcript containing the mouse exon 9a was rapidly down regulated. In addition...

Dual roles of palladin protein in in vitro myogenesis: inhibition of early induction but promotion of myotube maturation.

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Ngoc-Uyen-Nhi Nguyen

Full Text Available Palladin is a microfilament-associated phosphoprotein whose function in skeletal muscle has rarely been studied. Therefore, we investigate whether myogenesis is influenced by the depletion of palladin expression known to interfere with the actin cytoskeleton dynamic required for skeletal muscle differentiation. The inhibition of palladin in C2C12 myoblasts leads to precocious myogenic differentiation with a concomitant reduction in cell apoptosis. This premature myogenesis is caused, in part, by an accelerated induction of p21, myogenin, and myosin heavy chain, suggesting that palladin acts as a negative regulator in early differentiation phases. Paradoxically, palladin-knockdown myoblasts are unable to differentiate terminally, despite their ability to perform some initial steps of differentiation. Cells with attenuated palladin expression form thinner myotubes with fewer myonuclei compared to those of the control. It is noteworthy that a negative regulator of myogenesis, myostatin, is activated in palladin-deficient myotubes, suggesting the palladin-mediated impairment of late-stage myogenesis. Additionally, overexpression of 140-kDa palladin inhibits myoblast differentiation while 200-kDa and 90-kDa palladin-overexpressed cells display an enhanced differentiation rate. Together, our data suggest that palladin might have both positive and negative roles in maintaining the proper skeletal myogenic differentiation in vitro.

The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes

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Cameron-Smith David

2011-06-01

Full Text Available Abstract Background The branched-chain amino acid (BCAA leucine has been identified to be a key regulator of skeletal muscle anabolism. Activation of anabolic signalling occurs via the mammalian target of rapamycin (mTOR through an undefined mechanism. System A and L solute carriers transport essential amino acids across plasma membranes; however it remains unknown whether an exogenous supply of leucine regulates their gene expression. The aim of the present study was to investigate the effects of acute and chronic leucine stimulation of anabolic signalling and specific amino acid transporters, using cultured primary human skeletal muscle cells. Results Human myotubes were treated with leucine, insulin or co-treated with leucine and insulin for 30 min, 3 h or 24 h. Activation of mTOR signalling kinases were examined, together with putative nutrient sensor human vacuolar protein sorting 34 (hVps34 and gene expression of selected amino acid transporters. Phosphorylation of mTOR and p70S6K was transiently increased following leucine exposure, independently to insulin. hVps34 protein expression was also significantly increased. However, genes encoding amino acid transporters were differentially regulated by insulin and not leucine. Conclusions mTOR signalling is transiently activated by leucine within human myotubes independently of insulin stimulation. While this occurred in the absence of changes in gene expression of amino acid transporters, protein expression of hVps34 increased.

Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

International Nuclear Information System (INIS)

Xu Qiuwei; Vu, Heather; Liu Liping; Wang, Ting-Chuan; Schaefer, William H.

2011-01-01

Mitochondrial toxicity has been a serious concern, not only in preclinical drug development but also in clinical trials. In mitochondria, there are several distinct metabolic processes including fatty acid β-oxidation, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS), and each process contains discrete but often intimately linked steps. Interruption in any one of those steps can cause mitochondrial dysfunction. Detection of inhibition to OXPHOS can be complicated in vivo because intermediate endogenous metabolites can be recycled in situ or circulated systemically for metabolism in other organs or tissues. Commonly used assays for evaluating mitochondrial function are often applied to ex vivo or in vitro samples; they include various enzymatic or protein assays, as well as functional assays such as measurement of oxygen consumption rate, membrane potential, or acidification rates. Metabolomics provides quantitative profiles of overall metabolic changes that can aid in the unraveling of explicit biochemical details of mitochondrial inhibition while providing a holistic view and heuristic understanding of cellular bioenergetics. In this paper, we showed the application of quantitative NMR metabolomics to in vitro myotube cells treated with mitochondrial toxicants, rotenone and antimycin A. The close coupling of the TCA cycle to the electron transfer chain (ETC) in OXPHOS enables specific diagnoses of inhibition to ETC complexes by discrete biochemical changes in the TCA cycle.

The dynamic equilibrium between ATP synthesis and ATP consumption is lower in isolated mitochondria from myotubes established from type 2 diabetic subjects compared to lean control

DEFF Research Database (Denmark)

Minet, Ariane D; Gaster, Michael

2011-01-01

compared to lean control. The ATP synthesis rate without ATP consumption was not different between groups and there were no significant gender differences. The mitochondrial dysfunction in type 2 diabetes in vivo is partly based on a primarily impaired ATP synthesis....... or not in the mitochondria of diabetic skeletal muscle from subjects with type 2 diabetes. ATP synthesis was measured on mitochondria isolated from cultured myotubes established from lean (11/9), obese (9/11) and subjects with type 2 diabetes (9/11) (female/male, n=20 in each group), precultured under normophysiological...... selects the mitochondria based on an antibody recognizing the mitochondrial outer membrane and not by size through gradient centrifugation. The dynamic equilibrium between ATP synthesis and ATP consumption is 35% lower in isolated mitochondria from myotubes established from type 2 diabetic subjects...

Riluzole increases the rate of glucose transport in L6 myotubes and NSC-34 motor neuron-like cells via AMPK pathway activation.

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Daniel, Bareket; Green, Omer; Viskind, Olga; Gruzman, Arie

2013-09-01

Riluzole is the only approved ALS drug. Riluzole influences several cellular pathways, but its exact mechanism of action remains unclear. Our goal was to study the drug's influence on the glucose transport rate in two ALS relevant cell types, neurons and myotubes. Stably transfected wild-type or mutant G93A human SOD1 NSC-34 motor neuron-like cells and rat L6 myotubes were exposed to riluzole. The rate of glucose uptake, translocation of glucose transporters to the cell's plasma membrane and the main glucose transport regulatory proteins' phosphorylation levels were measured. We found that riluzole increases the glucose transport rate and up-regulates the translocation of glucose transporters to plasma membrane in both types of cells. Riluzole leads to AMPK phosphorylation and to the phosphorylation of its downstream target, AS-160. In conclusion, increasing the glucose transport rate in ALS affected cells might be one of the mechanisms of riluzole's therapeutic effect. These findings can be used to rationally design and synthesize novel anti-ALS drugs that modulate glucose transport in neurons and skeletal muscles.

Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner

International Nuclear Information System (INIS)

Takegahara, Yuki; Yamanouchi, Keitaro; Nakamura, Katsuyuki; Nakano, Shin-ichi; Nishihara, Masugi

2014-01-01

Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis. For this purpose, skeletal muscle progenitor cells were transfected with siRNA of PPARγ (siPPARγ) in an attempt to inhibit adipogenesis. Myosin heavy chain (MHC)-positive myotube formation was promoted in cells transfected with siPPARγ compared to that of cells transfected with control siRNA. To determine whether direct cell-to-cell contact between adipocytes and myoblasts is a prerequisite for adipocytes to affect myogenesis, skeletal muscle progenitor cells were cocultured with pre- or mature adipocytes in a Transwell coculture system. MHC-positive myotube formation was inhibited when skeletal muscle progenitor cells were cocultured with mature adipocytes, but was promoted when they were cocultured with preadipocytes. Similar effects were observed when pre- or mature adipocyte-conditioned medium was used. These results indicate that preadipocytes play an important role in maintaining skeletal muscle mass by promoting myogenesis; once differentiated, the resulting mature adipocytes negatively affect myogenesis, leading to the muscle deterioration observed in skeletal muscle pathologies. - Highlights: • We examined the effects of pre- and mature adipocytes on myogenesis in vitro. • Preadipocytes and mature adipocytes affect myoblast fusion. • Preadipocytes play an important role in maintaining skeletal muscle mass. • Mature adipocytes lead to muscle deterioration observed in skeletal muscle pathologies

Myotube formation is affected by adipogenic lineage cells in a cell-to-cell contact-independent manner

Energy Technology Data Exchange (ETDEWEB)

Takegahara, Yuki; Yamanouchi, Keitaro, E-mail: akeita@mail.ecc.u-tokyo.ac.jp; Nakamura, Katsuyuki; Nakano, Shin-ichi; Nishihara, Masugi

2014-05-15

Intramuscular adipose tissue (IMAT) formation is observed in some pathological conditions such as Duchenne muscular dystrophy (DMD) and sarcopenia. Several studies have suggested that IMAT formation is not only negatively correlated with skeletal muscle mass but also causes decreased muscle contraction in sarcopenia. In the present study, we examined w hether adipocytes affect myogenesis. For this purpose, skeletal muscle progenitor cells were transfected with siRNA of PPARγ (siPPARγ) in an attempt to inhibit adipogenesis. Myosin heavy chain (MHC)-positive myotube formation was promoted in cells transfected with siPPARγ compared to that of cells transfected with control siRNA. To determine whether direct cell-to-cell contact between adipocytes and myoblasts is a prerequisite for adipocytes to affect myogenesis, skeletal muscle progenitor cells were cocultured with pre- or mature adipocytes in a Transwell coculture system. MHC-positive myotube formation was inhibited when skeletal muscle progenitor cells were cocultured with mature adipocytes, but was promoted when they were cocultured with preadipocytes. Similar effects were observed when pre- or mature adipocyte-conditioned medium was used. These results indicate that preadipocytes play an important role in maintaining skeletal muscle mass by promoting myogenesis; once differentiated, the resulting mature adipocytes negatively affect myogenesis, leading to the muscle deterioration observed in skeletal muscle pathologies. - Highlights: • We examined the effects of pre- and mature adipocytes on myogenesis in vitro. • Preadipocytes and mature adipocytes affect myoblast fusion. • Preadipocytes play an important role in maintaining skeletal muscle mass. • Mature adipocytes lead to muscle deterioration observed in skeletal muscle pathologies.

Glycogen Reduction in Myotubes of Late-Onset Pompe Disease Patients Using Antisense Technology.

Science.gov (United States)

Goina, Elisa; Peruzzo, Paolo; Bembi, Bruno; Dardis, Andrea; Buratti, Emanuele

2017-09-06

Glycogen storage disease type II (GSDII) is a lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme, leading to the accumulation of glycogen within the lysosomes. The disease has been classified in infantile and late-onset forms. Most late-onset patients share a splicing mutation c.-32-13T > G in intron 1 of the GAA gene that prevents efficient recognition of exon 2 by the spliceosome. In this study, we have mapped the splicing silencers of GAA exon 2 and developed antisense morpholino oligonucleotides (AMOs) to inhibit those regions and rescue normal splicing in the presence of the c.-32-13T > G mutation. Using a minigene approach and patient fibroblasts, we successfully increased inclusion of exon 2 in the mRNA and GAA enzyme production by targeting a specific silencer with a combination of AMOs. Most importantly, the use of these AMOs in patient myotubes results in a decreased accumulation of glycogen. To our knowledge, this is the only therapeutic approach resulting in a decrease of glycogen accumulation in patient tissues beside enzyme replacement therapy (ERT) and TFEB overexpression. As a result, it may represent a highly novel and promising therapeutic line for GSDII. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

DEFF Research Database (Denmark)

Green, C J; Bunprajun, T; Pedersen, B K

2013-01-01

in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

Caveolae regulation of mechanosensitive channel function in myotubes.

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Haixia Huang

Full Text Available Mutations that lead to muscular dystrophy often create deficiencies in cytoskeletal support of the muscle sarcolemma causing hyperactive mechanosensitive cation channel (MSC activity and elevated intracellular Ca(2+. Caveolae are cholesterol-rich microdomains that form mechanically deformable invaginations of the sarcolemma. Mutations to caveolin-3, the main scaffolding protein of caveolae in muscle, cause Limbe-Girdle muscular dystrophy. Using genetic and acute chemical perturbations of developing myotubes we investigated whether caveolae are functionally linked to MSCs. MSC sensitivity was assayed using suction application to patches and probe-induced indentation during whole-cell recordings. Membrane mechanical stress in patches was monitored using patch capacitance/impedance. Cholesterol depletion disrupted caveolae and caused a large increase in MSC current. It also decreased the membrane mechanical relaxation time, likely reflecting cytoskeleton dissociation from the bilayer. Reduction of Cav3 expression with miRNA also increased MSC current and decreased patch relaxation time. In contrast Cav3 overexpression produced a small decrease in MSC currents. To acutely and specifically inhibit Cav3 interactions, we made a chimeric peptide containing the antennapedia membrane translocation domain and the Cav3 scaffolding domain (A-CSD3. A-CSD3 action was time dependent initially producing a mild Ca(2+ leak and increased MSC current, while longer exposures decreased MSC currents coinciding with increased patch stiffening. Images of GFP labeled Cav3 in patches showed that Cav3 doesn't enter the pipette, showing patch composition differed from the cell surface. However, disruption via cholesterol depletion caused Cav3 to become uniformly distributed over the sarcolemma and Cav3 appearance in the patch dome. The whole-cell indentation currents elicited under the different caveolae modifying conditions mirror the patch response supporting the role of

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

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Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

2017-10-01

The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

Characterization of human myotubes from type 2 diabetic and non-diabetic subjects using complementary quantitative mass spectrometric methods

DEFF Research Database (Denmark)

Thingholm, Tine E; Bak, Steffen; Beck-Nielsen, Henning

2011-01-01

2 diabetes. Several abnormalities have been identified in skeletal muscle from type 2 diabetic subjects, however, the exact molecular mechanisms leading to the diabetic phenotype has still not been found. Here we present a large-scale study in which we combine a quantitative proteomic discovery...... strategy using iTRAQ and a label-free study with a targeted quantitative proteomic approach using selected reaction monitoring (SRM) to identify, quantify and validate changes in protein abundance between human myotubes obtained from non-diabetic lean, non-diabetic obese and type 2 diabetic subjects...

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

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Yano, Claudia L; Ventrucci, Gislaine; Field, William N; Tisdale, Michael J; Gomes-Marcondes, Maria Cristina C

2008-01-01

Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C 2 C 12 muscle cells. WF decreased the viability of C 2 C 12 myotubes, especially at concentrations of 20–25 μg.mL -1 . There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

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Tisdale Michael J

2008-01-01

Full Text Available Abstract Background Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. Methods In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF, which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. Results WF decreased the viability of C2C12 myotubes, especially at concentrations of 20–25 μg.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. Conclusion These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance

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Eriksen, Mette Brandt; Glintborg, Dorte; Nielsen, Michael Friberg Bruun

2014-01-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity is conse......Polycystic ovary syndrome (PCOS) is associated with insulin resistance and increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin mediated glucose disposal and the skeletal muscle tissue is capable to synthesize, convert and degrade androgens. Insulin sensitivity...... is conserved in cultured myotubes (in vitro) from patients with PCOS, but the effect of testosterone on this insulin sensitivity is unknown. We investigated the effect of 7days testosterone treatment (100nmol/l) on glucose transport and gene expression levels of hormone receptors and enzymes involved...... in the synthesis and conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-α, HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched controls. Testosterone treatment significantly increased aromatase and androgen receptor gene expression levels in patients and controls...

Inhibiting c-Jun N-terminal kinase partially attenuates caffeine-dependent cell death without alleviating the caffeine-induced reduction in mitochondrial respiration in C2C12 skeletal myotubes

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Downs, R.M.; Hughes, M.A.; Kinsey, S.T.; Johnson, M.C.; Baumgarner, B.L.

2016-01-01

Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration. We specifically examined the role of c-Jun N-terminal kinase (JNK), which has previously been shown to simultaneously increase caspase-dependent cell death and reduce mitochondrial respiration in other mammalian cell lines. We found that caffeine promoted a dose-dependent increase in cell death in multinucleated myotubes but did not in mononucleated myoblasts. The addition of 10 μM Z-DEVD-FMK, a specific inhibitor of executioner caspases, completely inhibited caffeine-dependent cell death. Further, the addition of 400 μM dantrolene, a specific ryanodine receptor (RYR) inhibitor, prevented the caffeine-dependent increase in cell death and the reduction in basal and maximal OCR. We also discovered that caffeine treatment significantly increased the phosphorylation of JNK and that the addition of 30 μM SP600125 (JNKi), a specific JNK inhibitor, partially attenuated caffeine-induced cell death without preventing the caffeine-dependent reduction in basal and maximal OCR. Our results suggest that JNK partially mediates the increase in caspase-dependent cell death but does not contribute to reduced mitochondrial respiration in caffeine-treated skeletal muscle cells. We conclude that caffeine increased cell death and reduced mitochondrial respiration in a calcium-dependent manner by activating the RYR and promoting reticular calcium release. - Highlights: • Caffeine

Short (16-mer locked nucleic acid splice-switching oligonucleotides restore dystrophin production in Duchenne Muscular Dystrophy myotubes.

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Vanessa Borges Pires

Full Text Available Splice-switching antisense oligonucleotides (SSOs offer great potential for RNA-targeting therapies, and two SSO drugs have been recently approved for treating Duchenne Muscular Dystrophy (DMD and Spinal Muscular Atrophy (SMA. Despite promising results, new developments are still needed for more efficient chemistries and delivery systems. Locked nucleic acid (LNA is a chemically modified nucleic acid that presents several attractive properties, such as high melting temperature when bound to RNA, potent biological activity, high stability and low toxicity in vivo. Here, we designed a series of LNA-based SSOs complementary to two sequences of the human dystrophin exon 51 that are most evolutionary conserved and evaluated their ability to induce exon skipping upon transfection into myoblasts derived from a DMD patient. We show that 16-mers with 60% of LNA modification efficiently induce exon skipping and restore synthesis of a truncated dystrophin isoform that localizes to the plasma membrane of patient-derived myotubes differentiated in culture. In sum, this study underscores the value of short LNA-modified SSOs for therapeutic applications.

ATP synthesis is impaired in isolated mitochondria from myotubes established from type 2 diabetic subjects

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Minet, Ariane D; Gaster, Michael

2010-01-01

To date, it is unknown whether mitochondrial dysfunction in skeletal muscle from subjects with type 2 diabetes is based on primarily reduced mitochondrial mass and/or a primarily decreased mitochondrial ATP synthesis. Mitochondrial mass were determined in myotubes established from eight lean, eight...... mass and the ATP synthesis rate, neither at baseline nor during acute insulin stimulation, were not different between groups. The ratio of ATP synthesis rate at hexokinase versus ATP synthesis rate at baseline was lower in diabetic mitochondria compared to lean mitochondria. Thus the lower content...... obese and eight subjects with type 2 diabetes precultured under normophysiological conditions. Furthermore, mitochondria were isolated and ATP production was measured by luminescence at baseline and during acute insulin stimulation with or without concomitant ATP utilization by hexokinase. Mitochondrial...

Melatonin protects against uric acid-induced mitochondrial dysfunction, oxidative stress, and triglyceride accumulation in C2C12 myotubes.

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Maarman, Gerald J; Andrew, Brittany M; Blackhurst, Dee M; Ojuka, Edward O

2017-04-01

Excess uric acid has been shown to induce oxidative stress, triglyceride accumulation, and mitochondrial dysfunction in the liver and is an independent predictor of type-2 diabetes. Skeletal muscle plays a dominant role in type 2 diabetes and presents a large surface area to plasma uric acid. However, the effects of uric acid on skeletal muscle are underinvestigated. Our aim was therefore to characterize the effects of excessive uric acid on oxidative stress, triglyceride content, and mitochondrial function in skeletal muscle C 2 C 12 myotubes and assess how these are modulated by the antioxidant molecule melatonin. Differentiated C 2 C 12 myotubes were exposed to 750 µM uric acid or uric acid + 10 nM melatonin for 72 h. Compared with control, uric acid increased triglyceride content by ~237%, oxidative stress by 32%, and antioxidant capacity by 135%. Uric acid also reduced endogenous ROUTINE respiration, complex II-linked oxidative phosphorylation, and electron transfer system capacities. Melatonin counteracted the effects of uric acid without further altering antioxidant capacity. Our data demonstrate that excess uric acid has adverse effects on skeletal muscle similar to those previously reported in hepatocytes and suggest that melatonin at a low physiological concentration of 10 nM may be a possible therapy against some adverse effects of excess uric acid. NEW & NOTEWORTHY Few studies have investigated the effects of uric acid on skeletal muscle. This study shows that hyperuricemia induces mitochondrial dysfunction and triglyceride accumulation in skeletal muscle. The findings may explain why hyperuricemia is an independent predictor of diabetes. Copyright © 2017 the American Physiological Society.

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C{sub 2}C{sub 12} myotubes

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Yano, Claudia L; Ventrucci, Gislaine [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil); Field, William N; Tisdale, Michael J [Cancer Research Laboratory, Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET (United Kingdom); Gomes-Marcondes, Maria Cristina C [Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, 13083-970, Campinas, São Paulo (Brazil)

2008-01-28

Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C{sub 2}C{sub 12} muscle cells. WF decreased the viability of C{sub 2}C{sub 12} myotubes, especially at concentrations of 20–25 μg.mL{sup -1}. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model.

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

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Maide Ö. Raeker

2011-01-01

Full Text Available During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues.

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

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Raeker, Maide Ö.; Russell, Mark W.

2011-01-01

During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues. PMID:22190853

Polyurethane acrylates as effective substrates for sustained in vitro culture of human myotubes.

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Andriani, Yosephine; Chua, Jason Min-Wen; Chua, Benjamin Yan-Jiang; Phang, In Yee; Shyh-Chang, Ng; Tan, Wui Siew

2017-07-15

Muscular disease has debilitating effects with severe damage leading to death. Our knowledge of muscle biology, disease and treatment is largely derived from non-human cell models, even though non-human cells are known to differ from human cells in their biochemical responses. Attempts to develop highly sought after in vitro human cell models have been plagued by early cell delamination and difficulties in achieving human myotube culture in vitro. In this work, we developed polyurethane acrylate (PUA) materials to support long-term in vitro culture of human skeletal muscle tissue. Using a constant base with modulated crosslink density we were able to vary the material modulus while keeping surface chemistry and roughness constant. While previous studies have focused on materials that mimic soft muscle tissue with stiffness ca. 12kPa, we investigated materials with tendon-like surface moduli in the higher 150MPa to 2.4GPa range, which has remained unexplored. We found that PUA of an optimal modulus within this range can support human myoblast proliferation, terminal differentiation and sustenance beyond 35days, without use of any extracellular protein coating. Results show that PUA materials can serve as effective substrates for successful development of human skeletal muscle cell models and are suitable for long-term in vitro studies. We developed polyurethane acrylates (PUA) to modulate the human skeletal muscle cell growth and maturation in vitro by controlling surface chemistry, morphology and tuning material's stiffness. PUA was able to maintain muscle cell viability for over a month without any detectable signs of material degradation. The best performing PUA prevented premature cell detachment from the substrate which often hampered long-term muscle cell studies. It also supported muscle cell maturation up to the late stages of differentiation. The significance of these findings lies in the possibility to advance studies on muscle cell biology, disease and

Generation of functional neuromuscular junctions from human pluripotent stem cell lines

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Katja ePuttonen

2015-12-01

Full Text Available Several neuromuscular diseases involve dysfunction of neuromuscular junctions (NMJs, yet there are no patient-specific human models for electrophysiological characterization of NMJ. We seeded cells of neurally-induced embryoid body-like spheres derived from induced pluripotent stem cell (iPSC or embryonic stem cell (ESC lines as monolayers without basic fibroblast factor (bFGF and observed differentiation of neuronal as well as spontaneously contracting, multinucleated skeletal myotubes. The myotubes showed striation, immunoreactivity for myosin heavy chain, actin bundles typical for myo-oriented cells, and generated spontaneous and evoked action potentials (APs. The myogenic differentiation was associated with expression of MyoD1, myogenin and type I ryanodine receptor. Neurons formed end plate like structures with strong binding of α-bungarotoxin, a marker of nicotinic acetylcholine receptors highly expressed in the postsynaptic membrane of NMJs, and expressed SMI-32, a motoneuron marker, as well as SV2, a marker for synapses. Pharmacological stimulation of cholinergic receptors resulted in strong depolarization of myotube membrane and raised Ca2+ concentration in sarcoplasm, while electrical stimulation evoked Ca2+ transients in myotubes. Stimulation of motoneurons with N-Methyl-D-aspartate resulted in reproducible APs in myotubes and end plates displayed typical MEPs and tonic activity depolarizing myotubes of about 10 mV. We conclude that simultaneous differentiation of neurons and myotubes from patient-specific iPSCs or ESCs results also in the development of functional NMJs. Our human model of NMJ may serve as an important tool to investigate normal development, mechanisms of diseases and novel drug targets involving NMJ dysfunction and degeneration.

Cytoprotective Role of Nrf2 in Electrical Pulse Stimulated C2C12 Myotube.

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Masaki Horie

Full Text Available Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2 transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.

Mononuclear Cells from Dedifferentiation of Mouse Myotubes display Remarkable Regenerative Capability

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Yang, Zhong; Liu, Qiang; Mannix, Robert J.; Xu, Xiaoyin; Li, Hongli; Ma, Zhiyuan; Ingber, Donald E.; Allen, Paul D.; Wang, Yaming

2015-01-01

Certain lower organisms achieve organ regeneration by reverting differentiated cells into tissue-specific progenitors that re-enter embryonic programs. During muscle regeneration in the urodele amphibian, post-mitotic multinucleated skeletal myofibers transform into mononucleated proliferating cells upon injury, and a transcription factor-msx1 plays a role in their reprograming. Whether this powerful regeneration strategy can be leveraged in mammals remains unknown, as it has not been demonstrated that the dedifferentiated progenitor cells arising from muscle cells overexpressing Msx1 are lineage-specific and possess the same potent regenerative capability as their amphibian counterparts. Here we show that ectopic expression of Msx1 reprograms post-mitotic, multinucleated, primary mouse myotubes to become proliferating mononuclear cells. These dedifferentiated cells reactivate genes expressed by embryonic muscle progenitor cells and generate only muscle tissue in vivo both in an ectopic location and inside existing muscle. More importantly, distinct from adult muscle satellite cells, these cells appear both to fuse with existing fibers and to regenerate myofibers in a robust and time-dependent manner. Upon transplantation into a degenerating muscle, these dedifferentiated cells generated a large number of myofibers that increased over time and replenished almost half of the cross-sectional area of the muscle in only 12 weeks. Our study demonstrates that mammals can harness a muscle regeneration strategy used by lower organisms when the same molecular pathway is activated. PMID:24916688

Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

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Jung, Jong Gab; Choi, Sung-E; Hwang, Yoon-Jung; Lee, Sang-A; Kim, Eun Kyoung; Lee, Min-Seok; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

2011-10-15

Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

Insights into skeletal muscle development and applications in regenerative medicine.

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Tran, T; Andersen, R; Sherman, S P; Pyle, A D

2013-01-01

Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development. Copyright © 2013 Elsevier Inc. All rights reserved.

Glucose dependence of glycogen synthase activity regulation by GSK3 and MEK/ERK inhibitors and angiotensin-(1-7) action on these pathways in cultured human myotubes.

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Montori-Grau, Marta; Tarrats, Núria; Osorio-Conles, Oscar; Orozco, Anna; Serrano-Marco, Lucía; Vázquez-Carrera, Manuel; Gómez-Foix, Anna M

2013-05-01

Glycogen synthase (GS) is activated by glucose/glycogen depletion in skeletal muscle cells, but the contributing signaling pathways, including the chief GS regulator GSK3, have not been fully defined. The MEK/ERK pathway is known to regulate GSK3 and respond to glucose. The aim of this study was to elucidate the GSK3 and MEK/ERK pathway contribution to GS activation by glucose deprivation in cultured human myotubes. Moreover, we tested the glucose-dependence of GSK3 and MEK/ERK effects on GS and angiotensin (1-7) actions on these pathways. We show that glucose deprivation activated GS, but did not change phospho-GS (Ser640/1), GSK3β activity or activity-activating phosphorylation of ERK1/2. We then treated glucose-replete and -depleted cells with SB415286, U0126, LY294 and rapamycin to inhibit GSK3, MEK1/2, PI3K and mTOR, respectively. SB415286 activated GS and decreased the relative phospho-GS (Ser640/1) level, more in glucose-depleted than -replete cells. U0126 activated GS and reduced the phospho-GS (Ser640/1) content significantly in glucose-depleted cells, while GSK3β activity tended to increase. LY294 inactivated GS in glucose-depleted cells only, without affecting relative phospho-GS (Ser640/1) level. Rapamycin had no effect on GS activation. Angiotensin-(1-7) raised phospho-ERK1/2 but not phospho-GSK3β (Ser9) content, while it inactivated GS and increased GS phosphorylation on Ser640/1, in glucose-replete cells. In glucose-depleted cells, angiotensin-(1-7) effects on ERK1/2 and GS were reverted, while relative phospho-GSK3β (Ser9) content decreased. In conclusion, activation of GS by glucose deprivation is not due to GS Ser640/1 dephosphorylation, GSK3β or ERK1/2 regulation in cultured myotubes. However, glucose depletion enhances GS activation/Ser640/1 dephosphorylation due to both GSK3 and MEK/ERK inhibition. Angiotensin-(1-7) inactivates GS in glucose-replete cells in association with ERK1/2 activation, not with GSK3 regulation, and glucose

Topologically Micropatterned Collagen and Poly(ε-caprolactone) Struts Fabricated Using the Poly(vinyl alcohol) Fibrillation/Leaching Process To Develop Efficiently Engineered Skeletal Muscle Tissue.

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Kim, Minseong; Kim, WonJin; Kim, GeunHyung

2017-12-20

Optimally designed three-dimensional (3D) biomedical scaffolds for skeletal muscle tissue regeneration pose significant research challenges. Currently, most studies on scaffolds focus on the two-dimensional (2D) surface structures that are patterned in the micro-/nanoscales with various repeating sizes and shapes to induce the alignment of myoblasts and myotube formation. The 2D patterned surface clearly provides effective analytical results of pattern size and shape of the myoblast alignment and differentiation. However, it is inconvenient in terms of the direct application for clinical usage due to the limited thickness and 3D shapeability. Hence, the present study suggests an innovative hydrogel or synthetic structure that consists of uniaxially surface-patterned cylindrical struts for skeleton muscle regeneration. The alignment of the pattern on the hydrogel (collagen) and poly(ε-caprolactone) struts was attained with the fibrillation of poly(vinyl alcohol) and the leaching process. Various cell culture results indicate that the C2C12 cells on the micropatterned collagen structure were fully aligned, and that a significantly high level of myotube formation was achieved when compared to the collagen structures that were not treated with the micropatterning process.

Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes.

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Sartor, Francesco; Jackson, Matthew J; Squillace, Cesare; Shepherd, Anthony; Moore, Jonathan P; Ayer, Donald E; Kubis, Hans-Peter

2013-04-01

Chronic sugar-sweetened beverage (SSB) consumption is associated with obesity and type 2 diabetes mellitus (T2DM). Hyperglycaemia contributes to metabolic alterations observed in T2DM, such as reduced oxidative capacity and elevated glycolytic and lipogenic enzyme expressions in skeletal muscle tissue. We aimed to investigate the metabolic alterations induced by SSB supplementation in healthy individuals and to compare these with the effects of chronic hyperglycaemia on primary muscle cell cultures. Lightly active, healthy, lean subjects (n = 11) with sporadic soft drink consumption underwent a 4-week SSB supplementation (140 ± 15 g/day, ~2 g glucose/kg body weight/day, glucose syrup). Before and after the intervention, body composition, respiratory exchange ratio (RER), insulin sensitivity, muscle metabolic gene and protein expression were assessed. Adaptive responses to hyperglycaemia (7 days, 15 mM) were tested in primary human myotubes. SSB supplementation increased fat mass (+1.0 kg, P < 0.05), fasting RER (+0.12, P < 0.05), fasting glucose (+0.3 mmol/L, P < 0.05) and muscle GAPDH mRNA expressions (+0.94 AU, P < 0.05). PGC1α mRNA was reduced (-0.20 AU, P < 0.05). Trends were found for insulin resistance (+0.16 mU/L, P = 0.09), and MondoA protein levels (+1.58 AU, P = 0.08). Primary myotubes showed elevations in GAPDH, ACC, MondoA and TXNIP protein expressions (P < 0.05). Four weeks of SSB supplementation in healthy individuals shifted substrate metabolism towards carbohydrates, increasing glycolytic and lipogenic gene expression and reducing mitochondrial markers. Glucose-sensing protein MondoA might contribute to this shift, although further in vivo evidence is needed to corroborate this.

Hypomorphic Smn knockdown C2C12 myoblasts reveal intrinsic defects in myoblast fusion and myotube morphology

International Nuclear Information System (INIS)

Shafey, Dina; Cote, Patrice D.; Kothary, Rashmi

2005-01-01

Dosage of the survival motor neuron (SMN) protein has been directly correlated with the severity of disease in patients diagnosed with spinal muscular atrophy (SMA). It is also clear that SMA is a neurodegenerative disorder characterized by the degeneration of the α-motor neurons in the anterior horn of the spinal cord and atrophy of the associated skeletal muscle. What is more controversial is whether it is neuronal and/or muscle-cell-autonomous defects that are responsible for the disease per se. Although motor neuron degeneration is generally accepted as the primary event in SMA, intrinsic muscle defects in this disease have not been ruled out. To gain a better understanding of the influence of SMN protein dosage in muscle, we have generated a hypomorphic series of myoblast (C2C12) stable cell lines with variable Smn knockdown. We show that depletion of Smn in these cells resulted in a decrease in the number of nuclear 'gems' (gemini of coiled bodies), reduced proliferation with no increase in cell death, defects in myoblast fusion, and malformed myotubes. Importantly, the severity of these abnormalities is directly correlated with the decrease in Smn dosage. Taken together, our work supports the view that there is an intrinsic defect in skeletal muscle cells of SMA patients and that this defect contributes to the overall pathogenesis in this devastating disease

Space Structure Development

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Smith, Thomas

2015-01-01

The duration of my Summer 2015 Internship Tour at NASA's Johnson Space Center was spent working in the Structural Engineering Division's Structures Branch. One of the two main roles of the Structures Branch, ES2, is to ensure the structural integrity of spacecraft vehicles and the structural subsystems needed to support those vehicles. The other main objective of this branch is to develop the lightweight structures that are necessary to take humans beyond Low-Earth Orbit. Within ES2, my four projects involved inflatable space structure air bladder material testing; thermal and impact material testing for spacecraft windows; structural analysis on a joint used in the Boeing CST-100 airbag system; and an additive manufacturing design project.

Role of the water extract from Coccinia indica stem on the stimulation of glucose transport in L8 myotubes

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Chaweewan Jansakul

2006-11-01

Full Text Available Hypoglycemic effect of Coccinia indica used for treatment of diabetes in traditional remedies has known to relate with increased transport of glucose into peripheral tissues. However, the cellular mechanisms for this effect remain unclear. This present study reports that the water extract (WE of C. indica stem exhibited a dose-dependent induction of 2-deoxyglucose (2-DG uptake in rat L8 myotubes. Maximal uptake was observed with approximately 3-fold increase in 2-DG transport in 16 h treatment compared with the control. Effect of WE was stronger than that of 1 mM metformin. The effects of insulin and WE were additive. WE-induced glucose uptake was significantly inhibited by cycloheximide and partially reversed by SB203580. GLUT1 protein was markedly increased in response to WE. Conversely, WE had no effect on GLUT4 protein level. Redistribution of GLUT4 to the plasma membrane was demonstrated. Triterpenoids and carbohydrates were detected in WE. In conclusion, new GLUT1 protein synthesis is necessary for WEstimulated glucose transport while p38-MAPK-dependent activation of transporter intrinsic activity partly contributes to WE action. These results may explain and support the use of C. indica for the prevention and treatment of diabetes.

Differentiation and sarcomere formation in skeletal myocytes directly prepared from human induced pluripotent stem cells using a sphere-based culture.

Science.gov (United States)

Jiwlawat, Saowanee; Lynch, Eileen; Glaser, Jennifer; Smit-Oistad, Ivy; Jeffrey, Jeremy; Van Dyke, Jonathan M; Suzuki, Masatoshi

Human induced-pluripotent stem cells (iPSCs) are a promising resource for propagation of myogenic progenitors. Our group recently reported a unique protocol for the derivation of myogenic progenitors directly (without genetic modification) from human pluripotent cells using free-floating spherical culture. Here we expand our previous efforts and attempt to determine how differentiation duration, culture surface coatings, and nutrient supplements in the medium influence progenitor differentiation and formation of skeletal myotubes containing sarcomeric structures. A long differentiation period (over 6 weeks) promoted the differentiation of iPSC-derived myogenic progenitors and subsequent myotube formation. These iPSC-derived myotubes contained representative sarcomeric structures, consisting of organized myosin and actin filaments, and could spontaneously contract. We also found that a bioengineering approach using three-dimensional (3D) artificial muscle constructs could facilitate the formation of elongated myotubes. Lastly, we determined how culture surface coating matrices and different supplements would influence terminal differentiation. While both Matrigel and laminin coatings showed comparable effects on muscle differentiation, B27 serum-free supplement in the differentiation medium significantly enhanced myogenesis compared to horse serum. Our findings support the possibility to create an in vitro model of contractile sarcomeric myofibrils for disease modeling and drug screening to study neuromuscular diseases. Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Adult fast myosin pattern and Ca2+-induced slow myosin pattern in primary skeletal muscle culture

Science.gov (United States)

Kubis, Hans-Peter; Haller, Ernst-August; Wetzel, Petra; Gros, Gerolf

1997-01-01

A primary muscle cell culture derived from newborn rabbit muscle and growing on microcarriers in suspension was established. When cultured for several weeks, the myotubes in this model develop the completely adult pattern of fast myosin light and heavy chains. When Ca2+ ionophore is added to the culture medium on day 11, raising intracellular [Ca2+] about 10-fold, the myotubes develop to exhibit properties of an adult slow muscle by day 30, expressing slow myosin light as well as heavy chains, elevated citrate synthase, and reduced lactate dehydrogenase. The remarkable plasticity of these myotubes becomes apparent, when 8 days after withdrawal of the ionophore a marked slow-to-fast transition, as judged from the expression of isomyosins and metabolic enzymes, occurs. PMID:9108130

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

Science.gov (United States)

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Conversion of leucine to β‐hydroxy‐β‐methylbutyrate by α‐keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes

Science.gov (United States)

Vílchez, José D.; Salto, Rafael; Manzano, Manuel; Sevillano, Natalia; Campos, Nefertiti; Argilés, Josep M.; Rueda, Ricardo; López‐Pedrosa, José M.

2015-01-01

Abstract Background L‐Leu and its metabolite β‐hydroxy‐β‐methylbutyrate (HMB) stimulate muscle protein synthesis enhancing the phosphorylation of proteins that regulate anabolic signalling pathways. Alterations in these pathways are observed in many catabolic diseases, and HMB and L‐Leu have proven their anabolic effects in in vivo and in vitro models. The aim of this study was to compare the anabolic effects of L‐Leu and HMB in myotubes grown in the absence of any catabolic stimuli. Methods Studies were conducted in vitro using rat L6 myotubes under normal growth conditions (non‐involving L‐Leu‐deprived conditions). Protein synthesis and mechanistic target of rapamycin signalling pathway were determined. Results Only HMB was able to increase protein synthesis through a mechanism that involves the phosphorylation of the mechanistic target of rapamycin as well as its downstream elements, pS6 kinase, 4E binding protein‐1, and eIF4E. HMB was significantly more effective than L‐Leu in promoting these effects through an activation of protein kinase B/Akt. Because the conversion of L‐Leu to HMB is limited in muscle, L6 cells were transfected with a plasmid that codes for α‐keto isocaproate dioxygenase, the key enzyme involved in the catabolic conversion of α‐keto isocaproate into HMB. In these transfected cells, L‐Leu was able to promote protein synthesis and mechanistic target of rapamycin regulated pathway activation equally to HMB. Additionally, these effects of leucine were reverted to a normal state by mesotrione, a specific inhibitor of α‐keto isocaproate dioxygenase. Conclusion Our results suggest that HMB is an active L‐Leu metabolite able to maximize protein synthesis in skeletal muscle under conditions, in which no amino acid deprivation occurred. It may be proposed that supplementation with HMB may be very useful to stimulate protein synthesis in wasting conditions associated with chronic diseases, such as cancer or

Soil Retaining Structures : Development of models for structural analysis

NARCIS (Netherlands)

Bakker, K.J.

2000-01-01

The topic of this thesis is the development of models for the structural analysis of soil retaining structures. The soil retaining structures being looked at are; block revetments, flexible retaining walls and bored tunnels in soft soil. Within this context typical structural behavior of these

Probabilistic Structural Analysis Theory Development

Science.gov (United States)

Burnside, O. H.

