WorldWideScience

Sample records for dystrophins carrying spectrin-like

  1. Spectrin-like proteins in plant nuclei

    NARCIS (Netherlands)

    Ruijter, de N.C.A.; Ketelaar, T.; Blumenthal, S.S.D.; Emons, A.M.C.; Schel, J.H.N.

    2000-01-01

    We analysed the presence and localization of spectrin-like proteins in nuclei of various plant tissues, using several anti-erythrocyte spectrin antibodies on isolated pea nuclei and nuclei in cells. Western blots of extracted purified pea nuclei show a cross-reactive pair of bands at 220–240 kDa,

  2. Disruption of Spectrin-Like Cytoskeleton in Differentiating Keratinocytes by PKCδ Activation Is Associated with Phosphorylated Adducin

    Science.gov (United States)

    Zhao, Kong-Nan; Masci, Paul P.; Lavin, Martin F.

    2011-01-01

    Spectrin is a central component of the cytoskeletal protein network in a variety of erythroid and non-erythroid cells. In keratinocytes, this protein has been shown to be pericytoplasmic and plasma membrane associated, but its characteristics and function have not been established in these cells. Here we demonstrate that spectrin increases dramatically in amount and is assembled into the cytoskeleton during differentiation in mouse and human keratinocytes. The spectrin-like cytoskeleton was predominantly organized in the granular and cornified layers of the epidermis and disrupted by actin filament inhibitors, but not by anti-mitotic drugs. When the cytoskeleton was disrupted PKCδ was activated by phosphorylation on Thr505. Specific inhibition of PKCδ(Thr505) activation with rottlerin prevented disruption of the spectrin-like cytoskeleton and the associated morphological changes that accompany differentiation. Rottlerin also inhibited specific phosphorylation of the PKCδ substrate adducin, a cytoskeletal protein. Furthermore, knock-down of endogenous adducin affected not only expression of adducin, but also spectrin and PKCδ, and severely disrupted organization of the spectrin-like cytoskeleton and cytoskeletal distribution of both adducin and PKCδ. These results demonstrate that organization of a spectrin-like cytoskeleton is associated with keratinocytes differentiation, and disruption of this cytoskeleton is mediated by either PKCδ(Thr505) phosphorylation associated with phosphorylated adducin or due to reduction of endogenous adducin, which normally connects and stabilizes the spectrin-actin complex. PMID:22163289

  3. Characterization of a 65 kDa NIF in the nuclear matrix of the monocot Allium cepa that interacts with nuclear spectrin-like proteins.

    Science.gov (United States)

    Pérez-Munive, Clara; Blumenthal, Sonal S D; de la Espina, Susana Moreno Díaz

    2012-01-01

    Plant cells have a well organized nucleus and nuclear matrix, but lack orthologues of the main structural components of the metazoan nuclear matrix. Although data is limited, most plant nuclear structural proteins are coiled-coil proteins, such as the NIFs (nuclear intermediate filaments) in Pisum sativum that cross-react with anti-intermediate filament and anti-lamin antibodies, form filaments 6-12 nm in diameter in vitro, and may play the role of lamins. We have investigated the conservation and features of NIFs in a monocot species, Allium cepa, and compared them with onion lamin-like proteins. Polyclonal antisera against the pea 65 kDa NIF were used in 1D and 2D Western blots, ICM (imunofluorescence confocal microscopy) and IEM (immunoelectron microscopy). Their presence in the nuclear matrix was analysed by differential extraction of nuclei, and their association with structural spectrin-like proteins by co-immunoprecipitation and co-localization in ICM. NIF is a conserved structural component of the nucleus and its matrix in monocots with Mr and pI values similar to those of pea 65 kDa NIF, which localized to the nuclear envelope, perichromatin domains and foci, and to the nuclear matrix, interacting directly with structural nuclear spectrin-like proteins. Its similarities with some of the proteins described as onion lamin-like proteins suggest that they are highly related or perhaps the same proteins.

  4. Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Baptiste Legrand

    Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

  5. The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins.

    Directory of Open Access Journals (Sweden)

    Glen B Banks

    2010-05-01

    Full Text Available Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophin(DeltaR4-R23/DeltaCT with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophin(DeltaR4-R23/DeltaCT led to small myofibers (12% smaller than wild-type, Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophin(DeltaR4-R23/DeltaCT with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid alpha-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.

  6. Carry

    DEFF Research Database (Denmark)

    Koijen, Ralph S.J.; Moskowitz, Tobias J.; Heje Pedersen, Lasse

    that include global equities, global bonds, currencies, commodities, US Treasuries, credit, and equity index options. This predictability underlies the strong returns to "carry trades" that go long high-carry and short low-carry securities, applied almost exclusively to currencies, but shown here...

  7. Carry

    DEFF Research Database (Denmark)

    Koijen, Ralph S.J.; Moskowitz, Tobias; Pedersen, Lasse Heje

    2018-01-01

    -sectionally and in time series for a host of different asset classes, including global equities, global bonds, commodities, US Treasuries, credit, and options. Carry is not explained by known predictors of returns from these asset classes, and it captures many of these predictors, providing a unifying framework...... for return predictability. We reject a generalized version of Uncovered Interest Parity and the Expectations Hypothesis in favor of models with varying risk premia, in which carry strategies are commonly exposed to global recession, liquidity, and volatility risks, though none fully explains carry’s premium....

  8. Generation of induced pluripotent stem cells from a Becker muscular dystrophy patient carrying a deletion of exons 45-55 of the dystrophin gene (CCMi002BMD-A-9 ∆45-55

    Directory of Open Access Journals (Sweden)

    Aoife Gowran

    2018-04-01

    Full Text Available Becker muscular dystrophy (BMD is a dystrophinopathy caused by mutations in the dystrophin gene on chromosome Xp21. BMD mutations result in truncated semi-functional dystrophin isoforms. Consequently, less severe clinical symptoms become apparent later in life compared to Duchenne muscular dystrophy. Dermal fibroblasts from a BMD patient were electroporated with episomal plasmids containing reprogramming factors to create the induced pluripotent stem cell line: CCMi002BMD-A-9 that showed pluripotent markers, were karyotypically normal and capable of trilineage differentiation. MLPA analyses performed on DNA extracted from CCMi002BMD-A-9 showed an in-frame deletion of exons 45 to 55 (CCMi002BMD-A-9 Δ45-55.

  9. Generation of induced pluripotent stem cells from a Becker muscular dystrophy patient carrying a deletion of exons 45-55 of the dystrophin gene (CCMi002BMD-A-9 ∆45-55).

    Science.gov (United States)

    Gowran, Aoife; Spaltro, Gabriella; Casalnuovo, Federica; Vigorelli, Vera; Spinelli, Pietro; Castiglioni, Elisa; Rovina, Davide; Paganini, Stefania; Di Segni, Marina; Gervasini, Cristina; Nigro, Patrizia; Pompilio, Giulio

    2018-04-01

    Becker muscular dystrophy (BMD) is a dystrophinopathy caused by mutations in the dystrophin gene on chromosome Xp21. BMD mutations result in truncated semi-functional dystrophin isoforms. Consequently, less severe clinical symptoms become apparent later in life compared to Duchenne muscular dystrophy. Dermal fibroblasts from a BMD patient were electroporated with episomal plasmids containing reprogramming factors to create the induced pluripotent stem cell line: CCMi002BMD-A-9 that showed pluripotent markers, were karyotypically normal and capable of trilineage differentiation. MLPA analyses performed on DNA extracted from CCMi002BMD-A-9 showed an in-frame deletion of exons 45 to 55 (CCMi002BMD-A-9 Δ45-55). Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  10. Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Jennifer England

    2017-07-01

    Full Text Available Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T and canine (dystrophin dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

  11. Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy.

    Science.gov (United States)

    England, Jennifer; Loughna, Siobhan; Rutland, Catrin Sian

    2017-07-07

    Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

  12. Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

    OpenAIRE

    Chen, Hung-Chih; Chin, Yu-Feng; Lundy, David J.; Liang, Chung-Tiang; Chi, Ya-Hui; Kuo, Paolin; Hsieh, Patrick C. H.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn ?/? mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/? mouse models, we demonstrate the contribution of Dp427 (f...

  13. Dystrophin Hot-Spot Mutants Leading to Becker Muscular Dystrophy Insert More Deeply into Membrane Models than the Native Protein.

    Science.gov (United States)

    Ameziane-Le Hir, Sarah; Paboeuf, Gilles; Tascon, Christophe; Hubert, Jean-François; Le Rumeur, Elisabeth; Vié, Véronique; Raguénès-Nicol, Céline

    2016-07-26

    Dystrophin (DYS) is a membrane skeleton protein whose mutations lead to lethal Duchenne muscular dystrophy or to the milder Becker muscular dystrophy (BMD). One third of BMD "in-frame" exon deletions are located in the region that codes for spectrin-like repeats R16 to R21. We focused on four prevalent mutated proteins deleted in this area (called RΔ45-47, RΔ45-48, RΔ45-49, and RΔ45-51 according to the deleted exon numbers), analyzing protein/membrane interactions. Two of the mutants, RΔ45-48 and RΔ45-51, led to mild pathologies and displayed a similar triple coiled-coil structure as the full-length DYS R16-21, whereas the two others, RΔ45-47 and RΔ45-49, induced more severe pathologies and showed "fractional" structures unrelated to the normal one. To explore lipid packing, small unilamellar liposomes (SUVs) and planar monolayers were used at various initial surface pressures. The dissociation constants determined by microscale thermophoresis (MST) were much higher for the full-length DYS R161-21 than for the mutants; thus the wild type protein has weaker SUV binding. Comparing surface pressures after protein adsorption and analysis of atomic force microscopy images of mixed protein/lipid monolayers revealed that the mutants insert more into the lipid monolayer than the wild type does. In fact, in both models every deletion mutant showed more interactions with membranes than the full-length protein did. This means that mutations in the R16-21 part of dystrophin disturb the protein's molecular behavior as it relates to membranes, regardless of whether the accompanying pathology is mild or severe.

  14. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    OpenAIRE

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao

    2010-01-01

    We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from th...

  15. Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, Edo M.; Ginjaar, Ieke B.; Bakker, Egbert; de Visser, Marianne

    2005-01-01

    Associations between clinical phenotype (muscle weakness, dilated cardiomyopathy) and dystrophin abnormalities in muscle tissue among definite carriers of Duchenne (DMD) and Becker muscular dystrophy (BMD) were investigated. No associations between dystrophin abnormalities and clinical variables in

  16. Detection of new paternal dystrophin gene mutations in isolated cases of dystrophinopathy in females

    Energy Technology Data Exchange (ETDEWEB)

    Pegoraro, E.; Wessel, H.B.; Schwartz, L.; Hoffman, E.P. (Univ. of Pittsburgh, PA (United States)); Schimke, R.N. (Kansas Univ. Medical Center, Kansas City (United States)); Arahata, Kiichi; Hayashi, Yukiko (National Institute of Neurosciences, Tokyo (Japan)); Stern, H. (Children' s National Medical Center, Washington, DC (United States)); Marks, H. (A.I. duPont Institute, Wilmington (United States)); Glasberg, M.R. (Henry Ford Hospital, Detroit, MI (United States)) (and others)

    1994-06-01

    Duchenne muscular dystrophy is one of the most common lethal monogenic disorders and is caused by dystrophin deficiency. The disease is transmitted as an X-linked recessive trait; however, recent biochemical and clinical studies have shown that many girls and women with a primary myopathy have an underlying dystrophinopathy, despite a negative family history for Duchenne dystrophy. These isolated female dystrophinopathy patients carried ambiguous diagnoses with presumed autosomal recessive inheritance (limb-girdle muscular dystrophy) prior to biochemical detection of dystrophin abnormalities in their muscle biopsy. It has been assumed that these female dystrophinopathy patients are heterozygous carries who show preferential inactivation of the X chromosome harboring the normal dystrophin gene, although this has been shown for only a few X:autosome translocations and for two cases of discordant monozygotic twin female carriers. Here the authors study X-inactivation patterns of 13 female dystrophinopathy patients - 10 isolated cases and 3 cases with a positive family history for Duchenne dystrophy in males. They show that all cases have skewed X-inactivation patterns in peripheral blood DNA. Of the nine isolated cases informative in the assay, eight showed inheritance of the dystrophin gene mutation from the paternal germ line. Only a single case showed maternal inheritance. The 10-fold higher incidence of paternal transmission of dystrophin gene mutations in these cases is at 30-fold variance with Bayesian predictions and gene mutation rates. Thus, the results suggest some mechanistic interaction between new dystrophin gene mutations, paternal inheritance, and skewed X inactivation. The results provide both empirical risk data and a molecular diagnostic test method, which permit genetic counseling and prenatal diagnosis of this new category of patients. 58 refs., 7 figs., 2 tabs.

  17. Targeted Exon Skipping to Correct Exon Duplications in the Dystrophin Gene

    Directory of Open Access Journals (Sweden)

    Kane L Greer

    2014-01-01

    Full Text Available Duchenne muscular dystrophy is a severe muscle-wasting disease caused by mutations in the dystrophin gene that ablate functional protein expression. Although exonic deletions are the most common Duchenne muscular dystrophy lesion, duplications account for 10–15% of reported disease-causing mutations, and exon 2 is the most commonly duplicated exon. Here, we describe the in vitro evaluation of phosphorodiamidate morpholino oligomers coupled to a cell-penetrating peptide and 2′-O-methyl phosphorothioate oligonucleotides, using three distinct strategies to reframe the dystrophin transcript in patient cells carrying an exon 2 duplication. Differences in exon-skipping efficiencies in vitro were observed between oligomer analogues of the same sequence, with the phosphorodiamidate morpholino oligomer coupled to a cell-penetrating peptide proving the most effective. Differences in exon 2 excision efficiency between normal and exon 2 duplication cells, were apparent, indicating that exon context influences oligomer-induced splice switching. Skipping of a single copy of exon 2 was induced in the cells carrying an exon 2 duplication, the simplest strategy to restore the reading frame and generate a normal dystrophin transcript. In contrast, multiexon skipping of exons 2–7 to generate a Becker muscular dystrophy-like dystrophin transcript was more challenging and could only be induced efficiently with the phosphorodiamidate morpholino oligomer chemistry.

  18. Complete restoration of multiple dystrophin isoforms in genetically corrected Duchenne muscular dystrophy patient–derived cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Susi Zatti

    2014-01-01

    Full Text Available Duchenne muscular dystrophy (DMD–associated cardiac diseases are emerging as a major cause of morbidity and mortality in DMD patients, and many therapies for treatment of skeletal muscle failed to improve cardiac function. The reprogramming of patients' somatic cells into pluripotent stem cells, combined with technologies for correcting the genetic defect, possesses great potential for the development of new treatments for genetic diseases. In this study, we obtained human cardiomyocytes from DMD patient–derived, induced pluripotent stem cells genetically corrected with a human artificial chromosome carrying the whole dystrophin genomic sequence. Stimulation by cytokines was combined with cell culturing on hydrogel with physiological stiffness, allowing an adhesion-dependent maturation and a proper dystrophin expression. The obtained cardiomyocytes showed remarkable sarcomeric organization of cardiac troponin T and α-actinin, expressed cardiac-specific markers, and displayed electrically induced calcium transients lasting less than 1 second. We demonstrated that the human artificial chromosome carrying the whole dystrophin genomic sequence is stably maintained throughout the cardiac differentiation process and that multiple promoters of the dystrophin gene are properly activated, driving expression of different isoforms. These dystrophic cardiomyocytes can be a valuable source for in vitro modeling of DMD-associated cardiac disease. Furthermore, the derivation of genetically corrected, patient-specific cardiomyocytes represents a step toward the development of innovative cell and gene therapy approaches for DMD.

  19. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    Science.gov (United States)

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

    2010-01-01

    SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

  20. Laryngeal Muscles Are Spared in the Dystrophin Deficient "mdx" Mouse

    Science.gov (United States)

    Thomas, Lisa B.; Joseph, Gayle L.; Adkins, Tracey D.; Andrade, Francisco H.; Stemple, Joseph C.

    2008-01-01

    Purpose: "Duchenne muscular dystrophy (DMD)" is caused by the loss of the cytoskeletal protein, dystrophin. The disease leads to severe and progressive skeletal muscle wasting. Interestingly, the disease spares some muscles. The purpose of the study was to determine the effects of dystrophin deficiency on 2 intrinsic laryngeal muscles, the…

  1. Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family

    Energy Technology Data Exchange (ETDEWEB)

    Hoop, R.C.; Schwartz, L.S.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Russo, L.S. [Univ. of Florida, Jacksonville, FL (United States); Riconda, D.L. [Orlando Regional Medical Center, Orlando, FL (United States)

    1994-02-01

    Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions-one in the 5{prime}, proximal deletional hotspot region, and the other in the 3{prime}, more distal deletional hotspot region. The second propositus showed only the 5{prime} deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, the authors show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier`s dystrophin genes, giving rise to a son with a partially {open_quotes}repaired{close_quotes} gene retaining only the 5{prime} deletion. 20 refs., 4 figs.

  2. Evaluation of point mutations in dystrophin gene in Iranian ...

    Indian Academy of Sciences (India)

    5Department of Biology, Science and Research Branch, Islamic Azad ... Dystrophin protein is found ... Duchenne and Becker muscular dystrophy; neuromuscular disorder; point mutation. ..... modern diagnostic techniques to a large cohort.

  3. [Clinical features of patients with Becker muscular dystrophy and deletions of the rod domain of dystrophin gene].

    Science.gov (United States)

    Wang, Yanyun; Zhu, Yuling; Yang, Juan; Li, Yaqin; Sun, Jiangwen; Zhan, Yixin; Zhang, Cheng

    2018-02-10

    OBJECTIVE To explore the clinical features of patients carrying deletions of the rod domain of the dystrophin gene. METHODS Clinical data of 12 Chinese patients with Becker muscular dystrophy (BMD) and such deletions was reviewed. RESULTS Most patients complained of muscle weakness of lower limbs. Two patients had muscle cramps, one had increased creatine kinase (CK) level, and one had dilated cardiomyopathy. CONCLUSION Compared with DMD, the clinical features of BMD are much more variable, particularly for those carrying deletions of the rod domain of the dystrophin gene. Muscular weakness may not be the sole complaint of BMD. The diagnosis of BMD cannot be excluded by moderately elevated CK. For male patients with dilated cardiomyopathy, the possibility of BMD should be considered.

  4. Marginal level dystrophin expression improves clinical outcome in a strain of dystrophin/utrophin double knockout mice.

    Directory of Open Access Journals (Sweden)

    Dejia Li

    2010-12-01

    Full Text Available Inactivation of all utrophin isoforms in dystrophin-deficient mdx mice results in a strain of utrophin knockout mdx (uko/mdx mice. Uko/mdx mice display severe clinical symptoms and die prematurely as in Duchenne muscular dystrophy (DMD patients. Here we tested the hypothesis that marginal level dystrophin expression may improve the clinical outcome of uko/mdx mice. It is well established that mdx3cv (3cv mice express a near-full length dystrophin protein at ∼5% of the normal level. We crossed utrophin-null mutation to the 3cv background. The resulting uko/3cv mice expressed the same level of dystrophin as 3cv mice but utrophin expression was completely eliminated. Surprisingly, uko/3cv mice showed a much milder phenotype. Compared to uko/mdx mice, uko/3cv mice had significantly higher body weight and stronger specific muscle force. Most importantly, uko/3cv outlived uko/mdx mice by several folds. Our results suggest that a threshold level dystrophin expression may provide vital clinical support in a severely affected DMD mouse model. This finding may hold clinical implications in developing novel DMD therapies.

  5. Screening of point mutations by multiple SSCP analysis in the dystrophin gene

    Energy Technology Data Exchange (ETDEWEB)

    Lasa, A.; Baiget, M.; Gallano, P. [Hospital Sant Pau, Barcelona (Spain)

    1994-09-01

    Duchenne muscular dystrophy (DMD) is a lethal, X-linked neuromuscular disorder. The population frequency of DMD is one in approximately 3500 boys, of which one third is thought to be a new mutant. The DMD gene is the largest known to date, spanning over 2,3 Mb in band Xp21.2; 79 exons are transcribed into a 14 Kb mRNA coding for a protein of 427 kD which has been named dystrophin. It has been shown that about 65% of affected boys have a gene deletion with a wide variation in localization and size. The remaining affected individuals who have no detectable deletions or duplications would probably carry more subtle mutations that are difficult to detect. These mutations occur in several different exons and seem to be unique to single patients. Their identification represents a formidable goal because of the large size and complexity of the dystrophin gene. SSCP is a very efficient method for the detection of point mutations if the parameters that affect the separation of the strands are optimized for a particular DNA fragment. The multiple SSCP allows the simultaneous study of several exons, and implies the use of different conditions because no single set of conditions will be optimal for all fragments. Seventy-eight DMD patients with no deletion or duplication in the dystrophin gene were selected for the multiple SSCP analysis. Genomic DNA from these patients was amplified using the primers described for the diagnosis procedure (muscle promoter and exons 3, 8, 12, 16, 17, 19, 32, 45, 48 and 51). We have observed different mobility shifts in bands corresponding to exons 8, 12, 43 and 51. In exons 17 and 45, altered electrophoretic patterns were found in different samples identifying polymorphisms already described.

  6. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies.

  7. Evolutionary study of vertebrate and invertebrate members of the dystrophin and utrophin gene family

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, R.G.; Nicholson, L.; Bobrow, M. [Paediatric Research Unit, London (United Kingdom)] [and others

    1994-09-01

    Vertebrates express two members of the dystrophin gene family. The prototype, dystrophin, is expressed in muscle and neural tissue, and is defective in the human disorders Duchenne and Becker muscular dystrophy (DMD, BMD). The dystrophin homologue utrophin is more generally expressed but has not yet been associated with a genetic disorder. The function of neither protein is clear. A comparison of human utrophin with the known dystrophins (human, mouse, chicken, Torpedo) suggests that dystrophin and utrophin diverged before the vertebrate radiation. We have used reverse-transcript PCR (RT-PCR) directed by degenerate primers to characterize dystrophin and utrophin transcripts from a range of vertebrate and invertebrate animals. Our results suggest that the duplication leading to distinct dystrophin and utrophin genes occurred close to the point of divergence of urochordates from the cephalochordate-vertebrate lineage. This divergence may have occurred to fulfill a novel role which arose at this point, or may reflect a need for separate regulation of the neuromuscular and other functions of the ancient dystrophin. Our data include sequences of the first non-human utrophins to be characterized, and show these to be substantially more divergent than their cognate dystrophins. In addition, our results provide a large body of information regarding the tolerance of amino acid positions in the cysteine-rich and C-terminal domains to substitution. This will aid the interpretations of DMD and BMD missense mutations in these regions.

  8. Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

    1992-09-01

    In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

  9. Spectrum of small mutations in the dystrophin coding region

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Bartolo, C.; Pearl, D.K. [Ohio State Univ., Columbus, OH (United States)] [and others

    1995-07-01

    Duchenne and Becker muscular dystrophies (DMD and BMD) are caused by defects in the dystrophin gene. About two-thirds of the affected patients have large deletions or duplications, which occur in the 5` and central portion of the gene. The nondeletion/duplication cases are most likely the result of smaller mutations that cannot be identified by current diagnostic screening strategies. We screened {approximately} 80% of the dystrophin coding sequence for small mutations in 158 patients without deletions or duplications and identified 29 mutations. The study indicates that many of the DMD and the majority of the BMD small mutations lie in noncoding regions of the gene. All of the mutations identified were unique to single patients, and most of the mutations resulted in protein truncation. We did not find a clustering of small mutations similar to the deletion distribution but found > 40% of the small mutations 3` of exon 55. The extent of protein truncation caused by the 3` mutations did not determine the phenotype, since even the exon 76 nonsense mutation resulted in the severe DMD phenotype. Our study confirms that the dystrophin gene is subject to a high rate of mutation in CpG sequences. As a consequence of not finding any hotspots or prevalent small mutations, we conclude that it is presently not possible to perform direct carrier and prenatal diagnostics for many families without deletions or duplications. 71 refs., 2 figs., 2 tabs.

  10. Increased susceptibility of dystrophin-deficient brain to mild hypoxia

    International Nuclear Information System (INIS)

    Wallis, T.; Rae, C.; Bubb, W.A.; Head, S.I.

    2002-01-01

    Full text: Duchenne muscular dystrophy is an X-linked disorder resulting from total absence of the 427 kDa protein dystrophin. Dystrophin is normally expressed in the brain mainly in a neuronal subpopulation: cortical pyramidal cells, hippocampal CA1 neurons and cerebellar Purkinje cells. One suggested role for dystrophin is in colocalising mitochondrial creatine kinase with ADP translocase and ATP synthase in mitochondria. Brain tissue slices in the murine model of Duchenne dystrophy, the mdx mouse, have been shown to be more sensitive to hypoxia than control. In this work, we used 13 C NMR to monitor the metabolic response of mdx cortical brain tissue slices to normoxia (95%O 2 /5% CO 2 ) and mild hypoxia (95%air/5% CO 2 ). Under normoxic conditions, mdx cortical slices displayed increased net flux through the Krebs cycle and glutamate/glutamine cycle, consistent with the proposed GABA A lesion which results in decreased inhibitory input. By contrast, mild hypoxia resulted in a significant increase in the total pool size of lactate and decreased net flux of 13 C from [3- 13 C]pyruvate into glutamate C4, GABA C2 and Ala C2, as well as decreased anaplerotic activity as measured by the ratio of Asp C2: Asp C3 label. Mild hypoxia has a significantly greater effect on brain oxidative metabolism in mdx mice, than in control

  11. Targeted Exon Skipping to Address “Leaky” Mutations in the Dystrophin Gene

    Directory of Open Access Journals (Sweden)

    Sue Fletcher

    2012-01-01

    Full Text Available Protein-truncating mutations in the dystrophin gene lead to the progressive muscle wasting disorder Duchenne muscular dystrophy, whereas in-frame deletions typically manifest as the milder allelic condition, Becker muscular dystrophy. Antisense oligomer-induced exon skipping can modify dystrophin gene expression so that a disease-associated dystrophin pre-mRNA is processed into a Becker muscular dystrophy-like mature transcript. Despite genomic deletions that may encompass hundreds of kilobases of the gene, some dystrophin mutations appear “leaky”, and low levels of high molecular weight, and presumably semi-functional, dystrophin are produced. A likely causative mechanism is endogenous exon skipping, and Duchenne individuals with higher baseline levels of dystrophin may respond more efficiently to the administration of splice-switching antisense oligomers. We optimized excision of exons 8 and 9 in normal human myoblasts, and evaluated several oligomers in cells from eight Duchenne muscular dystrophy patients with deletions in a known “leaky” region of the dystrophin gene. Inter-patient variation in response to antisense oligomer induced skipping in vitro appeared minimal. We describe oligomers targeting exon 8, that unequivocally increase dystrophin above baseline in vitro, and propose that patients with leaky mutations are ideally suited for participation in antisense oligomer mediated splice-switching clinical studies.

  12. The influence of low dystrophin levels on disease pathology in mouse models for Duchenne Muscular Dystrophy

    NARCIS (Netherlands)

    Putten, Maaike van

    2013-01-01

    Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disorder, caused by mutations in the DMD gene that prevent synthesis of dystrophin. Fibers that lack dystrophin are sensitive to exercise-induced damage, resulting in progressive muscle wasting, loss of ambulation and premature

  13. Carrying Capacity

    DEFF Research Database (Denmark)

    Schroll, Henning; Andersen, Jan; Kjærgård, Bente

    2012-01-01

    A spatial planning act was introduced inIndonesia 1992 and renewed in 2008. It emphasised the planning role of decentralised authorities. The spatial planning act covers both spatial and environmental issues. It defines the concept of carrying capacity and includes definitions of supportive....../cities. Four different sectors (water, food production, waste, and forests) were selected as core areas for decentralised spatial planning. Indicators for SCC and ACC were identified and assessed with regard to relevance and quantifiability. For each of the indicators selected, a legal threshold or guiding...... was introduced inIndonesia 1992 and renewed in 2008. It emphasised the planning role of decentralised authorities. The spatial planning act covers both spatial and environmental issues. It defines the concept of carrying capacity and includes definitions of supportive carrying capacity (SCC) and assimilative...

  14. Carrier detection of duchenne and becker muscular dystrophy using muscle dystrophin immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Acary S. Bulle Oliveira

    1992-12-01

    Full Text Available To ascertain whether dystrophin immunohistochemistry could improve DMD/ BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, KMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measuremens, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

  15. Role of dystrophin in airway smooth muscle phenotype, contraction and lung function.

    Directory of Open Access Journals (Sweden)

    Pawan Sharma

    Full Text Available Dystrophin links the transmembrane dystrophin-glycoprotein complex to the actin cytoskeleton. We have shown that dystrophin-glycoprotein complex subunits are markers for airway smooth muscle phenotype maturation and together with caveolin-1, play an important role in calcium homeostasis. We tested if dystrophin affects phenotype maturation, tracheal contraction and lung physiology. We used dystrophin deficient Golden Retriever dogs (GRMD and mdx mice vs healthy control animals in our approach. We found significant reduction of contractile protein markers: smooth muscle myosin heavy chain (smMHC and calponin and reduced Ca2+ response to contractile agonist in dystrophin deficient cells. Immunocytochemistry revealed reduced stress fibers and number of smMHC positive cells in dystrophin-deficient cells, when compared to control. Immunoblot analysis of Akt1, GSK3β and mTOR phosphorylation further revealed that downstream PI3K signaling, which is essential for phenotype maturation, was suppressed in dystrophin deficient cell cultures. Tracheal rings from mdx mice showed significant reduction in the isometric contraction to methacholine (MCh when compared to genetic control BL10ScSnJ mice (wild-type. In vivo lung function studies using a small animal ventilator revealed a significant reduction in peak airway resistance induced by maximum concentrations of inhaled MCh in mdx mice, while there was no change in other lung function parameters. These data show that the lack of dystrophin is associated with a concomitant suppression of ASM cell phenotype maturation in vitro, ASM contraction ex vivo and lung function in vivo, indicating that a linkage between the DGC and the actin cytoskeleton via dystrophin is a determinant of the phenotype and functional properties of ASM.

  16. MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy.

    Science.gov (United States)

    Zimowski, Janusz G; Massalska, Diana; Holding, Mariola; Jadczak, Sylwia; Fidziańska, Elżbieta; Lusakowska, Anna; Kostera-Pruszczyk, Anna; Kamińska, Anna; Zaremba, Jacek

    2014-01-01

    Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60-65% of mutations, duplications for 5-10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009-2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45-54 and 3-21, whereas most duplications involved exons 3-18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots - different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers. Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials.

    Science.gov (United States)

    Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco

    2011-12-01

    Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both

  18. Exon skipping and translation in patients with frameshift deletions in the dystrophin gene

    Energy Technology Data Exchange (ETDEWEB)

    Sherratt, T.G.; Dubowitz, V.; Sewry, C.A.; Strong, P.N. (Royal Postgraduate Medical School, London (United Kingdom)); Vulliamy, T. (Hammersmith Hospital, London (United Kingdom))

    1993-11-01

    Although many Duchenne muscular dystrophy patients have a deletion in the dystrophin gene which disrupts the translational reading frame, they express dystrophin in a small proportion of skeletal muscle fibers ([open quotes]revertant fibers[close quotes]). Antibody studies have shown, indirectly, that dystrophin synthesis in revertant fibers is facilitated by a frame-restoring mechanism; in the present study, the feasibility of mRNA splicing was investigated. Dystrophin transcripts were analyzed in skeletal muscle from individuals possessing revertant fibers and a frameshift deletion in the dystrophin gene. In each case a minor in-frame transcript was detected, in which exons adjacent to those deleted from the genome had been skipped. There appeared to be some correlation between the levels of in-frame transcripts and the predicted translation products. Low levels of alternatively spliced transcripts were also present in normal muscle. The results provide further evidence of exon skipping in the dystrophin gene and indicate that this may be involved in the synthesis of dystrophin by revertant fibers. 44 refs., 12 figs.

  19. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

    Science.gov (United States)

    Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

    2015-09-08

    The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Alyson A. Fiorillo

    2015-09-01

    Full Text Available The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31. microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

  1. Structure of a WW domain-containing fragment of dystrophin complexed with {beta}-dystroglycan.

    Energy Technology Data Exchange (ETDEWEB)

    Huang, X.; Poy, F.; Zhang, R.; Joachimiak, A.; Sudol, M.; Eck, M. J.; Biosciences Division; Dana Farber Cancer Inst.; Harvard Medical School; Mount Sinai School of Medicine

    2000-08-01

    Dystrophin and {beta}-dystroglycan are components of the dystrophin--glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of {beta}-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of {beta}-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in {beta}-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The {beta}-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

  2. Muscular dystrophy in a family of Labrador Retrievers with no muscle dystrophin and a mild phenotype.

    Science.gov (United States)

    Vieira, Natassia M; Guo, Ling T; Estrela, Elicia; Kunkel, Louis M; Zatz, Mayana; Shelton, G Diane

    2015-05-01

    Animal models of dystrophin deficient muscular dystrophy, most notably canine X-linked muscular dystrophy, play an important role in developing new therapies for human Duchenne muscular dystrophy. Although the canine disease is a model of the human disease, the variable severity of clinical presentations in the canine may be problematic for pre-clinical trials, but also informative. Here we describe a family of Labrador Retrievers with three generations of male dogs having markedly increased serum creatine kinase activity, absence of membrane dystrophin, but with undetectable clinical signs of muscle weakness. Clinically normal young male Labrador Retriever puppies were evaluated prior to surgical neuter by screening laboratory blood work, including serum creatine kinase activity. Serum creatine kinase activities were markedly increased in the absence of clinical signs of muscle weakness. Evaluation of muscle biopsies confirmed a dystrophic phenotype with both degeneration and regeneration. Further evaluations by immunofluorescence and western blot analysis confirmed the absence of muscle dystrophin. Although dystrophin was not identified in the muscles, we did not find any detectable deletions or duplications in the dystrophin gene. Sequencing is now ongoing to search for point mutations. Our findings in this family of Labrador Retriever dogs lend support to the hypothesis that, in exceptional situations, muscle with no dystrophin may be functional. Unlocking the secrets that protect these dogs from a severe clinical myopathy is a great challenge which may have important implications for future treatment of human muscular dystrophies. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A Translational Pathway Toward a Clinical Trial Using the Second-Generation AAV Micro-Dystrophin Vector

    Science.gov (United States)

    2016-09-01

    mune system a few weeks later. It is now clear that the gene delivery vehicle (AAV virus capsid), cargo (transgene), or the protein produced from the...Ideally, delivery of a full-length dystrophin cDNA will yield the production of a full- length dystrophin protein and the maximum pro- tection of...investigational new drug (IND) application can be filed for a gene therapy trial with systemic delivery of dystrophin? Dr. Duan: A number of IND

  4. Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.

    Directory of Open Access Journals (Sweden)

    Fernanda P Prado

    Full Text Available Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF. Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps. Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when p<0.05. After 90 dps, 70% of the animals showed hypertrophic hearts (HH and 30% hypertrophic+dilated hearts (HD. Systolic and diastolic functions were preserved at 30 and 60 dps, however, decreased in the HD group. Blood pressure, cardiomyocyte diameter and collagen content were increased at all time points. Dystrophin expression was lightly increased at 30 and 60 dps and HH group. HD group showed decreased expression of dystrophin and calpastatin and increased expression of calpain-1 and alpha-fodrin fragments. The first signals of dystrophin reduction were observed as early as 60 dps. In conclusion, some hearts present a distinct molecular pattern at an early stage of the disease; this pattern could provide an opportunity to identify these failure-prone hearts during the development of the cardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible

  5. Functional substitution by TAT-utrophin in dystrophin-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kevin J Sonnemann

    2009-05-01

    Full Text Available The loss of dystrophin compromises muscle cell membrane stability and causes Duchenne muscular dystrophy and/or various forms of cardiomyopathy. Increased expression of the dystrophin homolog utrophin by gene delivery or pharmacologic up-regulation has been demonstrated to restore membrane integrity and improve the phenotype in the dystrophin-deficient mdx mouse. However, the lack of a viable therapy in humans predicates the need to explore alternative methods to combat dystrophin deficiency. We investigated whether systemic administration of recombinant full-length utrophin (Utr or DeltaR4-21 "micro" utrophin (muUtr protein modified with the cell-penetrating TAT protein transduction domain could attenuate the phenotype of mdx mice.Recombinant TAT-Utr and TAT-muUtr proteins were expressed using the baculovirus system and purified using FLAG-affinity chromatography. Age-matched mdx mice received six twice-weekly intraperitoneal injections of either recombinant protein or PBS. Three days after the final injection, mice were analyzed for several phenotypic parameters of dystrophin deficiency. Injected TAT-muUtr transduced all tissues examined, integrated with members of the dystrophin complex, reduced serum levels of creatine kinase (11,290+/-920 U versus 5,950+/-1,120 U; PBS versus TAT, the prevalence of muscle degeneration/regeneration (54%+/-5% versus 37%+/-4% of centrally nucleated fibers; PBS versus TAT, the susceptibility to eccentric contraction-induced force drop (72%+/-5% versus 40%+/-8% drop; PBS versus TAT, and increased specific force production (9.7+/-1.1 N/cm(2 versus 12.8+/-0.9 N/cm(2; PBS versus TAT.These results are, to our knowledge, the first to establish the efficacy and feasibility of TAT-utrophin-based constructs as a novel direct protein-replacement therapy for the treatment of skeletal and cardiac muscle diseases caused by loss of dystrophin.

  6. Novel dystrophin mutations revealed by analysis of dystrophin mRNA: alternative splicing suppresses the phenotypic effect of a nonsense mutation

    Czech Academy of Sciences Publication Activity Database

    Fajkusová, L.; Lukáš, Z.; Tvrdíková, M.; Kuhrová, V.; Hájek, J.; Fajkus, Jiří

    2001-01-01

    Roč. 11, č. 2 (2001), s. 133-138 ISSN 0960-8966 R&D Projects: GA MZd IZ3700; GA MZd NM19; GA MZd NA5227 Institutional research plan: CEZ:AV0Z5004920 Keywords : Duchenne muscular dystrophy * Becker muscular dystrophy * dystrophin mRNA Subject RIV: BO - Biophysics Impact factor: 2.547, year: 2001

  7. Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching

    Directory of Open Access Journals (Sweden)

    Kole Ryszard

    2011-10-01

    Full Text Available Abstract Background Antisense oligomer induced exon skipping aims to reduce the severity of Duchenne muscular dystrophy by redirecting splicing during pre-RNA processing such that the causative mutation is by-passed and a shorter but partially functional Becker muscular dystrophy-like dystrophin isoform is produced. Normal exons are generally targeted to restore the dystrophin reading frame however, an appreciable subset of dystrophin mutations are intra-exonic and therefore have the potential to compromise oligomer efficiency, necessitating personalised oligomer design for some patients. Although antisense oligomers are easily personalised, it remains unclear whether all patient polymorphisms within antisense oligomer target sequences will require the costly process of producing and validating patient specific compounds. Methods Here we report preclinical testing of a panel of splice switching antisense oligomers, designed to excise exon 25 from the dystrophin transcript, in normal and dystrophic patient cells. These patient cells harbour a single base insertion in exon 25 that lies within the target sequence of an oligomer shown to be effective at removing exon 25. Results It was anticipated that such a mutation would compromise oligomer binding and efficiency. However, we show that, despite the mismatch an oligomer, designed and optimised to excise exon 25 from the normal dystrophin mRNA, removes the mutated exon 25 more efficiently than the mutation-specific oligomer. Conclusion This raises the possibility that mismatched AOs could still be therapeutically applicable in some cases, negating the necessity to produce patient-specific compounds.

  8. Functional rescue of dystrophin-deficient mdx mice by a chimeric peptide-PMO.

    Science.gov (United States)

    Yin, Haifang; Moulton, Hong M; Betts, Corinne; Merritt, Thomas; Seow, Yiqi; Ashraf, Shirin; Wang, Qingsong; Boutilier, Jordan; Wood, Matthew Ja

    2010-10-01

    Splice modulation using antisense oligonucleotides (AOs) has been shown to yield targeted exon exclusion to restore the open reading frame and generate truncated but partially functional dystrophin protein. This has been successfully demonstrated in dystrophin-deficient mdx mice and in Duchenne muscular dystrophy (DMD) patients. However, DMD is a systemic disease; successful therapeutic exploitation of this approach will therefore depend on effective systemic delivery of AOs to all affected tissues. We have previously shown the potential of a muscle-specific/arginine-rich chimeric peptide-phosphorodiamidate morpholino (PMO) conjugate, but its long-term activity, optimized dosing regimen, capacity for functional correction and safety profile remain to be established. Here, we report the results of this chimeric peptide-PMO conjugate in the mdx mouse using low doses (3 and 6 mg/kg) administered via a 6 biweekly systemic intravenous injection protocol. We show 100% dystrophin-positive fibers and near complete correction of the dystrophin transcript defect in all peripheral muscle groups, with restoration of 50% dystrophin protein over 12 weeks, leading to correction of the DMD pathological phenotype and restoration of muscle function in the absence of detectable toxicity or immune response. Chimeric muscle-specific/cell-penetrating peptides therefore represent highly promising agents for systemic delivery of splice-correcting PMO oligomers for DMD therapy.

  9. Deficiency in Cardiac Dystrophin Affects the Abundance of the α-/β-Dystroglycan Complex

    Directory of Open Access Journals (Sweden)

    James Lohan

    2005-01-01

    Full Text Available Although Duchenne muscular dystrophy is primarily categorised as a skeletal muscle disease, deficiency in the membrane cytoskeletal protein dystrophin also affects the heart. The central transsarcolemmal linker between the actin membrane cytoskeleton and the extracellular matrix is represented by the dystrophin-associated dystroglycans. Chemical cross-linking analysis revealed no significant differences in the dimeric status of the α-/β-dystroglycan subcomplex in the dystrophic mdx heart as compared to normal cardiac tissue. In analogy to skeletal muscle fibres, heart muscle also exhibited a greatly reduced abundance of both dystroglycans in dystrophin-deficient cells. Immunoblotting demonstrated that the degree of reduction in α-dystroglycan is more pronounced in matured mdx skeletal muscle as contrasted to the mdx heart. The fact that the deficiency in dystrophin triggers a similar pathobiochemical response in both types of muscle suggests that the cardiomyopathic complications observed in x-linked muscular dystrophy might be initiated by the loss of the dystrophin-associated surface glycoprotein complex.

  10. Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2017-03-04

    Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current I K1 , which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential I K1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that I K1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.

  11. Heteroduplex analysis of the dystrophin gene: Application to point mutation and carrier detection

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Papp, A.C.; Snyder, P.J.; Sedra, M.S.; Western, L.M.; Bartolo, C.; Mendell, J.R. [Ohio State Univ., Columbus, OH (United States); Moxley, R.T. [Univ. of Rochester Medical Center, NY (United States)

    1994-03-01

    Approximately one-third of Duchenne muscular dystrophy patients have undefined mutations in the dystrophin gene. For carrier and prenatal studies in families without detectable mutations, the indirect restriction fragment length polymorphism linkage approach is used. Using a multiplex amplification and heteroduplex analysis of dystrophin exons, the authors identified nonsense mutations in two DMD patients. Although the nonsense mutations are predicted to severely truncate the dystrophin protein, both patients presented with mild clinical courses of the disease. As a result of identifying the mutation in the affected boys, direct carrier studies by heteroduplex analysis were extended to other relatives. The authors conclude that the technique is not only ideal for mutation detection but is also useful for diagnostic testing. 29 refs., 4 figs.

  12. Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Siemionow, Maria; Cwykiel, Joanna; Heydemann, Ahlke; Garcia, Jesus; Marchese, Enza; Siemionow, Krzysztof; Szilagyi, Erzsebet

    2018-06-01

    Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MB N1 /MB N2 ), and normal and DMD donors (MB N /MB DMD ). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 10 6 ) restored dystrophin expression (17.27%±8.05-MB N1 /MB N2 and 23.79%±3.82-MB N /MB DMD ) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.

  13. Use of epitope libraries to identify exon-specific monoclonal antibodies for characterization of altered dystrophins in muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen thi Man; Morris, G.E. (North East Wales Inst., Clwyd (United Kingdom))

    1993-06-01

    The majority of mutations in Xp21-linked muscular dystrophy (MD) can be identified by PCR or Southern blotting, as deletions or duplications of groups of exons in the dystrophin gene, but it is not always possible to predict how much altered dystrophin, if any, will be produced. Use of exon-specific monoclonal antibodies (mAbs) on muscle biopsies from MD patients can, in principle, provide information on both the amount of altered dystrophin produced and, when dystrophin is present, the nature of the genetic deletion or point mutation. For this purpose, mAbs which recognize regions of dystrophin encoded by known exons and whose binding is unaffected by the absence of adjacent exons are required. To map mAbs to specific exons, random [open quotes]libraries[close quotes] of expressed dystrophin fragments were created by cloning DNAseI digestion fragments of a 4.3-kb dystrophin cDNA into a pTEX expression vector. The libraries were then used to locate the epitopes recognized by 48 mAbs to fragments of 25--60 amino acids within the 1,434-amino-acid dystrophin fragment used to produce the antibodies. This is sufficiently detailed to allow further refinement by using synthetic peptides and, in many cases, to identify the exon in the DMD (Duchenne MD) gene which encodes the epitope. To illustrate their use in dystrophin analysis, a Duchenne patient with a frameshift deletion of exons 42 and 43 makes a truncated dystrophin encoded by exons 1--41, and the authors now show that this can be detected in the sarcolemma by mAbs up to and including those specific for exon 41 epitopes but not by mAbs specific for exon 43 or later epitopes. 38 refs., 2 figs., 4 tabs.

  14. 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...

  15. EzrA: a spectrin-like scaffold in the bacterial cell division machinery

    Directory of Open Access Journals (Sweden)

    Robert M Cleverley

    2015-01-01

    Full Text Available Much progress has been made in identifying the components of the divisome, the assembly of proteins that undertakes the vital process of cell division in bacteria. However, how the highly interdependent processes on either side of the membrane are coordinated during division is a major unresolved question. How is the degradation and synthesis of the cell wall on the outside of the cell coordinated with cytokinesis and membrane fission, which are driven from the inside of the cell by the tubulin homologue FtsZ? A possible key mediator of such coordination is the membrane protein EzrA, as it interacts both with FtsZ and the penicillin binding proteins (PBPs that synthesize peptidoglycan. Cleverley et al. [Nature Communications (2014 5, 5421] have recently solved the crystal structure of the cytoplasmic domain of B. subtilis EzrA, which points to an important scaffolding role for EzrA in the divisome. The structure resembles the eukaryotic, cytoskeletal spectrin proteins, which link actin filaments in the cytoskeleton and also connect the actin cytoskeleton to membrane-bound integrin proteins.

  16. Studying the role of dystrophin-associated proteins in influencing Becker muscular dystrophy disease severity.

    Science.gov (United States)

    van den Bergen, J C; Wokke, B H A; Hulsker, M A; Verschuuren, J J G M; Aartsma-Rus, A M

    2015-03-01

    Becker muscular dystrophy is characterized by a variable disease course. Many factors have been implicated to contribute to this diversity, among which the expression of several components of the dystrophin associated glycoprotein complex. Together with dystrophin, most of these proteins anchor the muscle fiber cytoskeleton to the extracellular matrix, thus protecting the muscle from contraction induced injury, while nNOS is primarily involved in inducing vasodilation during muscle contraction, enabling adequate muscle oxygenation. In the current study, we investigated the role of three components of the dystrophin associated glycoprotein complex (beta-dystroglycan, gamma-sarcoglycan and nNOS) and the dystrophin homologue utrophin on disease severity in Becker patients. Strength measurements, data about disease course and fresh muscle biopsies of the anterior tibial muscle were obtained from 24 Becker patients aged 19 to 66. The designation of Becker muscular dystrophy in this study was based on the mutation and not on the clinical severity. Contrary to previous studies, we were unable to find a relationship between expression of nNOS, beta-dystroglycan and gamma-sarcoglycan at the sarcolemma and disease severity, as measured by muscle strength in five muscle groups and age at reaching several disease milestones. Unexpectedly, we found an inverse correlation between utrophin expression at the sarcolemma and age at reaching disease milestones. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients

    Directory of Open Access Journals (Sweden)

    Aziza Sbiti

    2002-01-01

    Full Text Available Duchenne and Becker muscular dystrophy (DMD and BMD are X-linked diseases resulting from a defect in the dystrophin gene located on Xp21. DMD is the most frequent neuromuscular disease in humans (1/3500 male newborn. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. We found dystrophin gene deletions in 37 cases. Therefore the frequency in Moroccan DMD/BMD patients is about 51.3%. All deletions were clustered in the two known hot-spots regions, and in 81% of cases deletions were detected in the region from exon 43 to exon 52. These findings are comparable to those reported in other studies. It is important to note that in our population, we can first search for deletions of DMD gene in the most frequently deleted exons determined by this study. This may facilitate the molecular diagnosis of DMD and BMD in our country.

  18. Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

    Science.gov (United States)

    Pozzoli, Uberto; Elgar, Greg; Cagliani, Rachele; Riva, Laura; Comi, Giacomo P.; Bresolin, Nereo; Bardoni, Alessandra; Sironi, Manuela

    2003-01-01

    The human DMD gene is the largest known to date, spanning > 2000 kb on the X chromosome. The gene size is mainly accounted for by huge intronic regions. We sequenced 190 kb of Fugu rubripes (pufferfish) genomic DNA corresponding to the complete dystrophin gene (FrDMD) and provide the first report of gene structure and sequence comparison among dystrophin genomic sequences from different vertebrate organisms. Almost all intron positions and phases are conserved between FrDMD and its mammalian counterparts, and the predicted protein product of the Fugu gene displays 55% identity and 71% similarity to human dystrophin. In analogy to the human gene, FrDMD presents several-fold longer than average intronic regions. Analysis of intron sequences of the human and murine genes revealed that they are extremely conserved in size and that a similar fraction of total intron length is represented by repetitive elements; moreover, our data indicate that intron expansion through repeat accumulation in the two orthologs is the result of independent insertional events. The hypothesis that intron length might be functionally relevant to the DMD gene regulation is proposed and substantiated by the finding that dystrophin intron gigantism is common to the three vertebrate genes. [Supplemental material is available online at www.genome.org.] PMID:12727896

  19. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  20. Evaluation of multiplex ligation-dependent probe amplification analysis versus multiplex polymerase chain reaction assays in the detection of dystrophin gene rearrangements in an Iranian population subset

    Directory of Open Access Journals (Sweden)

    Nayereh Nouri

    2014-01-01

    Full Text Available Background: The Duchenne muscular dystrophy (DMD gene is located in the short arm of the X chromosome (Xp21. It spans 2.4 Mb of the human genomic DNA and is composed of 79 exons. Mutations in the Dystrophin gene result in DMD and Becker muscular dystrophy. In this study, the efficiency of multiplex ligation-dependent probe amplification (MLPA over multiplex polymerase chain reaction (PCR assays in an Iranian population was investigated. Materials and Methods: Multiplex PCR assays and MLPA analysis were carried out in 74 patients affected with DMD. Results: Multiplex PCR detected deletions in 51% of the patients with DMD. MLPA analysis could determine all the deletions detected by the multiplex PCR. Additionally, MLPA was able to identify one more deletion and duplication in patients without detectable mutations by multiplex PCR. Moreover, MLPA precisely determined the exact size of the deletions. Conclusion: Although MLPA analysis is more sensitive for detection of deletions and duplications in the dystrophin gene, multiplex PCR might be used for the initial analysis of the boys affected with DMD in the Iranian population as it was able to detect 95% of the rearrangements in patients with DMD.

  1. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Chicoine Louis G

    2007-09-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1 A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2 an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3 the use of viral doses to accommodate current limitations imposed by vector production methods; 4 and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. Methods The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL. The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Results Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month, 91.3 ± 3.1 (2 months, and 89.6 ± 1.6% (3 months. rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month, 78.9 ± 7.4 (2 months, and 81.2 ± 6.2% (3 months transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month, 2.1 ± 0.8 (2 months, and 2.1 ± 0.7% (3 months] by vascular delivery. Micro-dystrophin

  2. Ex vivo gene editing of the dystrophin gene in muscle stem cells mediated by peptide nucleic acid single stranded oligodeoxynucleotides induces stable expression of dystrophin in a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Nik-Ahd, Farnoosh; Bertoni, Carmen

    2014-07-01

    Duchenne muscular dystrophy (DMD) is a fatal disease caused by mutations in the dystrophin gene, which result in the complete absence of dystrophin protein throughout the body. Gene correction strategies hold promise to treating DMD. Our laboratory has previously demonstrated the ability of peptide nucleic acid single-stranded oligodeoxynucleotides (PNA-ssODNs) to permanently correct single-point mutations at the genomic level. In this study, we show that PNA-ssODNs can target and correct muscle satellite cells (SCs), a population of stem cells capable of self-renewing and differentiating into muscle fibers. When transplanted into skeletal muscles, SCs transfected with correcting PNA-ssODNs were able to engraft and to restore dystrophin expression. The number of dystrophin-positive fibers was shown to significantly increase over time. Expression was confirmed to be the result of the activation of a subpopulation of SCs that had undergone repair as demonstrated by immunofluorescence analyses of engrafted muscles using antibodies specific to full-length dystrophin transcripts and by genomic DNA analysis of dystrophin-positive fibers. Furthermore, the increase in dystrophin expression detected over time resulted in a significant improvement in muscle morphology. The ability of transplanted cells to return into quiescence and to activate upon demand was confirmed in all engrafted muscles following injury. These results demonstrate the feasibility of using gene editing strategies to target and correct SCs and further establish the therapeutic potential of this approach to permanently restore dystrophin expression into muscle of DMD patients. © 2014 AlphaMed Press.