1985-01-01

The objective of the Probabilistic Structural Analysis Methods (PSAM) project is to develop analysis techniques and computer programs for predicting the probabilistic response of critical structural components for current and future space propulsion systems. This technology will play a central role in establishing system performance and durability. The first year's technical activity is concentrating on probabilistic finite element formulation strategy and code development. Work is also in progress to survey critical materials and space shuttle mian engine components. The probabilistic finite element computer program NESSUS (Numerical Evaluation of Stochastic Structures Under Stress) is being developed. The final probabilistic code will have, in the general case, the capability of performing nonlinear dynamic of stochastic structures. It is the goal of the approximate methods effort to increase problem solving efficiency relative to finite element methods by using energy methods to generate trial solutions which satisfy the structural boundary conditions. These approximate methods will be less computer intensive relative to the finite element approach.

Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes.

Science.gov (United States)

Sun, Shishuo; Tan, Pengcheng; Huang, Xiaoheng; Zhang, Wei; Kong, Chen; Ren, Fangfang; Su, Xiong

2018-02-16

Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands, and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared with WT cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of WT CD36, but not a ubiquitination-defective CD36 mutant, delayed IRS1 degradation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Structural development of child's artistic expression

OpenAIRE

Sanja Filipović; Milica Vojvodić

2017-01-01

Abstract Structural development implies control and capability of the expression usage in terms of independent creative expression and making. Understanding of structural development of child's artistic expression as a phenomenon (which is suitable to child's age) has some implications on methodical acts considering artistic education of children and youngsters. Therefore, it is of unexceptional importance to know these laws as well as methodical acts which encourage the structural develop...

Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion

International Nuclear Information System (INIS)

Mukai, Atsushi; Hashimoto, Naohiro

2008-01-01

Multinucleated myotubes are formed by fusion of mononucleated myogenic progenitor cells (myoblasts) during terminal skeletal muscle differentiation. In addition, myoblasts fuse with myotubes, but terminally differentiated myotubes have not been shown to fuse with each other. We show here that an adenylate cyclase activator, forskolin, and other reagents that elevate intracellular cyclic AMP (cAMP) levels induced cell fusion between small bipolar myotubes in vitro. Then an extra-large myotube, designated a 'myosheet,' was produced by both primary and established mouse myogenic cells. Myotube-to-myotube fusion always occurred between the leading edge of lamellipodia at the polar end of one myotube and the lateral plasma membrane of the other. Forskolin enhanced the formation of lamellipodia where cAMP-dependent protein kinase (PKA) was accumulated. Blocking enzymatic activity or anchoring of PKA suppressed forskolin-enhanced lamellipodium formation and prevented fusion of multinucleated myotubes. Localized PKA activity was also required for fusion of mononucleated myoblasts. The present results suggest that localized PKA plays a pivotal role in the early steps of myogenic cell fusion, such as cell-to-cell contact/recognition through lamellipodium formation. Furthermore, the localized cAMP-PKA pathway might be involved in the specification of the fusion-competent areas of the plasma membrane in lamellipodia of myogenic cells

A role for Insulin-like growth factor 2 in specification of the fast skeletal muscle fibre

Directory of Open Access Journals (Sweden)

Ting Tao

2007-06-01

Full Text Available Abstract Background Fibre type specification is a poorly understood process beginning in embryogenesis in which skeletal muscle myotubes switch myosin-type to establish fast, slow and mixed fibre muscle groups with distinct function. Growth factors are required to establish slow fibres; it is unknown how fast twitch fibres are specified. Igf-2 is an embryonically expressed growth factor with established in vitro roles in skeletal muscle. Its localisation and role in embryonic muscle differentiation had not been established. Results Between E11.5 and E15.5 fast Myosin (FMyHC localises to secondary myotubes evenly distributed throughout the embryonic musculature and gradually increasing in number so that by E15.5 around half contain FMyHC. The Igf-2 pattern closely correlates with FMyHC from E13.5 and peaks at E15.5 when over 90% of FMyHC+ myotubes also contain Igf-2. Igf-2 lags FMyHC and it is absent from muscle myotubes until E13.5. Igf-2 strongly down-regulates by E17.5. A striking feature of the FMyHC pattern is its increased heterogeneity and attenuation in many fibres from E15.5 to day one after birth (P1. Transgenic mice (MIG which express Igf-2 in all of their myotubes, have increased FMyHC staining, a higher proportion of FMyHC+ myotubes and loose their FMyHC staining heterogeneity. In Igf-2 deficient mice (MatDi FMyHC+ myotubes are reduced to 60% of WT by E15.5. In vitro, MIG induces a 50% excess of FMyHC+ and a 30% reduction of SMHyC+ myotubes in C2 cells which can be reversed by Igf-2-targeted ShRNA resulting in 50% reduction of FMyHC. Total number of myotubes was not affected. Conclusion In WT embryos the appearance of Igf-2 in embryonic myotubes lags FMyHC, but by E15.5 around 45% of secondary myotubes contain both proteins. Forced expression of Igf-2 into all myotubes causes an excess, and absence of Igf-2 suppresses, the FMyHC+ myotube component in both embryonic muscle and differentiated myoblasts. Igf-2 is thus required, not for

Effects of BTS (N-benzyl-p-toluene sulphonamide), an inhibitor for myosin-actin interaction, on myofibrillogenesis in skeletal muscle cells in culture.

Science.gov (United States)

Kagawa, Maiko; Sato, Naruki; Obinata, Takashi

2006-11-01

Actin filaments align around myosin filaments in the correct polarity and in a hexagonal arrangement to form cross-striated structures. It has been postulated that this myosin-actin interaction is important in the initial phase of myofibrillogenesis. It was previously demonstrated that an inhibitor of actin-myosin interaction, BDM (2,3-butanedione monoxime), suppresses myofibril formation in muscle cells in culture. However, further study showed that BDM also exerts several additional effects on living cells. In this study, we further examined the role of actin-myosin interaction in myofibril assembly in primary cultures of chick embryonic skeletal muscle by applying a more specific inhibitor, BTS (N-benzyl-p-toluene sulphonamide), of myosin ATPase and actin-myosin interaction. The assembly of sarcomeric structures from myofibrillar proteins was examined by immunocytochemical methods with the application of BTS to myotubes just after fusion. Addition of BTS (10-50 microM) significantly suppressed the organization of actin and myosin into cross-striated structures. BTS also interfered in the organization of alpha-actinin, C-protein (or MyBP-C), and connectin (or titin) into ordered striated structures, though the sensitivity was less. Moreover, when myotubes cultured in the presence of BTS were transferred to a control medium, sarcomeric structures were formed in 2-3 days, indicating that the inhibitory effect of BTS on myotubes is reversible. These results show that actin-myosin interaction plays a critical role in the process of myofibrillogenesis.

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

PRSEUS Structural Concept Development

Science.gov (United States)

Velicki, Alex; Jegley, Dawn

2014-01-01

A lighter, more robust airframe is one of the key technological advancements necessary for the successful launch of any large next-generation transport aircraft. Such a premise dictates that considerable improvements beyond current state-of-the-art aluminum structures is needed, and that improvements of this magnitude will require an extensive use of composite materials that are not only lightweight, but also economical to produce. To address this challenge, researchers at NASA and The Boeing Company are developing a novel structural concept called the Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) under the Environmentally Responsible Aviation (ERA) Project. It is an integrally stiffened panel concept that is stitched together and designed to maintain residual load-carrying capabilities under a variety of damage scenarios. In addition to improved structural performance, an important facet of this unique arrangement of stitched carbon fibers is its innovative manufacturing method that has the potential to lower fabrication costs by eliminating fasteners and autoclave cures. The rationale and development status for this new approach forms the basis of the work described in this paper. The test specimens described herein were fabricated, or are currently being fabricated, by The Boeing Company, while the structural analyses and testing tasks are being performed by NASA and Boeing personnel.

Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and β1 integrin expression in vitro

International Nuclear Information System (INIS)

Lluri, Gentian; Langlois, Garret D.; Soloway, Paul D.; Jaworski, Diane M.

2008-01-01

Myogenesis in vitro involves myoblast cell cycle arrest, migration, and fusion to form multinucleated myotubes. Extracellular matrix (ECM) integrity during these processes is maintained by the opposing actions of matrix metalloproteinase (MMP) proteases and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Here, we report that TIMP-2, MMP-2, and MT1-MMP are differentially expressed during mouse myoblast differentiation in vitro. A specific role for TIMP-2 in myogenesis is demonstrated by altered TIMP-2 -/- myotube formation. When differentiated in horse serum-containing medium, TIMP-2 -/- myotubes are larger than wild-type myotubes. In contrast, when serum-free medium is used, TIMP-2 -/- myotubes are smaller than wild-type myotubes. Regardless of culture condition, myotube size is directly correlated with MMP activity and inversely correlated with β1 integrin expression. Treatment with recombinant TIMP-2 rescues reduced TIMP-2 -/- myotube size and induces increased MMP-9 activation and decreased β1 integrin expression. Treatment with either MMP-2 or MMP-9 similarly rescues reduced myotube size, but has no effect on β1 integrin expression. These data suggest a specific regulatory relationship between TIMP-2 and β1 integrin during myogenesis. Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

International Nuclear Information System (INIS)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

2015-01-01

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

Energy Technology Data Exchange (ETDEWEB)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T. [Department of Kinesiology, The University of Toledo, Toledo, OH (United States); Pierre, Philippe [Centre d’Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille (France); INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille (France); CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille (France); Chadee, Deborah N. [Department of Biological Sciences, The University of Toledo, Toledo, OH (United States); Pizza, Francis X., E-mail: Francis.Pizza@utoledo.edu [Department of Kinesiology, The University of Toledo, Toledo, OH (United States)

2015-02-15

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice

Directory of Open Access Journals (Sweden)

Chien-Kei Wei

2017-01-01

Full Text Available The anti-diabetic activity of ginger powder (Zingiber officinale has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5′ adenosine monophosphate-activated protein kinase (AMPK phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.

Structural development of child's artistic expression

Directory of Open Access Journals (Sweden)

Sanja Filipović

2017-03-01

Full Text Available Structural development implies control and capability of the expression usage in terms of independent creative expression and making. Understanding of structural development of child's artistic expression as a phenomenon (which is suitable to child's age has some implications on methodical acts considering the artistic education of children and youngsters. Therefore, it is of unexceptional importance to know these laws as well as methodical acts which encourage the structural development of artistic capabilities from an early age. Various experts dealt with this phenomenon, particularly Bogomil Karlavaris. In his methodical research, he has given an unexceptional part to this problem. It has been a starting point for analysis of certain methodical questions which are included in this work.

Development of thermoplastic composite aircraft structures

Science.gov (United States)

Renieri, Michael P.; Burpo, Steven J.; Roundy, Lance M.; Todd, Stephanie A.; Kim, H. J.

1992-01-01

Efforts focused on the use of thermoplastic composite materials in the development of structural details associated with an advanced fighter fuselage section with applicability to transport design. In support of these designs, mechanics developments were conducted in two areas. First, a dissipative strain energy approach to material characterization and failure prediction, developed at the Naval Research Laboratory, was evaluated as a design/analysis tool. Second, a finite element formulation for thick composites was developed and incorporated into a lug analysis method which incorporates pin bending effects. Manufacturing concepts were developed for an upper fuel cell cover. A detailed trade study produced two promising concepts: fiber placement and single-step diaphragm forming. Based on the innovative design/manufacturing concepts for the fuselage section primary structure, elements were designed, fabricated, and structurally tested. These elements focused on key issues such as thick composite lugs and low cost forming of fastenerless, stiffener/moldine concepts. Manufacturing techniques included autoclave consolidation, single diaphragm consolidation (SDCC) and roll-forming.

FSHD myoblasts fail to downregulate intermediate filament protein vimentin during myogenic differentiation.

Directory of Open Access Journals (Sweden)

Lipinski M.

2011-10-01

Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an autosomal dominant hereditary neuromuscular disorder. The clinical features of FSHD include weakness of the facial and shoulder girdle muscles followed by wasting of skeletal muscles of the pelvic girdle and lower extremities. Although FSHD myoblasts grown in vitro can be induced to differentiate into myotubes by serum starvation, the resulting FSHD myotubes have been shown previously to be morphologically abnormal. Aim. In order to find the cause of morphological anomalies of FSHD myotubes we compared in vitro myogenic differentiation of normal and FSHD myoblasts at the protein level. Methods. We induced myogenic differentiation of normal and FSHD myoblasts by serum starvation. We then compared protein extracts from proliferating myoblasts and differentiated myotubes using SDS-PAGE followed by mass spectrometry identification of differentially expressed proteins. Results. We demonstrated that the expression of vimentin was elevated at the protein and mRNA levels in FSHD myotubes as compared to normal myotubes. Conclusions. We demonstrate for the first time that in contrast to normal myoblasts, FSHD myoblasts fail to downregulate vimentin after induction of in vitro myogenic differentiation. We suggest that vimentin could be an easily detectable marker of FSHD myotubes

Development of mechanical structure design technology for LMR

Energy Technology Data Exchange (ETDEWEB)

Yoo, Bong; Lee, Jae Han; Joo, Young Sang [and others

2000-05-01

In this project, fundamentals for conceptual design of mechanical structure system for LMR are independently established. The research contents are as follow; at first, conceptual design for SSC, design integration of interfaces, design consistency to keep functions and interfaces by developing arrangement of reactor system and 3 dimensional concept drawings, development and revision of preliminary design requirements and structural design basis, and evaluation of structural integrity for SSC following structural design criteria to check the conceptual design to be proper, at second, development of high temperature structure design and analysis technology and establishment of high temperature structural analysis codes and scheme, development of seismic isolation design concept to reduce seismic design loads to SCC and establishment of seismic analysis codes and scheme.

Development of mechanical structure design technology for LMR

International Nuclear Information System (INIS)

Yoo, Bong; Lee, Jae Han; Joo, Young Sang

2000-05-01

In this project, fundamentals for conceptual design of mechanical structure system for LMR are independently established. The research contents are as follow; at first, conceptual design for SSC, design integration of interfaces, design consistency to keep functions and interfaces by developing arrangement of reactor system and 3 dimensional concept drawings, development and revision of preliminary design requirements and structural design basis, and evaluation of structural integrity for SSC following structural design criteria to check the conceptual design to be proper, at second, development of high temperature structure design and analysis technology and establishment of high temperature structural analysis codes and scheme, development of seismic isolation design concept to reduce seismic design loads to SCC and establishment of seismic analysis codes and scheme

Development of Technology for Structural Integrity Evaluation

International Nuclear Information System (INIS)

Choun, Young Sun; Choi, I. K.; Kim, M. K. and others

2005-03-01

The purpose of this study is a development of seismic safety and structural integrity evaluation method of the structure in the Nuclear Power plant (NPP). The purpose of 1st sub-Topic is the development and improvement of the seismic safety evaluation methodology for the Nuclear Power Plant structures and safety related equipment. The purpose of 2nd sub-topic is the increasing of structure and equipment seismic capacity through the reducing of seismic force. The purpose of 3rd sub-topic is the development of 3-D nonlinear finite element analysis program for prestressed concrete containment building. The last purpose if the evaluation of the failure mechanism of containment structure and structure capacity and the assessment of integrity of containment through the of leakage test. As a result of this research, there are many research results were produced. The scenario earthquake developing method was developed and the effect of the structures and equipment was analyzed. The effectiveness of isolation system was determined and optimum isolation systems for each equipment were selected. The NUCAS-3D program for the 3 dimensional numerical analysis of containment building using the embedded tendon element and rebar element was developed. The tension behavior of containment building was examined and the leakage rate of the concrete crack was determined. The results of this research can be successfully used for many fields of integrity of NPP site. It can be used for development of design earthquake for the seismic design and safety evaluation and establishment of seismic safety evaluation program and seismic capacity improvement program for existing NPP. In case of seismic isolation part, it can be used for the application to the selection of optimum isolation devices for equipment isolation and to the effective evaluation of each seismic isolation devices. In containment analysis part, it can be used for ultimate pressure capacity evaluation of prestressed concrete

Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

DEFF Research Database (Denmark)

Wensaas, Andreas J; Rustan, Arild C; Just, Marlene

2008-01-01

Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence...... these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA....... EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased...

Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4

Directory of Open Access Journals (Sweden)

Sachiko Homma

2016-12-01

Full Text Available Abstract Background Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD. However, questions remained about nuclear bodies in human myogenesis and in muscle disease. Methods We examined nucleoli, PML bodies, SC35 speckles, TDP-43, and FUS in myoblasts and myotubes derived from healthy donors and from patients with FSHD, laminin-alpha-2-deficiency (MDC1A, and alpha-sarcoglycan-deficiency (LGMD2D. We further examined how these nuclear bodies and proteins were affected by DUX4-FL expression. Results We found that nucleoli, PML bodies, and SC35 speckles reorganized during differentiation in vitro, with all three becoming less abundant in myotube vs. myoblast nuclei. In addition, though PML bodies did not change in size, both nucleoli and SC35 speckles were larger in myotube than myoblast nuclei. Similar patterns of nuclear body reorganization occurred in healthy control, MDC1A, and LGMD2D cultures, as well as in the large fraction of nuclei that did not show DUX4-FL expression in FSHD cultures. In contrast, nuclei that expressed endogenous or exogenous DUX4-FL, though retaining normal nucleoli, showed disrupted morphology of some PML bodies and most SC35 speckles and also co-aggregation of FUS with TDP-43. Conclusions Nucleoli, PML bodies, and SC35 speckles reorganize during human myotube formation in vitro. These nuclear body reorganizations are likely needed to carry out the distinct gene transcription and

Optimum Criteria for Developing Defined Structures

Directory of Open Access Journals (Sweden)

Ion IVAN

2008-01-01

Full Text Available Basic aspects concerning distributed applications are presented: definition, particularities and importance. For distributed applications linear, arborescent, graph structures are defined with different versions and aggregation methods. Distributed applications have associated structures which through their characteristics influence the costs of the stages in the development cycle and the exploitation costs transferred to each user. The complexity of the defined structures is analyzed. The minimum and maximum criteria are enumerated for optimizing distributed application structures.

Metabolic and transcriptional changes in cultured muscle stem cells from low birth weight subjects

DEFF Research Database (Denmark)

Hansen, Ninna S; Hjort, Line; Broholm, Christa

2016-01-01

and cultured into fully differentiated myotubes. MAIN OUTCOME MEASURES: We studied glucose uptake, glucose transporters, insulin signaling, key transcriptional markers of myotube maturity, selected site specific DNA methylation, and mitochondrial gene expression. RESULTS: We found reduced glucose uptake...... as well as decreased levels of glucose transporter-1 and -4 mRNA and of the Akt substrate of 160 kDa mRNA and protein in myotubes from LBW individuals compared with NBW individuals. The myogenic differentiation markers, myogenin and myosin heavy chain 1 and 2, were decreased during late differentiation...... in LBW myotubes. Additionally, the mRNA level of the peroxisome proliferator-activated receptor-γ coactivator-1α and cytochrome c oxidase polypeptide 7A, were reduced in LBW myotubes. Decreased gene expression was not explained by changes in DNA methylation levels. CONCLUSION: We demonstrate...

Manipulation of environmental oxygen modifies reactive oxygen and nitrogen species generation during myogenesis

Directory of Open Access Journals (Sweden)

Rachel McCormick

2016-08-01

Data demonstrate that satellite cell proliferation increased when cells were grown in 6% O2 compared with 20% O2. Myoblasts grown in 20% O2 showed an increase in DCF fluorescence and DHE oxidation compared with myoblasts grown at 6% O2. Myotubes grown in 20% O2 also showed an increase in DCF and DAF-FM fluorescence and DHE oxidation compared with myotubes grown in 6% O2. The catalase and MnSOD contents were also increased in myoblasts and myotubes that were maintained in 20% O2 compared with myoblasts and myotubes grown in 6% O2. These data indicate that intracellular RONS activities in myoblasts and myotubes at rest are influenced by changes in environmental oxygen concentration and that the increased ROS may influence myogenesis in a negative manner.

Induction of group VIA phospholipase A2 activity during in vitro ischemia in C2C12 myotubes is associated with changes in the level of its splice variants

DEFF Research Database (Denmark)

Poulsen, K A; Petersen, Stine Helene Falsig; Kolko, M

2007-01-01

to catalytically inactive 50-kDa iPLA(2)-VIA-ankyrin variants previously identified in humans. Both the mRNA and protein levels of this approximately 50-kDa variant were reduced significantly within 1 h following OGD. In C2C12 myoblasts, iPLA(2)-VIA seemed to predominantly reside at the endoplasmatic reticulum......The involvement of group VI Ca(2+)-independent PLA(2)s (iPLA(2)-VI) in in vitro ischemia [oxygen and glucose deprivation (OGD)] in mouse C2C12 myotubes was investigated. OGD induced a time-dependent (0-6 h) increase in bromoenol lactone (BEL)-sensitive iPLA(2) activity, which was suppressed...... by specific short interfering (si)RNA knockdown of iPLA(2)-VIA. OGD was associated with an increase in iPLA(2)-VIA protein levels, whereas mRNA levels were unchanged. The levels of iPLA(2)-VIB mRNA and protein were not increased by OGD. RT-PCR and Western blot analysis identified a mouse iPLA(2)-VIA homolog...

Development of structural health monitoring techniques using dynamics testing

Energy Technology Data Exchange (ETDEWEB)

James, G.H. III [Sandia National Labs., Albuquerque, NM (United States). Experimental Structural Dynamics Dept.

1996-03-01

Today`s society depends upon many structures (such as aircraft, bridges, wind turbines, offshore platforms, buildings, and nuclear weapons) which are nearing the end of their design lifetime. Since these structures cannot be economically replaced, techniques for structural health monitoring must be developed and implemented. Modal and structural dynamics measurements hold promise for the global non-destructive inspection of a variety of structures since surface measurements of a vibrating structure can provide information about the health of the internal members without costly (or impossible) dismantling of the structure. In order to develop structural health monitoring for application to operational structures, developments in four areas have been undertaken within this project: operational evaluation, diagnostic measurements, information condensation, and damage identification. The developments in each of these four aspects of structural health monitoring have been exercised on a broad range of experimental data. This experimental data has been extracted from structures from several application areas which include aging aircraft, wind energy, aging bridges, offshore structures, structural supports, and mechanical parts. As a result of these advances, Sandia National Laboratories is in a position to perform further advanced development, operational implementation, and technical consulting for a broad class of the nation`s aging infrastructure problems.

The development of structural x-ray crystallography

Science.gov (United States)

Woolfson, M. M.

2018-03-01

From its birth in 1912, when only the simplest structures could be solved, x-ray structural crystallography is now able to solve macromolecular structures containing many thousands of independent non-hydrogen atoms. This progress has depended on, and been driven by, great technical advances in the development of powerful synchrotron x-ray sources, advanced automated equipment for the collection and storage of large data sets and powerful computers to deal with everything from data processing to running programmes employing complex algorithms for the automatic solution of structures. The sheer number of developments in the subject over the past century makes it impossible for this review to be exhaustive, but it will describe some major developments that will enable the reader to understand how the subject has grown from its humble beginnings to what it is today.

Structural reliability methods: Code development status

Science.gov (United States)

Millwater, Harry R.; Thacker, Ben H.; Wu, Y.-T.; Cruse, T. A.

1991-05-01

The Probabilistic Structures Analysis Method (PSAM) program integrates state of the art probabilistic algorithms with structural analysis methods in order to quantify the behavior of Space Shuttle Main Engine structures subject to uncertain loadings, boundary conditions, material parameters, and geometric conditions. An advanced, efficient probabilistic structural analysis software program, NESSUS (Numerical Evaluation of Stochastic Structures Under Stress) was developed as a deliverable. NESSUS contains a number of integrated software components to perform probabilistic analysis of complex structures. A nonlinear finite element module NESSUS/FEM is used to model the structure and obtain structural sensitivities. Some of the capabilities of NESSUS/FEM are shown. A Fast Probability Integration module NESSUS/FPI estimates the probability given the structural sensitivities. A driver module, PFEM, couples the FEM and FPI. NESSUS, version 5.0, addresses component reliability, resistance, and risk.

Development of the field of structural physiology

Science.gov (United States)

FUJIYOSHI, Yoshinori

2015-01-01

Electron crystallography is especially useful for studying the structure and function of membrane proteins — key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 Å resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named “adhennels” based on structures analyzed using electron and X-ray crystallography. PMID:26560835

Mechanical Model Development for Composite Structural Supercapacitors

Science.gov (United States)

Ricks, Trenton M.; Lacy, Thomas E., Jr.; Santiago, Diana; Bednarcyk, Brett A.

2016-01-01

Novel composite structural supercapacitor concepts have recently been developed as a means both to store electrical charge and to provide modest mechanical load carrying capability. Double-layer composite supercapacitors are often fabricated by impregnating a woven carbon fiber fabric, which serves as the electrodes, with a structural polymer electrolyte. Polypropylene or a glass fabric is often used as the separator material. Recent research has been primarily limited to evaluating these composites experimentally. In this study, mechanical models based on the Multiscale Generalized Method of Cells (MSGMC) were developed and used to calculate the shear and tensile properties and response of two composite structural supercapacitors from the literature. The modeling approach was first validated against traditional composite laminate data. MSGMC models for composite supercapacitors were developed, and accurate elastic shear/tensile properties were obtained. It is envisioned that further development of the models presented in this work will facilitate the design of composite components for aerospace and automotive applications and can be used to screen candidate constituent materials for inclusion in future composite structural supercapacitor concepts.

THE ESSENCE OF STRATEGY DEVELOPMENT COMPANY IN THE INTEGRATED STRUCTURE

Directory of Open Access Journals (Sweden)

A. I. Khorev

2014-01-01

Full Text Available Summary. In the beginning of the article is defined a rational sequence of the consideration of the nature of the strategy of a company development, included into an integrated structure. Further the article describes the following items separately: "a strategy", "a development of a company", and "an integrational structure", applying them to companies included to the integrated structure; separating them from a strategy of development of an autonomous company. The article defines functions which such strategy must define, taking into consideration the nature of the strategy of the company development, included into an integrated structure. Next, the article defines six steps which describe a sequence of development of the strategy of the company development, included into an integrated structure. The analysis which is defined in the article allows determining a complete definition of essence of the strategy of the company development, included into an integrated structure. The article also defines a place of the strategy of development into the hierarchical structure of the strategies. The strategy of the company development, included into an integrated structure (as well as the strategy of development of an autonomous company -- is a competition strategy, and it separates "strategy of leadership for costs", “differentiation strategy”, and “strategy of focusing for costs”. Also authors are analyzed the strategy of the cost optimization. According to the complex definition of the strategy, and the strategy's place inside the hierarchical structure, the article defines functions which corporate, competitive, and functional strategies execute during the management of companies inside an integrational structure. The article presents characteristics of applied strategic decisions at different levels of all three types of strategies. The article's researches allow companies included to the integrated structure define their place inside the

Expert Cold Structure Development

Science.gov (United States)

Atkins, T.; Demuysere, P.

2011-05-01

The EXPERT Program is funded by ESA. The objective of the EXPERT mission is to perform a sub-orbital flight during which measurements of critical aero- thermodynamic phenomena will be obtained by using state-of-the-art instrumentation. As part of the EXPERT Flight Segment, the responsibility of the Cold Structure Development Design, Manufacturing and Validation was committed to the Belgian industrial team SONACA/SABCA. The EXPERT Cold Structure includes the Launcher Adapter, the Bottom Panel, the Upper Panel, two Cross Panels and the Parachute Bay. An additional Launcher Adapter was manufactured for the separation tests. The selected assembly definition and manufacturing technologies ( machined parts and sandwich panels) were dictated classically by the mass and stiffness, but also by the CoG location and the sensitive separation interface. Used as support for the various on-board equipment, the Cold Structure is fixed to but thermally uncoupled from the PM 1000 thermal shield. It is protect on its bottom panel by a thermal blanket. As it is a protoflight, analysis was the main tool for the verification. Low level stiffness and modal analysis tests have also been performed on the Cold Structure equipped with its ballast. It allowed to complete its qualification and to prepare SONACA/SABCA support for the system dynamic tests foreseen in 2011. The structure was finally coated with a thermal control black painting and delivered on time to Thales Alenia Space-Italy end of March 201.

Development of the structural materials information center

International Nuclear Information System (INIS)

Oland, C.B.; Naus, D.J.

1990-01-01

The U.S. Nuclear Regulatory Commission has initiated a Structural Aging Program at the Oak Ridge National Laboratory to identify potential structural safety issues related to continued service of nuclear power plants and to establish criteria for evaluating and resolving these issues. One of the tasks in this program focuses on the establishment of a Structural Materials Information Center where data and information on the time variation of concrete and other structural material properties under the influence of pertinent environmental stressors and aging factors are being collected and assembled into a database. This database will be used to assist in the prediction of potential long-term deterioration of critical structural components in nuclear power plants and to establish limits on hostile environmental exposure for these structures and materials. Two complementary database formats have been developed. The Structural Materials Handbook is an expandable, hard copy handbook that contains complete sets of data and information for selected portland cement concrete, metallic reinforcement, prestressing tendon, and structural steel materials. The Structural Materials Electronic Database is accessible by an IBM-compatible personal computer and provides an efficient means for searching the various database files to locate materials with similar properties. The database formats have been developed to accommodate data and information on the time-variation of concrete and other structural material properties. To date, the database includes information on concrete, reinforcement, prestressing, and structural steel materials

Gain-of-function screen for genes that affect Drosophila muscle pattern formation.

Directory of Open Access Journals (Sweden)

Nicole Staudt

2005-10-01

Full Text Available This article reports the production of an EP-element insertion library with more than 3,700 unique target sites within the Drosophila melanogaster genome and its use to systematically identify genes that affect embryonic muscle pattern formation. We designed a UAS/GAL4 system to drive GAL4-responsive expression of the EP-targeted genes in developing apodeme cells to which migrating myotubes finally attach and in an intrasegmental pattern of cells that serve myotubes as a migration substrate on their way towards the apodemes. The results suggest that misexpression of more than 1.5% of the Drosophila genes can interfere with proper myotube guidance and/or muscle attachment. In addition to factors already known to participate in these processes, we identified a number of enzymes that participate in the synthesis or modification of protein carbohydrate side chains and in Ubiquitin modifications and/or the Ubiquitin-dependent degradation of proteins, suggesting that these processes are relevant for muscle pattern formation.

Developing a network-level structural capacity index for structural evaluation of pavements.

Science.gov (United States)

2013-03-01

The objective of this project was to develop a structural index for use in network-level pavement evaluation to facilitate : the inclusion of the pavements structural condition in pavement management applications. The primary goal of network-level...

Effect of TCEA3 on the differentiation of bovine skeletal muscle satellite cells

International Nuclear Information System (INIS)

Zhu, Yue; Tong, Hui-Li; Li, Shu-Feng; Yan, Yun-Qin

2017-01-01

Bovine muscle-derived satellite cells (MDSCs) are important for animal growth. In this study, the effect of transcription elongation factor A3 (TCEA3) on bovine MDSC differentiation was investigated. Western blotting, immunofluorescence assays, and cytoplasmic and nuclear protein isolation and purification techniques were used to determine the expression pattern and protein localization of TCEA3 in bovine MDSCs during in vitro differentiation. TCEA3 expression was upregulated using the CRISPR/Cas9 technique to study its effects on MDSC differentiation in vitro. TCEA3 expression gradually increased during the in vitro differentiation of bovine MDSCs and peaked on the 5th day of differentiation. TCEA3 was mainly localized in the cytoplasm of bovine MDSCs, and its expression was not detected in the nucleus. The level of TCEA3 was relatively higher in myotubes at a higher degree of differentiation than during early differentiation. After transfection with a TCEA3-activating plasmid vector (TCEA3 overexpression) for 24 h, the myotube fusion rate, number of myotubes, and expression levels of the muscle differentiation-related loci myogenin (MYOG) and myosin heavy chain 3 (MYH3) increased significantly during the in vitro differentiation of bovine MDSCs. After transfection with a TCEA3-inhibiting plasmid vector for 24 h, the myotube fusion rate, number of myotubes, and expression levels of MYOG and MYH3 decreased significantly. Our results indicated, for the first time, that TCEA3 promotes the differentiation of bovine MDSCs and have implications for meat production and animal rearing. - Highlights: • Muscle-derived satellite cell differentiation is promoted by TCEA3. • TCEA3 protein was localized in the cytoplasm, but not nuclei of bovine MDSCs. • TCEA3 levels increased as myotube differentiation increased. • TCEA3 affected myotube fusion, myotube counts, and MYOG and MYH3 levels.

Study on the Evolution Mechanism and Development Forecasting of China’s Power Supply Structure Clean Development

Directory of Open Access Journals (Sweden)

Xiaohua Song

2017-02-01

Full Text Available The clean development of China’s power supply structure has become a crucial strategic problem for the low-carbon, green development of Chinese society. Considering the subsistent developments of optimized allocation of energy resources and efficient utilization, the urgent need to solve environmental pollution, and the continuously promoted power market-oriented reform, further study of China’s power structure clean development has certain theoretical value. Based on the data analysis, this paper analyzes the key factors that influence the evolution process of the structure with the help of system dynamics theory and carries out comprehensive assessments after the construction of the structure evaluation system. Additionally, a forecasting model of the power supply structure development based on the Vector Autoregressive Model (VAR has been put forward to forecast the future structure. Through the research of policy review and scenario analysis, the paths and directions of structure optimization are proposed. In this paper, the system dynamics, vector autoregressive model (VAR, policy mining, and scenario analysis methods are combined to systematically demonstrate the evolution of China’s power structure, and predict the future direction of development. This research may provide a methodological and practical reference for the analysis of China’s power supply structure optimization development and for theoretical studies.

Membrane glycoproteins of differentiating skeletal muscle cells

International Nuclear Information System (INIS)

Miller, K.R.; Remy, C.N.; Smith, P.B.

1987-01-01

The composition of N-linked glycoprotein oligosaccharides was studied in myoblasts and myotubes of the C2 muscle cell line. Oligosaccharides were radioactively labelled for 15 hr with [ 3 H] mannose and plasma membranes isolated. Ten glycopeptides were detected by SDS-PAGE and fluorography. The extent of labelling was 4-6 fold greater in myoblasts vs myotubes. A glycopeptide of Mr > 100,000 was found exclusively in myoblast membranes. Lectin chromatography revealed that the proportion of tri-, tetranntenary, biantennary and high mannose chains was similar throughout differentiation. The high mannose chain fraction was devoid of hybrid chains. The major high mannose chain contained nine mannose residues. The higher level of glycopeptide labelling in myoblasts vs myotubes corresponded to a 5-fold greater rate of protein synthesis. Pulse-chase experiments were used to follow the synthesis of the Dol-oligosaccharides. Myoblasts and myotubes labelled equivalently the glucosylated tetradecasaccharide but myoblasts labelled the smaller intermediates 3-4 greater than myotubes. Myoblasts also exhibited a 2-3 fold higher Dol-P dependent glycosyl transferase activity for chain elongation and Dol-sugar synthesis. Together these results show that the degree of protein synthesis and level of Dol-P are contributing factors in the higher capacity of myoblasts to produce N-glycoproteins compared to myotubes

Development and evaluation of a removable tissue-engineered muscle with artificial tendons.

Science.gov (United States)

Nakamura, Tomohiro; Takagi, Shunya; Kamon, Takafumi; Yamasaki, Ken-Ichi; Fujisato, Toshia

2017-02-01

Tissue-engineered skeletal muscles were potentially useful as physiological and biochemical in vitro models. Currently, most of the similar models were constructed without tendons. In this study, we aimed to develop a simple, highly versatile tissue-engineered muscle with artificial tendons, and to evaluate the contractile, histological and molecular dynamics during differentiation. C2C12 cells were embedded in a cold type-І collagen gel and placed between two artificial tendons on a silicone sheet. The construct shrank and tightly attached to the artificial tendons with differentiation, finally detaching from the silicone sheet within 1 week of culture onset. We successfully developed a tissue-engineered skeletal muscle with two artificial tendons from C2C12 myoblasts embedded in type-І collagen gel. The isometric twitch contractile force (TCF) significantly increased during differentiation. Time to Peak Tension (TPT) and Half-Relaxation Time (1/2RT) were significantly shortened during differentiation. Myogenic regulatory factors were maximally expressed at 2 weeks, and subsequently decreased at 3 weeks of culture. Histological analysis indicated that myotube formation increased markedly from 2 weeks and well-ordered sarcomere structures were observed on the surface of the 3D engineered muscle at 3 weeks of culture. These results suggested that robust muscle structure occurred by 3 weeks in the tissue-engineered skeletal muscle. Moreover, during the developmental process, the artificial tendons might contribute to well-ordered sarcomere formation. Our results indicated that this simple culture system could be used to evaluate the effects of various pharmacological and mechanical cues on muscle contractility in a variety of research areas. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Accelerator structure development for NLC

International Nuclear Information System (INIS)

Hoag, H.A.; Deruyter, H.; Pearson, C.; Ruth, R.D.; Wang, J.W.; Schaefer, J.

1993-04-01

In the program of work directed towards the development of an X-Band Next Linear Collider accelerator structure, two different test accelerator sections have been completed, and a third is being fabricated. The first is a simple 30-cell constant-impedance section in which no special attention was given to surface finish, pumping, and alignment. The second is an 86-cell section in which the cells were precision diamond-turned by Texas Instruments Inc. The structure has internal water-cooling and vacuum pumping manifolds. Some design details are given for the third section, which is a 206-cell structure with cavities dimensioned to give a Gaussian distribution of dipole mode frequencies. It has conventional-machining surface finishes and external water and pumping manifolds. Component design, fabrication, and assembly brazing are described for the first two experimental sections

Insulin stimulates phospholipase D-dependent phosphatidylcholine hydrolysis, Rho translocation, de novo phospholipid synthesis, and diacylglycerol/protein kinase C signaling in L6 myotubes.

Science.gov (United States)

Standaert, M L; Bandyopadhyay, G; Zhou, X; Galloway, L; Farese, R V

1996-07-01

Previous studies have provided conflicting findings on whether insulin activates certain, potentially important, phospholipid signaling systems in skeletal muscle preparations. In particular, insulin effects on the hydrolysis of phosphatidylcholine (PC) and subsequent activation of protein kinase C (PKC) have not been apparent in some studies. Presently, we examined insulin effects on phospholipid signaling systems, diacylglycerol (DAG) production, and PKC translocation/activation in L6 myotubes. We found that insulin provoked rapid increases in phospholipase D (PLD)-dependent hydrolysis of PC, as evidenced by increases in choline release and phosphatidylethanol production in cells incubated in the presence of ethanol. In association with PC-PLD activation, Rho, a small G protein that is known to activate PC-PLD activation, translocated from the cytosol to the membrane fraction in response to insulin treatment. PC-PLD activation was also accompanied by increases in total DAG production and increases in the translocation of both PKC enzyme activity and DAG-sensitive PKC-alpha, -beta, -delta, and -epsilon from the cytosol to the membrane fraction. A potential role for PKC or a related protein kinase in insulin action was suggested by the finding that RO 31-8220 inhibited both PKC enzyme activity and insulin-stimulated [3H]2-deoxyglucose uptake. Our findings provide the first evidence that insulin stimulates Rho translocation and activates PC-PLD in L6 skeletal muscle cells. Moreover, this signaling system appears to lead to increases in DAG/PKC signaling, which, along with other related signaling factors, may regulate certain metabolic processes, such as glucose transport, in these cells.

Development of analysis methods for seismically isolated nuclear structures

International Nuclear Information System (INIS)

Yoo, Bong; Lee, Jae-Han; Koo, Gyeng-Hoi

2002-01-01

KAERI's contributions to the project entitled Development of Analysis Methods for Seismically Isolated Nuclear Structures under IAEA CRP of the intercomparison of analysis methods for predicting the behaviour of seismically isolated nuclear structures during 1996-1999 in effort to develop the numerical analysis methods and to compare the analysis results with the benchmark test results of seismic isolation bearings and isolated nuclear structures provided by participating countries are briefly described. Certain progress in the analysis procedures for isolation bearings and isolated nuclear structures has been made throughout the IAEA CRPs and the analysis methods developed can be improved for future nuclear facility applications. (author)

The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

International Nuclear Information System (INIS)

Kamolrat, Torkamol; Gray, Stuart R.

2013-01-01

Highlights: ► EPA can enhance protein synthesis and retard protein breakdown in muscle cells. ► These effects were concurrent with increases in p70s6k and FOXO3a phosphorylation. ► EPA may be a useful tool in the treatment of muscle wasting conditions. -- Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24 h with 0.1% ethanol (control), 50 μM EPA or 50 μM DHA prior to experimentation. After serum (4 h) and amino acid (1 h) starvation cells were stimulated with 2 mM L-leucine and protein synthesis measured using 3 H-labelled phenylalanine. Protein breakdown was measured using 3 H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P < 0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P < 0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P < 0.05) p70s6k phosphorylation, EPA increased (P < 0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion

The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

Energy Technology Data Exchange (ETDEWEB)

Kamolrat, Torkamol [Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD (United Kingdom); Gray, Stuart R., E-mail: s.r.gray@abdn.ac.uk [Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD (United Kingdom)

2013-03-22

Highlights: ► EPA can enhance protein synthesis and retard protein breakdown in muscle cells. ► These effects were concurrent with increases in p70s6k and FOXO3a phosphorylation. ► EPA may be a useful tool in the treatment of muscle wasting conditions. -- Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24 h with 0.1% ethanol (control), 50 μM EPA or 50 μM DHA prior to experimentation. After serum (4 h) and amino acid (1 h) starvation cells were stimulated with 2 mM L-leucine and protein synthesis measured using {sup 3}H-labelled phenylalanine. Protein breakdown was measured using {sup 3}H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P < 0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P < 0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P < 0.05) p70s6k phosphorylation, EPA increased (P < 0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion.

Development of XAFS Into a Structure Determination Technique

Science.gov (United States)

Stern, E. A.

After the detection of diffraction of x-rays by M. Laue in 1912, the technique was soon applied to structure determination by Bragg within a year. On the other hand, although the edge steps in X-Ray absorption were discovered even earlier by Barkla and both the near edge (XANES) and extended X-Ray fine structure (EXAFS) past the edge were detected by 1929, it still took over 40 years to realize the structure information contained in this X-Ray absorption fine structure (XAFS). To understand this delay a brief historical review of the development of the scientific ideas that transformed XAFS into the premiere technique for local structure determination is given. The development includes both advances in theoretical understanding and calculational capabilities, and in experimental facilities, especially synchrotron radiation sources. The present state of the XAFS technique and its capabilities are summarized.

Effects of creatine and its analog, β-guanidinopropionic acid, on the differentiation of and nucleoli in myoblasts.

Science.gov (United States)

Ohira, Yoshinobu; Matsuoka, Yoshikazu; Kawano, Fuminori; Ogura, Akihiko; Higo, Yoko; Ohira, Takashi; Terada, Masahiro; Oke, Yoshihiko; Nakai, Naoya

2011-01-01

The effects of supplementation with creatine (Cr) and its analog, β-guanidinopropionic acid (β-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4 d. Then Cr (1 mM) or β-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2 d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and β-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the β-GPA group. Supplementation with β-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas β-GPA increased nucleolar sizes in the myotubes. These results suggest that β-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.

Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

Science.gov (United States)

Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

2015-04-09

Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

History of Planning Structure Development in Irkutsk

Science.gov (United States)

Kulakov, A. I.; Ree, A. U.

2017-11-01

The development of Irkutsk was spontaneous; the first streets represented a rather complex system of streets, dead ends, lanes. Throughout the history of the city, several general plans and development projects have been implemented (but not completely). Unlike other large Siberian cities (Novosibirsk, Krasnoyarsk), Irkutsk managed to preserve its historical appearance, architecture and initial planning. During its history the city has passed five stages of the planning structure development. The first stage of the city’s history coincides with the formation of the Russian settlements network in Eastern Siberia from the middle of the 17th to the end of the 18th centuries. Like many other Siberian cities, Irkutsk began its evolution from a fortified stockaded town. By the end of the 17th century a trading quarter appeared outside its walls. Currently, the city is developing and growing, so, a relevant issue of the further development direction of the Irkutsk planning structure naturally arises.

Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

Science.gov (United States)

Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

2016-07-01

Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

Regularities development of entrepreneurial structures in regions

Directory of Open Access Journals (Sweden)

Julia Semenovna Pinkovetskaya

2012-12-01

Full Text Available Consider regularities and tendencies for the three types of entrepreneurial structures — small enterprises, medium enterprises and individual entrepreneurs. The aim of the research was to confirm the possibilities of describing indicators of aggregate entrepreneurial structures with the use of normal law distribution functions. Presented proposed by the author the methodological approach and results of construction of the functions of the density distribution for the main indicators for the various objects: the Russian Federation, regions, as well as aggregates ofentrepreneurial structures, specialized in certain forms ofeconomic activity. All the developed functions, as shown by the logical and statistical analysis, are of high quality and well-approximate the original data. In general, the proposed methodological approach is versatile and can be used in further studies of aggregates of entrepreneurial structures. The received results can be applied in solving a wide range of problems justify the need for personnel and financial resources at the federal, regional and municipal levels, as well as the formation of plans and forecasts of development entrepreneurship and improvement of this sector of the economy.

European structural materials development for fusion applications

Energy Technology Data Exchange (ETDEWEB)

Schaaf, B. van der E-mail: vanderschaaf@nrg-nl.com; Ehrlich, K.; Fenici, P.; Tavassoli, A.A.; Victoria, M

2000-09-01

Leading long term considerations for choices in the European Long Term Technology programme are the high temperature mechanical- and compatibility properties of structural materials under neutron irradiation. The degrees of fabrication process freedom are closely investigated to allow the construction of complex shapes. Another important consideration is the activation behaviour of the structural material. The ideal solution is the recycling of the structural materials after a relatively short 'cooling' period. The structural materials development in Europe has three streams. The first serves the design and construction of ITER and is closely connected to the choice made: water cooled austenitic stainless steel. The second development stream is to support the design and construction of DEMO relevant blanket modules to be tested in ITER. The helium cooled pebble bed and the water cooled liquid lithium concept rely both on RAFM steel. The goal of the third stream is to investigate the potential of advanced materials for fusion power reactors beyond DEMO. The major contending materials: SiCSiC composites, vanadium, titanium and chromium alloys hold the promise of high operating temperatures, but RAFM has also a high temperature potential applying oxide dispersion strengthening. The development of materials for fusion power application requires a high flux 14 MeV neutron source to simulate the fusion power environment.

Developing fair compensation structures

International Nuclear Information System (INIS)

Trousdale, W.J.

1998-01-01

The issue of finding an effective way to incorporate Aboriginal values into the process of developing fair compensation structures was discussed. This paper discusses pricing intangible values using dollars, but it was emphasized that 'values' are whatever are important to us. Therefore, in order to achieve fair compensation, creative alternatives that are value-focused should be pursued. In addition to the more straight-forward monetary compensation, compensation could also be about avoiding losses, mitigating adverse impacts, achieving better communication, and promoting cultural understanding. 25 refs., 2 tabs

Epigenetic control of cell identity and plasticity

KAUST Repository

Orlando, Valerio

2014-04-02

The DNA centered dogma for genetic information and cell identity is now evolving into a much more complex and flexible dimension provided by the discovery of the Epigenome. This comprises those chromosome structural and topological components that complement DNA information and contribute to genome functional organization. Current concept is that the Epigenome constitutes the dynamic molecular interface allowing the Genome to interact with the Environment. Exploring how the genome interacts with the environment is a key to fully understand cellular and complex organism mechanisms of adaptation and plasticity. Our work focuses on the role of an essential, specialized group or chromatin associated proteins named Polycomb (PcG) that control maintenance of transcription programs during development and in adult life. In particular PcG proteins exert epigenetic “memory” function by modifying chromosome structures at various levels to maintain gene silencing in particular through cell division. While in the past decade substantial progress was made in understanding PcG mechanisms acting in development and partially during cell cycle, very little is known about their role in adult post-mitotic tissues and more in general the role of the epigenome in adaptation. To this, we studied the role of PcG in the context of mammalian skeletal muscle cell differentiation. We previously reported specific dynamics of PRC2 proteins in myoblasts and myotubes, in particular the dynamics of PcG Histone H3 K27 Methyl Transferases (HMT), EZH2 and EZH1, the latter apparently replacing for EZH2 in differentiated myotubes. Ezh1 protein, although almost identical to Ezh2, shows a weak H3K27 HMT activity and its primary function remains elusive. Recent ChIPseq studies performed in differentiating muscle cells revealed that Ezh1 associates with active and not repressed regulatory regions to control RNA pol II elongation. Since H3K27 tri-methylation levels are virtually steady in non

Development of SC structure modularization in Nuclear Power Plant

International Nuclear Information System (INIS)

Mun, Taeyoup

2008-01-01

New Focus on NPP are Rising Concerns on Global Warming, Potential energy crisis (geo-political), Improved reliability and safety of nuclear power plant, Advent of Generation 3+ NPP technology and Economical Energy Resource. New NPPs are 6 units in Korea and 23 in Asia being built, 32 units being planned in China by 2020 (150 by 2050), 10 units being planned in US by 2020 and IAEA expects $200 billions on NPP construction next 25 years (up to 30% of total world energy). □ SC(Steel Plate Concrete) structure · Steel Plate is used as a Structural Element instead of Reinforcing Bars in RC · SC structure consists of Steel Plate with Headed Studs. Connected by Tie-bars - The Primary Purpose of Tie-bars is to Stiffen and Hold Together the Plates during Construction Process - Headed Studs are Welded to the Inside of Steel Plate for composite action □ Benefits of SC Structure · Shorten Construction Duration for Re bar, Forming and Scaffolding Works · Minimize Site Labors · Improve the Construction Quality · Enable Construction Sites to be kept Clean □ SC Modularization · Fit for Modular Construction for Structural Features · Fit for Modular Construction for Structural Features · Inattentively Effective for Integrated Modules · Pre-fabrication, Pre-assembly and Modularization □ Project Overview · Project Name: Development of SC structure for Modularization in NPP · Project Type: Electric Power Industry R and D (Ministry of Knowledge Economy) · Duration: Sep. 2005 ∼ Aug. 2008 (36 Months) · Research Team and Scopes - Project Management: Korea Hydro and Nuclear Power Company (KHNP) - Development of Code and Standards for SC Structure: Korea Society of Steel Construction (KSSC) Korea Electric Power Research Institute (KEPRI) - Development of SC Structural Analysis and Design: Korea Power Engineering Company (KOPEC) - Development of Construction Techniques for SC Modularization: KHNP, Korea Institute of Nuclear Safety(KINS), KOPEC □ Performance

System reliability developments in structural engineering

International Nuclear Information System (INIS)

Moses, F.

1982-01-01

Two major limitations occur in present structural design code developments utilizing reliability theory. The notional system reliabilities may differ significantly from calibrated component reliabilities. Secondly, actual failures are often due to gross errors not reflected in most present code formats. A review is presented of system reliability methods and further new concepts are developed. The incremental load approach for identifying and expressing collapse modes is expanded by employing a strategy to identify and enumerate the significant structural collapse modes. It further isolates the importance of critical components in the system performance. Ductile and brittle component behavior and strength correlation is reflected in the system model and illustrated in several examples. Modal combinations for the system reliability are also reviewed. From these developments a system factor can be addended to component safety checking equations. Values may be derived from system behavior by substituting in a damage model which accounts for the response range from component failure to collapse. Other strategies are discussed which emphasize quality assurance during design and in-service inspection for components whose behavior is critical to the system reliability. (Auth.)

Study of muscle cell dedifferentiation after skeletal muscle injury of mice with a Cre-Lox system.

Science.gov (United States)

Mu, Xiaodong; Peng, Hairong; Pan, Haiying; Huard, Johnny; Li, Yong

2011-02-03

Dedifferentiation of muscle cells in the tissue of mammals has yet to be observed. One of the challenges facing the study of skeletal muscle cell dedifferentiation is the availability of a reliable model that can confidentially distinguish differentiated cell populations of myotubes and non-fused mononuclear cells, including stem cells that can coexist within the population of cells being studied. In the current study, we created a Cre/Lox-β-galactosidase system, which can specifically tag differentiated multinuclear myotubes and myotube-generated mononuclear cells based on the activation of the marker gene, β-galactosidase. By using this system in an adult mouse model, we found that β-galactosidase positive mononuclear cells were generated from β-galactosidase positive multinuclear myofibers upon muscle injury. We also demonstrated that these mononuclear cells can develop into a variety of different muscle cell lineages, i.e., myoblasts, satellite cells, and muscle derived stem cells. These novel findings demonstrated, for the first time, that cellular dedifferentiation of skeletal muscle cells actually occurs in mammalian skeletal muscle following traumatic injury in vivo.

Role of Lithology and Rock Structure in Drainage Development in ...

African Journals Online (AJOL)

Lithology and Rock structure play a vital role in the development of Drainage Network in any drainage basin. The drainage patterns upon land surface develop as directed by the underlying lithology and rock structure. In fact, lithology and rock structure together shape the basin and are decisive parameters of nature and ...

Design development of graphite primary structures enables SSTO success

Science.gov (United States)

Biagiotti, V. A.; Yahiro, J. S.; Suh, Daniel E.; Hodges, Eric R.; Prior, Donald J.

1997-01-01

This paper describes the development of a graphite composite wing and a graphite composite intertank primary structure for application toward Single-Stage to Orbit space vehicles such as those under development in NASA's X-33/Reusable Launch Vehicle (RLV) Program. The trade study and designs are based on a Rockwell vertical take-off and horizontal landing (VTHL) wing-body RLV vehicle. Northrop Grumman's approach using a building block development technique is described. Composite Graphite/Bismaleimide (Gr/BMI) material characterization test results are presented. Unique intertank and wing composite subcomponent test article designs are described and test results to date are presented. Wing and intertank Full Scale Section Test Article (FSTA) objectives and designs are outlined. Trade studies, supporting building block testing, and FSTA demonstrations combine to develop graphite primary structure composite technology that enables developing X-33/RLV design programs to meet critical SSTO structural weight and operations performance criteria.

Changes in Nuclear Structure During Wheat Endosperm Development

NARCIS (Netherlands)

Wegel, E.

2005-01-01

This thesis is an investigation into the structure of wheat endosperm nuclei starting with nuclear divisions and migration during syncytium formation followed by the development of nuclear shape and positioning of chromosome territories and ending with changes in subchromosomal structure during the

CD36 is required for myoblast fusion during myogenic differentiation

International Nuclear Information System (INIS)

Park, Seung-Yoon; Yun, Youngeun; Kim, In-San

2012-01-01

Highlights: ► CD36 expression was induced during myogenic differentiation. ► CD36 expression was localized in multinucleated myotubes. ► The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. ► Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

CD36 is required for myoblast fusion during myogenic differentiation

Energy Technology Data Exchange (ETDEWEB)

Park, Seung-Yoon [Department of Biochemistry, College of Medicine, Dongguk University and Medical Institute of Dongguk University, Gyeongju 780-714 (Korea, Republic of); Yun, Youngeun [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, In-San, E-mail: iskim@knu.ac.kr [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Biomedical Research Institute, Korea Institute Science and Technology, Seoul (Korea, Republic of)

2012-11-02

Highlights: Black-Right-Pointing-Pointer CD36 expression was induced during myogenic differentiation. Black-Right-Pointing-Pointer CD36 expression was localized in multinucleated myotubes. Black-Right-Pointing-Pointer The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. Black-Right-Pointing-Pointer Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

Structural and Maturational Covariance in Early Childhood Brain Development.

Science.gov (United States)

Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

2017-03-01

Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Graphene-Based Patterning and Differentiation of C2C12 Myoblasts

DEFF Research Database (Denmark)

Bajaj, Piyush; Rivera, Jose A; Marchwiany, Daniel

2014-01-01

This study aims at generating highly aligned functional myotubes using graphene as the underlying scaffold. Graphene not only supports the growth of C2C12 muscle cells but also enhances its differentiation and leads to spontaneous patterning of myotubes....

Development of SC structure modularization in Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Mun, Taeyoup [Korea Hydro and Nuclear Power Co., Ltd., Seoul (Korea, Republic of)

2008-04-15

New Focus on NPP are Rising Concerns on Global Warming, Potential energy crisis (geo-political), Improved reliability and safety of nuclear power plant, Advent of Generation 3+ NPP technology and Economical Energy Resource. New NPPs are 6 units in Korea and 23 in Asia being built, 32 units being planned in China by 2020 (150 by 2050), 10 units being planned in US by 2020 and IAEA expects $200 billions on NPP construction next 25 years (up to 30% of total world energy). {open_square} SC(Steel Plate Concrete) structure {center_dot} Steel Plate is used as a Structural Element instead of Reinforcing Bars in RC {center_dot} SC structure consists of Steel Plate with Headed Studs. Connected by Tie-bars - The Primary Purpose of Tie-bars is to Stiffen and Hold Together the Plates during Construction Process - Headed Studs are Welded to the Inside of Steel Plate for composite action {open_square} Benefits of SC Structure {center_dot} Shorten Construction Duration for Re bar, Forming and Scaffolding Works {center_dot} Minimize Site Labors {center_dot} Improve the Construction Quality {center_dot} Enable Construction Sites to be kept Clean {open_square} SC Modularization {center_dot} Fit for Modular Construction for Structural Features {center_dot} Fit for Modular Construction for Structural Features {center_dot} Inattentively Effective for Integrated Modules {center_dot} Pre-fabrication, Pre-assembly and Modularization {open_square} Project Overview {center_dot} Project Name: Development of SC structure for Modularization in NPP {center_dot} Project Type: Electric Power Industry R and D (Ministry of Knowledge Economy) {center_dot} Duration: Sep. 2005 {approx} Aug. 2008 (36 Months) {center_dot} Research Team and Scopes - Project Management: Korea Hydro and Nuclear Power Company (KHNP) - Development of Code and Standards for SC Structure: Korea Society of Steel Construction (KSSC) Korea Electric Power Research Institute (KEPRI) - Development of SC Structural Analysis and Design

Poverty—A structural problem of developing countries

OpenAIRE

Wülker, Gabriele

1981-01-01

The contrast between industrialized and developing countries is often seen as one between two opposites: Rich countries—poor countries. But the poverty in the developing countries is by no means identical with the need for help as perceived in the industrialized societies. Poverty in the Third World is, as the following article shows, a structural problem.

Recent developments in low cost stable structures for space

International Nuclear Information System (INIS)

Thompson, T.C.; Grastataro, C.; Smith, B.G.

1994-01-01

The Los Alamos National Laboratory (LANL) in partnership with Composite Optics Incorporated (COI) is advancing the development of low cost, lightweight, composite technology for use in spacecraft and stable structures. The use of advanced composites is well developed, but the application of an all-composite tracker structure has never been achieved. This paper investigates the application of composite technology to the design and fabrication of an all-composite spacecraft bus for small satellites, using technology directly applicable to central tracking in a high luminosity environment. The satellite program Fast On-Orbit Recording of Transient Events (FORTE) is the second in a series of satellites to be launched into orbit for the US Department of Energy (DOE). This paper will discuss recent developments in the area of low cost composites, used for either spacecraft or ultra stable applications in high energy physics (HEP) detectors. The use of advanced composites is a relatively new development in the area of HEP. The Superconducting Super Collider (SSC) spawned a new generation of Trackers which made extensive use of graphite fiber reinforced plastic (GFRP) composite systems. LANL has designed a structure employing new fabrication technology. This concept will lower the cost of composite structures to a point that they may now compete with conventional materials. This paper will discuss the design, analysis and proposed fabrication of a small satellite structure. Central tracking structures using advanced materials capable of operating in an adverse environment typical of that found in a high luminosity collider could use identical concepts

Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes

DEFF Research Database (Denmark)

Ørtenblad, Niels; Mogensen, Martin; Petersen, Ingrid

2005-01-01

In myotubes established from patients with type 2 diabetes (T2D), lipid oxidation and insulin-mediated glucose oxidation are reduced, whereas in myotubes from obese non-diabetic subjects, exposure to palmitate impairs insulin-mediated glucose oxidation. To determine the underlying mechanisms...

High-temperature-structural design and research and development for reactor system components

International Nuclear Information System (INIS)

Matsumura, Makoto; Hada, Mikio

1985-01-01

The design of reactor system components requires high-temperature-structural design guide with the consideration of the creep effect of materials related to research and development on structural design. The high-temperature-structural design guideline for the fast prototype reactor MONJU has been developed under the active leadership by Power Reactor and Nuclear Fuel Development Corporation and Toshiba has actively participated to this work with responsibility on in-vessel components, performing research and development programs. This paper reports the current status of high-temperature-structural-design-oriented research and development programs and development of analytical system including stress-evaluation program. (author)

Distance Learning Plan Development: Initiating Organizational Structures

National Research Council Canada - National Science Library

Poole, Clifton

1998-01-01

.... Army distance learning plan managers to examine the DLPs they were directing. The analysis showed that neither army nor civilian distance learning plan managers used formalized requirements for organizational structure development (OSD...

Nursing Competency: Definition, Structure and Development.

Science.gov (United States)

Fukada, Mika

2018-03-01

Nursing competency includes core abilities that are required for fulfilling one's role as a nurse. Therefore, it is important to clearly define nursing competency to establish a foundation for nursing education curriculum. However, while the concepts surrounding nursing competency are important for improving nursing quality, they are still not yet completely developed. Thus, challenges remain in establishing definitions and structures for nursing competency, competency levels necessary for nursing professionals, training methods and so on. In the present study, we reviewed the research on definitions and attributes of nursing competency in Japan as well as competency structure, its elements and evaluation. Furthermore, we investigated training methods to teach nursing competency.

Integrating centralized and decentralized organization structures: an education and development model.

Science.gov (United States)

Sheriff, R; Banks, A

2001-01-01

Organization change efforts have led to critically examining the structure of education and development departments within hospitals. This qualitative study evaluated an education and development model in an academic health sciences center. The model combines centralization and decentralization. The study results can be used by staff development educators and administrators when organization structure is questioned. This particular model maximizes the benefits and minimizes the limitations of centralized and decentralized structures.

Development and modeling of self-deployable structures

Science.gov (United States)

Neogi, Depankar

Deployable space structures are prefabricated structures which can be transformed from a closed, compact configuration to a predetermined expanded form in which they are stable and can bear loads. The present research effort investigates a new family of deployable structures, called the Self-Deployable Structures (SDS). Unlike other deployable structures, which have rigid members, the SDS members are flexible while the connecting joints are rigid. The joints store the predefined geometry of the deployed structure in the collapsed state. The SDS is stress-free in both deployed and collapsed configurations and results in a self-standing structure which acquires its structural properties after a chemical reaction. Reliability of deployment is one of the most important features of the SDS, since it does not rely on mechanisms that can lock during deployment. The unit building block of these structures is the self-deployable structural element (SDSE). Several SDSE members can be linked to generate a complex building block such as a triangular or a tetrahedral structure. Different SDSE and SDS concepts are investigated in the research work, and the performance of SDS's are experimentally and theoretically explored. Triangular and tetrahedral prototype SDS have been developed and presented. Theoretical efforts include modeling the behavior of 2-dimensional SDSs. Using this design tool, engineers can study the effects of different packing configurations and deployment sequence; and perform optimization on the collapsed state of a structure with different external constraints. The model also predicts if any lockup or entanglement occurs during deployment.

Structured illumination microscopy and its new developments

Directory of Open Access Journals (Sweden)

Jianling Chen

2016-05-01

Full Text Available Optical microscopy allows us to observe the biological structures and processes within living cells. However, the spatial resolution of the optical microscopy is limited to about half of the wavelength by the light diffraction. Structured illumination microscopy (SIM, a type of new emerging super-resolution microscopy, doubles the spatial resolution by illuminating the specimen with a patterned light, and the sample and light source requirements of SIM are not as strict as the other super-resolution microscopy. In addition, SIM is easier to combine with the other imaging techniques to improve their imaging resolution, leading to the developments of diverse types of SIM. SIM has great potential to meet the various requirements of living cells imaging. Here, we review the recent developments of SIM and its combination with other imaging techniques.

Development of the SSTL-300-S1 Composite Imager Barrel Structure

Science.gov (United States)

Hamar, Chris; Wood, Trevor; Alsami, Sami; Hallett, Ben

2014-06-01

The SSTL-300-S1 is the latest in the family of highly capable SSTL-300 platforms, providing high resolution imagery with all the existing mission performance of the heritage platform. In developing the product, SSTL has had to undertake the development of a composite imager barrel assembly, which forms the payload instrument's primary structure. Working to a nominal schedule of 24 months from requirements definition to structural qualification, the barrel's development philosophy has had to carefully balance the interdependent optical, structural and programmatic requirements. This paper provides a brief summary description of that development.

Ecosocial System: Structure, Development Laws and Functioning

Directory of Open Access Journals (Sweden)

E. I. Alekseev

2004-01-01

Full Text Available The paper substantiates necessity to develop a unified system of socio-ecological knowledge. Ecosophy being a forming component of dialectic-materialistic philosophy has been proposed as such system. Structure, development laws and functioning of eco-social system are considered as a part of ecosophy theory. Standard laws and ecological principles being widely recognized by ecologically orientated theorists are stated in the paper.

Narciclasine attenuates diet-induced obesity by promoting oxidative metabolism in skeletal muscle.

Directory of Open Access Journals (Sweden)

Sofi G Julien

2017-02-01

Full Text Available Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls, attenuates diet-induced obesity (DIO in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity. Further investigation suggested that ncls achieves these beneficial effects by promoting a shift from glycolytic to oxidative muscle fibers in the DIO mice thereby enhancing mitochondrial respiration and fatty acid oxidation (FAO in the skeletal muscle. Moreover, ncls strongly activates AMPK signaling specifically in the skeletal muscle. The beneficial effects of ncls treatment in fat clearance and AMPK activation were faithfully reproduced in vitro in cultured murine and human primary myotubes. Mechanistically, ncls increases cellular cAMP concentration and ADP/ATP ratio, which further lead to the activation of AMPK signaling. Blocking AMPK signaling through a specific inhibitor significantly reduces FAO in myotubes. Finally, ncls also enhances mitochondrial membrane potential and reduces the formation of reactive oxygen species in cultured myotubes.

Specificity of chicken and mammalian transferrins in myogenesis

International Nuclear Information System (INIS)

Beach, R.L.; Popiela, Heinz; Festoff, B.W.

1985-01-01

Chicken transferrins isolated from eggs, embryo extract, serum or ischiatic-peroneal nerves are able to stimulate incorporation of ( 3 H)thymidine, and promote myogenesis by primary chicken muscles cells in vitro. Mammalian transferrins (bovine, rat, mouse, horse, rabbit, and human) do not promote ( 3 H)thymidine incorporation or myotube development. Comparison of the peptide fragments obtained after chemical or limited proteolytic cleavage demonstrates that the four chicken transferrins are all indistinguishable, but they differ considerably from the mammalian transferrins. The structural differences between chicken and mammalian transferrins probably account for the inability of mammalian transferrins to act as mitogens for, and to support myogenesis of, primary chicken muscle cells. (author)

Nursing Competency: Definition, Structure and Development

Science.gov (United States)

Fukada, Mika

2018-01-01

Nursing competency includes core abilities that are required for fulfilling one’s role as a nurse. Therefore, it is important to clearly define nursing competency to establish a foundation for nursing education curriculum. However, while the concepts surrounding nursing competency are important for improving nursing quality, they are still not yet completely developed. Thus, challenges remain in establishing definitions and structures for nursing competency, competency levels necessary for nursing professionals, training methods and so on. In the present study, we reviewed the research on definitions and attributes of nursing competency in Japan as well as competency structure, its elements and evaluation. Furthermore, we investigated training methods to teach nursing competency. PMID:29599616

Photogrammetry Methodology Development for Gossamer Spacecraft Structures

Science.gov (United States)

Pappa, Richard S.; Jones, Thomas W.; Black, Jonathan T.; Walford, Alan; Robson, Stuart; Shortis, Mark R.

2002-01-01

Photogrammetry--the science of calculating 3D object coordinates from images--is a flexible and robust approach for measuring the static and dynamic characteristics of future ultra-lightweight and inflatable space structures (a.k.a., Gossamer structures), such as large membrane reflectors, solar sails, and thin-film solar arrays. Shape and dynamic measurements are required to validate new structural modeling techniques and corresponding analytical models for these unconventional systems. This paper summarizes experiences at NASA Langley Research Center over the past three years to develop or adapt photogrammetry methods for the specific problem of measuring Gossamer space structures. Turnkey industrial photogrammetry systems were not considered a cost-effective choice for this basic research effort because of their high purchase and maintenance costs. Instead, this research uses mainly off-the-shelf digital-camera and software technologies that are affordable to most organizations and provide acceptable accuracy.

Development of Textile Reinforced Composites for Aircraft Structures

Science.gov (United States)

Dexter, H. Benson

1998-01-01

NASA has been a leader in development of composite materials for aircraft applications during the past 25 years. In the early 1980's NASA and others conducted research to improve damage tolerance of composite structures through the use of toughened resins but these resins were not cost-effective. The aircraft industry wanted affordable, robust structures that could withstand the rigors of flight service with minimal damage. The cost and damage tolerance barriers of conventional laminated composites led NASA to focus on new concepts in composites which would incorporate the automated manufacturing methods of the textiles industry and which would incorporate through-the-thickness reinforcements. The NASA Advanced Composites Technology (ACT) Program provided the resources to extensively investigate the application of textile processes to next generation aircraft wing and fuselage structures. This paper discusses advanced textile material forms that have been developed, innovative machine concepts and key technology advancements required for future application of textile reinforced composites in commercial transport aircraft. Multiaxial warp knitting, triaxial braiding and through-the-thickness stitching are the three textile processes that have surfaced as the most promising for further development. Textile reinforced composite structural elements that have been developed in the NASA ACT Program are discussed. Included are braided fuselage frames and window-belt reinforcements, woven/stitched lower fuselage side panels, stitched multiaxial warp knit wing skins, and braided wing stiffeners. In addition, low-cost processing concepts such as resin transfer molding (RTM), resin film infusion (RFI), and vacuum-assisted resin transfer molding (VARTM) are discussed. Process modeling concepts to predict resin flow and cure in textile preforms are also discussed.

Differentiation-Associated Downregulation of Poly(ADP-Ribose Polymerase-1 Expression in Myoblasts Serves to Increase Their Resistance to Oxidative Stress.

Directory of Open Access Journals (Sweden)

Gábor Oláh

Full Text Available Poly(ADP-ribose polymerase 1 (PARP-1, the major isoform of the poly (ADP-ribose polymerase family, is a constitutive nuclear and mitochondrial protein with well-recognized roles in various essential cellular functions such as DNA repair, signal transduction, apoptosis, as well as in a variety of pathophysiological conditions including sepsis, diabetes and cancer. Activation of PARP-1 in response to oxidative stress catalyzes the covalent attachment of the poly (ADP-ribose (PAR groups on itself and other acceptor proteins, utilizing NAD+ as a substrate. Overactivation of PARP-1 depletes intracellular NAD+ influencing mitochondrial electron transport, cellular ATP generation and, if persistent, can result in necrotic cell death. Due to their high metabolic activity, skeletal muscle cells are particularly exposed to constant oxidative stress insults. In this study, we investigated the role of PARP-1 in a well-defined model of murine skeletal muscle differentiation (C2C12 and compare the responses to oxidative stress of undifferentiated myoblasts and differentiated myotubes. We observed a marked reduction of PARP-1 expression as myoblasts differentiated into myotubes. This alteration correlated with an increased resistance to oxidative stress of the myotubes, as measured by MTT and LDH assays. Mitochondrial function, assessed by measuring mitochondrial membrane potential, was preserved under oxidative stress in myotubes compared to myoblasts. Moreover, basal respiration, ATP synthesis, and the maximal respiratory capacity of mitochondria were higher in myotubes than in myoblasts. Inhibition of the catalytic activity of PARP-1 by PJ34 (a phenanthridinone PARP inhibitor exerted greater protective effects in undifferentiated myoblasts than in differentiated myotubes. The above observations in C2C12 cells were also confirmed in a rat-derived skeletal muscle cell line (L6. Forced overexpression of PARP1 in C2C12 myotubes sensitized the cells to oxidant

Financial Structure and Economic Development in Nigieria

Directory of Open Access Journals (Sweden)

Ph. D. Olusegun Olowe

2012-05-01

Full Text Available In this study , the measurement of the Nigerian financial interrelation ratio was considered in line with the structure and development of financial system between 1999 and 2008 with a view to examining the incidences of the financial liberalization . The financial intermediation role for Nigeria on current basic prices was computed to determining the extent of stability and /or positive cum negative changes. This is to ensure the involvement of government as well as thedegree of financial institutions’ involvement in the economic growth and development of the country. In essence, the results of this study will be of relevance to formulate and execute policy formulation in its entirety. The result of the study revealed a pure neglect in the country with emphasis on financial intermediation. The earlier we put an enhanced financial structure in place, , the better for the economy.

Development of structural steels for nuclear application

Energy Technology Data Exchange (ETDEWEB)

Hong, Jun Hwa; Chi, S. H.; Ryu, W. S.; Lee, B. S.; Kim, D. H.; Kim, J. H.; Oh, Y. J.; Byun, T. S.; Yoon, J. H.; Park, D. K.; Oh, J. M.; Cho, H. D.; Kim, H.; Kim, H. D.; Kang, S. S.; Kim, J. W.; Ahn, S. B.

1997-08-01

To established the bases of nuclear structural material technologies, this study was focused on the localization and improvement of nuclear structural steels, the production of material property data, and technology developments for integrity evaluation. The important test and analysis technologies for material integrity assessment were developed, and the materials properties of the pressure vessel steels were evaluated systematically on the basis of those technologies, they are microstructural characteristics, tensile and indentation deformation properties, impact properties, and static and dynamic fracture toughness, fatigue and corrosion fatigue etc. Irradiation tests in the research reactors were prepared or completed to obtain the mechanical properties of irradiated materials. The improvement of low alloy steel was also attempted through the comparative study on the manufacturing processes, computer assisted alloy and process design, and application of the inter critical heat treatment. On the other hand, type 304 stainless steels for reactor internals were developed and tested successfully. High strength type 316LN stainless steels for reactor internals were developed and the microstructural characteristics, corrosion resistance, mechanical properties at high temperatures, low cycle fatigue property etc. were tested and analyzed in the view point of the effect of nitrogen. Type 347 stainless steels with high corrosion resistance and toughness for pipings and tubes and low-activated Cr-Mn steels were also developed and their basic properties were evaluated. Finally, the martensitic stainless steels for turbine blade were developed and tests. (author). 242 refs., 100 tabs., 304 figs.

Development of structural steels for nuclear application

International Nuclear Information System (INIS)

Hong, Jun Hwa; Chi, S. H.; Ryu, W. S.; Lee, B. S.; Kim, D. H.; Kim, J. H.; Oh, Y. J.; Byun, T. S.; Yoon, J. H.; Park, D. K.; Oh, J. M.; Cho, H. D.; Kim, H.; Kim, H. D.; Kang, S. S.; Kim, J. W.; Ahn, S. B.

1997-08-01

To established the bases of nuclear structural material technologies, this study was focused on the localization and improvement of nuclear structural steels, the production of material property data, and technology developments for integrity evaluation. The important test and analysis technologies for material integrity assessment were developed, and the materials properties of the pressure vessel steels were evaluated systematically on the basis of those technologies, they are microstructural characteristics, tensile and indentation deformation properties, impact properties, and static and dynamic fracture toughness, fatigue and corrosion fatigue etc. Irradiation tests in the research reactors were prepared or completed to obtain the mechanical properties of irradiated materials. The improvement of low alloy steel was also attempted through the comparative study on the manufacturing processes, computer assisted alloy and process design, and application of the inter critical heat treatment. On the other hand, type 304 stainless steels for reactor internals were developed and tested successfully. High strength type 316LN stainless steels for reactor internals were developed and the microstructural characteristics, corrosion resistance, mechanical properties at high temperatures, low cycle fatigue property etc. were tested and analyzed in the view point of the effect of nitrogen. Type 347 stainless steels with high corrosion resistance and toughness for pipings and tubes and low-activated Cr-Mn steels were also developed and their basic properties were evaluated. Finally, the martensitic stainless steels for turbine blade were developed and tests. (author). 242 refs., 100 tabs., 304 figs

Development of annular coupled structure

International Nuclear Information System (INIS)

Kageyama, T.; Morozumi, Y.; Yoshino, K.; Yamazaki, Y.

1992-01-01

A π/2-mode standing-wave linac of an Annular Coupled Structure (ACS) has been developed for the 1-GeV proton linac of the Japanese Hadron Project (JHP). This ACS has four coupling slots between accelerating and coupling cells in order to overcome difficulties in putting the ACS to practical use. Two prototypes of a four-slot ACS (f = 1296 MHz, β = v/c = 0.8) have been constructed and tested: one with a staggered slot-orientation from cell to cell; and the other with a uniform one. The staggered configuration gives a larger coupling constant and a larger shunt impedance than the uniform one with the same size of coupling slot. Both models have been conditioned up to the design input RF power. The four-slot ACS gives a distortion-free accelerating field around the beam axis, while a Side-Coupled Structure cavity gives an accelerating field mixed with a TE111-like mode. (Author) 7 figs., 2 tabs., 9 refs

Scientific methods for developing ultrastable structures

International Nuclear Information System (INIS)

Gamble, M.; Thompson, T.; Miller, W.

1990-01-01

Scientific methods used by the Los Alamos National Laboratory for developing an ultrastable structure for study of silicon-based elementary particle tracking systems are addressed. In particular, the design, analysis, and monitoring of this system are explored. The development methodology was based on a triad of analytical, computational, and experimental techniques. These were used to achieve a significant degree of mechanical stability (alignment accuracy >1 μrad) and yet allow dynamic manipulation of the system. Estimates of system thermal and vibratory stability and component performance are compared with experimental data collected using laser interferometry and accelerometers. 8 refs., 5 figs., 4 tabs

Pacific ciguatoxin-1b effect over Na+ and K+ currents, inositol 1,4,5-triphosphate content and intracellular Ca2+ signals in cultured rat myotubes

Science.gov (United States)

Hidalgo, Jorge; Liberona, José Luis; Molgó, Jordi; Jaimovich, Enrique

2002-01-01

The action of the main ciguatoxin involved in ciguatera fish poisoning in the Pacific region (P-CTX-1b) was studied in myotubes originated from rat skeletal muscle cells kept in primary culture. The effect of P-CTX-1b on sodium currents at short times of exposure (up to 1 min) showed a moderate increase in peak Na+ current. During prolonged exposures, P-CTX-1b decreased the peak Na+ current. This action was always accompanied by an increase of leakage currents, tail currents and outward Na+ currents, resulting in an intracellular Na+ accumulation. This effect is blocked by prior exposure to tetrodotoxin (TTX) and becomes evident only after washout of TTX. Low to moderate concentrations of P-CTX-1b (2–5 nM) partially blocked potassium currents in a manner that was dependent on the membrane potential. P-CTX-1b (2–12 nM) caused a small membrane depolarization (3–5 mV) and an increase in the frequency of spontaneous action potential discharges that reached in general low frequencies (0.1–0.5 Hz). P-CTX-1b (10 nM) caused a transient increase of intracellular inositol 1,4,5-trisphosphate (IP3) mass levels, which was blocked by TTX. In the presence of P-CTX-1b (10 nM) and in the absence of external Ca2+, the intracellular Ca2+ levels show a transient increase in the cytoplasm as well as in the nuclei. The time course of this effect may reflect the action of IP3 over internal stores activated by P-CTX-1b-induced membrane depolarization. PMID:12429578

Designing organizational structures: Key thoughts for development.

Science.gov (United States)

Killingsworth, Patricia; Eschenbacher, Lynn

2018-04-01

Current strategies and concepts to consider in developing a system-level organizational structure for the pharmacy enterprise are discussed. There are many different ways to design an organizational structure for the pharmacy enterprise within a health system. The size of the organization, the number of states in which it operates, and the geographic spread and complexity of the pharmacy business lines should be among the key considerations in determining the optimal organizational and decision-making structures for the pharmacy enterprise. The structure needs to support incorporation of the pharmacy leadership (both system-level executives and local leaders) into all strategic planning and discussions at the hospital and health-system levels so that they can directly represent the pharmacy enterprise instead of relying on others to develop strategy on their behalf. It is important that leaders of all aspects of the pharmacy enterprise report through the system's top pharmacy executive, who should be a pharmacist and have a title consistent with those of other leaders reporting at the same organizational level (e.g., chief pharmacy officer). Pharmacy leaders need to be well positioned within an organization to advocate for the pharmacy enterprise and use all resources to the best of their ability. As the scope and complexity of pharmacy services grow, it is critical to ensure that leadership of the pharmacy enterprise is unified under a single pharmacy executive team. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Geopressured-geothermal energy development: government incentives and institutional structures

Energy Technology Data Exchange (ETDEWEB)

Frederick, D.O.; Prestwood, D.C.L.; Roberts, K.; Vanston, J.H. Jr.