  3. Myoblots: dystrophin quantification by in-cell western assay for a streamlined development of Duchenne muscular dystrophy (DMD) treatments.

    Science.gov (United States)

    Ruiz-Del-Yerro, E; Garcia-Jimenez, I; Mamchaoui, K; Arechavala-Gomeza, V

    2017-10-31

    New therapies for neuromuscular disorders are often mutation specific and require to be studied in patient's cell cultures. In Duchenne muscular dystrophy (DMD) dystrophin restoration drugs are being developed but as muscle cell cultures from DMD patients are scarce and do not grow or differentiate well, only a limited number of candidate drugs are tested. Moreover, dystrophin quantification by western blotting requires a large number of cultured cells; so fewer compounds are as thoroughly screened as is desirable. We aimed to develop a quantitative assessment tool using fewer cells to contribute in the study of dystrophin and to identify better drug candidates. An 'in-cell western' assay is a quantitative immunofluorescence assay performed in cell culture microplates that allows protein quantification directly in culture, allowing a higher number of experimental repeats and throughput. We have optimized the assay ('myoblot') to be applied to the study of differentiated myoblast cultures. After an exhaustive optimization of the technique to adapt it to the growth and differentiation rates of our cultures and the low intrinsic expression of our proteins of interests, our myoblot protocol allows the quantification of dystrophin and other muscle-associated proteins in muscle cell cultures. We are able to distinguish accurately between the different sets of patients based on their dystrophin expression and detect dystrophin restoration after treatment. We expect that this new tool to quantify muscle proteins in DMD and other muscle disorders will aid in their diagnosis and in the development of new therapies. © 2017 British Neuropathological Society.

  4. Assessment of the structural and functional impact of in-frame mutations of the DMD gene, using the tools included in the eDystrophin online database

    Directory of Open Access Journals (Sweden)

    Nicolas Aurélie

    2012-07-01

    Full Text Available Abstract Background Dystrophin is a large essential protein of skeletal and heart muscle. It is a filamentous scaffolding protein with numerous binding domains. Mutations in the DMD gene, which encodes dystrophin, mostly result in the deletion of one or several exons and cause Duchenne (DMD and Becker (BMD muscular dystrophies. The most common DMD mutations are frameshift mutations resulting in an absence of dystrophin from tissues. In-frame DMD mutations are less frequent and result in a protein with partial wild-type dystrophin function. The aim of this study was to highlight structural and functional modifications of dystrophin caused by in-frame mutations. Methods and results We developed a dedicated database for dystrophin, the eDystrophin database. It contains 209 different non frame-shifting mutations found in 945 patients from a French cohort and previous studies. Bioinformatics tools provide models of the three-dimensional structure of the protein at deletion sites, making it possible to determine whether the mutated protein retains the typical filamentous structure of dystrophin. An analysis of the structure of mutated dystrophin molecules showed that hybrid repeats were reconstituted at the deletion site in some cases. These hybrid repeats harbored the typical triple coiled-coil structure of native repeats, which may be correlated with better function in muscle cells. Conclusion This new database focuses on the dystrophin protein and its modification due to in-frame deletions in BMD patients. The observation of hybrid repeat reconstitution in some cases provides insight into phenotype-genotype correlations in dystrophin diseases and possible strategies for gene therapy. The eDystrophin database is freely available: http://edystrophin.genouest.org/.

  5. Duchenne muscular dystrophy diagnosed by dystrophin gene deletion test: A case report

    Directory of Open Access Journals (Sweden)

    Rathod Kishor G, Dawre Rahul M, Kamble Milind B,Tambe Saleem H

    2014-04-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disease affecting 1 in 3600—6000 live male births. A muscle biopsy is not necessary if a genetic diagnosis is secured first, particularly as some families might view the procedure as traumatic. DMD occurs as a result of mutations (mainly deletions in the dystrophin gene (DMD; locus Xp21.2. Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration leading to loss of independent ambulation. Ninety percent of out frame mutations result in DMD, while 90% of in-frame mutations result in BMD. Electron microscopy is not required to confirm DMD. Genetic testing is mandatory irrespective of biopsy results. But the muscle biopsy is not required if the diagnosis is secured first by genetic testing.

  6. Electroporation Enhanced Effect of Dystrophin Splice Switching PNA Oligomers in Normal and Dystrophic Muscle

    DEFF Research Database (Denmark)

    Hjortkjær, Camilla Brolin; Shiraishi, Takehiko; Hojman, Pernille

    2015-01-01

    for improvement of in vivo cellular availability, we have investigated the effect of electrotransfer upon intramuscular (i.m.) PNA administration in vivo. Antisense PNA targeting exon 23 of the murine dystrophin gene was administered by i.m. injection to the tibialis anterior (TA) muscle of normal NMRI......Peptide nucleic acid (PNA) is a synthetic DNA mimic that has shown potential for discovery of novel splice switching antisense drugs. However, in vivo cellular delivery has been a limiting factor for development, and only few successful studies have been reported. As a possible modality...... switching was detected at the RNA level up to 4 weeks after a single-dose treatment. In dystrophic muscles of the MDX mouse, electroporation increased the number of dystrophin-positive fibers about 2.5-fold at 2 weeks after a single PNA administration compared to injection only. In conclusion, we find...

  7. Dystroglycan and muscular dystrophies related to the dystrophin-glycoprotein complex.

    Science.gov (United States)

    Sciandra, Francesca; Bozzi, Manuela; Bianchi, Marzia; Pavoni, Ernesto; Giardina, Bruno; Brancaccio, Andrea

    2003-01-01

    Dystroglycan (DG) is an adhesion molecule composed of two subunits, alpha and beta, that are produced by the post-translational cleavage of a single precursor molecule. DG is a pivotal component of the dystrophin-glycoprotein complex (DGC), which connects the extracellular matrix to the cytoskeleton in skeletal muscle and many other tissues. Some muscular dystrophies are caused by mutations of DGC components, such as dystrophin, sarcoglycan or laminin-2, or also of DGC-associated molecules, such as caveolin-3. DG-null mice died during early embriogenesis and no neuromuscular diseases directly associated to genetic abnormalities of DG were identified so far. However, DG plays a crucial role for muscle integrity since its targeting at the sarcolemma is often perturbed in DGC-related neuromuscular disorders.

  8. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  9. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

    OpenAIRE

    HaiFang Yin; Prisca Boisguerin; Hong M Moulton; Corinne Betts; Yiqi Seow; Jordan Boutilier; Qingsong Wang; Anthony Walsh; Bernard Lebleu; Matthew JA Wood

    2013-01-01

    We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was ...

  10. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

    Directory of Open Access Journals (Sweden)

    Matthew S Barnabei

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

  11. Intellectual Ability in the Duchenne Muscular Dystrophy and Dystrophin Gene Mutation Location

    Directory of Open Access Journals (Sweden)

    Rasic Milic V.

    2014-12-01

    Full Text Available Duchenne muscular dystrophy (DMD is the most common form of muscular dystrophy during childhood. Mutations in dystrophin (DMD gene are also recognized as a cause of cognitive impairment. We aimed to determine the association between intelligence level and mutation location in DMD genes in Serbian patients with DMD. Forty-one male patients with DMD, aged 3 to 16 years, were recruited at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia. All patients had defined DMD gene deletions or duplications [multiplex ligation- dependent probe amplification (MLPA, polymerase chain reaction (PCR] and cognitive status assessment (Wechsler Intelligence Scale for Children, Brunet-Lezine scale, Vineland-Doll scale. In 37 patients with an estimated full scale intelligence quotient (FSIQ, six (16.22% had borderline intelligence (70dystrophin isoforms and when mutations in the 5’-untranslated region (5’UTR of Dp140 (exons 45-50 were assigned to affect only Dp427 and Dp260. Mutations affecting Dp140 and Dp71/Dp40 have been associated with more frequent and more severe cognitive impairment. Finally, the same classification of mutations explained the greater proportion of FSIQ variability associated with cumulative loss of dystrophin isoforms. In conclusion, cumulative loss of dystrophin isoforms increases the risk of intellectual impairment in DMD and characterizing the genotype can define necessity of early cognitive interventions in DMD patients.

  12. Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy

    OpenAIRE

    England, Jennifer; Loughna, Siobhan; Rutland, Catrin S.

    2017-01-01

    Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canin...

  13. Haplotypes in the Dystrophin DNA Segment Point to a Mosaic Origin of Modern Human Diversity

    OpenAIRE

    Ziętkiewicz, Ewa; Yotova, Vania; Gehl, Dominik; Wambach, Tina; Arrieta, Isabel; Batzer, Mark; Cole, David E.C.; Hechtman, Peter; Kaplan, Feige; Modiano, David; Moisan, Jean-Paul; Michalski, Roman; Labuda, Damian

    2003-01-01

    Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one Tn microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences re...

  14. Becker muscular dystrophy due to an intronic splicing mutation inducing a dual dystrophin transcript.

    Science.gov (United States)

    Todeschini, Alice; Gualandi, Francesca; Trabanelli, Cecilia; Armaroli, Annarita; Ravani, Anna; Fanin, Marina; Rota, Silvia; Bello, Luca; Ferlini, Alessandra; Pegoraro, Elena; Padovani, Alessandro; Filosto, Massimiliano

    2016-10-01

    We describe a 29-year-old patient who complained of left thigh muscle weakness since he was 23 and of moderate proximal weakness of both lower limbs with difficulty in climbing stairs and running since he was 27. Mild weakness of iliopsoas and quadriceps muscles and muscle atrophy of both the distal forearm and thigh were observed upon clinical examination. He harboured a novel c.1150-3C>G substitution in the DMD gene, affecting the intron 10 acceptor splice site and causing exon 11 skipping and an out-of-frame transcript. However, protein of normal molecular weight but in reduced amounts was observed on Western Blot analysis. Reverse transcription analysis on muscle RNA showed production, via alternative splicing, of a transcript missing exon 11 as well as a low abundant full-length transcript which is enough to avoid the severe Duchenne phenotype. Our study showed that a reduced amount of full length dystrophin leads to a mild form of Becker muscular dystrophy. These results confirm earlier findings that low amounts of dystrophin can be associated with a milder phenotype, which is promising for therapies aiming at dystrophin restoration. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Screening of Dystrophin Gene Deletions in Egyptian Patients with DMD/BMD Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Laila K. Effat

    2000-01-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are allelic disorders caused by mutations within the dystrophin gene. Our study has identified 100 Egyptian families collected from the Human Genetics Clinic, National Research Center, Cairo. All cases were subjected to complete clinical evaluation pedigree analysis, electromyography studies, estimation of serum creatine phosphokinase enzyme (CPK levels and DNA analysis. Multiplex PCR using 18 pairs of specific primers were used for screening of deletion mutations within the dystrophin gene. A frequency of 55% among the families. Sixty per cent of detected deletions involved multiple exons spanning the major or the minor hot spot of the dystrophin gene. The remainder 40% which mainly involved exon 45. Comparing these findings with frequencies of other countries it was found that our figures fall within the reported range of 40%– for deletions. The distribution of deletions in our study and other different studies was variable and specific ethnic differences do not apparently account for specific deletions. In addition this study concluded that employment of the 18 exon analysis is a cost effective and a highly accurate (97% to launch a nationwide program.

  16. Dual exon skipping in myostatin and dystrophin for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    van Ommen Gert Jan B

    2011-04-01

    Full Text Available Abstract Background Myostatin is a potent muscle growth inhibitor that belongs to the Transforming Growth Factor-β (TGF-β family. Mutations leading to non functional myostatin have been associated with hypermuscularity in several organisms. By contrast, Duchenne muscular dystrophy (DMD is characterized by a loss of muscle fibers and impaired regeneration. In this study, we aim to knockdown myostatin by means of exon skipping, a technique which has been successfully applied to reframe the genetic defect of dystrophin gene in DMD patients. Methods We targeted myostatin exon 2 using antisense oligonucleotides (AON in healthy and DMD-derived myotubes cultures. We assessed the exon skipping level, transcriptional expression of myostatin and its target genes, and combined myostatin and several dystrophin AONs. These AONs were also applied in the mdx mice models via intramuscular injections. Results Myostatin AON induced exon 2 skipping in cell cultures and to a lower extent in the mdx mice. It was accompanied by decrease in myostatin mRNA and enhanced MYOG and MYF5 expression. Furthermore, combination of myostatin and dystrophin AONs induced simultaneous skipping of both genes. Conclusions We conclude that two AONs can be used to target two different genes, MSTN and DMD, in a straightforward manner. Targeting multiple ligands of TGF-beta family will be more promising as adjuvant therapies for DMD.

  17. Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy

    Science.gov (United States)

    Robinson-Hamm, Jacqueline N.; Gersbach, Charles A.

    2016-01-01

    Duchenne muscular dystrophy is one of the most common inherited genetic diseases and is caused by mutations to the DMD gene that encodes the dystrophin protein. Recent advances in genome editing and gene therapy offer hope for the development of potential therapeutics. Truncated versions of the DMD gene can be delivered to the affected tissues with viral vectors and show promising results in a variety of animal models. Genome editing with the CRISPR/Cas9 system has recently been used to restore dystrophin expression by deleting one or more exons of the DMD gene in patient cells and in a mouse model that led to functional improvement of muscle strength. Exon skipping with oligonucleotides has been successful in several animal models and evaluated in multiple clinical trials. Next-generation oligonucleotide formulations offer significant promise to build on these results. All these approaches to restoring dystrophin expression are encouraging, but many hurdles remain. This review summarizes the current state of these technologies and summarizes considerations for their future development. PMID:27542949

  18. Single Cell Analysis of Dystrophin and SRY Gene by Using Whole Genome Amplification

    Institute of Scientific and Technical Information of China (English)

    徐晨明; 金帆; 黄荷凤; 陶冶; 叶英辉

    2001-01-01

    Objective To develop a reliable and sensitive method for detection of sex and multiloci of Duchenne muscular dystrophy (DMD) gene in single cell Materials & methods Whole genome of single cell were amplified by using 15-base random primers (primer extension preamplification, PEP), then a small aliquot of PEP product were analyzed by using locus-specific nest PCR amplification. The procedure was evaluated by detection dystrophin exons 8, 17, 19, 44, 45, 48 and human testis-determining gene (SRY)in single lymphocytes from known sources and single blastomeres from the couples with no family history of DMD.Results The amplification efficiency rate of six dystrophin exons from single lymphocytes and single blastomeres were 97. 2% (175/180) and 100% (60/60) respectively.Results of SRY showed that 100% (15/15) amplification in single male-derived lymphocytes and 0% (0/15) amplification in single female-derived lymphocytes. Conclusion The technique of single cell PEP-nest PCR for dystrophin exons 8, 17,19, 44, 45, 48 and SRY is highly specifc. PEP-nest PCR is suitable for Preimplantation genetic diagnosis (PGD) of DMD at single cell level.

  19. Interdependence of laminin-mediated clustering of lipid rafts and the dystrophin complex in astrocytes.

    Science.gov (United States)

    Noël, Geoffroy; Tham, Daniel Kai Long; Moukhles, Hakima

    2009-07-17

    Astrocyte endfeet surrounding blood vessels are active domains involved in water and potassium ion transport crucial to the maintenance of water and potassium ion homeostasis in brain. A growing body of evidence points to a role for dystroglycan and its interaction with perivascular laminin in the targeting of the dystrophin complex and the water-permeable channel, aquaporin 4 (AQP4), at astrocyte endfeet. However, the mechanisms underlying such compartmentalization remain poorly understood. In the present study we found that AQP4 resided in Triton X-100-insoluble fraction, whereas dystroglycan was recovered in the soluble fraction in astrocytes. Cholesterol depletion resulted in the translocation of a pool of AQP4 to the soluble fraction indicating that its distribution is indeed associated with cholesterol-rich membrane domains. Upon laminin treatment AQP4 and the dystrophin complex, including dystroglycan, reorganized into laminin-associated clusters enriched for the lipid raft markers GM1 and flotillin-1 but not caveolin-1. Reduced diffusion rates of GM1 in the laminin-induced clusters were indicative of the reorganization of raft components in these domains. In addition, both cholesterol depletion and dystroglycan silencing reduced the number and area of laminin-induced clusters of GM1, AQP4, and dystroglycan. These findings demonstrate the interdependence between laminin binding to dystroglycan and GM1-containing lipid raft reorganization and provide novel insight into the dystrophin complex regulation of AQP4 polarization in astrocytes.

  20. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    International Nuclear Information System (INIS)

    Cação-Benedini, L.O.; Ribeiro, P.G.; Prado, C.M.; Chesca, D.L.; Mattiello-Sverzut, A.C.

    2014-01-01

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres

  1. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Cação-Benedini, L.O.; Ribeiro, P.G. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Prado, C.M.; Chesca, D.L. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattiello-Sverzut, A.C. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  2. Characterization of genetic deletions in Becker muscular dystrophy using monoclonal antibodies against a deletion-prone region of dystrophin

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, L.T.; Man, Nguyen Thi; Morris, G.E. [Wales Institute, Clwyd (United Kingdom)] [and others

    1995-08-28

    We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion-prone region of the Duchenne muscular dystrophy gene (exons 45-50). We show that immunohistochemistry or Western blotting with these {open_quotes}exon-specific{close_quotes} mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying {open_quotes}revertant{close_quotes} fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. 27 refs., 7 figs., 3 tabs.

  3. Cognitive dysfunction in the dystrophin-deficient mouse model of Duchenne muscular dystrophy: A reappraisal from sensory to executive processes.

    Science.gov (United States)

    Chaussenot, Rémi; Edeline, Jean-Marc; Le Bec, Benoit; El Massioui, Nicole; Laroche, Serge; Vaillend, Cyrille

    2015-10-01

    Duchenne muscular dystrophy (DMD) is associated with language disabilities and deficits in learning and memory, leading to intellectual disability in a patient subpopulation. Recent studies suggest the presence of broader deficits affecting information processing, short-term memory and executive functions. While the absence of the full-length dystrophin (Dp427) is a common feature in all patients, variable mutation profiles may additionally alter distinct dystrophin-gene products encoded by separate promoters. However, the nature of the cognitive dysfunctions specifically associated with the loss of distinct brain dystrophins is unclear. Here we show that the loss of the full-length brain dystrophin in mdx mice does not modify the perception and sensorimotor gating of auditory inputs, as assessed using auditory brainstem recordings and prepulse inhibition of startle reflex. In contrast, both acquisition and long-term retention of cued and trace fear memories were impaired in mdx mice, suggesting alteration in a functional circuit including the amygdala. Spatial learning in the water maze revealed reduced path efficiency, suggesting qualitative alteration in mdx mice learning strategy. However, spatial working memory performance and cognitive flexibility challenged in various behavioral paradigms in water and radial-arm mazes were unimpaired. The full-length brain dystrophin therefore appears to play a role during acquisition of associative learning as well as in general processes involved in memory consolidation, but no overt involvement in working memory and/or executive functions could be demonstrated in spatial learning tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

    Science.gov (United States)

    Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

    2016-12-12

    Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

  5. Deletion of Dystrophin In-Frame Exon 5 Leads to a Severe Phenotype: Guidance for Exon Skipping Strategies.

    Directory of Open Access Journals (Sweden)

    Zhi Yon Charles Toh

    Full Text Available Duchenne and Becker muscular dystrophy severity depends upon the nature and location of the DMD gene lesion and generally correlates with the dystrophin open reading frame. However, there are striking exceptions where an in-frame genomic deletion leads to severe pathology or protein-truncating mutations (nonsense or frame-shifting indels manifest as mild disease. Exceptions to the dystrophin reading frame rule are usually resolved after molecular diagnosis on muscle RNA. We report a moderate/severe Becker muscular dystrophy patient with an in-frame genomic deletion of DMD exon 5. This mutation has been reported by others as resulting in Duchenne or Intermediate muscular dystrophy, and the loss of this in-frame exon in one patient led to multiple splicing events, including omission of exon 6, that disrupts the open reading frame and is consistent with a severe phenotype. The patient described has a deletion of dystrophin exon 5 that does not compromise recognition of exon 6, and although the deletion does not disrupt the reading frame, his clinical presentation is more severe than would be expected for classical Becker muscular dystrophy. We suggest that the dystrophin isoform lacking the actin-binding sequence encoded by exon 5 is compromised, reflected by the phenotype resulting from induction of this dystrophin isoform in mouse muscle in vivo. Hence, exon skipping to address DMD-causing mutations within DMD exon 5 may not yield an isoform that confers marked clinical benefit. Additional studies will be required to determine whether multi-exon skipping strategies could yield more functional dystrophin isoforms, since some BMD patients with larger in-frame deletions in this region have been reported with mild phenotypes.

  6. Creation of Dystrophin Expressing Chimeric Cells of Myoblast Origin as a Novel Stem Cell Based Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Siemionow, M; Cwykiel, J; Heydemann, A; Garcia-Martinez, J; Siemionow, K; Szilagyi, E

    2018-04-01

    Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression. This proof of concept study tested feasibility of myoblast fusion for Dystrophin Expressing. Chimeric Cell (DEC) therapy through in vitro characterization and in vivo assessment of engraftment, survival, and efficacy in the mdx mouse model of DMD. Murine DEC were created via ex vivo fusion of normal (snj) and dystrophin-deficient (mdx) myoblasts using polyethylene glycol. Efficacy of myoblast fusion was confirmed by flow cytometry and dystrophin immunostaining, while proliferative and myogenic differentiation capacity of DEC were assessed in vitro. Therapeutic effect after DEC transplant (0.5 × 10 6 ) into the gastrocnemius muscle (GM) of mdx mice was assessed by muscle functional tests. At 30 days post-transplant dystrophin expression in GM of injected mdx mice increased to 37.27 ± 12.1% and correlated with improvement of muscle strength and function. Our study confirmed feasibility and efficacy of DEC therapy and represents a novel SC based approach for treatment of muscular dystrophies.

  7. A sensitive, reproducible and objective immunofluorescence analysis method of dystrophin in individual fibers in samples from patients with duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Chantal Beekman

    Full Text Available Duchenne muscular dystrophy (DMD is characterized by the absence or reduced levels of dystrophin expression on the inner surface of the sarcolemmal membrane of muscle fibers. Clinical development of therapeutic approaches aiming to increase dystrophin levels requires sensitive and reproducible measurement of differences in dystrophin expression in muscle biopsies of treated patients with DMD. This, however, poses a technical challenge due to intra- and inter-donor variance in the occurrence of revertant fibers and low trace dystrophin expression throughout the biopsies. We have developed an immunofluorescence and semi-automated image analysis method that measures the sarcolemmal dystrophin intensity per individual fiber for the entire fiber population in a muscle biopsy. Cross-sections of muscle co-stained for dystrophin and spectrin have been imaged by confocal microscopy, and image analysis was performed using Definiens software. Dystrophin intensity has been measured in the sarcolemmal mask of spectrin for each individual muscle fiber and multiple membrane intensity parameters (mean, maximum, quantiles per fiber were calculated. A histogram can depict the distribution of dystrophin intensities for the fiber population in the biopsy. This method was tested by measuring dystrophin in DMD, Becker muscular dystrophy, and healthy muscle samples. Analysis of duplicate or quadruplicate sections of DMD biopsies on the same or multiple days, by different operators, or using different antibodies, was shown to be objective and reproducible (inter-assay precision, CV 2-17% and intra-assay precision, CV 2-10%. Moreover, the method was sufficiently sensitive to detect consistently small differences in dystrophin between two biopsies from a patient with DMD before and after treatment with an investigational compound.

  8. Becker muscular dystrophy severity is linked to the structure of dystrophin.

    Science.gov (United States)

    Nicolas, Aurélie; Raguénès-Nicol, Céline; Ben Yaou, Rabah; Ameziane-Le Hir, Sarah; Chéron, Angélique; Vié, Véronique; Claustres, Mireille; Leturcq, France; Delalande, Olivier; Hubert, Jean-François; Tuffery-Giraud, Sylvie; Giudice, Emmanuel; Le Rumeur, Elisabeth

    2015-03-01

    In-frame exon deletions of the Duchenne muscular dystrophy (DMD) gene produce internally truncated proteins that typically lead to Becker muscular dystrophy (BMD), a milder allelic disorder of DMD. We hypothesized that differences in the structure of mutant dystrophin may be responsible for the clinical heterogeneity observed in Becker patients and we studied four prevalent in-frame exon deletions, i.e. Δ45-47, Δ45-48, Δ45-49 and Δ45-51. Molecular homology modelling revealed that the proteins corresponding to deletions Δ45-48 and Δ45-51 displayed a similar structure (hybrid repeat) than the wild-type dystrophin, whereas deletions Δ45-47 and Δ45-49 lead to proteins with an unrelated structure (fractional repeat). All four proteins in vitro expressed in a fragment encoding repeats 16-21 were folded in α-helices and remained highly stable. Refolding dynamics were slowed and molecular surface hydrophobicity were higher in fractional repeat containing Δ45-47 and Δ45-49 deletions compared with hybrid repeat containing Δ45-48 and Δ45-51 deletions. By retrospectively collecting data for a series of French BMD patients, we showed that the age of dilated cardiomyopathy (DCM) onset was delayed by 11 and 14 years in Δ45-48 and Δ45-49 compared with Δ45-47 patients, respectively. A clear trend toward earlier wheelchair dependency (minimum of 11 years) was also observed in Δ45-47 and Δ45-49 patients compared with Δ45-48 patients. Muscle dystrophin levels were moderately reduced in most patients without clear correlation with the deletion type. Disease progression in BMD patients appears to be dependent on the deletion itself and associated with a specific structure of dystrophin at the deletion site. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Nanopolymers improve delivery of exon skipping oligonucleotides and concomitant dystrophin expression in skeletal muscle of mdx mice

    Directory of Open Access Journals (Sweden)

    Sirsi Shashank R

    2008-04-01

    Full Text Available Abstract Background Exon skipping oligonucleotides (ESOs of 2'O-Methyl (2'OMe and morpholino chemistry have been shown to restore dystrophin expression in muscle fibers from the mdx mouse, and are currently being tested in phase I clinical trials for Duchenne Muscular Dystrophy (DMD. However, ESOs remain limited in their effectiveness because of an inadequate delivery profile. Synthetic cationic copolymers of poly(ethylene imine (PEI and poly(ethylene glycol (PEG are regarded as effective agents for enhanced delivery of nucleic acids in various applications. Results We examined whether PEG-PEI copolymers can facilitate ESO-mediated dystrophin expression after intramuscular injections into tibialis anterior (TA muscles of mdx mice. We utilized a set of PEG-PEI copolymers containing 2 kDa PEI and either 550 Da or 5 kDa PEG, both of which bind 2'OMe ESOs with high affinity and form stable nanoparticulates with a relatively low surface charge. Three weekly intramuscular injections of 5 μg of ESO complexed with PEI2K-PEG550 copolymers resulted in about 500 dystrophin-positive fibers and about 12% of normal levels of dystrophin expression at 3 weeks after the initial injection, which is significantly greater than for injections of ESO alone, which are known to be almost completely ineffective. In an effort to enhance biocompatibility and cellular uptake, the PEI2K-PEG550 and PEI2K-PEG5K copolymers were functionalized by covalent conjugation with nanogold (NG or adsorbtion of colloidal gold (CG, respectively. Surprisingly, using the same injection and dosing regimen, we found no significant difference in dystrophin expression by Western blot between the NG-PEI2K-PEG550, CG-PEI2K-PEG5K, and non-functionalized PEI2K-PEG550 copolymers. Dose-response experiments using the CG-PEI2K-PEG5K copolymer with total ESO ranging from 3–60 μg yielded a maximum of about 15% dystrophin expression. Further improvements in dystrophin expression up to 20% of normal

  10. Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

    Directory of Open Access Journals (Sweden)

    Bailey Nichols

    2015-07-01

    Full Text Available Dystrophin-glycoprotein complex (DGC is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin of a muscle fiber to the extracellular matrix (ECM. Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies, and limb-girdle muscular dystrophies (sarcoglycanopathies, are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS, which is localized at the muscle membrane by DGC members (dystrophin and syntrophins, plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.

  11. Fetal skeletal muscle progenitors have regenerative capacity after intramuscular engraftment in dystrophin deficient mice.

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakai

    Full Text Available Muscle satellite cells (SCs are stem cells that reside in skeletal muscles and contribute to regeneration upon muscle injury. SCs arise from skeletal muscle progenitors expressing transcription factors Pax3 and/or Pax7 during embryogenesis in mice. However, it is unclear whether these fetal progenitors possess regenerative ability when transplanted in adult muscle. Here we address this question by investigating whether fetal skeletal muscle progenitors (FMPs isolated from Pax3(GFP/+ embryos have the capacity to regenerate muscle after engraftment into Dystrophin-deficient mice, a model of Duchenne muscular dystrophy. The capacity of FMPs to engraft and enter the myogenic program in regenerating muscle was compared with that of SCs derived from adult Pax3(GFP/+ mice. Transplanted FMPs contributed to the reconstitution of damaged myofibers in Dystrophin-deficient mice. However, despite FMPs and SCs having similar myogenic ability in culture, the regenerative ability of FMPs was less than that of SCs in vivo. FMPs that had activated MyoD engrafted more efficiently to regenerate myofibers than MyoD-negative FMPs. Transcriptome and surface marker analyses of these cells suggest the importance of myogenic priming for the efficient myogenic engraftment. Our findings suggest the regenerative capability of FMPs in the context of muscle repair and cell therapy for degenerative muscle disease.

  12. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Larcher, Thibaut; Lafoux, Aude; Tesson, Laurent; Remy, Séverine; Thepenier, Virginie; François, Virginie; Le Guiner, Caroline; Goubin, Helicia; Dutilleul, Maéva; Guigand, Lydie; Toumaniantz, Gilles; De Cian, Anne; Boix, Charlotte; Renaud, Jean-Baptiste; Cherel, Yan; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio; Huchet, Corinne

    2014-01-01

    A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

  13. Electroporation Enhanced Effect of Dystrophin Splice Switching PNA Oligomers in Normal and Dystrophic Muscle

    Directory of Open Access Journals (Sweden)

    Camilla Brolin

    2015-01-01

    Full Text Available Peptide nucleic acid (PNA is a synthetic DNA mimic that has shown potential for discovery of novel splice switching antisense drugs. However, in vivo cellular delivery has been a limiting factor for development, and only few successful studies have been reported. As a possible modality for improvement of in vivo cellular availability, we have investigated the effect of electrotransfer upon intramuscular (i.m. PNA administration in vivo. Antisense PNA targeting exon 23 of the murine dystrophin gene was administered by i.m. injection to the tibialis anterior (TA muscle of normal NMRI and dystrophic mdx mice with or without electroporation. At low, single PNA doses (1.5, 3, or 10 µg/TA, electroporation augmented the antisense exon skipping induced by an unmodified PNA by twofold to fourfold in healthy mouse muscle with optimized electric parameters, measured after 7 days. The PNA splice switching was detected at the RNA level up to 4 weeks after a single-dose treatment. In dystrophic muscles of the MDX mouse, electroporation increased the number of dystrophin-positive fibers about 2.5-fold at 2 weeks after a single PNA administration compared to injection only. In conclusion, we find that electroporation can enhance PNA antisense effects in muscle tissue.

  14. Dystrophin-deficient cardiomyocytes derived from human urine: New biologic reagents for drug discovery

    Directory of Open Access Journals (Sweden)

    Xuan Guan

    2014-03-01

    Full Text Available The ability to extract somatic cells from a patient and reprogram them to pluripotency opens up new possibilities for personalized medicine. Induced pluripotent stem cells (iPSCs have been employed to generate beating cardiomyocytes from a patient's skin or blood cells. Here, iPSC methods were used to generate cardiomyocytes starting from the urine of a patient with Duchenne muscular dystrophy (DMD. Urine was chosen as a starting material because it contains adult stem cells called urine-derived stem cells (USCs. USCs express the canonical reprogramming factors c-myc and klf4, and possess high telomerase activity. Pluripotency of urine-derived iPSC clones was confirmed by immunocytochemistry, RT-PCR and teratoma formation. Urine-derived iPSC clones generated from healthy volunteers and a DMD patient were differentiated into beating cardiomyocytes using a series of small molecules in monolayer culture. Results indicate that cardiomyocytes retain the DMD patient's dystrophin mutation. Physiological assays suggest that dystrophin-deficient cardiomyocytes possess phenotypic differences from normal cardiomyocytes. These results demonstrate the feasibility of generating cardiomyocytes from a urine sample and that urine-derived cardiomyocytes retain characteristic features that might be further exploited for mechanistic studies and drug discovery.

  15. Adhalin, the 50 kD dystrophin associated protein, is not the locus for severe childhood autosomal recessive dystrophy (SCARMD)

    Energy Technology Data Exchange (ETDEWEB)

    McNally, E.M.; Selig, S.; Kunkel, L.M. [Children`s Hospital, Boston, MA (United States)

    1994-09-01

    Mutations in the carboxyl-terminus in dystrophin are normally sufficient to produce severely dystrophic muscle. This portion of dystrophin binds a complex of dystrophin-associated glycoproteins (DAGs). The genes encoding these DAGs are candidate genes for causing neuromuscular disease. Immunoreactivity for adhalin, the 50 kD DAG, is absent in muscle biopsies from patients with SCARMD, a form of dystrophy clinically similar Duchenne muscular dystrophy. Prior linkage analysis in SCARMD families revealed that the disease gene segregates with markers on chromosome 13. To determine the molecular role that adhalin may play in SCARMD, human cDNA and genomic sequences were isolated. Primers were designed based on predicted areas of conservation in rabbit adhalin and used in RT-PCR with human skeletal and cardiac muscle. RT-PCR products were confirmed by sequence as human adhalin and then used as probes for screening human cDNA and genomic libraries. Human and rabbit adhalin are 90% identical, and among the cDNAs, a novel splice form of adhalin was seen which may encode part of the 35 kD component of the dystrophin-glycoprotein complex. To our surprise, only human/rodent hybrids containing human chromosome 17 amplified adhalin sequences in a PCR analysis. FISH analysis with three overlapping genomic sequences confirmed the chromosome 17 location and further delineated the map position to 17q21. Therefore, adhalin is excluded as the gene causing SCARMD.

  16. Dual AAV Gene Therapy for Duchenne Muscular Dystrophy with a 7-kb Mini-Dystrophin Gene in the Canine Model.

    Science.gov (United States)

    Kodippili, Kasun; Hakim, Chady H; Pan, Xiufang; Yang, Hsiao T; Yue, Yongping; Zhang, Yadong; Shin, Jin-Hong; Yang, N Nora; Duan, Dongsheng

    2018-03-01

    Dual adeno-associated virus (AAV) technology was developed in 2000 to double the packaging capacity of the AAV vector. The proof of principle has been demonstrated in various mouse models. Yet, pivotal evidence is lacking in large animal models of human diseases. Here we report expression of a 7-kb canine ΔH2-R15 mini-dystrophin gene using a pair of dual AAV vectors in the canine model of Duchenne muscular dystrophy (DMD). The ΔH2-R15 minigene is by far the most potent synthetic dystrophin gene engineered for DMD gene therapy. We packaged minigene dual vectors in Y731F tyrosine-modified AAV-9 and delivered to the extensor carpi ulnaris muscle of a 12-month-old affected dog at the dose of 2 × 10 13 viral genome particles/vector/muscle. Widespread mini-dystrophin expression was observed 2 months after gene transfer. The missing dystrophin-associated glycoprotein complex was restored. Treatment also reduced muscle degeneration and fibrosis and improved myofiber size distribution. Importantly, dual AAV therapy greatly protected the muscle from eccentric contraction-induced force loss. Our data provide the first clear evidence that dual AAV therapy can be translated to a diseased large mammal. Further development of dual AAV technology may lead to effective therapies for DMD and many other diseases in human patients.

  17. mRNA and microRNA transcriptomics analyses in a murine model of dystrophin loss and therapeutic restoration

    Directory of Open Access Journals (Sweden)

    Thomas C. Roberts

    2016-03-01

    Full Text Available Duchenne muscular dystrophy (DMD is a pediatric, X-linked, progressive muscle-wasting disorder caused by loss of function mutations affecting the gene encoding the dystrophin protein. While the primary genetic insult in DMD is well described, many details of the molecular and cellular pathologies that follow dystrophin loss are incompletely understood. To investigate gene expression in dystrophic muscle we have applied mRNA and microRNA (miRNA microarray technology to the mdx mouse model of DMD. This study was designed to generate a complete description of gene expression changes associated with dystrophic pathology and the response to an experimental therapy which restores dystrophin protein function. These datasets have enabled (1 the determination of gene expression changes associated with dystrophic pathology, (2 identification of differentially expressed genes that are restored towards wild-type levels after therapeutic dystrophin rescue, (3 investigation of the correlation between mRNA and protein expression (determined by parallel mass spectrometry proteomics analysis, and (4 prediction of pathology associated miRNA-target interactions. Here we describe in detail how the data were generated including the basic analysis as contained in the manuscript published in Human Molecular Genetics with PMID 26385637. The data have been deposited in the Gene Expression Omnibus (GEO with the accession number GSE64420.

  18. Mouse models of two missense mutations in actin-binding domain 1 of dystrophin associated with Duchenne or Becker muscular dystrophy.

    Science.gov (United States)

    McCourt, Jackie L; Talsness, Dana M; Lindsay, Angus; Arpke, Robert W; Chatterton, Paul D; Nelson, D'anna M; Chamberlain, Christopher M; Olthoff, John T; Belanto, Joseph J; McCourt, Preston M; Kyba, Michael; Lowe, Dawn A; Ervasti, James M

    2018-02-01

    Missense mutations in the dystrophin protein can cause Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) through an undefined pathomechanism. In vitro studies suggest that missense mutations in the N-terminal actin-binding domain (ABD1) cause protein instability, and cultured myoblast studies reveal decreased expression levels that can be restored to wild-type with proteasome inhibitors. To further elucidate the pathophysiology of missense dystrophin in vivo, we generated two transgenic mdx mouse lines expressing L54R or L172H mutant dystrophin, which correspond to missense mutations identified in human patients with DMD or BMD, respectively. Our biochemical, histologic and physiologic analysis of the L54R and L172H mice show decreased levels of dystrophin which are proportional to the phenotypic severity. Proteasome inhibitors were ineffective in both the L54R and L172H mice, yet mice homozygous for the L172H transgene were able to express even higher levels of dystrophin which caused further improvements in muscle histology and physiology. Given that missense dystrophin is likely being degraded by the proteasome but whole body proteasome inhibition was not possible, we screened for ubiquitin-conjugating enzymes involved in targeting dystrophin to the proteasome. A myoblast cell line expressing L54R mutant dystrophin was screened with an siRNA library targeting E1, E2 and E3 ligases which identified Amn1, FBXO33, Zfand5 and Trim75. Our study establishes new mouse models of dystrophinopathy and identifies candidate E3 ligases that may specifically regulate dystrophin protein turnover in vivo. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Modulation of splicing of the preceding intron by antisense oligonucleotide complementary to intra-exon sequence deleted in dystrophin Kobe

    Energy Technology Data Exchange (ETDEWEB)

    Takeshima, Y.; Matuso, M.; Sakamoto, H.; Nishio, H. [Kobe Univ. School of Medicine and Science (Japan)

    1994-09-01

    Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing a 52 bp deletion was skipped during splicing, although the known consensus sequences at the 5{prime} and 3{prime} splice site of exon 19 were maintained. These data suggest that the deleted sequence of exon 19 may function as a cis-acting factor for exact splicing for the upstream intron. To investigate this potential role, an in vitro splicing system using dystrophin precursors was established. A two-exon precursor containing exon 18, truncated intron 18, and exon 19 was accurately spliced. However, splicing of intron 18 was dramatically inhibited when wild exon 19 was replaced with mutated exon 19. Even though the length of exon 19 was restored to normal by replacing the deleted sequence with other sequence, splicing of intron 18 was not fully reactivated. Characteristically, splicing of intron 18 was inactivated more markedly when the replaced sequence contained less polypurine stretches. These data suggested that modification of the exon sequence would result in a splicing abnormality. Antisense 31 mer 2`-O-methyl ribonucleotide was targeted against 5{prime} end of deleted region of exon 19 to modulate splicing of the mRNA precursor. Splicing of intron 18 was inhibited in a dose- and time-dependent manner. This is the first in vitro evidence to show splicing of dystrophin pre-mRNA can be managed by antisense oligonucleotides. These experiments represent an approach in which antisense oligonucleotides are used to restore the function of a defective dystrophin gene in Duchenne muscular dystrophy by inducing skipping of certain exons during splicing.

  20. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Richard S Finkel

    Full Text Available Approximately 13% of boys with Duchenne muscular dystrophy (DMD have a nonsense mutation in the dystrophin gene, resulting in a premature stop codon in the corresponding mRNA and failure to generate a functional protein. Ataluren (PTC124 enables ribosomal readthrough of premature stop codons, leading to production of full-length, functional proteins.This Phase 2a open-label, sequential dose-ranging trial recruited 38 boys with nonsense mutation DMD. The first cohort (n = 6 received ataluren three times per day at morning, midday, and evening doses of 4, 4, and 8 mg/kg; the second cohort (n = 20 was dosed at 10, 10, 20 mg/kg; and the third cohort (n = 12 was dosed at 20, 20, 40 mg/kg. Treatment duration was 28 days. Change in full-length dystrophin expression, as assessed by immunostaining in pre- and post-treatment muscle biopsy specimens, was the primary endpoint.Twenty three of 38 (61% subjects demonstrated increases in post-treatment dystrophin expression in a quantitative analysis assessing the ratio of dystrophin/spectrin. A qualitative analysis also showed positive changes in dystrophin expression. Expression was not associated with nonsense mutation type or exon location. Ataluren trough plasma concentrations active in the mdx mouse model were consistently achieved at the mid- and high- dose levels in participants. Ataluren was generally well tolerated.Ataluren showed activity and safety in this short-term study, supporting evaluation of ataluren 10, 10, 20 mg/kg and 20, 20, 40 mg/kg in a Phase 2b, double-blind, long-term study in nonsense mutation DMD.ClinicalTrials.gov NCT00264888.

  1. Matrix metalloproteinase-2 ablation in dystrophin-deficient mdx muscles reduces angiogenesis resulting in impaired growth of regenerated muscle fibers.

    Science.gov (United States)

    Miyazaki, Daigo; Nakamura, Akinori; Fukushima, Kazuhiro; Yoshida, Kunihiro; Takeda, Shin'ichi; Ikeda, Shu-ichi

    2011-05-01

    Matrix metalloproteases (MMPs) are a family of endopeptidases classified into subgroups based on substrate preference in normal physiological processes such as embryonic development and tissue remodeling, as well as in various disease processes via degradation of extracellular matrix components. Among the MMPs, MMP-9 and MMP-2 have been reported to be up-regulated in skeletal muscles in the lethal X-linked muscle disorder Duchenne muscular dystrophy (DMD), which is caused by loss of dystrophin. A recent study showed that deletion of the MMP9 gene in mdx, a mouse model for DMD, improved skeletal muscle pathology and function; however, the role of MMP-2 in the dystrophin-deficient muscle is not well known. In this study, we aimed at verifying the role of MMP-2 in the dystrophin-deficient muscle by using mdx mice with genetic ablation of MMP-2 (mdx/MMP-2(-/-)). We found impairment of regenerated muscle fiber growth with reduction of angiogenesis in mdx/MMP-2(-/-) mice at 3 months of age. Expression of vascular endothelial growth factor-A (VEGF-A), an important angiogenesis-related factor, decreased in mdx/MMP-2(-/-) mice at 3 months of age. MMP-2 had not a critical role in the degradation of dystrophin-glycoprotein complex (DGC) components such as β-dystroglycan and β-sarcoglycan in the regeneration process of the dystrophic muscle. Accordingly, MMP-2 may be essential for growth of regenerated muscle fibers through VEGF-associated angiogenesis in the dystrophin-deficient skeletal muscle.

  2. Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing

    Directory of Open Access Journals (Sweden)

    Corti Stefania

    2011-03-01

    Full Text Available Abstract Background Duchenne and Becker Muscular dystrophies (DMD/BMD are allelic disorders caused by mutations in the dystrophin gene, which encodes a sarcolemmal protein responsible for muscle integrity. Deletions and duplications account for approximately 75% of mutations in DMD and 85% in BMD. The implementation of techniques allowing complete gene sequencing has focused attention on small point mutations and other mechanisms underlying complex rearrangements. Methods We selected 47 patients (41 families; 35 DMD, 6 BMD without deletions and duplications in DMD gene (excluded by multiplex ligation-dependent probe amplification and multiplex polymerase chain reaction analysis. This cohort was investigated by systematic direct sequence analysis to study sequence variation. We focused our attention on rare mutational events which were further studied through transcript analysis. Results We identified 40 different nucleotide alterations in DMD gene and their clinical correlates; altogether, 16 mutations were novel. DMD probands carried 9 microinsertions/microdeletions, 19 nonsense mutations, and 7 splice-site mutations. BMD patients carried 2 nonsense mutations, 2 splice-site mutations, 1 missense substitution, and 1 single base insertion. The most frequent stop codon was TGA (n = 10 patients, followed by TAG (n = 7 and TAA (n = 4. We also analyzed the molecular mechanisms of five rare mutational events. They are two frame-shifting mutations in the DMD gene 3'end in BMD and three novel splicing defects: IVS42: c.6118-3C>A, which causes a leaky splice-site; c.9560A>G, which determines a cryptic splice-site activation and c.9564-426 T>G, which creates pseudoexon retention within IVS65. Conclusion The analysis of our patients' sample, carrying point mutations or complex rearrangements in DMD gene, contributes to the knowledge on phenotypic correlations in dystrophinopatic patients and can provide a better understanding of pre-mRNA maturation defects

  3. Optical Carry Adder.

    Science.gov (United States)

    1987-03-01

    AOM’s) with the deflected beam as the modulator "on" state. These AOM’s ( TeO2 crystals, manufactured by Newport E.O. Systems) have high deflection...caused by the slow acoustic propagation (4.2 - 105 cm/s for TeO2 ), but this delay can be minimized by placing the laser beam close to the acoustic...dependent jitter in the optical carry to below 1 ns, the total carry path must be less than 30 cm long (or 20 cm in glass , 14 cm in LiNbO 3). Thus, a 32

  4. A BanI RFLP at a deletion hotspot in the human dystrophin gene

    Energy Technology Data Exchange (ETDEWEB)

    Read, A P; Mountford, R [St. Mary' s Hospital, Manchester (England)

    1990-01-25

    Cf56a is a 0.9 kb EcoRI fragment of dystrophin cDNA in pUC13. Cf56a is identical to Kunkel's cDNA probe 8. Constant bands of 14.4, 11.0, 8.1, 6.2 and 1.3 kb correspond to exons I, N, L, N and K respectively. The polymorphic band is exon J (exon 48, 1.2+3.9 kb HindIII bands). This exon is deleted in 25% of all Duchenne/Becker dystrophy boys. Therefore this RFLP is useful for determining carrier status of at-risk females by showing heterozygosity or apparent non-maternity.

  5. Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy.

    Science.gov (United States)

    Batchelor, Clare L; Winder, Steve J

    2006-04-01

    The dystrophin-glycoprotein complex (DGC) can be considered as a specialized adhesion complex, linking the extracellular matrix to the actin cytoskeleton, primarily in muscle cells. Mutations in several components of the DGC lead to its partial or total loss, resulting in various forms of muscular dystrophy. These typically manifest as progressive wasting diseases with loss of muscle integrity. Debate is ongoing about the precise function of the DGC: initially a strictly mechanical role was proposed but it has been suggested that there is aberrant calcium handling in muscular dystrophy and, more recently, changes in MAP kinase and GTPase signalling have been implicated in the aetiology of the disease. Here, we discuss new and interesting developments in these aspects of DGC function and attempt to rationalize the mechanical, calcium and signalling hypotheses to provide a unifying hypothesis of the underlying process of muscular dystrophy.

  6. A BanI RFLP at a deletion hotspot in the human dystrophin gene

    Energy Technology Data Exchange (ETDEWEB)

    Read, A.P.; Mountford, R. (St. Mary' s Hospital, Manchester (England))

    1990-01-25

    Cf56a is a 0.9 kb EcoRI fragment of dystrophin cDNA in pUC13. Cf56a is identical to Kunkel's cDNA probe 8. Constant bands of 14.4, 11.0, 8.1, 6.2 and 1.3 kb correspond to exons I, N, L, N and K respectively. The polymorphic band is exon J (exon 48, 1.2+3.9 kb HindIII bands). This exon is deleted in 25% of all Duchenne/Becker dystrophy boys. Therefore this RFLP is useful for determining carrier status of at-risk females by showing heterozygosity or apparent non-maternity.

  7. Neuronal differentiation modulates the dystrophin Dp71d binding to the nuclear matrix

    International Nuclear Information System (INIS)

    Rodriguez-Munoz, Rafael; Villarreal-Silva, Marcela; Gonzalez-Ramirez, Ricardo; Garcia-Sierra, Francisco; Mondragon, Monica; Mondragon, Ricardo; Cerna, Joel; Cisneros, Bulmaro

    2008-01-01

    The function of dystrophin Dp71 in neuronal cells remains unknown. To approach this issue, we have selected the PC12 neuronal cell line. These cells express both a Dp71f cytoplasmic variant and a Dp71d nuclear isoform. In this study, we demonstrated by electron and confocal microscopy analyses of in situ nuclear matrices and Western blotting evaluation of cell extracts that Dp71d associates with the nuclear matrix. Interestingly, this binding is modulated during NGF-induced neuronal differentiation of PC12 cells with a twofold increment in the differentiated cells, compared to control cells. Also, distribution of Dp71d along the periphery of the nuclear matrix observed in the undifferentiated cells is replaced by intense fluorescent foci localized in Center of the nucleoskeletal structure. In summary, we revealed that Dp71d is a dynamic component of nuclear matrix that might participate in the nuclear modeling occurring during neuronal differentiation

  8. Quantitative analysis of the dystrophin gene by real-time PCR

    Directory of Open Access Journals (Sweden)

    Maksimovic Nela

    2012-01-01

    Full Text Available Duchenne and Becker muscular dystrophy (DMD/BMD are severe X-linked neuromuscular disorders caused by mutations in the dystrophin gene. Our aim was to optimize a quantitative real-time PCR method based on SYBR® Green I chemistry for routine diagnostics of DMD/BMD deletion carriers. Twenty female relatives of DMD/BMD patients with previously detected partial gene deletions were studied. The relative quantity of the target exons was calculated by a comparative threshold cycle method (ΔΔCt. The carrier status of all subjects was successfully determined. The gene dosage ratio for non-carriers was 1.07±0.20, and for carriers 0.56±0.11. This assay proved to be simple, rapid, reliable and cost-effective.

  9. Pregnancy after preimplantation diagnosis for a deletion in the dystrophin gene by polymerase chain reaction in embryos obtained after intracytoplasmic sperm injection

    Energy Technology Data Exchange (ETDEWEB)

    Lissens, W.; Liu, J.; Van Broeckhoven, C. [University Hospital, Brussels (Belgium)] [and others

    1994-09-01

    Duchenne muscular dystrophy (DMD) is one of the most common X-linked recessive diseases. In order to be able to perform a DMD-specific preimplantation diagnosis (PID) in a female carrier of a deletion of exons 3 to 18 in the dystrophin gene, we have developed a PCR assay to detect the deletion based on sequences of exon 17. The efficiency of this PCR was evaluated on 50 single blastomeres from 12 normal control embryos and on 41 blastomeres for 9 male and 3 female embryos from the female DMD carrier, obtained after a first preimplantation diagnosis by sexing. The exon 17 region was amplified with 100% efficiency, except in all 21 blastomeres from 6 male embryos from the carrier where no PCR signals were observed. The negative results in these blastomeres were interpreted as being found only in male embryos carrying the deletion. Intracytoplasmic sperm injection was carried out on the carrier`s metaphase II oocytes retrieved after ovarian stimulation. Embryos were analyzed for the presence of exon 17 and 2 male embryos were found to be deleted, while 4 embryos showed normal amplification signals. Three of the latter embryos were replaced, resulting in a singleton pregnancy. Amniotic cell analysis showed a normal female karyotype and DNA analysis indicated a non-carrier.

  10. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency.

    Science.gov (United States)

    Yin, Haifang; Boisguerin, Prisca; Moulton, Hong M; Betts, Corinne; Seow, Yiqi; Boutilier, Jordan; Wang, Qingsong; Walsh, Anthony; Lebleu, Bernard; Wood, Matthew Ja

    2013-09-24

    We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO) and control peptide 3 (B-3-PMO and 3-B-PMO) were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO), further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO) was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG), indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.Molecular Therapy-Nucleic Acids (2013) 2, e124; doi:10.1038/mtna.2013

  11. Context Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping Efficiency

    Directory of Open Access Journals (Sweden)

    HaiFang Yin

    2013-01-01

    Full Text Available We have recently reported that cell-penetrating peptides (CPPs and novel chimeric peptides containing CPP (referred as B peptide and muscle-targeting peptide (referred as MSP motifs significantly improve the systemic exon-skipping activity of morpholino phosphorodiamidate oligomers (PMOs in dystrophin-deficient mdx mice. In the present study, the general mechanistic significance of the chimeric peptide configuration on the activity and tissue uptake of peptide conjugated PMOs in vivo was investigated. Four additional chimeric peptide-PMO conjugates including newly identified peptide 9 (B-9-PMO and 9-B-PMO and control peptide 3 (B-3-PMO and 3-B-PMO were tested in mdx mice. Immunohistochemical staining, RT-PCR and western blot results indicated that B-9-PMO induced significantly higher level of exon skipping and dystrophin restoration than its counterpart (9-B-PMO, further corroborating the notion that the activity of chimeric peptide-PMO conjugates is dependent on relative position of the tissue-targeting peptide motif within the chimeric peptide with respect to PMOs. Subsequent mechanistic studies showed that enhanced cellular uptake of B-MSP-PMO into muscle cells leads to increased exon-skipping activity in comparison with MSP-B-PMO. Surprisingly, further evidence showed that the uptake of chimeric peptide-PMO conjugates of both orientations (B-MSP-PMO and MSP-B-PMO was ATP- and temperature-dependent and also partially mediated by heparan sulfate proteoglycans (HSPG, indicating that endocytosis is likely the main uptake pathway for both chimeric peptide-PMO conjugates. Collectively, our data demonstrate that peptide orientation in chimeric peptides is an important parameter that determines cellular uptake and activity when conjugated directly to oligonucleotides. These observations provide insight into the design of improved cell targeting compounds for future therapeutics studies.

  12. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

    International Nuclear Information System (INIS)

    Fujimoto, Takahiro; Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2014-01-01

    Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH 2 -terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions

  13. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Takahiro; Itoh, Kyoko, E-mail: kxi14@koto.kpu-m.ac.jp; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH{sub 2}-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions.

  14. New Dystrophin/Dystroglycan interactors control neuron behavior in Drosophila eye

    Directory of Open Access Journals (Sweden)

    Rishko Valentyna M

    2011-09-01

    Full Text Available Abstract Background The Dystrophin Glycoprotein Complex (DGC is a large multi-component complex that is well known for its function in muscle tissue. When the main components of the DGC, Dystrophin (Dys and Dystroglycan (Dg are affected cognitive impairment and mental retardation in addition to muscle degeneration can occur. Previously we performed an array of genetic screens using a Drosophila model for muscular dystrophy in order to find novel DGC interactors aiming to elucidate the signaling role(s in which the complex is involved. Since the function of the DGC in the brain and nervous system has not been fully defined, we have here continued to analyze the DGC modifiers' function in the developing Drosophila brain and eye. Results Given that disruption of Dys and Dg leads to improper photoreceptor axon projections into the lamina and eye neuron elongation defects during development, we have determined the function of previously screened components and their genetic interaction with the DGC in this tissue. Our study first found that mutations in chif, CG34400, Nrk, Lis1, capt and Cam cause improper axon path-finding and loss of SP2353, Grh, Nrk, capt, CG34400, vimar, Lis1 and Cam cause shortened rhabdomere lengths. We determined that Nrk, mbl, capt and Cam genetically interact with Dys and/or Dg in these processes. It is notable that most of the neuronal DGC interacting components encountered are involved in regulation of actin dynamics. Conclusions Our data indicate possible DGC involvement in the process of cytoskeletal remodeling in neurons. The identification of new components that interact with the DGC not only helps to dissect the mechanism of axon guidance and eye neuron differentiation but also provides a great opportunity for understanding the signaling mechanisms by which the cell surface receptor Dg communicates via Dys with the actin cytoskeleton.

  15. The proton pump inhibitor lansoprazole improves the skeletal phenotype in dystrophin deficient mdx mice.

    Directory of Open Access Journals (Sweden)

    Arpana Sali

    Full Text Available In Duchenne muscular dystrophy (DMD, loss of the membrane stabilizing protein dystrophin results in myofiber damage. Microinjury to dystrophic myofibers also causes secondary imbalances in sarcolemmic ion permeability and resting membrane potential, which modifies excitation-contraction coupling and increases proinflammatory/apoptotic signaling cascades. Although glucocorticoids remain the standard of care for the treatment of DMD, there is a need to investigate the efficacy of other pharmacological agents targeting the involvement of imbalances in ion flux on dystrophic pathology.We designed a preclinical trial to investigate the effects of lansoprazole (LANZO administration, a proton pump inhibitor, on the dystrophic muscle phenotype in dystrophin deficient (mdx mice. Eight to ten week-old female mice were assigned to one of four treatment groups (n = 12 per group: (1 vehicle control; (2 5 mg/kg/day LANZO; (3 5 mg/kg/day prednisolone; and (4 combined treatment of 5 mg/kg/day prednisolone (PRED and 5 mg/kg/day LANZO. Treatment was administered orally 5 d/wk for 3 months. At the end of the study, behavioral (Digiscan and functional outcomes (grip strength and Rotarod were assessed prior to sacrifice. After sacrifice, body, tissue and organ masses, muscle histology, in vitro muscle force, and creatine kinase levels were measured. Mice in the combined treatment groups displayed significant reductions in the number of degenerating muscle fibers and number of inflammatory foci per muscle field relative to vehicle control. Additionally, mice in the combined treatment group displayed less of a decline in normalized forelimb and hindlimb grip strength and declines in in vitro EDL force after repeated eccentric contractions.Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings warrant future investigation of the clinical efficacy of LANZO and

  16. Use of capillary Western immunoassay (Wes) for quantification of dystrophin levels in skeletal muscle of healthy controls and individuals with Becker and Duchenne muscular dystrophy.

    Science.gov (United States)

    Beekman, Chantal; Janson, Anneke A; Baghat, Aabed; van Deutekom, Judith C; Datson, Nicole A

    2018-01-01

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by progressive weakness of the skeletal and cardiac muscles. This X-linked disorder is caused by open reading frame disrupting mutations in the DMD gene, resulting in strong reduction or complete absence of dystrophin protein. In order to use dystrophin as a supportive or even surrogate biomarker in clinical studies on investigational drugs aiming at correcting the primary cause of the disease, the ability to reliably quantify dystrophin expression in muscle biopsies of DMD patients pre- and post-treatment is essential. Here we demonstrate the application of the ProteinSimple capillary immunoassay (Wes) method, a gel- and blot-free method requiring less sample, antibody and time to run than conventional Western blot assay. We optimized dystrophin quantification by Wes using 2 different antibodies and found it to be highly sensitive, reproducible and quantitative over a large dynamic range. Using a healthy control muscle sample as a reference and α-actinin as a protein loading/muscle content control, a panel of skeletal muscle samples consisting of 31 healthy controls, 25 Becker Muscle dystrophy (BMD) and 17 DMD samples was subjected to Wes analysis. In healthy controls dystrophin levels varied 3 to 5-fold between the highest and lowest muscle samples, with the reference sample representing the average of all 31 samples. In BMD muscle samples dystrophin levels ranged from 10% to 90%, with an average of 33% of the healthy muscle average, while for the DMD samples the average dystrophin level was 1.3%, ranging from 0.7% to 7% of the healthy muscle average. In conclusion, Wes is a suitable, efficient and reliable method for quantification of dystrophin expression as a biomarker in DMD clinical drug development.

  17. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))

    1992-01-15

    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

  18. Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, Morten; Vissing, John

    2011-01-01

    With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD...... calf hypertrophy was noted. Creatine kinase was normal or raised maximally to 500 U/l. The muscle biopsy was myopathic with increased fiber size variation and many internal nuclei, but no dystrophy. No comorbidity was found. In both cases, western blot showed a reduced dystrophin band. Genetic...... skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK....

  19. Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse

    Energy Technology Data Exchange (ETDEWEB)

    Love, D.R.; Marsden, R.F.; Bloomfield, J.F.; Davies, K.E. (John Radcliffe Hospital, Oxford (England)); Morris, G.E.; Ellis, J.M. (North East Wales Inst., Deeside, Wales (England)); Fairbrother, U.; Edwards, Y.H. (Univ. College London (England)); Slater, C.P. (Newcastle General Hospital, Newcastle-upon-Tyne (England)); Parry, D.J. (Univ. of Ottawa, Ontario (Canada))

    1991-04-15

    The authors have previously reported a dystrophin-related locus (DMDL for Duchenne muscular dystrophy-like) on human chromosome 6 that maps close to the dy mutation on mouse chromosome 10. Here they show that this gene is expressed in a wide range of tissues at varying levels. The transcript is particularly abundant in several human fetal tissues, including heart, placenta, and intestine. Studies with antisera raised against a DMDL fusion protein identify a 400,000 M{sub r} protein in all mouse tissues tested, including those of mdx and dy mice. Unlike the dystrophin gene, the DMDL gene transcript is not differentially spliced at the 3{prime} end in either fetal muscle or brain.

  20. Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between exercise parameters and exacerbation of the dystrophic phenotype

    OpenAIRE

    Smythe, Gayle M; White, Jason D

    2012-01-01

    Voluntary wheel running can potentially be used to exacerbate the disease phenotype in dystrophin-deficient mdx mice. While it has been established that voluntary wheel running is highly variable between individuals, the key parameters of wheel running that impact the most on muscle pathology have not been examined in detail. We conducted a 2-week test of voluntary wheel running by mdx mice and the impact of wheel running on disease pathology. There was significant individual variation in the...

  1. Identification of small molecule and genetic modulators of AON-induced dystrophin exon skipping by high-throughput screening.

    Directory of Open Access Journals (Sweden)

    Debra A O'Leary

    Full Text Available One therapeutic approach to Duchenne Muscular Dystrophy (DMD recently entering clinical trials aims to convert DMD phenotypes to that of a milder disease variant, Becker Muscular Dystrophy (BMD, by employing antisense oligonucleotides (AONs targeting splice sites, to induce exon skipping and restore partial dystrophin function. In order to search for small molecule and genetic modulators of AON-dependent and independent exon skipping, we screened approximately 10,000 known small molecule drugs, >17,000 cDNA clones, and >2,000 kinase- targeted siRNAs against a 5.6 kb luciferase minigene construct, encompassing exon 71 to exon 73 of human dystrophin. As a result, we identified several enhancers of exon skipping, acting on both the reporter construct as well as endogenous dystrophin in mdx cells. Multiple mechanisms of action were identified, including histone deacetylase inhibition, tubulin modulation and pre-mRNA processing. Among others, the nucleolar protein NOL8 and staufen RNA binding protein homolog 2 (Stau2 were found to induce endogenous exon skipping in mdx cells in an AON-dependent fashion. An unexpected but recurrent theme observed in our screening efforts was the apparent link between the inhibition of cell cycle progression and the induction of exon skipping.

  2. Optimization of Peptide Nucleic Acid Antisense Oligonucleotides for Local and Systemic Dystrophin Splice Correction in the mdx Mouse

    Science.gov (United States)

    Yin, HaiFang; Betts, Corinne; Saleh, Amer F; Ivanova, Gabriela D; Lee, Hyunil; Seow, Yiqi; Kim, Dalsoo; Gait, Michael J; Wood, Matthew JA

    2010-01-01

    Antisense oligonucleotides (AOs) have the capacity to alter the processing of pre-mRNA transcripts in order to correct the function of aberrant disease-related genes. Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle degenerative disease that arises from mutations in the DMD gene leading to an absence of dystrophin protein. AOs have been shown to restore the expression of functional dystrophin via splice correction by intramuscular and systemic delivery in animal models of DMD and in DMD patients via intramuscular administration. Major challenges in developing this splice correction therapy are to optimize AO chemistry and to develop more effective systemic AO delivery. Peptide nucleic acid (PNA) AOs are an alternative AO chemistry with favorable in vivo biochemical properties and splice correcting abilities. Here, we show long-term splice correction of the DMD gene in mdx mice following intramuscular PNA delivery and effective splice correction in aged mdx mice. Further, we report detailed optimization of systemic PNA delivery dose regimens and PNA AO lengths to yield splice correction, with 25-mer PNA AOs providing the greatest splice correcting efficacy, restoring dystrophin protein in multiple peripheral muscle groups. PNA AOs therefore provide an attractive candidate AO chemistry for DMD exon skipping therapy. PMID:20068555

  3. A rare subclinical or mild type of Becker muscular dystrophy caused by a single exon 48 deletion of the dystrophin gene.

    Science.gov (United States)

    Zimowski, Janusz G; Pilch, Jacek; Pawelec, Magdalena; Purzycka, Joanna K; Kubalska, Jolanta; Ziora-Jakutowicz, Karolina; Dudzińska, Magdalena; Zaremba, Jacek

    2017-08-01

    In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation-a single exon 48 deletion of the dystrophin gene-who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered.

  4. Dystrophin-deficient dogs with reduced myostatin have unequal muscle growth and greater joint contractures.

    Science.gov (United States)

    Kornegay, Joe N; Bogan, Daniel J; Bogan, Janet R; Dow, Jennifer L; Wang, Jiahui; Fan, Zheng; Liu, Naili; Warsing, Leigh C; Grange, Robert W; Ahn, Mihye; Balog-Alvarez, Cynthia J; Cotten, Steven W; Willis, Monte S; Brinkmeyer-Langford, Candice; Zhu, Hongtu; Palandra, Joe; Morris, Carl A; Styner, Martin A; Wagner, Kathryn R

    2016-01-01

    Myostatin (Mstn) is a negative regulator of muscle growth whose inhibition promotes muscle growth and regeneration. Dystrophin-deficient mdx mice in which myostatin is knocked out or inhibited postnatally have a less severe phenotype with greater total mass and strength and less fibrosis and fatty replacement of muscles than mdx mice with wild-type myostatin expression. Dogs with golden retriever muscular dystrophy (GRMD) have previously been noted to have increased muscle mass and reduced fibrosis after systemic postnatal myostatin inhibition. Based partly on these results, myostatin inhibitors are in development for use in human muscular dystrophies. However, persisting concerns regarding the effects of long-term and profound myostatin inhibition will not be easily or imminently answered in clinical trials. To address these concerns, we developed a canine (GRippet) model by crossbreeding dystrophin-deficient GRMD dogs with Mstn-heterozygous (Mstn (+/-)) whippets. A total of four GRippets (dystrophic and Mstn (+/-)), three GRMD (dystrophic and Mstn wild-type) dogs, and three non-dystrophic controls from two litters were evaluated. Myostatin messenger ribonucleic acid (mRNA) and protein levels were downregulated in both GRMD and GRippet dogs. GRippets had more severe postural changes and larger (more restricted) maximal joint flexion angles, apparently due to further exaggeration of disproportionate effects on muscle size. Flexors such as the cranial sartorius were more hypertrophied on magnetic resonance imaging (MRI) in the GRippets, while extensors, including the quadriceps femoris, underwent greater atrophy. Myostatin protein levels negatively correlated with relative cranial sartorius muscle cross-sectional area on MRI, supporting a role in disproportionate muscle size. Activin receptor type IIB (ActRIIB) expression was higher in dystrophic versus control dogs, consistent with physiologic feedback between myostatin and ActRIIB. However, there was no

  5. Aberrant location of inhibitory synaptic marker proteins in the hippocampus of dystrophin-deficient mice: implications for cognitive impairment in duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Elżbieta Krasowska

    Full Text Available Duchenne muscular dystrophy (DMD is a neuromuscular disease that arises from mutations in the dystrophin-encoding gene. Apart from muscle pathology, cognitive impairment, primarily of developmental origin, is also a significant component of the disorder. Convergent lines of evidence point to an important role for dystrophin in regulating the molecular machinery of central synapses. The clustering of neurotransmitter receptors at inhibitory synapses, thus impacting on synaptic transmission, is of particular significance. However, less is known about the role of dystrophin in influencing the precise expression patterns of proteins located within the pre- and postsynaptic elements of inhibitory synapses. To this end, we exploited molecular markers of inhibitory synapses, interneurons and dystrophin-deficient mouse models to explore the role of dystrophin in determining the stereotypical patterning of inhibitory connectivity within the cellular networks of the hippocampus CA1 region. In tissue from wild-type (WT mice, immunoreactivity of neuroligin2 (NL2, an adhesion molecule expressed exclusively in postsynaptic elements of inhibitory synapses, and the vesicular GABA transporter (VGAT, a marker of GABAergic presynaptic elements, were predictably enriched in strata pyramidale and lacunosum moleculare. In acute contrast, NL2 and VGAT immunoreactivity was relatively evenly distributed across all CA1 layers in dystrophin-deficient mice. Similar changes were evident with the cannabinoid receptor 1, vesicular glutamate transporter 3, parvalbumin, somatostatin and the GABAA receptor alpha1 subunit. The data show that in the absence of dystrophin, there is a rearrangement of the molecular machinery, which underlies the precise spatio-temporal pattern of GABAergic synaptic transmission within the CA1 sub-field of the hippocampus.

  6. Serum cholinesterases are differentially regulated in normal and dystrophin-deficient mutant mice

    Directory of Open Access Journals (Sweden)

    Andrea R. Durrant

    2012-06-01

    Full Text Available The cholinesterases, acetylcholinesterase and butyrylcholinesterase (pseudocholinesterase, are abundant in the nervous system and in other tissues. The role of acetylcholinesterase in terminating transmitter action in the peripheral and central nervous system is well understood. However, both knowledge of the function(s of the cholinesterases in serum, and of their metabolic and endocrine regulation under normal and pathological conditions, is limited. This study investigates acetylcholinesterase and butyrylcholinesterase in sera of dystrophin-deficient mdx mutant mice, an animal model for the human Duchenne muscular dystrophy and in control healthy mice. The data show systematic and differential variations in the concentrations of both enzymes in the sera, and specific changes dictated by alteration of hormonal balance in both healthy and dystrophic mice. While acetylcholinesterase in mdx-sera is elevated, butyrylcholinesterase is markedly diminished, resulting in an overall cholinesterase decrease compared to sera of healthy controls. The androgen testosterone (T is a negative modulator of butyrylcholinesterase, but not of acetylcholinesterase, in male mouse sera. T-removal elevated both butyrylcholinesterase activity and the butyrylcholinesterase/acetylcholinesterase ratio in mdx male sera to values resembling those in healthy control male mice. Mechanisms of regulation of the circulating cholinesterases and their impairment in the dystrophic mice are suggested, and clinical implications for diagnosis and treatment are considered.

  7. Metabolic remodeling agents show beneficial effects in the dystrophin-deficient mdx mouse model

    Directory of Open Access Journals (Sweden)

    Jahnke Vanessa E

    2012-08-01

    Full Text Available Abstract Background Duchenne muscular dystrophy is a genetic disease involving a severe muscle wasting that is characterized by cycles of muscle degeneration/regeneration and culminates in early death in affected boys. Mitochondria are presumed to be involved in the regulation of myoblast proliferation/differentiation; enhancing mitochondrial activity with exercise mimetics (AMPK and PPAR-delta agonists increases muscle function and inhibits muscle wasting in healthy mice. We therefore asked whether metabolic remodeling agents that increase mitochondrial activity would improve muscle function in mdx mice. Methods Twelve-week-old mdx mice were treated with two different metabolic remodeling agents (GW501516 and AICAR, separately or in combination, for 4 weeks. Extensive systematic behavioral, functional, histological, biochemical, and molecular tests were conducted to assess the drug(s' effects. Results We found a gain in body and muscle weight in all treated mice. Histologic examination showed a decrease in muscle inflammation and in the number of fibers with central nuclei and an increase in fibers with peripheral nuclei, with significantly fewer activated satellite cells and regenerating fibers. Together with an inhibition of FoXO1 signaling, these results indicated that the treatments reduced ongoing muscle damage. Conclusions The three treatments produced significant improvements in disease phenotype, including an increase in overall behavioral activity and significant gains in forelimb and hind limb strength. Our findings suggest that triggering mitochondrial activity with exercise mimetics improves muscle function in dystrophin-deficient mdx mice.

  8. Recombinase-mediated reprogramming and dystrophin gene addition in mdx mouse induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Chunli Zhao

    Full Text Available A cell therapy strategy utilizing genetically-corrected induced pluripotent stem cells (iPSC may be an attractive approach for genetic disorders such as muscular dystrophies. Methods for genetic engineering of iPSC that emphasize precision and minimize random integration would be beneficial. We demonstrate here an approach in the mdx mouse model of Duchenne muscular dystrophy that focuses on the use of site-specific recombinases to achieve genetic engineering. We employed non-viral, plasmid-mediated methods to reprogram mdx fibroblasts, using phiC31 integrase to insert a single copy of the reprogramming genes at a safe location in the genome. We next used Bxb1 integrase to add the therapeutic full-length dystrophin cDNA to the iPSC in a site-specific manner. Unwanted DNA sequences, including the reprogramming genes, were then precisely deleted with Cre resolvase. Pluripotency of the iPSC was analyzed before and after gene addition, and ability of the genetically corrected iPSC to differentiate into myogenic precursors was evaluated by morphology, immunohistochemistry, qRT-PCR, FACS analysis, and intramuscular engraftment. These data demonstrate a non-viral, reprogramming-plus-gene addition genetic engineering strategy utilizing site-specific recombinases that can be applied easily to mouse cells. This work introduces a significant level of precision in the genetic engineering of iPSC that can be built upon in future studies.

  9. RT-PCR analysis of dystrophin mRNA in DND/BMD patients

    Energy Technology Data Exchange (ETDEWEB)

    Ciafaloni, E.; Silva, H.A.R. de; Roses, A.D. [Duke Univ. Medical Center, Durham, NC (United States)

    1994-09-01

    Duchenne and Becker muscular dystrophies (DMD, BMD) are X-linked recessive disorders caused by mutations in the dystrophin (dys) gene. The majority of these mutations are intragenic deletions of duplications routinely detected by Southern biots and multiplex PCR. The remainder are very likely, smaller mutations, mostly point-mutations. Detection of these mutations is very difficult due to the size and complexity of the dys gene. We applied RT-PCR to analyse the entire dys mRNA of three DMD patients with no detectable genomic defect. In two unrelated patients, a duplication of the 62 bp exon 2 was identified. This causes a frameshift sufficient to explain the DMD phenotype. In the third patient, who had congenital DMD and severe mental retardation, a complex pattern of aberrant splicing at the 3-prime exons 67-79 was observed. Sural nerve biopsy in this patient showed the complete absence of Dp116. PCR-SSCP studies are presently in progress to identify the mutations responsible for the aberrant splicing patterns.

  10. Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons.

    Science.gov (United States)

    Fujimoto, Takahiro; Itoh, Kyoko; Yaoi, Takeshi; Fushiki, Shinji

    2014-09-12

    The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remain unknown. In this study, we generated a polyclonal antibody against the NH2-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Sequence characterisation of deletion breakpoints in the dystrophin gene by PCR

    Energy Technology Data Exchange (ETDEWEB)

    Abbs, S.; Sandhu, S.; Bobrow, M. [Guy`s Hospital, London (United Kingdom)

    1994-09-01

    Partial deletions of the dystrophin gene account for 65% of cases of Duchenne muscular dystrophy. A high proportion of these structural changes are generated by new mutational events, and lie predominantly within two `hotspot` regions, yet the underlying reasons for this are not known. We are characterizing and sequencing the regions surrounding deletion breakpoints in order to: (i) investigate the mechanisms of deletion mutation, and (ii) enable the design of PCR assays to specifically amplify mutant and normal sequences, allowing us to search for the presence of somatic mosaicism in appropriate family members. Using this approach we have been able to demonstrate the presence of somatic mosaicism in a maternal grandfather of a DMD-affected male, deleted for exons 49-50. Three deletions, namely of exons 48-49, 49-50, and 50, have been characterized using a PCR approach that avoids any cloning procedures. Breakpoints were initially localized to within regions of a few kilobases using Southern blot restriction analyses with exon-specific probes and PCR amplification of exonic and intronic loci. Sequencing was performed directly on PCR products: (i) mutant sequences were obtained from long-range or inverse-PCR across the deletion junction fragments, and (ii) normal sequences were obtained from the products of standard PCR, vectorette PCR, or inverse-PCR performed on YACs. Further characterization of intronic sequences will allow us to amplify and sequence across other deletion breakpoints and increase our knowledge of the mechanisms of mutation in the dystophin gene.

  12. Haplotypes in the dystrophin DNA segment point to a mosaic origin of modern human diversity.

    Science.gov (United States)

    Zietkiewicz, Ewa; Yotova, Vania; Gehl, Dominik; Wambach, Tina; Arrieta, Isabel; Batzer, Mark; Cole, David E C; Hechtman, Peter; Kaplan, Feige; Modiano, David; Moisan, Jean-Paul; Michalski, Roman; Labuda, Damian

    2003-11-01

    Although Africa has played a central role in human evolutionary history, certain studies have suggested that not all contemporary human genetic diversity is of recent African origin. We investigated 35 simple polymorphic sites and one T(n) microsatellite in an 8-kb segment of the dystrophin gene. We found 86 haplotypes in 1,343 chromosomes from around the world. Although a classical out-of-Africa topology was observed in trees based on the variant frequencies, the tree of haplotype sequences reveals three lineages accounting for present-day diversity. The proportion of new recombinants and the diversity of the T(n) microsatellite were used to estimate the age of haplotype lineages and the time of colonization events. The lineage that underwent the great expansion originated in Africa prior to the Upper Paleolithic (27,000-56,000 years ago). A second group, of structurally distinct haplotypes that occupy a central position on the tree, has never left Africa. The third lineage is represented by the haplotype that lies closest to the root, is virtually absent in Africa, and appears older than the recent out-of-Africa expansion. We propose that this lineage could have left Africa before the expansion (as early as 160,000 years ago) and admixed, outside of Africa, with the expanding lineage. Contemporary human diversity, although dominated by the recently expanded African lineage, thus represents a mosaic of different contributions.

  13. Simultaneous Pathoproteomic Evaluation of the Dystrophin-Glycoprotein Complex and Secondary Changes in the mdx-4cv Mouse Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Sandra Murphy

    2015-06-01

    Full Text Available In skeletal muscle, the dystrophin-glycoprotein complex forms a membrane-associated assembly of relatively low abundance, making its detailed proteomic characterization in normal versus dystrophic tissues technically challenging. To overcome this analytical problem, we have enriched the muscle membrane fraction by a minimal differential centrifugation step followed by the comprehensive label-free mass spectrometric analysis of microsomal membrane preparations. This organelle proteomic approach successfully identified dystrophin and its binding partners in normal versus dystrophic hind limb muscles. The introduction of a simple pre-fractionation step enabled the simultaneous proteomic comparison of the reduction in the dystrophin-glycoprotein complex and secondary changes in the mdx-4cv mouse model of dystrophinopathy in a single analytical run. The proteomic screening of the microsomal fraction from dystrophic hind limb muscle identified the full-length dystrophin isoform Dp427 as the most drastically reduced protein in dystrophinopathy, demonstrating the remarkable analytical power of comparative muscle proteomics. Secondary pathoproteomic expression patterns were established for 281 proteins, including dystrophin-associated proteins and components involved in metabolism, signalling, contraction, ion-regulation, protein folding, the extracellular matrix and the cytoskeleton. Key findings were verified by immunoblotting. Increased levels of the sarcolemmal Na+/K+-ATPase in dystrophic leg muscles were also confirmed by immunofluorescence microscopy. Thus, the reduction of sample complexity in organelle-focused proteomics can be advantageous for the profiling of supramolecular protein complexes in highly intricate systems, such as skeletal muscle tissue.

  14. Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

    Science.gov (United States)

    Cho, Anna; Seong, Moon-Woo; Lim, Byung Chan; Lee, Hwa Jeen; Byeon, Jung Hye; Kim, Seung Soo; Kim, Soo Yeon; Choi, Sun Ah; Wong, Ai-Lynn; Lee, Jeongho; Kim, Jon Soo; Ryu, Hye Won; Lee, Jin Sook; Kim, Hunmin; Hwang, Hee; Choi, Ji Eun; Kim, Ki Joong; Hwang, Young Seung; Hong, Ki Ho; Park, Seungman; Cho, Sung Im; Lee, Seung Jun; Park, Hyunwoong; Seo, Soo Hyun; Park, Sung Sup; Chae, Jong Hee

    2017-05-01

    Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017. © 2016 Wiley Periodicals, Inc.

  15. Dystrophin is required for the normal function of the cardio-protective K(ATP channel in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Laura Graciotti

    Full Text Available Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx, which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC. In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K(ATP complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K(ATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K(ATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K(ATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K(ATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients.

  16. Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations

    Directory of Open Access Journals (Sweden)

    Miller Jeffrey

    2005-04-01

    Full Text Available Abstract Background Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells. Methods We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient or Lama2-/- (laminin-α2-deficient mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation. Results We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles. Conclusion The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.

  17. Astrogliosis and impaired aquaporin-4 and dystrophin systems in idiopathic normal pressure hydrocephalus.

    Science.gov (United States)

    Eide, P K; Hansson, H-A

    2017-06-19

    Idiopathic normal pressure hydrocephalus (iNPH) is one subtype of dementia that may improve following drainage of cerebrospinal fluid (CSF). This prospective observational study explored whether expression of the water channel aquaporin-4 (AQP4) and the anchoring molecule dystrophin 71 (Dp71) are altered at astrocytic perivascular endfeet and in adjacent neuropil of iNPH patient. Observations were related to measurements of pulsatile and static intracranial pressure (ICP). The study included iNPH patients undergoing overnight monitoring of the pulsatile/static ICP in whom a biopsy was taken from the frontal cerebral cortex during placement of the ICP sensor. Reference (Ref) biopsies were sampled from 13 patients who underwent brain surgery for epilepsy, tumours or cerebral aneurysms. The brain tissue specimens were examined by light microscopy, immunohistochemistry, densitometry and morphometry. iNPH patients responding to surgery (n = 44) had elevated pulsatile ICP, indicative of impaired intracranial compliance. As compared to the Ref patients, the cortical biopsies of iNPH patients revealed prominent astrogliosis and reduced expression of AQP4 and Dp71 immunoreactivities in the astrocytic perivascular endfeet and in parts of the adjacent neuropil. There was a significant correlation between degree of astrogliosis and reduction of AQP4 and Dp71 at astrocytic perivascular endfeet. Idiopathic normal pressure hydrocephalus patients responding to CSF diversion present with abnormal pulsatile ICP, indicative of impaired intracranial compliance. A main histopathological finding was astrogliosis and reduction of AQP4 and of Dp71 in astrocytic perivascular endfeet. We propose that the altered AQP4 and Dp71 complex contributes to the subischaemia prevalent in the brain tissue of iNPH. © 2017 British Neuropathological Society.

  18. Sensitivity and Frequencies of Dystrophin Gene Mutations in Thai DMD/BMD Patients As Detected by Multiplex PCR

    Directory of Open Access Journals (Sweden)

    Thanyachai Sura

    2008-01-01

    Full Text Available Background: Duchenne muscular dystrophy (DMD, a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD, are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.

  19. GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice.

    Science.gov (United States)

    Lenhart, Kaitlin C; O'Neill, Thomas J; Cheng, Zhaokang; Dee, Rachel; Demonbreun, Alexis R; Li, Jianbin; Xiao, Xiao; McNally, Elizabeth M; Mack, Christopher P; Taylor, Joan M

    2015-01-01

    The plasma membranes of striated muscle cells are particularly susceptible to rupture as they endure significant mechanical stress and strain during muscle contraction, and studies have shown that defects in membrane repair can contribute to the progression of muscular dystrophy. The synaptotagmin-related protein, dysferlin, has been implicated in mediating rapid membrane repair through its ability to direct intracellular vesicles to sites of membrane injury. However, further work is required to identify the precise molecular mechanisms that govern dysferlin targeting and membrane repair. We previously showed that the bin-amphiphysin-Rvs (BAR)-pleckstrin homology (PH) domain containing Rho-GAP GTPase regulator associated with focal adhesion kinase-1 (GRAF1) was dynamically recruited to the tips of fusing myoblasts wherein it promoted membrane merging by facilitating ferlin-dependent capturing of intracellular vesicles. Because acute membrane repair responses involve similar vesicle trafficking complexes/events and because our prior studies in GRAF1-deficient tadpoles revealed a putative role for GRAF1 in maintaining muscle membrane integrity, we postulated that GRAF1 might also play an important role in facilitating dysferlin-dependent plasma membrane repair. We used an in vitro laser-injury model to test whether GRAF1 was necessary for efficient muscle membrane repair. We also generated dystrophin/GRAF1 doubledeficient mice by breeding mdx mice with GRAF1 hypomorphic mice. Evans blue dye uptake and extensive morphometric analyses were used to assess sarcolemmal integrity and related pathologies in cardiac and skeletal muscles isolated from these mice. Herein, we show that GRAF1 is dynamically recruited to damaged skeletal and cardiac muscle plasma membranes and that GRAF1-depleted muscle cells have reduced membrane healing abilities. Moreover, we show that dystrophin depletion exacerbated muscle damage in GRAF1-deficient mice and that mice with dystrophin/GRAF1

  20. Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene.

    Science.gov (United States)

    Gonçalves, Ana; Oliveira, Jorge; Coelho, Teresa; Taipa, Ricardo; Melo-Pires, Manuel; Sousa, Mário; Santos, Rosário

    2017-10-03

    A broad mutational spectrum in the dystrophin ( DMD ) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD , adding to the diversity of mutational events that give rise to D/BMD.

  1. Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

    Science.gov (United States)

    Gonçalves, Ana; Coelho, Teresa; Melo-Pires, Manuel; Sousa, Mário

    2017-01-01

    A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD. PMID:28972564

  2. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Yongping Yue

    2016-01-01

    Full Text Available Dystrophin gene replacement holds the promise of treating Duchenne muscular dystrophy. Supraphysiological expression is a concern for all gene therapy studies. In the case of Duchenne muscular dystrophy, Chamberlain and colleagues found that 50-fold overexpression did not cause deleterious side effect in skeletal muscle. To determine whether excessive dystrophin expression in the heart is safe, we studied two lines of transgenic mdx mice that selectively expressed a therapeutic minidystrophin gene in the heart at 50-fold and 100-fold of the normal levels. In the line with 50-fold overexpression, minidystrophin showed sarcolemmal localization and electrocardiogram abnormalities were corrected. However, in the line with 100-fold overexpression, we not only detected sarcolemmal minidystrophin expression but also observed accumulation of minidystrophin vesicles in the sarcoplasm. Excessive minidystrophin expression did not correct tachycardia, a characteristic feature of Duchenne muscular dystrophy. Importantly, several electrocardiogram parameters (QT interval, QRS duration and the cardiomyopathy index became worse than that of mdx mice. Our data suggests that the mouse heart can tolerate 50-fold minidystrophin overexpression, but 100-fold overexpression leads to cardiac toxicity.

  3. Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

    Science.gov (United States)

    Cai, B.; Spencer, M. J.; Nakamura, G.; Tseng-Ong, L.; Tidball, J. G.

    2000-01-01

    Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to muscular dystrophy. Quantitative immunohistochemistry confirmed that eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperitoneal injection resulted in muscle eosinophilia in the recipient mice. Double-mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentration of CTLs in dystrophic muscle, produced a significant reduction in eosinophilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells. However, some eosinophilia of mdx muscle is independent of perforin-mediated processes.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy.

    Science.gov (United States)

    Yang, Hee Seok; Ieronimakis, Nicholas; Tsui, Jonathan H; Kim, Hong Nam; Suh, Kahp-Yang; Reyes, Morayma; Kim, Deok-Ho

    2014-02-01

    Skeletal muscle is a highly organized tissue in which the extracellular matrix (ECM) is composed of highly-aligned cables of collagen with nanoscale feature sizes, and provides structural and functional support to muscle fibers. As such, the transplantation of disorganized tissues or the direct injection of cells into muscles for regenerative therapy often results in suboptimal functional improvement due to a failure to integrate with native tissue properly. Here, we present a simple method in which biodegradable, biomimetic substrates with precisely controlled nanotopography were fabricated using solvent-assisted capillary force lithography (CFL) and were able to induce the proper development and differentiation of primary mononucleated cells to form mature muscle patches. Cells cultured on these nanopatterned substrates were highly-aligned and elongated, and formed more mature myotubes as evidenced by up-regulated expression of the myogenic regulatory factors Myf5, MyoD and myogenin (MyoG). When transplanted into mdx mice models for Duchenne muscular dystrophy (DMD), the proposed muscle patches led to the formation of a significantly greater number of dystrophin-positive muscle fibers, indicating that dystrophin replacement and myogenesis is achievable in vivo with this approach. These results demonstrate the feasibility of utilizing biomimetic substrates not only as platforms for studying the influences of the ECM on skeletal muscle function and maturation, but also to create transplantable muscle cell patches for the treatment of chronic and acute muscle diseases or injuries. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Immobilization of Dystrophin and Laminin α2-Chain Deficient Zebrafish Larvae In Vivo Prevents the Development of Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Mei Li

    Full Text Available Muscular dystrophies are often caused by genetic alterations in the dystrophin-dystroglycan complex or its extracellular ligands. These structures are associated with the cell membrane and provide mechanical links between the cytoskeleton and the matrix. Mechanical stress is considered a pathological mechanism and muscle immobilization has been shown to be beneficial in some mouse models of muscular dystrophy. The zebrafish enables novel and less complex models to examine the effects of extended immobilization or muscle relaxation in vivo in different dystrophy models. We have examined effects of immobilization in larvae from two zebrafish strains with muscular dystrophy, the Sapje dystrophin-deficient and the Candyfloss laminin α2-chain-deficient strains. Larvae (4 days post fertilization, dpf of both mutants have significantly lower active force in vitro, alterations in the muscle structure with gaps between muscle fibers and altered birefringence patterns compared to their normal siblings. Complete immobilization (18 hrs to 4 dpf was achieved using a small molecular inhibitor of actin-myosin interaction (BTS, 50 μM. This treatment resulted in a significantly weaker active contraction at 4 dpf in both mutated larvae and normal siblings, most likely reflecting a general effect of immobilization on myofibrillogenesis. The immobilization also significantly reduced the structural damage in the mutated strains, showing that muscle activity is an important pathological mechanism. Following one-day washout of BTS, muscle tension partly recovered in the Candyfloss siblings and caused structural damage in these mutants, indicating activity-induced muscle recovery and damage, respectively.

  7. Gentamicin treatment in exercised mdx mice: Identification of dystrophin-sensitive pathways and evaluation of efficacy in work-loaded dystrophic muscle.

    Science.gov (United States)

    De Luca, Annamaria; Nico, Beatrice; Rolland, Jean-François; Cozzoli, Anna; Burdi, Rosa; Mangieri, Domenica; Giannuzzi, Viviana; Liantonio, Antonella; Cippone, Valentina; De Bellis, Michela; Nicchia, Grazia Paola; Camerino, Giulia Maria; Frigeri, Antonio; Svelto, Maria; Camerino, Diana Conte

    2008-11-01

    Aminoglycosides force read through of premature stop codon mutations and introduce new mutation-specific gene-corrective strategies in Duchenne muscular dystrophy. A chronic treatment with gentamicin (32 mg/kg/daily i.p., 8-12 weeks) was performed in exercised mdx mice with the dual aim to clarify the dependence on dystrophin of the functional, biochemical and histological alterations present in dystrophic muscle and to verify the long term efficiency of small molecule gene-corrective strategies in work-loaded dystrophic muscle. The treatment counteracted the exercise-induced impairment of in vivo forelimb strength after 6-8 weeks. We observed an increase in dystrophin expression level in all the fibers, although lower than that observed in normal fibers, and found a concomitant recovery of aquaporin-4 at sarcolemma. A significant reduction in centronucleated fibers, in the area of necrosis and in the percentage of nuclear factor-kB-positive nuclei was observed in gastrocnemious muscle of treated animals. Plasma creatine kinase was reduced by 70%. Ex vivo, gentamicin restored membrane ionic conductance in mdx diaphragm and limb muscle fibers. No effects were observed on the altered calcium homeostasis and sarcolemmal calcium permeability, detected by electrophysiological and microspectrofluorimetric approaches. Thus, the maintenance of a partial level of dystrophin is sufficient to reinforce sarcolemmal stability, reducing leakiness, inflammation and fiber damage, while correction of altered calcium homeostasis needs greater expression of dystrophin or direct interventions on the channels involved.

  8. Protein truncation test: analysis of two novel point mutations at the carboxy-terminus of the human dystrophin gene associated with mental retardation.

    Science.gov (United States)

    Tuffery, S; Lenk, U; Roberts, R G; Coubes, C; Demaille, J; Claustres, M

    1995-01-01

    Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-terminating mutations. A number of data raised the possibility that the C-terminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutations in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation termination of dystrophin. The possible effects on the reading frame were analyzed by the study of reverse transcripts amplified from peripheral blood lymphocytes mRNA and by the protein truncation test.

  9. Concurrent Label-Free Mass Spectrometric Analysis of Dystrophin Isoform Dp427 and the Myofibrosis Marker Collagen in Crude Extracts from mdx-4cv Skeletal Muscles

    Science.gov (United States)

    Murphy, Sandra; Zweyer, Margit; Mundegar, Rustam R.; Henry, Michael; Meleady, Paula; Swandulla, Dieter; Ohlendieck, Kay

    2015-01-01

    The full-length dystrophin protein isoform of 427 kDa (Dp427), the absence of which represents the principal abnormality in X-linked muscular dystrophy, is difficult to identify and characterize by routine proteomic screening approaches of crude tissue extracts. This is probably related to its large molecular size, its close association with the sarcolemmal membrane, and its existence within a heterogeneous glycoprotein complex. Here, we used a careful extraction procedure to isolate the total protein repertoire from normal versus dystrophic mdx-4cv skeletal muscles, in conjunction with label-free mass spectrometry, and successfully identified Dp427 by proteomic means. In contrast to a considerable number of previous comparative studies of the total skeletal muscle proteome, using whole tissue proteomics we show here for the first time that the reduced expression of this membrane cytoskeletal protein is the most significant alteration in dystrophinopathy. This agrees with the pathobiochemical concept that the almost complete absence of dystrophin is the main defect in Duchenne muscular dystrophy and that the mdx-4cv mouse model of dystrophinopathy exhibits only very few revertant fibers. Significant increases in collagens and associated fibrotic marker proteins, such as fibronectin, biglycan, asporin, decorin, prolargin, mimecan, and lumican were identified in dystrophin-deficient muscles. The up-regulation of collagen in mdx-4cv muscles was confirmed by immunofluorescence microscopy and immunoblotting. Thus, this is the first mass spectrometric study of crude tissue extracts that puts the proteomic identification of dystrophin in its proper pathophysiological context. PMID:28248273

  10. Somatic mosaicism of a point mutation in the dystrophin gene in a patient presenting with an asymmetrical muscle weakness and contractures

    NARCIS (Netherlands)

    Helderman-van den Enden, A. T. J. M.; Ginjaar, H. B.; Kneppers, A. L. J.; Bakker, E.; Breuning, M. H.; de Visser, M.

    2003-01-01

    We describe a patient with somatic mosaicism of a point mutation in the dystrophin gene causing benign muscular dystrophy with an unusual asymmetrical distribution of muscle weakness and contractures. To our knowledge this is the first patient with asymmetrical weakness and contractures in an

  11. Fetal microchimeric cells in a fetus-treats-its-mother paradigm do not contribute to dystrophin production in serially parous mdx females.

    Science.gov (United States)

    Seppanen, Elke Jane; Hodgson, Samantha Susan; Khosrotehrani, Kiarash; Bou-Gharios, George; Fisk, Nicholas M

    2012-10-10

    Throughout every pregnancy, genetically distinct fetal microchimeric stem/progenitor cells (FMCs) engraft in the mother, persist long after delivery, and may home to damaged maternal tissues. Phenotypically normal fetal lymphoid progenitors have been described to develop in immunodeficient mothers in a fetus-treats-its-mother paradigm. Since stem cells contribute to muscle repair, we assessed this paradigm in the mdx mouse model of Duchenne muscular dystrophy. mdx females were bred serially to either ROSAeGFP males or mdx males to obtain postpartum microchimeras that received either wild-type FMCs or dystrophin-deficient FMCs through serial gestations. To enhance regeneration, notexin was injected into the tibialis anterior of postpartum mice. FMCs were detected by qPCR at a higher frequency in injected compared to noninjected side muscle (P=0.02). However, the number of dystrophin-positive fibers was similar in mothers delivering wild-type compared to mdx pups. In addition, there was no correlation between FMC detection and percentage dystrophin, and no GFP+ve FMCs were identified that expressed dystrophin. In 10/11 animals, GFP+ve FMCs were detected by immunohistochemistry, of which 60% expressed CD45 with 96% outside the basal lamina defining myofiber contours. Finally we confirmed lack of FMC contribution to statellite cells in postpartum mdx females mated with Myf5-LacZ males. We conclude that the FMC contribution to regenerating muscles is insufficient to have a functional impact.

  12. More deletions in the 5{prime} region than in the central region of the dystrophin gene were identified among Filipino Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-06

    This report describes mutations in the dystrophin gene and the frequency of these mutations in Filipino pedigrees with Duchenne and Becker muscular dystrophy (DMD/BMD). The findings suggest the presence of genetic variability among DMD/BMD patients in different populations. 13 refs., 1 tab.

  13. Identification of a novel first exon in the human dystrophin gene and of a new promoter located more than 500 kb upstream of the nearest known promoter

    Energy Technology Data Exchange (ETDEWEB)

    Yanagawa, H.; Nishio, H.; Takeshima, Y. [Kobe Univ. School of Medicine (Japan)] [and others

    1994-09-01

    The dystrophin gene, which is muted in patients with Duchenne and Becker muscular dystrophies, is the largest known human gene. Five alternative promoters have been characterized until now. Here we show that a novel dystrophin isoform with a different first exon can be produced through transcription initiation at a previously-unidentified alternative promoter. The case study presented is that of patient with Duchenne muscular dystrophy who had a deletion extending from 5{prime} end of the dystrophin gene to exon 2, including all promoters previously mapped in the 5{prime} part of the gene. Transcripts from lymphoblastoid cells were found to contain sequences corresponding to exon 3, indicating the presence of new promoter upstream of this exon. The nucleotide sequence of amplified cDNA corresponding to the 5{prime} end of the new transcript indicated that the 5{prime} end of exon 3 was extended by 9 codons, only the last (most 3{prime}) of which codes for methionine. The genomic nucleotide sequence upstream from the new exon, as determined using inverse polymerase chain reaction, revealed the presence of sequences similar to a TATA box, an octamer motif and an MEF-2 element. The identified promoter/exon did not map to intron 2, as might have been expected, but to a position more than 500 kb upstream of the most 5{prime} of the previously-identified promoters, thereby adding 500 kb to the dystrophin gene. The sequence of part of the new promoter region is very similar to that of certain medium reiteration frequency repetitive sequences. These findings may help us understand the molecular evolution of the dystrophin gene.

  14. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino.

    Science.gov (United States)

    Wu, Bo; Lu, Peijuan; Cloer, Caryn; Shaban, Mona; Grewal, Snimar; Milazi, Stephanie; Shah, Sapana N; Moulton, Hong M; Lu, Qi Long

    2012-08-01

    Exon skipping is capable of correcting frameshift and nonsense mutations in Duchenne muscular dystrophy. Phase 2 clinical trials in the United Kingdom and the Netherlands have reported induction of dystrophin expression in muscle of Duchenne muscular dystrophy patients by systemic administration of both phosphorodiamidate morpholino oligomers (PMO) and 2'-O-methyl phosphorothioate. Peptide-conjugated phosphorodiamidate morpholino offers significantly higher efficiency than phosphorodiamidate morpholino, with the ability to induce near-normal levels of dystrophin, and restores function in both skeletal and cardiac muscle. We examined 1-year systemic efficacy of peptide-conjugated phosphorodiamidate morpholino targeting exon 23 in dystrophic mdx mice. The LD(50) of peptide-conjugated phosphorodiamidate morpholino was determined to be approximately 85 mg/kg. The half-life of dystrophin expression was approximately 2 months in skeletal muscle, but shorter in cardiac muscle. Biweekly injection of 6 mg/kg peptide-conjugated phosphorodiamidate morpholino produced >20% dystrophin expression in all skeletal muscles and ≤5% in cardiac muscle, with improvement in muscle function and pathology and reduction in levels of serum creatine kinase. Monthly injections of 30 mg/kg peptide-conjugated phosphorodiamidate morpholino restored dystrophin to >50% normal levels in skeletal muscle, and 15% in cardiac muscle. This was associated with greatly reduced serum creatine kinase levels, near-normal histology, and functional improvement of skeletal muscle. Our results demonstrate for the first time that regular 1-year administration of peptide-conjugated phosphorodiamidate morpholino can be safely applied to achieve significant therapeutic effects in an animal model. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Evaluation of point mutations in dystrophin gene in Iranian Duchenne and Becker muscular dystrophy patients: introducing three novel variants.

    Science.gov (United States)

    Haghshenas, Maryam; Akbari, Mohammad Taghi; Karizi, Shohreh Zare; Deilamani, Faravareh Khordadpoor; Nafissi, Shahriar; Salehi, Zivar

    2016-06-01

    Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked neuromuscular diseases characterized by progressive muscular weakness and degeneration of skeletal muscles. Approximately two-thirds of the patients have large deletions or duplications in the dystrophin gene and the remaining one-third have point mutations. This study was performed to evaluate point mutations in Iranian DMD/BMD male patients. A total of 29 DNA samples from patients who did not show any large deletion/duplication mutations following multiplex polymerase chain reaction (PCR) and multiplex ligation-dependent probe amplification (MLPA) screening were sequenced for detection of point mutations in exons 50-79. Also exon 44 was sequenced in one sample in which a false positive deletion was detected by MLPA method. Cycle sequencing revealed four nonsense, one frameshift and two splice site mutations as well as two missense variants.

  16. Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, Morten; Vissing, John

    2011-01-01

    With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD...... skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK....... associated with an exon 26 deletion. The proband, a 23-year-old man, had slightly delayed motor milestones, walking 1 1/2 years old. He had no complaints of muscle weakness, but had muscle pain. Clinical examination revealed no muscle wasting or loss of power, but his CK was 1500-7000 U/l. Muscle biopsy...

  17. Defects in mitochondrial ATP synthesis in dystrophin-deficient mdx skeletal muscles may be caused by complex I insufficiency.

    Directory of Open Access Journals (Sweden)

    Emma Rybalka

    Full Text Available Duchenne Muscular Dystrophy is a chronic, progressive and ultimately fatal skeletal muscle wasting disease characterised by sarcolemmal fragility and intracellular Ca2+ dysregulation secondary to the absence of dystrophin. Mounting literature also suggests that the dysfunction of key energy systems within the muscle may contribute to pathological muscle wasting by reducing ATP availability to Ca2+ regulation and fibre regeneration. No study to date has biochemically quantified and contrasted mitochondrial ATP production capacity by dystrophic mitochondria isolated from their pathophysiological environment such to determine whether mitochondria are indeed capable of meeting this heightened cellular ATP demand, or examined the effects of an increasing extramitochondrial Ca2+ environment. Using isolated mitochondria from the diaphragm and tibialis anterior of 12 week-old dystrophin-deficient mdx and healthy control mice (C57BL10/ScSn we have demonstrated severely depressed Complex I-mediated mitochondrial ATP production rate in mdx mitochondria that occurs irrespective of the macronutrient-derivative substrate combination fed into the Kreb's cycle, and, which is partially, but significantly, ameliorated by inhibition of Complex I with rotenone and stimulation of Complex II-mediated ATP-production with succinate. There was no difference in the MAPR response of mdx mitochondria to increasing extramitochondrial Ca2+ load in comparison to controls, and 400 nM extramitochondrial Ca2+ was generally shown to be inhibitory to MAPR in both groups. Our data suggests that DMD pathology is exacerbated by a Complex I deficiency, which may contribute in part to the severe reductions in ATP production previously observed in dystrophic skeletal muscle.

  18. Sparing of the dystrophin-deficient cranial sartorius muscle is associated with classical and novel hypertrophy pathways in GRMD dogs.

    Science.gov (United States)

    Nghiem, Peter P; Hoffman, Eric P; Mittal, Priya; Brown, Kristy J; Schatzberg, Scott J; Ghimbovschi, Svetlana; Wang, Zuyi; Kornegay, Joe N

    2013-11-01

    Both Duchenne and golden retriever muscular dystrophy (GRMD) are caused by dystrophin deficiency. The Duchenne muscular dystrophy sartorius muscle and orthologous GRMD cranial sartorius (CS) are relatively spared/hypertrophied. We completed hierarchical clustering studies to define molecular mechanisms contributing to this differential involvement and their role in the GRMD phenotype. GRMD dogs with larger CS muscles had more severe deficits, suggesting that selective hypertrophy could be detrimental. Serial biopsies from the hypertrophied CS and other atrophied muscles were studied in a subset of these dogs. Myostatin showed an age-dependent decrease and an inverse correlation with the degree of GRMD CS hypertrophy. Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional rescue of this muscle. mRNA and proteomic profiling was used to identify additional candidate genes associated with CS hypertrophy. The top-ranked network included α-dystroglycan and like-acetylglucosaminyltransferase. Proteomics demonstrated increases in myotrophin and spectrin that could promote hypertrophy and cytoskeletal stability, respectively. Our results suggest that multiple pathways, including decreased myostatin and up-regulated miRNAs, α-dystroglycan/like-acetylglucosaminyltransferase, spectrin, and myotrophin, contribute to hypertrophy and functional sparing of the CS. These data also underscore the muscle-specific responses to dystrophin deficiency and the potential deleterious effects of differential muscle involvement. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs.

    Directory of Open Access Journals (Sweden)

    Lluís Sánchez

    Full Text Available Four full-sibling intact male Miniature Poodles were evaluated at 4-19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog.