1979-01-01

The following subjects are included: a geothermal resource overview, the evolution of the current Texas geopressured-geothermal institutional structure, project evaluation with uncertainty and the structure of incentives, the natural gas industry, the electric utility industry, potential governmental participants in resource development, industrial users of thermal energy, current government incentives bearing on geopressured-geothermal development, six profiles for utilization of the geopressured-geothermal resources in the mid-term, and probable impacts of new government incentives on mid-term resource utilization profiles. (MHR)

Development of the Structural Materials Information Center

International Nuclear Information System (INIS)

Oland, C.B.; Naus, D.J.

1990-01-01

The US Nuclear Regulatory Commission has initiated a Structural Aging Program at the Oak Ridge National Laboratory to identify potential structural safety issues related to continued service of nuclear power plants and to establish criteria for evaluating and resolving these issues. One of the tasks in this program focuses on the establishment of a Structural Materials Information Center where data and information on the time variation of concrete and other structural material properties under the influence of pertinent environmental stressors and aging factors are being collected and assembled into a data base. This data base will be used to assist in the prediction of potential long-term deterioration of critical structural components in nuclear power plants and to establish limits on hostile environmental exposure for these structures and materials. Two complementary data base formats have been developed. The Structural Materials Handbook is an expandable, hard-copy reference document that contains complete sets of data and information for selected portland cement concrete, metallic reinforcement, prestressing tendon, and structural steel materials. Baseline data, reference properties and environmental information are presented in the handbook as tables, notes and graphs. The handbook, which will be published in four volumes, serves as the information source for the electronic data base. The Structural Materials Electronic Data Base is accessible by an IBM-compatible personal computer and provides an efficient means for searching the various data base files to locate materials with similar properties. Properties will be reported in the International System of Units (SI) and in customary units whenever possible. 7 refs., 3 figs., 4 tabs

Injury and subsequent regeneration of muscles for activation of local innate immunity to facilitate the development and relapse of autoimmune myositis in C57BL/6 mice.

Science.gov (United States)

Kimura, Naoki; Hirata, Shinya; Miyasaka, Nobuyuki; Kawahata, Kimito; Kohsaka, Hitoshi

2015-04-01

To determine whether injury and regeneration of the skeletal muscles induce an inflammatory milieu that facilitates the development and relapse of autoimmune myositis. The quadriceps of C57BL/6 mice were injured with bupivacaine hydrochloride (BPVC) and evaluated histologically. Macrophages and regenerating myofibers in the treated muscles and differentiating C2C12 myotubes were examined for cytokine expression. Mice were immunized with C protein fragments at the base of the tail and in the right hind footpads (day 0) to evoke systemic anti-C protein immunity and to induce local myositis in the right hind limbs. The contralateral quadriceps muscles were injured with BPVC or phosphate buffered saline (PBS) on day 7 or after spontaneous regression of myositis (day 42). The quadriceps muscle in nonimmunized mice was injured with BPVC on day 7. The muscles were examined histologically 14 days after treatment. The BPVC-injured muscles had macrophage infiltration most abundantly at 3 days after the injection, with emergence of regenerating fibers from day 5. The macrophages expressed inflammatory cytokines, including tumor necrosis factor α, interleukin-1β, and CCL2. Regenerating myofibers and C2C12 myotubes also expressed the cytokines. The BPVC-injected muscles from nonimmunized mice had regenerating myofibers with resolved cell infiltration 14 days after treatment. In mice preimmunized with C protein fragments, the muscles injected with BPVC on day 7 as well as on day 42, but not those injected with PBS, had myositis accompanied by CD8+ T cell infiltration. Injury and regeneration could set up an inflammatory milieu in the muscles and facilitate the development and relapse of autoimmune myositis. Copyright © 2015 by the American College of Rheumatology.

Monitoring structure development in milk acidification using diffuse reflectance profiles

DEFF Research Database (Denmark)

Skytte, Jacob Lercke; Andersen, Ulf; Møller, Flemming

2012-01-01

are needed so that the production can be carried out consistently, regardless of day-to-day variations in the raw materials. Casein micelles aggregate during milk acidification, which leads to formation of a gel network. This change of structure is important for the development of a range of dairy products......, protein, and temperature in the acidification process is conducted. The purpose of the experiment is to investigate how the change of these parameters affects the diffuse reflectance properties as well as to demonstrate the relation between the optical parameters and structure formation in milk......The structure of dairy products is important for the consumer, and milk acidification plays a central role for structural development. To ensure the best possible consumer experience, it is important that a product’s structural properties are stable. Therefore process and quality control tools...

Ductile electroactive biodegradable hyperbranched polylactide copolymers enhancing myoblast differentiation.

Science.gov (United States)

Xie, Meihua; Wang, Ling; Guo, Baolin; Wang, Zhong; Chen, Y Eugene; Ma, Peter X

2015-12-01

Myotube formation is crucial to restoring muscular functions, and biomaterials that enhance the myoblast differentiation into myotubes are highly desirable for muscular repair. Here, we report the synthesis of electroactive, ductile, and degradable copolymers and their application in enhancing the differentiation of myoblasts to myotubes. A hyperbranched ductile polylactide (HPLA) was synthesized and then copolymerized with aniline tetramer (AT) to produce a series of electroactive, ductile and degradable copolymers (HPLAAT). The HPLA and HPLAAT showed excellent ductility with strain to failure from 158.9% to 42.7% and modulus from 265.2 to 758.2 MPa. The high electroactivity of the HPLAAT was confirmed by UV spectrometer and cyclic voltammogram measurements. These HPLAAT polymers also showed improved thermal stability and controlled biodegradation rate compared to HPLA. Importantly, when applying these polymers for myotube formation, the HPLAAT significantly improved the proliferation of C2C12 myoblasts in vitro compared to HPLA. Furthermore, these polymers greatly promoted myogenic differentiation of C2C12 cells as measured by quantitative analysis of myotube number, length, diameter, maturation index, and gene expression of MyoD and TNNT. Together, our study shows that these electroactive, ductile and degradable HPLAAT copolymers represent significantly improved biomaterials for muscle tissue engineering compared to HPLA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of Probabilistic Structural Analysis Integrated with Manufacturing Processes

Science.gov (United States)

Pai, Shantaram S.; Nagpal, Vinod K.

2007-01-01

An effort has been initiated to integrate manufacturing process simulations with probabilistic structural analyses in order to capture the important impacts of manufacturing uncertainties on component stress levels and life. Two physics-based manufacturing process models (one for powdered metal forging and the other for annular deformation resistance welding) have been linked to the NESSUS structural analysis code. This paper describes the methodology developed to perform this integration including several examples. Although this effort is still underway, particularly for full integration of a probabilistic analysis, the progress to date has been encouraging and a software interface that implements the methodology has been developed. The purpose of this paper is to report this preliminary development.

Development of Hybrid Product Breakdown Structure for NASA Ground Systems

Science.gov (United States)

Monaghan, Mark W.; Henry, Robert J.

2013-01-01

The Product Breakdown Structure is traditionally a method of identification of the products of a project in a tree structure. It is a tool used to assess, plan, document, and display the equipment requirements for a project. It is part of a product based planning technique, and attempts to break down all components of a project in as much detail as possible, so that nothing is overlooked. The PBS for ground systems at the Kennedy Space Center is being developed to encompass the traditional requirements including the alignment of facility, systems, and components to the organizational hierarchy. The Ground Operations Product Breakdown Structure is a hybrid in nature in that some aspects of a work breakdown structure will be incorporated and merged with the Architecture Concept of Operations, Master Subsystem List, customer interface, and assigned management responsibility. The Ground Operations Product Breakdown Structure needs to be able to identify the flexibility of support differing customers (internal and external) usage of ground support equipment within the Kennedy Space Center launch and processing complex. The development of the Product Breakdown Structure is an iterative activity Initially documenting the organization hierarchy structure and relationships. The Product Breakdown Structure identifies the linkage between the customer program requirements, allocation of system resources, development of design goals, and identification logistics products. As the Product Breakdown Structure progresses the incorporation of the results of requirement planning for the customer occurs identifying facility needs and systems. The mature Product Breakdown Structure is baselined with a hierarchical drawing, the Product Breakdown Structure database, and an associated document identifying the verification of the data through the life cycle of the program/product line. This paper will document, demonstrate, and identify key aspects of the life cycle of a Hybrid Product

Nursing Competency: Definition, Structure and Development

OpenAIRE

Fukada, Mika

2018-01-01

Nursing competency includes core abilities that are required for fulfilling one’s role as a nurse. Therefore, it is important to learly define nursing competency to　establish a foundation for nursing education curriculum. However, while the concepts surrounding nursing competency are important for improving nursing quality, they are still not yet completely developed. Thus, challenges remain in establishing finitions and structures for nursing competency, competency levels necessary for　nurs...

Development of Fluid and I and C Systems Design Technology for LMR - Development of mechanical structure design technology for LMR

International Nuclear Information System (INIS)

Lee, Jae Han; Joo, Young Sang; Lee, Hueong Yeon and others

2005-03-01

The key research items during the fiscal years of Phase 3 of the mechanical design technology development for liquid metal reactor are described. The objective of this project is to develop the design technology for the mechanical system of 600MWe, pool type liquid metal reactor with sodium coolant, and the structural integrity evaluation technology for mechanical system of the reactor system, structures and equipments. In the design technology development for mechanical structures, the reactor internal structures, reactor head and piping system, reactor containment structures have been studied, and new structural concepts compatible with the new reactor have been proposed. The thermal protection devices of reactor vessel and the refueling system have been conceptually established and the feasibility study for 3-D seismic isolation of reactor building was performed. The structural damage detection technology for reactor internal structures has been studied and its application has been confirmed. In the structural integrity evaluation technology development, the sensitivities of material constants for inelastic analysis codes have been studied and the applicabilities of the developed codes are enhanced. The high temperature creep-fatigue structural behavior test has been conducted so that high temperature structural damage test and evaluation technology were ensured at first in domestic. The high temperature seismic buckling analysis method to evaluate the buckling of thin reactor shell structure under the transient thermal load was established. In addition, the core seismic response analysis code reflected the fluid effect of core was developed and its accuracy was confirmed with a scale-down model test

Nucleon structure in view of recent developments

International Nuclear Information System (INIS)

Martin, A.D.

1993-01-01

We review the present knowledge of the parton structure of the proton. We discuss recent developments concerning deep-inelastic scattering and parton distributions at small x, with emphasis on the predictions of perturbative QCD that are relevant to the experiment at HERA. (author). 37 refs, 16 figs, 1 tab

Systematic methodological review: developing a framework for a qualitative semi-structured interview guide.

Science.gov (United States)

Kallio, Hanna; Pietilä, Anna-Maija; Johnson, Martin; Kangasniemi, Mari

2016-12-01

To produce a framework for the development of a qualitative semi-structured interview guide. Rigorous data collection procedures fundamentally influence the results of studies. The semi-structured interview is a common data collection method, but methodological research on the development of a semi-structured interview guide is sparse. Systematic methodological review. We searched PubMed, CINAHL, Scopus and Web of Science for methodological papers on semi-structured interview guides from October 2004-September 2014. Having examined 2,703 titles and abstracts and 21 full texts, we finally selected 10 papers. We analysed the data using the qualitative content analysis method. Our analysis resulted in new synthesized knowledge on the development of a semi-structured interview guide, including five phases: (1) identifying the prerequisites for using semi-structured interviews; (2) retrieving and using previous knowledge; (3) formulating the preliminary semi-structured interview guide; (4) pilot testing the guide; and (5) presenting the complete semi-structured interview guide. Rigorous development of a qualitative semi-structured interview guide contributes to the objectivity and trustworthiness of studies and makes the results more plausible. Researchers should consider using this five-step process to develop a semi-structured interview guide and justify the decisions made during it. © 2016 John Wiley & Sons Ltd.

Skills development and structural change: Possibilities for and limitations of redressing structural racial inequalities in South Africa

Science.gov (United States)

Groener, Zelda

2013-12-01

Improving structural racial equality for historically-disadvantaged Black South Africans, including low-skilled and unemployed adults and youths, is a pertinent challenge for the South African government during the ongoing transition from apartheid capitalism to post-apartheid capitalism. Within the framework of the National Skills Development Strategy (NSDS), the introduction of "learnerships" and "learning programmes", which include structured learning programmes, learnerships, apprenticeships and skills programmes, has had some impact. But emerging theoretical perspectives assert that apartheid structural racial inequalities persist and that structural reform is imperative. Opposing positions translate into two perspectives on social transition: either capitalism can be de-racialised, or capitalism in South Africa should be dismantled in order to de-racialise it. After a review of relevant literature and governmental documents, the author identifies five structural and pedagogical barriers as likely causes for low completion rates of skills development courses and concludes that structural reform needs more favourable political and economic conditions in order to be successful.

Development of a Computer Application to Simulate Porous Structures

Directory of Open Access Journals (Sweden)

S.C. Reis

2002-09-01

Full Text Available Geometric modeling is an important tool to evaluate structural parameters as well as to follow the application of stereological relationships. The obtention, visualization and analysis of volumetric images of the structure of materials, using computational geometric modeling, facilitates the determination of structural parameters of difficult experimental access, such as topological and morphological parameters. In this work, we developed a geometrical model implemented by computer software that simulates random pore structures. The number of nodes, number of branches (connections between nodes and the number of isolated parts, are obtained. Also, the connectivity (C is obtained from this application. Using a list of elements, nodes and branches, generated by the software, in AutoCAD® command line format, the obtained structure can be viewed and analyzed.

Recent developments in structure-preserving algorithms for oscillatory differential equations

CERN Document Server

Wu, Xinyuan

2018-01-01

The main theme of this book is recent progress in structure-preserving algorithms for solving initial value problems of oscillatory differential equations arising in a variety of research areas, such as astronomy, theoretical physics, electronics, quantum mechanics and engineering. It systematically describes the latest advances in the development of structure-preserving integrators for oscillatory differential equations, such as structure-preserving exponential integrators, functionally fitted energy-preserving integrators, exponential Fourier collocation methods, trigonometric collocation methods, and symmetric and arbitrarily high-order time-stepping methods. Most of the material presented here is drawn from the recent literature. Theoretical analysis of the newly developed schemes shows their advantages in the context of structure preservation. All the new methods introduced in this book are proven to be highly effective compared with the well-known codes in the scientific literature. This book also addre...

Development of Stitched Composite Structure for Advanced Aircraft

Science.gov (United States)

Jegley, Dawn; Przekop, Adam; Rouse, Marshall; Lovejoy, Andrew; Velicki, Alex; Linton, Kim; Wu, Hsi-Yung; Baraja, Jaime; Thrash, Patrick; Hoffman, Krishna

2015-01-01

NASA has created the Environmentally Responsible Aviation Project to develop technologies which will reduce the impact of aviation on the environment. A critical aspect of this pursuit is the development of a lighter, more robust airframe that will enable the introduction of unconventional aircraft configurations. NASA and The Boeing Company are working together to develop a structural concept that is lightweight and an advancement beyond state-of-the-art composites. The Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) is an integrally stiffened panel design where elements are stitched together and designed to maintain residual load-carrying capabilities under a variety of damage scenarios. With the PRSEUS concept, through-the-thickness stitches are applied through dry fabric prior to resin infusion, and replace fasteners throughout each integral panel. Through-the-thickness reinforcement at discontinuities, such as along flange edges, has been shown to suppress delamination and turn cracks, which expands the design space and leads to lighter designs. The pultruded rod provides stiffening away from the more vulnerable skin surface and improves bending stiffness. A series of building blocks were evaluated to explore the fundamental assumptions related to the capability and advantages of PRSEUS panels. These building blocks addressed tension, compression, and pressure loading conditions. The emphasis of the development work has been to assess the loading capability, damage arrestment features, repairability, post-buckling behavior, and response of PRSEUS flat panels to out-of plane pressure loading. The results of this building-block program from coupons through an 80%-scale pressure box have demonstrated the viability of a PRSEUS center body for the Hybrid Wing Body (HWB) transport aircraft. This development program shows that the PRSEUS benefits are also applicable to traditional tube-andwing aircraft, those of advanced configurations, and other

Financial Development, Financial Structure, and Macroeconomic Volatility: Evidence from China

Directory of Open Access Journals (Sweden)

Feng Wei

2016-11-01

Full Text Available Using annual data from 1997–2014 of 30 provinces, municipalities, and autonomous regions, subdividing trended and cyclical volatility of macroeconomics and inflation, considering different indicators of financial development and financial structure, this paper investigated the impact of financial development and financial structure on macroeconomic volatility. The empirical results found that (1 the trended and cyclical volatility of the previous macroeconomic period had a significantly positive impact on that of the current period, and the impact of trended volatility was greater than that of cyclical volatility; (2 financial development had a significantly negative impact on macroeconomic cyclical volatility through inflation cyclical volatility, but inflation trended volatility would amplify macroeconomic volatility; financial markets have no significant effect on macroeconomic volatility; financial structure measured with the ratio of stock market turnover and the efficiency of the financial development had a significant positive impact on macroeconomic cyclical volatility; and (3 inflation trended volatility had a significantly negative impact on macroeconomic cyclical volatility and trended volatility, while inflation cyclical volatility had a significantly positive impact on macroeconomic cyclical volatility.

Stance and strategy: post-structural perspective and post-colonial engagement to develop nursing knowledge.

Science.gov (United States)

Sochan, Anne M

2011-07-01

How should nursing knowledge advance? This exploration contextualizes its evolution past and present. In addressing how it evolved in the past, a probable historical evolution of its development draws on the perspectives of Frank & Gills's World System Theory, Kuhn's treatise on Scientific Revolutions, and Foucault's notions of Discontinuities in scientific knowledge development. By describing plausible scenarios of how nursing knowledge evolved, I create a case for why nursing knowledge developers should adopt a post-structural stance in prioritizing their research agenda(s). Further, by adopting a post-structural stance, I create a case on how nurses can advance their disciplinary knowledge using an engaging post-colonial strategy. Given an interrupted history caused by influence(s) constraining nursing's knowledge development by power structures external, and internal, to nursing, knowledge development can evolve in the future by drawing on post-structural interpretation, and post-colonial strategy. The post-structural writings of Deleuze & Guattari's understanding of 'Nomadology' as a subtle means to resist being constrained by existing knowledge development structures, might be a useful stance to understanding the urgency of why nursing knowledge should advance addressing the structural influences on its development. Furthermore, Bhabha's post-colonial elucidation of 'Hybridity' as an equally discreet means to change the culture of those constraining structures is an appropriate strategy to enact how nursing knowledge developers can engage with existing power structures, and simultaneously influence that engagement. Taken together, 'post-structural stance' and 'post-colonial strategy' can refocus nursing scholarship to learn from its past, in order to develop relevant disciplinary knowledge in its future. © 2011 Blackwell Publishing Ltd.

Recent developments for fast reactor structural design standard (FDS)

International Nuclear Information System (INIS)

Kasahara, N.; Nakamuria, K.; Morishita, M.; Shibamoto, H.; Nagashima, H.; Inoue, K.

2005-01-01

For realization of reliable and economical fast reactor (FR) plants, Japan Nuclear Cycle Development Institute(JNC) and Japan Atomic Power Company(JAPC) are cooperating on 'Feasibility Study on Commercialized FR Cycle Systems'. To certify the design concepts through evaluation of their structural integrity, the research and development of 'Elevated Temperature Structural Design Guide for Commercialized Fast Reactor (FDS)' is recognized as an essential theme. FDS focuses on particular failure modes of FRs such as ratchet deformation and creep fatigue damages due to cyclic thermal loads. To evaluate these modes, three main developments are in progress. One is 'Refinement of Failure Criteria' for particular modes of FRs. Next is development of 'Guidelines for Inelastic Design Analysis' in order to predict elastic plastic and creep behaviors. Furthermore, efforts are being made toward preparing 'Guidelines for Thermal Load Modeling' for FR component design where thermal loads are dominant. These studies were performed under the sponsorship of the Ministry of Economy, Trade and Industry of Japanese government. (authors)

Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

Energy Technology Data Exchange (ETDEWEB)

Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

Muscle cell culture (L/sub 6/) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 ..mu..M compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of (/sup 3/H) leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using (/sup 3/H) leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 ..mu..M level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle.

Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture

International Nuclear Information System (INIS)

Roeder, R.A.; Thorpe, S.D.; Byers, F.M.; Schelling, G.T.; Gunn, J.M.

1986-01-01

Muscle cell culture (L 6 ) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effect of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 μM compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of [ 3 H] leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using [ 3 H] leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes by dexamethasone, but increased in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 μM level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle

Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression.

Science.gov (United States)

Hinds, Terry D; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S

2016-02-11

Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C₂C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C₂C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

Directory of Open Access Journals (Sweden)

Terry D. Hinds

2016-02-01

Full Text Available Unlike the glucocorticoid receptor α (GRα, GR β (GRβ has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx and muscle ring finger 1 (MuRF1 response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

Degree of Suppression of Mouse Myoblast Cell Line C₂C12 Differentiation Varies According to Chondroitin Sulfate Subtype.

Science.gov (United States)

Warita, Katsuhiko; Oshima, Nana; Takeda-Okuda, Naoko; Tamura, Jun-Ichi; Hosaka, Yoshinao Z

2016-10-21

Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C₂C 12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion.

Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

DEFF Research Database (Denmark)

Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

2014-01-01

Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

Design of an X-band accelerating structure using a newly developed structural optimization procedure

Energy Technology Data Exchange (ETDEWEB)

Huang, Xiaoxia [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Fang, Wencheng; Gu, Qiang [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhao, Zhentang, E-mail: zhaozhentang@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing 100049 (China)

2017-05-11

An X-band high gradient accelerating structure is a challenging technology for implementation in advanced electron linear accelerator facilities. The present work discusses the design of an X-band accelerating structure for dedicated application to a compact hard X-ray free electron laser facility at the Shanghai Institute of Applied Physics, and numerous design optimizations are conducted with consideration for radio frequency (RF) breakdown, RF efficiency, short-range wakefields, and dipole/quadrupole field modes, to ensure good beam quality and a high accelerating gradient. The designed X-band accelerating structure is a constant gradient structure with a 4π/5 operating mode and input and output dual-feed couplers in a racetrack shape. The design process employs a newly developed effective optimization procedure for optimization of the X-band accelerating structure. In addition, the specific design of couplers providing high beam quality by eliminating dipole field components and reducing quadrupole field components is discussed in detail.

Technology development on the assessment of structural integrity of nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Seo, Jeong Moon; Choun, Y. S.; Choi, I. K. and others

1999-04-01

Nuclear power plants in Korea show drop off in their performance and safety margin as the age of plants increase. The reevaluation of Kori-1 Unit on its performance and safety for life extension is expected in the near future. However, technologies and information related are insufficient to quantitatively estimate them. The final goal of this study is to develop the basic testing and evaluation techniques related with structural integrity of important nuclear equipment and structures. A part of the study includes development of equipment qualification technique. To ensure the structural integrity of structures, systems, and equipment in nuclear power plants, the following 5 research tasks were performed in the first year. - Analysis of dynamic characteristics of reactor internals - Analysis of engineering characteristics of instrumental earthquakes recorded in Korea - Analysis of ultimate pressure capacity and failure mode of containments building - Development of advanced NDE techniques using ultrasonic resonance scattering - Development of equipment qualification technique against vibration aging. These technologies developed in this study can be used to ensure the structural safety of operational nuclear power plants, and for the long-term life management. (author)

Development of magnetostrictive active members for control of space structures

Science.gov (United States)

Johnson, Bruce G.; Avakian, Kevin M.; Fenn, Ralph C.; Gaffney, Monique S.; Gerver, Michael J.; Hawkey, Timothy J.; Boudreau, Donald J.

1992-08-01

The goal of this Phase 2 Small Business Innovative Research (SBIR) project was to determine the technical feasibility of developing magnetostrictive active members for use as truss elements in space structures. Active members control elastic vibrations of truss-based space structures and integrate the functions of truss structure element, actively controlled actuator, and sensor. The active members must control structural motion to the sub-micron level and, for many proposed space applications, work at cryogenic temperatures. Under this program both room temperature and cryogenic temperature magnetostrictive active members were designed, fabricated, and tested. The results of these performance tests indicated that room temperature magnetostrictive actuators feature higher strain, stiffness, and force capability with lower amplifier requirements than similarly sized piezoelectric or electrostrictive active members, at the cost of higher mass. Two different cryogenic temperature magnetostrictive materials were tested at liquid nitrogen temperatures, both with larger strain capability than the room temperature magnetostrictive materials. The cryogenic active member development included the design and fabrication of a cryostat that allows operation of the cryogenic active member in a space structure testbed.

Development of children’s early understanding of numeric structure

Directory of Open Access Journals (Sweden)

Vasilyeva, Marina

2016-09-01

Full Text Available Understanding of the base-10 structure of multi-digit numbers is one of the critical aspects in early mathematics learning. It has been documented that children from different countries vary in their use of base-10 representations. Questions concerning potential sources of this variability have been debated for decades. One commonly posited explanation is that some languages provide explicit cues about the structure of multi-digit numbers, facilitating the development of base-10 representations. In the present study, we tested this view against an alternative view, positing that variability in children’s learning of numeric structure may reflect differences in their experiences with numbers. The study examined kindergartners and first-graders from four countries: Taiwan, South Korea, the USA, and Russia. Results showed that the use of base-10 representations by American first-graders increased dramatically over the last decades, following changes in curricular guidelines. First-graders across the four countries showed some differences in performance (however, not consistent with the language account, whereas kindergartners performed comparably despite the differences in their languages. The results suggest that the nature of early math instruction may be critical for children’s developing understanding of numeric structure.

Multiple roles of biosurfactants in structural biofilm development by Pseudomonas aeruginosa

DEFF Research Database (Denmark)

Pamp, Sünje Johanna; Tolker-Nielsen, Tim

2007-01-01

Recent studies have indicated that biosurfactants produced by Pseudomonas aeruginosa play a role both in maintaining channels between multicellular structures in biofilms and in dispersal of cells from biofilms. Through the use of flow cell technology and enhanced confocal laser scanning microscopy......, we have obtained results which suggest that the biosurfactants produced by P. aeruginosa play additional roles in structural biofilm development. We present genetic evidence that during biofilm development by P. aeruginosa, biosurfactants promote microcolony formation in the initial phase...... and facilitate migration-dependent structural development in the later phase. P. aeruginosa rhl4 mutants, deficient in synthesis of biosurfactants, were not capable of forming microcolonies in the initial phase of biofilm formation. Experiments involving two-color-coded mixed-strain biofilms showed that P...

Development and implementation of the TPX structural and cryogenic design criteria

International Nuclear Information System (INIS)

Zatz, I.; Heitzenroeder, P.; Schultz, J.H.

1993-01-01

The Tokamak Physics Experiment (TPX) is a superconducting tokamak utilizing both Nb 3 Sn and NbTi superconducting magnets and will feature a low-activation titanium alloy vacuum vessel and carbon-carbon composite divertors. Due to the unique nature of the component designs, materials, and environment, the TPX project felt it necessary to develop a design criteria (code) which will specifically address the structural and cryogenic design aspects of such a device. The developed code is intended to serve all components of the device; namely, the TF and PF magnets, vacuum vessel, first wall and divertor, cryostat, diagnostics, heating devices, shielding, and all associated structural elements. The structural portion is based largely on that developed for the Burning Plasma Experiment (BPX), which was modeled after the CIT Vacuum Vessel Structural Design Criteria and ASME Boiler and Pressure Vessel (B ampersand PV) Code. The cryogenic criteria is largely modeled after that proposed in the ITER CDA. This paper summarizes the TPX Criteria document

Integrating personality structure, personality process, and personality development

NARCIS (Netherlands)

Baumert, Anna; Schmitt, Manfred; Perugini, Marco; Johnson, Wendy; Blum, Gabriela; Borkenau, Peter; Costantini, Giulio; Denissen, J.J.A.; Fleeson, William; Grafton, Ben; Jayawickreme, Eranda; Kurzius, Elena; MacLeod, Colin; Miller, Lynn C.; Read, Stephen J.; Robinson, Michael D.; Wood, Dustin; Wrzus, Cornelia

2017-01-01

In this target article, we argue that personality processes, personality structure, and personality development have to be understood and investigated in integrated ways in order to provide comprehensive responses to the key questions of personality psychology. The psychological processes and

The Structure of the Managerial System of Higher Education's Development

Science.gov (United States)

Levina, Elena Y.; Kutuev, Ruslan A.; Balakhnina, Lidia V.; Tumarov, Konstantin B.; Chudnovskiy, Alexey D.; Shagiev, ?ulat V.

2016-01-01

The research urgency is caused by necessity of planning regulation of higher education development at all levels of management. The purpose of this article is to develop the structure of a control system of higher education development, the Foundation of which is understanding of the quality of higher education as factor for development of the…

The human brain. Prenatal development and structure

International Nuclear Information System (INIS)

Marin-Padilla, Miguel

2011-01-01

This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

The human brain. Prenatal development and structure

Energy Technology Data Exchange (ETDEWEB)

Marin-Padilla, Miguel

2011-07-01

This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

Development of all-beryllium riveted structures

International Nuclear Information System (INIS)

Floyd, D.R.; Leslie, W.W.; Miley, D.V.; Nokes, R.W.

1976-01-01

Results are presented of a development program aimed at making a full-scale, all-beryllium frustrum by riveted assembly methods. Included are descriptions of the sheet-metal fabrication practices and assembly plans. Results of extensive mechanical testing of both ingot- and powder-source beryllium products that are presented include tensile, notch-tensile, bearing, and shear tests. Although the full-size structure has not been built, examples are given of several conical and cylindrical structures that were made. The largest of these is a 20-in. diameter, 15-in. long cylinder that was roll-formed from one 0.050-in. thick ingot sheet and assembled with 60 countersunk rivets. Tensile testing of riveted flat coupons is also reported as is bulge testing of riveted cylindrical shells. A cost comparison of riveted deep-drawn and powder-source cylinders is made. Results show that when strength and dimensional tolerance requirements are not severe, a riveted assembly approach is warranted. 33 figures, 8 tables

The Use of the STAGS Finite Element Code in Stitched Structures Development

Science.gov (United States)

Jegley, Dawn C.; Lovejoy, Andrew E.

2014-01-01

In the last 30 years NASA has worked in collaboration with industry to develop enabling technologies needed to make aircraft more fuel-efficient and more affordable. The focus on the airframe has been to reduce weight, improve damage tolerance and better understand structural behavior under realistic flight and ground loading conditions. Stitched structure is a technology that can address the weight savings, cost reduction, and damage tolerance goals, but only if it is supported by accurate analytical techniques. Development of stitched technology began in the 1990's as a partnership between NASA and Boeing (McDonnell Douglas at the time) under the Advanced Composites Technology Program and has continued under various titles and programs and into the Environmentally Responsible Aviation Project today. These programs contained development efforts involving manufacturing development, design, detailed analysis, and testing. Each phase of development, from coupons to large aircraft components was supported by detailed analysis to prove that the behavior of these structures was well-understood and predictable. The Structural Analysis of General Shells (STAGS) computer code was a critical tool used in the development of many stitched structures. As a key developer of STAGS, Charles Rankin's contribution to the programs was quite significant. Key features of STAGS used in these analyses and discussed in this paper include its accurate nonlinear and post-buckling capabilities, its ability to predict damage growth, and the use of Lagrange constraints and follower forces.

Development of Mechanical Structure Design Technology for LMR

International Nuclear Information System (INIS)

Lee, Jae Han; Joo, Young Sang; Lee, Hyeong Yeon

2007-03-01

Structural integrity and design simplifications were secured on reactor core support system, upper internal structure and core catcher of KALIMER-600. The evaluation on the suitability of high temperature and seismic design of reactor structures, and the structural integrity evaluation on reactor components and high temperature pipings are performed. The interfaces between the components and ISI accessibility are checked. Lightening of reactor building by 7%, the seismic design for 0.3g seismic loads and improvement of reactor structural design concept for KALIMER-600 have been carried out. Remote inspection technique using ultrasonic wave guide sensor was acquired as a visualization method for reactor internals under opaque sodium environments. The basic guideline on high temperature structure assessment as an assessment procedure on high temperature inelastic behaviour has been completed. In high temperature creep-fatigue test, totally 500 cycles (totally 700 hold time) were carried on cylindrical test and IHTS co-axial pipe test models. The behaviors of creep-fatigue damage and creep-fatigue crack behaviour were investigated, and the DB on the structural test were established. The seismic response tests on 19-sub assembly validation test model in air and in water were carried out, and its multi-purpose characteristics and reliability on the SAC-CORE3.0 code developed for core seismic response analysis were validated

Implementing the leadership development plans of faculty education fellows: a structured approach.

Science.gov (United States)

Goldman, Ellen F; Wesner, Marilyn; Karnchanomai, Ornpawee; Haywood, Yolanda

2012-09-01

The literature about medical education faculty fellowship programs, which have grown in popularity, quantifies program characteristics, provides exemplars, and reports on delivery strategies. Evaluation is generally limited to satisfaction measures, with a few longitudinal studies of postprogram achievements, but none on the process of making these changes.The authors describe the development of faculty members' postfellowship leadership plans and a structured process to support plan implementation. They also compare the implementation of initiatives specified in individual leadership development plans of two cohorts of faculty. The participants were graduates of a fellowship program at the George Washington University School of Medicine and Health Sciences. One cohort participated in a structured process of monthly reciprocal peer coaching, followed by journaling and quarterly interviews with the program director; a second cohort functioned as a comparison with no structured process supporting them. (Study years are not provided because they could inadvertently lead to the identification of the participants.) Despite similar implementation challenges expressed by both cohorts, the cohort participating in the structured process implemented 23% more of their planned initiatives, including 2 times as many educational leadership initiatives and 3.5 times as many initiatives related to developing new curriculum. The combination of plan development, reciprocal peer coaching, journaling, and interview discussions provided faculty with focus, structure, and personal support. This structured process supporting leadership plan development and implementation can be easily transferred to other fellowship programs in medical education, adapted for use with residents and fellows, and used in similar development programs.

Development and optimization of containment structure concepts

International Nuclear Information System (INIS)

Reuter, H.R.; Whitcraft, J.S. Jr.

1976-01-01

The development of prestressed concrete containment structures for nuclear power plants designed, constructed, and tested by Bechtel Power Corporation has been divided into three general stages or generations. The distinctions that characterize these generations are: the shape of the dome, the number of buttresses, the size and arrangement of the post-tensioning tendons, and the design level of the prestressing forces. (author)

Study on structural seismic margin and probabilistic seismic risk. Development of a structural capacity-seismic risk diagram

International Nuclear Information System (INIS)

Nakajima, Masato; Ohtori, Yasuki; Hirata, Kazuta

2010-01-01

Seismic margin is extremely important index and information when we evaluate and account seismic safety of critical structures, systems and components quantitatively. Therefore, it is required that electric power companies evaluate the seismic margin of each plant in back-check of nuclear power plants in Japan. The seismic margin of structures is usually defined as a structural capacity margin corresponding to design earthquake ground motion. However, there is little agreement as to the definition of the seismic margin and we have no knowledge about a relationship between the seismic margin and seismic risk (annual failure probability) which is obtained in PSA (Probabilistic Safety Assessment). The purpose of this report is to discuss a definition of structural seismic margin and to develop a diagram which can identify a relation between seismic margin and seismic risk. The main results of this paper are described as follows: (1) We develop seismic margin which is defined based on the fact that intensity of earthquake ground motion is more appropriate than the conventional definition (i.e., the response-based seismic margin) for the following reasons: -seismic margin based on earthquake ground motion is invariant where different typed structures are considered, -stakeholders can understand the seismic margin based on the earthquake ground motion better than the response-based one. (2) The developed seismic margin-risk diagram facilitates us to judge easily whether we need to perform detailed probabilistic risk analysis or only deterministic analysis, given that the reference risk level although information on the uncertainty parameter beta is not obtained. (3) We have performed numerical simulations based on the developed method for four sites in Japan. The structural capacity-risk diagram differs depending on each location because the diagram is greatly influenced by seismic hazard information for a target site. Furthermore, the required structural capacity

Development and Application of an Evaluation Method for the Supporting Structure

International Nuclear Information System (INIS)

Lee, Young Ho; Lee, Kang Hee; Kim, Jae Yong; Yoon, Kyung Ho; Kim, Hyung Kyu

2009-01-01

A dual cooled fuel (i.e. annular fuel) has both internal and external cooling which would allow a substantial increase in power density and safety margins compared to a solid fuel in operating PWR plants. When considering the sufficient cross-sectional area of the internal cooling channel and an acceptable amount of fuel pellet, the diameter of an outer tube should be increased for applying the compatible design concept of the dual cooled fuel to current operating PWRs. However, this results in a narrow gap between a dual cooled fuel rod and its supporting structure due to a fixed fuel assembly size. As all the fuel rods should be supported with safety and reliability for operating periods, any kinds of supporting structures should be installed in a dual cooled fuel assembly. Consequently, the positions of supporting structures around the dual cooled fuel rod should be modified from the rod-to-rod center to subchannel regions of grid structure and their shapes are designed and improved based on the advantages of current spacer grid technologies. Even though the vibration characteristics of the dual cooled fuel rod itself were not systematically evaluated, the characteristics of designed supporting structures and their wear resistances should be evaluated at the initial development stage. In this study, the evaluation method for the characteristics of designed supporting structures is developed by using a new test rig and compared with the analytical results. The final objective is to develop the evaluation method of their fretting wear resistances which accommodates the various shape of supporting structures without actual Zirconium supporting structures

Students' Development of Structure Sense for the Distributive Law

Science.gov (United States)

Schüler-Meyer, Alexander

2017-01-01

After being introduced to the distributive law in meaningful contexts, students need to extend its scope of application to unfamiliar expressions. In this article, a process model for the development of structure sense is developed. Building on this model, this article reports on a design research project in which exercise tasks support students…

Development of Additive Construction Technologies for Application to Development of Lunar/Martian Surface Structures Using In-Situ Materials

Science.gov (United States)

Werkheiser, Niki J.; Fiske, Michael R.; Edmunson, Jennifer E.; Khoshnevis, Berokh

2015-01-01

For long-duration missions on other planetary bodies, the use of in situ materials will become increasingly critical. As human presence on these bodies expands, so must the breadth of the structures required to accommodate them including habitats, laboratories, berms, radiation shielding for natural radiation and surface reactors, garages, solar storm shelters, greenhouses, etc. Planetary surface structure manufacturing and assembly technologies that incorporate in situ resources provide options for autonomous, affordable, pre-positioned environments with radiation shielding features and protection from micrometeorites, exhaust plume debris, and other hazards. The ability to use in-situ materials to construct these structures will provide a benefit in the reduction of up-mass that would otherwise make long-term Moon or Mars structures cost prohibitive. The ability to fabricate structures in situ brings with it the ability to repair these structures, which allows for the self-sufficiency and sustainability necessary for long-duration habitation. Previously, under the auspices of the MSFC In-Situ Fabrication and Repair (ISFR) project and more recently, under the jointly-managed MSFC/KSC Additive Construction with Mobile Emplacement (ACME) project, the MSFC Surface Structures Group has been developing materials and construction technologies to support future planetary habitats with in-situ resources. One such additive construction technology is known as Contour Crafting. This paper presents the results to date of these efforts, including development of novel nozzle concepts for advanced layer deposition using this process. Conceived initially for rapid development of cementitious structures on Earth, it also lends itself exceptionally well to the automated fabrication of planetary surface structures using minimally processed regolith as aggregate, and binders developed from in situ materials as well. This process has been used successfully in the fabrication of

Deepening structural reform, and speeding up self-reliant nuclear power development

International Nuclear Information System (INIS)

Wang Binghua

2010-01-01

Combining the implementation practices of the strategy on self-reliant development of the third generation nuclear power plant, the paper set forth that speeding up self-reliant nuclear power development has strategic significance to the national economy and the people's livelihood, which need further deepening structural reform and nuclear power structural reform with an aim to enhance the international competitiveness of China's nuclear industry. (author)

Development of Human Brain Structural Networks Through Infancy and Childhood

Science.gov (United States)

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-01-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

Development of a Structural Model for Tourism Destination Competitiveness from Stakeholders' Perspectives

OpenAIRE

Yoon, Yooshik

2002-01-01

This study was conducted to theoretically develop and empirically test a structural equation model of tourism destination competitiveness from the tourism stakeholders'perspective. The proposed hypotheses that attempted to identify the structural relationships among the five constructs in the model were examined through a series of analyses in LISREL: 1) perceived tourism development impacts, 2) environmental attitudes, 3) place attachment, 4) development preferences about destination attract...

Regional Institutional Structure in the Context of Innovative Industry Development

Directory of Open Access Journals (Sweden)

Anastasia Y. Nikitaeva

2017-03-01

Full Text Available The paper proves that successful innovation-oriented development of the industrial complex of the region can be ensured through the creation of adequate institutional structure. As a theoretical and conceptual platform for this task the use of regional institutionalism is suggested. It is reasoned that integration component plays an important role in providing of the innovative development of the industry in modern economic realities and the potential effects of integration on meso- and micro-levels of economy are provided. Integration of industrial structures potential at the same time assumes expansion of a partner segment of the entities relations in the market environment on the basis of network, cluster, and integration approaches convergence to management in the industrial development. On the basis of the international experience analysis it is illustrated that forming of multichannel partnership of actors in the industrial sphere with a vector on an innovatization requires creation of the corresponding institutional conditions. It is established that the main objectives of the relevant institutes consist in legitimization of various forms and technologies of partnership and stimulation of economic entities interactions. The first problem is solved by means of legal support of integration and partners’ interactions, the second one - with the use of a program and project approach. The basic structural elements and functional areas of regional institutional structure in the context of innovative industry development are determined. It is shown that the institutions of the partnership and monitoring of the obligations implementation by integration formations participants can have formal and informal nature, at the same time the trust institution is especially important. In work significant influence of regional specifics on institutional structure and integration of economic entities is proved.

Development of inter digital transducers to the control structures

International Nuclear Information System (INIS)

Takpara, R.; Fall, D.; Duquennoy, M.; Ouaftouh, M.; Courtois, C.; Rguiti, M.; Gonon, M.; Maurye, N.; Martic, G.; Lardot, V.; Seronveaux, L.; Halleux, J.; Pelegris, C.; Guessasma, M.

2015-01-01

This work deals with the realization of interdigital transducers (IDT) in order to characterize the quality of coatings and surfaces of structures. The challenge of this study is three fold. Firstly, the aim is to have efficient sensors to generate surface acoustic wave (SAW) since these wave sare well suited for this type of characterization. The second objective ofthis study is to provide flexible sensors so that they can adapt to different shapes of structures. Finally, relatively inexpensive technologies are favored for the development of these sensors because this allows continuous monitoring (structural health monitoring) by incorporating these sensors permanently on the structures to be tested. To meet these goals, several French and Belgian laboratories have gathered around the PRISTIFLEX project INTERREG IV. After a presentation of the manufacturing process and the characteristics of the piezo electric material developed in this study, we discussed modeling which helped to define the dimensional parameters of the piezo electric plate that composes the sensor. Then, the techniques for producing the electrodes (laserablation and inkjet printing) were presented and an example of performed electrode was provided. Finally, the effectiveness of these sensors from the measurement of the displacement caused by the surface wave excited by these IDT sensors were demonstrated. (author)

THE DEVELOPMENT OF SELF STRUCTURES AND ACTIVE COPING

Directory of Open Access Journals (Sweden)

J. Knežević

2016-03-01

Full Text Available In addition to cope with usual stressful circumstances at work, nowadays, it is important to examine what kind of mental capacities of medical staff are adaptive in respect of a new type of stress – job insecurity. Special focus is put upon self structures as personality determinants and the role they have in coping.. The aim of the study was to determine the role of the self structures in active coping with job insecurity. It was supposed that the increasing integration of self structures leads to increasing use of active coping strategies. Perceived job insecurity was measured by The job insecurity perception scale (Knežević and Majstorović, 2013. The Ego Functioning Questionnaire (Majstorović, Legault and Green-Demers, 2008 was used to evaluate types of ego-functioning; coping were assessed by the Cybernetic coping scale (Edwards and Baglioni, 1993. In order to test the hypothesis the multivariate regression analysis was developed with self-regulation as predictor and active coping strategy as a criterion. A significant model F(3, 306 = 26,73, p < 0,001, was obtained with all the predictors selected as significant. The prediction directions were as expected - Integrated and Ego-investing self were positive predictors (β = 0,35, p < 0,001, and β = 0,16, p < 0,01, respectively, while the impersonal self singled out as a negative predictor (β = –0,13, p < 0,05. The results have shown that the development of self structures is valid predictor for the active coping of medical staff when facing with job insecurity.

Theoretical development of atomic structure: Past, present and future

International Nuclear Information System (INIS)

Tiwary, S.N.

1994-11-01

Theoretical development of atomic structure is briefly discussed. The role of correlation, relativity, quantum electrodynamic (QED), finite nuclear size (FNS) and parity nonconservation (PNC) in high precision theoretical investigation of properties of atomic and ionic systems is demonstrated. At present, we do not have a comprehensive and practical atomic structure theory which accounts all these physical effects on an equal footing. Suggestions are made for future directions. (author). 108 refs, 5 figs, 9 tabs

Prefabricated elements and structures: Developments, tests and experiences

DEFF Research Database (Denmark)

Goltermann, Per

2014-01-01

Danish concrete structures are often built with prefabricated elements, joined together on the site and this provides a large challenge to constantly improve and optimize the elements, the joints and the models. DTU Byg has been active in the development, testing and modelling of new elements...

Horticultural marketing channels in Kenya : structure and development

NARCIS (Netherlands)

Dijkstra, T.

1997-01-01

This study analyses the structure and development of horticultural marketing channels in Kenya. It is based primarily on a farm survey among some 500 farmers in Nyandarua, Kisii and Taita Taveta Districts and a trade survey of about 750 horticultural traders in 18 different market places.

Development Directions for Various Types of the Light Wood-Framed Structures

Science.gov (United States)

Malesza, J.; Baszeń, M.; Miedziałowski, Cz

2017-11-01

The paper presents current trends in the development of the wood-framed structures. Authors describe the evolution of the technology of implementation, the production process of precast elements of buildings as well as selected realization on the site of these kinds of structures. The attention has been paid to the effect of implementation phases on construction and erecting technology of the wood-framed structures. The paper draws attention to the importance and enhancement of structural analysis of structures in individual phases of building realization.

Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?

Directory of Open Access Journals (Sweden)

Sofia Mikkelsen Berg

2017-03-01

Full Text Available Carnitine acetyltransferase (CRAT deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16 and octadecanoylcarnitine (C18 were slightly reduced in myotubes derived from T2DM patients (p<0.05 compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

High Field Studies for CLIC Accelerating Structures Development

CERN Document Server

Profatilova, I

2017-01-01

Compact Linear Collider RF structures need to be able to achieve the very high average accelerating gradient of 100 MV/m. One of the main challenges in reaching such high accelerating gradients is to avoid vacuum electrical breakdown within CLIC accelerating structures. Accelerating structure tests are carried out in the klystron-based test stands known as the XBoxes. In order to investigate vacuum breakdown phenomena and its statistical characteristics in a simpler system and get results in a faster way, pulsed dc systems have been developed at CERN. To acquire sufficient breakdown data in a reasonable period of time, high repetition rate pulse generators are used in the systems for breakdown studies, so-called pulsed dc system. This paper describes the pulsed dc systems and the two high repetition rate circuits, which produce high-voltage pulses for it, available at CERN.

Research and development on materials, structural strength and seismic integrity of FBR components

International Nuclear Information System (INIS)

Sumikawa, Masaharu; Kirihara, Seishin; Shigeta, Masayuki; Shimoyashiki, Shigehiro; Nishioka, Akio.

1982-01-01

For designing high temperature structures of FBRs, highly reliable design is required on the basis of safety requirement. At the same time, it is necessary to guarantee the soundness of structures over the total design life of plants. Since the high temperature equipments are operated in a creep temperature region and show nonlinear behaviour, nonlinear structural analysis is required. Hitachi Ltd., based on the concept of verifying the latest technology to reflect it to the design along with its adoption, has progressed various research and development by organizing a project team collecting specialists in the company, independently developing and modifying the nonlinear structural analysis and evaluation program, and establishing the organization through the introduction of a general purpose large scale computer. The research and development for materials include the development of the strength standards for high temperature structural materials and the improvement of the high temperature characteristics of JIS stainless steel SUS 321. In the R and D for high temperature strength, the test on the deforming behaviour of plates due to bending creep, the thermal shock test for steam generator tube plates and others were performed. In the R and D for seismic integrity, the vibration test of piping support structure and the development of detailed seismic property evaluation program are mentioned. (Wakatsuki, Y.)

Patterns of structural - qualitative changes in the development of complex systems

OpenAIRE

S Holtier

1992-01-01

This paper is an attempt to outline, in an emancipatory fashion, a framework of thinking to deal with the general patterns of development. As decision problems in society are increasingly of a developmental nature compared with simple performance in equilibrium systems, the author pleads in favour of an operational approach centred on 'the algebra' of structural change. It is argued that for describing and understanding development patterns better we need a proper 'structural' and 'ontologica...

Development of Cranial Bone Surrogate Structures Using Stereolithographic Additive Manufacturing

Science.gov (United States)

2017-09-29

Additive Manufacturing by Jared M Gardner and Thomas A Plaisted Approved for public release; distribution is unlimited...Laboratory Development of Cranial Bone Surrogate Structures Using Stereolithographic Additive Manufacturing by Thomas A Plaisted Weapons...Structures Using Stereolithographic Additive Manufacturing 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jared

Development of structural materials on the base of new technology

International Nuclear Information System (INIS)

Belov, A.F.; Anoshkin, N.F.

1982-01-01

Some results are considered and possibilities which discovered in development of structural materials connected with development of such new technological processes as skull melting of titanium alloys, granule metallurgy, hot isostatic, diffusion welding are estimated. The method of skull melting with remelted skull is developed. The method assures sufficient possibilities for dissolving of high-heat components of charge and obtaining homogeneous ingots of series of new alloys. Granule metallurgy based on crystallization of the metal with high rate in the form of small (up to 300 μkm) particles and subsequent consolidation of them into compact billet discoveres a wide possibilities of creation of new structural material with more high operation indexes. It is noted that developed processes of granule production, their treatment, compacting and thermal treatment of the billets assure production of metal of high quality, satisfied the strong requirements of present standards. The process of hot isostatic pressing at which the workable metal is subjected to through uniform pressure by compressed gas after heating or semultaneously with its heating up to the temperatures of working in gasostats is one of new technological processes. A certain experience of the HIP use for production of compact billets from granules for diffusion welding of the billets is accumulated. This process has a great possibilities for densification of shaped castings. Investigation and application of the diffusion welding represent combination of elements into details of complex form in vacuum at the temperatures low of melting point under effect of small pressures are investigated both in our country and abroad. Diffusion welding gives a wide possibilities in the development of materials with higher properties at the expence of production of products of large dimensions from thin elements with fine-grained structure as well as products with assigned gradient of chemical composition, structure

Development of human brain structural networks through infancy and childhood.

Science.gov (United States)

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-05-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

ANL-1(A) - Development of nondestructive evaluation methods for structural ceramics

International Nuclear Information System (INIS)

Ellingson, W.A.; Roberts, R.A.; Gopalsami, N.; Dieckman, S.; Hentea, T.; Vaitekunas, J.J.

1989-01-01

This section includes the following papers: Development of Nondestructive Evaluation Methods for Structural Ceramics; Effects of Flaws on the Fracture Behavior of Structural Ceramics; Design, Fabrication, and Interface Characterization of Ceramic Fiber-Ceramic Matrix Composites; Development of Advanced Fiber-Reinforced Ceramics; Modeling of Fibrous Preforms for CVD Infiltration; NDT of Advanced Ceramic Composite Materials; Joining of Silicon Carbide Reinforced Ceramics; Superconducting Film Fabrication Research; Short Fiber Reinforced Structural Ceramics; Structural Reliability and Damage Tolerance of Ceramic Composites for High-Temperature Applications; Fabrication of Ceramic Fiber-Ceramic Matrix Composites by Chemical Vapor Infiltration; Characterization of Fiber-CVD Matrix interfacial Bonds; Microwave Sintering of Superconducting Ceramics; Improved Ceramic Composites Through Controlled Fiber-Matrix Interactions; Evaluation of Candidate Materials for Solid Oxide Fuel Cells; Ceramic Catalyst Materials: Hydrous Metal Oxide Ion-Exchange Supports for Coal Liquefaction; and Investigation of Properties and Performance of Ceramic Composite Components

Development of a national code of practice for structural masonry ...

African Journals Online (AJOL)

The problems and constraints faced by most developing countries, particularly Ghana, in developing codes of practice for structural masonry are highlighted. The steps that must be undertaken through the coordinated efforts of the National Standards Boards, Research Institutions, Universities and Professional Bodies in the ...

New types of organizational structures of accounting departments and their development

OpenAIRE

Шигун, Марія Михайлівна

2015-01-01

Development directions of new types of organizational structures of accounting departments, emergence of which has been caused by present-day conditions of keeping economics relationships, have been researched, as well as peculiarity of complex hierarchical and adaptive structures has been disclosed.

Recent developments of discrete material optimization of laminated composite structures

DEFF Research Database (Denmark)

Lund, Erik; Sørensen, Rene

2015-01-01

This work will give a quick summary of recent developments of the Discrete Material Optimization approach for structural optimization of laminated composite structures. This approach can be seen as a multi-material topology optimization approach for selecting the best ply material and number...... of plies in a laminated composite structure. The conceptual combinatorial design problem is relaxed to a continuous problem such that well-established gradient based optimization techniques can be applied, and the optimization problem is solved on basis of interpolation schemes with penalization...

Family Structure Experiences and Child Socioemotional Development During the First Nine Years of Life: Examining Heterogeneity by Family Structure at Birth

Science.gov (United States)

Berger, Lawrence M.

2018-01-01

A vast amount of literature has documented negative associations between family instability and child development, with the largest associations being in the socioemotional (behavioral) domain. Yet, prior work has paid limited attention to differentiating the role of the number, types, and sequencing of family transitions that children experience, as well as to understanding potential heterogeneity in these associations by family structure at birth. We use data from the Fragile Families and Child Wellbeing Study and hierarchical linear models to examine associations of family structure states and transitions with children’s socioemotional development during the first nine years of life. We pay close attention to the type and number of family structure transitions experienced and examine whether associations differ depending on family structure at birth. For children born to cohabiting or noncoresident parents, we find little evidence that subsequent family structure experiences are associated with socioemotional development. For children born to married parents, we find associations between family instability and poorer socioemotional development. However, this largely reflects the influence of parental breakup; we find little evidence that socioemotional trajectories differ for children with various family structure experiences subsequent to their parents’ breakup. PMID:28299560

Family Structure Experiences and Child Socioemotional Development During the First Nine Years of Life: Examining Heterogeneity by Family Structure at Birth.

Science.gov (United States)

Bzostek, Sharon H; Berger, Lawrence M

2017-04-01

A vast amount of literature has documented negative associations between family instability and child development, with the largest associations being in the socioemotional (behavioral) domain. Yet, prior work has paid limited attention to differentiating the role of the number, types, and sequencing of family transitions that children experience, as well as to understanding potential heterogeneity in these associations by family structure at birth. We use data from the Fragile Families and Child Wellbeing Study and hierarchical linear models to examine associations of family structure states and transitions with children's socioemotional development during the first nine years of life. We pay close attention to the type and number of family structure transitions experienced and examine whether associations differ depending on family structure at birth. For children born to cohabiting or noncoresident parents, we find little evidence that subsequent family structure experiences are associated with socioemotional development. For children born to married parents, we find associations between family instability and poorer socioemotional development. However, this largely reflects the influence of parental breakup; we find little evidence that socioemotional trajectories differ for children with various family structure experiences subsequent to their parents' breakup.

Development priorities for non-destructive examination of concrete structures in nuclear plant

International Nuclear Information System (INIS)

1998-01-01

The objective of this report is to provide a basis for assessing development priorities for NDE of safety related concrete structures in nuclear plants, taking account of both the benefit and the cost of potential developments in NDE techniques. An OECD/NEA Workshop which considered the requirements for NDE of safety related concrete structures was held in the UK on 12 November 97. NDE techniques have the potential to satisfy at least some of the needs of the nuclear industry. NDE techniques have been used successfully on a variety of reinforced and post-tensioned concrete structures, notably highway and reservoir structures. However, there is limited experience of their use to evaluate typical nuclear safety related structures having thick sections, steel liners or access to one side only. There is a general lack of confidence in the techniques because there is very little independent advice on their applicability, capability, accuracy and reliability. The information obtained by techniques such as RADAR, ultrasonics, stress wave and radiography appears qualitative rather than quantitative and there is concern that NDE procedures lack the necessary qualification to permit their use on safety critical structures. There is no authoritative international guidance or standard for NDE of concrete structures. NDE of concrete structures is often based upon equipment developed for other materials and technologies, eg. examination of steel, evaluation of ground conditions. Other industries are developing equipment specifically for civil engineering applications and at the recent OECD workshop a number of relevant national and European programmes were identified. The nuclear industry maintain its awareness of developments and should seek to influence the development of equipment. The quantification of the capabilities of NDE techniques is seen as a priority area for development. The provision of authoritative documentation in the form of reports and Standards is desirable

Research, development and application of noncombustible Beta fiber structures. [for Apollo

Science.gov (United States)

Dillon, J. J.; Cobb, E. S.

1975-01-01

Beta fiber was selected as the primary material for flexible fibrous structures used in spacecraft and crew systems applications in the Apollo program because it was noncombustible in a 100 percent oxygen atmosphere up to 16.5 psia. It met NASA criteria for outgassing, toxicity, odor, and crew comfort, and possessed sufficient durability to last through the mission. Topics discussed include: study of spacecraft applications; design of Beta fiber textile structures to meet the requirements; selection of surface treatments (finishes, coatings, and printing systems) to impart the required durability and special functional use to the textile structures; development of sewing and fabrication techniques; and testing and evaluation programs, and development of production sources.

Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes

Science.gov (United States)

White, Jennifer; Barro, Marietta V.; Makarenkova, Helen P.; Sanger, Joseph W.; Sanger, Jean M.

2014-01-01

It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, non-muscle myosin II, muscle myosin II, and α-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that non-muscle myosins II A and B are components of the Z-Bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-Bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. PMID:25125171

Development of an active structure flight experiment

Science.gov (United States)

Manning, R. A.; Wyse, R. E.; Schubert, S. R.

1993-02-01

The design and development of the Air Force and TRW's Advanced Control Technology Experiment (ACTEX) flight experiment is described in this paper. The overall objective of ACTEX is to provide an active structure trailblazer which will demonstrate the compatibility of active structures with operational spacecraft performance and lifetime measures. At the heart of the experiment is an active tripod driven by a digitally-programmable analog control electronics subsystem. Piezoceramic sensors and actuators embedded in a graphite epoxy host material provide the sensing and actuation mechanism for the active tripod. Low noise ground-programmable electronics provide a virtually unlimited number of control schemes that can be implemented in the space environment. The flight experiment program provides the opportunity to gather performance, reliability, adaptability, and lifetime performance data on vibration suppression hardware for the next generation of DoD and NASA spacecraft.

Extracellular matrix organization in developing muscle: correlation with acetylcholine receptor aggregates.

Science.gov (United States)

Bayne, E K; Anderson, M J; Fambrough, D M

1984-10-01

Monoclonal antibodies recognizing laminin, heparan sulfate proteoglycan, fibronectin, and two apparently novel connective tissue components have been used to examine the organization of extracellular matrix of skeletal muscle in vivo and in vitro. Four of the five monoclonal antibodies are described for the first time here. Immunocytochemical experiments with frozen-sectioned muscle demonstrated that both the heparan sulfate proteoglycan and laminin exhibited staining patterns identical to that expected for components of the basal lamina. In contrast, the remaining matrix constituents were detected in all regions of muscle connective tissue: the endomysium, perimysium, and epimysium. Embryonic muscle cells developing in culture elaborated an extracellular matrix, each antigen exhibiting a unique distribution. Of particular interest was the organization of extracellular matrix on myotubes: the build-up of matrix components was most apparent in plaques overlying clusters of an integral membrane protein, the acetylcholine receptor (AChR). The heparan sulfate proteoglycan was concentrated at virtually all AChR clusters and showed a remarkable level of congruence with receptor organization; laminin was detected at 70-95% of AChR clusters but often was not completely co-distributed with AChR within the cluster; fibronectin and the two other extracellular matrix antigens occurred at approximately 20, 8, and 2% of the AChR clusters, respectively, and showed little or no congruence with AChR. From observations on the distribution of extracellular matrix components in tissue cultured fibroblasts and myogenic cells, several ideas about the organization of extracellular matrix are suggested. (a) Congruence between AChR clusters and heparan sulfate proteoglycan suggests the existence of some linkage between the two molecules, possibly important for regulation of AChR distribution within the muscle membrane. (b) The qualitatively different patterns of extracellular matrix

Development of laboratory acceleration test method for service life prediction of concrete structures

International Nuclear Information System (INIS)

Cho, M. S.; Song, Y. C.; Bang, K. S.; Lee, J. S.; Kim, D. K.

1999-01-01

Service life prediction of nuclear power plants depends on the application of history of structures, field inspection and test, the development of laboratory acceleration tests, their analysis method and predictive model. In this study, laboratory acceleration test method for service life prediction of concrete structures and application of experimental test results are introduced. This study is concerned with environmental condition of concrete structures and is to develop the acceleration test method for durability factors of concrete structures e.g. carbonation, sulfate attack, freeze-thaw cycles and shrinkage-expansion etc

Lipid content and response to insulin are not invariably linked in human muscle cells

OpenAIRE

Aguer , Céline; Mercier , Jacques; Kitzmann , Magali

2009-01-01

Abstract In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a signif...

CURRENT TRENDS FOR DEVELOPMENT AND IMPROVEMENT OF THE ORGANIZATIONAL STRUCTURES IN MANAGEMENT

Directory of Open Access Journals (Sweden)

Angel Doraliyski

2017-03-01

Full Text Available One of the key components of the management system is the organizational structure of management. This report presents the current trends of development and improvement of organizational structures of management. The semantics of the term "organizational structure" used in the report is clarified. Key aspects of structural policy of organizations are discussed, as well as the introduction of flexible organizational forms. The main directions for analysis of organizational policy of organizations are also mentioned. It is stressed that the analysis of current trends for the future development of organizational structures of management should be an integral component of the management policy of every organization. The trends are flexibility and adaptability of the organizational structure, rational proportion between centralization and decentralization, an appropriate balance between the rights, duties and responsibilities, reducing regulations, rules and other normative documents. A recommendetaion is made that organizational governance structures must be adapted constantly in accordance with changes in the overall management system, as they are one of its main components.

Definition of technology development missions for early space stations: Large space structures

Science.gov (United States)

Gates, R. M.; Reid, G.

1984-01-01

The objectives studied are the definition of the tested role of an early Space Station for the construction of large space structures. This is accomplished by defining the LSS technology development missions (TDMs) identified in phase 1. Design and operations trade studies are used to identify the best structural concepts and procedures for each TDMs. Details of the TDM designs are then developed along with their operational requirements. Space Station resources required for each mission, both human and physical, are identified. The costs and development schedules for the TDMs provide an indication of the programs needed to develop these missions.

Development of expert system for structural design of FBR components

International Nuclear Information System (INIS)

Ueda, Hiroyoshi; Uno, Masayoshi; Ogawa, Hiroshi; Shimakawa, Takashi; Yoshimura, Shinobu; Yagawa, Genki.

1995-01-01

The characteristics of structural design processes for nuclear components can be summarized as follows : (1) Many engineers belonging to different fields are working in parallel, exchanging a huge amount of data and information. (2) A final solution is determined after a number of iterative design processes. (3) Solutions have to be examined many times based on sophisticated design codes. (4) Sophisticated calculation methods such as the finite element method are frequently utilized, and experts' knowledge on such analyses plays important roles in the design process. Taking these issues into consideration, a new expert system for structural design is developed in the present study. Here, the object-oriented data flow mechanism and the blackboard model are utilized to systematize structural design processes in a computer. An automated finite element calculation module is implemented, and experts' knowledge is stored in knowledge base. In addition, a new algorithm is employed to automatically draw the design window, which is defined as an area of permissible solutions in a design parameter space. The developed system is successfully applied to obtain the design windows of four components selected from the demonstration FBR structures. (author)

DEVELOPMENT OF STRUCTURES FROM SOLID WOOD FOR OBJECTS OF INFRASTRUCTURE

Directory of Open Access Journals (Sweden)

Konstantin P. Pyatikrestovsky

2018-03-01

Full Text Available New prefabricated lightweight structures made of solid wood with connections for joining and building metal screws for wood are proposed. Manufacture and assembly of basic elements-bars with a cross-section of 15x15 cm can be carried out in line conditions on the simplest woodworking equipment. The use of local tim-ber material has a number of advantages (ecological, economic and operational. The description of structures with manufacturing process, examples of buildings with vaulted and hipped roofing, connection arrangement, preparation of experimental samples with the use of new equipment of the National Research Moscow State University of Civil Engineering are given. The method of analysis with allowance for plastic deformations is under consideration. It provides additional economic advantages. The analysis is carried out by the method of integral estimates developed by Prof. V.M. Bondarenko for reinforced concrete structures and adapted to wooden structures by Prof. K.P. Pyatikrestovsky. Special strength criteria are used for the analysis of decks working together with the ribs (in a combined stressed state. It is planned to build buildings for various purposes in the ar-eas of development of the Far North of Russia.

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots.

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Anje Sporbert

Full Text Available This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts.

The primate fovea: Structure, function and development.

Science.gov (United States)

Bringmann, Andreas; Syrbe, Steffen; Görner, Katja; Kacza, Johannes; Francke, Mike; Wiedemann, Peter; Reichenbach, Andreas

2018-03-30

A fovea is a pitted invagination in the inner retinal tissue (fovea interna) that overlies an area of photoreceptors specialized for high acuity vision (fovea externa). Although the shape of the vertebrate fovea varies considerably among the species, there are two basic types. The retina of many predatory fish, reptilians, and birds possess one (or two) convexiclivate fovea(s), while the retina of higher primates contains a concaviclivate fovea. By refraction of the incoming light, the convexiclivate fovea may function as image enlarger, focus indicator, and movement detector. By centrifugal displacement of the inner retinal layers, which increases the transparency of the central foveal tissue (the foveola), the primate fovea interna improves the quality of the image received by the central photoreceptors. In this review, we summarize ‒ with the focus on Müller cells of the human and macaque fovea ‒ data regarding the structure of the primate fovea, discuss various aspects of the optical function of the fovea, and propose a model of foveal development. The "Müller cell cone" of the foveola comprises specialized Müller cells which do not support neuronal activity but may serve optical and structural functions. In addition to the "Müller cell cone", structural stabilization of the foveal morphology may be provided by the 'z-shaped' Müller cells of the fovea walls, via exerting tractional forces onto Henle fibers. The spatial distribution of glial fibrillary acidic protein may suggest that the foveola and the Henle fiber layer are subjects to mechanical stress. During development, the foveal pit is proposed to be formed by a vertical contraction of the centralmost Müller cells. After widening of the foveal pit likely mediated by retracting astrocytes, Henle fibers are formed by horizontal contraction of Müller cell processes in the outer plexiform layer and the centripetal displacement of photoreceptors. A better understanding of the molecular, cellular

In vitro myogenesis induced by human recombinant elastin-like proteins.

Science.gov (United States)

D'Andrea, Paola; Scaini, Denis; Ulloa Severino, Luisa; Borelli, Violetta; Passamonti, Sabina; Lorenzon, Paola; Bandiera, Antonella

2015-10-01

Mammalian adult skeletal muscle has a limited ability to regenerate after injury, usage or trauma. A promising strategy for successful regenerative technology is the engineering of bio interfaces that mimic the characteristics of the extracellular matrix. Human elastin-like polypeptides (HELPs) have been synthesized as biomimetic materials that maintain some peculiar properties of the native protein. We developed a novel Human Elastin Like Polypeptide obtained by fusing the elastin-like backbone to a domain present in the α2 chain of type IV collagen, containing two RGD motives. We employed this peptide as adhesion substrate for C2C12 myoblasts and compared its effects to those induced by two other polypeptides of the HELP series. Myoblast adhered to all HELPs coatings, where they assumed morphology and cytoarchitecture that depended on the polypeptide structure. Adhesion to HELPs stimulated at a different extent cell proliferation and differentiation, the expression of Myosin Heavy Chain and the fusion of aligned fibers into multinucleated myotubes. Adhesion substrates significantly altered myotubes stiffness, measured by Atomic Force Microscopy, and differently affected the cells Ca(2+) handling capacity and the maturation of excitation-contraction coupling machinery, evaluated by Ca(2+) imaging. Overall, our findings indicate that the properties of HELP biopolymers can be exploited for dissecting the molecular connections underlying myogenic differentiation and for designing novel substrates for skeletal muscle regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Muscle and neural isoforms of agrin increase utrophin expression in cultured myotubes via a transcriptional regulatory mechanism.

Science.gov (United States)

Gramolini, A O; Burton, E A; Tinsley, J M; Ferns, M J; Cartaud, A; Cartaud, J; Davies, K E; Lunde, J A; Jasmin, B J

1998-01-09

Duchenne muscular dystrophy is a prevalent X-linked neuromuscular disease for which there is currently no cure. Recently, it was demonstrated in a transgenic mouse model that utrophin could functionally compensate for the lack of dystrophin and alleviate the muscle pathology (Tinsley, J. M., Potter, A. C., Phelps, S. R., Fisher, R., Trickett, J. I., and Davies, K. E. (1996) Nature 384, 349-353). In this context, it thus becomes essential to determine the cellular and molecular mechanisms presiding over utrophin expression in attempts to overexpress the endogenous gene product throughout skeletal muscle fibers. In a recent study, we showed that the nerve exerts a profound influence on utrophin gene expression and postulated that nerve-derived trophic factors mediate the local transcriptional activation of the utrophin gene within nuclei located in the postsynaptic sarcoplasm (Gramolini, A. O., Dennis, C. L., Tinsley, J. M., Robertson, G. S., Davies, K. E, Cartaud, J., and Jasmin, B. J. (1997) J. Biol. Chem. 272, 8117-8120). In the present study, we have therefore focused on the effect of agrin on utrophin expression in cultured C2 myotubes. In response to Torpedo-, muscle-, or nerve-derived agrin, we observed a significant 2-fold increase in utrophin mRNAs. By contrast, CGRP treatment failed to affect expression of utrophin transcripts. Western blotting experiments also revealed that the increase in utrophin mRNAs was accompanied by an increase in the levels of utrophin. To determine whether these changes were caused by parallel increases in the transcriptional activity of the utrophin gene, we transfected muscle cells with a 1. 3-kilobase pair utrophin promoter-reporter (nlsLacZ) gene construct and treated them with agrin for 24-48 h. Under these conditions, both muscle- and nerve-derived agrin increased the activity of beta-galactosidase, indicating that agrin treatment led, directly or indirectly, to the transcriptional activation of the utrophin gene

Development of Structural Health Monitoring System for pipes in Nuclear Power Plants

International Nuclear Information System (INIS)

Eom, H. S.; Choi, Y. C.; Shin, S. H.; Youn, D. B.; Park, J. H.

2010-01-01

Structural health monitoring (SHM) has becoming an important issue in the maintenance of various structures such as large steel plates, vessels, and pipes in nuclear power plants. There are important factors to be considered in developing an SHM system. With consideration of these factors, we have developed a computerized multi-channel ultrasonic system that can handle array transducers and generate a high-power pulse for online SHM of the plates and pipes. The proposed system is compact but has all the necessary functions for SHM of important structure such as pipes and plates in a NPP

Development of a structural model for the nonlinear shear deformation behavior of a seismic isolator

International Nuclear Information System (INIS)

Lee, Jae Han; Koo, Gyeong Hoi; Yoo, Bong

2002-02-01

The seismic excitation test results of an isolated test structure for artificial time history excitation are summarized for structure models of the isolated structure and isolation bearing. To simulate the response characteristic of isolated structure, shear hysteresis curves of isolators are analyzed. A simple analysis model is developed representing the actual dynamic behaviors of the test model, and the seismic responses using the simple model of the isolated structure and structure models, which are developed such as linear and bilinear models for isolators, are performed and compared with those of the seismic tests. The developed bilinear model is well applicable only to large shear strain area of LLRB

Deciphering structural and temporal interplays during the architectural development of mango trees.

Science.gov (United States)

Dambreville, Anaëlle; Lauri, Pierre-Éric; Trottier, Catherine; Guédon, Yann; Normand, Frédéric

2013-05-01

Plant architecture is commonly defined by the adjacency of organs within the structure and their properties. Few studies consider the effect of endogenous temporal factors, namely phenological factors, on the establishment of plant architecture. This study hypothesized that, in addition to the effect of environmental factors, the observed plant architecture results from both endogenous structural and temporal components, and their interplays. Mango tree, which is characterized by strong phenological asynchronisms within and between trees and by repeated vegetative and reproductive flushes during a growing cycle, was chosen as a plant model. During two consecutive growing cycles, this study described vegetative and reproductive development of 20 trees submitted to the same environmental conditions. Four mango cultivars were considered to assess possible cultivar-specific patterns. Integrative vegetative and reproductive development models incorporating generalized linear models as components were built. These models described the occurrence, intensity, and timing of vegetative and reproductive development at the growth unit scale. This study showed significant interplays between structural and temporal components of plant architectural development at two temporal scales. Within a growing cycle, earliness of bud burst was highly and positively related to earliness of vegetative development and flowering. Between growing cycles, flowering growth units delayed vegetative development compared to growth units that did not flower. These interplays explained how vegetative and reproductive phenological asynchronisms within and between trees were generated and maintained. It is suggested that causation networks involving structural and temporal components may give rise to contrasted tree architectures.

PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

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Estibaliz Castillero

Full Text Available FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.

Some recent developments in the risk- and reliability analysis of structures

International Nuclear Information System (INIS)

Bauer, J.; Choi, H.S.; Kappler, H.; Melzer, H.J.; Panggabean, H.; Reichmann, K.H.; Schueller, G.I.; Schwarz, R.F.

1979-01-01

This report consists of six contributions divided into four general topics. While Part I concentrates on the development of Analytical Methods in Structural Reliability, Part II to IV are devoted to the application of these methods to Offshore-, Nuclear - and generally to Wind- and Earthquake Exposed Structures. (orig.) [de

Effect of space structures against development of transport infrastructure in Banda Aceh by using the concept of transit oriented development

Science.gov (United States)

Noer, Fadhly; Matondang, A. Rahim; Sirojuzilam, Saleh, Sofyan M.

2017-11-01

Due to the shifting of city urban development causing the shift of city services center, so there is a change in space pattern and space structure in Banda Aceh, then resulting urban sprawl which can lead to congestion problem occurs on the arterial road in Banda Aceh, it can be seen from the increasing number of vehicles per year by 6%. Another issue occurs by urban sprawl is not well organized of settlement due to the uncontrolled use of space so that caused grouping or the differences in socioeconomic strata that can impact to the complexity of population mobility problem. From this background problem considered to be solved by a concept that is Transit Oriented Development (TOD), that is a concept of transportation development in co-operation with spatial. This research will get the model of transportation infrastructure development with TOD concept that can handle transportation problem in Banda Aceh, due to change of spatial structure, and to find whether TOD concept can use for the area that has a population in medium density range. The result that is obtained equation so the space structure is: Space Structure = 0.520 + 0.206X3 + 0.264X6 + 0.100X7 and Transportation Infrastructure Development = -1.457 + 0.652X1 + 0.388X5 + 0.235X6 + 0.222X7 + 0.327X8, So results obtained with path analysis method obtained variable influences, node ratio, network connectivity, travel frequency, travel destination, travel cost, and travel time, it has a lower value when direct effect with transportation infrastructure development, but if the indirect effect through the structure of space has a greater influence, can be seen from spatial structure path scheme - transportation infrastructure development.

Financial structure, financial development and banking fragility: International evidence

OpenAIRE

Ruiz-Porras, Antonio

2008-01-01

We study the effects of financial structure and financial development on banking fragility. We develop our study by using fixed-effects panel-data regressions and by controlling the effects of certain banking indicators. We use individual and principal-components indicators of the activity, size and efficiency of intermediaries and markets. The indicators include data for 211 countries between 1990 and 2003. Our main findings suggest that banking stability is enhanced in market-based financia...

Integrated structural analysis tool using the linear matching method part 1 – Software development

International Nuclear Information System (INIS)

Ure, James; Chen, Haofeng; Tipping, David

2014-01-01

A number of direct methods based upon the Linear Matching Method (LMM) framework have been developed to address structural integrity issues for components subjected to cyclic thermal and mechanical load conditions. This paper presents a new integrated structural analysis tool using the LMM framework for the assessment of load carrying capacity, shakedown limit, ratchet limit and steady state cyclic response of structures. First, the development of the LMM for the evaluation of design limits in plasticity is introduced. Second, preliminary considerations for the development of the LMM into a tool which can be used on a regular basis by engineers are discussed. After the re-structuring of the LMM subroutines for multiple central processing unit (CPU) solution, the LMM software tool for the assessment of design limits in plasticity is implemented by developing an Abaqus CAE plug-in with graphical user interfaces. Further demonstration of this new LMM analysis tool including practical application and verification is presented in an accompanying paper. - Highlights: • A new structural analysis tool using the Linear Matching Method (LMM) is developed. • The software tool is able to evaluate the design limits in plasticity. • Able to assess limit load, shakedown, ratchet limit and steady state cyclic response. • Re-structuring of the LMM subroutines for multiple CPU solution is conducted. • The software tool is implemented by developing an Abaqus CAE plug-in with GUI

Innovative economic structures – support for development of urban systems

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Florin Marian Buhociu

2013-12-01

Full Text Available Training and development of urban systems (US is a main direction of territorial and regional development which requires multiple studies, including those of economic background. They should aim to highlight, on the one hand, the economic potential of geographical areas making up the urban system and secondly to assess development trends you need to focus their own resources and those that are to be attracted to getting a economic trend upward in that area. It is therefore very important a zonal configuration of the urban system by following the joint capitalization of existing human and material resources, including by building synergy effect to be achieved following the joint evolution of settlements in the US. Along with the development of US is required, from the economical point of view, to implement new forms of economic structures to directly potentate the development of the area through constant cooperation, innovation and transfer of know-how. Romania currently has seven major urban centers that were selected and were assigned the role of growth poles. There were also 13 designated urban growth poles, including Galati and Braila. Urban agglomeration formed by the two municipalities, located at a distance from each other of about 25 km, is the second largest in the country after Bucharest. There is currently underway specialized documentation to achieve an optimal configuration for US Galati-Braila. From the economic point of view in the respective area can be implemented new development structures of cluster (Porter, M.E.,2000 type aimed at achieving the competitiveness poles and which will constitute the true engine of economic development. These two new structures of economic development are characterized by the fact that they allow and provide the necessary conditions to attract the systems and modern technologies to build local innovation systems that can be integrated into similar systems at regional and even national level. It is

The Structural Engineering Strategy for Photonic Material Research and Device Development

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Yalin Lu

2007-01-01

Full Text Available A new structural engineering strategy is introduced for optimizing the fabrication of arrayed nanorod materials, optimizing superlattice structures for realizing a strong coupling, and directly developing nanophotonic devices. The strategy can be regarded as “combinatorial” because of the high efficiency in optimizing structures. In this article, this strategy was applied to grow ZnO nanorod arrays, and to develop a new multifunctional photodetector using such nanorod arrays, which is able to simultaneously detect power, energy, and polarization of an incident ultraviolet radiation. The strategy was also used to study the extraordinary dielectric behavior of relaxor ferroelectric lead titanate doped lead magnesium niobate heterophase superlattices in the terahertz frequencies, in order to investigate their dielectric polariton physics and the potential to be integrated with tunable surface resonant plasmonics devices.

Physical modeling of river spanning rock structures: Evaluating interstitial flow, local hydraulics, downstream scour development, and structure stability

Science.gov (United States)

Collins, K.L.; Thornton, C.I.; Mefford, B.; Holmquist-Johnson, C. L.

2009-01-01

Rock weir and ramp structures uniquely serve a necessary role in river management: to meet water deliveries in an ecologically sound manner. Uses include functioning as low head diversion dams, permitting fish passage, creating habitat diversity, and stabilizing stream banks and profiles. Existing information on design and performance of in-stream rock structures does not provide the guidance necessary to implement repeatable and sustainable construction and retrofit techniques. As widespread use of rock structures increases, the need for reliable design methods with a broad range of applicability at individual sites grows as well. Rigorous laboratory testing programs were implemented at the U.S. Bureau of Reclamation (Reclamation) and at Colorado State University (CSU) as part of a multifaceted research project focused on expanding the current knowledge base and developing design methods to improve the success rate of river spanning rock structures in meeting project goals. Physical modeling at Reclamation is being used to measure, predict, and reduce interstitial flow through rock ramps. CSU is using physical testing to quantify and predict scour development downstream of rock weirs and its impact on the stability of rock structures. ?? 2009 ASCE.