  20. Motor physical therapy affects muscle collagen type I and decreases gait speed in dystrophin-deficient dogs.

    Directory of Open Access Journals (Sweden)

    Thaís P Gaiad

    Full Text Available Golden Retriever Muscular Dystrophy (GRMD is a dystrophin-deficient canine model genetically homologous to Duchenne Muscular Dystrophy (DMD in humans. Muscular fibrosis secondary to cycles of degeneration/regeneration of dystrophic muscle tissue and muscular weakness leads to biomechanical adaptation that impairs the quality of gait. Physical therapy (PT is one of the supportive therapies available for DMD, however, motor PT approaches have controversial recommendations and there is no consensus regarding the type and intensity of physical therapy. In this study we investigated the effect of physical therapy on gait biomechanics and muscular collagen deposition types I and III in dystrophin-deficient dogs. Two dystrophic dogs (treated dogs-TD underwent a PT protocol of active walking exercise, 3×/week, 40 minutes/day, 12 weeks. Two dystrophic control dogs (CD maintained their routine of activities of daily living. At t0 (pre and t1 (post-physical therapy, collagen type I and III were assessed by immunohistochemistry and gait biomechanics were analyzed. Angular displacement of shoulder, elbow, carpal, hip, stifle and tarsal joint and vertical (Fy, mediolateral (Fz and craniocaudal (Fx ground reaction forces (GRF were assessed. Wilcoxon test was used to verify the difference of biomechanical variables between t0 and t1, considering p<.05. Type I collagen of endomysium suffered the influence of PT, as well as gait speed that had decreased from t0 to t1 (p<.000. The PT protocol employed accelerates morphological alterations on dystrophic muscle and promotes a slower velocity of gait. Control dogs which maintained their routine of activities of daily living seem to have found a better balance between movement and preservation of motor function.

  1. Motor Physical Therapy Affects Muscle Collagen Type I and Decreases Gait Speed in Dystrophin-Deficient Dogs

    Science.gov (United States)

    Gaiad, Thaís P.; Araujo, Karla P. C.; Serrão, Júlio C.; Miglino, Maria A.; Ambrósio, Carlos Eduardo

    2014-01-01

    Golden Retriever Muscular Dystrophy (GRMD) is a dystrophin-deficient canine model genetically homologous to Duchenne Muscular Dystrophy (DMD) in humans. Muscular fibrosis secondary to cycles of degeneration/regeneration of dystrophic muscle tissue and muscular weakness leads to biomechanical adaptation that impairs the quality of gait. Physical therapy (PT) is one of the supportive therapies available for DMD, however, motor PT approaches have controversial recommendations and there is no consensus regarding the type and intensity of physical therapy. In this study we investigated the effect of physical therapy on gait biomechanics and muscular collagen deposition types I and III in dystrophin-deficient dogs. Two dystrophic dogs (treated dogs-TD) underwent a PT protocol of active walking exercise, 3×/week, 40 minutes/day, 12 weeks. Two dystrophic control dogs (CD) maintained their routine of activities of daily living. At t0 (pre) and t1 (post-physical therapy), collagen type I and III were assessed by immunohistochemistry and gait biomechanics were analyzed. Angular displacement of shoulder, elbow, carpal, hip, stifle and tarsal joint and vertical (Fy), mediolateral (Fz) and craniocaudal (Fx) ground reaction forces (GRF) were assessed. Wilcoxon test was used to verify the difference of biomechanical variables between t0 and t1, considering p<.05. Type I collagen of endomysium suffered the influence of PT, as well as gait speed that had decreased from t0 to t1 (p<.000). The PT protocol employed accelerates morphological alterations on dystrophic muscle and promotes a slower velocity of gait. Control dogs which maintained their routine of activities of daily living seem to have found a better balance between movement and preservation of motor function. PMID:24713872

  2. Evaluation of skeletal and cardiac muscle function after chronic administration of thymosin beta-4 in the dystrophin deficient mouse.

    Directory of Open Access Journals (Sweden)

    Christopher F Spurney

    2010-01-01

    Full Text Available Thymosin beta-4 (Tbeta4 is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tbeta4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ and mdx mice, 8-10 weeks old, were treated with 150 microg of Tbeta4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tbeta4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tbeta4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tbeta4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tbeta4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy.

  3. Distal mdx muscle groups exhibiting up-regulation of utrophin and rescue of dystrophin-associated glycoproteins exemplify a protected phenotype in muscular dystrophy

    Science.gov (United States)

    Dowling, Paul; Culligan, Kevin; Ohlendieck, Kay

    2002-02-01

    Unique unaffected skeletal muscle fibres, unlike necrotic torso and limb muscles, may pave the way for a more detailed understanding of the molecular pathogenesis of inherited neuromuscular disorders and help to develop new treatment strategies for muscular dystrophies. The sparing of extraocular muscle in Duchenne muscular dystrophy is mostly attributed to the special protective properties of extremely fast-twitching small-diameter fibres, but here we show that distal muscles also represent a particular phenotype that is more resistant to necrosis. Immunoblot analysis of membranes isolated from the well established dystrophic animal model mdx shows that, in contrast to dystrophic limb muscles, the toe musculature exhibits an up-regulation of the autosomal dystrophin homologue utrophin and a concomitant rescue of dystrophin-associated glycoproteins. Thus distal mdx muscle groups provide a cellular system that naturally avoids myofibre degeneration which might be useful in the search for naturally occurring compensatory mechanisms in inherited skeletal muscle diseases.

  4. Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies.

    Science.gov (United States)

    Janghra, Narinder; Morgan, Jennifer E; Sewry, Caroline A; Wilson, Francis X; Davies, Kay E; Muntoni, Francesco; Tinsley, Jonathon

    2016-01-01

    Duchenne muscular dystrophy is a severe and currently incurable progressive neuromuscular condition, caused by mutations in the DMD gene that result in the inability to produce dystrophin. Lack of dystrophin leads to loss of muscle fibres and a reduction in muscle mass and function. There is evidence from dystrophin-deficient mouse models that increasing levels of utrophin at the muscle fibre sarcolemma by genetic or pharmacological means significantly reduces the muscular dystrophy pathology. In order to determine the efficacy of utrophin modulators in clinical trials, it is necessary to accurately measure utrophin levels and other biomarkers on a fibre by fibre basis within a biopsy section. Our aim was to develop robust and reproducible staining and imaging protocols to quantify sarcolemmal utrophin levels, sarcolemmal dystrophin complex members and numbers of regenerating fibres within a biopsy section. We quantified sarcolemmal utrophin in mature and regenerating fibres and the percentage of regenerating muscle fibres, in muscle biopsies from Duchenne, the milder Becker muscular dystrophy and controls. Fluorescent immunostaining followed by image analysis was performed to quantify utrophin intensity and β-dystrogylcan and ɣ -sarcoglycan intensity at the sarcolemma. Antibodies to fetal and developmental myosins were used to identify regenerating muscle fibres allowing the accurate calculation of percentage regeneration fibres in the biopsy. Our results indicate that muscle biopsies from Becker muscular dystrophy patients have fewer numbers of regenerating fibres and reduced utrophin intensity compared to muscle biopsies from Duchenne muscular dystrophy patients. Of particular interest, we show for the first time that the percentage of regenerating muscle fibres within the muscle biopsy correlate with the clinical severity of Becker and Duchenne muscular dystrophy patients from whom the biopsy was taken. The ongoing development of these tools to quantify

  5. Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies.

    Directory of Open Access Journals (Sweden)

    Narinder Janghra

    Full Text Available Duchenne muscular dystrophy is a severe and currently incurable progressive neuromuscular condition, caused by mutations in the DMD gene that result in the inability to produce dystrophin. Lack of dystrophin leads to loss of muscle fibres and a reduction in muscle mass and function. There is evidence from dystrophin-deficient mouse models that increasing levels of utrophin at the muscle fibre sarcolemma by genetic or pharmacological means significantly reduces the muscular dystrophy pathology. In order to determine the efficacy of utrophin modulators in clinical trials, it is necessary to accurately measure utrophin levels and other biomarkers on a fibre by fibre basis within a biopsy section. Our aim was to develop robust and reproducible staining and imaging protocols to quantify sarcolemmal utrophin levels, sarcolemmal dystrophin complex members and numbers of regenerating fibres within a biopsy section. We quantified sarcolemmal utrophin in mature and regenerating fibres and the percentage of regenerating muscle fibres, in muscle biopsies from Duchenne, the milder Becker muscular dystrophy and controls. Fluorescent immunostaining followed by image analysis was performed to quantify utrophin intensity and β-dystrogylcan and ɣ -sarcoglycan intensity at the sarcolemma. Antibodies to fetal and developmental myosins were used to identify regenerating muscle fibres allowing the accurate calculation of percentage regeneration fibres in the biopsy. Our results indicate that muscle biopsies from Becker muscular dystrophy patients have fewer numbers of regenerating fibres and reduced utrophin intensity compared to muscle biopsies from Duchenne muscular dystrophy patients. Of particular interest, we show for the first time that the percentage of regenerating muscle fibres within the muscle biopsy correlate with the clinical severity of Becker and Duchenne muscular dystrophy patients from whom the biopsy was taken. The ongoing development of these

  6. A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping.

    Directory of Open Access Journals (Sweden)

    Gemma L Walmsley

    2010-01-01

    Full Text Available Duchenne muscular dystrophy (DMD, which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion "hot spot" is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD "hot spot".Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD. The dogs harbour a missense mutation in the 5' donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression.Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD.

  7. 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.

  8. 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.

  9. Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9.

    Science.gov (United States)

    Li, Hongmei Lisa; Fujimoto, Naoko; Sasakawa, Noriko; Shirai, Saya; Ohkame, Tokiko; Sakuma, Tetsushi; Tanaka, Michihiro; Amano, Naoki; Watanabe, Akira; Sakurai, Hidetoshi; Yamamoto, Takashi; Yamanaka, Shinya; Hotta, Akitsu

    2015-01-13

    Duchenne muscular dystrophy (DMD) is a severe muscle-degenerative disease caused by a mutation in the dystrophin gene. Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined. Using a unique k-mer database, we systematically identified a unique target region that reduces off-target sites. To restore the dystrophin protein, we performed three correction methods (exon skipping, frameshifting, and exon knockin) in DMD-patient-derived iPSCs, and found that exon knockin was the most effective approach. We further investigated the genomic integrity by karyotyping, copy number variation array, and exome sequencing to identify clones with a minimal mutation load. Finally, we differentiated the corrected iPSCs toward skeletal muscle cells and successfully detected the expression of full-length dystrophin protein. These results provide an important framework for developing iPSC-based gene therapy for genetic disorders using programmable nucleases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Long-Term Efficacy of Systemic Multiexon Skipping Targeting Dystrophin Exons 45–55 With a Cocktail of Vivo-Morpholinos in Mdx52 Mice

    Directory of Open Access Journals (Sweden)

    Yusuke Echigoya

    2015-01-01

    Full Text Available Antisense-mediated exon skipping, which can restore the reading frame, is a most promising therapeutic approach for Duchenne muscular dystrophy. Remaining challenges include the limited applicability to patients and unclear function of truncated dystrophin proteins. Multiexon skipping targeting exons 45–55 at the mutation hotspot of the dystrophin gene could overcome both of these challenges. Previously, we described the feasibility of exons 45–55 skipping with a cocktail of Vivo-Morpholinos in vivo; however, the long-term efficacy and safety of Vivo-Morpholinos remains to be determined. In this study, we examined the efficacy and toxicity of exons 45–55 skipping by intravenous injections of 6 mg/kg 10-Vivo-Morpholino cocktail (0.6 mg/kg each vPMO every 2 weeks for 18 weeks to dystrophic exon-52 knockout (mdx52 mice. Systemic skipping of the entire exons 45–55 region was induced, and the Western blot analysis exhibited the restoration of 5–27% of normal levels of dystrophin protein in skeletal muscles, accompanied by improvements in histopathology and muscle strength. No obvious immune response and renal and hepatic toxicity were detected at the end-point of the treatment. We demonstrate our new regimen with the 10-Vivo-Morpholino cocktail is effective and safe for long-term repeated systemic administration in the dystrophic mouse model.

  11. How honey bees carry pollen

    Science.gov (United States)

    Matherne, Marguerite E.; Anyanwu, Gabriel; Leavey, Jennifer K.; Hu, David L.

    2017-11-01

    Honey bees are the tanker of the skies, carrying thirty percent of their weight in pollen per foraging trip using specialized orifices on their body. How do they manage to hang onto those pesky pollen grains? In this experimental study, we investigate the adhesion force of pollen to the honeybee. To affix pollen to themselves, honey bees form a suspension of pollen in nectar, creating a putty-like pollen basket that is skewered by leg hairs. We use tensile tests to show that the viscous force of the pollen basket is more than ten times the honeybee's flight force. This work may provide inspiration for the design of robotic flying pollinators.

  12. Voluntary wheel running in dystrophin-deficient (mdx) mice: Relationships between exercise parameters and exacerbation of the dystrophic phenotype.

    Science.gov (United States)

    Smythe, Gayle M; White, Jason D

    2011-12-18

    Voluntary wheel running can potentially be used to exacerbate the disease phenotype in dystrophin-deficient mdx mice. While it has been established that voluntary wheel running is highly variable between individuals, the key parameters of wheel running that impact the most on muscle pathology have not been examined in detail. We conducted a 2-week test of voluntary wheel running by mdx mice and the impact of wheel running on disease pathology. There was significant individual variation in the average daily distance (ranging from 0.003 ± 0.005 km to 4.48 ± 0.96 km), culminating in a wide range (0.040 km to 67.24 km) of total cumulative distances run by individuals. There was also variation in the number and length of run/rest cycles per night, and the average running rate. Correlation analyses demonstrated that in the quadriceps muscle, a low number of high distance run/rest cycles was the most consistent indicator for increased tissue damage. The amount of rest time between running bouts was a key factor associated with gastrocnemius damage. These data emphasize the need for detailed analysis of individual running performance, consideration of the length of wheel exposure time, and the selection of appropriate muscle groups for analysis, when applying the use of voluntary wheel running to disease exacerbation and/or pre-clinical testing of the efficacy of therapeutic agents in the mdx mouse.

  13. Metabolic dysfunction and altered mitochondrial dynamics in the utrophin-dystrophin deficient mouse model of duchenne muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Meghna Pant

    Full Text Available The utrophin-dystrophin deficient (DKO mouse model has been widely used to understand the progression of Duchenne muscular dystrophy (DMD. However, it is unclear as to what extent muscle pathology affects metabolism. Therefore, the present study was focused on understanding energy expenditure in the whole animal and in isolated extensor digitorum longus (EDL muscle and to determine changes in metabolic enzymes. Our results show that the 8 week-old DKO mice consume higher oxygen relative to activity levels. Interestingly the EDL muscle from DKO mouse consumes higher oxygen per unit integral force, generates less force and performs better in the presence of pyruvate thus mimicking a slow twitch muscle. We also found that the expression of hexokinase 1 and pyruvate kinase M2 was upregulated several fold suggesting increased glycolytic flux. Additionally, there is a dramatic increase in dynamin-related protein 1 (Drp 1 and mitofusin 2 protein levels suggesting increased mitochondrial fission and fusion, a feature associated with increased energy demand and altered mitochondrial dynamics. Collectively our studies point out that the dystrophic disease has caused significant changes in muscle metabolism. To meet the increased energetic demand, upregulation of metabolic enzymes and regulators of mitochondrial fusion and fission is observed in the dystrophic muscle. A better understanding of the metabolic demands and the accompanied alterations in the dystrophic muscle can help us design improved intervention therapies along with existing drug treatments for the DMD patients.

  14. A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain.

    Science.gov (United States)

    Simon, Matthew J; Murchison, Charles; Iliff, Jeffrey J

    2018-02-01

    Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes. © 2017 Wiley Periodicals, Inc.

  15. The Role of Nanobiotechnology in the Study of Dystrophin and B-Dystroglycan in Membrane Stability of Aging Skeletal Muscles

    Science.gov (United States)

    Vaseashta, Ashok

    2005-03-01

    Duchene muscular dystrophy (DMD) is one of nine types of muscular dystrophy, a group of genetic degenerative diseases, primarily affecting voluntary muscles, caused by absence of dystrophin. New experiments on mice with DMD has shown that gene therapy can reverse some symptoms of the disease. The ultimate goal of gene therapy for muscle diseases is improvement of strength and function, which will require treatment in multiple muscles simultaneously. A major limitation to gene therapy until now has been that no one had found a method by which a new gene could be delivered to all the muscles of an adult animal. Recent utilization of nanotechnology to life sciences has shown exciting promises in a wide range of disciplines, showing advances in the ability to manipulate, fabricate and alter tiny subjects at the nanometer scale. In the present investigation, we have employed such techniques to study single motors such as myosin and kinesin, as well elastic proteins viz. titin and nebulin, muscle filaments, cytoskeletal filaments, and receptors in cellular membranes and cellular organelles viz. myofibril, ribosome, and chromatin. Application of AFM to images and measures the elastic properties of single monomeric and oligomeric protein, genetically engineered titin, and nebulin molecules will be presented.

  16. A novel point mutation (G[sup [minus]1] to T) in a 5[prime] splice donor site of intron 13 of the dystrophin gene results in exon skipping and is responsible for Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, Yoko; Nishio, Hisahide; Kitoh, Yoshihiko; Takeshima, Yasuhiro; Narita, Naoko; Wada, Hiroko; Yokoyama, Mitsuhiro; Nakamura, Hajime; Matsuo, Masafumi (Kobe Univ. School of Medicine (Japan))

    1994-01-01

    The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. The authors now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with Becker muscular dystrophy. This defect results from a G-to-T transversion at the terminal nucleotide of exon 13, within the 5[prime] splice site of intron 13, and causes complete skipping of exon 13 during processing of dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a truncated dystrophin lacking 40 amino acids from the amino-proximal end of the rod domain. This is the first report of an intraexon point mutation that completely inactivates a 5[prime] splice donor site in dystrophin pre-mRNA. Analysis of the genomic context of the G[sup [minus]1]-to-T mutation at the 5[prime] splice site supports the exon-definition model of pre-mRNA splicing and contributes to the understanding of splice-site selection. 48 refs., 5 figs.

  17. Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice.

    Science.gov (United States)

    Koo, Taeyoung; Malerba, Alberto; Athanasopoulos, Takis; Trollet, Capucine; Boldrin, Luisa; Ferry, Arnaud; Popplewell, Linda; Foster, Helen; Foster, Keith; Dickson, George

    2011-11-01

    Duchenne muscular dystrophy is a severe X-linked inherited muscle wasting disorder caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vectors have been extensively used to deliver genes efficiently for dystrophin expression in skeletal muscles. To overcome limited packaging capacity of AAV vectors (pathology of dystrophic mdx mice. However, the CT domain of dystrophin is thought to recruit part of the dystrophin-associated protein complex, which acts as a mediator of signaling between extracellular matrix and cytoskeleton in muscle fibers. In this study, we extended the ΔR4-23/ΔCT microdystrophin by incorporating helix 1 of the coiled-coil motif in the CT domain of dystrophin (MD2), which contains the α1-syntrophin and α-dystrobrevin binding sites. Intramuscular injection of AAV2/9 expressing CT domain-extended microdystrophin showed efficient dystrophin expression in tibialis anterior muscles of mdx mice. The presence of the CT domain of dystrophin in MD2 increased the recruitment of α1-syntrophin and α-dystrobrevin at the sarcolemma and significantly improved the muscle resistance to lengthening contraction-induced muscle damage in the mdx mice compared with MD1. These results suggest that the incorporation of helix 1 of the coiled-coil motif in the CT domain of dystrophin to the microdystrophins will substantially improve their efficiency in restoring muscle function in patients with Duchenne muscular dystrophy.

  18. Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, A.H. [Harvard Medical School, Boston, MA (United States); Yoshida, Mikiharu; Hagiwara, Yasuko; Ozawa, Eijiro [National Institute of Neuroscience, Ogawa Higashi, Kodaira (Japan); Anderson, M.S.; Feener, C.A.; Selig, S. [Howard Hughes Medical Institute at Children`s Hospital, Boston, MA (United States); Kunkel, L.M. [Harvard Medical School, Boston, MA (United States)]|[Howard Hughes Medical Institute at Children`s Hosptial, Boston, MA (United States)

    1994-05-10

    Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic ({alpha}-A1) and a distinct basic ({beta}-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of the human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human homologue of the published mouse syntrophin 2. The authors have mapped the human basic component of A1 and EST25263 genes to chromosomes 8q23-24 and 16, respectively.

  19. Dual Myostatin and Dystrophin Exon Skipping by Morpholino Nucleic Acid Oligomers Conjugated to a Cell-penetrating Peptide Is a Promising Therapeutic Strategy for the Treatment of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Alberto Malerba

    2012-01-01

    Full Text Available The knockdown of myostatin, a negative regulator of skeletal muscle mass may have important implications in disease conditions accompanied by muscle mass loss like cancer, HIV/AIDS, sarcopenia, muscle atrophy, and Duchenne muscular dystrophy (DMD. In DMD patients, where major muscle loss has occurred due to a lack of dystrophin, the therapeutic restoration of dystrophin expression alone in older patients may not be sufficient to restore the functionality of the muscles. We recently demonstrated that phosphorodiamidate morpholino oligomers (PMOs can be used to re-direct myostatin splicing and promote the expression of an out-of-frame transcript so reducing the amount of the synthesized myostatin protein. Furthermore, the systemic administration of the same PMO conjugated to an octaguanidine moiety (Vivo-PMO led to a significant increase in the mass of soleus muscle of treated mice. Here, we have further optimized the use of Vivo-PMO in normal mice and also tested the efficacy of the same PMO conjugated to an arginine-rich cell-penetrating peptide (B-PMO. Similar experiments conducted in mdx dystrophic mice showed that B-PMO targeting myostatin is able to significantly increase the tibialis anterior (TA muscle weight and when coadministered with a B-PMO targeting the dystrophin exon 23, it does not have a detrimental interaction. This study confirms that myostatin knockdown by exon skipping is a potential therapeutic strategy to counteract muscle wasting conditions and dual myostatin and dystrophin skipping has potential as a therapy for DMD.

  20. Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

    Directory of Open Access Journals (Sweden)

    Elena Bassi

    2012-01-01

    Full Text Available In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week of 2′-O-methyl-phosphorothioate antisense oligoribonucleotides (AONs adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage. In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules.

  1. Consumerism and the Sister Carrie's American Dream%Consumerism and the Sister Carrie''s American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  2. Energetics of load carrying in Nepalese porters.

    Science.gov (United States)

    Bastien, Guillaume J; Schepens, Bénédicte; Willems, Patrick A; Heglund, Norman C

    2005-06-17

    Nepalese porters routinely carry head-supported loads equal to 100 to 200% of their body weight (Mb) for many days up and down steep mountain footpaths at high altitudes. Previous studies have shown that African women carry head-supported loads of up to 60% of their Mb far more economically than army recruits carrying equivalent loads in backpacks. Here we show that Nepalese porters carry heavier loads even more economically than African women. Female Nepalese porters, for example, carry on average loads that are 10% of their Mb heavier than the maximum loads carried by the African women, yet do so at a 25% smaller metabolic cost.

  3. Consumerism and the Sister Carrie's American Dream

    Institute of Scientific and Technical Information of China (English)

    卢亚丽

    2017-01-01

    From the aspect of consumerism to this text analyze Sister Carrie's"American dream"destruction. The author wholly and deeply analyzes the embodiment of consumerism in Dreiser's Sister Carrie and Dreiser's outlook and values under the effect of consumerism. To prove that the reason for destruction of Carrie's American dream is consumerism.

  4. Local Dynamic Stability Associated with Load Carrying

    Directory of Open Access Journals (Sweden)

    Jian Liu

    2013-03-01

    Conclusion: Current study confirmed the sensitivity of local dynamic stability measure in load carrying situation. It was concluded that load carrying tasks were associated with declined local dynamic stability, which may result in increased risk of fall accident. This finding has implications in preventing fall accidents associated with occupational load carrying.

  5. Immunohistochemical alterations of dystrophin in congenital muscular dystrophy Alterações imuno-hístoquímicas da distrofina na distrofia muscular congênita

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1995-09-01

    Full Text Available The dystrophin distribution in the plasma muscle membrane using immunohystochemistry was studied in 22 children with congenital muscular dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy through a polyclonal antibody. All the cases had patchy interruptions of the fluorescence in the plasma membrane. A large patchy interruption of the sarcolemma was found in 17 cases, small interruption in 12, and a combination of large and small patchy discontinuity in 7. Small gaps around the fiber like a rosary were found in 15 cases. The frequency of these abnormalities ranged cases from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five cases had total absence of immunofluorescence. These results suggest that the dystrophin expression is abnormal in this group of children and that this type of abnormalities can not be differentiated from early Becker muscular dystrophy nor childhood autosomal recessive muscular dystrophy through immunohystochemistry alone.Foi estudada a distribuição da distrofina na membrana plasmática das fibras musculares em 22 crianças com distrofia muscular congênita, através de técnicas de imuno-histoquímica. A distrofina foi identificada nas biópsias musculares processadas a fresco, por técnicas de imunofluorescência utilizando anticorpos policlonais. Todos os casos tinham interrupções da imunofluorescência na membrana plasmática. Em 17 elas eram grandes, em 12 eram pequenas e em 7 eram de ambos os tipos. Fibras com interrupções pequenas e constantes, como um rosário, foram vistas em 15 casos. Essas anormalidades estavam presentes em todas as fibras em 5 casos, eram frequentes em 8, ocasionais em 5 e raras em 4. Cinco casos mostraram fibras sem distrofina. Esses dados sugerem que a expressão da distrofina é anormal nesse grupo de crianças. Essas anormalidades podem também ser encontradas em casos precoces de distrofia muscular de Becker e distrofia autoss

  6. Life-threatening Arrhythmias in a Becker Muscular Dystrophy Family due to the Duplication of Exons 3-4 of the Dystrophin Gene.

    Science.gov (United States)

    Ishizaki, Masatoshi; Fujimoto, Akiko; Ueyama, Hidetsugu; Nishida, Yasuto; Imamura, Shigehiro; Uchino, Makoto; Ando, Yukio

    2015-01-01

    We herein present a report of three patients with Becker muscular dystrophy in the same family who developed complete atrioventricular block or ventricular tachycardia with severe cardiomyopathy. Our cases became unable to walk in their teens, and were introduced to mechanical ventilation due to respiratory muscle weakness in their twenties and thirties. In all three cases, a medical device such as a permanent cardiac pacemaker or an implantable cardiac defibrillator was considered to be necessary. The duplication of exons 3-4 in the dystrophin gene was detected in two of the patients. In patients with Becker muscular dystrophy, complete atrioventricular block or ventricular tachycardia within a family has rarely been reported. Thus attention should be paid to the possibility of severe arrhythmias in the severe phenotype of Becker muscular dystrophy.

  7. Linkage disequilibria among (CA){sub n} polymorphisms in the human dystrophin gene and their implications in carrier detection and prenatal diagnosis in Duchenne and Becker musclar dystrophies

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, R.; Zhong, Y.; Andrade, M. de [Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States)] [and others

    1994-06-01

    Four short tandem repeat loci, characterized by length polymorphisms of (CA){sub n} repeats, have been detected within introns 44, 45, 49, and 50 of the human dystrophin gene. The predicted heterozygosites for these loci range from 72 to 93%, and observed allele numbers range from 6 to 19 in 57 normal chromosomes, revealing their high degree of polymorphism. Evidence for significant disequilibria between the loci within introns 49 and 50 is found. These data appear to be consistent with observations of recombination frequencies between these markers and the length of the intron 44 in relation to the entire region. In addition, these four loci are collectively found to be 100% informative in carrier detection/prenatal diagnosis of Becker and Duchenne muscular dystrophies (B/DMD), whereas scoring the (CA){sub n} markers within introns 45 and 49 alone gives a 99.6% success rate. 13 refs., 4 tabs.

  8. Compensation for dystrophin-deficiency: ADAM12 overexpression in skeletal muscle results in increased alpha 7 integrin, utrophin and associated glycoproteins

    DEFF Research Database (Denmark)

    Moghadaszadeh, Behzad; Albrechtsen, Reidar; Guo, Ling T

    2003-01-01

    Mouse models for genetic diseases are among the most powerful tools available for developing and testing new treatment strategies. ADAM12 is a disintegrin and metalloprotease, previously demonstrated to significantly alleviate the pathology of mdx mice, a model for Duchenne muscular dystrophy...... in humans. More specifically ADAM12 appeared to prevent muscle cell necrosis in the mdx mice as evidenced by morphological analysis and by the reduced levels of serum creatine kinase. In the present study we demonstrated that ADAM12 may compensate for the dystrophin deficiency in mdx mice by increasing...... the expression and redistribution of several components of the muscle cell-adhesion complexes. First, we analyzed transgenic mice that overexpress ADAM12 and found mild myopathic changes and accelerated regeneration following acute injury. We then analyzed changes in gene-expression profiles in mdx/ADAM12...

  9. Measuring Social carrying Capacity: An Exploratory Study

    OpenAIRE

    López-Bonilla, Jesús Manuel; López-Bonilla, Luis Miguel

    2007-01-01

    The tourist carrying capacity commands a growing interest given that it is closely linked with sustainable tourist development. The justification of the utility of this concept is given by means of a simple and efficient methodological proposal, by analysing the social carrying capacity. To this end, an empirical application is carried out in the Western Andalusia. In some of the cases analysed, the satisfaction of the tourist is found to decline when the levels of the tourist use are higher ...

  10. Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane.

    Directory of Open Access Journals (Sweden)

    Michelle Wehling-Henricks

    Full Text Available Survival of dystrophin/utrophin double-knockout (dko mice was increased by muscle-specific expression of a neuronal nitric oxide synthase (nNOS transgene. Dko mice expressing the transgene (nNOS TG+/dko experienced delayed onset of mortality and increased life-span. The nNOS TG+/dko mice demonstrated a significant decrease in the concentration of CD163+, M2c macrophages that can express arginase and promote fibrosis. The decrease in M2c macrophages was associated with a significant reduction in fibrosis of heart, diaphragm and hindlimb muscles of nNOS TG+/dko mice. The nNOS transgene had no effect on the concentration of cytolytic, CD68+, M1 macrophages. Accordingly, we did not observe any change in the extent of muscle fiber lysis in the nNOS TG+/dko mice. These findings show that nNOS/NO (nitric oxide-mediated decreases in M2c macrophages lead to a reduction in the muscle fibrosis that is associated with increased mortality in mice lacking dystrophin and utrophin. Interestingly, the dramatic and beneficial effects of the nNOS transgene were not attributable to localization of nNOS protein at the cell membrane. We did not detect any nNOS protein at the sarcolemma in nNOS TG+/dko muscles. This important observation shows that sarcolemmal localization is not necessary for nNOS to have beneficial effects in dystrophic tissue and the presence of nNOS in the cytosol of dystrophic muscle fibers can ameliorate the pathology and most importantly, significantly increase life-span.

  11. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

  12. Deletion of Galgt2 (B4Galnt2) reduces muscle growth in response to acute injury and increases muscle inflammation and pathology in dystrophin-deficient mice.

    Science.gov (United States)

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A; Janssen, Paulus M L; Martin, Paul T

    2015-10-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2(-/-)mdx). Galgt2(-/-) mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. The Concept of Carrying Capacity in Tourism

    Directory of Open Access Journals (Sweden)

    Josef Zelenka

    2014-05-01

    Full Text Available Carrying capacity is often pragmatically, theoretically as well as purely intuitively considered as a concept in the context of tourism sustainability. The carrying capacity application has the greatest potential in protected areas, in frequently visited cultural and natural attractions, and in relation to sustaining of the lifestyle of the local community and tourism destination potential in general. Despite its importance, partial applications, determination of basic theoretical principles, and specifying connection to the other theoretical concepts in tourism (particularly destination life cycle, LAC concept, visitors management, there still is a rightful opinion of some authors suggesting that there is no consistent theory of tourism carrying capacity. This theory would be the base for sophisticated practical carrying capacity applications. This paper is therefore focused on introduction of the theoretical concept of carrying capacity, which can be discussed and possibly further elaborated.

  14. Parallelization of Reversible Ripple-carry Adders

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock

    2009-01-01

    The design of fast arithmetic logic circuits is an important research topic for reversible and quantum computing. A special challenge in this setting is the computation of standard arithmetical functions without the generation of \\emph{garbage}. Here, we present a novel parallelization scheme...... wherein $m$ parallel $k$-bit reversible ripple-carry adders are combined to form a reversible $mk$-bit \\emph{ripple-block carry adder} with logic depth $\\mathcal{O}(m+k)$ for a \\emph{minimal} logic depth $\\mathcal{O}(\\sqrt{mk})$, thus improving on the $mk$-bit ripple-carry adder logic depth $\\mathcal...

  15. Gun Carrying by High School Students in Boston, MA: Does Overestimation of Peer Gun Carrying Matter?

    Science.gov (United States)

    Hemenway, David; Vriniotis, Mary; Johnson, Renee M.; Miller, Matthew; Azrael, Deborah

    2011-01-01

    This paper investigates: (1) whether high school students overestimate gun carrying by their peers, and (2) whether those students who overestimate peer gun carrying are more likely to carry firearms. Data come from a randomly sampled survey conducted in 2008 of over 1700 high school students in Boston, MA. Over 5% of students reported carrying a…

  16. Missense mutation Lys18Asn in dystrophin that triggers X-linked dilated cardiomyopathy decreases protein stability, increases protein unfolding, and perturbs protein structure, but does not affect protein function.

    Directory of Open Access Journals (Sweden)

    Surinder M Singh

    Full Text Available Genetic mutations in a vital muscle protein dystrophin trigger X-linked dilated cardiomyopathy (XLDCM. However, disease mechanisms at the fundamental protein level are not understood. Such molecular knowledge is essential for developing therapies for XLDCM. Our main objective is to understand the effect of disease-causing mutations on the structure and function of dystrophin. This study is on a missense mutation K18N. The K18N mutation occurs in the N-terminal actin binding domain (N-ABD. We created and expressed the wild-type (WT N-ABD and its K18N mutant, and purified to homogeneity. Reversible folding experiments demonstrated that both mutant and WT did not aggregate upon refolding. Mutation did not affect the protein's overall secondary structure, as indicated by no changes in circular dichroism of the protein. However, the mutant is thermodynamically less stable than the WT (denaturant melts, and unfolds faster than the WT (stopped-flow kinetics. Despite having global secondary structure similar to that of the WT, mutant showed significant local structural changes at many amino acids when compared with the WT (heteronuclear NMR experiments. These structural changes indicate that the effect of mutation is propagated over long distances in the protein structure. Contrary to these structural and stability changes, the mutant had no significant effect on the actin-binding function as evident from co-sedimentation and depolymerization assays. These results summarize that the K18N mutation decreases thermodynamic stability, accelerates unfolding, perturbs protein structure, but does not affect the function. Therefore, K18N is a stability defect rather than a functional defect. Decrease in stability and increase in unfolding decrease the net population of dystrophin molecules available for function, which might trigger XLDCM. Consistently, XLDCM patients have decreased levels of dystrophin in cardiac muscle.

  17. Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

    International Nuclear Information System (INIS)

    Fuentes-Mera, Lizeth; Rodriguez-Munoz, Rafael; Gonzalez-Ramirez, Ricardo; Garcia-Sierra, Francisco; Gonzalez, Everardo; Mornet, Dominique; Cisneros, Bulmaro

    2006-01-01

    Dystrophin is an essential component in the assembly and maintenance of the dystrophin-associated protein complex (DAPC), which includes members of the dystroglycan, syntrophin, sarcoglycan and dystrobrevin protein families. Distinctive complexes have been described in the cell membrane of different tissues and cultured cells. In this work, we report the identification and characterization of a novel DAPC present in the nuclei of HeLa cells, which contains dystrophin Dp71 as a key component. Using confocal microscopy and cell fractionation analyses, we found the presence of Dp71, β-sarcoglycan, β-dystroglycan, α- and β-syntrophin, α1- and β-dystrobrevin and nNOS in the nuclei of HeLa cells. Furthermore, we demonstrated by co-immunoprecipitation experiments that most of these proteins form a complex in the nuclear compartment. Next, we analyze the possible association of the nuclear DAPC with the nuclear matrix. We found the presence of Dp71, β-dystroglycan, nNOS, β-sarcoglycan, α/β syntrophin, α1-dystrobrevin and β-dystrobrevin in the nuclear matrix protein fractions and in situ nuclear matrix preparations from HeLa cells. Moreover, we found that Dp71, β-dystroglycan and β-dystrobrevin co-immunoprecipitated with the nuclear matrix proteins lamin B1 and actin. The association of members of the nuclear DAPC with the nuclear matrix indicates that they may work as scaffolding proteins involved in nuclear architecture

  18. Abstraction carrying code and resource-awareness

    OpenAIRE

    Hermenegildo, Manuel V.; Albert Albiol, Elvira; López García, Pedro; Puebla Sánchez, Alvaro Germán

    2005-01-01

    Proof-Carrying Code (PCC) is a general approach to mobile code safety in which the code supplier augments the program with a certifícate (or proof). The intended benefit is that the program consumer can locally validate the certifícate w.r.t. the "untrusted" program by means of a certifícate checker—a process which should be much simpler, eíñcient, and automatic than generating the original proof. Abstraction Carrying Code (ACC) is an enabling technology for PCC in which an abstract mod...

  19. Transgenic cassava lines carrying heterologous alternative oxidase ...

    African Journals Online (AJOL)

    Afuape

    2013-07-03

    Jul 3, 2013 ... production of flowers, apomixis (Nassar et al., 2000; ... In order to increase the stress tolerance capacity of ... stress-related procedure due to the activities of auxin ... the evaluation of the transgenic lines for rate of OES .... Some transgenic lines carrying the 35S-AOX fragment amplified using 35S303F1 and.

  20. Infections That Pets Carry (For Parents)

    Science.gov (United States)

    ... how to protect your family from infections. How Pets Spread Infections Like people, all animals carry germs . Illnesses common among housepets — ... get an infection that can be passed to people. Safely Caring for Your Pet Here are some tips to help your family ...

  1. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in ... pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively.

  2. Magnetoacoustic waves in current-carrying plasmas

    International Nuclear Information System (INIS)

    Brennan, M.H.

    1980-04-01

    The results of theoretical and experimental investigations of the characteristics of magnetoacoustic waves in non-uniform, current-carrying plasmas are reviewed. Dissipative MHD and collisionless theories are considered. Also discussed is the use of magnetoacoustic waves in plasma diagnostics and plasma heating

  3. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-16

    Nov 16, 2009 ... The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene. (PEP-cDNA) in prokaryotic and mammalian expression vectors in chimeric cDNA types, encompassing. GST and FLAG with PEP-cDNA. PEP-cDNA was sub-cloned in pGEX6p2 prokaryotic expression ...

  4. Transgenic cassava lines carrying heterologous alternative oxidase ...

    African Journals Online (AJOL)

    Afuape

    2013-07-03

    Jul 3, 2013 ... Organized embryogenic callus development: In our experiment, somatic embryos were developed from leaf lobes collected from transgenic cassava lines carrying the AtAOX1a gene. Immature leaf lobes measuring about 1 to 6 mm obtained from about six weeks old in vitro derived plants were used.

  5. Black bear parathyroid hormone has greater anabolic effects on trabecular bone in dystrophin-deficient mice than in wild type mice.

    Science.gov (United States)

    Gray, Sarah K; McGee-Lawrence, Meghan E; Sanders, Jennifer L; Condon, Keith W; Tsai, Chung-Jui; Donahue, Seth W

    2012-09-01

    Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease that has deleterious consequences in muscle and bone, leading to decreased mobility, progressive osteoporosis, and premature death. Patients with DMD experience a higher-than-average fracture rate, particularly in the proximal and distal femur and proximal tibia. The dystrophin-deficient mdx mouse is a model of DMD that demonstrates muscle degeneration and fibrosis and osteoporosis. Parathyroid hormone, an effective anabolic agent for post-menopausal and glucocorticoid-induced osteoporosis, has not been explored for DMD. Black bear parathyroid hormone (bbPTH) has been implicated in the maintenance of bone properties during extended periods of disuse (hibernation). We cloned bbPTH and found 9 amino acid residue differences from human PTH. Apoptosis was mitigated and cAMP was activated by bbPTH in osteoblast cultures. We administered 28nmol/kg of bbPTH 1-84 to 4-week old male mdx and wild type mice via daily (5×/week) subcutaneous injection for 6 weeks. Vehicle-treated mdx mice had 44% lower trabecular bone volume fraction than wild type mice. No changes were found in femoral cortical bone geometry or mechanical properties with bbPTH treatment in wild type mice, and only medio-lateral moment of inertia changed with bbPTH treatment in mdx femurs. However, μCT analyses of the trabecular regions of the distal femur and proximal tibia showed marked increases in bone volume fraction with bbPTH treatment, with a greater anabolic response (7-fold increase) in mdx mice than wild type mice (2-fold increase). Trabecular number increased in mdx long bone, but not wild type bone. Additionally, greater osteoblast area and decreased osteoclast area were observed with bbPTH treatment in mdx mice. The heightened response to PTH in mdx bone compared to wild type suggests a link between dystrophin deficiency, altered calcium signaling, and bone. These findings support further investigation of PTH as an anabolic

  6. Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents.

    Science.gov (United States)

    Robertson, Alan S; Majchrzak, Mark J; Smith, Courtney M; Gagnon, Robert C; Devidze, Nino; Banks, Glen B; Little, Sean C; Nabbie, Fizal; Bounous, Denise I; DiPiero, Janet; Jacobsen, Leslie K; Bristow, Linda J; Ahlijanian, Michael K; Stimpson, Stephen A

    2017-07-01

    Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmd mdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Research on Water Resources Design Carrying Capacity

    Directory of Open Access Journals (Sweden)

    Guanghua Qin

    2016-04-01

    Full Text Available Water resources carrying capacity (WRCC is a recently proposed management concept, which aims to support sustainable socio-economic development in a region or basin. However, the calculation of future WRCC is not well considered in most studies, because water resources and the socio-economic development mode for one area or city in the future are quite uncertain. This paper focused on the limits of traditional methods of WRCC and proposed a new concept, water resources design carrying capacity (WRDCC, which incorporated the concept of design. In WRDCC, the population size that the local water resources can support is calculated based on the balance of water supply and water consumption, under the design water supply and design socio-economic development mode. The WRDCC of Chengdu city in China is calculated. Results show that the WRDCC (population size of Chengdu city in development modeI (II, III will be 997 ×104 (770 × 104, 504 × 104 in 2020, and 934 × 104 (759 × 104, 462 × 104 in 2030. Comparing the actual population to the carrying population (WRDCC in 2020 and 2030, a bigger gap will appear, which means there will be more and more pressure on the society-economic sustainable development.

  8. Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.

    Science.gov (United States)

    Tsuda, Takeshi; Fitzgerald, Kristi; Scavena, Mena; Gidding, Samuel; Cox, Mary O; Marks, Harold; Flanigan, Kevin M; Moore, Steven A

    2015-03-01

    We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.

  9. Placarding of road vehicles carrying radioactive materials

    International Nuclear Information System (INIS)

    1977-09-01

    The purpose of this Code is to give guidance on the placarding requirements for vehicles carrying radioactive materials by road in Great Britain and on the continent of Europe. Additional placards may be required regarding dangerous properties other than radioactivity. The labelling of packages for transport is dealt with in AECP 1030. This Code deals with two aspects of road vehicle placarding:-(a) placarding on the outside of road vehicles in Great Britain and on the continent of Europe, (b) a fireproof placard fixed in the driver's cab. Responsibility for placarding the vehicle rests with the carrier, but in practice the consignor may need to provide the placards. (U.K.)

  10. Cryptococcus neoformans carried by Odontomachus bauri ants

    Directory of Open Access Journals (Sweden)

    Mariana Santos de Jesus

    2012-06-01

    Full Text Available Cryptococcus neoformans is the most common causative agent of cryptococcosis worldwide. Although this fungus has been isolated from a variety of organic substrates, several studies suggest that hollow trees constitute an important natural niche for C. neoformans. A previously surveyed hollow of a living pink shower tree (Cassia grandis positive for C. neoformans in the city of Rio de Janeiro, Brazil, was chosen for further investigation. Odontomachus bauri ants (trap-jaw ants found inside the hollow were collected for evaluation as possible carriers of Cryptococcus spp. Two out of 10 ants were found to carry phenoloxidase-positive colonies identified as C. neoformans molecular types VNI and VNII. The ants may have acted as a mechanical vector of C. neoformans and possibly contributed to the dispersal of the fungi from one substrate to another. To the best of our knowledge, this is the first report on the association of C. neoformans with ants of the genus Odontomachus.

  11. A comparative study of N-glycolylneuraminic acid (Neu5Gc and cytotoxic T cell (CT carbohydrate expression in normal and dystrophin-deficient dog and human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Paul T Martin

    Full Text Available The expression of N-glycolylneuraminic acid (Neu5Gc and the cytotoxic T cell (CT carbohydrate can impact the severity of muscular dystrophy arising from the loss of dystrophin in mdx mice. Here, we describe the expression of these two glycans in skeletal muscles of dogs and humans with or without dystrophin-deficiency. Neu5Gc expression was highly reduced (>95% in muscle from normal golden retriever crosses (GR, n = 3 and from golden retriever with muscular dystrophy (GRMD, n = 5 dogs at multiple ages (3, 6 and 13 months when compared to mouse muscle, however, overall sialic acid expression in GR and GRMD muscles remained high at all ages. Neu5Gc was expressed on only a minority of GRMD satellite cells, CD8⁺ T lymphocytes and macrophages. Human muscle from normal (no evident disease, n = 3, Becker (BMD, n = 3 and Duchenne (DMD, n = 3 muscular dystrophy individuals had absent to very low Neu5Gc staining, but some punctate intracellular muscle staining was present in BMD and DMD muscles. The CT carbohydrate was localized to the neuromuscular junction in GR muscle, while GRMD muscles had increased expression on a subset of myofibers and macrophages. In humans, the CT carbohydrate was ectopically expressed on the sarcolemmal membrane of some BMD muscles, but not normal human or DMD muscles. These data are consistent with the notion that altered Neu5Gc and CT carbohydrate expression may modify disease severity resulting from dystrophin deficiency in dogs and humans.

  12. Voltage-carrying states in superconducting microstrips

    International Nuclear Information System (INIS)

    Stuivinga, M.E.C.

    1983-01-01

    When the critical current is exceeded in a superconducting microstrip, voltage-carrying states with a resistance significantly below the normal state resistance can occur. Phase-slip centers (PSC) appear at about the critical temperature. These are successive local voltage units which manifest themselves as strip-like increments in voltage in the I-V characteristic. For temperatures off the critical temperature the PSC regime degenerates into a region of normal material, a so-called hot spot. These two phenomena, PSC and hot spots, form the subject of this thesis. To gain a better understanding of the phase-slip center process, an experiment was designed to measure local values of the quasi-particle and pair potential. The results of local potential and gap measurements at a PSC in aluminium are presented and discussed. Special attention is paid to pair-breaking interactions which can shorten the relaxation time. A non-linear differential equation is derived which describes the development of a PSC into a normal hot spot under the influence of Joule heating. It incorporates the temperature rise due to the dissipative processes occurring in the charge imbalance tails. Numerical solutions are presented for a set of parameters, including those for aluminium and tin. Subsequently, they are compared with experiments. (Auth.)

  13. Detecting Vessels Carrying Migrants Using Machine Learning

    Science.gov (United States)

    Sfyridis, A.; Cheng, T.; Vespe, M.

    2017-10-01

    Political instability, conflicts and inequalities result into significant flows of people worldwide, moving to different countries in search of a better life, safety or to be reunited with their families. Irregular crossings into Europe via sea routes, despite not being new, have recently increased together with the loss of lives of people in the attempt to reach EU shores. This highlights the need to find ways to improve the understanding of what is happening at sea. This paper, intends to expand the knowledge available on practices among smugglers and contribute to early warning and maritime situational awareness. By identifying smuggling techniques and based on anomaly detection methods, behaviours of interest are modelled and one class support vector machines are used to classify unlabelled data and detect potential smuggling vessels. Nine vessels are identified as potentially carrying irregular migrants and refugees. Though, further inspection of the results highlights possible misclassifications caused by data gaps and limited knowledge on smuggling tactics. Accepted classifications are considered subject to further investigation by the authorities.

  14. Retinal oscillations carry visual information to cortex

    Directory of Open Access Journals (Sweden)

    Kilian Koepsell

    2009-04-01

    Full Text Available Thalamic relay cells fire action potentials that transmit information from retina to cortex. The amount of information that spike trains encode is usually estimated from the precision of spike timing with respect to the stimulus. Sensory input, however, is only one factor that influences neural activity. For example, intrinsic dynamics, such as oscillations of networks of neurons, also modulate firing pattern. Here, we asked if retinal oscillations might help to convey information to neurons downstream. Specifically, we made whole-cell recordings from relay cells to reveal retinal inputs (EPSPs and thalamic outputs (spikes and then analyzed these events with information theory. Our results show that thalamic spike trains operate as two multiplexed channels. One channel, which occupies a low frequency band (<30 Hz, is encoded by average firing rate with respect to the stimulus and carries information about local changes in the visual field over time. The other operates in the gamma frequency band (40-80 Hz and is encoded by spike timing relative to retinal oscillations. At times, the second channel conveyed even more information than the first. Because retinal oscillations involve extensive networks of ganglion cells, it is likely that the second channel transmits information about global features of the visual scene.

  15. DETECTING VESSELS CARRYING MIGRANTS USING MACHINE LEARNING

    Directory of Open Access Journals (Sweden)

    A. Sfyridis

    2017-10-01

    Full Text Available Political instability, conflicts and inequalities result into significant flows of people worldwide, moving to different countries in search of a better life, safety or to be reunited with their families. Irregular crossings into Europe via sea routes, despite not being new, have recently increased together with the loss of lives of people in the attempt to reach EU shores. This highlights the need to find ways to improve the understanding of what is happening at sea. This paper, intends to expand the knowledge available on practices among smugglers and contribute to early warning and maritime situational awareness. By identifying smuggling techniques and based on anomaly detection methods, behaviours of interest are modelled and one class support vector machines are used to classify unlabelled data and detect potential smuggling vessels. Nine vessels are identified as potentially carrying irregular migrants and refugees. Though, further inspection of the results highlights possible misclassifications caused by data gaps and limited knowledge on smuggling tactics. Accepted classifications are considered subject to further investigation by the authorities.

  16. Functional muscle ischemia in Duchenne and Becker muscular dystrophy

    OpenAIRE

    Thomas, Gail D.

    2013-01-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) comprise a spectrum of devastating X-linked muscle wasting disease for which there is no treatment. DMD/BMD is caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that stabilizes the muscle membrane and also targets other proteins to the sarcolemma. Among these is the muscle-specific isoform of neuronal nitric oxide synthase (nNOSµ) which binds spectrin-like repeats within dystrophin’s rod domain and the adaptor pro...

  17. Can `loss and damage' carry the load?

    Science.gov (United States)

    Verchick, Robert R. M.

    2018-05-01

    Even assuming a heroic rush towards carbon reduction and adaptation, some regions of the world will be hammered hard by climate impacts. Thus, a global consensus now sees the need for a supplemental plan to deal with the kind of harms that cannot be avoided-what Parties call `loss and damage'. For a loss-and-damage plan to work, it must be capable of carrying the load, the load being whatever minimal standards that morality and political consensus require. But if residual risk climbs too high, it will fall short of even the most basic expectations. The Paris Agreement calls for holding the rise in global average temperature to `well below 2°C above pre-industrial levels', while working to limit the increase to 1.5°C. How much difference is in that half-degree? From the point of view of residual risk, quite a lot. According to a 2016 study published by the European Geosciences Union, a jump from 1.5°C to 2°C could produce outsize impacts, particularly in tropical latitudes. That difference could mark the line between a plan that is politically and morally defensible and one that is not. At the very least, the difference is enough to inform the design and expectations of any future plan. This article is part of the theme issue `The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

  18. BLOOD SUBSTITUTES: EVOLUTION FROM NON-CARRYING TO OXYGEN AND GAS CARRYING FLUIDS

    Science.gov (United States)

    Cabrales, Pedro; Intaglietta, Marcos

    2013-01-01

    The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity. PMID:23820271

  19. Treatment with the anti-IL-6 receptor antibody attenuates muscular dystrophy via promoting skeletal muscle regeneration in dystrophin-/utrophin-deficient mice.

    Science.gov (United States)

    Wada, Eiji; Tanihata, Jun; Iwamura, Akira; Takeda, Shin'ichi; Hayashi, Yukiko K; Matsuda, Ryoichi

    2017-10-27

    Chronic increases in the levels of the inflammatory cytokine interleukin-6 (IL-6) in serum and skeletal muscle are thought to contribute to the progression of muscular dystrophy. Dystrophin/utrophin double-knockout (dKO) mice develop a more severe and progressive muscular dystrophy than the mdx mice, the most common murine model of Duchenne muscular dystrophy (DMD). In particular, dKO mice have smaller body sizes and muscle diameters, and develop progressive kyphosis and fibrosis in skeletal and cardiac muscles. As mdx mice and DMD patients, we found that IL-6 levels in the skeletal muscle were significantly increased in dKO mice. Thus, in this study, we aimed to analyze the effects of IL-6 receptor (IL-6R) blockade on the muscle pathology of dKO mice. Male dKO mice were administered an initial injection (200 mg/kg intraperitoneally (i.p.)) of either the anti-IL-6R antibody MR16-1 or an isotype-matched control rat IgG at the age of 14 days, and were then given weekly injections (25 mg/kg i.p.) until 90 days of age. Treatment of dKO mice with the MR16-1 antibody successfully inhibited the IL-6 pathway in the skeletal muscle and resulted in a significant reduction in the expression levels of phosphorylated signal transducer and activator of transcription 3 in the skeletal muscle. Pathologically, a significant increase in the area of embryonic myosin heavy chain-positive myofibers and muscle diameter, and reduced fibrosis in the quadriceps muscle were observed. These results demonstrated the therapeutic effects of IL-6R blockade on promoting muscle regeneration. Consistently, serum creatine kinase levels were decreased. Despite these improvements observed in the limb muscles, degeneration of the diaphragm and cardiac muscles was not ameliorated by the treatment of mice with the MR16-1 antibody. As no adverse effects of treatment with the MR16-1 antibody were observed, our results indicate that the anti-IL-6R antibody is a potential therapy for muscular dystrophy

  20. 30 CFR 56.16014 - Operator-carrying overhead cranes.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operator-carrying overhead cranes. 56.16014 Section 56.16014 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Storage and Handling § 56.16014 Operator-carrying overhead cranes. Operator-carrying overhead cranes shall...

  1. 30 CFR 57.16014 - Operator-carrying overhead cranes.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operator-carrying overhead cranes. 57.16014 Section 57.16014 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Storage and Handling § 57.16014 Operator-carrying overhead cranes. Operator-carrying overhead cranes shall...

  2. 46 CFR 111.105-35 - Vessels carrying coal.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Vessels carrying coal. 111.105-35 Section 111.105-35...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-35 Vessels carrying coal. (a) The following are Class II, Division 1, (Zone 10 or Z) locations on a vessel that carries coal: (1) The interior of each coal...

  3. Training to Increase Safe Tray Carrying Among Cocktail Servers

    OpenAIRE

    Scherrer, Megan D; Wilder, David A

    2008-01-01

    We evaluated the effects of training on proper carrying techniques among 3 cocktail servers to increase safe tray carrying on the job and reduce participants' risk of developing musculoskeletal disorders. As participants delivered drinks to their tables, their finger, arm, and neck positions were observed and recorded. Each participant received individual safety training that focused on proper carrying positions and techniques after baseline data were collected. A multiple baseline design acr...

  4. Organization and carrying out the triathlon competitions in Ukraine

    Directory of Open Access Journals (Sweden)

    Volodymyr Vodlozerov

    2016-02-01

    Full Text Available Purpose: the aim is analyzing of system of organization and carrying out the triathlon competitions in Ukraine in accordance with rules of triathlon international federation. Material & Methods: comparative analysis of process of organization and carrying out the triathlon competitions in the world and Ukraine was carried out on basis of specialist literature studying, normative base of sports organizations (triathlon federation. Results: inconsistencies were identified in competitions carried out in cold season, particularity of triathlon that intends overcoming the combined distance without time durations between stages. Conclusions: recommendation in eliminate inconsistencies that affect to performance of triathlon competitions in Ukraine was suggested.

  5. The Population Growth and Carrying Capacity in Semarang City

    Science.gov (United States)

    Hariyanto; Hadi, Sudharto P.; Buchori, Imam

    2018-02-01

    Population growth and development of city activities take some lands to carry them. As a result, land use competition happens among persons, society or sector. Land necessity for settlement, industry, or sector has taken over farm land, therefore farm land has been converted intensively and massively. Chronologically, population growth will cause land necessity increase. Unproductive land, especially farm land will be converted. Furthermore, farm land conversion will cause carrying capacity change. Carrying capacity has certain bio capacity. With the population growth, it will increase resource consumption; on the other side, farm land conversion will decrease carrying capacity. The objective of the study is to know about the influence of population growth towards carrying capacity (bio capacity) in Semarang city. Land consumption per capita is indeed influenced by city population, the higher the population is, the lower the land consumption per capita. With the population growth, it will influence carrying capacity. Carrying capacity here is the ratio of area to population. Analytical descriptive method is applied in the study with all sub-districts in Semarang city as the analysis unit. Population here is sub-district area and population per sub-district in Semarang city. Population growth data period is from 2000 until 2015. Main variables of the study are area per sub-district, population, population growth, carrying capacity. Result of the study shows significant influence of carrying capacity decrease, especially some outskirts in Semarang city. This condition happens because the outskirts in Semarang city tend to have dense population growth. Range of carrying capacity in Semarang city is from 0,007 to 0,117 of 0 to 1. Almost all sub-districts in Semarang city show miserable condition, except Mijen and Tugu. The conclusion of the study is that population will decrease carrying capacity. Therefore, the government should control population growth by paying

  6. 46 CFR 111.105-45 - Vessels carrying agricultural products.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Vessels carrying agricultural products. 111.105-45... ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-45 Vessels carrying agricultural products. (a) The following areas are Class II, Division 1, (Zone 10 or Z) locations on vessels...

  7. 25 CFR 23.51 - Grant carry-over authority.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Grant carry-over authority. 23.51 Section 23.51 Indians... Uniform Grant Administration Provisions and Requirements § 23.51 Grant carry-over authority. Unless... two years beyond the initial grant funding period and must be utilized only for the intent, purpose...

  8. 14 CFR 121.589 - Carry-on baggage.

    Science.gov (United States)

    2010-01-01

    ... (c) and (d). (c) No certificate holder may allow an airplane to take off or land unless each article... holder may allow the boarding of carry-on baggage on an airplane unless each passenger's baggage has been... program in its operations specifications. In addition, no passenger may board an airplane if his/her carry...

  9. Evaluating total carrying capacity of tourism using impact indicators

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2016-03-01

    Full Text Available The carrying capacity is well identified tool to manage problems due to uncontrolled tourism for any destination. This report highlights the carrying capacity estimation of Kerwa tourism area, Bhopal, India. The methodology used in this report is a new two-tier mechanism of impact analysis using index numbers derived from a survey of 123 stakeholders. From this the individual component impact analysis and the total carrying capacity of the area is computed in order to state the insight of the total carrying capacity left for the tourism activities in Kerwa tourism area. It is calculated from, the results so obtained, that the Kerwa catchment area falls in “very low impact category” and hence in a healthy state of the artwork in terms of total carrying capacity. The study conveys the current need in the destination management and tourism development as a road map for the destination managers for implementing sustainable tourism.

  10. The flexible application of carrying capacity in ecology

    Directory of Open Access Journals (Sweden)

    Eric J. Chapman

    2018-01-01

    Full Text Available Carrying capacity encompasses a broad collection of approaches used to better understand biotic interactions in ecosystems and is often applied with no explicit regard to its historical origin. In this paper, we reviewed the primary literature to examine how carrying capacity is applied in ecology. We focused our review on ecosystem studies—studies that frame their results at the ecosystem level—published after the 1950s and highlight emerging trends of this concept. We found that while carrying capacity offers some underlying commonalities, a wide range of definitions and approaches hinders a unified framework to better understand biotic ecosystem interactions. Not surprisingly, these studies most often use K—the number of individuals that the environment “can support” in a given area—to define carrying capacity, despite considerable ambiguity and uncertainty in this approach. Furthermore, the studies that we reviewed spanned several levels of ecological organization: molecules to communities and up to landscapes. To add further complexity, it is not clear whether carrying capacity was intended as a dynamic concept subject to temporal variability as it was often applied in the reviewed studies. We found that carrying capacity is most often applied to studies in conservation biology, rangeland and wildlife management, aquaculture, and fisheries biology. We explore ecosystem level responses to implications of “carrying capacity” overshoot and discuss proposed mechanisms that govern ecosystem carrying capacity. We discuss the usefulness of the concept and end with suggestions to improve carrying capacity's general application in ecosystem studies. Keywords: Carrying capacity, Conservation biology, Ecosystems, Ecosystem management, Natural resources

  11. US Public Opinion on Carrying Firearms in Public Places.

    Science.gov (United States)

    Wolfson, Julia A; Teret, Stephen P; Azrael, Deborah; Miller, Matthew

    2017-06-01

    To estimate US public opinion, overall and by gun ownership status, about the public places where legal gun owners should be allowed to carry firearms. We fielded an online survey among 3949 adults, including an oversample of gun owners and veterans, in April 2015. We used cross-tabulations with survey weights to generate nationally representative estimates. Fewer than 1 in 3 US adults supported gun carrying in any of the specified venues. Support for carrying in public was consistently higher among gun owners than among non-gun owners. Overall, support for carrying in public was lowest for schools (19%; 95% confidence interval [CI] = 16.7, 21.1), bars (18%; 95% CI = 15.9, 20.6), and sports stadiums (17%; 95% CI = 15.0, 19.5). Most Americans, including most gun owners, support restricting public places legal gun owners can carry firearms. These views contrast sharply with the current trend in state legislatures of expanding where, how, and by whom guns can be carried in public. Recent state laws and proposed federal legislation that would force states to honor out-of-state concealed carry permits are out of step with American public opinion.

  12. Research on Psychological Carrying Capacity of Tourism Destination

    Institute of Scientific and Technical Information of China (English)

    Fan Zhiyong; Zhong Sheng

    2009-01-01

    As a part of the carrying capacity system of tourism destination,tourism psychological carrying capacity and its makeup are very important indexes which reflect the harmonious development of tourism destination develops harmoniously,but the academy has not paid enough attention to them.Based on the concept and connotation of psychological carrying capacity,this paper explains the influencing factors which affect the psychological capacity of the tourist and the resident after the acknowledged concept,and then designs a harmonious development model of tourism destination.Finally,it offers some countermeasures against the overloading psychological capacity.

  13. Foreign exchange predictability and the carry trade: a decomposition approach

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Gospodinov, N.; Jamali, I.; Liu, X.

    2017-01-01

    Roč. 42, June (2017), s. 199-211 ISSN 0927-5398 Institutional support: RVO:67985998 Keywords : exchange rate forecasting * carry trade * return decomposition Subject RIV: AH - Economics OBOR OECD: Finance Impact factor: 0.979, year: 2016

  14. Study on Tourist Carrying Capacity Based on Matter Element Analysis

    Institute of Scientific and Technical Information of China (English)

    LiuYunguo; FanTing; LiXin; ZhouMing; WangXianhai

    2005-01-01

    This paper proposes that it is necessary to implement the concept of tourist carrying capacity to facilitate the tourism planning, and presents a method to evaluate the carrying capacity. The method called matter element analysis can solve the uncertain and incompatible problem of the evaluated factors in assessing carrying capacity.The current state of a destination's carrying capacity can be determined by establishing the standard indexes and the matter element model. Through the evaluating of the travel industry zones of the Autonomous Prefecture of Western Hunan, the method is proved to be simple and feasible, and it is improved to be significant for the tourism planning and determination as well as the sustainable development of the regional tourism.

  15. Estimating the recreational carrying capacity of a lowland river section.

    Science.gov (United States)

    Lorenz, Stefan; Pusch, Martin T

    2012-01-01

    Recreational boating represents a major human use of inland waters in many regions. However, boating tourism may affect the ecological integrity of surface waters in multiple ways. In particular, surface waves produced by boating may disturb freshwater invertebrates, such as interrupting the filtration activity of benthic mussels. As mussels may significantly contribute to self-purification, disturbance may have crucial impacts on water quality, and thus on water tourism. In this paper we calculate the carrying capacity of a river section for sustainable boating tourism based on the preservation of water quality. This approach is complemented by spatial and social approaches for carrying capacity estimates. The ecological carrying capacity significantly decreases with lower water levels during summer. Hence, the analysis of variables that influence the river's carrying capacity allows the formation of recommendations for management measures that integrate social, touristic and ecological aspects.

  16. Assessment of feeding value of vegetable-carried pineapple fruit ...

    African Journals Online (AJOL)

    This study compared the sun-drying characteristics of five blends each (w/w; 1:1, 1:1.5, 1:2, 1:2.5, 1:3) of wheat offal-carried pineapple waste (WO:PW) and brewers' dried grains-carried pineapple waste (BDG:PW), assessed the blends for their nutrient contents and the feeding value of the optimum blends with Red Sokoto ...

  17. Carrying capacity: the tradition and policy implications of limits

    Directory of Open Access Journals (Sweden)

    Virginia Deane Abernethy

    2001-01-01

    Full Text Available ABSTRACT: Within just the last few centuries, science and technology have enlarged human capabilities and population size until humans now take, for their own use, nearly half of the Earth's net terrestrial primary production. An ethical perspective suggests that potentials to alter, or further increase, humanity's use of global resources should be scrutinized through the lenses of self-interested foresightedness and respect for non-human life. Without overtly invoking ethics, studies of the carrying capacity achieve just this objective. Carrying capacity is an ecological concept that expresses the relationship between a population and the natural environment on which it depends for ongoing sustenance. Carrying capacity assumes limits on the number of individuals that can be supported at a given level of consumption without degrading the environment and, therefore, reducing future carrying capacity. That is, carrying capacity addresses long-term sustainability. Worldviews differ in the importance accorded to the carrying capacity concept. This paper addresses three worldviews - ecological, romantic, and entrepreneurial - and explores the ethics and the policy implications of their contrasting perspectives.

  18. Method for rendering harmless sulfur dioxide-carrying gases and sulfur-carrying waste water from pyrolysis of oil shale

    Energy Technology Data Exchange (ETDEWEB)

    Aspegren, O E.A.; Eklund, A J

    1951-03-15

    A method is described for rendering harmless sulfur dioxide-carrying gases, which are formed in processes for the manufacture of solid, liquid, or gaseous products by pyrolysis of oil shale, and thereby to extract valuable products, characterized in that the sulfur dioxide-carrying gases are washed with a solution or sludge obtained by leaching wholly or partly burned-out residues from the pyrolysis.

  19. [Ecological carrying capacity and Chongming Island's ecological construction].

    Science.gov (United States)

    Wang, Kaiyun; Zou, Chunjing; Kong, Zhenghong; Wang, Tianhou; Chen, Xiaoyong

    2005-12-01

    This paper overviewed the goals of Chongming Island's ecological construction and its background, analyzed the current eco-economic status and constraints of the Island, and put forward some scientific issues on its ecological construction. It was suggested that for the resources-saving and sustainable development of the Island, the researches on its ecological construction should be based on its ecological carrying capacity, fully take the regional characteristics into consideration, and refer the successful development modes at home and abroad. The carrying capacity study should ground on systemic and dynamic views, give a thorough evaluation of the Island's present carrying capacity, simulate its possible changes, and forecast its demands and risks. Operable countermeasures to promote the Island's carrying capacity should be worked out, new industry structure, population scale, and optimized distribution projects conforming to regional carrying capacity should be formulated, and effective ecological security alarming and control system should be built, with the aim of providing suggestions and strategic evidences for the decision-making of economic development and sustainable environmental resources use of the region.

  20. Carrying capacity of water resources in Bandung Basin

    Science.gov (United States)

    Marganingrum, D.

    2018-02-01

    The concept of carrying capacity is widely used in various sectors as a management tool for sustainable development processes. This idea has also been applied in watershed or basin scale. Bandung Basin is the upstream of Citarum watershed known as one of the national strategic areas. This area has developed into a metropolitan area loaded with various environmental problems. Therefore, research that is related to environmental carrying capacity in this area becomes a strategic issue. However, research on environmental carrying capacity that has been done in this area is still partial either in water balance terminology, land suitability, ecological footprint, or balance of supply and demand of resources. This paper describes the application of the concept of integrated environmental carrying capacity in order to overcome the increasing complexity and dynamic environmental problems. The sector that becomes the focus of attention is the issue of water resources. The approach method to be carried out is to combine the concept of maximum balance and system dynamics. The dynamics of the proposed system is the ecological dynamics and population that cannot be separated from one another as a unity of the Bandung Basin ecosystem.

  1. Concepts for reducing nuclear utility inventory carrying costs

    International Nuclear Information System (INIS)

    Graybill, R.E.; DiCola, F.E.; Solanas, C.H.

    1985-01-01

    Nuclear utilities are under pressure to reduce their operating and maintenance expenses such that the total cost of generating electricity through nuclear power remains an economically attractive option. One area in which expenses may be reduced is total inventory carrying cost. The total inventory carrying cost consists of financing an inventory, managing the inventory, assuring quality, engineering of acceptable parts specifications, and procuring initial and replenishment stock. Concepts and methodology must be developed to reduce the remaining expenses of a utility's total inventory carrying cost. Currently, two concepts exist: pooled inventory management system (PIMS), originally established by General Electric Company and a group of boiling water reactor owners, and Nuclear Parts Associates' (NUPA) shared inventory management program (SIMP). Both concepts share or pool parts and components among utilities. The SIMP program objectives and technical activities are summarized

  2. Delay model and performance testing for FPGA carry chain TDC

    International Nuclear Information System (INIS)

    Kang Xiaowen; Liu Yaqiang; Cui Junjian Yang Zhangcan; Jin Yongjie

    2011-01-01

    Time-of-flight (TOF) information would improve the performance of PET (position emission tomography). TDC design is a key technique. It proposed Carry Chain TDC Delay model. Through changing the significant delay parameter of model, paper compared the difference of TDC performance, and finally realized Time-to-Digital Convertor (TDC) based on Carry Chain Method using FPGA EP2C20Q240C8N with 69 ps LSB, max error below 2 LSB. Such result could meet the TOF demand. It also proposed a Coaxial Cable Measuring method for TDC testing, without High-precision test equipment. (authors)

  3. Evaluation of carrying capacity and territorial environmental sustainability

    Directory of Open Access Journals (Sweden)

    Giuseppe Ruggiero

    2012-09-01

    Full Text Available Land use has a great impact on environmental quality, use of resources, state of ecosystems and socio-economic development. Land use can be considered sustainable if the environmental pressures of human activities do not exceed the ecological carrying capacity. A scientific knowledge of the capability of ecosystems to provide resources and absorb waste is a useful and innovative means of supporting territorial planning. This study examines the area of the Province of Bari to estimate the ecosystems’ carrying capacity, and compare it with the current environmental pressures exerted by human activities. The adapted methodology identified the environmentally sustainable level for one province.

  4. Carry trade as a speculative investment strategy in Serbia

    Directory of Open Access Journals (Sweden)

    Bungin Sanja

    2012-12-01

    Full Text Available This paper is analyses causes and the consequences of a speculative investment carry trade strategy in the exchange market in Serbia. The presence of such type of investor is related to high yields of risk free securities denominated in dinars, as well as the perception of future movements of dinar exchange rate related to currency that serves as source of investment. The consequences of carry trade may significantly influence exchange rate movements when monetary policy has limited facilities to combat negative and sudden shocks.

  5. General relativistic galvano-gravitomagnetic effect in current carrying conductors

    International Nuclear Information System (INIS)

    Ahmedov, B.J.

    1998-11-01

    The analogy between general relativity and electromagnetism suggests that there is a galvano-gravitomagnetic effect, which is the gravitational analogue of the Hall effect. This new effect takes place when a current carrying conductor is placed in a gravitomagnetic field and the conduction electrons moving inside the conductor are deflected transversally with respect to the current flow. In connection with this galvano-gravitomagnetic effect, we explore the possibility of using current carrying conductors for detecting the gravitomagnetic field of the Earth. (author)

  6. Foreign exchange predictability and the carry trade: a decomposition approach

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Gospodinov, N.; Jamali, I.; Liu, X.

    2017-01-01

    Roč. 42, June (2017), s. 199-211 ISSN 0927-5398 Institutional support: Progres-Q24 Keywords : exchange rate forecasting * carry trade * return decomposition Subject RIV: AH - Economics OBOR OECD: Finance Impact factor: 0.979, year: 2016

  7. Debris-carrying camouflage among diverse lineages of Cretaceous insects.

    Science.gov (United States)

    Wang, Bo; Xia, Fangyuan; Engel, Michael S; Perrichot, Vincent; Shi, Gongle; Zhang, Haichun; Chen, Jun; Jarzembowski, Edmund A; Wappler, Torsten; Rust, Jes

    2016-06-01

    Insects have evolved diverse methods of camouflage that have played an important role in their evolutionary success. Debris-carrying, a behavior of actively harvesting and carrying exogenous materials, is among the most fascinating and complex behaviors because it requires not only an ability to recognize, collect, and carry materials but also evolutionary adaptations in related morphological characteristics. However, the fossil record of such behavior is extremely scarce, and only a single Mesozoic example from Spanish amber has been recorded; therefore, little is known about the early evolution of this complicated behavior and its underlying anatomy. We report a diverse insect assemblage of exceptionally preserved debris carriers from Cretaceous Burmese, French, and Lebanese ambers, including the earliest known chrysopoid larvae (green lacewings), myrmeleontoid larvae (split-footed lacewings and owlflies), and reduviids (assassin bugs). These ancient insects used a variety of debris material, including insect exoskeletons, sand grains, soil dust, leaf trichomes of gleicheniacean ferns, wood fibers, and other vegetal debris. They convergently evolved their debris-carrying behavior through multiple pathways, which expressed a high degree of evolutionary plasticity. We demonstrate that the behavioral repertoire, which is associated with considerable morphological adaptations, was already widespread among insects by at least the Mid-Cretaceous. Together with the previously known Spanish specimen, these fossils are the oldest direct evidence of camouflaging behavior in the fossil record. Our findings provide a novel insight into early evolution of camouflage in insects and ancient ecological associations among plants and insects.

  8. MRSA carrying mecC in captive mara

    DEFF Research Database (Denmark)

    Gongora, Carmen Espinosa; Harrison, Ewan M; Moodley, Arshnee

    2015-01-01

    C-carrying MRSA ST130 clone is widespread in a variety of unrelated hosts in Denmark. Since the mara at Copenhagen Zoo have limited contact with humans and other animal species, it remains unclear whether mara are natural hosts of ST130 or acquired this lineage from unknown sources. The broad host range of MRSA...

  9. Development of heavy load carrying vehicle for nuclear power station

    International Nuclear Information System (INIS)

    Terabayashi, Yasuharu; Oono, Hiroo; Aizu, Takao; Kawaguchi, Kaname; Yamanaka, Masayuki; Hirobe, Tamio; Inagaki, Yoshiaki.

    1985-01-01

    In nuclear power stations, in order to carry out sound and stable operation, the routine inspection and regular inspection of machinery and equipment are performed, therefore, the transportation of heavy things is frequently carried out. Especially, the transportation of heavy things over the steps of passages and stairs requires much labor. Therefore, Chubu Electric Power Co., Inc. and Chubu Plant Service Co., Ltd. carried out the research on the development of a vehicle for transporting heavy components of nuclear power plants. In this research, it was aimed at developing a vehicle which can carry heavy components and get over a step, climb and descend stairs, and run through a narrow passage having many curves as well as running on flat ground. For this purpose, the actual state of the transportation of heavy things was investigated during the regular inspection of a nuclear power station, and on the basis of this results, a prototype vehicle was made and tested. Thereafter, a transporting vehicle of actual scale was made and tested. The investigation of actual state and the examination of the fundamental concept, the design, trial manufacture and verifying test are reported. (Kako, I.)

  10. Stress Carry-Over and College Student Health Outcomes

    Science.gov (United States)

    Pedersen, Daphne E.

    2012-01-01

    Objective: Using a stress carry-over perspective, this study examines the relationship between stress stemming from school and family domains and physical and mental health outcomes. Methods: The study sample included 268 undergraduate men and women from a Midwestern university. Participants completed an anonymous online questionnaire. OLS…

  11. Carrying capacity of a heterogeneous lake for migrating swans

    NARCIS (Netherlands)

    Gyimesi, A.

    2010-01-01

    One way to express the value of a natural habitat is its capacity to harbour a particular target species. In the case of migratory birds, the cumulative number of birds that can be accommodated at a site for a given period of time (‘bird-days’) became an accepted currency for this carrying capacity.

  12. Plasma generator utilizing dielectric member for carrying microwave energy

    International Nuclear Information System (INIS)

    Aklufi, M.E.; Brock, D.W.

    1991-01-01

    This patent describes a system in which electromagnetic energy is used to generate a plasma from a gas. It comprises a reaction chamber which is evacuated to less than ambient pressure and into which the gas is introduced; and a nonconductive member for carrying the electromagnetic energy and for emitting the electromagnetic energy so that a plasma is formed from the gas

  13. "The Bell Curve" and Carrie Buck: Eugenics Revisited.

    Science.gov (United States)

    Smith, J. David

    1995-01-01

    The 1994 publication of "The Bell Curve" by R. Herrnstein and C. Murray is compared to other examples of eugenic principles, including the sterilization of "feebleminded" Carrie Buck, family degeneracy studies focusing on lower class Caucasian families, and other works that view the poorest and least educated members of society…

  14. Carrying capacity of Chaetoceros gracilis in Homa Lagoon and the ...

    African Journals Online (AJOL)

    The possibility for nutrient limitation to affect C. gracilis was assessed from two different ecosystems (Izmir Bay and Homa Lagoon). Our goal was to determine the growth rate of all nutrients and the maximum levels of the C. gracilis phytoplankton biomass (the maximum biomass carrying capacity) on the extent of its full ...

  15. Hotspot relaxation dynamics in a current-carrying superconductor

    Science.gov (United States)

    Marsili, F.; Stevens, M. J.; Kozorezov, A.; Verma, V. B.; Lambert, Colin; Stern, J. A.; Horansky, R. D.; Dyer, S.; Duff, S.; Pappas, D. P.; Lita, A. E.; Shaw, M. D.; Mirin, R. P.; Nam, S. W.

    2016-03-01

    We experimentally studied the dynamics of optically excited hotspots in current-carrying WSi superconducting nanowires as a function of bias current, bath temperature, and excitation wavelength. We observed that the hotspot relaxation time depends on bias current, temperature, and wavelength. We explained this effect with a model based on quasiparticle recombination, which provides insight into the quasiparticle dynamics of superconductors.

  16. The logistic model-generated carrying capacities for wild herbivores ...

    African Journals Online (AJOL)

    Jesse

    Under this formulation, both carrying capacity and exchange ratios are endogenously determined (Kinyua and Njoka, 2001), making it possible to empirically estimate the population growth models for Grant's gazelle, Thompson's gazelle and Zebra. (1) for i = 1,…,n-1 j = 1,…,2 and i ≠ j. Here Hit+1, measured in animal units, ...

  17. Cognitive Load in Voice Therapy Carry-Over Exercises

    Science.gov (United States)

    Iwarsson, Jenny; Morris, David Jackson; Balling, Laura Winther

    2017-01-01

    Purpose: The cognitive load generated by online speech production may vary with the nature of the speech task. This article examines 3 speech tasks used in voice therapy carry-over exercises, in which a patient is required to adopt and automatize new voice behaviors, ultimately in daily spontaneous communication. Method: Twelve subjects produced…

  18. The KB WOT Fisheries Programme carried out in 2015

    NARCIS (Netherlands)

    Damme, van C.J.G.; Verver, S.W.

    2017-01-01

    The KB WOT Fisheries programme is established to maintain and develop the expertise needed to carry out the statutory obligations of the Netherlands in fisheries monitoring and advice. It is also a flexible program which responds to changes over time in WOT requirements, fisheries management and

  19. Trials carried out on corrosive (fluorinated) atmosphere vacuum gauges

    International Nuclear Information System (INIS)

    Constant, M.; Houyvet, A.; Noe, P.

    1966-01-01

    Study of the stability of readings given by a modified Pirani type measurement probe with a view to long term operation in the presence of corrosive gases. Results of measurements carried out before and after use under these conditions. (author) [fr

  20. Random noise characterization on the carrying capacities of a ...

    African Journals Online (AJOL)

    The process of the survival of species dependent on a limited resource in a polluted environment which isnot a new idea can be described by the technique of a mathematical modelling. We have utilised the technique of a numerical simulation to study the impact of environmental random noise on the carrying capacities of ...

  1. Application of Load Carrying Sandwich Elements in Wind Turbine Blades

    DEFF Research Database (Denmark)

    Jensen, Jacob Fisker; Schultz, Jacob Pagh; Berggreen, Carl Christian

    2005-01-01

    The present work investigates the possibilities and drawbacks when applying sandwich as opposed to single skin composites in the flanges of the load carrying spar in a future 180 m wind turbine rotor. FEA is applied to investigate two basic designs with single skin and sandwich flanges respectively...

  2. Must-carry regulation: a must or a burden?

    NARCIS (Netherlands)

    van Eijk, N.; van der Sloot, B.; Nikoltchev, S.

    2012-01-01

    The first must-carry rules date back to 1990, the time when space on analogue broadcasting networks was limited and when supply grew quickly due to the introduction of private broadcasters. To ensure that channels of general interest would still be transmitted, countries introduced rules to regulate

  3. El naturalismo americano: Theodore Dreiser y Sister Carrie

    Directory of Open Access Journals (Sweden)

    Dolores G. ALONSO MULAS

    2009-08-01

    Full Text Available Para situar a un escritor, como Theodore Dreiser, y especialmente su novela Sister Carrie dentro de un movimiento literario y de una etapa determinada de la historia americana, es necesario dar un breve repaso al naturalismo, llegado a América a través de Stephen Crane

  4. Violence and weapon carrying in music videos. A content analysis.

    Science.gov (United States)

    DuRant, R H; Rich, M; Emans, S J; Rome, E S; Allred, E; Woods, E R

    1997-05-01

    The positive portrayal of violence and weapon carrying in televised music videos is thought to have a considerable influence on the normative expectations of adolescents about these behaviors. To perform a content analysis of the depictions of violence and weapon carrying in music videos, including 5 genres of music (rock, rap, adult contemporary, rhythm and blues, and country), from 4 television networks and to analyze the degree of sexuality or eroticism portrayed in each video and its association with violence and weapon carrying, as an indicator of the desirability of violent behaviors. Five hundred eighteen videos were recorded during randomly selected days and times of the day from the Music Television, Video Hits One, Black Entertainment Television, and Country Music Television networks. Four female and 4 male observers aged 17 to 24 years were trained to use a standardized content analysis instrument. Interobserver reliability testing resulted in a mean (+/- SD) percentage agreement of 89.25% +/- 7.10% and a mean (+/- SD) kappa of 0.73 +/- 0.20. All videos were observed by rotating 2-person, male-female teams that were required to reach agreement on each behavior that was scored. Music genre and network differences in behaviors were analyzed with chi 2 tests. A higher percentage (22.4%) of Music Television videos portrayed overt violence than Video Hits One (11.8%), Country Music Television (11.8%), and Black Entertainment Television (11.5%) videos (P = .02). Rap (20.4%) had the highest portrayal of violence, followed by rock (19.8%), country (10.8%), adult contemporary (9.7%), and rhythm and blues (5.9%) (P = .006). Weapon carrying was higher on Music Television (25.0%) than on Black Entertainment Television (11.5%), Video Hits One (8.4%), and Country Music Television (6.9%) (P violence (P violence and weapon carrying, which is glamorized by music artists, actors, and actresses.

  5. A METHOD OF SECURITY SCANNING OF CARRY-ON ITEMS, AND A CARRY-ON ITEMS SECURITY SCANNING SYSTEM

    DEFF Research Database (Denmark)

    2017-01-01

    A security scanning system (1) comprises a first stage module (3) having at least one X-ray source (6) and at least three first detectors (7) that are line-shaped and arranged in mutually different orientations and have at least dual energy resolution. A group of carry-on items (4) on a carrier...

  6. Carrying capacity in a heterogeneous environment with habitat connectivity.

    Science.gov (United States)

    Zhang, Bo; Kula, Alex; Mack, Keenan M L; Zhai, Lu; Ryce, Arrix L; Ni, Wei-Ming; DeAngelis, Donald L; Van Dyken, J David

    2017-09-01

    A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non-diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments. © 2017 John Wiley & Sons Ltd/CNRS.

  7. Experiments on criticality carried out from 1975 till 1980

    International Nuclear Information System (INIS)

    Heinicke, W.; Tischer, A.; Weber, W.J.

    1981-11-01

    The report on hand includes the experiments on criticality published from 1975 till 1980. About 90 experiments with the most important related data are listed. They are capable of being called up, with the data base system KRITEXP, by 14 different descriptors or printed in any arrangement or order. This is the basis for a global or purposeful verification of the calculating method for criticality safety. The proof of reliability of the calculations for the criticality analysis are immediately relevant for the licencing procedure under atomic law for all plants of the nuclear fuel cycle where nuclear fuels are handled. Since no criticality experiments are being carried out in the Federal Republic of Germany, the data collection on hand will help to fill this gap with regard to the assessment of experiments carried out in other countries. (orig.) [de

  8. Apparatus for carrying out ultrasonic inspection of pressure vessels

    International Nuclear Information System (INIS)

    Dent, K.H.; Challender, R.S.

    1975-01-01

    Apparatus is described for use in carrying out ultrasonic inspection of coolant nozzles of nuclear reactor pressure vessels. It comprises a manipulator for supporting an ultrasonic scanning transducer within the coolant nozzle. The manipulator is carried by a support located within the pressure vessel and comprises a pair of legs pivotable in caliper manner to span the base of the nozzle. Means are provided for pivoting the legs together to enable free entry of the manipulator and scanning transducer into the nozzle, and for pivoting the legs apart to bring the transducer into an operating position adjacent to the wall of the nozzle. The manipulator is rotatable within the nozzle to enable scanning of its interior surface. (U.K.)

  9. Behavioral Indicators of Legal and Illegal Gun Carrying

    Science.gov (United States)

    2015-05-01

    foundation to develop training for law enforcement and security personnel to utilize behavioral indicators in a safe, legal, and effective manner...hope to develop more efficient and effective means of assisting the police to identify and safely interdict persons carrying illegal firearms. This...by Velcro hook and loop fastener tape. Attached to the elastic wrap is a pocket with a security strap that holds the gun in place. When fastened to

  10. A portable virtual machine target for proof-carrying code

    DEFF Research Database (Denmark)

    Franz, Michael; Chandra, Deepak; Gal, Andreas

    2005-01-01

    Virtual Machines (VMs) and Proof-Carrying Code (PCC) are two techniques that have been used independently to provide safety for (mobile) code. Existing virtual machines, such as the Java VM, have several drawbacks: First, the effort required for safety verification is considerable. Second and mor...... simultaneously providing efficient justin-time compilation and target-machine independence. In particular, our approach reduces the complexity of the required proofs, resulting in fewer proof obligations that need to be discharged at the target machine....

  11. Cognitive Load in Voice Therapy Carry-Over Exercises

    DEFF Research Database (Denmark)

    Iwarsson, Jenny; Morris, David Jackson; Balling, Laura Winther

    2017-01-01

    Purpose The cognitive load generated by online speech production may vary with the nature of the speech task. This article examines 3 speech tasks used in voice therapy carry-over exercises, in which a patient is required to adopt and automatize new voice behaviors, ultimately in daily spontaneous...... to automation of revised speech behavior and that self-reports may be a reliable index of cognitive load....

  12. Digitization Projects Carried out by the Mathematical Institute Belgrade

    OpenAIRE

    Ognjanovič, Zoran; Mijajlovič, Žarco

    2004-01-01

    In this paper some current digitization projects carried out by the Mathematical Institute of Serbian Academy of Science and Arts Belgrade and the Faculty of Mathematics Belgrade are described. The projects concern developing of a virtual library of retro-digitized books and an Internet data base and presentation of electronic editions of some leading Serbian journals in science and arts, and the work on the South-Eastern European Digitization Initiative (SEEDI).

  13. Effect of multipurpose solutions against Acinetobacter carrying QAC genes.

    Science.gov (United States)

    Boost, Maureen V; Chan, Jessica; Shi, Guang-sen; Cho, Pauline

    2014-03-01

    Acinetobacter has low virulence but causes infections in subjects with reduced immunity. It has been reported in ocular infections including those of patients using contact lenses. Treatment is difficult because Acinetobacter is frequently multidrug resistant. Antibiotic-resistant strains frequently also harbor genes for antiseptic resistance (quaternary ammonium compound [QAC]) genes. Because Acinetobacter is part of the normal flora, it may contaminate contact lens and accessories. This study aims to investigate carriage rates of QAC genes in household and clinical isolates of Acinetobacter and to determine the effectiveness of two multipurpose solutions (MPSs) for soft lenses against organisms carrying QAC genes. DNA was extracted from 11 bathroom isolates and 15 clinical isolates and amplified by polymerase chain reaction to determine the presence of qacEΔ1. Gene-positive and gene-negative control strains were used to challenge the two MPSs, and minimum inhibitory concentrations (MICs) of these organisms to benzalkonium chloride and chlorhexidine gluconate were determined. More than 90% of isolates carried qacEΔ1. The MICs of clinical isolates were higher than those of isolates of bathrooms. Both MPSs were able to produce a 3-log reduction in the numbers of all isolates. Although most isolates carried qacEΔ1 and elevated MICs to benzalkonium chloride and chlorhexidine gluconate were observed, all were susceptible to both MPSs tested. However, if there were to be poor compliance with care procedures, it is probable that such organisms could survive in the presence of diluted or expired solutions.

  14. Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿

    Science.gov (United States)

    Yacoby, Iftach; Bar, Hagit; Benhar, Itai

    2007-01-01

    While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004

  15. Urban development control based on transportation carrying capacity

    Science.gov (United States)

    Miharja, M.; Sjafruddin, A. H.

    2017-06-01

    Severe transportation problems in Indonesian urban areas are stimulated by one fundamental factor, namely lack of awareness on transportation carrying capacity in these areas development control. Urban land use development towards more physical coverage is typically not related with the capability of transportation system to accommodate additional trips volume. Lack of clear connection between development permit with its implication on the transportation side has led to a phenomenon of exceeding transport demand over supply capacity. This paper discusses the concept of urban land use development control which will be related with transport carrying capacity. The discussion would cover both supply and demand sides of transportation. From supply side, the analysis regarding the capacity of transport system would take both existing as well as potential road network capacity could be developed. From demand side, the analysis would be through the control of a maximum floor area and public transport provision. Allowed maximum floor area for development would be at the level of generating traffic at reasonable volume. Ultimately, the objective of this paper is to introduce model to incorporate transport carrying capacity in Indonesian urban land use development control.

  16. Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.

    Science.gov (United States)

    Coulter, Jess M; Warme, Winston J

    2015-09-01

    We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  17. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Directory of Open Access Journals (Sweden)

    Yacoby Iftach

    2008-04-01

    Full Text Available Abstract Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates.

  18. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Science.gov (United States)

    Bar, Hagit; Yacoby, Iftach; Benhar, Itai

    2008-01-01

    Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates. PMID:18387177

  19. Detector for the liquid carried over in a gas

    International Nuclear Information System (INIS)

    Delisle, J.P.; Eperonnat, P.; Lions, N.

    1965-01-01

    This report describes an optical detector for the detection of a liquid carried over by a gas. The device is sensitive to a cumulated quantity of liquid equal to a few cubic millimetres and is capable of operating an alarm from a distance. The prototype was constructed and tested as detector for the oil leaking in the argon compressed by a diaphragm compressor. A patent for this apparatus under the number: P.V.954.703, has been deposited on 22.11.1963. (authors) [fr

  20. Shielding calculations for ships carrying irradiated nuclear fuel

    International Nuclear Information System (INIS)

    Burstall, R.F.; Dean, M.H.

    1983-01-01

    A number of ships have been constructed to carry irradiated fuel from Japan to the UK and France, for reprocessing. About twenty transport flasks may be carried on each voyage. Permanent shielding must be provided on the ships to ensure that no member of the crew receives an annual dose rate greater than a specified limit. As the fuel is of varying type and radiation history, and as flasks of differing designs are used, many calculations are needed. There are a number of difficulties in making shielding calculations for the ships. The geometry is complex, dimensions are large, and considerable air spaces are involved. The paper considers possible methods of calculation. The line-of-sight method is chosen for most of the calculations, for both gamma radiation and neutrons. The basic data which is used in the calculations is described. As the methods of calculation are somewhat approximate, it is necessary to provide confirmation that they are sufficiently accurate. Validation has been provided in two ways. First, measurements have been made on board the ships, and these have been checked against calculation. Second, a simplified model of the flasks and ship has been set up, and calculations checked against more sophisticated methods. Results of the validation checks are presented, and it is shown that adequate accuracy is achieved. (author)

  1. Shielding calculations for ships carrying irradiated nuclear fuel

    International Nuclear Information System (INIS)

    Dean, M.H.

    1985-01-01

    A number of ships have been constructed to carry irradiated fuel from Japan to the U.K. and France, for reprocessing. About 20 transport flasks may be carried on each voyage. Permanent shielding must be provided on the ships to ensure that no member of the crew receives an annual dose greater than a specified limit. As the fuel is of varying type and radiation history, and as flasks of differing designs are used, many shielding calculations are needed. There are a number of difficulties in making shielding calculations for the ships. The geometry is complex, dimensions are large and considerable air spaces are involved. The paper considers possible methods of calculation. The line-of-sight method is chosen for most of the calculations, for both γ-radiation and neutrons. The basic data which is used in the calculations is described. As the methods of calculation are somewhat approximate, it is necessary to provide confirmation that they are sufficiently accurate. Validation has been provided in two ways. First, measurements have been made on board one of the ships, Pacific Crane, and these have been checked against calculation. Second, a simplified model of the flasks and ship has been set up, and calculations checked against more sophisticated methods. Results of the validation checks are presented, and it is shown that adequate accuracy is achieved. (author)

  2. Extinguishing experiments of sodium fires carried out by TNO

    International Nuclear Information System (INIS)

    Meijer, G.J.A.M.; Rulkens, W.H.

    1979-01-01

    For the collection of burning sodium from the components and pipes of the secondary circuit of SNR 300, spill-trays are foreseen which are connected to dump tanks. These spill-trays are covered with a sieve in order to reduce the flow of air to the sodium in the spill-tray and hence to reduce the burning rate. In order to further minimize the consequences of a large sodium fire for the components, the licensing authority required as a back-up the installation of a remotely operated distribution system by means of which an extinguishing powder can be sprayed upon the spill-trays. Experiments were carried out in which the effectiveness of different extinguishing powders in combination with the sieve covered spill-trays were tested in a comparative manner. Attention was paid to the question whether such a spray system would have also additional benefits in the case of smaller sodium leaks. To this purpose three commercially available extinguishing powders were tested, one on a sodium chloride, two on a carbonate base. Also the effectiveness of the sieves proper with respect to reducing the burning rate was tested without applying any extinguishing powders. Finally for a reference some tests were done on open spill-trays, i.e. spill-trays not covered with a sieve.The investigations which were carried out in 1976-1977 were limited to fire experiments, aspects of transport of the powder in the distribution system were not investigated

  3. Langkawi Island, Social Aspect and the Carrying Capacity

    Directory of Open Access Journals (Sweden)

    Mohamad Diana

    2014-01-01

    Full Text Available The aptitude to convince a range of preferences has facilitated the island tourism attractions to achieve international recognition and at present KILIM Geopark is enjoyed by a prominent percentage of individuals wide-reaching. Conventional knowledge has that the island attractions are operating on the limited immobile resources, of which, have raised the scholars’ concerns over the carrying capacity issue. When analyzing carrying capacity, scholars have traditionally focused on the environmental part, hence, this working paper is motivated to convey onto the table issues relating to the social characteristics. This particular paper employed the self-administered questionnaire survey instrument which was structured to answer the two-fold objective specifically the tourists’ satisfaction level with their tourism experience and knowledge gap in relation to improving the island tourism. Targeting the tourists with minimum age of 18, this working paper collects information on the tourists’ perception towards hospitality, facilities and safety issues. In addition, this working paper comes to scrutinize different results of demographic factors as compared to what have been documented by earlier studies. Besides, it is learned that ‘safety issue’ variable plays an important role when it comes to the following factors: tourist arrival, access to facilities and tourism experience.

  4. Exosomes carrying immunoinhibitory proteins and their role in cancer.

    Science.gov (United States)

    Whiteside, T L

    2017-09-01

    Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi-directional cross-talk mediated by exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour-derived exosomes carry multiple immunoinhibitory signals, disable anti-tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non-invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome. © 2017 British Society for Immunology.

  5. Necking down of sausages in current-carrying plasma pinches

    International Nuclear Information System (INIS)

    Trubnikov, B.A.; Zhdanov, S.K.

    1986-01-01

    The evolution of long-wave perturbations is shown to be equivalent, for various unstable media, to the dynamics of a gas with a negative adiabatic index γ. This evolution is described (for various values at N) by the quasi-Chaplygin system of equations Several examples of such media are considered, including a ''Chaplygin gas'' (N = 3), drops on a ceiling or ''solitons which have broken'' (N = 0), necks in a current-carrying plasma pinch with a skin effect, for both incompressible and compressible models (N = 2), and the breakup of liquid jets into drops (N = 3/2). A principle for selecting evolutionary solutions corresponding to the absence of perturbations in the limit t → -∞ is formulated. In the cases N = 0 and N = 2, a hodograph transformation reduces system (1) to a magnetostatic equation (ΔA)/sub phi/ = -(4π/c)j/sub phi/ and all the instability modes are equivalent to multipoles of circular currents which are localized on a circle. Exact solutions are given for periodic and isolated (localized) perturbations. The breakup of a medium into distinct blobs, in particular, the rupture of necks in a current-carrying plasma pinch, is demonstrated

  6. Oxygen carrying perfluorochemical emulsion as an adjuvant to radiation therapy

    International Nuclear Information System (INIS)

    Teicher, B.A.; Rose, C.M.

    1984-01-01

    The potential of a perfluorochemical emulsion which as an excellent carrying capacity for oxygen to enhance the ability of radiation therapy to delay the growth of Lewis lung tumor was examined. There was a highly significant effect produced by the addition of perfluorochemical emulsion and carbogen breathing in combination with irradiation. With single dose x-ray treatment the dose of perfluorochemical emulsion was varied from 0.05-0.6 ml addition to the blood volume of the animals. The dose response effect was very broad peaking at 0.3-0.4 ml which gave a dose modifying effect of 2.8 +- 0.6 with 1000 rad of x-rays. The addition of 0.3 ml of perfluorochemical free annex solution with carbogen breathing produced a small enhancement in tumor growth delay addition of the same volume of the complete emulsion increased the tumor growth delay time about 3-fold compared to the annex solution. When the perfluorochemical emulsion was added to a fractionated course of radiation therapy a dose modifying effect of 1.8 +- 0.3 was obtained. Oxygen carrying perfluorochemical emulsions may provide a nontoxic clinically useful means of increasing the effectiveness of radiation therapy and of certain chemotherapeutic agents

  7. STS-99 workers carry new Master Events Controller to Endeavour

    Science.gov (United States)

    2000-01-01

    Workers carry the replacement Enhanced Main Events Controller (E- MEC) to Shuttle Endeavour at Launch Pad 39A for installation in the aft compartment of the payload bay. The original E-MEC became suspect during the Jan. 31 launch countdown and mission STS-99 was delayed when NASA managers decided to replace it. Each Shuttle carries two enhanced master events controllers (E-MECs), which provide relays for onboard flight computers to send signals to arm and fire pyrotechnics that separate the solid rockets and external tank during assent. Both E-MECs are needed for the Shuttle to be cleared for flight. Currently Endeavour and Columbia are the only two orbiters with the E-MECs. Built by Rockwell's Satellite Space Electronics Division, Anaheim, Calif., each unit weighs 65 pounds and is approximately 20 inches long, 13 inches wide and 8 inches tall. Previously, three Shuttle flights have been scrubbed or delayed due to faulty MECs: STS-73, STS-49 and STS-41-D. The next scheduled date for launch of STS-99 is Feb. 11 at 12:30 p.m. EST.

  8. Modelling of carry-over in recovery furnaces

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrai, Reza [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Metallurgy

    2000-04-01

    Development of mathematical modelling of the combustion process in the furnace of recovery boilers is the subject of this work. This work as a continuation of many years of modelling efforts carried out at KTH/Vaerme- och Ugnsteknik focussed particularly on: char bed modelling; droplets-wall interaction modelling; and carry-over modelling. The char bed model has been studied. Droplets/parcels were considered as a single reactor working independently of the other droplets. The mass of the droplets was not distributed uniformly but induced in the landing place. The droplets hitting the char bed will stick to it and they are alive and part of the calculation. In this way the distribution of the mass on the char bed is only dependent on the parameters which effect flight history such as droplet/parcel diameter, boilers flow field, etc. The droplet- wall interaction model has been studied and found to be very important for obtaining the correct temperature distribution in the recovery furnace. The new approach is based on removal of droplets which hits the wall in the upper part of the recovery boiler from carryover calculation. This model has been proposed and implemented into the GRFM (General Recovery Furnace Model). The carryover modelling effort was based on mass balance in which the number and physical statistics of the droplets/parcel were estimated and the amount of unburned mass was calculated. All of the above listed models were tested together with all other models of heat and mass transfer processes in recovery furnaces using a GRFM. Three-dimensional numerical simulations of the industrial recovery boiler (63 kg/s, 82 bar, 480 deg C) were performed. The number of grid was 232,000 and the number of air ports in this simulation was 178. The air entering the furnace by these ports has different flow rates. Flow and temperature fields as well as species distributions were calculated. The results show good agreement with previously published data and modelling

  9. Time dependent variation of carrying capacity of prestressed precast beam

    Science.gov (United States)

    Le, Tuan D.; Konečný, Petr; Matečková, Pavlína

    2018-04-01

    The article deals with the evaluation of the precast concrete element time dependent carrying capacity. The variation of the resistance is inherited property of laboratory as well as in-situ members. Thus the specification of highest, yet possible, laboratory sample resistance is important with respect to evaluation of laboratory experiments based on the test machine loading capabilities. The ultimate capacity is evaluated through the bending moment resistance of a simply supported prestressed concrete beam. The probabilistic assessment is applied. Scatter of random variables of compressive strength of concrete and effective height of the cross section is considered. Monte Carlo simulation technique is used to investigate the performance of the cross section of the beam with changes of tendons’ positions and compressive strength of concrete.

  10. Tax shields, financial expenses and losses carried forward

    Directory of Open Access Journals (Sweden)

    Ignacio Vélez-Pareja

    2016-09-01

    Full Text Available This article deals with the proper procedure for calculating Tax Shields (TS. The calculation includes cases where Losses Carried Forward are allowed and there is financial Other Income (OI. The procedure takes into account the magnitude of Adjusted Earnings before Interest and Taxes (EBITAdj –that is, EBIT + OI – OE excluding Financial- compared with Financial Expenses (FE. This comparison defines three intervals and results for TS. If EBITAdj. 0 and less than FE, TSis T × EBITAdj.; finally if EBITAdj. > FE, TSis T × FE. When firm possesses OI, TS are not equivalent to the difference in taxes and an adjustment is needed. Proper calculation of TS is important because their value might represent a substantial part of firm value.

  11. Stabilization of magnetohydrodynamic instabilities in a current-carrying stellarator

    International Nuclear Information System (INIS)

    Matsuoka, K.; Miyamoto, K.

    1979-02-01

    Stable profiles against MHD instabilities are given in a cylindrical current-carrying stellarator. The comparison theorem, i.e., guiding principle for stabilization, is obtained in the same way as in a tokamak. As the external rotational transform due to an l = 2 helical field increases, MHD properties in a stellarator are improved than in a tokamak and the minimum value of q(a) which provides simultaneous stabilization of MHD modes can be lowered less than 2 even without a conducting shell. In an l = 3 stellarator, however, as shown from the Euler equation, the configuration becomes more unstable than in a tokamak and strong tailoring of the current profile is necessary in order to stabilize MHD modes. (author)

  12. Process for carrying out analyses based on concurrent reactions

    Energy Technology Data Exchange (ETDEWEB)

    Glover, J S; Shepherd, B P

    1980-01-03

    The invention refers to a process for carrying out analyses based on concurrent reactions. A part of a compound to be analysed is subjected with a standard quantity of this compound in a labelled form to a common reaction with a standard quantity of a reagent, which must be less than the sum of the two parts of the reacting compound. The parts of the marked reaction compound and the labelled final compound resulting from the concurrence are separated in a tube (e.g. by centrifuging) after forced phase change (precipitation, absorption etc.) and the radio-activity of both phases in contact is measured separately. The shielded measuring device developed for this and suitable for centrifuge tubes of known dimensions is also included in the patent claims. The insulin concentration of a defined serum is measured as an example of the applications of the method (Radioimmunoassay).

  13. IRSN safety research carried out for reviewing safety cases

    International Nuclear Information System (INIS)

    Serres, Ch.

    2010-01-01

    Christophe Serres from IRSN (France) described the independent role of the IRSN regarding research related to nuclear safety in the context of the French Planning Act of 28 June 2006 foreseeing a licence application to be submitted in 2015 for the creation of a deep geological repository. IRSN research programme is organised along research activities devoted to addressing independently-identified k ey safety issues . These 'key issues' should also be of prime concern for the implementer since they relate to the demonstration of the overall safety of the repository, and the level of funding that the implementer should afford to research activities of concern for safety. He explained that the quality and independency of the research programme carried out by IRSN allow building and improving a set of scientific knowledge and technical skills that serves the public mission of delivering technical appraisal and advice, e.g., on behalf of the national safety authority. In particular they contribute to improving the decisional process by making possible scientific dialogue with stakeholders independently from regulator or implementer. The current IRSN R and D programme is developed along the following lines: - Test the adequacy of experimental methods for which feedback is not sufficient. - Develop basic scientific knowledge in the fields where there is a need for better understanding of complex phenomena and interactions. - Develop and use numerical modelling tools to support studies on complex phenomena and interactions. - Perform specific experimental tests aiming at assessing the key parameters that may warrant the performances of the different components of the repository. These studies are carried out by means of experiments performed either at IRSN surface laboratories, or in the Tournemire Experimental Station (TES), an underground facility operated by IRSN in the south-east of France. Targeted actions on research related to operational safety and reversibility

  14. Characterization of LH induced current carrying fast electrons in JET

    Energy Technology Data Exchange (ETDEWEB)

    Ramponi, G.; Airoldi, A. [Consiglio Nazionale delle Ricerche, Milan (Italy). Lab. di Fisica del Plasma; Bartlett, D.; Brusati, M.; Froissard, P.; Gormezano, C.; Rimini, F.; Silva, R.P. da; Tanzi, C.P. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking

    1992-12-31

    Lower Hybrid Current Drive (LHCD) experiments have recently been made at JET by coupling up to 2.4 MW of RF power at 3.7 GHz, with a power spectrum centered at n{sub ||} = 1.8 {+-} 0.2 corresponding to a resonating electron energy of about 100 keV via Electron Landau Damping. The Current Drive (CD) efficiency has been observed to increase when LH and ICRH power are applied simultaneously to the plasma, suggesting that a part of the fast magnetosonic wave is absorbed on the LH-generated fast electrons. An important problem of CD experiments in tokamaks is the determination of the radial distribution of the driven current and the characterization in the momentum space of the current carrying fast electrons by using appropriate diagnostic tools. For this purpose, a combined analysis of the Electron Cyclotron Emission (ECE) and of the Fast Electron Bremsstrahlung (FEB) measurements has been made, allowing the relevant parameters of the suprathermal electrons to be estimated. (author) 5 refs., 5 figs., 2 tabs.