Using Learning Trajectories for Teacher Learning to Structure Professional Development

Science.gov (United States)

Bargagliotti, Anna E.; Anderson, Celia Rousseau

2017-01-01

As a result of the increased focus on data literacy and data science across the world, there has been a large demand for professional development in statistics. However, exactly how these professional development opportunities should be structured remains an open question. The purpose of this paper is to describe the first iteration of a design…

Postnatal development of collagen structure in ovine articular cartilage

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Kranenbarg Sander

2010-06-01

Full Text Available Abstract Background Articular cartilage (AC is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries as our model animal. Results Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure. Conclusions The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the

DEVELOPMENT OF THE STRUCTURAL MATRIX APPROACH IN ORGANIZATIONAL DIAGNOSTICS

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Mishlanova Marina Yur'evna

2012-07-01

The proposed approach discloses private constituents of elements, communications, organizational layers, generalized characteristics of layers, and partial effects. This approach may be used to simulate a system of forces, items of pressure, and organizational problems. The most advanced state of stability and sustainable development is now provided with the structure within which the elements remain in certain natural interdependence (symmetry, or balance. Formation of this model is based on thorough diagnostics of an organization through the employment of the structural matrix approach and the audit of the following characteristics: labour efficiency, reliability and flexibility of communications, uniformity of distribution of communications and their coordination, connectivity of elements and layers with account for their impact, degree of freedom of elements, layers and the system as a whole, reliability, rigidity, adaptability, stability of the organizational structure.

Research and development issues for fast reactor structural design standard (FDS)

International Nuclear Information System (INIS)

Kasahara, Naoto; Ando, Masanori; Morishita, Masaki

2003-01-01

For realization of safe and economical fast reactor (FR) plants, Japan Nuclear Cycle Development Institute (JNC) and Japan Atomic Power Company (JAPC) are cooperating on 'Feasibility Study on Commercialized FR Cycle Systems'. To certify the design concepts and validate their structural integrity, the research and development of 'Fast Reactor Structural Design Standard (FDS)' is recognized as an essential theme. FDS considers general characteristics of FRs and design needs for their rationalization. Three main subjects were settled in research and development issues of FDS. One is rationalization of failure criteria' taking characteristic design conditions into account. Next is development of 'a guideline on inelastic analysis for design' in order to predict elastic plastic and creep behaviours of high temperature components. Furthermore, efforts are being made toward preparing a guideline on thermal loads modeling' for FR component design where thermal loads are dominant. (author)

Nonlinear Time Domain Seismic Soil-Structure Interaction (SSI) Deep Soil Site Methodology Development

International Nuclear Information System (INIS)

Spears, Robert Edward; Coleman, Justin Leigh

2015-01-01

Currently the Department of Energy (DOE) and the nuclear industry perform seismic soil-structure interaction (SSI) analysis using equivalent linear numerical analysis tools. For lower levels of ground motion, these tools should produce reasonable in-structure response values for evaluation of existing and new facilities. For larger levels of ground motion these tools likely overestimate the in-structure response (and therefore structural demand) since they do not consider geometric nonlinearities (such as gaping and sliding between the soil and structure) and are limited in the ability to model nonlinear soil behavior. The current equivalent linear SSI (SASSI) analysis approach either joins the soil and structure together in both tension and compression or releases the soil from the structure for both tension and compression. It also makes linear approximations for material nonlinearities and generalizes energy absorption with viscous damping. This produces the potential for inaccurately establishing where the structural concerns exist and/or inaccurately establishing the amplitude of the in-structure responses. Seismic hazard curves at nuclear facilities have continued to increase over the years as more information has been developed on seismic sources (i.e. faults), additional information gathered on seismic events, and additional research performed to determine local site effects. Seismic hazard curves are used to develop design basis earthquakes (DBE) that are used to evaluate nuclear facility response. As the seismic hazard curves increase, the input ground motions (DBE's) used to numerically evaluation nuclear facility response increase causing larger in-structure response. As ground motions increase so does the importance of including nonlinear effects in numerical SSI models. To include material nonlinearity in the soil and geometric nonlinearity using contact (gaping and sliding) it is necessary to develop a nonlinear time domain methodology. This

Development of structural technology for a high performance spacer grid

International Nuclear Information System (INIS)

Song, Kee Nam; Kim, H. K.; Kang, H. S.

2003-03-01

A spacer grid in a LWR fuel assembly is a key structural component to support fuel rods and to enhance the heat transfer from the fuel rod to the coolant. In this research, the main research items are the development of inherent and high performance spacer grid shapes, the establishment of mechanical/structural analysis and test technology, and the set-up of basic test facilities for the spacer grid. The main research areas and results are as follows. 1. 14 different spacer grid candidates have been invented and applied for domestic and US patents. Among the candidates six are chosen from the patent. 2. Two kinds of spacer grids are finally selected for the advanced LWR fuel after detailed performance tests on the candidates and commercial spacer grids from a mechanical/structural point of view. According to the test results the features of the selected spacer grids are better than those of the commercial spacer grids. 3. Four kinds of basic test facilities are set up and the relevant test technologies are established. 4. Mechanical/structural analysis models and technology for spacer grid performance are developed and the analysis results are compared with the test results to enhance the reliability of the models

Development of a dual-layered dielectric-loaded accelerating structure

International Nuclear Information System (INIS)

Jing Chunguang; Kanareykin, Alexei; Kazakov, Sergey; Liu Wanming; Nenasheva, Elizaveta; Schoessow, Paul; Gai Wei

2008-01-01

rf Power attenuation is a critical problem in the development of dielectric-loaded structures for particle acceleration. In a previous paper [C. Jing, W. Liu, W. Gai, J. Power, T. Wong, Nucl. Instr. Meth. A 539 (2005) 445] we suggested the use of a Multilayer Dielectric-Loaded Accelerating Structure (MDLA) as a possible approach for reducing the rf losses in a single layer device. The MDLA is based on the principle of Bragg reflection familiar from optics that is used to partially confine the fields inside the dielectric layers and reduce the wall current losses at the outer boundary. We report here on the design, construction and testing of a prototype X-band double-layer structure (2DLA). The measurements show an rf power attenuation for the 2DLA more than ten times smaller than that of a comparable single-layer structure, in good agreement with the analytic results. Testing and operation of MDLAs also requires efficient power coupling from test equipment or rf power systems to the device. We describe the design and construction of two novel structures: a TM 03 mode launcher for cold testing and a power coupler for planned high-gradient experiments

Three New Malyngamides from the Marine Cyanobacterium Moorea producens

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Kosuke Sueyoshi

2017-11-01

Full Text Available Three new compounds of the malyngamide series, 6,8-di-O-acetylmalyngamide 2 (1, 6-O-acetylmalyngamide 2 (2, and N-demethyl-isomalyngamide I (3, were isolated from the marine cyanobacterium Moorea producens. Their structures were determined by spectroscopic analysis and chemical derivatization and degradation. These compounds stimulated glucose uptake in cultured L6 myotubes. In particular, 6,8-di-O-acetylmalyngamide 2 (1 showed potent activity and activated adenosine monophosphate-activated protein kinase (AMPK.

MO-DE-BRA-05: Developing Effective Medical Physics Knowledge Structures: Models and Methods

International Nuclear Information System (INIS)

Sprawls, P

2015-01-01

Purpose: Develop a method and supporting online resources to be used by medical physics educators for teaching medical imaging professionals and trainees so they develop highly-effective physics knowledge structures that can contribute to improved diagnostic image quality on a global basis. Methods: The different types of mental knowledge structures were analyzed and modeled with respect to both the learning and teaching process for their development and the functions or tasks that can be performed with the knowledge. While symbolic verbal and mathematical knowledge structures are very important in medical physics for many purposes, the tasks of applying physics in clinical imaging--especially to optimize image quality and diagnostic accuracy--requires a sensory conceptual knowledge structure, specifically, an interconnected network of visually based concepts. This type of knowledge supports tasks such as analysis, evaluation, problem solving, interacting, and creating solutions. Traditional educational methods including lectures, online modules, and many texts are serial procedures and limited with respect to developing interconnected conceptual networks. A method consisting of the synergistic combination of on-site medical physics teachers and the online resource, CONET (Concept network developer), has been developed and made available for the topic Radiographic Image Quality. This was selected as the inaugural topic, others to follow, because it can be used by medical physicists teaching the large population of medical imaging professionals, such as radiology residents, who can apply the knowledge. Results: Tutorials for medical physics educators on developing effective knowledge structures are being presented and published and CONET is available with open access for all to use. Conclusion: An adjunct to traditional medical physics educational methods with the added focus on sensory concept development provides opportunities for medical physics teachers to share

MO-DE-BRA-05: Developing Effective Medical Physics Knowledge Structures: Models and Methods

Energy Technology Data Exchange (ETDEWEB)

Sprawls, P [Sprawls Educational Foundation, Montreat, NC (United States)

2015-06-15

Purpose: Develop a method and supporting online resources to be used by medical physics educators for teaching medical imaging professionals and trainees so they develop highly-effective physics knowledge structures that can contribute to improved diagnostic image quality on a global basis. Methods: The different types of mental knowledge structures were analyzed and modeled with respect to both the learning and teaching process for their development and the functions or tasks that can be performed with the knowledge. While symbolic verbal and mathematical knowledge structures are very important in medical physics for many purposes, the tasks of applying physics in clinical imaging--especially to optimize image quality and diagnostic accuracy--requires a sensory conceptual knowledge structure, specifically, an interconnected network of visually based concepts. This type of knowledge supports tasks such as analysis, evaluation, problem solving, interacting, and creating solutions. Traditional educational methods including lectures, online modules, and many texts are serial procedures and limited with respect to developing interconnected conceptual networks. A method consisting of the synergistic combination of on-site medical physics teachers and the online resource, CONET (Concept network developer), has been developed and made available for the topic Radiographic Image Quality. This was selected as the inaugural topic, others to follow, because it can be used by medical physicists teaching the large population of medical imaging professionals, such as radiology residents, who can apply the knowledge. Results: Tutorials for medical physics educators on developing effective knowledge structures are being presented and published and CONET is available with open access for all to use. Conclusion: An adjunct to traditional medical physics educational methods with the added focus on sensory concept development provides opportunities for medical physics teachers to share

Coupling Neumann development and component mode synthesis methods for stochastic analysis of random structures

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Driss Sarsri

2014-05-01

Full Text Available In this paper, we propose a method to calculate the first two moments (mean and variance of the structural dynamics response of a structure with uncertain variables and subjected to random excitation. For this, Newmark method is used to transform the equation of motion of the structure into a quasistatic equilibrium equation in the time domain. The Neumann development method was coupled with Monte Carlo simulations to calculate the statistical values of the random response. The use of modal synthesis methods can reduce the dimensions of the model before integration of the equation of motion. Numerical applications have been developed to highlight effectiveness of the method developed to analyze the stochastic response of large structures.

Recent developments of advanced structures for space optics at Astrium, Germany

Science.gov (United States)

Stute, Thomas; Wulz, Georg; Scheulen, Dietmar

2003-12-01

The mechanical division of EADS Astrium GmbH, Friedrichshafen Germany, the former Dornier Satellitensystem GmbH is currently engaged with the development, manufacturing and testing of three different advanced dimensionally stable composite and ceramic material structures for satellite borne optics: -CFRP Camera Structure -Planck Telescope Reflectors -NIRSpec Optical Bench Breadboard for James Web Space Telescope The paper gives an overview over the requirements and the main structural features how these requirements are met. Special production aspects and available test results are reported.

The Structural Model of Future Employees̕ Personal and Professional Self-Development

Directory of Open Access Journals (Sweden)

Zhanna G. Garanina

2017-12-01

Full Text Available Introduction: the main purpose of this paper is to present the theoretical and practical aspects of professional and personal self-development of future professionals, the construction of the structural model and the determination of levels of self-development. The study of personal and professional self-development attributes of future professionals is of special interest to modern researchers, as well as for practicing psychologists studying the problem of self-realization and self-improvement in their professional fields. This article discusses the theoretical approaches to the study of the model and structure of personal and professional self- development. It analyses the results of the comparative empirical study of the features of students self-development with various levels of formation of motivational-semantic sphere. The authors carried out the detailed theoretical analysis of the problem of personal and professional self-development. They offer the structural model of the process, including the set of interrelated value-semantic, reflexive and regulatory components. The study revealed that the personal and professional self-development is a comprehensive system based on the active personal transformation being carried out in the course of behavior and activities self-regulation of their behavior, designed to achieve personal and professional goals. Materials and Methods: diagnostic methods were used to identify the level of self-development and personal qualities of students. Processing of the data was carried out by means of correlation, factor and cluster analysis. Results: this article considers the results of the empirical study conducted with the help of psycho-diagnostic methods aimed at identifying the level of self-development of future professionals, its structure and features. The scientifically valid results are obtained, allowing to identify the levels of self-development of students as well as to identify factors af

Tunable Laser Development for In-flight Fiber Optic Based Structural Health Monitoring Systems

Science.gov (United States)

Richards, Lance; Parker, Allen; Chan, Patrick

2014-01-01

The objective of this task is to investigate, develop, and demonstrate a low-cost swept lasing light source for NASA DFRC's fiber optics sensing system (FOSS) to perform structural health monitoring on current and future aerospace vehicles. This is the regular update of the Tunable Laser Development for In-flight Fiber Optic Based Structural Health Monitoring Systems website.

Protein structure similarity clustering (PSSC) and natural product structure as inspiration sources for drug development and chemical genomics

NARCIS (Netherlands)

Dekker, Frank J; Koch, Marcus A; Waldmann, Herbert; Dekker, Frans

Finding small molecules that modulate protein function is of primary importance in drug development and in the emerging field of chemical genomics. To facilitate the identification of such molecules, we developed a novel strategy making use of structural conservatism found in protein domain

Development of Ultra-Fine-Grained Structure in AISI 321 Austenitic Stainless Steel

Science.gov (United States)

Tiamiyu, A. A.; Szpunar, J. A.; Odeshi, A. G.; Oguocha, I.; Eskandari, M.

2017-12-01

Ultra-fine-grained (UFG) structure was developed in AISI 321 austenitic stainless steel (ASS) using cryogenic rolling followed by annealing treatments at 923 K, 973 K, 1023 K, and 1073 K (650 °C, 700 °C, 750 °C, and 800 °C) for different lengths of time. The α'-martensite to γ-austenite reversion behavior and the associated texture development were analyzed in the cryo-rolled specimens after annealing. The activation energy, Q, required for the reversion of α'-martensite to γ-austenite in the steel was estimated to be 80 kJ mol-1. TiC precipitates and unreversed triple junction α'-martensite played major roles in the development of UFG structure through the Zener pinning of grain boundaries. The optimum annealing temperature and time for the development of UFG structure in the cryo-rolled AISI 321 steel are (a) 923 K (650 °C) for approximately 28800 seconds and (b) 1023 K (750 °C) for 600 seconds, with average grain sizes of 0.22 and 0.31 µm, respectively. Annealing at 1023 K (750 °C) is considered a better alternative since the volume fraction of precipitated carbides in specimens annealed at 1023 K (750 °C) are less than those annealed at 923 K (650 °C). More so, the energy consumption during prolonged annealing time to achieve an UFG structure at 923 K (650 °C) is higher due to low phase reversion rate. The hardness of the UFG specimens is 195 pct greater than that of the as-received steel. The higher volume fraction of TiC precipitates in the UFG structure may be an additional source of hardening. Micro and macrotexture analysis indicated {110}〈uvw〉 as the major texture component of the austenite grains in the UFG structure. Its intensity is stronger in the specimen annealed at low temperatures.

Current Challenges in Development of a Database of Three-Dimensional Chemical Structures

Science.gov (United States)

Maeda, Miki H.

2015-01-01

We are developing a database named 3DMET, a three-dimensional structure database of natural metabolites. There are two major impediments to the creation of 3D chemical structures from a set of planar structure drawings: the limited accuracy of computer programs and insufficient human resources for manual curation. We have tested some 2D–3D converters to convert 2D structure files from external databases. These automatic conversion processes yielded an excessive number of improper conversions. To ascertain the quality of the conversions, we compared IUPAC Chemical Identifier and canonical SMILES notations before and after conversion. Structures whose notations correspond to each other were regarded as a correct conversion in our present work. We found that chiral inversion is the most serious factor during the improper conversion. In the current stage of our database construction, published books or articles have been resources for additions to our database. Chemicals are usually drawn as pictures on the paper. To save human resources, an optical structure reader was introduced. The program was quite useful but some particular errors were observed during our operation. We hope our trials for producing correct 3D structures will help other developers of chemical programs and curators of chemical databases. PMID:26075200

Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans.

Science.gov (United States)

Tubbs, Emily; Chanon, Stéphanie; Robert, Maud; Bendridi, Nadia; Bidaux, Gabriel; Chauvin, Marie-Agnès; Ji-Cao, Jingwei; Durand, Christine; Gauvrit-Ramette, Daphné; Vidal, Hubert; Lefai, Etienne; Rieusset, Jennifer

2018-04-01

Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D. © 2018 by the American Diabetes Association.

Summary of Structural Concept Development and High Temperature Structural Integrity Evaluation Technology for a Gen-IV SFR

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae Han; Joo, Young Sang; Lee, Hyeong Yeon (and others)

2008-04-15

The economic improvement is a hot issue as one of Gen IV nuclear plant goals. It requires many researches and development works to meet the goal by securing the same level of plant safety. One of the key research items is the increase of the plant capacity with the minimum number of components and loops. Through the successful conceptual design experience for the KALIMER-600, the structural design study for a 1200MWe large capacity of sodium-cooled fast reactor has been performed to achieve the above plant size effects. The component number and reactor structural sizing were determined based on the core and fluid system design information. Several researches were performed to reduce the construction cost of NSSS in structural point of view, for example, a simplified component arrangement, concept proposals of integrated components, a high temperature LBB application technology, and an innovative in-service inspection (ISI) tool, and a computer program development of the ASME-NH design procedure of the class 1 structure and component under high temperature over 500 .deg. C. The IHTS piping arrangement was also proposed to minimize the length through the properly locating the SG and pump by 126m. Further studies of these concepts are required to confirm on the fabricability and the structural integrity for the operating and design loads. The proposed concepts will be optimized to a unified conceptual design through several trade-off studies.

Early structural development in melt-quenched polymer PTT from atomistic molecular dynamic simulations

Science.gov (United States)

Hsieh, Min-Kang; Lin, Shiang-Tai

2009-12-01

Molecular dynamics simulations are performed to study the initial structural development in poly(trimethylene terephthalate) (PTT) when quenched below its melting point. The development of local ordering has been observed in our simulations. The thermal properties, such as the glass transition temperature (Tg) and the melting temperature (Tm), determined from our simulations are in reasonable agreement with experimental values. It is found that, between these two temperatures, the number of local structures quickly increases during the thermal relaxation period soon after the system is quenched and starts to fluctuate afterwards. The formation and development of local structures is found to be driven mainly by the torsional and van der Waals forces and follows the classical nucleation-growth mechanism. The variation of local structures' fraction with temperature exhibits a maximum between Tg and Tm, resembling the temperature dependence of the crystallization rate for most polymers. In addition, the backbone torsion distribution for segments within the local structures preferentially reorganizes to the trans-gauche-gauche-trans (t-g-g-t) conformation, the same as that in the crystalline state. As a consequence, we believe that such local structural ordering could be the baby nuclei that have been suggested to form in the early stage of polymer crystallization.

Measurement of contractile stress generated by cultured rat muscle on silicon cantilevers for toxin detection and muscle performance enhancement.

Directory of Open Access Journals (Sweden)

Kerry Wilson

2010-06-01

Full Text Available To date, biological components have been incorporated into MEMS devices to create cell-based sensors and assays, motors and actuators, and pumps. Bio-MEMS technologies present a unique opportunity to study fundamental biological processes at a level unrealized with previous methods. The capability to miniaturize analytical systems enables researchers to perform multiple experiments in parallel and with a high degree of control over experimental variables for high-content screening applications.We have demonstrated a biological microelectromechanical system (BioMEMS based on silicon cantilevers and an AFM detection system for studying the physiology and kinetics of myotubes derived from embryonic rat skeletal muscle. It was shown that it is possible to interrogate and observe muscle behavior in real time, as well as selectively stimulate the contraction of myotubes with the device. Stress generation of the tissue was estimated using a modification of Stoney's equation. Calculated stress values were in excellent agreement with previously published results for cultured myotubes, but not adult skeletal muscle. Other parameters such as time to peak tension (TPT, the time to half relaxation ((1/2RT were compared to the literature. It was observed that the myotubes grown on the BioMEMS device, while generating stress magnitudes comparable to those previously published, exhibited slower TPT and (1/2RT values. However, growth in an enhanced media increased these values. From these data it was concluded that the myotubes cultured on the cantilevers were of an embryonic phenotype. The system was also shown to be responsive to the application of a toxin, veratridine.The device demonstrated here will provide a useful foundation for studying various aspects of muscle physiology and behavior in a controlled high-throughput manner as well as be useful for biosensor and drug discovery applications.

N-myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle.

Science.gov (United States)

Ochi, Arisa; Abe, Tomoki; Nakao, Reiko; Yamamoto, Yoriko; Kitahata, Kanako; Takagi, Marina; Hirasaka, Katsuya; Ohno, Ayako; Teshima-Kondo, Shigetada; Taesik, Gwag; Choi, Inho; Kawamura, Tomoyuki; Nemoto, Hisao; Mukai, Rie; Terao, Junji; Nikawa, Takeshi

2015-03-15

A DGpYMP peptide mimetic of tyrosine(608)-phosphorylated insulin receptor substrate-1 (IRS-1), named Cblin, was previously shown to significantly inhibit Cbl-b-mediated IRS-1 ubiquitination. In the present study, we developed N-myristoylated Cblin and investigated whether it was effective in preventing glucocorticoid-induced muscle atrophy. Using HEK293 cells overexpressing Cbl-b, IRS-1 and ubiquitin, we showed that the 50% inhibitory concentrations of Cbl-b-mediated IRS-1 ubiquitination by N-myristoylated Cblin and Cblin were 30 and 120 μM, respectively. Regarding the DEX-induced atrophy of C2C12 myotubes, N-myristoylated Cblin was more effective than Cblin for inhibiting the DEX-induced decreases in C2C12 myotube diameter and IRS-1 degradation. The inhibitory efficacy of N-myristoylated Cblin on IRS-1 ubiquitination in C2C12 myotubes was approximately fourfold larger than that of Cblin. Furthermore, N-myristoylation increased the incorporation of Cblin into HEK293 cells approximately 10-folds. Finally, we demonstrated that N-myristoylated Cblin prevented the wet weight loss, IRS-1 degradation, and MAFbx/atrogin-1 and MuRF-1 expression in gastrocnemius muscle of DEX-treated mice approximately fourfold more effectively than Cblin. Taken together, these results suggest that N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and that N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin. Copyright © 2015 Elsevier Inc. All rights reserved.

Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

Science.gov (United States)

Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

2017-01-01

Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

Structural Framework for Flight: NASA's Role in Development of Advanced Composite Materials for Aircraft and Space Structures

Science.gov (United States)

Tenney, Darrel R.; Davis, John G., Jr.; Johnston, Norman J.; Pipes, R. Byron; McGuire, Jack F.

2011-01-01

This serves as a source of collated information on Composite Research over the past four decades at NASA Langley Research Center, and is a key reference for readers wishing to grasp the underlying principles and challenges associated with developing and applying advanced composite materials to new aerospace vehicle concepts. Second, it identifies the major obstacles encountered in developing and applying composites on advanced flight vehicles, as well as lessons learned in overcoming these obstacles. Third, it points out current barriers and challenges to further application of composites on future vehicles. This is extremely valuable for steering research in the future, when new breakthroughs in materials or processing science may eliminate/minimize some of the barriers that have traditionally blocked the expanded application of composite to new structural or revolutionary vehicle concepts. Finally, a review of past work and identification of future challenges will hopefully inspire new research opportunities and development of revolutionary materials and structural concepts to revolutionize future flight vehicles.

Understanding Structures and Affordances of Extended Teams in Global Software Development

DEFF Research Database (Denmark)

Ali Babar, Muhammad; Zahedi, Mansooreh

2013-01-01

Growing popularity of Global Software Development (GSD) has resulted in an increasing number of cross-organizational teams that are formed according to Extended Team Model (ETM). There is little known about the structures (work, social, and communication) that may exist in ETM and what affordances...... in the studied team help deal with different GSD challenges, these structures appear to have certain challenges inherent in them and the affordances they provide. We make a few recommendations for improving the current structures to deal with the observed challenges. Our findings are expected to provide insights...

Improved tank car design development : ongoing studies on sandwich structures

Science.gov (United States)

2009-03-02

The Government and industry have a common interest in : improving the safety performance of railroad tank cars carrying : hazardous materials. Research is ongoing to develop strategies : to maintain the structural integrity of railroad tank cars carr...

Community investment in wind farms: funding structure effects in wind energy infrastructure development.

Science.gov (United States)

Beery, Joshua A; Day, Jennifer E

2015-03-03

Wind energy development is an increasingly popular form of renewable energy infrastructure in rural areas. Communities generally perceive socioeconomic benefits accrue and that community funding structures are preferable to corporate structures, yet lack supporting quantitative data to inform energy policy. This study uses the Everpower wind development, to be located in Midwestern Ohio, as a hypothetical modeling environment to identify and examine socioeconomic impact trends arising from corporate, community and diversified funding structures. Analysis of five National Renewable Energy Laboratory Jobs and Economic Development Impact models incorporating local economic data and review of relevant literature were conducted. The findings suggest that community and diversified funding structures exhibit 40-100% higher socioeconomic impact levels than corporate structures. Prioritization of funding sources and retention of federal tax incentives were identified as key elements. The incorporation of local shares was found to mitigate the negative effects of foreign private equity, local debt financing increased economic output and opportunities for private equity investment were identified. The results provide the groundwork for energy policies focused to maximize socioeconomic impacts while creating opportunities for inclusive economic participation and improved social acceptance levels fundamental to the deployment of renewable energy technology.

Structure and development of the saccular sensory epithelium in ...

African Journals Online (AJOL)

Structure and development of the saccular sensory epithelium in relation to otolith growth in the perch Perca fluviatilis (Telostei) ... Electron microscopy indicated: 1) The apical surface of each hair cell is covered with a ciliary bundle which varies in length in different epithelial regions. Each bundle is formed from a long ...

Myostatin Activates the Ubiquitin-Proteasome and Autophagy-Lysosome Systems Contributing to Muscle Wasting in Chronic Kidney Disease

Science.gov (United States)

Wang, Dong-Tao; Yang, Ya-Jun; Huang, Ren-Hua; Zhang, Zhi-Hua; Lin, Xin

2015-01-01

Our evidence demonstrated that CKD upregulated the expression of myostatin, TNF-α, and p-IkBa and downregulated the phosphorylation of PI3K, Akt, and FoxO3a, which were also associated with protein degradation and muscle atrophy. The autophagosome formation and protein expression of autophagy-related genes were increased in muscle of CKD rats. The mRNA level and protein expression of MAFbx and MuRF-1 were also upregulated in CKD rats, as well as proteasome activity of 26S. Moreover, activation of myostatin elicited by TNF-α induces C2C12 myotube atrophy via upregulating the expression of autophagy-related genes, including MAFbx and MuRF1 and proteasome subunits. Inactivation of FoxO3a triggered by PI3K inhibitor LY294002 prevented the myostatin-induced increase of expression of MuRF1, MAFbx, and LC3-II protein in C2C12 myotubes. The findings were further consolidated by using siRNA interference and overexpression of myostatin. Additionally, expression of myostatin was activated by TNF-α via a NF-κB dependent pathway in C2C12 myotubes, while inhibition of NF-κB activity suppressed myostatin and improved myotube atrophy. Collectively, myostatin mediated CKD-induced muscle catabolism via coordinate activation of the autophagy and the ubiquitin-proteasome systems. PMID:26448817

Influence of ownership capital structure of Refinery's operation and development

International Nuclear Information System (INIS)

Hadzhi-Mishev, Dimitar

1999-01-01

Refineries are part of the energetic infrastructure of one country. Their significance is dependent on the geographic country position (whether it has sea exit or not), and on structure of primary energy spends in the country. According these facts, country's attitude to the refineries on its territory could be different. The possibility of ownership structure transformation in refineries and necessary legislation in the energetic sector of the state, needed for transformation realization are analyzed in this paper. Essential conditions for transformation fulfilling are protection 'mechanisms for domestic production in crude oil economy, manners of crude oil products price defining, and manners of excise determination and payment. As a function of these conditions, the conditions under which transformation of ownership structure in refineries is possible, as well as their influence on the operation and development of this part of energetic structure in transition country are defined in this paper. (Original)

Development of a remote inspection robot for high pressure structures

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae C.; Kim, Jae H.; Choi, Yu R.; Moon, Soon S

1999-10-01

The high pressure structures in industrial plants must be periodically inspected for ensure their safety. Currently, the examination of them is manually performed by human inspectors, and there are many restrictions to examine the large containers which enclose dangerous chemicals or radioactive materials. We developed a remotely operated robot to examine these structures using recent mobile robot and computer technologies. Our robot has two magnetic caterpillars that make the robot can adhere to the structures made of steel like materials. The robot moves to the position for examination, and scans that position using ultrasonic probes equipped on it's arm, and transmits the result to the inspector according to his/her commands. Without building any auxiliary structures the robot can inspect the places where manual inspection can't reach. Therefore the robot can make shortening the inspection time as well as preventing the inspector from an accident. (author)

Development of a remote inspection robot for high pressure structures

International Nuclear Information System (INIS)

Lee, Jae C.; Kim, Jae H.; Choi, Yu R.; Moon, Soon S.

1999-10-01

The high pressure structures in industrial plants must be periodically inspected for ensure their safety. Currently, the examination of them is manually performed by human inspectors, and there are many restrictions to examine the large containers which enclose dangerous chemicals or radioactive materials. We developed a remotely operated robot to examine these structures using recent mobile robot and computer technologies. Our robot has two magnetic caterpillars that make the robot can adhere to the structures made of steel like materials. The robot moves to the position for examination, and scans that position using ultrasonic probes equipped on it's arm, and transmits the result to the inspector according to his/her commands. Without building any auxiliary structures the robot can inspect the places where manual inspection can't reach. Therefore the robot can make shortening the inspection time as well as preventing the inspector from an accident. (author)

Residents’ attitudes toward tourism development: A structural model via Akcakoca sample

OpenAIRE

Erol Duran; Emrah Özkul

2012-01-01

The objective of this study is to showcase a structural model that explores residents’ attitudes towards sustainable tourism development. Factors influencing residents’ attitudes were examined using a model consisting five latent constructs and six path hypotheses. Within this context, findings from 300 resident-respondents from Akcakoca, Turkey were analyzed. Utilizing LISREL 8,54 structural equation analysis package, a confirmatory factor analysis and path analysis were performed successi...

Development of paint area estimation software for ship compartments and structures

Directory of Open Access Journals (Sweden)

Doo-Yeoun Cho

2016-03-01

Full Text Available The painting process of large ships is an intense manual operation that typically comprises 9–12% of the total shipbuilding cost. Accordingly, shipbuilders need to estimate the required amount of anti-corrosive coatings and painting resources for inventory and cost control. This study aims to develop a software system which enables the shipbuilders to estimate paint area using existing 3D CAD ship structural models. The geometric information of the ships structure are extracted from the existing shipbuilding CAD/CAM system and used to create painting zones. After specifying the painting zones, users can generate the paint faces by clipping structural parts inside each zone. Finally, the paint resources may be obtained from the product of the paint areas and required paint thickness. Implementing the developed software system to real shipbuilders' operations has contributed to improved productivity, faster resource estimation, better accuracy, and fewer coating defects over their conventional manual calculation methods for painting resource estimation.

Development of strongly coupled FSI technology involving thin walled structures

CSIR Research Space (South Africa)

Suliman, Ridhwaan

2011-01-01

Full Text Available A strongly coupled finite volume-finite element fluid-structure interaction (FSI) scheme is developed. Both an edge-based finite volume and Galerkin finite element scheme are implemented and evaluated for modelling the mechanics of solids...

Developing Ill-Structured Problem-Solving Skills through Wilderness Education

Science.gov (United States)

Collins, Rachel H.; Sibthorp, Jim; Gookin, John

2016-01-01

In a society that is becoming more dynamic, complex, and diverse, the ability to solve ill-structured problems (ISPs) has become an increasingly critical skill. Students who enter adult roles with the cognitive skills to address ISPs will be better able to assume roles in the emerging economies. Opportunities to develop and practice these skills…

Structural challenges in the development of a truck shipping cask for the OCRWM cask systems development program

International Nuclear Information System (INIS)

Mello, R.M.; Severson, W.J.; Nair, B.R.

1990-01-01

The development of a spent fuel transportation cask design based on a structural material without licensing precedent presents many challenges. The U.S. Nuclear Regulatory Commission (NRC) requires that any new material be qualified to meet the design and fabrication requirements of the ASME Boiler and Pressure Vessel Code, Section III, Class 1. This paper discusses the strategy that is being implemented towards obtaining Code Acceptance of a titanium alloy (3A1-2.5V). This alloy has been chosen as the principal structural material for a Legal Weight Truck cask being developed by Westinghouse for the U.S. Department of Energy. The analysis approach used on some of the principal cask components is also presented

Development of integrated D/B system for the safety-related structures in nuclear power plant

International Nuclear Information System (INIS)

Cho, M. S.; Song, Y. C.; Lee, J. S.; Choi, W. S.

2002-01-01

The integrated D/B system is developed for digitalizing the history of the safety-related structures of nuclear power plant. It have 5 database which are consist of Generals, Structural and Design, Materials, Construction, Aging and repair information D/B. For efficient operation of the system, we are to set up the outline of the system, find out data field for target structures, and develop utilities. Utilities will be the aging and repair data management program, the close examination management program, the data search engine with various options which help users to find the information quickly, and the data management program restoring, updating and exchanging input data. Development of the integrated D/B system of the safety-related structures will contribute to management of the structures of nuclear power plant with advanced technology

Development and internal structure investigation of the Dimensional Clinical Personality Inventory

Directory of Open Access Journals (Sweden)

Lucas de Francisco Carvalho

2015-06-01

Full Text Available This study aimed to develop a dimensional instrument to assess personality disorders based on Millon's theoretical perspective and on DSM-IV-TR diagnoses criteria, and seek validity evidence based on internal structure and reliability indexes of the factors. In order to do that, a self-report test composed of 215 items, the Dimensional Clinical Personality Inventory (DCPI was developed and applied to 561 respondents aged between 18 and 90 years (M = 28,8; SD = 11.4, with 51.8% females. Exploratory factor analysis and verification of reliability were performed using Cronbach's alpha. Data provided validity evidence based on internal structure of the instrument according to the theory of Millon and DSM-IV-TR.

A Framework for Developing the Structure of Public Health Economic Models.

Science.gov (United States)

Squires, Hazel; Chilcott, James; Akehurst, Ronald; Burr, Jennifer; Kelly, Michael P

2016-01-01

A conceptual modeling framework is a methodology that assists modelers through the process of developing a model structure. Public health interventions tend to operate in dynamically complex systems. Modeling public health interventions requires broader considerations than clinical ones. Inappropriately simple models may lead to poor validity and credibility, resulting in suboptimal allocation of resources. This article presents the first conceptual modeling framework for public health economic evaluation. The framework presented here was informed by literature reviews of the key challenges in public health economic modeling and existing conceptual modeling frameworks; qualitative research to understand the experiences of modelers when developing public health economic models; and piloting a draft version of the framework. The conceptual modeling framework comprises four key principles of good practice and a proposed methodology. The key principles are that 1) a systems approach to modeling should be taken; 2) a documented understanding of the problem is imperative before and alongside developing and justifying the model structure; 3) strong communication with stakeholders and members of the team throughout model development is essential; and 4) a systematic consideration of the determinants of health is central to identifying the key impacts of public health interventions. The methodology consists of four phases: phase A, aligning the framework with the decision-making process; phase B, identifying relevant stakeholders; phase C, understanding the problem; and phase D, developing and justifying the model structure. Key areas for further research involve evaluation of the framework in diverse case studies and the development of methods for modeling individual and social behavior. This approach could improve the quality of Public Health economic models, supporting efficient allocation of scarce resources. Copyright © 2016 International Society for Pharmacoeconomics

Puberty and structural brain development in humans.

Science.gov (United States)

Herting, Megan M; Sowell, Elizabeth R

2017-01-01

Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

Review of Structural Social Determinants of Health in Early Childhood Development

Directory of Open Access Journals (Sweden)

Firoozeh Sajedi

2015-09-01

Full Text Available Development is a dynamic and continuous phenomenon  that is under the influence of various factors forming a complicated multidimensional system together. Any impairment in these factors can lead to impaired development in children, which is one of the most common problems in children. Therefore, this study provides a brief overview of these factors and the way they affect early childhood development. A brief review was performed in databases including Google scholar, PUBMED, Proquest, SID, Magiran, Iranmedex, Irandoc with following keywords: child  development, income, occupation, education, employment, boy, girl,  gender, sex, social class, Race and Ethnicity. All of article was reviewed then categorized based on WHO model. Among the papers reviewed, most of the studies were about employment, education, and income and most of them investigated these risk factors in terms of socioeconomic status. Structural factors of social determinants of health had a close relationship with each other, and they  had affected development through each other. Given that, only few studies on structural factors, except for socioeconomic factors, have been conducted and little attention has been paid to the way these factors affect child development, further studies in this area are required to propose a model in order to better understand the interaction between these factors.

MOTOR STRUCTURE AND BASIC MOVEMENT COMPETENCES IN EARLY CHILD DEVELOPMENT

Directory of Open Access Journals (Sweden)

Rado Pišot

2010-12-01

Full Text Available Motor development consists of dynamic and continuous development in motor behaviour and is reflected in motor competences (on the locomotive, manipulative and postural level and motor abilities (coordination, strength, speed, balance, flexibility, precision and endurance. This is a complex process in which a child acquires motor abilities and knowledge in interaction with inherited and environmental factors. A sample of 603 boys and girls, of which 263 were aged five (age deviation +/- 3 days; 18,5 ± 3,1kg body weight; 109,4 ± 4,3 cm body height and 340 were aged six and a half (age deviation +/- 3 days; 23, 7 ± 4, 3 kg body weight; 121 ± 4,8 cm body height, were involved in this study after written consent was obtained from their parents. The children's motor structure was established through the application of 28 tests that had been verified on the Slovene population and established as adequate for the study of motor abilities in the sample children. The factor analysis was applied to uncover the latent structure of motor space, and PB (Štalec Momirović criteria were used to establish the number of significant basic components. The analysis of the motor space structure revealed certain particularities for each age period. In the sample of 5 year old children, the use of PB criterion revealed four latent motor dimensions, in 6.5 year old children, the latent motor space structure was described with four (boys and five (girls factors. Despite the existence of gender differences in motor space structure and certain particularities in each age period mostly related to the factors which influence movement coordination, several very similar dimensions were discovered in both sexes.

Centrosome proteins form an insoluble perinuclear matrix during muscle cell differentiation

Directory of Open Access Journals (Sweden)

Srsen Vlastimil

2009-04-01

Full Text Available Abstract Background Muscle fibres are formed by elongation and fusion of myoblasts into myotubes. During this differentiation process, the cytoskeleton is reorganized, and proteins of the centrosome re-localize to the surface of the nucleus. The exact timing of this event, and the underlying molecular mechanisms are still poorly understood. Results We performed studies on mouse myoblast cell lines that were induced to differentiate in culture, to characterize the early events of centrosome protein re-localization. We demonstrate that this re-localization occurs already at the single cell stage, prior to fusion into myotubes. Centrosome proteins that accumulate at the nuclear surface form an insoluble matrix that can be reversibly disassembled if isolated nuclei are exposed to mitotic cytoplasm from Xenopus egg extract. Our microscopy data suggest that this perinuclear matrix of centrosome proteins consists of a system of interconnected fibrils. Conclusion Our data provide new insights into the reorganization of centrosome proteins during muscular differentiation, at the structural and biochemical level. Because we observe that centrosome protein re-localization occurs early during differentiation, we believe that it is of functional importance for the reorganization of the cytoskeleton in the differentiation process.