  15. Characterization of LH induced current carrying fast electrons in JET

    International Nuclear Information System (INIS)

    Ramponi, G.; Airoldi, A.; Bartlett, D.; Brusati, M.; Froissard, P.; Gormezano, C.; Rimini, F.; Silva, R.P. da; Tanzi, C.P.

    1992-01-01

    Lower Hybrid Current Drive (LHCD) experiments have recently been made at JET by coupling up to 2.4 MW of RF power at 3.7 GHz, with a power spectrum centered at n || = 1.8 ± 0.2 corresponding to a resonating electron energy of about 100 keV via Electron Landau Damping. The Current Drive (CD) efficiency has been observed to increase when LH and ICRH power are applied simultaneously to the plasma, suggesting that a part of the fast magnetosonic wave is absorbed on the LH-generated fast electrons. An important problem of CD experiments in tokamaks is the determination of the radial distribution of the driven current and the characterization in the momentum space of the current carrying fast electrons by using appropriate diagnostic tools. For this purpose, a combined analysis of the Electron Cyclotron Emission (ECE) and of the Fast Electron Bremsstrahlung (FEB) measurements has been made, allowing the relevant parameters of the suprathermal electrons to be estimated. (author) 5 refs., 5 figs., 2 tabs

  16. Mutagenic effects on indica rice carried by satellite

    International Nuclear Information System (INIS)

    Wu Dezhi; Liu Yongzhu; Guo Tao; Zhang Jianguo; Chen Zhiqiang; Wang Hui

    2010-01-01

    Dried seeds of four indica rice varieties were carried into space by satellite Shijia No.8, the mutagenic effects of space condition on the seeds vigor and agronomic traits in the SP 1 generation, and on the agronomic traits, amylose conent and bacterial resistance in the SP 2 generation were studied. The results showed that the space condition slightly damaged rice seeds, with the physiological damage rate of germination rate, bud length, plant height and seed-setting rate in the SP 1 ranged from 0 to 26.9%. Different varieties responded differently to the space conditions, and the order from strong to weak was Gui 99, Hanghui 7, R998, Jinhang 138. Compared with the control, no trait showed segregation in the SP 1 generation. Some traits appeared larger segregation in the SP 2 generation, and the mutants of plant height, number of tillers, weight of grain, amylose content and bacterial blight resistance were isolated in the SP 2 generation, and these mutation traits could be inherited the SP 3 generation. Space conditions not only produced mutants of rice agronomic traits, but also produced mutants of rice quality and disease resistance. (authors)

  17. Carrying photosynthesis genes increases ecological fitness of cyanophage in silico.

    Science.gov (United States)

    Hellweger, Ferdi L

    2009-06-01

    Several viruses infecting marine cyanobacteria carry photosynthesis genes (e.g. psbA, hli) that are expressed, yield proteins (D1, HLIP) and help maintain the cell's photosynthesis apparatus during the latent period. This increases energy and speeds up virus production, allowing for a reduced latent period (a fitness benefit), but it also increases the DNA size, which slows down new virus production and reduces burst size (a fitness cost). How do these genes affect the net ecological fitness of the virus? Here, this question is explored using a combined systems biology and systems ecology ('systems bioecology') approach. A novel agent-based model simulates individual cyanobacteria cells and virus particles, each with their own genes, transcripts, proteins and other properties. The effect of D1 and HLIP proteins is explicitly considered using a mechanistic photosynthesis component. The model is calibrated to the available database for Prochlorococcus ecotype MED4 and podovirus P-SSP7. Laboratory- and field-scale in silico survival, competition and evolution (gene packaging error) experiments with wild type and genetically engineered viruses are performed to develop vertical survival and fitness profiles, and to determine the optimal gene content. The results suggest that photosynthesis genes are nonessential, increase fitness in a manner correlated with irradiance, and that the wild type has an optimal gene content.

  18. Interchain interactions in charged diacetylenic oligomers carrying bulk substituents revisited

    International Nuclear Information System (INIS)

    Ottonelli, M.; Izzo, G.M.M.; Comoretto, D.; Musso, G.F.; Dellepiane, G.

    2006-01-01

    We are studying how the electronic properties of an aggregate, built with conjugated oligomers carrying bulk substituents, are affected by intermolecular interactions. In this paper we apply the CEO (Collective Electronic Oscillator) method, on the basis of the semiempirical INDO/S Hamiltonian, to compute the electronic density matrix modifications following the photon absorption in a doubly charged cluster of two units of a fully carbazolyl-substituted oligodiacetylene tetramer, taken as a model system. The picture that had emerged from our previous calculations based on the less sophisticated CIS (Configuration Interaction including Singles) approach is seen to be confirmed. Despite the large separation between the backbones, a through-space charge transfer occurs between the two oligomers due to the fact that the excess charge, contrary to what is generally believed, is not localized on the conjugated backbone, but is spread out over the carbazolyl moieties of the charged molecule. Consideration of this kind of interaction improves the theoretical results obtained for the isolated charged oligomer chain, and aids in better explaining some features of the experimental photoinduced spectra of the corresponding polymer

  19. Single-electron states near a current-carrying core

    International Nuclear Information System (INIS)

    Masale, M.

    2004-01-01

    The energy spectrum of an electron confined near a current-carrying core is obtained as a function of the azimuthal applied magnetic field within the effective-mass approximation. The double degeneracy of the non-zero electron's axial wave number (k z ) states is lifted by the current-induced magnetic field while that of the non-zero azimuthal quantum number (m) states is preserved. A further analysis is the evaluations of the oscillator strengths for optical transitions involving the lowest-order pair of the electron's energy subbands within the dipole approximation. The radiation field is taken as that of elliptically polarized light incident along the core axis. In this polarization and within the dipole approximation, the allowed transitions are only those governed by the following specific selection rules. The azimuthal quantum numbers of the initial and final states must differ by unity while the electron's axial wave number is conserved. The azimuthal magnetic field is also found to lift the multiple degeneracies of the k z ≠0 interaction integrals as well as those of the oscillator strengths for optical transitions

  20. Roadmap and performance carried out during Ciemat site decommissioning

    International Nuclear Information System (INIS)

    Quinones, Javier; Diaz Diaz, Jose Luis

    2005-01-01

    Ciemat (Research Centre for Energy, Environment and Technology) located in the heart of the Ciudad Universitaria of Madrid, occupies a property of 20 Ha. Since its creation in 1951 as JEN, and in 1986 renowned as Ciemat, it has involved on R and D projects in the field of Energy and Environment, i.e., Nuclear Fission, Nuclear Fusion, Fossils Fuels, Renewable Energy. As a consequence of the R and D projects developed between 1951 - 1986 on Nuclear Fission field (fuel design, fabrication, characterization on irradiated fuels, safety studies, etc) and to the diversification of the goals as well, it is necessary to Decommissioning and Dismantling (D and D) from nuclear facilities (nuclear reactor, Hot Cells, Irradiation facility), buildings and soils. Preparations for D and D included a staged shutdown of operations, planning documentation and licensing for decommissioning. As a prerequisite to Ciemat application for a decommissioning license and nuclear environmental assessment was carried out according to Spanish Nuclear Council (CSN) and approval of the site decommissioning project was obtained in 2000 and valid until December 31, 2006. Since 2001 - 2003 is underway and focussed on the radiological characterization of the site (divided in pieces of ground), when each piece of ground is characterized a planning for D and D is presented to CSN in order to obtain a license for actuation. Nowadays several pieces of ground are decontaminated and modifications have been done in order to achieve a safe state of storage-with-surveillance. Later phases have planned waste management improvements for selected wastes already on temporally storage, eventually followed by final decommissioning of facilities and buildings and cleaning of contaminants from soils and removal of waste from the site. This paper describes the planning, nuclear and environment assessment and descriptions of decommissioning activities currently underway at Ciemat. (Author)

  1. Tensorial spacetime geometries carrying predictive, interpretable and quantizable matter dynamics

    International Nuclear Information System (INIS)

    Rivera Hernandez, Sergio

    2012-01-01

    Which tensor fields G on a smooth manifold M can serve as a spacetime structure? In the first part of this thesis, it is found that only a severely restricted class of tensor fields can provide classical spacetime geometries, namely those that can carry predictive, interpretable and quantizable matter dynamics. The obvious dependence of this characterization of admissible tensorial spacetime geometries on specific matter is not a weakness, but rather presents an insight: it was Maxwell theory that justified Einstein to promote Lorentzian manifolds to the status of a spacetime geometry. Any matter that does not mimick the structure of Maxwell theory, will force us to choose another geometry on which the matter dynamics of interest are predictive, interpretable and quantizable. These three physical conditions on matter impose three corresponding algebraic conditions on the totally symmetric contravariant coefficient tensor field P that determines the principal symbol of the matter field equations in terms of the geometric tensor G: the tensor field P must be hyperbolic, time-orientable and energy-distinguishing. Remarkably, these physically necessary conditions on the geometry are mathematically already sufficient to realize all kinematical constructions familiar from Lorentzian geometry, for precisely the same structural reasons. This we were able to show employing a subtle interplay of convex analysis, the theory of partial differential equations and real algebraic geometry. In the second part of this thesis, we then explore general properties of any hyperbolic, time-orientable and energy-distinguishing tensorial geometry. Physically most important are the construction of freely falling non-rotating laboratories, the appearance of admissible modified dispersion relations to particular observers, and the identification of a mechanism that explains why massive particles that are faster than some massless particles can radiate off energy until they are slower than all

  2. Tensorial spacetime geometries carrying predictive, interpretable and quantizable matter dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Rivera Hernandez, Sergio

    2012-02-15

    Which tensor fields G on a smooth manifold M can serve as a spacetime structure? In the first part of this thesis, it is found that only a severely restricted class of tensor fields can provide classical spacetime geometries, namely those that can carry predictive, interpretable and quantizable matter dynamics. The obvious dependence of this characterization of admissible tensorial spacetime geometries on specific matter is not a weakness, but rather presents an insight: it was Maxwell theory that justified Einstein to promote Lorentzian manifolds to the status of a spacetime geometry. Any matter that does not mimick the structure of Maxwell theory, will force us to choose another geometry on which the matter dynamics of interest are predictive, interpretable and quantizable. These three physical conditions on matter impose three corresponding algebraic conditions on the totally symmetric contravariant coefficient tensor field P that determines the principal symbol of the matter field equations in terms of the geometric tensor G: the tensor field P must be hyperbolic, time-orientable and energy-distinguishing. Remarkably, these physically necessary conditions on the geometry are mathematically already sufficient to realize all kinematical constructions familiar from Lorentzian geometry, for precisely the same structural reasons. This we were able to show employing a subtle interplay of convex analysis, the theory of partial differential equations and real algebraic geometry. In the second part of this thesis, we then explore general properties of any hyperbolic, time-orientable and energy-distinguishing tensorial geometry. Physically most important are the construction of freely falling non-rotating laboratories, the appearance of admissible modified dispersion relations to particular observers, and the identification of a mechanism that explains why massive particles that are faster than some massless particles can radiate off energy until they are slower than all

  3. Do Weapons Facilitate Adolescent Delinquency? An Examination of Weapon Carrying and Delinquency Among Adolescents.

    Science.gov (United States)

    Emmert, Amanda D; Hall, Gina Penly; Lizotte, Alan J

    2018-03-01

    This article examines whether weapon carrying influences the frequency and variety of violent, property, and drug delinquency adolescents commit through fixed-effects analyses of data from the Rochester Youth Development Study (RYDS). We conclude that weapon carrying contributes to violent, substance, and property delinquency, and delinquent behaviors learned during weapon carrying continue to affect substance and property delinquency long after carrying has ceased.

  4. [Ecotourism carrying capacity of Hangzhou Xixi National Wetland Park in China].

    Science.gov (United States)

    Li, Rui; Rong, Liang

    2007-10-01

    In this paper, an integrated estimation on the ecotourism carrying capacity of Hangzhou Xixi National Wetland Park in China was made from the aspects of ecological carrying capacity, spatial carrying capacity, facility carrying capacity, management carrying capacity, and psychological carrying capacity. The results indicated that the tourism carrying capacity of the Park was 4 145 - 6 450 persons per day. The rational distance between man and bird was first adopted to determine the ecotourism carrying capacity of wetland, which provided an effective solution both to fully ensure bird safety and to appropriately develop wetland tourism. The estimation of psychological carrying capacity based on tourist satisfaction degree reflected more objectively the extent the tourist demands satisfied at the planning, construction and management of tour places. Such an integrated estimation method based on the distance between man and bird and the tourist satisfaction degree could be of practical and instructive significances in the planning and management of wetland parks.

  5. Weapon carrying and psychopathic-like features in a population-based sample of Finnish adolescents.

    Science.gov (United States)

    Saukkonen, Suvi; Laajasalo, Taina; Jokela, Markus; Kivivuori, Janne; Salmi, Venla; Aronen, Eeva T

    2016-02-01

    We investigated the prevalence of juvenile weapon carrying and psychosocial and personality-related risk factors for carrying different types of weapons in a nationally representative, population-based sample of Finnish adolescents. Specifically, we aimed to investigate psychopathic-like personality features as a risk factor for weapon carrying. The participants were 15-16-year-old adolescents from the Finnish self-report delinquency study (n = 4855). Four different groups were formed based on self-reported weapon carrying: no weapon carrying, carrying knife, gun or other weapon. The associations between psychosocial factors, psychopathic-like features and weapon carrying were examined with multinomial logistic regression analysis. 9% of the participants had carried a weapon in the past 12 months. Adolescents with a history of delinquency, victimization and antisocial friends were more likely to carry weapons in general; however, delinquency and victimization were most strongly related to gun carrying, while perceived peer delinquency (antisocial friends) was most strongly related to carrying a knife. Better academic performance was associated with a reduced likelihood of carrying a gun and knife, while feeling secure correlated with a reduced likelihood of gun carrying only. Psychopathic-like features were related to a higher likelihood of weapon carrying, even after adjusting for other risk factors. The findings of the study suggest that adolescents carrying a weapon have a large cluster of problems in their lives, which may vary based on the type of weapon carried. Furthermore, psychopathic-like features strongly relate to a higher risk of carrying a weapon.

  6. Sdelki carry trade ne roskosh, a sredstvo nakoplenija / Darius Gecevicius, Dmitri Fokin

    Index Scriptorium Estoniae

    Gecevicius, Darius

    2007-01-01

    Strateegia carry trade kasutamisest valuutaturgudel. Carry trade on tehing, mis enamasti toimub valuutaturul, kus investor laenab raha sisse valuutas, mille intressid on madalamad ning paigutab selle valuutas, kus intressid on kõrgemad. Diagramm

  7. Human Factors Evaluation of the Modular Lightweight Load-Carrying Equipment (MOLLE) System

    National Research Council Canada - National Science Library

    Sampson, James

    2001-01-01

    .... The FEA was used in drafting a new user requirements document and initiating the development of a modular load-carrying system which ultimately became known as the Modular Lightweight Load-carrying Equipment (MOLLE...

  8. Biomechanical, Physiological, and Agility Performance of Soldiers Carrying Loads: A Comparison of the Modular Lightweight Load Carrying Equipment and a Lightning Packs, LLC, Prototype

    Science.gov (United States)

    2016-12-27

    angle, hip angle, and sagittal plane hip moments. In terms of energy harvesting and production during walking, the current weight penalty of carrying...MODULAR LIGHTWEIGHT LOAD CARRYING EQUIPMENT) HUMAN FACTORS ENGINEERING U.S. Army Natick Soldier Research, Development and Engineering Center ATTN...pack type and walking speed at a 0% grade. .......................................................35  vii Table 20: Means (SE) of the mean and

  9. 46 CFR 25.45-2 - Cooking systems on vessels carrying passengers for hire.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Cooking systems on vessels carrying passengers for hire... REQUIREMENTS Cooking, Heating, and Lighting Systems § 25.45-2 Cooking systems on vessels carrying passengers for hire. (a) No fuel may be used in any cooking system on any vessel carrying passengers for hire...

  10. 36 CFR 1005.4 - Commercial passenger-carrying motor vehicles.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Commercial passenger-carrying motor vehicles. 1005.4 Section 1005.4 Parks, Forests, and Public Property PRESIDIO TRUST COMMERCIAL AND PRIVATE OPERATIONS § 1005.4 Commercial passenger-carrying motor vehicles. Passenger-carrying motor...

  11. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

    Science.gov (United States)

    Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

    2012-11-28

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

  12. Introducing carrying capacity-based normalisation in LCA: framework and development of references at midpoint level

    DEFF Research Database (Denmark)

    Bjørn, Anders; Hauschild, Michael Zwicky

    2015-01-01

    carrying capacity-based normalisation references. The purpose of this article is to present a framework for normalisation against carrying capacity-based references and to develop average normalisation references (NR) for Europe and the world for all those midpoint impact categories commonly included....... A literature review was carried out to identify scientifically sound thresholds for each impact category. Carrying capacities were then calculated from these thresholds and expressed in metrics identical to midpoint indicators giving priority to those recommended by ILCD. NR was expressed as the carrying...... ozone formation and soil quality were found to exceed carrying capacities several times.The developed carrying capacity-based normalisation references offer relevant supplementary reference information to the currently applied references based on society’s background interventions by supporting...

  13. Kinetic characteristics of the gait of a musician carrying or not his instrument

    Directory of Open Access Journals (Sweden)

    Carlos Bolli Mota

    2009-01-01

    Full Text Available The integrity of the locomotor system can be compromised by the transport of certain objects, especially when done in an inadequate manner. Due to their weight and size, the transport of musical instruments can contribute to body dysfunctions in musicians who frequently have to carry their instruments, influencing balance andbody posture. Thus, the soil reaction force was investigated during the gait of a musician carrying or not his instrument. Two AMTI (Advanced Mechanical Technologies, Inc. platforms were used for kinetic data acquisition. A total of 40 measurements were obtainedfor gait and balance: 20 without carrying the instrument and 20 while carrying the instrument. The t test showed significant differences between the two situations for all variables analyzed. The results suggest that the locomotor system suffers alterationswhen carrying any kind of load, as was the case here in which the subject carried 7.75% of his own weight.

  14. Rural Settlement Development and Environment Carrying Capacity Changes in Progo River Basin

    OpenAIRE

    Su Ritohardoyo; P Priyono

    2016-01-01

    Generally the broader rural settlement the heavier population pressure on agricultural land. It indicates that carrying capacity of the rural environment threatened lower. The spatial distribution of the threat in a river basin is quite important as one of the river basin management inputs. Therefore, this article aims at exposing result of research about influence rural population growth and rural settlement land changes to environment carrying capacity. This research was carried out in the ...

  15. Infant carrying methods: Correlates and associated musculoskeletal disorders among nursing mothers in Nigeria.

    Science.gov (United States)

    Ojukwu, Chidiebele Petronilla; Anyanwu, Godson Emeka; Anekwu, Emelie Morris; Chukwu, Sylvester Caesar; Fab-Agbo, Chukwubuikem

    2017-10-01

    Infant carrying is an integral part of the mothering occupation. Paucity of data exists on its correlates and associated musculoskeletal injuries. In this study, factors and musculoskeletal injuries associated with infant carrying were investigated in 227 nursing mothers, using a structured questionnaire. 77.1% utilised the back infant carrying methods (ICM). Maternal comfort was the major factor influencing participants' (37.4%) choices of ICMs. Infant's age (p = .000) and transportation means (p = .045) were significantly associated with ICMs. Low back pain (82.8%) and upper back pain (74.9%) were the most reported musculoskeletal discomforts associated with ICMs, especially among women who utilised back ICM. Back ICM is predominantly used by nursing mothers. Impact statement Infant carrying has been associated with increased energy cost and biomechanical changes. Currently, there is a paucity of data on infant carrying-related musculoskeletal injuries. In this study, investigating factors and musculoskeletal injuries associated with infant carrying, the results showed that back infant carrying method is predominantly used by nursing mothers. Age of the infant and mothers' means of transportation were determinant factors of infant carrying methods. Among the several reported infant carrying-related musculoskeletal disorders, low back and upper back pain were the most prevalent, especially among women who utilised the back infant carrying method. There is need for women's health specialists to introduce appropriate ergonomic training and interventions on infant carrying tasks in order to improve maternal musculoskeletal health during the childbearing years and beyond. Further experimental studies on the effects of various infant carrying methods on the musculoskeletal system are recommended.

  16. 46 CFR 35.25-15 - Carrying of excess steam-TB/ALL.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Carrying of excess steam-TB/ALL. 35.25-15 Section 35.25... § 35.25-15 Carrying of excess steam—TB/ALL. It shall be the duty of the chief engineer of any tank vessel to see that a steam pressure is not carried in excess of that allowed by the certificate of...

  17. Specifying the Role of Exposure to Violence and Violent Behavior on Initiation of Gun Carrying: A Longitudinal Test of Three Models of Youth Gun Carrying

    Science.gov (United States)

    Spano, Richard; Pridemore, William Alex; Bolland, John

    2012-01-01

    Two waves of longitudinal data from 1,049 African American youth living in extreme poverty are used to examine the impact of exposure to violence (Time 1) and violent behavior (Time 1) on first time gun carrying (Time 2). Multivariate logistic regression results indicate that (a) violent behavior (Time 1) increased the likelihood of initiation of…

  18. Preliminary research on quantitative methods of water resources carrying capacity based on water resources balance sheet

    Science.gov (United States)

    Wang, Yanqiu; Huang, Xiaorong; Gao, Linyun; Guo, Biying; Ma, Kai

    2018-06-01

    Water resources are not only basic natural resources, but also strategic economic resources and ecological control factors. Water resources carrying capacity constrains the sustainable development of regional economy and society. Studies of water resources carrying capacity can provide helpful information about how the socioeconomic system is both supported and restrained by the water resources system. Based on the research of different scholars, major problems in the study of water resources carrying capacity were summarized as follows: the definition of water resources carrying capacity is not yet unified; the methods of carrying capacity quantification based on the definition of inconsistency are poor in operability; the current quantitative research methods of water resources carrying capacity did not fully reflect the principles of sustainable development; it is difficult to quantify the relationship among the water resources, economic society and ecological environment. Therefore, it is necessary to develop a better quantitative evaluation method to determine the regional water resources carrying capacity. This paper proposes a new approach to quantifying water resources carrying capacity (that is, through the compilation of the water resources balance sheet) to get a grasp of the regional water resources depletion and water environmental degradation (as well as regional water resources stock assets and liabilities), figure out the squeeze of socioeconomic activities on the environment, and discuss the quantitative calculation methods and technical route of water resources carrying capacity which are able to embody the substance of sustainable development.

  19. Review on the Evaluation System of Public Safety Carrying Capacity about Small Town Community

    Institute of Scientific and Technical Information of China (English)

    Ming; SUN; Tianyu; ZHU

    2014-01-01

    Recently,small town community public safety problem has been increasingly highlighted,but its research is short on public safety carrying capacity. Through the investigation and study of community public safety carrying capacity,this paper analyzes the problem of community public safety in our country,to construct index evaluation system of public safety carrying capacity in small town community. DEA method is used to evaluate public safety carrying capacity in small town community,to provide scientific basis for the design of support and standardization theory about small town community in public safety planning.

  20. New insights in the role of working memory in carry and borrow operations

    Directory of Open Access Journals (Sweden)

    Ineke Imbo

    2005-06-01

    Full Text Available The present paper provides a state-of-the-art overview concerning the role of working memory in carry and borrow operations in mental arithmetic. The role of the executive working-memory component is discussed, alongside the contribution of the phonological and visuo-spatial working-memory components. Moreover, a broad view on various carry characteristics (such as the number of carry/borrow operations and the value of the carry and various operations (addition, subtraction, and multiplication is provided. Finally, some ideas for further research are offered.

  1. Concept and Connotation of Water Resources Carrying Capacity in Water Ecological Civilization Construction

    Science.gov (United States)

    Chao, Zhilong; Song, Xiaoyu; Feng, Xianghua

    2018-01-01

    Water ecological civilization construction is based on the water resources carrying capacity, guided by the sustainable development concept, adhered to the human-water harmony thoughts. This paper has comprehensive analyzed the concept and characteristics of the carrying capacity of water resources in the water ecological civilization construction, and discussed the research methods and evaluation index system of water carrying capacity in the water ecological civilization construction, finally pointed out that the problems and solutions of water carrying capacity in the water ecological civilization construction and put forward the future research prospect.

  2. 42 CFR 71.56 - African rodents and other animals that may carry the monkeypox virus.

    Science.gov (United States)

    2010-10-01

    ... the monkeypox virus. 71.56 Section 71.56 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND... and other animals that may carry the monkeypox virus. (a) What actions are prohibited? What animals... transmitting or carrying the monkeypox virus. Such products include, but are not limited to, fully taxidermied...

  3. Free vibrations of a multi-span Timoshenko beam carrying multiple ...

    Indian Academy of Sciences (India)

    natural frequency values and mode shapes for a beam carrying any number of spring masses. Naguleswaran (2002, 2003) obtained the natural frequency values of the beams on up to five resilient supports including ends and carrying several particles by using EBT and obtained a fourth-order determinant equated to zero.

  4. Form and Function of Carrying Tools in Traditional and Contemporary Culture

    Directory of Open Access Journals (Sweden)

    Hendriana Werdhaningsih

    2009-07-01

    Full Text Available The Javanese Traditional Carrying Tools are categorized into two kinds based used of materials: anyaman made of woven bamboo or rattan and the other was made of cloth. The Traditional Javanese Carrying Tools that were made of bamboo/ rattan is actually a kind of container with different shapes. The types of goods that were brought was related to the shapes of the containers, demonstrate the type of interactions between the carrier and the goods. The Traditional Carrying Tools made of cloth have the flexibility in terms of being the containers of the carried goods. Selendang is used to carry goods, including the bamboo/ rattan containers and to carry babies. It can be used rumpled and straightened depends on the technical needs of carrying tools preferred by the user. In contemporary culture, the form and design of carrying tools more less construct by fashion and trends besides those practical used. Some product are being 'classic', some other are being 'fad'. Both products, traditional and contemporary have their own style, uniqueness, and own context. Analyzing both in design point of view is important as evaluation process, to finding new problems that will be starting point to create new products. Indonesia is well known for its abundant richness in traditions, which include the culture, the art, and the traditional products. Such treasure of traditions can inspire the development and invention of various kinds of artwork and current products.

  5. 33 CFR 151.33 - Certificates needed to carry Category C Oil-like NLS.

    Science.gov (United States)

    2010-07-01

    ... Inspection endorsed to allow the NLS to be carried in that cargo tank, and if the ship engages in a foreign... unless the ship has a Certificate of Inspection endorsed to allow the NLS to be carried in that cargo... Environmental Protection to the Antarctic Treaty as it Pertains to Pollution from Ships Noxious Liquid Substance...

  6. Gun Cultures or Honor Cultures? Explaining Regional and Race Differences in Weapon Carrying

    Science.gov (United States)

    Felson, Richard B.; Pare, Paul-Philippe

    2010-01-01

    We use the National Violence against Women (and Men) Survey to examine the effects of region and race on the tendency to carry weapons for protection. We find that Southern and Western whites are much more likely than Northern whites to carry guns for self-protection, controlling for their risk of victimization. The difference between Southern and…

  7. Effect of Gun Carrying on Perceptions of Risk Among Adolescent Offenders.

    Science.gov (United States)

    Loughran, Thomas A; Reid, Joan A; Collins, Megan Eileen; Mulvey, Edward P

    2016-02-01

    We observed how perceptions of risks, costs, crime rewards, and violence exposure change as individual gun-carrying behavior changes among high-risk adolescents. We analyzed a longitudinal study (2000-2010) of serious juvenile offenders in Maricopa County, Arizona, or Philadelphia County, Pennsylvania, assessing within-person changes in risk and reward perceptions, and violence exposure as individuals initiated or ceased gun carrying. Despite being associated with heightened exposure to violence, gun carrying was linked to lower perceptions of risks and costs and higher perceived rewards of offending. Gun carrying was not time-stable, as certain individuals both started and stopped carrying during the study. Within-person changes in carrying guns were associated with shifting perceptions of risks, costs, and rewards of crime, and changes in exposure to violence in expected directions. Gun carrying reduces perceptions of risks associated with offending while increasing actual risk of violence exposure. This suggests that there is an important disconnect between perceptions and objective levels of safety among high-risk youths. Gun-carrying decisions may not only be influenced by factors of protection and self-defense, but also by perceptions of risks and reward associated with engaging in crime more generally.

  8. Carry A. Nation: "The Famous and Original Bar Room Smasher" Curriculum Packet.

    Science.gov (United States)

    Kansas State Historical Society, Topeka.

    Carry Nation's personality, religious beliefs, and marriages to Charles Gloyd and, after his death, to David Nation all formed her into the reformer for which she became known. Carry Nation was involved in a variety of reform causes including prohibition, anti-smoking, women's health, and suffrage. Her prohibition reform efforts took place after…

  9. Prediction of bird-day carrying capacity on a staging site: a test of depletion models

    NARCIS (Netherlands)

    Nolet, B.A.; Gyimesi, A.; Klaassen, R.H.G.

    2006-01-01

    1. The carrying capacity of a site for migratory water birds, expressed in bird-days, can be of particular conservation value. Several attempts have been made to model this carrying capacity using ideal free distribution models such as, for instance, depletion models, in which the distribution is

  10. Youths Carrying a Weapon or Using a Weapon in a Fight: What Makes the Difference?

    Science.gov (United States)

    Thurnherr, Judit; Michaud, Pierre-Andre; Berchtold, Andre; Akre, Christina; Suris, Joan-Carles

    2009-01-01

    The objective of this study was to characterize weapon-carrying adolescents and to assess whether weapon carriers differ from weapon users. Data were drawn from a cross-sectional school-based survey of 7548 adolescents aged 16-20 years in Switzerland. Youths carrying a weapon were compared with those who do not. Subsequently, weapon carriers were…

  11. Revisiting the carry-over effects of advertising in franchise industries

    OpenAIRE

    Park, Kwangmin; Jang, SooCheong (Shawn)

    2016-01-01

    Despite prior studies, little has been done to understand the advertising carry-over effect. The purpose of this study is to investigate the heterogeneous attributes of the carry-over effect by focusing on the differences between the franchise and the non-franchise firms. pp.785-800

  12. Adolescents Carrying Handguns and Taking Them to School: Psychosocial Correlates among Public School Students in Illinois.

    Science.gov (United States)

    Williams, Sunyna S.; Mulhall, Peter F.; Reis, Janet S.; DeVille, John O.

    2002-01-01

    Examines psychosocial correlates of adolescents carrying a handgun and taking a handgun to school. Survey participants were approximately 22,000 6th, 8th, and 10th grade public school students from Illinois. Results showed that the strongest correlates of handgun carrying behaviors were variables directly associated with handguns and violence,…

  13. 46 CFR 98.25-5 - How anhydrous ammonia may be carried.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false How anhydrous ammonia may be carried. 98.25-5 Section 98... Anhydrous Ammonia in Bulk § 98.25-5 How anhydrous ammonia may be carried. (a) Anhydrous ammonia shall be..., except as otherwise provided in paragraph (b) of this section. (b) When anhydrous ammonia is to be...

  14. Examining Adolescent Suicidal Behaviors in Relation to Gun Carrying and Bullying

    Science.gov (United States)

    Romero, Andrea; Bauman, Sheri; Ritter, Marissa; Anand, Payal

    2017-01-01

    Guided by the interpersonal theory of suicide, this study examines the associations between gun carrying, bullying, and suicidal behaviors among high school students. Arizona Youth Risk Behavior Surveys were completed by 2,677 students in 2011; 9.0% reported suicide attempt in the past year, 5.5% carried a gun in the past 30 days, 8.5% were…

  15. The qualification requirements for personnel carry out the testing for the pressure equipment materials

    International Nuclear Information System (INIS)

    Wojas, M.; Walczak, M.

    2006-01-01

    The article contains information about qualification requirements for personnel carry out the destructive and non-destructive testing for the pressure equipment materials based on the Directive 97/23/CE(PED). Competence laboratory carry out the testing. The responsibility lies with producer / employer. The producer / employer could elaborate the written practice procedure for qualification and certification testing personnel. (authors)

  16. 36 CFR 702.8 - Use and carrying of food and beverages in Library buildings.

    Science.gov (United States)

    2010-07-01

    ... CONDUCT ON LIBRARY PREMISES § 702.8 Use and carrying of food and beverages in Library buildings. Consumption of food and beverages in Library buildings is prohibited except at point of purchase or other authorized eating places. Under no circumstances may food or beverages be carried to the bookstacks or other...

  17. Isometric arm strength and subjective rating of upper limb fatigue in two-handed carrying tasks.

    Science.gov (United States)

    Li, Kai Way; Chiu, Wen-Sheng

    2015-01-01

    Sustained carrying could result in muscular fatigue of the upper limb. Ten male and ten female subjects were recruited for measurements of isometric arm strength before and during carrying a load for a period of 4 minutes. Two levels of load of carrying were tested for each of the male and female subjects. Exponential function based predictive equations for the isometric arm strength were established. The mean absolute deviations of these models in predicting the isometric arm strength were in the range of 3.24 to 17.34 N. Regression analyses between the subjective ratings of upper limb fatigue and force change index (FCI) for the carrying were also performed. The results indicated that the subjective rating of muscular fatigue may be estimated by multiplying the FCI with a constant. The FCI may, therefore, be adopted as an index to assess muscular fatigue for two-handed carrying tasks.

  18. Environmental sustainability control by water resources carrying capacity concept: application significance in Indonesia

    Science.gov (United States)

    Djuwansyah, M. R.

    2018-02-01

    This paper reviews the use of Water Resources carrying capacity concept to control environmental sustainability with the particular note for the case in Indonesia. Carrying capacity is a capability measure of an environment or an area to support human and the other lives as well as their activities in a sustainable manner. Recurrently water-related hazards and environmental problems indicate that the environments are exploited over its carrying capacity. Environmental carrying capacity (ECC) assessment includes Land and Water Carrying Capacity analysis of an area, suggested to always refer to the dimension of the related watershed as an incorporated hydrologic unit on the basis of resources availability estimation. Many countries use this measure to forecast the future sustainability of regional development based on water availability. Direct water Resource Carrying Capacity (WRCC) assessment involves population number determination together with their activities could be supported by available water, whereas indirect WRCC assessment comprises the analysis of supply-demand balance status of water. Water resource limits primarily environmental carrying capacity rather than the land resource since land capability constraints are easier. WRCC is a crucial factor known to control land and water resource utilization, particularly in a growing densely populated area. Even though capability of water resources is relatively perpetual, the utilization pattern of these resources may change by socio-economic and cultural technology level of the users, because of which WRCC should be evaluated periodically to maintain usage sustainability of water resource and environment.

  19. State Gun Law Environment and Youth Gun Carrying in the United States.

    Science.gov (United States)

    Xuan, Ziming; Hemenway, David

    2015-11-01

    Gun violence and injuries pose a substantial threat to children and youth in the United States. Existing evidence points to the need for interventions and policies for keeping guns out of the hands of children and youth. (1) To examine the association between state gun law environment and youth gun carrying in the United States, and (2) to determine whether adult gun ownership mediates this association. This was a repeated cross-sectional observational study design with 3 years of data on youth gun carrying from US states. The Youth Risk Behavior Survey comprises data of representative samples of students in grades 9 to 12 from biennial years of 2007, 2009, and 2011. We hypothesized that states with more restrictive gun laws have lower rates of youth gun carrying, and this association is mediated by adult gun ownership. State gun law environment as measured by state gun law score. Youth gun carrying was defined as having carried a gun on at least 1 day during the 30 days before the survey. In the fully adjusted model, a 10-point increase in the state gun law score, which represented a more restrictive gun law environment, was associated with a 9% decrease in the odds of youth gun carrying (adjusted odds ratio [AOR], 0.91 [95% CI, 0.86-0.96]). Adult gun ownership mediated the association between state gun law score and youth gun carrying (AOR, 0.94 [ 95% CI, 0.86-1.01], with 29% attenuation of the regression coefficient from -0.09 to -0.07 based on bootstrap resampling). More restrictive overall gun control policies are associated with a reduced likelihood of youth gun carrying. These findings are relevant to gun policy debates about the critical importance of strengthening overall gun law environment to prevent youth gun carrying.

  20. Physical and emotional health problems experienced by youth engaged in physical fighting and weapon carrying.

    Directory of Open Access Journals (Sweden)

    Sophie D Walsh

    Full Text Available Then aims of the current study were 1 to provide cross-national estimates of the prevalence of physical fighting and weapon carrying among adolescents aged 11-15 years; (2 To examine the possible effects of physical fighting and weapon carrying on the occurrence of physical (medically treated injuries and emotional health outcomes (multiple health complaints among adolescents within the theoretical framework of Problem Behaviour Theory. 20,125 adolescents aged 11-15 in five countries (Belgium, Israel, USA, Canada, FYR Macedonia were surveyed via the 2006 Health Behaviour in School Aged Children survey. Prevalence was calculated for physical fighting and weapon carrying along with physical and emotional measures that potentially result from violence. Regression analyses were used to quantify associations between violence/weapon carrying and the potential health consequences within each country. Large variations in fighting and weapon carrying were observed across countries. Boys reported more frequent episodes of fighting/weapon carrying and medically attended injuries in every country, while girls reported more emotional symptoms. Although there were some notable variations in findings between different participating countries, increased weapon carrying and physical fighting were both independently and consistently associated with more frequent reports of the potential health outcomes. Adolescents engaging in fighting and weapon carrying are also at risk for physical and emotional health outcomes. Involvement in fighting and weapon carrying can be seen as part of a constellation of risk behaviours with obvious health implications. Our findings also highlight the importance of the cultural context when examining the nature of violent behaviour for adolescents.

  1. Glove powder's carrying capacity for latex protein: analysis using the ASTM ELISA test.

    Science.gov (United States)

    Beezhold, D; Horton, K; Hickey, V; Daddona, J; Kostyal, D

    2003-01-01

    Glove donning powders carry latex proteins and disperse them into the workplace environment. We have used the ASTM D6499 ELISA to quantify the amount of latex antigen bound to and carried by glove powders. We could differentiate between a small amount of protein actually bound to the powders and a larger amount carried by the powder. Enhanced binding of a major allergen, Hev b 5, to the starch powders was demonstrated by Western blot. The D6499 ELISA is able to measure total latex antigen, soluble and powder bound, simultaneously without the need to centrifuge the samples.

  2. On-line measurements of liquid carry-over from scrubbers using radioactive tracers

    Energy Technology Data Exchange (ETDEWEB)

    Haugan, A; Hassfjell, S [Institute for Energy Technology, Kjeller (Norway); Finborud, A [Mator, Porsgrunn (Norway)

    2004-07-01

    A method to measure liquid carry-over from scrubbers using gamma-emitting tracers is described and results from field tests at two onshore installations are presented. One water/1,2-ethanediol (MEG) and two hydrocarbon liquid (condensate) tracers have been used in the tests. One of the condensate tracers deposited to some extent inside the process pipe, while the other had a too high vapor pressure. The water/MEG tracer showed no MEG carry-over while the carry-over of MEG was documented to be considerable. (author)

  3. On-line measurements of liquid carry-over from scrubbers using radioactive tracers

    International Nuclear Information System (INIS)

    Haugan, A.; Hassfjell, S.; Finborud, A.

    2004-01-01

    A method to measure liquid carry-over from scrubbers using gamma-emitting tracers is described and results from field tests at two onshore installations are presented. One water/1,2-ethanediol (MEG) and two hydrocarbon liquid (condensate) tracers have been used in the tests. One of the condensate tracers deposited to some extent inside the process pipe, while the other had a too high vapor pressure. The water/MEG tracer showed no MEG carry-over while the carry-over of MEG was documented to be considerable. (author)

  4. Impact of Flexibility Options on Grid Economic Carrying Capacity of Solar and Wind: Three Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Denholm, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Novacheck, Joshua [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jorgenson, Jennie [National Renewable Energy Lab. (NREL), Golden, CO (United States); O' Connell, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-12-01

    In this study, we attempt to quantify the benefits of various options of grid flexibility by measuring their impact on two measures: economic carrying capacity and system costs. Flexibility can increase economic carrying capacity and reduce overall system costs. In some cases, options that provide a limited increase in economic carrying capacity can provide significant operational savings, thus demonstrating the need to evaluate flexibility options using multiple metrics. The value of flexibility options varies regionally due to different generation mixes and types of renewables. The more rapid decline in PV value compared to wind makes PV more dependent on adding flexibility options, including transmission and energy storage.

  5. Quantifying spatially derived carrying capacity occupation: Framework for characterisation modelling and application to terrestrial acidification

    DEFF Research Database (Denmark)

    Bjørn, Anders; Margni, M.; Bulle, C.

    *year. This metric resembles that of the ecological footprint method and may be compared to the availability of land or water. The framework was applied to the terrestrial acidification impact category. The geochemical steady-state model PROFILE was used to quantify carrying capacities as deposition levels......The popularity of the ecological footprint method and the planetary boundaries concept shows an increasing interest among decision makers in comparing environmental impacts to carrying capacities of natural systems. Recently carrying capacity-based normalisation references were developed for impact...

  6. Correlates of Weapon Carrying in School among Adolescents in Three Countries

    Czech Academy of Sciences Publication Activity Database

    Stickley, A.; Koyanagi, A.; Koposov, R.; Blatný, Marek; Hrdlička, M.; Schwab-Stone, M.; Ruchkin, V.

    2015-01-01

    Roč. 39, č. 1 (2015), s. 99-108 ISSN 1945-7359 Institutional support: RVO:68081740 Keywords : adolescent * Czech Republic * Russia * United States * weapon carrying Subject RIV: AN - Psychology Impact factor: 1.270, year: 2015

  7. Information technologies in carrying out monitoring comparisons of pedagogical higher education institutions

    Directory of Open Access Journals (Sweden)

    Вадим Валерьевич Гриншкун

    2014-12-01

    Full Text Available In article various approaches to use of information technologies when carrying out monitoring researches of higher educational institutions are described. Results of researches are considered on the example of indicators of pedagogical university.

  8. 46 CFR 167.60-15 - Manning and persons allowed to be carried.

    Science.gov (United States)

    2010-10-01

    ... PUBLIC NAUTICAL SCHOOL SHIPS Certificates of Inspection § 167.60-15 Manning and persons allowed to be carried. The Officer in Charge, Marine Inspection, shall specify in the Certificate of Inspection the...

  9. Temperature dependences of growth rates and carrying capacities of marine bacteria depart from metabolic theoretical predictions

    KAUST Repository

    Huete-Stauffer, Tamara Megan; Arandia-Gorostidi, Nestor; Dí az-Pé rez, Laura; Moran, Xose Anxelu G.

    2015-01-01

    Using the metabolic theory of ecology (MTE) framework, we evaluated over a whole annual cycle the monthly responses to temperature of the growth rates (μ) and carrying capacities (K) of heterotrophic bacterioplankton at a temperate coastal site. We

  10. Geometry of carrying simplices of 3-species competitive Lotka–Volterra systems

    International Nuclear Information System (INIS)

    Baigent, Stephen

    2013-01-01

    We investigate the existence, uniqueness and Gaussian curvature of the invariant carrying simplices of 3 species autonomous totally competitive Lotka–Volterra systems. Explicit examples are given where the carrying simplex is convex or concave, but also where the curvature is not single-signed. Our method monitors the curvature of an evolving surface that converges uniformly to the carrying simplex, and generally relies on establishing that the Gaussian image of the evolving surface is confined to an invariant cone. We also discuss the relationship between the curvature of the carrying simplex near an interior fixed point and its Split Lyapunov stability. Finally we comment on extensions to general Lotka–Volterra systems that are not competitive. (paper)

  11. Carrying capacities for nature parks as engines for sustainable regional development

    DEFF Research Database (Denmark)

    Brandt, Jesper; Holmes, Esbern

    as a departure for the comparison of the protectional conditions for the parks. Many other aspects of the nature and social carrying capacities however also constitute important conditions for the park management. Increasing emphasis on visitor experience is not only a challenge for the nature protection......Growth in the number of visitors is an upcoming problem in nature parks. Nature parks are at the same time facing increasing demand, falling public appropriations and receding focus on their conservation functions. To ensure a balancing of nature protection and economic utilization the concept...... of carrying capacity has received increasing attention among park-authorities all over the world. A comparative analysis of conditions and initiatives related to visitor/nature carrying capacities in 8 nature parks in the Baltic region has been carried out. All the parks are candidates for recognition...

  12. Carrying Capacity Model Applied to Coastal Ecotourism of Baluran National Park, Indonesia

    Science.gov (United States)

    Armono, H. D.; Rosyid, D. M.; Nuzula, N. I.

    2017-07-01

    The resources of Baluran National Park have been used for marine and coastal ecotourism. The increasing number of visitors has led to the increasing of tourists and its related activities. This condition will cause the degradation of resources and the welfare of local communities. This research aims to determine the sustainability of coastal ecotourism management by calculating the effective number of tourists who can be accepted. The study uses the concept of tourism carrying capacity, consists the ecological environment, economic, social and physical carrying capacity. The results of the combined carrying capacity analysis in Baluran National Park ecotourism shows that the number of 3.288 people per day (151.248 tourists per year) is the maximum number of accepted tourists. The current number of tourist arrivals is only 241 people per day (87.990 tourists per year) which is far below the carrying capacity.

  13. Modifications carried out in Heavy Water Plant, Tuticorin for maximising productivity (Paper No. 1.6)

    International Nuclear Information System (INIS)

    Periakaruppan, M.; Sunderesan, S.; Chellapandi, D.

    1992-01-01

    Many modifications have been carried out in Heavy Water Plant, Tuticorin, after commissioning of the plant in July 1978. During the initial 4/5 years many teething problems were faced and they have been tackled effectively with suitable modifications which resulted in sustained production from the year 1984 onwards. In this paper some modifications carried out and changes in operational procedures adopted which resulted in achieving sustained production year after year since 1984 are described. (author)

  14. Review of the Main Activities Carried out by the CSN in the Last Five Years

    International Nuclear Information System (INIS)

    2006-01-01

    Nearing the time to finalise a new phase for the Consejo de Seguridad Nuclear, it is time to make a brief account of the main activities carried out over the past five years. During this period, one in which the CSN celebrated its 25th Anniversary, the organisation has served a social demand in a modernisation and adjustment process, followed by the continuous improvement process which throughout its history the former management, teams have carried out with great stamina and dedication. (Author)

  15. Carry-Over Effects on the Annual Cycle of a Migratory Seabird: an Experimental Study

    OpenAIRE

    Fayet, Annette; Freeman, R; Shoji, A; Kirk, HL; Padget, O; Perrins, CM; Guilford, T

    2016-01-01

    1. Long-lived migratory animals must balance the cost of current reproduction with their own condition ahead of a challenging migration and future reproduction. In these species, carry-over effects, which occur when events in one season affect the outcome of the subsequent season, may be particularly exacerbated. However, how carry-over effects influence future breeding outcomes and whether (and how) they also affect behaviour during migration and wintering is unclear. 2. Here we inve...

  16. Works carried out in the south of Cerro Largo district. Uranium prospection programme. Preliminary report

    International Nuclear Information System (INIS)

    Goso, H.

    1978-01-01

    During the carried out work of radimetric preliminary Investigation in the northeast of the uraniferous country were detected radimetric anonalias which are associated to the formation San Gregorio and Tres Islas. Later the works of prospection ratified those anomalies to which they defined in the environs other anomalies. The studies of revision of these conducted anomalies they took to conclude the necessity to carry out a detailed study of the area to that district was denominated Cerro Largo Sur

  17. Reproductive and life cycle strategies in egg-carrying cyclopoid and free-spawning calanoid copepods

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Sabatini, Marian

    1994-01-01

    Egg-carrying cyclopoid copepods have lower fecundity and feeding rates, and longer egg hatching times, than free-spawning calanoid copepods. Simple demographic considerations suggest that the lower feeding and fecundity of egg-carrying cyclopoids are adaptations to the potentially elevated...... mortality of ovigerous females, while the shorter egg hatching time and higher feeding and fecundity rates found in free-spawning calanoid copepods represent adaptations to the very high mortality rates experienced by suspended eggs....

  18. Carrying capacity of Peucang Island for ecotourism management in Ujung Kulon National Park

    Science.gov (United States)

    Wiyono, K. H.; Muntasib, E. K. S. H.; Yulianda, F.

    2018-05-01

    Peucang Island is one of island in Ujung Kulon National Park (UKNP), appointed as priority area and welcome area for tourism. This research aimed to calculate the carrying capacity of Peucang Island for ecotourism development (Study sites of this research are Karang Copong jungle trail and 8 sites of Peucangs beach). This research used observation method (wildlife exploration, measure the lenght of jungle track, and measure 10 parameters of beach), literature study and and interview method to collect data. The data of jungle track analyzed use Cifuentes’s formula. The result showed that Karang Copong jungle trekking had 20,000 visitors/day for Physical Carrying Capacity (PCC), 4 838 visitors/day for Real Carrying Capacity (RCC), and 6 visitors/day for Efective Carrying Capacity (ECC). Observation of biological aspect showed that there were some damages of vegetation along the track, and the changes in animal behavior. The data of beach carrying capacity analyzed use Yulianda’s formula that measured with the suitability map approach. Based on the suitability map, two beaches were classified in suitable category, while six beaches) were classified in highly suitable category for tourism activities. All of the beaches had different number of carrying capacity, specifically there are 70 visitors/day in highly suitable beach and 27 visitors/day in suitable beach. The number of visitor nowadays still not exceed from carrying capacity number of PCC, RCC of jungle trails and carrying capacity of the beach area, but the number has exceeded from the ECC numbers.

  19. An apparatus for separating and continuously recovering a particulate material carried by a gas stream

    International Nuclear Information System (INIS)

    Becker, W.R.; Dada, A.G.; Dehollander, W.R.; Sloat, R.J.

    1974-01-01

    Description is given of an apparatus adapted to separate and recover a particulate material carried by hot corrosive gases. The apparatus comprises a flow-channel connected to a gas stream source carrying a particulate material, a first and second tubes connected to said flow-channel, filtrating devices, recovery containers and flow-restricting valves. This can be applied to the recovery of uranium oxides generated by flame reactions [fr

  20. Quadruped robots for nuclear facilities. Development of cooperative carrying and unloading functions

    International Nuclear Information System (INIS)

    2016-01-01

    As the Fukushima Daiichi Nuclear Power Station (hereafter refers to as 1F) became the high dose environment by the Great East Japan Earthquake, remotely operated robots were required in order to reduce workers' radiation exposure. We developed a quadruped robot to walk the stairs and narrow passages with carrying burdens such as investigation tools. This robot investigated water leakage from vent pipes at underground of 1F unit 2. There are various works towards the decommissioning such as measuring doses of radiation, cutting pipes, connecting wires and more. It is desirable to carry various work tools and to unload them at destinations with remotely operated robots. To this end, we have developed carrying and unloading functions of the robot. In addition, we have developed cooperative carrying functions that two quadruped robots carry and unload a burden which is too long or heavy for individual robot. As a result, it was realized that two robots carried the pipe of 48 kg while getting over a step of 100 mm and unloading it at a destination. (author)

  1. Sensitivity of the speed evaluation tests of carrying the ball in youth soccer players

    Directory of Open Access Journals (Sweden)

    Rakojević Bojan

    2016-01-01

    Full Text Available This research is aimed at examining sensitivity of the speed evaluation tests while carrying the ball. The research included 76 male examinees, aged 17 years (+/- 6 months, who were divided into two qualitatively different subgroups. For determining the speed while carrying the ball, the tests of M type of carrying the ball between cones and slalom ball carrying with a pass were performed. The obtained results proved that the examinees from the group of more successful soccer players (Group 1 scored better on the applied tests when compared to the results of the group consisting of the soccer players from lower ranked clubs and who are not national team members (Group 2. High values of the result homogeneity in the two groups (for the Groups 1 and 2 it was 75% and 68.75% respectively lead to the conclusion that this ability is essential characteristics of young soccer players. The coefficient of discrimination of 0.269 for the results of M type test and 0.197 for the results of the test of carrying the ball with a pass indicate that the results of the two tests provide possibility to qualitatively distinguish youth players. Therefore, it can be concluded that as a technical element, carrying the ball significantly affects the quality of players' performance.

  2. [Knowledge, attitudes, and practices about Carrión's disease in rural Ancash, Peru].

    Science.gov (United States)

    Llerena Luna, Carolina; Schweig Groisman, Maggie; Ugarte-Gil, César Augusto

    2013-05-01

    To assess knowledge, attitudes, and practices about Carrión's disease (bartonellosis) in rural communities with a history of epidemic outbreaks. A cross-sectional survey study was conducted in the communities of Huaripampa, Orcosh, and Opayaco (Ancash, Peru) in July 2010, to assess knowledge, attitudes, and practices about Carrión's disease. Interviewees were aged >18 years and had resided in the community for at least one year. A total of 276 residents were surveyed; 36.6% were men, and 72.5% had not heard of Carrión's disease. Of those familiar with it, most (38.7%) said that it spreads through bites, and 26% did not know how it spreads. Regarding actions to take if Carrión's disease develops, 69.3% of respondents said they would go to a health center and over half reported having recommended preventive practices to relatives or acquaintances in the past. Even though these three communities have a history of Carrión's disease, their inhabitants did not demonstrate adequate knowledge, attitudes, or practices for preventing it. In view of this, and given that this illness has cyclical outbreaks, it is imperative to design and implement a program to educate residents of these communities-focusing on the role of habits and customs-about how to prevent Carrión's disease, as well as the region's other main endemic diseases.