Institutional Structure and International Competitiveness Relationship in Developed Countries

Directory of Open Access Journals (Sweden)

Aynur Yıldırım

2016-06-01

Full Text Available This study analyzes the effects of institutional structure on the international competitiveness of developed countries econometrically by employing a “Panel Data Analysis” with a sample of 21 developed countries and 23 institutional variables for the period 2000-2011. The results of the analysis indicate that while judicial independence, protection of intellectual property rights, integrity of the juridical system, marginal tax, political freedoms, black market exchange rate, restrictions on foreign investment, private sector’s share in the banking system, hiring-minimum wage, and hiring-dismissal have a positive effect; the nature of legal arrangements, government spending, transfers and subsidies, civil liberties, tariffs, regulations regarding trade barriers, collective bargaining, and military tutelage have a negative effect on the international competitiveness of developed countries.

Structural challenges in the development of a truck shipping cask for the OCRWM Cask Systems Development Program

International Nuclear Information System (INIS)

Mello, R.M.; Severson, W.J.; Nair, B.R.

1990-01-01

The development of a spent fuel transportation cask design based on a structural material without licensing precedent presents many challenges. The US Nuclear Regulatory Commission (NRC) requires that any new material be qualified to meet the design and fabrication requirements of the ASME Boiler ampersand Pressure Vessel Code, Section III, Class 1. This paper discusses the strategy that is being implemented towards obtaining Code acceptance of a titanium alloy (3A1-2.5V). This alloy has been chosen as the principal structural material for a Legal Weight Truck cask being developed by Westinghouse for the US Department of Energy. The analysis approach used on some of the principal cask components is also presented. 5 refs., 8 figs., 3 tabs

Developing Structured-Learning Exercises for a Community Advanced Pharmacy Practice Experience

OpenAIRE

Thomas, Renee Ahrens

2006-01-01

The recent growth in the number of pharmacy schools across the nation has resulted in the need for high-quality community advanced pharmacy practice experience (APPE) sites. A vital part of a student's education, these APPEs should be structured and formalized to provide an environment conducive to student learning. This paper discusses how to use a calendar, structured-learning activities, and scheduled evaluations to develop students' knowledge, skills, and abilities in a community pharmacy...

Developing structured-learning exercises for a community advanced pharmacy practice experience.

Science.gov (United States)

Thomas, Renee Ahrens

2006-02-15

The recent growth in the number of pharmacy schools across the nation has resulted in the need for high-quality community advanced pharmacy practice experience (APPE) sites. A vital part of a student's education, these APPEs should be structured and formalized to provide an environment conducive to student learning. This paper discusses how to use a calendar, structured-learning activities, and scheduled evaluations to develop students' knowledge, skills, and abilities in a community pharmacy setting.

Department of Defense Research, Development, Test, and Evaluation (RDT and E): Appropriations Structure

Science.gov (United States)

2016-12-13

Research Projects Agency website, accessed December 5, 2016, http://www.darpa.mil/about-us/mission. Appropriations Structure of Defense RDT&E...funding streams. Among the many other factors that may affect the effectiveness of the performance of RDT&E are: organizational structures and...Department of Defense Research, Development, Test, and Evaluation (RDT&E): Appropriations Structure John F. Sargent Jr. Specialist in

PROGRESS ON DEVELOPING SONIC INFRARED IMAGING FOR DEFECT DETECTION IN COMPOSITE STRUCTURES

International Nuclear Information System (INIS)

Han Xiaoyan; He Qi; Li Wei; Newaz, Golam; Favro, Lawrence D.; Thomas, Robert L.

2010-01-01

At last year's QNDE conference, we presented our development of Sonic IR imaging technology in metal structures, with results from both experimental studies and theoretical computing. In the latest aircraft designs, such as the B787 from Boeing, composites have become the major materials in structures such as the fuselage and wings. This is in contrast to composites' use only in auxiliary components such as flaps and spoilers in the past. With today's advanced technology of fabrication, it is expected the new materials can be put in use in even more aircraft structures due to its light weight and high strength (high strength-to-weight ratio), high specific stiffness, tailorability of properties, design flexibility etc. Especially, with increases in fuel cost, reducing the aircraft's body weight becomes more and more appealing. In this presentation, we describe the progress on our development of Sonic IR imaging for aircraft composite structures. In particular, we describe the some unexpected results discovered while modeling delaminations. These results were later experimentally verified with an engineered delamination.

The peculiarities of structurizing enclosing rock massif while developing a coal seam

Science.gov (United States)

Kozyreva, E. N.; Shinkevich, M. V.

2017-09-01

Different concepts of the development of geo-mechanical processes during longwall mining of a seam which are fundamentally different from the conventional ones are introduced in the article. Fundamental principles of the model for structurizing enclosing rock mass while longwall mining along the strike are described. The model was developed on the bases of non-linear geomechanical laws. According to the model, rock mass in the area of mining operation is organized as rock geomechanical layers with shifting arches. And the formation period of shifting arches in disintegrated rock mass is divisible by the length of the stope. Undulate characteristic of a massif as a peculiarity of man-made structurization of a massif is defined. It is shown that structuring the broken massif causes the formation of block-structured system and it can be detected while monitoring the ground pressure in powered support props. The results of the research allow decreasing the negative influence of a ground pressure and can be applied to specify parameters for controlling the roof, defining geometrical dimensions of a mining section and positioning of holing chute (face entry).

Development of image analysis for graphite pore-structure determination using fluorescence techniques

International Nuclear Information System (INIS)

Stephen, W.J.; Bowden, E.A.T.; Wickham, A.J.

1983-03-01

The use of image analysis to assess the pore structure of graphite has been developed to the point at which it may be considered available for routine use. A definitive pore structure in terms of the geometry-independent ''characteristic pore dimension'' is derived from the computer analysis of polished specimens whose open-pore structure has been impregnated with bismuth or a fluorescent epoxy resin, with the very small pores identified separately by mercury porosimetry as in the past. The pore-size distributions obtained from these combined techniques have been used successfully to predict the corrosion rates of nine graphites, of widely differing pore structure, in a variety of gas compositions and, indirectly, to confirm appropriate mean ranges and rate constants for the reaction of the oxidising species in these gas mixtures. The development of the fluorescent-impregnant technique is discussed in detail and its use is justified in preference to ''traditional'' methods. Further possible refinements are discussed, including the eventual aim of obtaining a computer prediction of the future oxidation behaviour of the graphite directly from the image analyser. (author)

Supplier integration in product development: A matter of designing the project structure

Directory of Open Access Journals (Sweden)

Mike Danilovic

2007-11-01

Full Text Available In product development close collaboration between systems integrators and suppliers is important. The purpose of this article is to investigate the impact of the work breakdown structure (WBS and work packages (WPs in product development on the possibility of carrying through the strategy of supplier involvement into collaborative practice and to investigate how supplier involvement can be improved by altering the design of collaborative WBS and WP structures. Dependence Structure Matrix (DSM is introduced in order to analyse, visualise and manage interdependencies, in terms of information exchange between the systems integrator and supplier. This article shows how DSM can support the alternative design of integrated and collaborative WBS and integrated WPs following the logic of dependencies and the flow of information in order to support a strategy focusing on integration of suppliers on project and team level.

Structural maturation and brain activity predict future working memory capacity during childhood development.

Science.gov (United States)

Ullman, Henrik; Almeida, Rita; Klingberg, Torkel

2014-01-29

Human working memory capacity develops during childhood and is a strong predictor of future academic performance, in particular, achievements in mathematics and reading. Predicting working memory development is important for the early identification of children at risk for poor cognitive and academic development. Here we show that structural and functional magnetic resonance imaging data explain variance in children's working memory capacity 2 years later, which was unique variance in addition to that predicted using cognitive tests. While current working memory capacity correlated with frontoparietal cortical activity, the future capacity could be inferred from structure and activity in basal ganglia and thalamus. This gives a novel insight into the neural mechanisms of childhood development and supports the idea that neuroimaging can have a unique role in predicting children's cognitive development.

Dystrophin deficiency leads to disturbance of LAMP1-vesicle-associated protein secretion

DEFF Research Database (Denmark)

Duguez, S.; Duddy, W.; Johnston, H.

2013-01-01

Duchenne muscular dystrophy results from loss of the protein dystrophin, which links the intracellular cytoskeletal network with the extracellular matrix, but deficiency in this function does not fully explain the onset or progression of the disease. While some intracellular events involved...... in the degeneration of dystrophin-deficient muscle fibers have been well characterized, changes in their secretory profile are undescribed. To analyze the secretome profile of mdx myotubes independently of myonecrosis, we labeled the proteins of mdx and wild-type myotubes with stable isotope-labeled amino acids...

Development of pressure containment and damage tolerance technology for composite fuselage structures in large transport aircraft

Science.gov (United States)

Smith, P. J.; Thomson, L. W.; Wilson, R. D.

1986-01-01

NASA sponsored composites research and development programs were set in place to develop the critical engineering technologies in large transport aircraft structures. This NASA-Boeing program focused on the critical issues of damage tolerance and pressure containment generic to the fuselage structure of large pressurized aircraft. Skin-stringer and honeycomb sandwich composite fuselage shell designs were evaluated to resolve these issues. Analyses were developed to model the structural response of the fuselage shell designs, and a development test program evaluated the selected design configurations to appropriate load conditions.

Development of Ultrasonic Visual Inspection Program for In-Vessel Structures of SFR

International Nuclear Information System (INIS)

Joo, Y. S.; Park, C. G.; Lee, J. H.

2009-02-01

As the liquid sodium of a sodium-cooled fast reactor (SFR) is opaque to light, a conventional visual inspection is unavailable for the evaluation of the in-vessel structures under a sodium level. ASME Section XI Division 3 provides rules and guidelines for an in-service inspection (ISI) and testing of the components of SFR. For the ISI of in-vessel structures, the ASME code specifies visual examinations. An ultrasonic wave should be applied for an under-sodium visual inspection of the in-vessel structures. The plate-type waveguide sensor has been developed and the feasibility of the waveguide sensor technique has been successfully demonstrated for an ultrasonic visual inspection of the in-vessel structures of SFR. In this study, the C-scan image mapping program (Under-Sodium MultiView) is developed to apply this waveguide sensor technology to an under-sodium visual inspection of in-vessel structures in SFR by using a LabVIEW graphical programming language. The Under-Sodium MultiVIEW program has the functions of a double rotating scanner motion control, a high power pulser receiver control, a image mapping and a signal processing. The performance of Under-Sodium MultiVIEW program was verified by a C-scanning test

Radial Structure Scaffolds Convolution Patterns of Developing Cerebral Cortex

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Mir Jalil Razavi

2017-08-01

Full Text Available Commonly-preserved radial convolution is a prominent characteristic of the mammalian cerebral cortex. Endeavors from multiple disciplines have been devoted for decades to explore the causes for this enigmatic structure. However, the underlying mechanisms that lead to consistent cortical convolution patterns still remain poorly understood. In this work, inspired by prior studies, we propose and evaluate a plausible theory that radial convolution during the early development of the brain is sculptured by radial structures consisting of radial glial cells (RGCs and maturing axons. Specifically, the regionally heterogeneous development and distribution of RGCs controlled by Trnp1 regulate the convex and concave convolution patterns (gyri and sulci in the radial direction, while the interplay of RGCs' effects on convolution and axons regulates the convex (gyral convolution patterns. This theory is assessed by observations and measurements in literature from multiple disciplines such as neurobiology, genetics, biomechanics, etc., at multiple scales to date. Particularly, this theory is further validated by multimodal imaging data analysis and computational simulations in this study. We offer a versatile and descriptive study model that can provide reasonable explanations of observations, experiments, and simulations of the characteristic mammalian cortical folding.

Technology Development Benefits and the Economics Breakdown Structure

Science.gov (United States)

Shaw, Eric J.

1998-01-01

This paper describes the construction and application of the EBS (Economics Breakdown Structure) in evaluating technology investments across multiple systems and organizations, illustrated with examples in space transportation technology. The United States Government (USG) has a long history of investing in technology to enable its missions. Agencies such as the National Aeronautics and Space Administration (NASA) and the Department of Defense (DoD) have evaluated their technology development programs primarily on their effects on mission performance and cost. More and more, though, USG agencies are being evaluated on their technology transfer to the commercial sector. In addition, an increasing number of USG missions are being accomplished by industry-led or joint efforts, where the USG provides technology and funding but tasks industry with development and operation of the mission systems.

Development of on-line condition monitoring system in aerospace structures using advanced composite materials

International Nuclear Information System (INIS)

Khan, Z.M.

2005-01-01

This research aims to develop condition monitoring systems for advanced aerospace composite structures. To perform these functions successfully a smart system is required that could autonomously respond to environmental changes. The integrated structure senses the environments, conveys the message to central processing unit and reacts instantaneously to external stimuli. Such structures not only monitor their own health but also for warn about onset of failures, fatigue and impending disasters. This required development of methods for embedding optical fibers in composite panels for sensing given defect. The thick and cylindrical composite structures have layer waviness due to fiber microbend defect. Such kind of defect is characteristically hard to detect. It leads to delamination, cracking and deterioration of mechanical properties. The experimental investigation revealed correlation of the intensity of light with the microbend defect in composite structure. (author)

Effect of nano- and micro-scale topological features on alignment of muscle cells and commitment of myogenic differentiation

International Nuclear Information System (INIS)

Jana, Soumen; Leung, Matthew; Zhang, Miqin; Chang, Julia

2014-01-01

Skeletal muscle injury can lead to severe motor deficits that adversely affect movement and quality of life. Current surgical treatments for skeletal muscle are hindered by the poor formation of organized myotube bundles at the wound site. Tissue-engineered skeletal muscle constructs to date have been unable to generate high degrees of myotube density and alignment. Generating a suitable in vitro tissue-engineered skeletal muscle construct requires the design of a scaffold that recapitulates the structural combination of nanoscale collagen fibrils and aligned microscale basal lamina tracks present in the native extracellular matrix (ECM). We hypothesized that a 3D aligned tubular porous scaffold containing aligned nanofibers inside the pores can mimic the native muscle tissue environment. We constructed a laminar section of the hypothesized scaffold with aligned chitosan-PCL nanofibers arranged co-axially with the aligned microscale chitosan scaffold bands to mimic the required myogenic environment. A 6-day study of C2C12 mouse myoblast cells cultured on this hybrid scaffold indicated that the nanofibers and scaffold bands in the scaffold played a synergetic role in directing cell orientation, interaction, migration and organization. Our results showed that aligned nanofibers mediated cell alignment and the aligned scaffold bands induced the formation of a more compact assembly of myotube cells as compared to various control substrates including chitosan films, nanofibers, and chitosan bands. The expression levels of both early and late-stage myogenic differentiation genes associated with myogenin and myosin heavy chain, respectively, were higher on the hybrid substrate than on control substrates. Our study suggests that the combination of nano and microscale topological features in the ECM can direct myogenic differentiation, and the hybrid material has the potential to improve the outcome of skeletal tissue engineering. (papers)

Development of the Main Wing Structure of a High Altitude Long Endurance UAV

Science.gov (United States)

Park, Sang Wook; Shin, Jeong Woo; Kim, Tae-Uk

2018-04-01

To enhance the flight endurance of a HALE UAV, the main wing of the UAV should have a high aspect ratio and low structural weight. Since a main wing constructed with the thin walled and slender components needed for low structural weight can suffer catastrophic failure during flight, it is important to develop a light-weight airframe without sacrificing structural integrity. In this paper, the design of the main wing of the HALE UAV was conducted using spars which were composed of a carbon-epoxy cylindrical tube and bulkheads to achieve both the weight reduction and structural integrity. The spars were sized using numerical analysis considering non-linear deformation under bending moment. Static strength testing of the wing was conducted under the most critical load condition. Then, the experimental results obtained for the wing were compared to the analytical result from the non-linear finite-element analysis. It was found that the developed main wing reduced its structural weight without any failure under the ultimate load condition of the static strength testing.

Family Structure Transitions and Child Development: Instability, Selection, and Population Heterogeneity.

Science.gov (United States)

Lee, Dohoon; McLanahan, Sara

2015-08-01

A growing literature documents the importance of family instability for child wellbeing. In this article, we use longitudinal data from the Fragile Families and Child Wellbeing Study to examine the impacts of family instability on children's cognitive and socioemotional development in early and middle childhood. We extend existing research in several ways: (1) by distinguishing between the number and types of family structure changes; (2) by accounting for time-varying as well as time-constant confounding; and (3) by assessing racial/ethnic and gender differences in family instability effects. Our results indicate that family instability has a causal effect on children's development, but the effect depends on the type of change, the outcome assessed, and the population examined. Generally speaking, transitions out of a two-parent family are more negative for children's development than transitions into a two-parent family. The effect of family instability is stronger for children's socioemotional development than for their cognitive achievement. For socioemotional development, transitions out of a two-parent family are more negative for white children, whereas transitions into a two-parent family are more negative for Hispanic children. These findings suggest that future research should pay more attention to the type of family structure transition and to population heterogeneity.

High-Reliable PLC RTOS Development and RPS Structure Analysis

Energy Technology Data Exchange (ETDEWEB)

Sohn, H. S.; Song, D. Y.; Sohn, D. S.; Kim, J. H. [Enersys Co., Daejeon (Korea, Republic of)

2008-04-15

One of the KNICS objectives is to develop a platform for Nuclear Power Plant(NPP) I and C(Instrumentation and Control) system, especially plant protection system. The developed platform is POSAFE-Q and this work supports the development of POSAFE-Q with the development of high-reliable real-time operating system(RTOS) and programmable logic device(PLD) software. Another KNICS objective is to develop safety I and C systems, such as Reactor Protection System(RPS) and Engineered Safety Feature-Component Control System(ESF-CCS). This work plays an important role in the structure analysis for RPS. Validation and verification(V and V) of the safety critical software is an essential work to make digital plant protection system highly reliable and safe. Generally, the reliability and safety of software based system can be improved by strict quality assurance framework including the software development itself. In other words, through V and V, the reliability and safety of a system can be improved and the development activities like software requirement specification, software design specification, component tests, integration tests, and system tests shall be appropriately documented for V and V.

High-Reliable PLC RTOS Development and RPS Structure Analysis

International Nuclear Information System (INIS)

Sohn, H. S.; Song, D. Y.; Sohn, D. S.; Kim, J. H.

2008-04-01

One of the KNICS objectives is to develop a platform for Nuclear Power Plant(NPP) I and C(Instrumentation and Control) system, especially plant protection system. The developed platform is POSAFE-Q and this work supports the development of POSAFE-Q with the development of high-reliable real-time operating system(RTOS) and programmable logic device(PLD) software. Another KNICS objective is to develop safety I and C systems, such as Reactor Protection System(RPS) and Engineered Safety Feature-Component Control System(ESF-CCS). This work plays an important role in the structure analysis for RPS. Validation and verification(V and V) of the safety critical software is an essential work to make digital plant protection system highly reliable and safe. Generally, the reliability and safety of software based system can be improved by strict quality assurance framework including the software development itself. In other words, through V and V, the reliability and safety of a system can be improved and the development activities like software requirement specification, software design specification, component tests, integration tests, and system tests shall be appropriately documented for V and V.

Supporting Structures for Education for Sustainable Development and School-Based Health Promotion

Science.gov (United States)

Madsen, Katrine Dahl; Nordin, Lone Lindegaard; Simovska, Venka

2016-01-01

The article aims to explore the following question: "How is education for sustainable development and health education in schools approached and contextualized at a municipal level, and what contradictions and tensions might local structures imply for sustainable health promoting school development?" Based on interviews with key agents…

Development of Applicabe Methods for Evaluating the Safety of Offsshore Structures

DEFF Research Database (Denmark)

Sørensen, John Dalsgaard; Thoft-Christensen, Palle; Sigurdsson, Gudfinnur

] was published in January 1985 and describes the computer programme package UNZIP by which the reliability of 3-dimensional structures can be evaluated. The present paper describes progress made during the first four months of 1985. A new program package called MEKBETA is described. By this program fundamental......The research project "Development of applicable methods for evaluating the safety of offshore structures" was initiated in August 1984. It is in 1985 supported by Danish Ministry of Energy with D. kr. 380.000. The results obtained will be published in a series of papers. The first paper [1...... mechanisms can be identified automatically. Also significant mechanisms in plane and space frame and lattice structures are identified automatically. Finally, the reliability of the structural system is estimated on the basis of the identified significant mechanisms. The automatic generation of fundamental...

Student perception and conceptual development as represented by student mental models of atomic structure

Science.gov (United States)

Park, Eun Jung

The nature of matter based upon atomic theory is a principal concept in science; hence, how to teach and how to learn about atoms is an important subject for science education. To this end, this study explored student perceptions of atomic structure and how students learn about this concept by analyzing student mental models of atomic structure. Changes in student mental models serve as a valuable resource for comprehending student conceptual development. Data was collected from students who were taking the introductory chemistry course. Responses to course examinations, pre- and post-questionnaires, and pre- and post-interviews were used to analyze student mental models of atomic structure. First, this study reveals that conceptual development can be achieved, either by elevating mental models toward higher levels of understanding or by developing a single mental model. This study reinforces the importance of higher-order thinking skills to enable students to relate concepts in order to construct a target model of atomic structure. Second, Bohr's orbital structure seems to have had a strong influence on student perceptions of atomic structure. With regard to this finding, this study suggests that it is instructionally important to teach the concept of "orbitals" related to "quantum theory." Third, there were relatively few students who had developed understanding at the level of the target model, which required student understanding of the basic ideas of quantum theory. This study suggests that the understanding of atomic structure based on the idea of quantum theory is both important and difficult. Fourth, this study included different student assessments comprised of course examinations, questionnaires, and interviews. Each assessment can be used to gather information to map out student mental models. Fifth, in the comparison of the pre- and post-interview responses, this study showed that high achieving students moved toward more improved models or to advanced

Development and verification testing of automation and robotics for assembly of space structures

Science.gov (United States)

Rhodes, Marvin D.; Will, Ralph W.; Quach, Cuong C.

1993-01-01

A program was initiated within the past several years to develop operational procedures for automated assembly of truss structures suitable for large-aperture antennas. The assembly operations require the use of a robotic manipulator and are based on the principle of supervised autonomy to minimize crew resources. A hardware testbed was established to support development and evaluation testing. A brute-force automation approach was used to develop the baseline assembly hardware and software techniques. As the system matured and an operation was proven, upgrades were incorprated and assessed against the baseline test results. This paper summarizes the developmental phases of the program, the results of several assembly tests, the current status, and a series of proposed developments for additional hardware and software control capability. No problems that would preclude automated in-space assembly of truss structures have been encountered. The current system was developed at a breadboard level and continued development at an enhanced level is warranted.

Automated Reconstruction of Historic Roof Structures from Point Clouds - Development and Examples

Science.gov (United States)

Pöchtrager, M.; Styhler-Aydın, G.; Döring-Williams, M.; Pfeifer, N.

2017-08-01

The analysis of historic roof constructions is an important task for planning the adaptive reuse of buildings or for maintenance and restoration issues. Current approaches to modeling roof constructions consist of several consecutive operations that need to be done manually or using semi-automatic routines. To increase efficiency and allow the focus to be on analysis rather than on data processing, a set of methods was developed for the fully automated analysis of the roof constructions, including integration of architectural and structural modeling. Terrestrial laser scanning permits high-detail surveying of large-scale structures within a short time. Whereas 3-D laser scan data consist of millions of single points on the object surface, we need a geometric description of structural elements in order to obtain a structural model consisting of beam axis and connections. Preliminary results showed that the developed methods work well for beams in flawless condition with a quadratic cross section and no bending. Deformations or damages such as cracks and cuts on the wooden beams can lead to incomplete representations in the model. Overall, a high degree of automation was achieved.

THE RESOURCE POTENTIAL AND THE DEVELOPMENT STRATEGY OF COMPETITIVE ADVANTAGES IN BUSINESS STRUCTURE

Directory of Open Access Journals (Sweden)

Okolnishnikova Irina Yurievna

2013-02-01

Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure. As the research methodology the complex of principles and tools of system and axiological approaches is used. According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified. Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.

Development of porous structure simulator for multi-scale simulation of irregular porous catalysts

International Nuclear Information System (INIS)

Koyama, Michihisa; Suzuki, Ai; Sahnoun, Riadh; Tsuboi, Hideyuki; Hatakeyama, Nozomu; Endou, Akira; Takaba, Hiromitsu; Kubo, Momoji; Del Carpio, Carlos A.; Miyamoto, Akira

2008-01-01

Efficient development of highly functional porous materials, used as catalysts in the automobile industry, demands a meticulous knowledge of the nano-scale interface at the electronic and atomistic scale. However, it is often difficult to correlate the microscopic interfacial interactions with macroscopic characteristics of the materials; for instance, the interaction between a precious metal and its support oxide with long-term sintering properties of the catalyst. Multi-scale computational chemistry approaches can contribute to bridge the gap between micro- and macroscopic characteristics of these materials; however this type of multi-scale simulations has been difficult to apply especially to porous materials. To overcome this problem, we have developed a novel mesoscopic approach based on a porous structure simulator. This simulator can construct automatically irregular porous structures on a computer, enabling simulations with complex meso-scale structures. Moreover, in this work we have developed a new method to simulate long-term sintering properties of metal particles on porous catalysts. Finally, we have applied the method to the simulation of sintering properties of Pt on alumina support. This newly developed method has enabled us to propose a multi-scale simulation approach for porous catalysts

A Structural Equation Modelling for CRM Development in rural Tourism in the Catalan Pyrenees

Directory of Open Access Journals (Sweden)

José Mª Prat Forga

2014-12-01

Full Text Available This paper investigates the interrelationships between customer relationship management development in rural tourism, information and communication technologies level in the territory, perceived economic impacts and rural tourism development. A total of 76 respondents completed a survey conducted in the Spanish Pyrenees Mountains in order to examine the structural effects of these impact factors. The results reveal that the support for customer relationship management development in rural tourism shown by rural tourism workers mainly depends on the level of development of information and communication technologies. A confirmatory factor analysis and structural equation modelling procedure were performed, respectively, using the AMOS software. 

Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

Energy Technology Data Exchange (ETDEWEB)

Gu, Y.

1989-01-01

The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the {alpha}-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced {sup 22}Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the {gamma}, {delta}, and {epsilon} subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four ({alpha}, {beta}, {gamma}, and {delta}) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the {alpha}, {beta}, and {delta} subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the {gamma}- and {epsilon}- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the {gamma} is replaced by {epsilon}.

Immunological studies on the structure and function of the nicotinic acetylcholine receptor in mammalian muscle

International Nuclear Information System (INIS)

Gu, Y.

1989-01-01

The specificity of the antibodies in the serum of a patient with myasthenia gravis for a the α-bungarotoxin binding sites of the acetylcholine receptor (AChR) was examined using AChRs in the C2 mouse muscle cell line as a model. The antibodies were shown to be specific for one of the two toxin-binding sites. The effect of the antibodies in this myasthenic serum on the functional response of the receptor to cholinergic agonists was also examined using carbamylcholine-induced 22 Na uptake into C2 myotubes as a measured of the receptor function. Antibodies specific for the γ, δ, and ε subunit, respectively, of mammalian muscle AChRs were developed using subunit-specific synthetic peptides as antigens. Using these antibodies and monoclonal antibodies for other subunits as probes, I have identified four (α, β, γ, and δ) subunits of mammalian muscle AChRs on immunoblots. When AChRs from embryonic, neonatal, normal and denervated adult muscles were compared on immunoblots, the α, β, and δ subunits were identical in all four receptor preparations, with or without endoglycosidase digestion. The spatial and temporal distribution of the γ- and ε- AChRs in developing and in denervated muscles corresponds to the distribution of AChRs with slow and fast channels, respectively, and that the development changes in the channel properties of the receptor arise from a change in the subunit composition of the receptor, in which the γ is replaced by ε

Development and validation of a strain-based Structural Health Monitoring system

Science.gov (United States)

Katsikeros, Ch. E.; Labeas, G. N.

2009-02-01

An innovative Structural Health Monitoring (SHM) methodology, based on structural strain measurements, which are processed by a back-propagation feed-forward Artificial Neural Network (ANN), is proposed. The demonstration of the SHM methodology and the identification of its capabilities and drawbacks are performed by applying the method in the prediction of fatigue damage states of a typical aircraft cracked lap-joint structure. An ANN of suitable architecture is developed and trained by numerically generated strain data sets, which have been preprocessed by Fast Fourier Transformation (FFT) for the extraction of the Fourier Descriptors (FDs). The Finite Element (FE) substructuring technique is implemented in the stress and strain analysis of the lap-joint structure, due to its efficiency in the calculation of the numerous strain data, which are necessary for the ANN training. The trained network is successfully validated, as it is proven capable to accurately predict crack positions and lengths of a lap-joint structure, which is damaged by fatigue cracks of unknown location and extent. The proposed methodology is applicable to the identification of more complex types of damage or to other critical structural locations, as its basic concept is generic.

Compositional effects on the development of damage structures in accelerator

International Nuclear Information System (INIS)

Williams, T.M.

A study of the development of dislocation structures in charged particle irradiated austenitic alloys has shown that the effects of irradiation and materials variables may be apparent at doses of the order approximately 1 dpa. Irradiation of identical specimens to much higher doses indicates that low and high dose behaviour are closely related

Continuous Release of Tumor-Derived Factors Improves the Modeling of Cachexia in Muscle Cell Culture

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Robert W. Jackman

2017-09-01

Full Text Available Cachexia is strongly associated with a poor prognosis in cancer patients but the biological trigger is unknown and therefore no therapeutics exist. The loss of skeletal muscle is the most deleterious aspect of cachexia and it appears to depend on secretions from tumor cells. Models for studying wasting in cell culture consist of experiments where skeletal muscle cells are incubated with medium conditioned by tumor cells. This has led to candidates for cachectic factors but some of the features of cachexia in vivo are not yet well-modeled in cell culture experiments. Mouse myotube atrophy measured by myotube diameter in response to medium conditioned by mouse colon carcinoma cells (C26 is consistently less than what is seen in muscles of mice bearing C26 tumors with moderate to severe cachexia. One possible reason for this discrepancy is that in vivo the C26 tumor and skeletal muscle share a circulatory system exposing the muscle to tumor factors in a constant and increasing way. We have applied Transwell®-adapted cell culture conditions to more closely simulate conditions found in vivo where muscle is exposed to the ongoing kinetics of constant tumor secretion of active factors. C26 cells were incubated on a microporous membrane (a Transwell® insert that constitutes the upper compartment of wells containing plated myotubes. In this model, myotubes are exposed to a constant supply of cancer cell secretions in the medium but without direct contact with the cancer cells, analogous to a shared circulation of muscle and cancer cells in tumor-bearing animals. The results for myotube diameter support the idea that the use of Transwell® inserts serves as a more physiological model of the muscle wasting associated with cancer cachexia than the bolus addition of cancer cell conditioned medium. The Transwell® model supports the notion that the dose and kinetics of cachectic factor delivery to muscle play a significant role in the extent of pathology.

EVOLUTIVE AND STRUCTURAL CHANGES OF MOUNTAIN TOURISM WITH IMPACT ON SUSTAINABLE DEVELOPMENT IN ROMANIA

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RODICA-MANUELA GOGONEA

2014-05-01

Full Text Available Following the global economic crisis, sustainable development of tourism in Romania, is still one of the main drivers of economic recovery mechanism. Treated in an integrating vision, sustainable tourism includes a wide range of matters affecting mountain tourism a basic shape of this area of activity. The study highlights the level of development and place of mountain tourism, among other forms of Romanian tourism through evolutionary and structural analysis of the number of structures for tourist arrivals and overnight stays within them. Purposes of determining aspects of mountain tourism development are aiming to detect its impact on sustainable development. However, the overall image of the development of mountain tourism has created the premises for the adoption of strategies for sustainable development of tourism in Romania

Development of structural health monitoring and early warning system for reinforced concrete system

International Nuclear Information System (INIS)

Iranata, Data; Wahyuni, Endah; Murtiadi, Suryawan; Widodo, Amien; Riksakomara, Edwin; Sani, Nisfu Asrul

2015-01-01

Many buildings have been damaged due to earthquakes that occurred recently in Indonesia. The main cause of the damage is the large deformation of the building structural component cannot accommodate properly. Therefore, it is necessary to develop the Structural Health Monitoring System (SHMS) to measure precisely the deformation of the building structural component in the real time conditions. This paper presents the development of SHMS for reinforced concrete structural system. This monitoring system is based on deformation component such as strain of reinforcement bar, concrete strain, and displacement of reinforced concrete component. Since the deformation component has exceeded the limit value, the warning message can be sent to the building occupies. This warning message has also can be performed as early warning system of the reinforced concrete structural system. The warning message can also be sent via Short Message Service (SMS) through the Global System for Mobile Communications (GSM) network. Hence, the SHMS should be integrated with internet modem to connect with GSM network. Additionally, the SHMS program is verified with experimental study of simply supported reinforced concrete beam. Verification results show that the SHMS has good agreement with experimental results

Developing and supporting coordinators of structured mentoring schemes in South Africa

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Penny Abbott

2010-10-01

Research purpose: The aim of this research is to discover what the characteristics of coordinators of structured mentoring schemes in South Africa are, what is required of such coordinators and how they feel about their role, with a view to improving development and support for them. Motivation for the study: The limited amount of information about role requirements for coordinators which is available in the literature is not based on empirical research. This study aims to supply the empirical basis for improved development and support for coordinators. Research design and method: A purposive sample of 25 schemes was identified and both quantitative and qualitative data, obtained through questionnaires and interviews, were analysed using descriptive statistics and thematic analysis. Main findings: Functions of coordinators tend to be similar across different types of mentoring schemes. A passion for mentoring is important, as the role involves many frustrations. There is little formalised development and support for coordinators. Practical/managerial implications: The study clarifies the functions of the coordinator, offers a job description and profile and makes suggestions on how to improve the development of the coordinator’s skills. Contribution/value-add: An understanding of what is required from a coordinator, how the necessary knowledge and skills can be developed and how the coordinator can be supported,adds value to an organisation setting up or reviewing its structured mentoring schemes.

Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy.

Science.gov (United States)

Nunes, Andreia M; Wuebbles, Ryan D; Sarathy, Apurva; Fontelonga, Tatiana M; Deries, Marianne; Burkin, Dean J; Thorsteinsdóttir, Sólveig

2017-06-01

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here, we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/- embryos. Fetal dyW-/- muscles display the same number of myofibers as wildtype (WT) muscles, but by E18.5 dyW-/- muscles are significantly smaller and muscle size is not recovered post-natally. These results suggest that fetal dyW-/- myofibers fail to grow at the same rate as WT myofibers. Consistent with this hypothesis between E17.5 and E18.5 dyW-/- muscles display a dramatic drop in the number of Pax7- and myogenin-positive cells relative to WT muscles, suggesting that dyW-/- muscles fail to generate enough muscle cells to sustain fetal myofiber growth. Gene expression analysis of dyW-/- E17.5 muscles identified a significant increase in the expression of the JAK-STAT target gene Pim1 and muscles from 2-day and 3-week old dyW-/- mice demonstrate a dramatic increase in pSTAT3 relative to WT muscles. Interestingly, myotubes lacking integrin α7β1, a laminin-receptor, also show a significant increase in pSTAT3 levels compared with WT myotubes, indicating that α7β1 can act as a negative regulator of STAT3 activity. Our data reveal for the first time that dyW-/- mice exhibit a myogenesis defect already in utero. We propose that overactivation of JAK-STAT signaling is part of the mechanism underlying disease onset and progression in dyW-/- mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Word Structures of Granada Spanish-Speaking Preschoolers with Typical versus Protracted Phonological Development

Science.gov (United States)

May Bernhardt, B.; Hanson, R.; Perez, D.; Ávila, C.; Lleó, C.; Stemberger, J. P.; Carballo, G.; Mendoza, E.; Fresneda, D.; Chávez-Peón, M.

2015-01-01

Background: Research on children's word structure development is limited. Yet, phonological intervention aims to accelerate the acquisition of both speech-sounds and word structure, such as word length, stress or shapes in CV sequences. Until normative studies and meta-analyses provide in-depth information on this topic, smaller investigations can…

Design and Development of Mechanical Structure and Control System for Tracked Trailing Mobile Robot

OpenAIRE

Hongchuan Xu; Jianxing Ren; Rui Zhu; Zhiwei Chen

2013-01-01

Along with the science and technology unceasing progress, the uses of tracing robots become more and more widely. Tracked tracing robot was adopted as the research object in this paper, mechanical structure and control system of robot was designed and developmented. In mechanical structure design part, structure designed and positioned  were completed, including design of robot body, wheel, underpan, transmission structure and the positioning of batteries, control panel, sensors, etc, and the...

Structural Connectivity of the Developing Human Amygdala

Science.gov (United States)

Saygin, Zeynep M.; Osher, David E.; Koldewyn, Kami; Martin, Rebecca E.; Finn, Amy; Saxe, Rebecca; Gabrieli, John D.E.; Sheridan, Margaret

2015-01-01

A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age. PMID:25875758

The Transparency of Reporting Information as a Guarantee to the Sustainable Development of Corporate Structures

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Ivchenko Viktoriia V.

2017-05-01

Full Text Available In the article, the author substantiates the view that one of the problematic aspects of the modern corporate reporting model is its low transparency, imperfection of the methods for generating indicators, which in turn does not allow for a comprehensive analysis of the activity of corporate structure. As a possible variant to improve the existing reporting model, it has been suggested to consider the basic concepts of sustainable development when disclosing information. In this context, corporate structures should also disclose the social and environmental aspects for a wide range of users – stakeholders. In the process of research, direct correlation between the transparency of banking information and the achievement of sustainable development has been substantiated; cautions regarding the asymmetry in information of banking institutions have been considered. Directions for further scientific research could be a study on the two-way communication system between the corporate structure and users of information; developing an integrated system of assessments of transparency and its impact on the sustainable development of corporate structure.

The effects of musical training on structural brain development: a longitudinal study.

Science.gov (United States)

Hyde, Krista L; Lerch, Jason; Norton, Andrea; Forgeard, Marie; Winner, Ellen; Evans, Alan C; Schlaug, Gottfried

2009-07-01

Long-term instrumental music training is an intense, multisensory and motor experience that offers an ideal opportunity to study structural brain plasticity in the developing brain in correlation with behavioral changes induced by training. Here, for the first time, we demonstrate structural brain changes after only 15 months of musical training in early childhood, which were correlated with improvements in musically relevant motor and auditory skills. These findings shed light on brain plasticity, and suggest that structural brain differences in adult experts (whether musicians or experts in other areas) are likely due to training-induced brain plasticity.

Development of Electromagnetic Band Gap Structures in the Perspective of Microstrip Antenna Design

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Md. Shahidul Alam

2013-01-01

Full Text Available Electromagnetic band gap (EBG technology has become a significant breakthrough in the radio frequency (RF and microwave applications due to their unique band gap characteristics at certain frequency ranges. Since 1999, the EBG structures have been investigated for improving performances of numerous RF and microwave devices utilizing the surface wave suppression and the artificial magnetic conductor (AMC properties of these special type metamaterial. Issues such as compactness, wide bandwidth with low attenuation level, tunability, and suitability with planar circuitry all play an important role in the design of EBG structures. Remarkable efforts have been undertaken for the development of EBG structures to be compatible with a wide range of wireless communication systems. This paper provides a comprehensive review on various EBG structures such as three-, two-, and one-dimensional (3D, 2D, and 1D EBG, mushroom and uniplanar EBG, and their successive advancement. Considering the related fabrication complexities, implementation of vialess EBG is an attractive topic for microwave engineers. For microstrip antennas, EBG structures are used in diversified ways, which of course found to be effective except in some cases. The EBG structures are also successfully utilized in antenna arrays for reducing the mutual coupling between elements of the array. Current challenges and limitations of the typical microstrip antennas and different EBG structures are discussed in details with some possible suggestions. Hopefully, this survey will guide to increasing efforts towards the development of more compact, wideband, and high-efficient uniplanar EBG structures for performance enhancement of antenna and other microwave devices.

Low-cost solar array structure development

Science.gov (United States)

Wilson, A. H.

1981-06-01

Early studies of flat-plate arrays have projected costs on the order of $50/square meter for installed array support structures. This report describes an optimized low-cost frame-truss structure that is estimated to cost below $25/square meter, including all markups, shipping an installation. The structure utilizes a planar frame made of members formed from light-gauge galvanized steel sheet and is supposed in the field by treated-wood trusses that are partially buried in trenches. The buried trusses use the overburden soil to carry uplift wind loads and thus to obviate reinforced-concrete foundations. Details of the concept, including design rationale, fabrication and assembly experience, structural testing and fabrication drawings are included.

The influence of the chain and network information and communication structure on sustainable business development

NARCIS (Netherlands)

Bremmers, H.J.; Haverkamp, D.J.; Omta, S.W.F.

2005-01-01

This article links the public-private information and communication structure (IC-structure) and Ajzen¿s model of planned behaviour to explain the development of environmental management systems (EMSs). The structure of the IC-system, especially the public-private information exchange, can influence

Development of a reliability-analysis method for category I structures

International Nuclear Information System (INIS)

Shinozuka, M.; Kako, T.; Hwang, H.; Reich, M.

1983-01-01

The present paper develops a reliability analysis method for category I nuclear structures, particularly for reinforced concrete containment structures subjected to various load combinations. The loads considered here include dead loads, accidental internal pressure and earthquake ground acceleration. For mathematical tractability, an earthquake occurrence is assumed to be governed by the Poisson arrival law, while its acceleration history is idealized as a Gaussian vector process of finite duration. A vector process consists of three component processes, each with zero mean. The second order statistics of this process are specified by a three-by-three spectral density matrix with a multiplying factor representing the overall intensity of the ground acceleration. With respect to accidental internal pressure, the following assumptions are made: (a) it occurs in accordance with the Poisson law; (b) its intensity and duration are random; and (c) its temporal rise and fall behaviors are such that a quasi-static structural analysis applies. A dead load is considered to be a deterministic constant

DEVELOPMENT AND VALIDATION OF NUMERICAL METHOD FOR STRENGTH ANALYSIS OF LATTICE COMPOSITE FUSELAGE STRUCTURES

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2016-01-01

Full Text Available Lattice composite fuselage structures are developed as an alternative to conventional composite structures based on laminated skin and stiffeners. Structure layout of lattice structures allows to realize advantages of current composite materials to a maximal extent, at the same time minimizing their main shortcomings, that allows to provide higher weight efficiency for these structures in comparison with conventional analogues.Development and creation of lattice composite structures requires development of novel methods of strength anal- ysis, as conventional methods, as a rule, are aiming to strength analysis of thin-walled elements and do not allow to get confident estimation of local strength of high-loaded unidirectional composite ribs.In the present work the method of operative strength analysis of lattice composite structure is presented, based onspecialized FE-models of unidirectional composite ribs and their intersections. In the frames of the method, every rib is modeled by a caisson structure, consisting of arbitrary number of flanges and webs, modeled by membrane finite elements. Parameters of flanges and webs are calculated automatically from the condition of stiffness characteristics equality of real rib and the model. This method allows to perform local strength analysis of high-loaded ribs of lattice structure without use of here-dimensional finite elements, that allows to shorten time of calculations and sufficiently simplify the procedure of analysis of results of calculations.For validation of the suggested method, the results of experimental investigations of full-scale prototype of shell of lattice composite fuselage section have been used. The prototype of the lattice section was manufactured in CRISM and tested in TsAGI within the frames of a number of Russian and International scientific projects. The results of validation have shown that the suggested method allows to provide high operability of strength analysis, keeping

Exploiting mAb structure characteristics for a directed QbD implementation in early process development.

Science.gov (United States)

Karlberg, Micael; von Stosch, Moritz; Glassey, Jarka

2018-03-07

In today's biopharmaceutical industries, the lead time to develop and produce a new monoclonal antibody takes years before it can be launched commercially. The reasons lie in the complexity of the monoclonal antibodies and the need for high product quality to ensure clinical safety which has a significant impact on the process development time. Frameworks such as quality by design are becoming widely used by the pharmaceutical industries as they introduce a systematic approach for building quality into the product. However, full implementation of quality by design has still not been achieved due to attrition mainly from limited risk assessment of product properties as well as the large number of process factors affecting product quality that needs to be investigated during the process development. This has introduced a need for better methods and tools that can be used for early risk assessment and predictions of critical product properties and process factors to enhance process development and reduce costs. In this review, we investigate how the quantitative structure-activity relationships framework can be applied to an existing process development framework such as quality by design in order to increase product understanding based on the protein structure of monoclonal antibodies. Compared to quality by design, where the effect of process parameters on the drug product are explored, quantitative structure-activity relationships gives a reversed perspective which investigates how the protein structure can affect the performance in different unit operations. This provides valuable information that can be used during the early process development of new drug products where limited process understanding is available. Thus, quantitative structure-activity relationships methodology is explored and explained in detail and we investigate the means of directly linking the structural properties of monoclonal antibodies to process data. The resulting information as a

Family structure and upbringing as factors of intellectual development of preschool children

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Golovey L.A.

2016-12-01

Full Text Available The paper is devoted to investigation of the influence of the family structure and family attitudes, child-parent relationship, styles of family upbringing on the intellectual develop- ment of pre-school-age children. Attention is paid to the analysis of the influence of parents and children gender. The sample included 150 children, 150 mothers and 75 fathers, all the families live in St. Petersburg. Results of the study reveal a significantly greater influence of the child's parent-child relationship and family atmosphere on the intellectual develop- ment in comparison with its structure. Negative impact of attitudes on the severity, harsh- ness, acceleration the development of the child on the intellectual development is revealed. Influence of parents’ gender on intellectual development of children manifests in the lead- ing role of the father’s relationship in girls IQ results, and mother’s parental attitudes in boys IQ results. The authors of the article reveal the importance of the adequacy of the system of regulation and control, severity of requirements for the development of girls; lack of parental custody and adequacy to meet the needs — for the development of boys. The authors outline the significant role of preschool children perception, especially girls, of the emotional atmosphere in the family in their intellectual development. This work was supported by the Russian Foundation for Humanities (project №13-06-008480 «Family as a resource for mental development of children in stable and critical periods of ontogeny»

Recent development of antifouling polymers: structure, evaluation, and biomedical applications in nano/micro-structures.

Science.gov (United States)

Liu, Lingyun; Li, Wenchen; Liu, Qingsheng

2014-01-01

Antifouling polymers have been proven to be vital to many biomedical applications such as medical implants, drug delivery, and biosensing. This review covers the major development of antifouling polymers in the last 2 decades, including the material chemistry, structural factors important to antifouling properties, and how to challenge or evaluate the antifouling performances. We then discuss the applications of antifouling polymers in nano/micro-biomedical applications in the form of nanoparticles, thin coatings for medical devices (e.g., artificial joint, catheter, wound dressing), and nano/microscale fibers. © 2014 Wiley Periodicals, Inc.

Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

Science.gov (United States)

Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

2009-02-01

Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

Development of the tube bundle structure for fluid-structure interaction analysis model

International Nuclear Information System (INIS)

Yoon, Kyung Ho; Kim, Jae Yong

2010-02-01

Tube bundle structures within a Boiler or heat exchanger are laid the fluid-structure, thermal-structure and fluid-thermal-structure coupled boundary condition. In these complicated boundary conditions, Fluid-structure interaction (FSI) occurs when fluid flow causes deformation of the structure. This deformation, in turn, changes the boundary conditions for the fluid flow. The structural analysis discipline, and then independently analyzed each other. However, the fluid dynamic force effect the behavior of the structure, and the vibration amplitude of the structure to fluid. FSI analysis model was separately created fluid and structure model, and then defined the fsi boundary condition, and simultaneously analyzed in one domain. The analysis results were compared with those of the experimental method for validating the analysis model. Flow-induced vibration test was executed with single rod configuration. The vibration amplitudes of a fuel rod were measured by the laser vibro-meter system in x and y-direction. The analyses results were not closely with the test data, but the trend was very similar with the test result. In fsi coupled analysis case, the turbulent model was very important with the reliability of the accuracy of the analysis model. Therefore, the analysis model will be needed to further study

Development of uncertainty-based work injury model using Bayesian structural equation modelling.

Science.gov (United States)

Chatterjee, Snehamoy

2014-01-01

This paper proposed a Bayesian method-based structural equation model (SEM) of miners' work injury for an underground coal mine in India. The environmental and behavioural variables for work injury were identified and causal relationships were developed. For Bayesian modelling, prior distributions of SEM parameters are necessary to develop the model. In this paper, two approaches were adopted to obtain prior distribution for factor loading parameters and structural parameters of SEM. In the first approach, the prior distributions were considered as a fixed distribution function with specific parameter values, whereas, in the second approach, prior distributions of the parameters were generated from experts' opinions. The posterior distributions of these parameters were obtained by applying Bayesian rule. The Markov Chain Monte Carlo sampling in the form Gibbs sampling was applied for sampling from the posterior distribution. The results revealed that all coefficients of structural and measurement model parameters are statistically significant in experts' opinion-based priors, whereas, two coefficients are not statistically significant when fixed prior-based distributions are applied. The error statistics reveals that Bayesian structural model provides reasonably good fit of work injury with high coefficient of determination (0.91) and less mean squared error as compared to traditional SEM.

Limits to the development of feed-forward structures in large recurrent neuronal networks

Directory of Open Access Journals (Sweden)

Susanne Kunkel

2011-02-01

Full Text Available Spike-timing dependent plasticity (STDP has traditionally been of great interest to theoreticians, as it seems to provide an answer to the question of how the brain can develop functional structure in response to repeated stimuli. However, despite this high level of interest, convincing demonstrations of this capacity in large, initially random networks have not been forthcoming. Such demonstrations as there are typically rely on constraining the problem artificially. Techniques include employing additional pruning mechanisms or STDP rules that enhance symmetry breaking, simulating networks with low connectivity that magnify competition between synapses, or combinations of the above. In this paper we first review modeling choices that carry particularly high risks of producing non-generalizable results in the context of STDP in recurrent networks. We then develop a theory for the development of feed-forward structure in random networks and conclude that an unstable fixed point in the dynamics prevents the stable propagation of structure in recurrent networks with weight-dependent STDP. We demonstrate that the key predictions of the theory hold in large-scale simulations. The theory provides insight into the reasons why such development does not take place in unconstrained systems and enables us to identify candidate biologically motivated adaptations to the balanced random network model that might enable it.

THE RESOURCE POTENTIAL AND THE DEVELOPMENT STRATEGY OF COMPETITIVE ADVANTAGES IN BUSINESS STRUCTURE

Directory of Open Access Journals (Sweden)

Ирина Юрьевна Окольнишникова

2013-04-01

Full Text Available The aim of the research is the development of theoretical approaches to the study of the essence and structure of the resource potential of entrepreneurship in the context of the development strategy of the competitive advantages in business structure.As the research methodology the complex of principles and tools of system and axiological approaches is used.According to the results of the conducted research, possessing the scientific novelty, the conceptual apparatus is clarified and the author's definition of the resource potential of the enterprise is given, a model of the resource potential structure in commercial organization is analyzed and the mechanism of strategy formation for sustainable competitive advantages provision of the organization on the basis of the effective use of its resource potential is identified.Area of application of the research results is the control of competitiveness in general and resource potential of entrepreneurial structures, in particular at all levels of the socio-economic system of society.DOI: http://dx.doi.org/10.12731/2218-7405-2013-2-39

Development of efficient finite elements for structural integrity analysis of solid rocket motor propellant grains

International Nuclear Information System (INIS)

Marimuthu, R.; Nageswara Rao, B.

2013-01-01

Solid propellant rocket motors (SRM) are regularly used in the satellite launch vehicles which consist of mainly three different structural materials viz., solid propellant, liner, and casing materials. It is essential to assess the structural integrity of solid propellant grains under the specified gravity, thermal and pressure loading conditions. For this purpose finite elements developed following the Herrmann formulation are: twenty node brick element (BH20), eight node quadrilateral plane strain element (PH8) and, eight node axi-symmetric solid of revolution element (AH8). The time-dependent nature of the solid propellant grains is taken into account utilizing the direct inverse method of Schepary to specify the effective Young's modulus and Poisson's ratio. The developed elements are tested considering various problems prior to implementation in the in-house software package (viz., Finite Element Analysis of STructures, FEAST). Several SRM configurations are analyzed to assess the structural integrity under different loading conditions. Finite element analysis results are found to be in good agreement with those obtained earlier from MARC software. -- Highlights: • Developed efficient Herrmann elements. • Accuracy of finite elements demonstrated solving several known solution problems. • Time dependent structural response obtained using the direct inverse method of Schepary. • Performed structural analysis of grains under gravity, thermal and pressure loads

Development of visual inspection technology for HTTR core support graphite structure

International Nuclear Information System (INIS)

Maruyama, So; Iyoku, Tatsuo; Inagaki, Yoshiyuki; Shiozawa, Shusaku; Masuma, Yoshitaka; Miki, Toshiya.

1996-01-01

The Japan Atomic Energy Research Institute is now constructing the High Temperature Engineering Test Reactor (HTTR), which employs a visual inspection of core support graphite structure, as an inservice inspection (ISI). In this inspection, TV camera will be used to investigate the alignment and integrity of the structure. Therefore, the ISI system, a combination of radiation tolerant TV camera and graphic processing system, is developed and examined its detectability and viewing angles using a simulated hot plenum of HTTR, which has artificial defects. As a result of a series of tests, it was confirmed that this system satisfied the requirements and was quite applicable for the ISI system of HTTR core support graphite structure. In addition, further improvement of the system, like a remote control procedure, will be investigated. (author)

Development of structure design program for venturi scrubber working at self-priming mode

International Nuclear Information System (INIS)

Wang Meng; Sun Zhongning; Gu Haifeng

2012-01-01

A structure design program was developed for Venturi scrubber working at the self-priming mode. This program proposed a complete logic for thermal parameters calculation and structure design of the throat. A revised calculation for resistance relationship was carried out based on experimental study. The relative error between revised results and experimental values is within 8.6%. (authors)

The Development of Micromachined Gyroscope Structure and Circuitry Technology

Directory of Open Access Journals (Sweden)

Dunzhu Xia

2014-01-01

Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

On The Development of Additive Construction Technologies for Application to Development of Lunar/Martian Surface Structures Using In-Situ Materials

Science.gov (United States)

Werkheiser, Niki; Fiske, Michael; Edmunson, Jennifer; Khoshnevis, Behrokh

2015-01-01

For long-duration missions on other planetary bodies, the use of in-situ materials will become increasingly critical. As man's presence on these bodies expands, so must the breadth of the structures required to accommodate them including habitats, laboratories, berms, radiation shielding for natural radiation and surface reactors, garages, solar storm shelters, greenhouses, etc. Planetary surface structure manufacturing and assembly technologies that incorporate in-situ resources provide options for autonomous, affordable, pre-positioned environments with radiation shielding features and protection from micrometeorites, exhaust plume debris, and other hazards. This is important because gamma and particle radiation constitute a serious but reducible threat to long-term survival of human beings, electronics, and other materials in space environments. Also, it is anticipated that surface structures will constitute the primary mass element of lunar or Martian launch requirements. The ability to use in-situ materials to construct these structures will provide a benefit in the reduction of up-mass that would otherwise make long-term Moon or Mars structures cost prohibitive. The ability to fabricate structures in situ brings with it the ability to repair these structures, which allows for self-sufficiency necessary for long-duration habitation. Previously, under the auspices of the MSFC In Situ Fabrication and Repair (ISFR) project and more recently, under the joint MSFC/KSC Additive Construction with Mobile Emplacement (ACME) project, the MSFC Surface Structures Group has been developing materials and construction technologies to support future planetary habitats with in situ resources. One such technology, known as Contour Crafting (additive construction), is shown in Figure 1, along with a typical structure fabricated using this technology. This paper will present the results to date of these efforts, including development of novel nozzle concepts for advanced layer

Relation between the development of structure and the properties of network polymers

International Nuclear Information System (INIS)

Williams, D.R.G.; Allen, P.E.M.; Simon, G.P.

1989-01-01

It was shown by various techniques that the development of structure in the early stages of cure determines the final structure and properties of glassy three-dimensional networks. Solid state [ 13 C]-nuclear magnetic resonance (NMR) techniques identified the structure groupings and the extent of heterogeneity soon after the commencement of polymerization through to the glassy state. Observations of the changes in mobility of groups during cure were correlated with the development of bulk properties such as the glass transition and compressive strength. Computer simulation of the kinetics of the polymerization based on a three-dimensional lattice closely followed the trends observed by experiment and provided insight into the formation of clusters of reacted polymer surrounded by pools of unreacted monomer. The difficulty in obtaining full cure was clearly associated with the presence of trapped reactive centres within the cluster. Observation of the behaviour of small probe or tracer molecules by NMR was shown to be a potent technique for investigating the organization of networks. 28 refs., 12 figs

Eicosapentaenoic acid abolishes inhibition of insulin-induced mTOR phosphorylation by LPS via PTP1B downregulation in skeletal muscle.

Science.gov (United States)

Wei, Hong-Kui; Deng, Zhao; Jiang, Shu-Zhong; Song, Tong-Xing; Zhou, Yuan-Fei; Peng, Jian; Tao, Ya-Xiong

2017-01-05

Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) increase insulin signaling in skeletal muscle. In the current study, we investigated the effect of eicosapentaenoic acid (EPA) on insulin-induced mammalian target of rapamycin (mTOR) phosphorylation in myotubes. We showed that EPA did not affect basal and insulin-induced mTOR phosphorylation in myotubes. However, EPA abolished lipopolysaccharide (LPS) -induced deficiency in insulin signaling (P  0.05). In myotubes, LPS stimulated PTP1B expression via NF-κB and activation protein-1 (AP1). Pre-incubation of 50 μM EPA prevented the LPS-induced activation of AP1 and NF-κΒ as well as PTP1B expression (P < 0.05). Interestingly, incubation of peroxisome proliferator-activated receptor γ (PPARγ) antagonist (GW9662) prior to EPA treatment, the effect of EPA on insulin-induced mTOR phosphorylation was blocked. Accordingly, EPA did not inhibit the LPS-induced activation of AP1 or NF-κΒ as well as PTP1B expression when incubation of GW9662 prior to EPA treatment. The in vivo study showed that EPA prevented LPS-induced PTPT1B expression and a decrease in insulin-induced mTOR phosphorylation in muscle of mice. In summary, EPA abolished LPS inhibition of insulin-induced mTOR phosphorylation in myotubes, and one of the key mechanisms was to inhibit AP1 and NF-κB activation and PTP1B transcription. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Research and Development of Rapid Design Systems for Aerospace Structure

Science.gov (United States)

Schaeffer, Harry G.

1999-01-01

This report describes the results of research activities associated with the development of rapid design systems for aerospace structures in support of the Intelligent Synthesis Environment (ISE). The specific subsystems investigated were the interface between model assembly and analysis; and, the high performance NASA GPS equation solver software system in the Windows NT environment on low cost high-performance PCs.

Development of a Wireless Unified-Maintenance System for the Structural Health Monitoring of Civil Structures.

Science.gov (United States)

Heo, Gwanghee; Son, Byungjik; Kim, Chunggil; Jeon, Seunggon; Jeon, Joonryong

2018-05-09

A disaster preventive structural health monitoring (SHM) system needs to be equipped with the following abilities: First, it should be able to simultaneously measure diverse types of data (e.g., displacement, velocity, acceleration, strain, load, temperature, humidity, etc.) for accurate diagnosis. Second, it also requires standalone power supply to guarantee its immediate response in crisis (e.g., sudden interruption of normal AC power in disaster situations). Furthermore, it should be capable of prompt processing and realtime wireless communication of a huge amount of data. Therefore, this study is aimed at developing a wireless unified-maintenance system (WUMS) that would satisfy all the requirements for a disaster preventive SHM system of civil structures. The WUMS is designed to measure diverse types of structural responses in realtime based on wireless communication, allowing users to selectively use WiFi RF band and finally working in standalone mode by means of the field-programmable gate array (FPGA) technology. To verify its performance, the following tests were performed: (i) A test to see how far communication is possible in open field, (ii) a test on a shaker to see how accurate responses are, (iii) a modal test on a bridge to see how exactly characteristic real-time dynamic responses are of structures. The test results proved that the WUMS was able to secure stable communication far up to nearly 800 m away by acquiring wireless responses in realtime accurately, when compared to the displacement and acceleration responses which were acquired through wired communication. The analysis of dynamic characteristics also showed that the wireless acceleration responses in real-time represented satisfactorily the dynamic properties of structures. Therefore, the WUMS is proved valid as a SHM, and its outstanding performance is also proven.

The Resource Structure of the Potential of Economic Development and Growth of Wealth of the Modern Macroeconomic Systems

Directory of Open Access Journals (Sweden)

Silantiev Oleh I.

2018-03-01

Full Text Available The publication is aimed at researching the features of formation and structure of economic potential of the economic development of modern macroeconomic systems. The research used the structural-functional, systemic, integral and logical approaches together with the methods of analysis and synthesis, induction and deduction. A formalization of the resource structure of the potential of economic development of modern macroeconomic systems with allocation of defining (mandatory kinds of resources (wealth and clarification of their (its specifics in the concrete historical conditions of society’s living was carried out. The bases of identification of essence and structure of the economic potential of development of the modern macroeconomic systems are clarified by its kinds. The factors of strategic influence on the process of formation of the economic development potential of the modern macroeconomic systems were researched. The value of the carried out research is the improved theoretical approaches to understanding the essence and structure of both the economic potential and the economic development potential of macroeconomic systems. Prospects for further research are the in-depth analysis of the individual components of the resource structure of the economic development potential of macroeconomic systems, especially the imperative types of wealth.

New Tools Being Developed for Engine- Airframe Blade-Out Structural Simulations

Science.gov (United States)

Lawrence, Charles

2003-01-01

One of the primary concerns of aircraft structure designers is the accurate simulation of the blade-out event. This is required for the aircraft to pass Federal Aviation Administration (FAA) certification and to ensure that the aircraft is safe for operation. Typically, the most severe blade-out occurs when a first-stage fan blade in a high-bypass gas turbine engine is released. Structural loading results from both the impact of the blade onto the containment ring and the subsequent instantaneous unbalance of the rotating components. Reliable simulations of blade-out are required to ensure structural integrity during flight as well as to guarantee successful blade-out certification testing. The loads generated by these analyses are critical to the design teams for several components of the airplane structures including the engine, nacelle, strut, and wing, as well as the aircraft fuselage. Currently, a collection of simulation tools is used for aircraft structural design. Detailed high-fidelity simulation tools are used to capture the structural loads resulting from blade loss, and then these loads are used as input into an overall system model that includes complete structural models of both the engines and the airframe. The detailed simulation (shown in the figure) includes the time-dependent trajectory of the lost blade and its interactions with the containment structure, and the system simulation includes the lost blade loadings and the interactions between the rotating turbomachinery and the remaining aircraft structural components. General-purpose finite element structural analysis codes are typically used, and special provisions are made to include transient effects from the blade loss and rotational effects resulting from the engine s turbomachinery. To develop and validate these new tools with test data, the NASA Glenn Research Center has teamed with GE Aircraft Engines, Pratt & Whitney, Boeing Commercial Aircraft, Rolls-Royce, and MSC.Software.

On the chromospheric network structure around deVeloped groups of sunspots

International Nuclear Information System (INIS)

Kartashova, L.G.

1980-01-01

The chromospheric network structure around several developed groups of sunspots were studied on the basis of the observations in the Hsub(α) line. The resolution on the filtergrams was of 2. The following was found: 1) in the neighbourhood of the groups of sunspots 70% (from 870) of network cells stretch along fibrils direction (with accuracy 30 deg), and 15% of cells stretch approximately across that (at angles 70-90 deg); 2) out of the boundary of the main radial fibrils structure the groups of sunspots is often rounded by the system of network cells stretched approximately perpendicular to radial direction

Development of risk benefit structural design method for innovative reactor plants

International Nuclear Information System (INIS)

Yoshio Kamishima; Tai Asayama; Yukio Takahashi; Masanori Tashimo; Hideo Machida; Yomomi Otani; Yasuharu Chuman

2005-01-01

The development of innovative nuclear plants where the energy in the future is carried out in Japan. The design method based on a risk benefit of having maintained mitigation of a risk and the improvement in economy is called for, in order to realize the national innovative nuclear plants. Main key technologies of the risk benefit structural design method are crack propagation evaluation technology and structural reliability evaluation technology. This research aims at pulling up these two technologies on an engineering practical use level. In this paper, requirements from the design of typical innovative nuclear plants and research plan are shown.(authors)

Structural Change and Economic Development in China and India

Directory of Open Access Journals (Sweden)

Vittorio Valli

2009-06-01

Full Text Available The comparison of the periods of rapid economic growth in China since 1978 and India since 1992 markedly show different patterns of development and structural change. However, both countries experienced some advantages of "relative economic backwardness" and some aspects of the "fordist model of growth". China had an anticipated and deeper structural change, spurred mainly by economic reforms and the growth of the internal market in the 1980s, and, since the mid-1990s, by a very rapid penetration of its industrial products in the world market. However, a substantial part of China's exports in medium and high tech sectors are due to joint-ventures with foreign multinationals. India had a more balanced structural change and a slower insertion in the world market, although some sectors, such as software, steel, automotive and pharmaceuticals are recently increasing their share in the world markets. Owing to the huge number of micro-enterprises and the great size of the informal sector, India benefited much less than China from the economies of scale and from the third wave of the "fordist model of growth". Both countries, but in particular China, experienced negative externalities of this recent phase of rapid growth, such as higher inequalities, pollution and urban congestion.

Computational structural mechanics for engine structures

Science.gov (United States)

Chamis, C. C.

1989-01-01

The computational structural mechanics (CSM) program at Lewis encompasses: (1) fundamental aspects for formulating and solving structural mechanics problems, and (2) development of integrated software systems to computationally simulate the performance/durability/life of engine structures. It is structured to mainly supplement, complement, and whenever possible replace, costly experimental efforts which are unavoidable during engineering research and development programs. Specific objectives include: investigate unique advantages of parallel and multiprocesses for: reformulating/solving structural mechanics and formulating/solving multidisciplinary mechanics and develop integrated structural system computational simulators for: predicting structural performances, evaluating newly developed methods, and for identifying and prioritizing improved/missing methods needed. Herein the CSM program is summarized with emphasis on the Engine Structures Computational Simulator (ESCS). Typical results obtained using ESCS are described to illustrate its versatility.

Bio-inspired Hybrid Carbon Nanotube Muscles

Science.gov (United States)

Kim, Tae Hyeob; Kwon, Cheong Hoon; Lee, Changsun; An, Jieun; Phuong, Tam Thi Thanh; Park, Sun Hwa; Lima, Márcio D.; Baughman, Ray H.; Kang, Tong Mook; Kim, Seon Jeong

2016-05-01

There has been continuous progress in the development for biomedical engineering systems of hybrid muscle generated by combining skeletal muscle and artificial structure. The main factor affecting the actuation performance of hybrid muscle relies on the compatibility between living cells and their muscle scaffolds during cell culture. Here, we developed a hybrid muscle powered by C2C12 skeletal muscle cells based on the functionalized multi-walled carbon nanotubes (MWCNT) sheets coated with poly(3,4-ethylenedioxythiophene) (PEDOT) to achieve biomimetic actuation. This hydrophilic hybrid muscle is physically durable in solution and responds to electric field stimulation with flexible movement. Furthermore, the biomimetic actuation when controlled by electric field stimulation results in movement similar to that of the hornworm by patterned cell culture method. The contraction and relaxation behavior of the PEDOT/MWCNT-based hybrid muscle is similar to that of the single myotube movement, but has faster relaxation kinetics because of the shape-maintenance properties of the freestanding PEDOT/MWCNT sheets in solution. Our development provides the potential possibility for substantial innovation in the next generation of cell-based biohybrid microsystems.

LIF is a contraction-induced myokine stimulating human myocyte proliferation

DEFF Research Database (Denmark)

Broholm, Christa; Laye, Matthew J; Brandt, Claus

2011-01-01

in skeletal muscle, but LIF was not detectable in plasma of the subjects. However, electrically stimulated cultured human myotubes produced and secreted LIF, suggesting that LIF is a myokine with local effects. The well-established exercise-induced signaling molecules PI3K, Akt and mTor contributed...... to the regulation of LIF in cultured human myotubes as chemical inhibition of PI3K and mTor and siRNA knockdown of Akt1 were independently sufficient to down regulate LIF. Human myoblast proliferation was increased by recombinant exogenous LIF and decreased by siRNA knockdown of the endogenous LIF receptor. Finally...

Development of cold source moderator structure

International Nuclear Information System (INIS)

Aso, Tomokaze; Ishikura, Syuichi; Terada, Atsuhiko; Teshigawara, Makoto; Watanabe, Noboru; HIno, Ryutaro

1999-01-01

The cold and thermal neutrons generated at the target (which works as a spallation neutron source under a 5MW proton beam condition) is filtered with cold source moderators using supercritical hydrogen. Preliminary structural analysis was carried out to clarify technical problems on the concept of the thin-walled structure for the cold source moderator. Structural analytical results showed that the maximum stress of 1 12MPa occurred on the moderator surface, which exceeded the allowable design stresses of ordinary aluminum alloys. Flow patterns measured by water flow experiments agreed well with hydraulic analytical results, which showed that an impinging jet flow from an inner pipe of the moderator caused a recirculation flow on a large scale. Based on analytical and experimental results, new moderator structures with minute frames, blowing flow holes etc. were proposed to keep its strength and to suppress the recirculation flow. (author)

Development of an In-Situ Decommissioning Sensor Network Test Bed for Structural Condition Monitoring - 12156

Energy Technology Data Exchange (ETDEWEB)

Zeigler, Kristine E.; Ferguson, Blythe A. [Savannah River National Laboratory, Aiken, South Carolina 29808 (United States)

2012-07-01

The Savannah River National Laboratory (SRNL) has established an In Situ Decommissioning (ISD) Sensor Network Test Bed, a unique, small scale, configurable environment, for the assessment of prospective sensors on actual ISD system material, at minimal cost. The Department of Energy (DOE) is presently implementing permanent entombment of contaminated, large nuclear structures via ISD. The ISD end state consists of a grout-filled concrete civil structure within the concrete frame of the original building. Validation of ISD system performance models and verification of actual system conditions can be achieved through the development a system of sensors to monitor the materials and condition of the structure. The ISD Sensor Network Test Bed has been designed and deployed to addresses the DOE-Environmental Management Technology Need to develop a remote monitoring system to determine and verify ISD system performance. Commercial off-the-shelf sensors have been installed on concrete blocks taken from walls of the P Reactor Building at the Savannah River Site. Deployment of this low-cost structural monitoring system provides hands-on experience with sensor networks. The initial sensor system consists of groutable thermistors for temperature and moisture monitoring, strain gauges for crack growth monitoring, tilt-meters for settlement monitoring, and a communication system for data collection. Baseline data and lessons learned from system design and installation and initial field testing will be utilized for future ISD sensor network development and deployment. The Sensor Network Test Bed at SRNL uses COTS sensors on concrete blocks from the outer wall of the P Reactor Building to measure conditions expected to occur in ISD structures. Knowledge and lessons learned gained from installation, testing, and monitoring of the equipment will be applied to sensor installation in a meso-scale test bed at FIU and in future ISD structures. The initial data collected from the sensors

MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

Science.gov (United States)

Shi, Lei; Zhou, Bo; Li, Pinghua; Schinckel, Allan P; Liang, Tingting; Wang, Han; Li, Huizhi; Fu, Lingling; Chu, Qingpo; Huang, Ruihua

2015-09-01

MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Developing a computerized aging management system for concrete structures in finnish nuclear power plants

International Nuclear Information System (INIS)

Al-Neshawy, F.; Piironen, J.; Sistonen, E.; Vesikari, E.; Tuomisto, M.; Hradil, P.; Ferreira, M.

2013-01-01

Finland has four nuclear reactors units in two power plants. The first unit started operation in 1977 and in the early 1980's all four units were in use. During the last few years the aging management of the Nuclear Power Plant's (NPP) concrete structures has grown an important issue because the existing structures are reaching the end of their licensed operating lifetime (about 40 years). Therefore the nuclear power companies are developing aging management systems to avoid premature degradation of NPP facilities and to be able to extend their operating lifetime. This paper is about the development of a computerized ageing management system for the nuclear power plants concrete structures. The computerized ageing management system is built upon central database and implementation applications. It will assist the personnel of power companies to implement the aging management activities at different phases of the lifetime of a power plant. It will provide systematic methods for planning, surveillance, inspection, monitoring, condition assessment, maintenance and repair of structures. (authors)

Development and Application of a Structural Health Monitoring System Based on Wireless Smart Aggregates.

Science.gov (United States)

Yan, Shi; Ma, Haoyan; Li, Peng; Song, Gangbing; Wu, Jianxin

2017-07-17

Structural health monitoring (SHM) systems can improve the safety and reliability of structures, reduce maintenance costs, and extend service life. Research on concrete SHMs using piezoelectric-based smart aggregates have reached great achievements. However, the newly developed techniques have not been widely applied in practical engineering, largely due to the wiring problems associated with large-scale structural health monitoring. The cumbersome wiring requires much material and labor work, and more importantly, the associated maintenance work is also very heavy. Targeting a practical large scale concrete crack detection (CCD) application, a smart aggregates-based wireless sensor network system is proposed for the CCD application. The developed CCD system uses Zigbee 802.15.4 protocols, and is able to perform dynamic stress monitoring, structural impact capturing, and internal crack detection. The system has been experimentally validated, and the experimental results demonstrated the effectiveness of the proposed system. This work provides important support for practical CCD applications using wireless smart aggregates.

Development of all-beryllium riveted structures. [Frustrum; cylinders; cones

Energy Technology Data Exchange (ETDEWEB)

Floyd, D. R.; Leslie, W. W.; Miley, D. V.; Nokes, R. W.

1976-04-20

Results are presented of a development program aimed at making a full-scale, all-beryllium frustrum by riveted assembly methods. Included are descriptions of the sheet-metal fabrication practices and assembly plans. Results of extensive mechanical testing of both ingot- and powder-source beryllium products that are presented include tensile, notch-tensile, bearing, and shear tests. Although the full-size structure has not been built, examples are given of several conical and cylindrical structures that were made. The largest of these is a 20-in. diameter, 15-in. long cylinder that was roll-formed from one 0.050-in. thick ingot sheet and assembled with 60 countersunk rivets. Tensile testing of riveted flat coupons is also reported as is bulge testing of riveted cylindrical shells. A cost comparison of riveted deep-drawn and powder-source cylinders is made. Results show that when strength and dimensional tolerance requirements are not severe, a riveted assembly approach is warranted. 33 figures, 8 tables. (auth)

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

Science.gov (United States)

Rønning, Sissel B; Carlson, Cathrine R; Stang, Espen; Kolset, Svein O; Hollung, Kristin; Pedersen, Mona E

2015-01-01

The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Syndecan-4 Regulates Muscle Differentiation and Is Internalized from the Plasma Membrane during Myogenesis.

Directory of Open Access Journals (Sweden)

Sissel B Rønning

Full Text Available The cell surface proteoglycan syndecan-4 has been reported to be crucial for muscle differentiation, but the molecular mechanisms still remain to be fully understood. During in vitro differentiation of bovine muscle cells immunocytochemical analyses showed strong labelling of syndecan-4 intracellularly, in close proximity with Golgi structures, in membranes of intracellular vesicles and finally, in the nuclear area including the nuclear envelope. Chase experiments showed that syndecan-4 was internalized from the plasma membrane during this process. Furthermore, when syndecan-4 was knocked down by siRNA more myotubes were formed, and the expression of myogenic transcription factors, β1-integrin and actin was influenced. However, when bovine muscle cells were treated with a cell-penetrating peptide containing the cytoplasmic region of syndecan-4, myoblast fusion and thus myotube formation was blocked, both in normal cells and in syndecan-4 knock down cells. Altogether this suggests that the cytoplasmic domain of syndecan-4 is important in regulation of myogenesis. The internalization of syndecan-4 from the plasma membrane during muscle differentiation and the nuclear localization of syndecan-4 in differentiated muscle cells may be part of this regulation, and is a novel aspect of syndecan biology which merits further studies.

Development of new CAD system for steel structures of nuclear power plants

International Nuclear Information System (INIS)

Morii, Yasuhiro; Kudou, Takashi; Kouno, Kenichi; Yamada, Koutarou

2000-01-01

IHI has developed a new Three-Dimensional Computer-Aided Design (3D-CAD) system to improve the design efficiency and quality of the steel structure of nuclear power plants. This system covers every design phase from the initial arrangement of structure to the production design sharing the same database. The system incorporates the design rules and professional expertise of designers, and enable easy and efficient design. The system can easily generate the three-dimensional data for structures, model data for stress analyses and composite arrangement data. The system has already been applied to several plants under construction and has achieved excellent results. The outline of the new CAD system is introduced. (author)

Development and mechanical properties of structural materials from lunar simulants

Science.gov (United States)

Desai, Chandra S.; Girdner, K.; Saadatmanesh, H.; Allen, T.

1991-01-01

Development of the technologies for manufacture of structural and construction materials on the Moon, utilizing local lunar soil (regolith), without the use of water, is an important element for habitats and explorations in space. Here, it is vital that the mechanical behavior such as strength and flexural properties, fracture toughness, ductility and deformation characteristics be defined toward establishment of the ranges of engineering applications of the materials developed. The objective is to describe the research results in two areas for the above goal: (1) liquefaction of lunar simulant (at about 100 C) with different additives (fibers, powders, etc.); and (2) development and use of a new triaxial test device in which lunar simulants are first compressed under cycles of loading, and then tested with different vacuums and initial confining or in situ stress.

24 CFR 1000.160 - Are non-dwelling structures developed, acquired or assisted under the IHBG program subject to...

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Are non-dwelling structures...-dwelling structures developed, acquired or assisted under the IHBG program subject to limitations on cost or design standards? Yes. Non-dwelling structures must be of a design, size and with features or...

A proposal to develop a high temperature structural design guideline for HTGR components

International Nuclear Information System (INIS)

Hada, K.

1989-01-01

This paper presents some proposals for developing a high-temperature structural design guideline for HTGR structural components. It is appropriate that a basis for developing high-temperature structural design rules is rested on well-established elevated-temperature design guidelines, if the same failure modes are expected for high-temperature components as considered in such design guidelines. As for the applicability of ASME B and PV Code Case N-47 to structural design rules for high-temperature components (service temperatures ≥ 900 deg. C), the following critical issues on material properties and service life evaluation rules have been pointed out. (i) no work-hardening of stress-strain curves at high temperatures due to dynamic recrystallization; (ii) issues relating to very significant creep; (iii) ductility loss after long-term ageing at high temperatures; (iv) validity of life-fraction rule (Robinson-Taira rule) as creep-fatigue damage evaluation rule. Furthermore, the validity of design margins of elevated-temperature structural design guidelines to high-temperature design rules should be clarified. Solutions and proposals to these issues are presented in this paper. Concerning no work-hardening due to dynamic recrystallization, it is shown that viscous effects cannot be neglected even at high extension rate for tensile tests, and that changes in viscous deformation rates by dynamic recrystallization should be taken into account. The extension rate for tensile tests is proposed to change at high temperatures. The solutions and proposals to the above-mentioned issues lead to the conclusion that the design methodologies of N-47 are basically applicable to the high-temperature structural design guideline for HTGR structural components in service at about 900 deg. C. (author). 9 refs, 5 figs

Analytical Assessment of Structural Shifts in the Economy of the Volgograd Region in Conditions of Development of Convergent Technologies

Directory of Open Access Journals (Sweden)

Irina Aleksandrovna Elkhina

2016-06-01

Full Text Available The article presents the results of the assessment of the structural shifts in the economy of the Volgograd region due to the development of convergent technologies, innovation and technology. The development of convergent technologies is one of the factors for the transition of the economy to a new technological order. Industry structure undergoes quantitative and qualitative changes under the influence of scientific and technological progress, the development of cyclical economy and other factors. Such changes ultimately lead to structural shifts. The results of assessments of structural shifts in the economy of the Volgograd region in terms of gross value added, employment of economically active population and investment in fixed assets by economic activity are presented for the time period from 2005 to 2014. To count structural shifts in economy the author uses the index of Ryabtsev, as it has a scale of structural differences. Based on the findings, the author makes conclusions about the structural development of the region in time and as compared to the other regions in the Southern Russia. The smallest structural shifts have been obtained in terms of employment, the largest – in terms of investment in fixed assets. However, application of this index does not let to assess the degree of influence of the technological base on the development of economic system. Therefore, the author proposes to supplement the research of structural shifts by the author’s characteristic such as impulse of structural shifts, which serves as a measure of resource supply process of initiating structural shifts. Approbation of methodology for calculating impulse of structural shifts made on the basis of the Southern Russian regions with the rating on the author’s sample indicators, reflecting the state of infrastructure, innovation, human resources security, efficiency and the promotion of scientific development, amount of the costs of innovation

Developing eThread Pipeline Using SAGA-Pilot Abstraction for Large-Scale Structural Bioinformatics