  3. Estimation of carrying angle based on CT images in preoperative surgical planning for cubitus deformities

    International Nuclear Information System (INIS)

    Park, Shinsuk; Kim, Eugene

    2009-01-01

    Conventionally, the carrying angle of the elbow is measured using simple two-dimensional radiography or goniometry, which has questionable reliability. This study proposes a novel method for estimating carrying angles using computed tomography that can enhance the reliability of the angle measurement. Data of CT scans from 25 elbow joints were processed to build segmented three-dimensional models. The cross-sectional centerlines of the ulna and the humerus were traced from the 3D models, and the angle between 2 vectors formed from the centerlines of the humerus and the ulna was defined as the 'three-dimensional carrying angle.' These angles were compared with those measured by simple radiograph. Two cases of angular deformity were underwent surgery based on this preoperative surgical planning, and the postoperative 3D carrying angles were evaluated using the proposed method. The mean value of the calculated three-dimensional carrying angle was 20.7deg±3.61, while it was 16.3deg±3.21 based on simple radiography without statistical difference. Based on the 3D carrying angle estimations, 2 surgical cases of cubitus deformities were planned by comparison with the normal contra-lateral elbow. Postoperative angle estimations confirmed that the corrected angles were nearly identical to the planned angles for both cases. The results of this study showed that the carrying angle can be accurately estimated using three-dimensional CT and that the proposed method is useful in evaluating deformities of the elbow with high reliability. (author)

  4. Occurrence of Enterobacter hormaechei carrying blaNDM-1 and blaKPC-2 in China.

    Science.gov (United States)

    Yang, Biwei; Feng, Yu; McNally, Alan; Zong, Zhiyong

    2018-02-01

    Three carbapenem-resistant clinical isolates of the Enterobacter cloacae complex (ECC) were recovered from different patients in a hospital. All 3 isolates carried 2 carbapenemase genes bla KPC-2 and bla NDM-1 . A study was performed to characterize their relatedness and to investigate possible links among the patients. Whole genome sequencing revealed that the isolates were Enterobacter hormaechei and belonged to ST177 of the ECC. There were 19-142 single nucleotide polymorphisms (SNPs) between the isolates, suggesting that the isolates were likely from a central reservoir, which might have existed for some time. bla KPC-2 and bla NDM-1 were carried on 2 different IncF-type plasmids in the isolates. The 3 bla NDM-1 -carrying plasmids were almost identical and were self-transmissible, while the bla KPC-2 -carrying plasmids were only transmissible in the presence of the bla NDM-1 -carrying plasmid. The source of and direct links among them were not identified, suggesting a hospital transmission of a common multidrug resistant strain. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Analysis of Environmental Carrying Capacity with Emergy Perspective of Jeju Island

    Directory of Open Access Journals (Sweden)

    Chanhoon Jung

    2018-05-01

    Full Text Available Jeju Island experienced an approximately 42% increase in energy consumption from 2006 to 2015 and the demand for energy consumption is expected to continue to increase. Thus, Jeju Island is planning a project entitled “Carbon Free Island by 2030” to promote sustainable development and is required to estimate the environmental carrying capacity for future energy demand changes. The purpose of this study was to calculate the emergy inherent in Jeju Island’s energy, materials, and information in 2015 using the emergy analysis method and local characteristics. In addition, this study aimed to estimate the emergy indices to evaluate the environmental carrying capacity for sustainable development in 2005, 2015, and 2030 considering the future energy demand. This study’s outputs provide the environmental carrying capacity with emergy indices, such as the percent renewable (%Renew, emergy yield ratio (EYR, environmental loading ratio (ELR, sustainability index (SI, and carrying capacity of the population (CCP for social and economic activities on Jeju Island, which are expected to be saturated. These findings show regions with heavy tourism require development strategies, including the concept of environmental carrying capacity.

  6. Firearm carrying and concurrent substance use behaviours in a community-based sample of emerging adults.

    Science.gov (United States)

    Buschmann, Robert N; Prochaska, John D; Baillargeon, Jacques G; Temple, Jeff R

    2017-12-01

    This paper examines associations between high-risk gun carrying and substance use in emerging adults (ages 18-22). The coexistence of these high-risk behaviours in a general population of emerging adults can have disastrous consequences. Dating it Safe is an ongoing longitudinal (2010-2016) survey of emerging adults recruited from seven high schools in five south-east Texas-area school districts (current sample n=684). Multiple logistic regression modelling was used to examine the association between past-year use of legal and illegal substances and past-year firearm carrying for a reason other than sport or hunting. 6% of emerging adults carried firearms in the past year, with most (68%) carrying for protection. Use of cocaine, hallucinogens, methamphetamine, ecstasy and prescription medications in the past year, as well as episodic heavy drinking in the past month, was associated with increased risk of carrying a firearm (ppast-year substance use behaviours. These findings extend previous research and suggest directions for further exploration of the clustering of high-risk behaviours in emerging adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Modelling of carrying capacity in National Park - Fruška Gora (Serbia case study

    Directory of Open Access Journals (Sweden)

    Vujko Aleksandra

    2017-03-01

    Full Text Available Negative effects of tourism development in a destination are usually the consequence of the high concentration of tourists, accommodation facilities and the activities that are practiced in a relatively restricted area. One of the most important measures to protect the areas is to calculate the maximum number of tourists that can simultaneously reside in a region, i.e. the determination of the carrying capacity. This paper outlines a method for determining carrying capacity based on zoning of environmental resources and zoning within a region. The paper argues for a return to the idea of identifying maximum appropriate number of users. The main hypothesis of the paper is based on the statement that the development of tourism in Fruška Gora (Mountain National Park in Northern Serbia must be in accordance with the basic principles of sustainability, including the determination of carrying capacity. The main research goal was to show the opinion of local residents about the uncontrolled development of tourism, and to determine the carrying capacity in four sports and recreational zones of the mountain. The carrying capacity of the area is calculated by Lavery and Stanev formulas.

  8. Why do three-wheelers carrying schoolchildren suffer very low fatal crashes?

    Directory of Open Access Journals (Sweden)

    Gaurav Pandey

    2015-03-01

    Full Text Available This paper investigates the possible causes of low fatalities in three-wheelers (autorickshaw carrying schoolchildren in India. The data was collected in the form of First Information Report (FIR from local police stations from 2007 to 2012 and video-graphic surveys were done on four arterial roads running through Ludhiana, Punjab, India. Surveys were also done on one subarterial road near school zone which was used by three-wheelers carrying schoolchildren. The objective of the study was to investigate the hypothesis that drivers behave differently while following or overtaking three-wheelers carrying children. Many researchers have investigated the effect of passengers on the driver of the same vehicle, but there was no evidence of any study which investigated the effect of child passengers on nearby vehicles. It was found that heavy vehicles maintain more gaps while following or overtaking three-wheelers carrying children as compared to those not carrying children. It was also found that this effect is more prominent at speeds higher than 40 km/h. On the other hand lighter vehicles keep the highest lateral and longitudinal gaps to heavy vehicles and three-wheelers without children respectively.

  9. Carrying capacity of U.S. agricultural land: Ten diet scenarios

    Directory of Open Access Journals (Sweden)

    Christian J. Peters

    2016-07-01

    Full Text Available Abstract Strategies for environmental sustainability and global food security must account for dietary change. Using a biophysical simulation model we calculated human carrying capacity under ten diet scenarios. The scenarios included two reference diets based on actual consumption and eight “Healthy Diet” scenarios that complied with nutritional recommendations but varied in the level of meat content. We considered the U.S. agricultural land base and accounted for losses, processing conversions, livestock feed needs, suitability of land for crops or grazing, and land productivity. Annual per capita land requirements ranged from 0.13 to 1.08 ha person-1 year-1 across the ten diet scenarios. Carrying capacity varied from 402 to 807 million persons; 1.3 to 2.6 times the 2010 U.S. population. Carrying capacity was generally higher for scenarios with less meat and highest for the lacto-vegetarian diet. However, the carrying capacity of the vegan diet was lower than two of the healthy omnivore diet scenarios. Sensitivity analysis showed that carrying capacity estimates were highly influenced by starting assumptions about the proportion of cropland available for cultivated cropping. Population level dietary change can contribute substantially to meeting future food needs, though ongoing agricultural research and sustainable management practices are still needed to assure sufficient production levels.

  10. Modification Of Carry-Blair Transport Media For Storage Salmonella typhi

    Directory of Open Access Journals (Sweden)

    Yati Supriatin

    2016-09-01

    Full Text Available The aim of this study was to determine transport media modification as alternative media to replace Carry Blair. One type of transport media that often use to carry faeces specimens suspected to contain Salmonella typhi is Carry-Blair media. Studies have been conducted experimentally by storing Salmonella typhi on alternative transport media with Peptone composition, disodium Phosphate, Sodium chloride, Calcium chloride, which is made using a semi-solid and Carry-Blair as a control. Three variety of storage was done (0 hour,6 hours,9 hours at a temperature 4⁰-8⁰C and then Salmonella typhi was inoculated in Salmonella Shigella Agar using spread plate technique incubated during 24 hours at 37⁰C, counted the number of colonies by the plate count method using the colony counter. The results of ANOVA could be concluded that modification media could be use as alternative media replace Carry-Blair at 6 hours. Based on regression correlation test was assumed that the Salmonella typhi bacteria still life at less than 11 hours 54 minutes.

  11. Categorical and continuous - disentangling the neural correlates of the carry effect in multi-digit addition

    Directory of Open Access Journals (Sweden)

    Dressel Katharina

    2010-11-01

    Full Text Available Abstract Background Recently it was suggested that the carry effect observed in addition involves both categorical and continuous processing characteristics. Methods In the present study, we aimed at identifying the specific neural correlates associated with processing either categorical or continuous aspects of the carry effect in an fMRI study on multi-digit addition. Results In line with our expectations, we observed two distinct parts of the fronto-parietal network subserving numerical cognition to be associated with either one of these two characteristics. On the one hand, the categorical aspect of the carry effect was associated with left-hemispheric language areas and the basal ganglia probably reflecting increased demands on procedural and problem solving processes. Complementarily, the continuous aspect of the carry effect was associated with increased intraparietal activation indicating increasing demands on magnitude processing as well as place-value integration with increasing unit sum. Conclusions In summary, the findings suggest representations and processes underlying the carry effect in multi-digit addition to be more complex and interactive than assumed previously.

  12. Profile of women who carried out smoking cessation treatment: a systematic review.

    Science.gov (United States)

    Pereira, Caroline Figueira; de Vargas, Divane

    2015-01-01

    OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation. METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Biblioteca Virtual em Saúde (BVS), Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute. RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate. CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject.

  13. Profile of women who carried out smoking cessation treatment: a systematic review

    Directory of Open Access Journals (Sweden)

    Caroline Figueira Pereira

    2015-01-01

    Full Text Available OBJECTIVE Analyze the profile of women, in health services, who carry out treatment for smoking cessation. METHODS Systematic review that used the following sources of information: Cummulative Index to Nursing and Allied Health Literature (CINAHL, PubMed, Biblioteca Virtual em Saúde (BVS, Scopus and Web of Science. We included quantitative studies that addressed the characterization of women, in health services, who carried out treatment for smoking cessation, resulting in 12 articles for analysis. The assessment of the methodological quality of the studies was performed using the instrument MAStARI from Joanna Briggs Institute. RESULTS The predominant profile of women who carried out treatment for smoking cessation in health services was composed of white, married, employed, and highly level educated women. Women who carried out the treatment for smoking cessation in specialized services had a more advanced age, were white, were married and had a diagnosis of depression. The quality level of most studies was moderate. CONCLUSIONS The profile of women who carry out treatment for smoking cessation, either in general or specialized health services, is composed of white, married, and highly level educated women. Publications about smoking women are scarce and the lack of Brazilian studies characterizing the profile of women who start treatment for smoking cessation shows the need for studies that explore this subject.

  14. Axisymmetrical separator for separating particulate matter from a fluid carrying medium

    Science.gov (United States)

    Linhardt, Hans D.

    1984-09-04

    A separator for separating particles carried in a fluid carrying medium is disclosed. The separator includes an elongated duct and associated openings incorporated in a solid body. The duct is axisymmetrical relative to its longitudinal axis, and includes a curved wall portion having a curved cross-section taken along the longitudinal axis. An axisymmetrical opening located downstream of the curved wall portion leads from the duct into an axisymmetrical channel which is substantially radially disposed relative to the longitudinal axis. Continuation of the duct downstream of the opening is a discharge portion which is substantially colinear with the longitudinal axis. In operation, a substantial majority of the fluid carrying medium leaves the duct radially through the opening and channel in a state substantially free of particles. A remaining small portion of the fluid carrying medium and a substantial majority of the particles are channelled into the discharge portion by centrifugal forces arising due to travel of the particles along the curved walls. For industrial scale separation of particles from a fluid carrying medium, such as for the clean-up of stack gases, an array of several hundred to several thousand of the separators is provided.

  15. Evaluation of Resources Carrying Capacity in China Based on Remote Sensing and GIS

    Science.gov (United States)

    Liu, K.; Gan, Y. H.; Zhang, T.; Luo, Z. Y.; Wang, J. J.; Lin, F. N.

    2018-04-01

    This paper accurately extracted the information of arable land, grassland (wetland), forest land, water area and construction land, based on 1 : 250000 basic geographic information data. It made model modification of comprehensive CCRR to achieve carrying capacity calculation taking resource quality into consideration. Ultimately it achieved a comprehensive assessment of CCRR status in China. The top ten cities where the status of carrying capacity of resources was overloaded were Wenzhou, Shanghai, Chengdu, Baoding, Shantou, Jieyang, Dongguan, Fuyang, Zhoukou and Handan. The cities were basically distributed in the central and southern areas with convenient transportation and more economically developed areas. Among the cities in surplus status, resources carrying capacity in Hulun Buir was the most abundant, followed by Heihe, Bayingolin Mongol Autonomous Prefecture, Qiqihar, Chifeng and Jiamusi, all of which were located in northeastern China with a small population and plentiful cultivated land.

  16. Generalizability of carry-over effects in the emotional Stroop task.

    Science.gov (United States)

    Waters, Andrew J; Sayette, Michael A; Franken, Ingmar H A; Schwartz, Joseph E

    2005-06-01

    The emotional Stroop task has been the most widely used task to examine attentional bias to emotionally salient stimuli. In one format of this task, words are presented to participants in a mixed randomized or quasi-randomized sequence. Using a mixed smoking Stroop task, we have previously demonstrated that smokers are slower to respond to words which follow smoking-related words than words which follow neutral words. Here we show that this carry-over effect is present in heroin addicts-but not control subjects-in a heroin Stroop task, and in normal subjects in a stress Stroop task. Thus, the effect generalizes to other populations. In addition, an examination of the studies that have collected data from both mixed and blocked formats provides converging evidence for the presence of carry-over effects. We discuss the implications of the carry-over effect for research using the emotional Stroop task.

  17. Carrying an anti-nuclear-power badge in the teaching profession

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The carrying of an anti-nuclear-power badge by a teacher during school hours violates the order to practice reticence in political activities. At the beginning of 1977 some teachers, the plaintiff as well, carried anti-nuclear-power badges, i.e. a round badge with a stylized red sun on a yellow background with the inscription 'Nuclear power - No, thank you'. Following a general direction by the educational authorities, the headmistress forbade plaintiff on 4.11.77 to visibly carry this badge during lessons. This protest having been without success, action was brought with partial success at the Administrative and Higher Administrative Court. The Federal Administrative Court dismissed the case. (orig./HSCH) [de

  18. First Identification of a Patient Colonized With Klebsiella pneumoniae Carrying blaNDM-1 in Taiwan

    Directory of Open Access Journals (Sweden)

    Hua-Shin Wu

    2010-11-01

    Full Text Available New Delhi metallo-β-lactamase 1 (NDM-1 is a novel type of metallo-β-lactamase (MBL. Enterobacteriaceae carrying this NDM-1 encoding gene, blaNDM-1, have been identified worldwide. Bacteria carrying blaNDM-1 are not only resistant to carbapenem, but also highly resistant to many classes of antibiotics, which indicate the importance of prompt identification of these bacteria and implementation of strict infection control measures to prevent their transmission. Here, we report the first identification and management of a patient colonized with Klebsiella pneumoniae carrying blaNDM-1 in Taiwan, who returned from New Delhi where he had been hospitalized for a gun-shot injury.

  19. Trivial dynamics in discrete-time systems: carrying simplex and translation arcs

    Science.gov (United States)

    Niu, Lei; Ruiz-Herrera, Alfonso

    2018-06-01

    In this paper we show that the dynamical behavior in (first octant) of the classical Kolmogorov systems of competitive type admitting a carrying simplex can be sometimes determined completely by the number of fixed points on the boundary and the local behavior around them. Roughly speaking, T has trivial dynamics (i.e. the omega limit set of any orbit is a connected set contained in the set of fixed points) provided T has exactly four hyperbolic nontrivial fixed points in with local attractors on the carrying simplex and local repellers on the carrying simplex; and there exists a unique hyperbolic fixed point in Int. Our results are applied to some classical models including the Leslie–Gower models, Atkinson-Allen systems and Ricker maps.

  20. The effect of the spaceship carrying on the biological characters and sod activity of eggplant

    International Nuclear Information System (INIS)

    Wang Shiheng; Zhang Ya; Zhu Shuijin; Wang Yanfan

    2004-01-01

    The effects of the space shuttle carrying on the growth and biological characters of eggplant SP 1 population were studied. The results showed that the effect of space shuttle carrying on the growth and development of eggplant SP 1 were very significant on the characters such as the plant height, reproductive development, leaf size, fruit length, fruit quality and fruiting rate etc, especially on the plant development and the fruit size, and it is hopeful to select some good eggplant germplasm or cultivars from the population. The SOD activity showed that the SOD level in the mutant-1 plant was one time more than that in control plant, indicating that the space shuttle carrying may increase the expression of some genes and lead to the great change in morphological characters

  1. Performance of women with fibromyalgia in walking up stairs while carrying a load

    Directory of Open Access Journals (Sweden)

    Daniel Collado-Mateo

    2016-02-01

    Full Text Available Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy controls were recruited from a local association. Participants were asked to climb 10 stairs without carrying a load and 10 stairs carrying a load of 5 kg in each hand. Mediolateral trunk tilt was assessed using the “Functional Assessment of Biomechanics (FAB” wireless motion capture device, and the time between steps was assessed via weight-bearing insoles. Results. Trunk tilt in the stair-climbing task carrying a load was significantly higher in women with fibromyalgia when compared to the healthy controls (2.31 (0.63 vs. 1.69 (0.51 respectively. The effect of carrying a load was significantly higher for women with fibromyalgia compared with healthy controls at the intermediate and final part of the task. Discussion. Trunk tilt during stair climbing while carrying a load was higher in women with FM, which could increase the risk of falling. Additionally, women with FM experienced a higher pace slowdown as a consequence of the load, which supports the need of including specific strength and resistance training to physical therapies for this population.

  2. Botanical Composition, Grass Production, and Carrying Capacity of Pasture in Timor Tengah Selatan District

    Directory of Open Access Journals (Sweden)

    V. E. Se’u

    2015-12-01

    Full Text Available This study was conducted to analyze the botanical composition, grass production, carrying capacity, and potential production of nutrients in pasture located in Timor Tengah Selatan Regency. The experiment was conducted from February to July 2013, using field survey method. The botanical composition, grass production and carrying capacity on real condition were analyzed descriptively, while the grass production and carrying capacity based of cutting arrangement were analyzed by using randomized block factorial design with 3 altitude locations (Sub District of Mollo Utara with altitude of 1007 m above sea level; Sub District of Noebeba, 500 m ASL, and Sub District of Amanuban Selatan, 65 m ASL x 2 cutting intervals (1 and 2 month and 5 replications. The results showed that the grass type dominated the pasture in the Sub District of Mollo Utara, while legum type was more dominant in the pasture in the Sub Districts of Noebeba and Amanuban Selatan. The potential production of dry matter grass in Timor Tengah Selatan Regency based on real condition was 150 to 390 kg/ha/yr, this could accommodate 0.24 to 0.63 AU/ha/yr. The arrangement of cutting interval by 1 month in Mollo Utara and 2 months in Noebeba and Amanuban Selatan could increase (P<0.05 grass production and carrying capacity. The potential productions of grass nutrients were higher in Sub District of Mollo Utara, while potential production of grass dry matter was higher in Sub Districts of Noebeba and Amanuban Selatan. It was concluded that grass dry matter potential production and carrying capacity in Timor Tengah Selatan Regency were low. The arrangement of cutting interval could increase grass dry matter potential production, carrying capacity, nutrition production, and quality of nutrition.

  3. Performance of women with fibromyalgia in walking up stairs while carrying a load.

    Science.gov (United States)

    Collado-Mateo, Daniel; Adsuar, José C; Olivares, Pedro R; Dominguez-Muñoz, Francisco J; Maestre-Cascales, Cristina; Gusi, Narcis

    2016-01-01

    Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy controls were recruited from a local association. Participants were asked to climb 10 stairs without carrying a load and 10 stairs carrying a load of 5 kg in each hand. Mediolateral trunk tilt was assessed using the "Functional Assessment of Biomechanics (FAB)" wireless motion capture device, and the time between steps was assessed via weight-bearing insoles. Results. Trunk tilt in the stair-climbing task carrying a load was significantly higher in women with fibromyalgia when compared to the healthy controls (2.31 (0.63) vs. 1.69 (0.51) respectively). The effect of carrying a load was significantly higher for women with fibromyalgia compared with healthy controls at the intermediate and final part of the task. Discussion. Trunk tilt during stair climbing while carrying a load was higher in women with FM, which could increase the risk of falling. Additionally, women with FM experienced a higher pace slowdown as a consequence of the load, which supports the need of including specific strength and resistance training to physical therapies for this population.

  4. Carry-chain propagation delay impacts on resolution of FPGA-based TDC

    International Nuclear Information System (INIS)

    Dong Lei; Yang Junfeng; Song Kezhu

    2014-01-01

    The architecture of carry chains in Field-Programmable Gate Array (FPGA) is introduced in this paper. The propagation delay time of the rising and falling edges in the carry chains are calculated according to the architecture and they are predicted not equal in most cases. Tests show that the measuring results of the propagation delay time in EP3C120F484C8N series FPGA of Altera are in line with the inference. The difference of propagation delay time results in different accuracies of Time-to-Digital Converter (TDC). This phenomenon shall be considered in the design of TDC implemented in FPGA. It can ensure better accuracy. (authors)

  5. Risk-premia, Carry-trade Dynamics, and Economic Value of Currency Speculation

    DEFF Research Database (Denmark)

    Wagner, Christian

    2012-01-01

    In this paper, we derive the dynamics and assess the economic value of currency speculation by formalizing the concept of a trader inaction range. We show that exchange rate returns comprise a time-varying risk-premium and that uncovered interest parity (UIP) holds in a speculative sense. The often......-cited ‘forward bias puzzle’ originates from the omission of the risk-premium in standard UIP tests. Consistent with its popularity among market professionals, the carry-trade strategy can be rationalized as it systematically collects risk-premia, however, the economic value generated by bilateral carry-trades...

  6. EVALUATION OF SHEAR STRENGTH FOR UPPER SLABS OF CAISSON FOUNDATION BASED ON LOAD CARRYING MECHANISM

    Science.gov (United States)

    Hattori, Hisamichi; Tadokoro, Toshiya; Tanimura, Yukihiro; Nishioka, Hidetoshi; Watanabe, Tadatomo; Maruyama, Osamu

    In upper slabs of caisson foundation, a seismic desi gn is difficult with an incr ease in earthquake load. So we carried out loading tests and FEM analysis for upper slabs of caisson foundation. As a result, we proposed a new design method which takes into co nsideration the effective width on the pull out side based on crack pattern of test specimens, which is not considered in the existing design method. Moreover, we proposed a rational design method based on load carrying mechanism for upper slabs of caisson foundation.

  7. Investigation of diversity of plasmids carrying the blaTEM-52 gene

    DEFF Research Database (Denmark)

    Bielak, Eliza Maria; Bergenholtz, Rikke D.; Jørgensen, Mikael Skaanning

    2011-01-01

    OBJECTIVES: To investigate the diversity of plasmids that carry blaTEM-52 genes among Escherichia coli and Salmonella enterica originating from animals, meat products and humans. METHODS: A collection of 22 blaTEM-52-encoding plasmids was characterized by restriction fragment length polymorphism...... of self-transfer to a plasmid-free E. coli recipient. CONCLUSIONS: The blaTEM-52 gene found in humans could have been transmitted on transferable plasmids originating from animal sources. Some of the blaTEM-52 plasmids carry replicons that differ from the classical ones. Two novel replicons were detected...

  8. A Case Study in Carry Trade and Cross Pair Allegiance Switching, Pre and Post 2008

    OpenAIRE

    Brian Twomey

    2015-01-01

    EUR/USD, USD/JPY and the position of EUR/JPY was investigated in this paper using regression analysis with the overarching question where EUR/JPY sits in relation to both pairs and its position in terms of a carry trade. What was determined was EUR/JPY switches allegiance period to period. The carry trade premise is to borrow a low interest rate currency and lend in a high interest rate currency. The low interest rate currency becomes the fund currency while the high interest rate currency be...

  9. Cuttings-carried theory and erosion rule in gas drilling horizontal well

    Directory of Open Access Journals (Sweden)

    Wei Na

    2014-01-01

    Full Text Available In gas horizontal drilling, the gas with cuttings will go through the annulus at high speed which will lead strong erosion to the drill tools. This paper proposes a cuttings-carried theory and modified the critical cuttings-carried model for the gas-solid flow. Meanwhile, the erosive energy is obtained through simulating the gas-solid mixture in different conditions. The study result has positive significance on the determination of reasonable injection volume by optimizing construction parameters of horizontal well in gas drilling.

  10. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

    Science.gov (United States)

    Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

    2013-01-01

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

  11. Carrying Position Independent User Heading Estimation for Indoor Pedestrian Navigation with Smartphones

    Directory of Open Access Journals (Sweden)

    Zhi-An Deng

    2016-05-01

    Full Text Available This paper proposes a novel heading estimation approach for indoor pedestrian navigation using the built-in inertial sensors on a smartphone. Unlike previous approaches constraining the carrying position of a smartphone on the user’s body, our approach gives the user a larger freedom by implementing automatic recognition of the device carrying position and subsequent selection of an optimal strategy for heading estimation. We firstly predetermine the motion state by a decision tree using an accelerometer and a barometer. Then, to enable accurate and computational lightweight carrying position recognition, we combine a position classifier with a novel position transition detection algorithm, which may also be used to avoid the confusion between position transition and user turn during pedestrian walking. For a device placed in the trouser pockets or held in a swinging hand, the heading estimation is achieved by deploying a principal component analysis (PCA-based approach. For a device held in the hand or against the ear during a phone call, user heading is directly estimated by adding the yaw angle of the device to the related heading offset. Experimental results show that our approach can automatically detect carrying positions with high accuracy, and outperforms previous heading estimation approaches in terms of accuracy and applicability.

  12. Construction of a novel lentiviral vector carrying human B-domain ...

    African Journals Online (AJOL)

    ... integration were detected in all cell lines after transfection. A novel lentiviral vector carrying human FVIII³BD was constructed, which was able to transfect different mammalian cell types accompanied by high-level activity. This lentiviral vector may provide a theoretical basis for the gene therapy of patients with hemophilia ...

  13. On the Behaviour of Current-Carrying Wire-Conductors and Bucking of a Column

    DEFF Research Database (Denmark)

    Ganji, S. S.; Barari, Amin; Fereidoon, A.

    2013-01-01

    This paper applies approximate analytical methods namely Iteration Perturbation Method (IPM), variational approach (VA) and Parameter Expanding Method (PEM) to Single-Degree-Of-Freedom (SDOF) nonlinear oscillation systems. Some numerical cases as dynamic behavior of current-carrying wire-conductors...

  14. CEC paper on an overview of activities carried out by the WGCS

    International Nuclear Information System (INIS)

    Guinovart, J.

    1994-01-01

    The paper overviews the activities carried out by the WGCS (Working Group Codes and Standards). Summary of conclusions, established in some reports which were finalized in 1992, are outlined for three sub-groups of activity. Two tables summarize the LWR 1992-93 programs are attached. 2 tabs

  15. 34 CFR 656.5 - What activities may be carried out?

    Science.gov (United States)

    2010-07-01

    ... EDUCATION, DEPARTMENT OF EDUCATION NATIONAL RESOURCE CENTERS PROGRAM FOR FOREIGN LANGUAGE AND AREA STUDIES OR FOREIGN LANGUAGE AND INTERNATIONAL STUDIES General § 656.5 What activities may be carried out? (a... following purposes: (1) Linkage or outreach between foreign language, area studies, and other international...

  16. A device for determination of the electrical potential of a rocket carrying an electron gun

    International Nuclear Information System (INIS)

    Gringauz, K.I.; Musatov, L.S.; Shutte, N.M.; Beliashin, A.P.; Denstchikova, L.I.; Kopilov, V.F.

    1978-01-01

    Data on the principle of operation, sensors and electronics of a device for determination of the electrical potential relative to the surrounding medium of a rocket carrying an electric gun are presented. The device operated successfully on board an Eridan rocket during the ARAKS experiment. (Auth.)

  17. Citizen Science: A Gateway for Innovation in Disease-Carrying Mosquito Management?

    Science.gov (United States)

    Bartumeus, Frederic; Oltra, Aitana; Palmer, John R B

    2018-05-21

    Traditional methods for tracking disease-carrying mosquitoes are hitting budget constraints as the scales over which they must be implemented grow exponentially. Citizen science offers a novel solution to this problem but requires new models of innovation in the public health sector. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Utilization of Wheat Offal-Carried Pineapple Waste in the Diet of ...

    African Journals Online (AJOL)

    Utilization of Wheat Offal-Carried Pineapple Waste in the Diet of West African Dwarf (WAD) Goats. ... Although, the analysis of blood cells (red blood cell, white blood and packed cell volume counts) were significantly different (p<0.05) among the goats fed experimental diets, the counts fell within the normal physiological ...

  19. Process for carrying out a chemical reaction with ionic liquid and carbon dioxide under pressure

    NARCIS (Netherlands)

    Kroon, M.C.; Shariati, A.; Florusse, L.J.; Peters, C.J.; Van Spronsen, J.; Witkamp, G.J.; Sheldon, R.A.; Gutkowski, K.I.

    2006-01-01

    The invention is directed to a process for carrying out a chemical reaction in an ionic liquid as solvent and CO2 as cosolvent, in which process reactants are reacted in a homogeneous phase at selected pressure and temperature to generate a reaction product at least containing an end-product of the

  20. 34 CFR 608.10 - What activities may be carried out under a grant?

    Science.gov (United States)

    2010-07-01

    ... program of teacher education designed to qualify students to teach in a public elementary or secondary school in the State that shall include, as part of the program, preparation for teacher certification... UNIVERSITIES PROGRAM What Kind of Projects Does the Secretary Fund? § 608.10 What activities may be carried out...

  1. From "Thoughts and Prayers" to Practice: Narratives of Faculty Sensemaking during Campus-Carry Policy Enactment

    Science.gov (United States)

    Cradit, Nathaniel W.

    2017-01-01

    The 2007 mass shooting at Virginia Tech is one part of a decades-long increase in the frequency of gun violence on U.S. college and university campuses (Drysdale, Modzeleski, & Simons, 2010; Ferraro, 2015). The events at Virginia Tech also served as a catalyst for the spread of so-called "campus-carry" laws, or acts of state policy…

  2. Towards a strengthening of inspections carried out on pressurised equipment and pipework..

    International Nuclear Information System (INIS)

    Noel, St.

    2010-01-01

    Following the fast presidential election, a major restructuring of the administrative landscape was set in motion. Tasks that historically were the responsibility of the Ministry of Industry are now carried out by the Ministry of Sustainable Development, which in particular is responsible for the whole policy to do with the prevention of technological risks. The General Directorate for the Prevention of Risks (Direction generale de la prevention des risques (DGPR)) of this ministry is now responsible for controlling technological risks, opening up new perspectives in terms of managing accidental risks and offering a new opportunity for an 'integrated' approach, making it possible to deal with an industrial installation in all its facets. Within the DGPR, the Office for the Safety of Industrial Equipment (bureau de la securite des equipements industriels (BSEI)) is responsible for the safety of pressurised equipment, as well as pipes carrying gas, inflammable liquids and chemical products. After a quick presentation of the inspections carried out on this equipment, issues to do with their safety will be dealt with and in particular: - the suitability of inspections carried out in the tight of faults that are likely to occur and develop in the structures; - control of ageing; - management of the quality of new equipment. (author)

  3. Results of the Study of Helminths-Carrying as a Comorbidity in Children with Herpetic Stomatitis

    Directory of Open Access Journals (Sweden)

    E.S. Suerkulov

    2016-09-01

    Full Text Available The paper analyzes the helminths-carrying in children with herpetic stomatitis according to the data of the department of maxillofacial surgery of the National center of mother and child welfare, and determines the relationship of oral diseases with disorders of various parts of the gastrointestinal tract.

  4. Proteinase 3 carries small unusual carbohydrates and associates with αlpha-defensins

    DEFF Research Database (Denmark)

    Zoega, Morten; Ravnsborg, Tina; Højrup, Peter

    2012-01-01

    with carbohydrates at Asn 102 and 147 carrying unusual small moieties indicating heavy processing. Mass spectrometric analysis and immuno blotting revealed strong association of highly purified PR3 with α-defensins and oligomers hereof. Irreversible inhibition of PR3 by α1-antitrypsin did not affect its association...

  5. Aerodynamic Improvements to Cargo Carrying Rail Cars due to Roof Modifications

    Science.gov (United States)

    Condie, Robert; Maynes, Daniel

    2012-11-01

    The aerodynamic drag associated with the transport of commodities by rail is becoming increasingly important as the cost of diesel fuel increases. We provide an assessment of the influence of the roof structure on aerodynamic performance of two dissimilar rail cars, namely automobile carrying cars and coal carrying cars. Currently, the roof material for automobile carrying rail cars is corrugated steel, with the corrugation aligned perpendicular to the direction of travel. Coal cars are currently left uncovered for loading convenience and on the return leg from the power plant are empty. Aerodynamic drag data have been obtained through wind tunnel testing on 1/29 scale models to understand the savings that may be realized by judicious modification to the tops of both these car types. For the automobile-carrying cars, testing is performed for the corrugated and smooth roof configurations. This modification alone has the potential of reducing the car drag coefficient by nominally 25%. A broader study is performed for the coal cars, with data being acquired for coal filled models, empty models, and several cover prototype configurations. The results reveal that implementation of a cover may yield reductions in the aerodynamic drag for both coal filled (nominally 7%) and empty coal cars (nominally 30%).

  6. High-level methodology for carrying out combined red and blue teams

    CSIR Research Space (South Africa)

    Veerasamy, N

    2009-12-01

    Full Text Available This paper proposes a combined Red and Blue Team Methodology to guide the process of carrying out such security auditing and penetration testing tasks. Red and Blue Teams consist of various security auditing and penetration testing tasks which serve...

  7. 46 CFR 153.900 - Certificates and authorization to carry a bulk liquid hazardous material.

    Science.gov (United States)

    2010-10-01

    ... ship must have a Subchapter D or I Certificate of Inspection that is endorsed to allow the cargo tank... requirements for the bulk liquid cargo; and (2) The ship— (i) Has a Certificate of Inspection, Certificate of...) CERTAIN BULK DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS...

  8. 46 CFR 98.30-14 - Requirements for ships carrying NLSs in portable tanks.

    Science.gov (United States)

    2010-10-01

    ... portable tank shall ensure that— (1) The ship's Certificate of Inspection is endorsed with the name of the... condition for endorsement is met. (b) To have a ship's Certificate of Inspection endorsed to allow the... 46 Shipping 4 2010-10-01 2010-10-01 false Requirements for ships carrying NLSs in portable tanks...

  9. Estimating social carrying capacity through computer simulation modeling: an application to Arches National Park, Utah

    Science.gov (United States)

    Benjamin Wang; Robert E. Manning; Steven R. Lawson; William A. Valliere

    2001-01-01

    Recent research and management experience has led to several frameworks for defining and managing carrying capacity of national parks and related areas. These frameworks rely on monitoring indicator variables to ensure that standards of quality are maintained. The objective of this study was to develop a computer simulation model to estimate the relationships between...

  10. An evaluation of the carrying angle of the elbow joint in adolescents

    African Journals Online (AJOL)

    McRoy

    Department of Anatomy and Orthopedics, Sri Lakshmi Narayana Institute of Medical Sciences,. Pondicherry - 605 502 ... forearm deviates laterally from the long axis of the humerus, with the arm extended and the palm ... for elbow reconstruction. Key words: Carrying angle, elbow joint, adolescent, forearm, humerus, ulna ...

  11. Specific experiments carried out in Germany in order to demonstrate the safety of existing structures

    International Nuclear Information System (INIS)

    Krutzik, Norbert

    2002-01-01

    Specific experiments are carried out in Germany in order to demonstrate the safety of existing NPPs. HDR research program includes operational loads testing (pressure test, pressure and temperature test, thermal shock, fatigue); extreme loads (earthquake, aircraft crash, external explosion); internal emergency loads (blowdown, hydrogen combustion, fire, thermal shock, water hammer, condensation loads)

  12. Perceived popularity of adolescents who use weapons in violence and adolescents who only carry weapons.

    Science.gov (United States)

    Wallace, Lacey N

    2017-01-01

    Prior research has found that persistently delinquent youth or more violent youth were less popular than their less delinquent peers (Young, 2013). However, recent research has also found that weapon carrying is associated with being more popular in adolescence (Dijkstra et al., 2010). The present paper examines the perceived popularity of adolescents who carry weapons in comparison to those who both carry and use weapons in acts of violence or threatened violence. Data consist of two waves from the National Longitudinal Study of Adolescent to Adult Health. Analyses use OLS regression with lagged predictors. This paper found no differences in number of friends between weapon carriers and weapon users. However, among both male and female gang members, those who did not use or carry weapons (abstainers) named significantly fewer friends than weapon users. Among females, weapon abstainers both named and were named by significantly more people than weapon users. These differences were not observed for males. Implications of these results and directions for future research are discussed.

  13. Who Carries the Burden of Reproductive Health and AIDS Programs? - Evidence from OECD Donor Countries

    NARCIS (Netherlands)

    H.P. van Dalen (Hendrik)

    2006-01-01

    textabstractThis paper tries to establish who carries the burden in supporting reproductive health and AIDS programs worldwide. The 1994 International Conference of Population and Development (ICPD) in Cairo established goals for the expansion of assistance in matters of reproductive health and

  14. Shape invariant higher-order Bessel-like beams carrying orbital angular momentum

    CSIR Research Space (South Africa)

    Ismail, Y

    2012-09-01

    Full Text Available -1 Journal of Optics September 2012/ Vol. 14 Shape invariant higher-order Bessel-like beams carrying orbital angular momentum Y Ismail1,2, N Khilo3, V Belyi3 and A Forbes1,2 1 School of Physics, University of KwaZulu-Natal, Private Bag X54001...

  15. The Role of RT Carry-Over for Congruence Sequence Effects in Masked Priming

    Science.gov (United States)

    Huber-Huber, Christoph; Ansorge, Ulrich

    2017-01-01

    The present study disentangles 2 sources of the congruence sequence effect with masked primes: congruence and response time of the previous trial (reaction time [RT] carry-over). Using arrows as primes and targets and a metacontrast masking procedure we found congruence as well as congruence sequence effects. In addition, congruence sequence…

  16. Chaotic behavior of current-carrying plasmas in external periodic oscillations

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Noriyasu; Tanaka, Masayoshi; Komori, Akio; Kawai, Yoshinobu

    1989-01-01

    A set of cascading bifurcations and a chaotic state in the presence of an external periodic oscillation are experimentally investigated in a current-carrying plasma. The measured bifurcation sequence leading to chaos, which is controlled by changing plasma densities and the frequencies of external oscillations, is in qualitative agreement with a theory which describes anharmonic systems in periodic fields. (author).

  17. Summary of R and D work carried out in Sri Lanka for the development of RVNRL

    International Nuclear Information System (INIS)

    Karunaratne, S.W.

    1994-01-01

    This paper discusses the advantages of radiation vulcanization of natural rubber latex and research and development carried out in this particular field. It emphasises types of centrifuge latex used, stability of this centrifuged latex, use of sensitizer, effect of leaching, antioxidants, use of low energy electron beam and training and human resources development in this field

  18. DEMON/ANGEL - A SUITE OF PROGRAMS TO CARRY OUT DENSITY MODIFICATION

    NARCIS (Netherlands)

    VELLIEUX, FMDAP; HUNT, JF; ROY, S; READ, RJ

    1995-01-01

    The DEMON/ANGEL suite of computer programs has been developed to carry out density modification by non-crystallographic symmetry-averaging, solvent-flattening and histogram-mapping techniques. This suite consists of programs that allow molecular envelopes to be defined and modified,

  19. 12 CFR 615.5090 - Reduction in carrying value of collateral.

    Science.gov (United States)

    2010-01-01

    ... FISCAL AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Collateral § 615.5090 Reduction in carrying value of collateral. When the bank or Farm Credit Administration determines that a loan did not... withdrawn from collateral until the cause of ineligibility is remedied. When a loan has been classified as a...

  20. E-Books in Academic Libraries: Results of a Survey Carried out in Sweden and Lithuania

    Science.gov (United States)

    Maceviciute, Elena; Wilson, T. D.; Gudinavicius, Arunas; Šuminas, Andrius

    2017-01-01

    Introduction: This paper reports on a study of e-books issues in academic libraries in two European countries representative of small language markets--Sweden and Lithuania. Method: Questionnaire surveys, using the same instrument, were carried out in Swedish and Lithuanian academic libraries. Analysis: Quantitative analysis was performed using…

  1. Research programs in adsorption carried out in the low temperature laboratory of UFRJ (Brazil)

    International Nuclear Information System (INIS)

    Rapp, R.E.

    1981-01-01

    Research programs of gas adsorption in thin films carried out by the low temperature laboratory of UFRJ (Brazil) are reported. These programs were divided in two parts: 1) experiments of adsorption isotherm measurements by the volumetric method and 2) specific heat measurements of adsorbed gases. (L.C.) [pt

  2. Comment on "Invasive Harlequin Ladybird Carries Biological Weapons Against Native Competitors"

    NARCIS (Netherlands)

    Jong, de P.W.; Lenteren, van J.C.; Raak-van den Berg, C.L.

    2013-01-01

    We comment on the implications that Vilcinskas et al. (Reports, 17 May 2013, p. 862) attach to the finding that the exotic, invasive ladybird Harmonia axyridis carries microsporidia to which this species is insensitive but that is lethal to species that are native to the invaded areas. The authors

  3. Evaluation of tests in 4x4 assemblies carried out in Columbia University

    International Nuclear Information System (INIS)

    Pedron, M.Q.

    1989-01-01

    Tests in 4x4 assemblies with BWR characteristics carried out in Columbia University are analysed, using the PANTERA-1P computer code. The experiments aim for measuring fluid, flow and enthalpies in exits of two subchannels, the coldest and hottest using iso kinetic sampling method. (M.C.K.)

  4. Effect of Gamma Radiation on Amino Acid Based Vesicle Carrying Radiosensitizer

    International Nuclear Information System (INIS)

    Nur Ratasha Alia Mohd Rosli; Faizal Mohamed; Muhammad Amir Syafiq Mohd Sah; Irman Abdul Rahman

    2014-01-01

    Vesicles has been developed and studied to be used as a medium to transport radiosensitizer in treating cancer cells by increasing its sensitivity effectively towards the radiation given during radiotherapy. This study was conducted to investigate the effect of gamma radiation on amino acid-based vesicle carrying radiosensitizer. Amino acid based vesicles carrying radiosensitizer were synthesized using sonication method with sodium N-lauroylsarcosinate hydrate and decanol being the primary surfactant, while hydrogen peroxide and sodium hyaluronate as the encapsulated radiosensitizer. The synthesized vesicle was then irradiated at radiation doses equivalent to those given during radiotherapy. Irradiated vesicle carrying radiosensitizer were then characterized using Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and Polarized Light Microscope. Results obtained shows that there were no significant changes in morphology and molecular conformation of the synthesized vesicle after irradiation. Even at higher radiation dose of 100 Gray and 200 Gray, the results remained unchanged. This indicates that the synthesized vesicle carrying radiosensitizer is morphologically and spectroscopically stable even at high radiation doses. (author)

  5. Charged Particle Dynamics in the Magnetic Field of a Long Straight Current-Carrying Wire

    Science.gov (United States)

    Prentice, A.; Fatuzzo, M.; Toepker, T.

    2015-01-01

    By describing the motion of a charged particle in the well-known nonuniform field of a current-carrying long straight wire, a variety of teaching/learning opportunities are described: 1) Brief review of a standard problem; 2) Vector analysis; 3) Dimensionless variables; 4) Coupled differential equations; 5) Numerical solutions.

  6. Management of marine cage aquaculture. Environmental carrying capacity method based on dry feed conversion rate.

    Science.gov (United States)

    Cai, Huiwen; Sun, Yinglan

    2007-11-01

    Marine cage aquaculture produces a large amount of waste that is released directly into the environment. To effectively manage the mariculture environment, it is important to determine the carrying capacity of an aquaculture area. In many Asian countries trash fish is dominantly used in marine cage aquaculture, which contains more water than pellet feed. The traditional nutrient loading analysis is for pellet feed not for trash fish feed. So, a more critical analysis is necessary in trash fish feed culturing areas. Corresponding to FCR (feed conversion rate), dry feed conversion rate (DFCR) was used to analyze the nutrient loadings from marine cage aquaculture where trash fish is used. Based on the hydrodynamic model and the mass transport model in Xiangshan Harbor, the relationship between the water quality and the waste discharged from cage aquaculture has been determined. The environmental carrying capacity of the aquaculture sea area was calculated by applying the models noted above. Nitrogen and phosphorus are the water quality parameters considered in this study. The simulated results show that the maximum nitrogen and phosphorus concentrations were 0.216 mg/L and 0.039 mg/L, respectively. In most of the sea area, the nutrient concentrations were higher than the water quality standard. The calculated environmental carrying capacity of nitrogen and phosphorus in Xiangshan Harbor were 1,107.37 t/yr and 134.35 t/yr, respectively. The waste generated from cage culturing in 2000 has already exceeded the environmental carrying capacity. Unconsumed feed has been identified as the most important origin of all pollutants in cage culturing systems. It suggests the importance of increasing the feed utilization and improving the feed composition on the basis of nutrient requirement. For the sustainable development of the aquaculture industry, it is an effective management measure to keep the stocking density and pollution loadings below the environmental carrying

  7. In vivo characteristics of targeted drug-carrying filamentous bacteriophage nanomedicines

    Directory of Open Access Journals (Sweden)

    Vaks Lilach

    2011-12-01

    Full Text Available Abstract Background Targeted drug-carrying phage nanomedicines are a new class of nanomedicines that combines biological and chemical components into a modular nanometric drug delivery system. The core of the system is a filamentous phage particle that is produced in the bacterial host Escherichia coli. Target specificity is provided by a targeting moiety, usually an antibody that is displayed on the tip of the phage particle. A large drug payload is chemically conjugated to the protein coat of the phage via a chemically or genetically engineered linker that provides for controlled release of the drug after the particle homed to the target cell. Recently we have shown that targeted drug-carrying phage nanomedicines can be used to eradicate pathogenic bacteria and cultured tumor cells with great potentiation over the activity of the free untargeted drug. We have also shown that poorly water soluble drugs can be efficiently conjugated to the phage coat by applying hydrophilic aminoglycosides as branched solubility-enhancing linkers. Results With an intention to move to animal experimentation of efficacy, we tested anti-bacterial drug-carrying phage nanomedicines for toxicity and immunogenicity and blood pharmacokinetics upon injection into mice. Here we show that anti-bacterial drug-carrying phage nanomedicines that carry the antibiotic chloramphenicol conjugated via an aminoglycoside linker are non-toxic to mice and are greatly reduced in immunogenicity in comparison to native phage particles or particles to which the drug is conjugated directly and are cleared from the blood more slowly in comparison to native phage particles. Conclusion Our results suggest that aminoglycosides may serve as branched solubility enhancing linkers for drug conjugation that also provide for a better safety profile of the targeted nanomedicine.

  8. Water Quality Assessment and Determining the Carrying Capacity of Pollution Load Batang Kuranji River

    Science.gov (United States)

    Dewata, I.; Adri, Z.

    2018-04-01

    This study aims to determine the water quality and carrying capacity of pollution load Batang Kuranji River in the headwaters, middle, and downstream. This research is descriptive quantitative parameters of pH, BOD, COD, TSS, and DOES Depictions of river water quality refer to RegulationNo.82/2001, while determination of carrying capacity of pollution load river refers to the Kep Men LHNo.10/2003.The result is Kuranji Batang River water quality upstream region included in either category who meet the quality standard first class ofPP82/2001. TSS concentrations at head waters of 21 mg/L, BOD1,6 mg/L, COD7,99mg/L and DO 7,845 mg/L. While the carrying capacity of pollution load river in upstream region included in both categories namely BOD of 4,4 kg/sec, COD 273,60 kg/sec, TSS906,00kg/sec, and DO parameters of 49.20 kg/sec. Middle region (point 2, 3, and 4) water quality Batang Kuranji River has exceeded the quality standard of 82/2001 for class II and class III. Meanwhile, carrying capacity of pollution load river in area included in ugly category. The calculation is done with application Qual2Kw show that carrying capacity of pollution load river of BOD -857.3 kg/sec, COD -777.40 kg/sec, TSS +9511.5 kg/sec, and DO +69.30 kg/sec.

  9. Assessing the Social Carrying Capacity of Diving Sites in Mabul Island, Malaysia.

    Science.gov (United States)

    Zhang, Liye; Chung, ShanShan

    2015-12-01

    This study has explored social carrying capacity of an underwater environment based on divers' perceived crowding. Two dimensions were assessed, the number of divers seen and the proximity of diver. Data were obtained from a survey of 132 divers dived in Mabul Island, Malaysia during 2013-2014. Photographs depicting four levels of diver number and four levels of diver proximity in different combinations were shown to the respondents for assessing their acceptability. Between the two variables, the "number of divers" was the most influential factor for divers' perceived crowding. Divers would start to feel unacceptably crowded if 8-9 divers were visible to them at one time. Based on this, it is likely that the use level of diving sites in Mabul Island has already exceeded its social carrying capacity. Implications for future research and diving tourism management for Mabul Island are also discussed in the paper.

  10. Clonal spread of blaOXA-72-carrying Acinetobacter baumannii sequence type 512 in Taiwan.

    Science.gov (United States)

    Kuo, Han-Yueh; Hsu, Po-Jui; Chen, Jiann-Yuan; Liao, Po-Cheng; Lu, Chia-Wei; Chen, Chang-Hua; Liou, Ming-Li

    2016-07-01

    This is the first report to show an insidious outbreak of armA- and blaOXA-72-carrying Acinetobacter baumannii sequence type 512 (ST512) at a study hospital in northern Taiwan. Multilocus sequence typing revealed that this was a ST512 clone. All of the isolates with ST512 carried a novel 12,056-bp repGR2 in combination with a repGR12-type plasmid. This plasmid, designated pAB-ML, had one copy of the blaOXA-72 gene that was flanked by XerC/XerD-like sites and conferred resistance to carbapenems. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. Chemical composition shape form and size of suspended solids in the atmosphere carried by rain water

    International Nuclear Information System (INIS)

    Iturbe G, J.L.; Lopez M, B.E.; Torre O, J. De la

    2001-01-01

    The interest of this work is to know about shape form, size and chemical composition of the suspended solids in the atmosphere of Toluca city and which are carried by the rains. The harvest of the samples was carried out during january to november 1999. The separation of the particulate matter from the rain water was realized through centrifugation. The solids were analysed by Scanning Electron Microscopy to know the shape form and size and the chemical composition was determined by X-ray dispersive energy in general form and of some particles individually analysed. The p H was measured to the solutions and the quantification of some dissolved ions by the Icp technique was realized. The results of the solids showed C, O, Na, Mg, Al, Si, S, P, K, Ca, Ti and Fe. Moreover they present sizes which varying from a ten of nanometers until some tens of microns. (Author)

  12. Analysis on economic carrying capacity index of pig breeding in China

    Science.gov (United States)

    Leng, Bi-Bin; Liu, Jia-Ling; Xu, Yue-Feng

    2017-08-01

    In this paper, factor analysis method was employed to analyze and calculate the Gross Domestic Product (GDP) per capita in the last decade, the proportion of research and experiment development (R&D) expenditure equivalent to GDP, urban and rural residents’ pork consumption and explored the scale of Chinese pig breeding on economic carrying capacity index. The result showed that the growth of GDP had led to better techniques and higher field investment, and stronger support like science and technology from the government provided good conditions for large scale of pig breeding. Besides, the substantial increase of pork consumption between rural and urban residents has contributed to the pig breeding in large scale. As a result, the economic carrying capacity index in Chinese pig farming is on the rise.

  13. Assessing the Social Carrying Capacity of Diving Sites in Mabul Island, Malaysia

    Science.gov (United States)

    Zhang, Liye; Chung, ShanShan

    2015-12-01

    This study has explored social carrying capacity of an underwater environment based on divers' perceived crowding. Two dimensions were assessed, the number of divers seen and the proximity of diver. Data were obtained from a survey of 132 divers dived in Mabul Island, Malaysia during 2013-2014. Photographs depicting four levels of diver number and four levels of diver proximity in different combinations were shown to the respondents for assessing their acceptability. Between the two variables, the "number of divers" was the most influential factor for divers' perceived crowding. Divers would start to feel unacceptably crowded if 8-9 divers were visible to them at one time. Based on this, it is likely that the use level of diving sites in Mabul Island has already exceeded its social carrying capacity. Implications for future research and diving tourism management for Mabul Island are also discussed in the paper.

  14. Daniel Alcides Carrión: la teoría unicista

    OpenAIRE

    Salinas, David

    2016-01-01

    La enfermedad de Carrión presenta clásicamente dos fases clínicas: la fiebre de la Oroya y la verruga peruana. La teoría unicista reconoce que ambas formas clínicas pertenecen a la misma enfermedad, la obtención de este conocimiento representó un duro desafío para la ciencia peruana y mundial. A través de un histórico experimento en 1885, Daniel Alcides Carrión obtuvo la evidencia clínica-experimental que sentó las bases de la teoría unicista; el científico diseñó esta teoría solo hasta las h...

  15. Studies on solid-state physics carried out with the Saclay reactor (1962)

    International Nuclear Information System (INIS)

    Herpin, A.

    1962-01-01

    This paper deals only with solid-state physics experiments carried out on outgoing beams: rather than giving a general review of the work performed, if refers to only a few of the most important studies or those nearest completion. These are being made with the experimental beams of the two Saclay reactors EL-2, with a central flux of 10 13 n/cm 2 , and - since 1958 - EL-3, whose central flux is equal ta 10 14 n/cm 2 . The experiments are being carried out by two separate groups of physicists, employing different techniques, namely neutron diffraction using a crystal spectrometer, and inelastic scattering using a time-of-flight spectrometer. (author) [fr

  16. Some aspects of the quality assurance of personnel carrying out finite element analysis

    International Nuclear Information System (INIS)

    Dickenson, P.W.

    1990-01-01

    In this paper, the need to assess the competence of personnel carrying out finite element analysis is emphasised. In carrying out its regulatory role on behalf of the Health and Safety Executive, the Nuclear Installations Inspectorate (NII) must be satisfied that appropriate standards are developed and maintained by the licensee. Since finite element methods have an important bearing on the acceptance of a safety case, it follows that relevant codes should be adequately validated and the personnel applying the code should be competent. Attention is drawn to the work of the Quality Assurance Working Group of the National Agency for Finite Element Methods and Standards (NAFEMS) who are active in this area. The paper also considers the methods that are available to assess the competence of personnel engaged in finite element methods. (author)

  17. Load Carrying Capacity of Metal Dowel Type Connections of Timber Structures

    Science.gov (United States)

    Gocál, Jozef

    2014-12-01

    This paper deals with the load-carrying capacity calculation of laterally loaded metal dowel type connections according to Eurocode 5. It is based on analytically derived, relatively complicated mathematical relationships, and thus it can be quite laborious for practical use. The aim is to propose a possible simplification of the calculation. Due to quite a great variability of fasteners' types and the connection arrangements, the attention is paid to the most commonly used nailed connections. There was performed quite an extensive parametric study focused on the calculation of load-carrying capacity of the simple shear and double shear plane nail connections, joining two or three timber parts of softwood or hardwood. Based on the study results, in conclusion there are presented simplifying recommendations for practical design.

  18. Transfer of stem cells carrying engineered chromosomes with XY clone laser system.

    Science.gov (United States)

    Sinko, Ildiko; Katona, Robert L

    2011-01-01

    Current transgenic technologies for gene transfer into the germline of mammals cause a random integration of exogenous naked DNA into the host genome that can generate undesirable position effects as well as insertional mutations. The vectors used to generate transgenic animals are limited by the amount of foreign DNA they can carry. Mammalian artificial chromosomes have large DNA-carrying capacity and ability to replicate in parallel with, but without integration into, the host genome. Hence they are attractive vectors for transgenesis, cellular protein production, and gene therapy applications as well. ES cells mediated chromosome transfer by conventional blastocyst injection has a limitation in unpredictable germline transmission. The demonstrated protocol of laser-assisted microinjection of artificial chromosome containing ES cells into eight-cell mouse embryos protocol described here can solve the problem for faster production of germline transchromosomic mice.

  19. Influence of the volume ratio of solid phase on carrying capacity of regular porous structure

    Directory of Open Access Journals (Sweden)

    Monkova Katarina

    2017-01-01

    Full Text Available Direct metal laser sintering is spread technology today. The main advantage of this method is the ability to produce parts which have a very complex geometry and which can be produced only in very complicated way by classical conventional methods. Special category of such components are parts with porous structure, which can give to the product extraordinary combination of properties. The article deals with some aspects that influence the manufacturing of regular porous structures in spite of the fact that input technological parameters at various samples were the same. The main goal of presented research has been to investigate the influence of the volume ratio of solid phase on carrying capacity of regular porous structure. Realized tests have indicated that the unit of regular porous structure with lower volume ratio is able to carry a greater load to failure than the unit with higher volume ratio.

  20. Enhanced load-carrying capacity of hairy surfaces floating on water.

    Science.gov (United States)

    Xue, Yahui; Yuan, Huijing; Su, Weidong; Shi, Yipeng; Duan, Huiling

    2014-05-08

    Water repellency of hairy surfaces depends on the geometric arrangement of these hairs and enables different applications in both nature and engineering. We investigate the mechanism and optimization of a hairy surface floating on water to obtain its maximum load-carrying capacity by the free energy and force analyses. It is demonstrated that there is an optimum cylinder spacing, as a result of the compromise between the vertical capillary force and the gravity, so that the hairy surface has both high load-carrying capacity and mechanical stability. Our analysis makes it clear that the setae on water striders' legs or some insects' wings are in such an optimized geometry. Moreover, it is shown that surface hydrophobicity can further increase the capacity of a hairy surface with thick cylinders, while the influence is negligible when the cylinders are thin.

  1. Experiments recently carried out on the photoemission station at Beijing Synchrotron Radiation Facility

    International Nuclear Information System (INIS)

    Kurash Ibrahim; Wu Ziyu; Qian Haijie; Zhang Jing; Abbas, M.I.; Chen Zhigang; Su Run; Liu Fengqin

    2003-01-01

    With a sustained and steady operation of the photoemission station at Beijing Synchrotron Radiation Facility, users from different research fields have carried out their investigation on the electronic structure of metal surface-interface, metal doped fullerene as well as colossal magneto-resistance materials utilizing different experimental modes provided by the photoemission station. In this paper authors would present some representative experimental results obtained on the station

  2. Standard protocol for demographic and epidemiological survey to be carried out for nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, M L; Datta, D; Singh, Jitendra; Sardhi, I V; Verma, P C [Health Physics Division, Bhabha Atomic Research Centre, Mumbai (India)

    2007-11-15

    This document presents the standard procedures for conducting demographic and epidemiological studies for nuclear facilities. These studies are required to be carried out to prepare baseline data, the impact of the facility and the risk factors for the population residing in the vicinity of facility. This document includes the basic elements of these type surveys, their methodology and statistical analysis of the data collected during demographic and epidemiological surveillance. (author)

  3. Recreation Carrying Capacity Facts and Considerations. Report 11. Surry Mountain Lake Project Area.

    Science.gov (United States)

    1980-07-01

    contributions of practical experience and knowledge , along with their assistance in arranging schedules, have made this carrying capacity research effort...This survey obtained six responses from boaters and water- skiers . 29 A~ .~ ~ ~ ~ ~ ~ ~ ~~~~~~~PEEI PAG ... ._DIAN.K+.+.+ 3+ ,.+ -,++ + _-NO FILM...User characteristics Table 17 indicates the characteristics of the boaters and water- skiers surveyed at Surry. The small sample size at

  4. Standard protocol for demographic and epidemiological survey to be carried out for nuclear facilities

    International Nuclear Information System (INIS)

    Joshi, M.L.; Datta, D.; Singh, Jitendra; Sardhi, I.V.; Verma, P.C.

    2007-11-01

    This document presents the standard procedures for conducting demographic and epidemiological studies for nuclear facilities. These studies are required to be carried out to prepare baseline data, the impact of the facility and the risk factors for the population residing in the vicinity of facility. This document includes the basic elements of these type surveys, their methodology and statistical analysis of the data collected during demographic and epidemiological surveillance. (author)

  5. Reduced fertility after the crash of a U.S. bomber carrying nuclear weapons?

    DEFF Research Database (Denmark)

    Juel, K

    1995-01-01

    A register-based study was performed to elucidate whether workers employed on the Thule air base in the clean-up period after the crash of a U.S. B-52 bomber carrying nuclear bombs had reduced fertility, as measured by the numbers of liveborn children. The highest birth rates were among 25-34-year...... is that the accident has not reduced fertility....

  6. Carrying shopping bags does not alter static postural stability and gait parameters in healthy older females.

    Science.gov (United States)

    Bampouras, Theodoros M; Dewhurst, Susan

    2016-05-01

    Food shopping is an important aspect of maintaining independence and social interaction in older age. Carriage of shopping bags alters the body's weight distribution which, depending on load distribution, could potentially increase instability during standing and walking. The study examined the effect of carrying UK style shopping bags on static postural stability and gait in healthy older and young females. Nine older (71.0±6.0 years) and 10 young (26.7±5.2 years) females were assessed in five conditions carrying no bags, one 1.5kg bag in each hand, one 3kg bag in each hand, one 1.5kg bag in preferred hand, one 3kg bag in preferred hand. Antero-posterior and medio-lateral displacement, and 95% ellipse area from a 30s quiet standing were used for postural stability assessment. Stride length and its coefficient of variation, total double support time, step asymmetry and gait stability ratio were calculated from 1min treadmill walking at self-selected speed for gait assessment. Carrying shopping bags did not negatively affect postural stability or gait variables, in either group. Further, in older individuals, a decrease in sway velocity was found when holding bags during the postural stability assessment (pbags, irrespective of the load distribution, may have a stabilising effect during quiet standing. These results should help to alleviate concerns regarding safety of carrying shopping bags and help encourage shopping, both as a social and as a physical activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Thermal carrying capacity for a thermally-sensitive species at the warmest edge of its range.

    Directory of Open Access Journals (Sweden)

    Daniel Ayllón

    Full Text Available Anthropogenic environmental change is causing unprecedented rates of population extirpation and altering the setting of range limits for many species. Significant population declines may occur however before any reduction in range is observed. Determining and modelling the factors driving population size and trends is consequently critical to predict trajectories of change and future extinction risk. We tracked during 12 years 51 populations of a cold-water fish species (brown trout Salmo trutta living along a temperature gradient at the warmest thermal edge of its range. We developed a carrying capacity model in which maximum population size is limited by physical habitat conditions and regulated through territoriality. We first tested whether population numbers were driven by carrying capacity dynamics and then targeted on establishing (1 the temperature thresholds beyond which population numbers switch from being physical habitat- to temperature-limited; and (2 the rate at which carrying capacity declines with temperature within limiting thermal ranges. Carrying capacity along with emergent density-dependent responses explained up to 76% of spatio-temporal density variability of juveniles and adults but only 50% of young-of-the-year's. By contrast, young-of-the-year trout were highly sensitive to thermal conditions, their performance declining with temperature at a higher rate than older life stages, and disruptions being triggered at lower temperature thresholds. Results suggest that limiting temperature effects were progressively stronger with increasing anthropogenic disturbance. There was however a critical threshold, matching the incipient thermal limit for survival, beyond which realized density was always below potential numbers irrespective of disturbance intensity. We additionally found a lower threshold, matching the thermal limit for feeding, beyond which even unaltered populations declined. We predict that most of our study

  8. Proof-Carrying Hardware: Concept and Prototype Tool Flow for Online Verification

    OpenAIRE

    Drzevitzky, Stephanie; Kastens, Uwe; Platzner, Marco

    2010-01-01

    Dynamically reconfigurable hardware combines hardware performance with software-like flexibility and finds increasing use in networked systems. The capability to load hardware modules at runtime provides these systems with an unparalleled degree of adaptivity but at the same time poses new challenges for security and safety. In this paper, we elaborate on the presentation of proof carrying hardware (PCH) as a novel approach to reconfigurable system security. PCH takes ...

  9. Comprehensive preimplantation genetic screening and sperm deoxyribonucleic acid fragmentation from three males carrying balanced chromosome rearrangements.

    Science.gov (United States)

    Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima

    2015-09-01

    To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.

  10. Land Potential Productivity and Population Carrying Capacity of Yan’an City

    OpenAIRE

    Liu, Xiaoling; Zhang, Wei

    2013-01-01

    The productivity attenuation method is adopted to calculate land potential productivity of counties of Yan’an City and calculate population carrying capacity at current productivity level. Rsults shows that high photosynthetic potential productivity area and high light and temperature potential productivity area are mainly situated in the north, while high climatic potential area and high land potential productivity area are mainly concentrated in the south. From solar radiation, moisture a...

  11. On the number of independent cultural traits carried by individuals and populations

    OpenAIRE

    Lehmann, Laurent; Aoki, Kenichi; Feldman, Marcus W.

    2011-01-01

    In species subject to individual and social learning, each individual is likely to express a certain number of different cultural traits acquired during its lifetime. If the process of trait innovation and transmission reaches a steady state in the population, the number of different cultural traits carried by an individual converges to some stationary distribution. We call this the trait-number distribution. In this paper, we derive the trait-number distributions for both individuals and pop...

  12. On load carrying capacity of frames taking into account finite displacements

    International Nuclear Information System (INIS)

    Borkoaski, A.; Saran, M.

    1981-01-01

    An approximate method that takes into account the influence of finite displacements upon the load carrying capacity of planar unbraced frames is described. It is the iterative procedure where Quadratic Programming is applied for evaluation of subsequent configurations of the frame, whereas Linear Programming serves to find ultimate load factors for each configuration. Numerical tests show that the procedure gives practically acceptable results being at the same time much cheaper than the exact geometrically and physically non-linear incremental analysis. (orig.)

  13. Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain

    OpenAIRE

    Iwaniuk, Daniel P.; Whetmore, Eric D.; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian

    2009-01-01

    We report the synthesis and in vitro antimalarial activity of several new 4-amino-and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of P. falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11–15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain st...

  14. Performance of women with fibromyalgia in walking up stairs while carrying a load

    OpenAIRE

    Collado-Mateo, Daniel; Adsuar, Jos? C.; Olivares, Pedro R.; Dominguez-Mu?oz, Francisco J.; Maestre-Cascales, Cristina; Gusi, Narcis

    2016-01-01

    Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy co...

  15. Electronic Equipment of Self-Actuated Mobile Device for Load Carrying

    Directory of Open Access Journals (Sweden)

    T. Janecka

    1994-12-01

    Full Text Available The device dealt in this work is determined namely for carrying invalid persons on various types of stairs or other not flat surfaces. But it can serve also to other purposes.To enable fulfilling all given demands, the design was consulted with other research workers solving the tasks of similar features.Resulting mechanical device, enabling aspects of movement required, is controlled by electronic and microprocessor circuits that obtain the input information from sensitive units investigating the terrain.

  16. CARRYING OF FRENCH VISAS FOR HOLDERS OF CATEGORY 'EF' FRENCH ATTESTATIONS DE FONCTIONS

    CERN Multimedia

    Service des Relations avec les Pays Hôtes

    1999-01-01

    The French Ministry of Foreign Affairs has informed the Organisation that members of the personnel resident in Switzerland and holding Category 'EF' French Attestations de functions are not obliged to be in possession of French visas. When temporarily travelling through France on OFFICIAL CERN BUSINESS, provided they are carrying the valid Attestation and a valid national passport with them.Relations with the Host States Servicehttp://www.cern.ch/relations/Tel. 72848

  17. Handling and carrying head for nuclear fuel assemblies and installation including this head

    International Nuclear Information System (INIS)

    Artaud, R.; Cransac, J.P.; Jogand, P.

    1986-01-01

    The present invention proposes a handling and carrying head ensuring efficiently the cooling of the nuclear fuel asemblies it transports so that any storage in liquid metal in a drum within or adjacent the reactor vessel is suppressed. The invention claims also a nuclear fuel handling installation including the head; it allows a longer time between loading and unloading campaigns and the space surrounding the reactor vessel keeps free without occupying a storage zone within the vessel [fr

  18. Development of Uranium-Carrying Ball method for calibration of fuel element failure detecting systems

    International Nuclear Information System (INIS)

    Liu Yupu; Bao Wanping; Lu Cungang

    1988-01-01

    A Uranium-Carrying Ball method used for the determination of sensitivity, stability of the fuel element failure detecting systems is developed. A special facility for transporting the ball can be carried out by the flow of the cooling water, so that the failure signal can be simulated. Five different types of the Uranium-Carrying Ball have been developed. Type-I to Type-IV may provide failure signal in terms of uranium quantity or exposure area of uranium. Type-V can be used to simulate micro-flaw and examine the detectability of various detective methods for this kind of defect, at the same time it is difficult for the delayed neutron detector to detect micro-flaw. The results of long-time irradiation and washing test show that the working life of the balls is satisfactory. Using the experimentel facility with the balls, detailed study of the capability of various fuel failure detecting systems have been conducted successfully. The operation is easy and safe, the accuracy of this method is higher than that of other methods, the nuclear fuel consumption as well as the radioactive contamination is low. At present, the research on the failure mechanism is being conducted by means of this method

  19. Meta-analysis of carrying capacity and abundance-area relationships in marine fish species

    DEFF Research Database (Denmark)

    Mantzouni, Irene

    Knowledge on the carrying capacity and the abundance-area relationships of fish is critical to evaluate the impacts of exploitation and climate on the sustainability and also the recovery potential of the populations. Of particular interest is climate change, inducing major consequences for popul......Knowledge on the carrying capacity and the abundance-area relationships of fish is critical to evaluate the impacts of exploitation and climate on the sustainability and also the recovery potential of the populations. Of particular interest is climate change, inducing major consequences...... differences in the patterns were identified between stocks located in the upper and lower thermal range. In the latter, strong year-classes occurred mainly during warmer seasons and vice versa. For stocks located in the warmer waters, however, no significant patterns were obtained, suggesting that increased......, to incorporate the influence of ecosystem factors, mainly temperature and habitat size, on model parameters representing cod maximum reproductive rate and carrying capacity. The pattern of temperature effects on cod productivity at the species level were identified and SR model parameters were estimated...

  20. Carrying away and redistribution of radioisotopes on the Peyne catchment basin. Preliminary report

    International Nuclear Information System (INIS)

    Duffa, C.; Danic, F.

    2006-01-01

    The transfers of radioisotopes present in soils and sediments are essentially conditioned by the mobilities of the physical vectors which constitute their supports. The water is the main vector of natural transfer, radioisotopes being associated with it under dissolved or particulate shape. The rainout and the hydrous erosion are responsible in particular for the carrying away and for the redistribution of contaminants following an atmospheric deposit on a catchment basin. However their effect is not the same in any point of the catchment basin. The work begun here aims at elaborating a classification of the grounds sensitivity towards this phenomenon of radioisotopes carrying away. The different factors of sensitivity have been identified: pluviometry, slope, soils occupation and soils nature. The Peyne catchment basin, that presents an important variability of these four parameters, constitutes the experimental site for this study. On this catchment basin, we search to identify the areas the most sensitive to the carrying away of radioisotopes, by combining a theoretical predictive approach based on the cartography and a descriptive approach basing on the sampling and the analysis of soils samples. (N.C.)

  1. Evaluation of Water Resources Carrying Capacity in Shandong Province Based on Fuzzy Comprehensive Evaluation

    Directory of Open Access Journals (Sweden)

    Zhao Qiang

    2018-01-01

    Full Text Available Water resources carrying capacity is the maximum available water resources supporting by the social and economic development. Based on investigating and statisticing on the current situation of water resources in Shandong Province, this paper selects 13 factors including per capita water resources, water resources utilization, water supply modulus, rainfall, per capita GDP, population density, per capita water consumption, water consumption per million yuan, The water consumption of industrial output value, the agricultural output value of farmland, the irrigation rate of cultivated land, the water consumption rate of ecological environment and the forest coverage rate were used as the evaluation factors. Then,the fuzzy comprehensive evaluation model was used to analyze the water resources carrying capacity Force status evaluation. The results showed : The comprehensive evaluation results of water resources in Shandong Province were lower than 0.6 in 2001-2009 and higher than 0.6 in 2010-2015, which indicating that the water resources carrying capacity of Shandong Province has been improved.; In addition, most of the years a value of less than 0.6, individual years below 0.4, the interannual changes are relatively large, from that we can see the level of water resources is generally weak, the greater the interannual changes in Shandong Province.

  2. Ecological carrying capacity assessment of diving site: A case study of Mabul Island, Malaysia.

    Science.gov (United States)

    Zhang, Li-Ye; Chung, Shan-Shan; Qiu, Jian-Wen

    2016-12-01

    Despite considered a non-consumptive use of the marine environment, diving-related activities can cause damages to coral reefs. It is imminent to assess the maximum numbers of divers that can be accommodated by a diving site before it is subject to irreversible deterioration. This study aimed to assess the ecological carrying capacity of a diving site in Mabul Island, Malaysia. Photo-quadrat line transect method was used in the benthic survey. The ecological carrying capacity was assessed based on the relationship between the number of divers and the proportion of diver damaged hard corals in Mabul Island. The results indicated that the proportion of diver damaged hard corals occurred exponentially with increasing use. The ecological carrying capacity of Mabul Island is 15,600-16,800 divers per diving site per year at current levels of diver education and training with a quarterly threshold of 3900-4200 per site. Our calculation shows that management intervention (e.g. limiting diving) is justified at 8-14% of hard coral damage. In addition, the use of coral reef dominated diving sites should be managed according to their sensitivity to diver damage and the depth of the reefs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Carry-over effects of smoking cue exposure on working memory performance

    Science.gov (United States)

    Wilson, Stephen J.; Sayette, Michael A.; Fiez, Julie A.; Brough, Elizabeth

    2009-01-01

    The present study investigated the effects of drug cue exposure on working memory performance in cigarette smokers. Adult smokers (N=23) deprived for 12 hr performed a working memory task during which they were exposed to three types of task-irrelevant stimuli: Pictures containing smoking related-content, pictures devoid of smoking content, and a fixation cross. Consistent with prior research, we found that drug cue exposure affected the processing of subsequent items (i.e., carry-over effects). Specifically, we found that working memory performance was worse on trials containing neutral pictures preceded by trials containing smoking cues compared with performance on trials containing neutral pictures preceded by trials not containing smoking-related stimuli. Previously observed effects of smoking cue exposure on cognitive processing were replicated but only after removing trials subject to carry-over effects. These results replicate and extend previous research demonstrating similar effects and highlight the significant methodological and conceptual implications of carry-over effects. PMID:17454718

  4. Is Learning in Low Immersive Environments Carried over to High Immersive Environments?

    Directory of Open Access Journals (Sweden)

    Dror David Lev

    2012-01-01

    Full Text Available One of the more debated issues regarding training simulators is their validity for transfer of skills to sensory environments that differ from the simulator. In two experiments, the advantages of three-dimensional (3D and collocated (Col visual displays were evaluated in a realistic and complex visuomotor task. The two factors were evaluated independently, comparing Col-2D with dislocated-2D (experiment 1 and with Col-3D (experiment 2. As expected, in both cases the more immersive presentation condition facilitated better performance. Furthermore, improvement following training in the more immersive condition carried over to the following less immersive condition but there was no carry over in the opposing order of presentation. This is taken as an indication for the differential development of skills conditioned by the level of immersiveness of the training environment. This further suggests that learning of complex realistic tasks is not carried over from less immersive simulator to the complex sensory environment of reality, due to the large gap in sensory patterns.

  5. Measurement and assessment of carrying capacity of the environment in Ningbo, China.

    Science.gov (United States)

    Liu, R Z; Borthwick, Alistair G L

    2011-08-01

    Carrying Capacity of the Environment (CCE) provides a useful measure of the sustainable development of a region. Approaches that use integrated assessment instead of measurement can lead to misinterpretation of sustainable development because of confusion between Environmental Stress (ES) indexes and CCE indexes, and the selection of over-simple linear plus models. The present paper proposes a comprehensive measurement system for CCE which comprises models of natural resources capacity, environmental assimilative capacity, ecosystem services capacity, and society supporting capacity. The corresponding measurable indexes are designed to assess CCE using a carrying capacity surplus ratio model and a vector of surplus ratio of carrying capacity model. The former aims at direct comparison of ES and CCE based on the values of basic indexes, and the latter uses a Euclidean vector to assess CCE states. The measurement and assessment approaches are applicable to Strategic Environmental Assessment (SEA) and environmental planning and management. A case study is presented for Ningbo, China, whereby all the basic indexes of ECC are measured and the CCE states assessed for 2005 and 2010. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Social carry-over effects on non-social behavioral variation: mechanisms and consequences

    Directory of Open Access Journals (Sweden)

    Petri Toivo Niemelä

    2015-05-01

    Full Text Available The field of animal personality is interested in decomposing behaviors into different levels of variation, with its present focus on the ecological and evolutionary causes and consequences of expressed variation. Recently the role of the social environment, i.e. social partners, has been suggested to affect behavioral variation and induce selection on animal personality. Social partner effects exist because characters of social partners (e.g. size, behavior, affect the behavioral expression of a focal individual. Here, we 1 first review the proximate mechanisms underlying the social partner effects on behavioral expression and the timescales at which such effects might take place. We then 2 discuss how within- and among-individual variation in single behaviors and covariation between multiple behaviors, caused by social partners, can carry-over to non-social behaviors expressed outside the social context. Finally, we 3 highlight evolutionary consequences of social carry-over effects to non-social behaviors and 4 suggest study designs and statistical approaches which can be applied to study the nature and evolutionary consequences of social carry-over effects on non-social behaviors. Understanding the proximate mechanisms underpinning the social partner effects is important since it opens a door for deeper understanding of how social environments can affect behavioral variation and covariation at multiple levels, and the evolution of non-social behaviors (i.e. exploration, activity, boldness that are affected by social interactions.

  7. Study of information-orientation carry-out plan in energy sector

    Energy Technology Data Exchange (ETDEWEB)

    Kang, T W [Korea Energy Economics Institute, Euiwang (Korea, Republic of)

    1998-04-01

    Carrying out an information-orientation plan in the energy sector is indispensable if Korea is to survive in this unlimited competition age and global management system. It is also for maximizing the management efficiency of national energy resources as well as increasing the development of related industries and national welfare. The management of the energy resources sector of Korea, which is becoming diversified escaping from the past simple quantitative management of supplier-orientation, requires versatile and ample high-class information management system and high-level decision support system. In order to satisfy these requests, this study investigated and analyzed overall policies of the energy sector for carrying out information-orientation, neighborhood environment, organizational chart, information transfer method, the current condition of information-orientation, problems and improvements, demand of information-orientation of the future, and also reviewed the information-orientation status of advanced countries. Based on these, an information-orientation carryout plan in the energy sector is broken into three stages of `establishment of information transfer system`, `development of database`, and `establishment of decision support system` and presented per detailed work. It advised manpower, equipment and budget implementation plan, and a development schedule plan required for carrying out information-orientation as well as overall environmental build-up, and policy recommendation for the successful implementation of information-orientation. 24 refs., 27 figs., 15 tabs.

  8. Effects of carrying a backpack in a symmetrical manner on the shape of the feet.

    Science.gov (United States)

    Drzał-Grabiec, Justyna; Snela, Sławomir; Rachwał, Maciej; Rykała, Justyna; Podgórska, Justyna

    2013-01-01

    The aim of this study was to assess changes in the shape of the feet while carrying a backpack constituting 10% of a child's weight. It was an observational, cross-sectional study involving 118 primary school children aged 11-13 years. Selected parameters of foot shape were assessed in both a normal position and with a backpack using podoscopy and a CQ-ST examination device. The study revealed significant differences in the length and width of the right and left feet between assessments. Moreover, the longitudinal arch of the foot was significantly lowered and deformity of the great toe was reported. Carrying a backpack constituting 10% of a child's weight results in lowering of the longitudinal and traverse arches of the feet and advanced toe deformities. We performed an observational, cross-sectional study examining the effect of carrying a backpack constituting 10% of a child's weight on parameters of foot shape and observed significant lowering of the longitudinal and traverse arches of the feet and advanced toe deformities.

  9. Subjective and objective analysis of three water pump systems carried by forest firefighters.

    Science.gov (United States)

    Moser, Daniel J; Graham, Ryan B; Stevenson, Joan M; Costigan, Patrick A

    2014-01-01

    The Mark 3 (M3) water power pump is an integral piece of wildfire fighting equipment. However, it is provided to fire stations without a carrying harness. The currently-used carrying harness is very uncomfortable, especially when carrying the pumps considerable distance in a forest to reach a water source. The purpose of this study was to advise the Ontario Ministry of Natural Resources on the selection of a new M3 load carriage system. Twenty Fire Rangers wore the three systems (Original, Prototype, and Modified) through a circuit of tasks representative of their working environment. Subjective and objective approaches were combined to assess and rank the M3 carriage systems. Subjective visual analogue scale ratings were obtained for ease of loading/unloading, comfort, system stability, and overall performance. Tri-axial accelerometers were mounted on each pump and at the sternum of each participant to determine relative pump-carrier accelerations. Overall, the Prototype was ranked as the best system; it resulted in the lowest relative pump-carrier accelerations on 10 out of 15 objective measures, and also received a first place ranking on all subjective measures. It was recommended that the Prototype be implemented as the M3 carriage system for fire suppression teams.

  10. Identification of virulence genes carried by bacteriophages obtained from clinically isolated methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Karasartova, Djursun; Cavusoglu, Zeynep Burcin; Turegun, Buse; Ozsan, Murat T; Şahin, Fikret

    2016-12-01

    Bacteriophages play an important role in the pathogenicity of Staphylococcus aureus (S. aureus) either by carrying accessory virulence factors or several superantigens. Despite their importance, there are not many studies showing the actual distribution of the virulence genes carried by the prophages obtained from the clinically isolated Staphylococcus. In this study, we investigated prophages obtained from methicillin-resistant S. aureus (MRSA) strains isolated from hospital- and community-associated (HA-CA) infections for the virulence factors. In the study, 43 phages isolated from 48 MRSA were investigated for carrying toxin genes including the sak, eta, lukF-PV, sea, selp, sek, seg, seq chp, and scn virulence genes using polymerase chain reaction (PCR) and Southern blot. Restriction fragment length polymorphism was used to analyze phage genomes to investigate the relationship between the phage profiles and the toxin genes' presence. MRSA strains isolated from HA infections tended to have higher prophage presence than the MRSA strains obtained from the CA infections (97% and 67%, respectively). The study showed that all the phages with the exception of one phage contained one or more virulence genes in their genomes with different combinations. The most common toxin genes found were sea (83%) followed by sek (77%) and seq (64%). The study indicates that prophages encode a significant proportion of MRSA virulence factors.

  11. Carry-over effects on the annual cycle of a migratory seabird: an experimental study.

    Science.gov (United States)

    Fayet, Annette L; Freeman, Robin; Shoji, Akiko; Kirk, Holly L; Padget, Oliver; Perrins, Chris M; Guilford, Tim

    2016-11-01

    Long-lived migratory animals must balance the cost of current reproduction with their own condition ahead of a challenging migration and future reproduction. In these species, carry-over effects, which occur when events in one season affect the outcome of the subsequent season, may be particularly exacerbated. However, how carry-over effects influence future breeding outcomes and whether (and how) they also affect behaviour during migration and wintering is unclear. Here we investigate carry-over effects induced by a controlled, bidirectional manipulation of the duration of reproductive effort on the migratory, wintering and subsequent breeding behaviour of a long-lived migratory seabird, the Manx shearwater Puffinus puffinus. By cross-fostering chicks of different age between nests, we successfully prolonged or shortened by ∼25% the chick-rearing period of 42 breeding pairs. We tracked the adults with geolocators over the subsequent year and combined migration route data with at-sea activity budgets obtained from high-resolution saltwater-immersion data. Migratory behaviour was also recorded during non-experimental years (the year before and/or two years after manipulation) for a subset of birds, allowing comparison between experimental and non-experimental years within treatment groups. All birds cared for chicks until normal fledging age, resulting in birds with a longer breeding period delaying their departure on migration; however, birds that finished breeding earlier did not start migrating earlier. Increased reproductive effort resulted in less time spent at the wintering grounds, a reduction in time spent resting daily and a delayed start of breeding with lighter eggs and chicks and lower breeding success the following breeding season. Conversely, reduced reproductive effort resulted in more time resting and less time foraging during the winter, but a similar breeding phenology and success compared with control birds the following year, suggesting that

  12. Rural Settlement Development and Environment Carrying Capacity Changes in Progo River Basin

    Directory of Open Access Journals (Sweden)

    Su Ritohardoyo

    2016-12-01

    Full Text Available Generally the broader rural settlement the heavier population pressure on agricultural land. It indicates that carrying capacity of the rural environment threatened lower. The spatial distribution of the threat in a river basin is quite important as one of the river basin management inputs. Therefore, this article aims at exposing result of research about influence rural population growth and rural settlement land changes to environment carrying capacity. This research was carried out in the rural area in Progo river basin consists 56 sub districts (34 sub districts part of Jawa Tengah Province, and 22 sub districts part of Yogyakarta Special Region. The whole sub districts are such as unit analysis, and research method is based on secondary data analysis. Several data consist Districts Region in Figure 1997 and 2003 (Temanggung, Magelang, Kulon Progo, Sleman and Bantul such as secondary data analysis. Data analysis employs of frequency and cross tabulation, statistics of regression and test. Result of the research shows that population growth of the rural areas in Progo river basin are about 0.72% annum; or the household growth about 3.15% annum as long as five years (1996-2003. Spatial distribution of the population growth in the upper part of the Progo river basin is higher than in the middle and lower part of the basin. The number proportion of farmer in every sub district area in this river basin have increased from 69.95% in 1997 to 70.81% in the year of 2003. It means that work opportunities broadening are still sluggish. However, the number proportion of farmers in the upper part of the Progo river basin is lower than in the middle and lower part of the basin. The rates of settlement land areas changes (0.32 ha/annum as long as five years (1997-2003 is not as fast as the rates of agricultural land areas changes (0.47 ha/annum. Spatial land settlement areas changes in the lower (6.1 ha/annum and middle parts (2.4 ha/annum faster than

  13. The study of environmental carrying capacity for sustainable tourism in Telaga Warna Telaga Pengilon Nature Park, Dieng Plateu, Central Java

    Science.gov (United States)

    Melat Aryasa, Alexander; Nur Bambang, Azis; Muhammad, Fuad

    2017-06-01

    The increasing in quantity of the tourists visiting Telaga Warna Telaga Pengilon Nature Park, Dieng Plateau, Central Java, can cause a potential threat toward the conservation sustainability of the tourist attraction and the surrounding area. The utilization of conservation area for tourist attraction has to be carried out based on the principal of Environmental Carrying Capacity so that it will not affect the ecosystem. This study aims to determine the value of Telaga Warna Telaga Pengilon Nature Park environmental carrying capacity as a conservation area used for tourism activities. The environmental carrying capacities calculated in this study were physical carrying capacity, real carrying capacity, and effective carrying capacity. Results of this research show that the physical carrying capacity of The Telaga Warna Telaga Pengilon Nature Park was 31,302 visitors, the real capacity was 869 visitors/day and the effective carrying capacity was 579 visitors/day. Thus, the sustainable tourism development strategy is needed to manage the everlasting natural resources.

  14. Transport characteristics of nanoscale zero-valent iron carried by three different "vehicles" in porous media.

    Science.gov (United States)

    Su, Yan; Zhao, Yong S; Li, Lu L; Qin, Chuan Y; Wu, Fan; Geng, Nan N; Lei, Jian S

    2014-01-01

    This study investigated the transport properties of nanoscale zero-valent iron (Fe(0)) (nZVI) carried by three vehicles: water, sodium dodecyl sulfate (SDS) solution, and SDS foam. Batch experiments were conducted to assess the sedimentation capability of nZVI particles in these three vehicles. Column experiments were conducted to investigate the transport properties of nZVI in porous media formed with different sizes of sand (0.25 mm to 0.5 mm, 0.5 mm to 0.9 mm, and 0.9 mm to 1.4 mm). Three main results were obtained. First, the batch experiments revealed that the stabilities of nZVI particles in SDS solution and SDS foam were improved, compared with that of nZVI particles in water. Moreover, the sedimentation of nZVI in foam was closely associated with the foam drainage volume. The nZVI content in foam was similar to that in the original foaming suspension, and the nZVI particle distribution in foam became significantly more uniform at a stirring speed of 3000 r/min. Second, the transport of nZVI was enhanced by foam compared with water and SDS solution for 0.25 mm to 0.5 mm diameter sand. For sand with diameters of 0.5 mm to 0.9 mm and 0.9 mm to 1.4 mm, the mobility of nZVI carried by SDS solution was optimal, followed by that of nZVI carried by foam and water. Thus, the mobility of nZVI in finer sand was significantly enhanced by foam, compared with that in coarse sand. In contrast, compared with the bare nZVI suspension and nZVI-laden foam, the spatial distribution of nZVI particles carried by SDS solution was significantly uniform along the column length. Third, the SDS concentration significantly influenced the migration of nZVI in porous media. The enhancement in the migration of nZVI carried by SDS solution was greater at an SDS dose of 0.25% compared with that at the other three doses (0.2%, 0.5%, and 1%) for sand with a 0.25 mm to 0.5 mm diameter. Increased SDS concentrations positively affected the transport of nZVI by foam for sand with a

  15. Stress analysis on passenger deck due to modification from passenger ship to vehicle-carrying ship

    Science.gov (United States)

    Zubaydi, A.; Sujiatanti, S. H.; Hariyanto, T. R.

    2018-03-01

    Stress is a basic concept in learning about material mechanism. The main focus that needs to be brought to attention in analyzing stress is strength, which is the structural capacity to carry or distribute loads. The structural capacity not only measured by comparing the maximum stress with the material’s yield strength but also with the permissible stress required by the Indonesian Classification Bureau (BKI), which certainly makes it much safer. This final project analyzes stress in passenger deck that experiences modification due to load changes, from passenger load to vehicle one, carrying: 6-wheels truck with maximum weight of 14 tons, a passenger car with maximum weight of 3.5 tons, and a motorcycle with maximum weight of 0.4 tons. The deck structure is modelled using finite element software. The boundary conditions given to the structural model are fix and simple constraint. The load that works on this deck is the deck load which comes from the vehicles on deck with three vehicles’ arrangement plans. After that, software modelling is conducted for analysis purpose. Analysis result shows a variation of maximum stress that occurs i.e. 135 N/mm2, 133 N/mm2, and 152 N/mm2. Those maximum stresses will not affect the structure of passenger deck’s because the maximum stress that occurs indicates smaller value compared to the Indonesian Classification Bureau’s permissible stress (175 N/mm2) as well as the material’s yield strength (235 N/mm2). Thus, the structural strength of passenger deck is shown to be capable of carrying the weight of vehicles in accordance with the three vehicles’ arrangement plans.

  16. Modulation of 5' splice site selection using tailed oligonucleotides carrying splicing signals

    Directory of Open Access Journals (Sweden)

    Elela Sherif

    2006-01-01

    Full Text Available Abstract Background We previously described the use of tailed oligonucleotides as a means of reprogramming alternative pre-mRNA splicing in vitro and in vivo. The tailed oligonucleotides that were used interfere with splicing because they contain a portion complementary to sequences immediately upstream of the target 5' splice site combined with a non-hybridizing 5' tail carrying binding sites for the hnRNP A1/A2 proteins. In the present study, we have tested the inhibitory activity of RNA oligonucleotides carrying different tail structures. Results We show that an oligonucleotide with a 5' tail containing the human β-globin branch site sequence inhibits the use of the 5' splice site of Bcl-xL, albeit less efficiently than a tail containing binding sites for the hnRNP A1/A2 proteins. A branch site-containing tail positioned at the 3' end of the oligonucleotide also elicited splicing inhibition but not as efficiently as a 5' tail. The interfering activity of a 3' tail was improved by adding a 5' splice site sequence next to the branch site sequence. A 3' tail carrying a Y-shaped branch structure promoted similar splicing interference. The inclusion of branch site or 5' splice site sequences in the Y-shaped 3' tail further improved splicing inhibition. Conclusion Our in vitro results indicate that a variety of tail architectures can be used to elicit splicing interference at low nanomolar concentrations, thereby broadening the scope and the potential impact of this antisense technology.

  17. Area/latency optimized early output asynchronous full adders and relative-timed ripple carry adders.

    Science.gov (United States)

    Balasubramanian, P; Yamashita, S

    2016-01-01

    This article presents two area/latency optimized gate level asynchronous full adder designs which correspond to early output logic. The proposed full adders are constructed using the delay-insensitive dual-rail code and adhere to the four-phase return-to-zero handshaking. For an asynchronous ripple carry adder (RCA) constructed using the proposed early output full adders, the relative-timing assumption becomes necessary and the inherent advantages of the relative-timed RCA are: (1) computation with valid inputs, i.e., forward latency is data-dependent, and (2) computation with spacer inputs involves a bare minimum constant reverse latency of just one full adder delay, thus resulting in the optimal cycle time. With respect to different 32-bit RCA implementations, and in comparison with the optimized strong-indication, weak-indication, and early output full adder designs, one of the proposed early output full adders achieves respective reductions in latency by 67.8, 12.3 and 6.1 %, while the other proposed early output full adder achieves corresponding reductions in area by 32.6, 24.6 and 6.9 %, with practically no power penalty. Further, the proposed early output full adders based asynchronous RCAs enable minimum reductions in cycle time by 83.4, 15, and 8.8 % when considering carry-propagation over the entire RCA width of 32-bits, and maximum reductions in cycle time by 97.5, 27.4, and 22.4 % for the consideration of a typical carry chain length of 4 full adder stages, when compared to the least of the cycle time estimates of various strong-indication, weak-indication, and early output asynchronous RCAs of similar size. All the asynchronous full adders and RCAs were realized using standard cells in a semi-custom design fashion based on a 32/28 nm CMOS process technology.

  18. A method for prediction of extent of microbial pollution of seawater and carrying capacity of beaches

    Science.gov (United States)

    Kocasoy, Günay

    1989-07-01

    The increase in the number of tourists visiting a coast is desired by most of the countries for economic reasons. However, this increase in tourism may cause pollution of the sea. This can be only avoided by proper planning and by predicting the “carrying capacity” of the coast in terms of sea pollution. This is especially important for developing countries where part of the wastewater is discharged without any treatment into the sea. In the present study the beaches were classified according to their use — and consequently the amount of waste discharged into the sea — into four groups: (1) coasts that are used only for swimming and recreational purposes; (2) coasts used simultaneously for dwelling, swimming, and recreational purposes; (3) coasts along which only dwellings exist; and (4) natural and man-made harbors, i.e., coasts used as shelters. During the survey,40,320 observations were made between December 1985 and February 1988 to determine the effect of the number of tourists on seawater quality. The results obtained were analyzed by a multilinear regression program to obtain an empirical equation giving the extent of the sea pollution in terms of coliform concentration as a function of population density and some other environmental factors. The equations derived in this study enable the determination of the carrying capacity of a beach in terms of pollution as well as the expected degree of pollution corresponding to a given population density. Furthermore, it allows the prediction of the extra carrying capacity that can be obtained by improving the waste-disposal conditions.

  19. Estimating carrying capacity in a newly colonized sand fly Lutzomyia serrana (Diptera: Psychodidae).

    Science.gov (United States)

    Santamaría, Erika; Munstermann, Leonard E; Ferro, Cristina

    2002-02-01

    The phlebotomine sand fly Lutzomyia serrana (Damasceno & Arouck) was mass-reared tinder conditions of varying densities in an effort to improve colony production efficiency. To do this, the experimental carrying capacity of a standard rearing chamber was determined, i.e., the optimum population size in relation to density (individuals per unit of space). Rearing chambers of 100 cm3 were populated with 1-50 L. serrana engorged females and an equal number of males. Laboratory conditions were maintained at 23-26 degrees C and 85-95% RH. The following parameters were recorded for each experimental chamber (three replicates): (1) female mortality without oviposition, (2) number of eggs oviposited and (3) number of adults emerging from the egg cohort. Female mortality began to increase substantially in the 26-female chamber, from 5.7% to 15% and finally reaching 60.2% in the 46-50 female chambers. In the chambers containing 1-20 females, egg number and realized adult progeny increased linearly to reach an asymptote. In the 20-50 female chambers, the number of eggs ranged from 420 to 699, and adult production from 306 to 432. The optimum carrying capacity for the 100-cm3 chambers was 22 +/- 2 females. Beyond this number, auto-regulation was initiated, i.e., female mortality without oviposition increased as the number of females per chamber increased. Total number of eggs and adult production was similar in all chambers containing 20-50 females. In conclusion, for optimizing production of mass reared sand flies, determination of the carrying capacity is essential to optimize use of insectary resources, to avoid loss of valuable potentially ovipositing females, and to increase overall production efficiency.

  20. Estimation of the number of aphids carrying Citrus tristeza virus that visit adult citrus trees.

    Science.gov (United States)

    Marroquín, Carlos; Olmos, Antonio; Teresa Gorris, María; Bertolini, Edson; Carmen Martínez, M; Carbonell, Emilio A; Hermoso de Mendoza, Alfonso; Cambra, Mariano

    2004-03-01

    Aphid species were counted on citrus trees in orchards in Valencia, Spain, in the spring and autumn of 1997, 1998 and 1999. Moericke yellow water traps, the 'sticky shoot' method and counts of established colonies were used in extensive surveys in which 29,502 aphids were recorded and identified. Aphis spiraecola and Aphis gossypii were the most abundant aphid species. The numbers of aphid species landing on mature trees of grapefruit, sweet orange, lemon and clementine and satsuma mandarins, were estimated by counting the numbers of young shoots/tree and aphids trapped on sticky shoots. The proportions of the different aphid species captured were: A. gossypii (53%), A. spiraecola (32%), Toxoptera aurantii (11%), Myzus persicae (1%), Aphis craccivora (1%) and other species (2%). Clementine was the most visited species with 266,700 aphids landing/tree in spring 2000, followed by lemon (147,000), sweet orange (129,150), grapefruit (103,200), and satsuma (92,400). The numbers and relative percentages of aphids carrying Citrus tristeza virus (CTV) were assessed by nested RT-PCR in single closed tubes and analysed by extraction of RNA-CTV targets from trapped aphids. An average of 37,190 CTV-carrying aphids visited each tree in spring 2000 (29 per shoot). The percentage detection of viral RNA in the aphid species that landed were 27% for A. gossypii, 23% for A. spiraecola and 19% for T. aurantii. This high incidence of aphids carrying CTV is consistent with the high prevalence and rapid spread of CTV in sweet orange, clementine, and satsuma mandarins in recent years in the region. The infection rate was proportional to the number of aphids landing/tree.

  1. A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.

    Science.gov (United States)

    Boutoleau-Bretonnière, Claire; Camuzat, Agnès; Le Ber, Isabelle; Bouya-Ahmed, Kawtar; Guerreiro, Rita; Deruet, Anne-Laure; Evrard, Christelle; Bras, José; Lamy, Estelle; Auffray-Calvier, Elisabeth; Pallardy, Amandine; Hardy, John; Brice, Alexis; Derkinderen, Pascal; Vercelletto, Martine

    2015-01-01

    SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis. More recently, SQSTM1 mutations were identified in few families with frontotemporal dementia. We report a new family carrying SQSTM1 mutation and presenting with a clinical phenotype of speech apraxia or atypical behavioral disorders, associated with early visuo-contructional deficits. This study further supports the implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic spectrum associated with SQSTM1 mutations.

  2. MODELLING STUDIES ON THE USE OF ALUMINIUM ALLOYS IN LIGHTWEIGHT LOAD-CARRYING CRANE STRUCTURES

    Directory of Open Access Journals (Sweden)

    Damian GĄSKA

    2016-09-01

    Full Text Available The article presents the results of numerical analysis whose aim was to compare the basic dynamic and strength parameters of lightweight load-carrying crane structures made of aluminium alloys and steel. The analysis covered the typical construction of workshop cranes with a span of 3 to 5 meters, girders in the form of an I-beam and maximum load capacities amounting to 5 tons. The values of stresses, deflections and natural frequencies were compared and then matched with the masses of the various structures. In the simulation a girder model was used and computed by the finite element method.

  3. Soil Enzyme Activities in Pinus tabuliformis (Carriére) Plantations in Northern China

    OpenAIRE

    Weiwei Wang; Deborah Page-Dumroese; Ruiheng Lv; Chen Xiao; Guolei Li; Yong Liu

    2016-01-01

    Changes in forest stand structure may alter the activity of invertase, urease, catalase and phenol oxidase after thinning Pinus tabuliformis (Carriére) plantations in Yanqing County of Beijing, China. We examined changes in these soil enzymes as influenced by time since thinning (24, 32, and 40 years since thinning) for 3 seasons (spring, summer and autumn) following harvesting at two depths in the mineral soil (0–10 cm and 10–20 cm). Invertase and urease increased significantly with time sin...

  4. Ferromagnetism carried by highly delocalized hybrid states in Sc-doped ZnO thin films

    KAUST Repository

    Benali Kanoun, Mohammed

    2012-05-29

    We present first-principles results for Sc-doped ZnOthin films. Neighboring Sc atoms in the surface and/or subsurface layers are found to be coupled ferromagnetically, where only two of the possible configurations induce spin polarization. In the first configuration, the polarization is carried by the Sc d states as expected for transition metaldoping. However, there is a second configuration which is energetically favorable. It is governed by polarized hybrid states of the Zns, O p, and Sc d orbitals. Such highly delocalized states can be an important ingredient for understanding the magnetism of dopedZnOthin films.

  5. Streptococcus lutetiensis Bacteremia. First Clindamycin Resistant Isolate Carrying lnuB Gene

    OpenAIRE

    Almuzara, Marisa; Bonofiglio, Laura; Cittadini, Roberto Arnaldo; Vera Ocampo, C.; Montilla, A.; del Castillo, M.; Ramirez, Maria Soledad; Mollerach, Marta Eugenia; Vay, C.

    2015-01-01

    First Case of Streptococcus lutetiensis Bacteremia Involving a Clindamycin-Resistant Isolate Carrying the lnuB Gene Fil: Almuzara, Marisa. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina; Fil: Bonofiglio, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina; Fil: Cittadini, Roberto Arnaldo. Instituto Nacional de Tecnologia Agropecuaria;...

  6. Study on ac losses of HTS coil carrying ac transport current

    International Nuclear Information System (INIS)

    Dai Taozhen; Tang Yuejin; Li Jingdong; Zhou Yusheng; Cheng Shijie; Pan Yuan

    2005-01-01

    Ac loss has an important influence on the thermal performances of HTS coil. It is necessary to quantify ac loss to ascertain its impact on coil stability and for sizing the coil refrigeration system. In this paper, we analyzed in detail the ac loss components, hysteresis loss, eddy loss and flux flow loss in the pancake HTS coil carrying ac transport current by finite element method. We also investigated the distribution of the ac losses in the coil to study the effects of magnetic field distribution on ac losses

  7. Sound insulation property of membrane-type acoustic metamaterials carrying different masses at adjacent cells

    Science.gov (United States)

    Zhang, Yuguang; Wen, Jihong; Zhao, Honggang; Yu, Dianlong; Cai, Li; Wen, Xisen

    2013-08-01

    We present the experimental realization and theoretical understanding of membrane-type acoustic metamaterials embedded with different masses at adjacent cells, capable of increasing the transmission loss at low frequency. Owing to the reverse vibration of adjacent cells, Transmission loss (TL) peaks appear, and the magnitudes of the TL peaks exceed the predicted results of the composite wall. Compared with commonly used configuration, i.e., all cells carrying with identical mass, the nonuniformity of attaching masses causes another much low TL peak. Finite element analysis was employed to validate and provide insights into the TL behavior of the structure.

  8. Levitation of current carrying states in the lattice model for the integer quantum Hall effect.

    Science.gov (United States)

    Koschny, T; Potempa, H; Schweitzer, L

    2001-04-23

    The disorder driven quantum Hall to insulator transition is investigated for a two-dimensional lattice model. The Hall conductivity and the localization length are calculated numerically near the transition. For uncorrelated and weakly correlated disorder potentials the current carrying states are annihilated by the negative Chern states originating from the band center. In the presence of correlated disorder potentials with correlation length larger than approximately half the lattice constant the floating up of the critical states in energy without merging is observed. This behavior is similar to the levitation scenario proposed for the continuum model.

  9. The energy-carrying velocity and rolling of tachyons of unstable D-branes

    International Nuclear Information System (INIS)

    Chung, Jin Hyun; L'Yi, Won Sik

    2004-01-01

    We show that the tachyons that originate from unstable D-branes carry energy and momentum at a velocity β = c 2 /v; where v is the phase velocity, which is greater than c. For an observer who moves with velocity β, the tachyon is observed to be moving from one of the ground states of the tachyon potential to a potential hill. The tachyon is found to either pass over the hill or bounce back to the original ground state. Another possible solution is the case that is margial to these; that is, the tachyon reaches the top of the potential hill and stays there forever.

  10. Generation of zonal magnetic fields by drift waves in a current carrying nonuniform magnetoplasma

    International Nuclear Information System (INIS)

    Shukla, Nitin; Shukla, P.K.

    2010-01-01

    It is shown that zonal magnetic fields (ZMFs) can be nonlinearly excited by incoherent drift waves (DWs) in a current carrying nonuniform magnetoplasma. The dynamics of incoherent DWs in the presence of ZMFs is governed by a wave-kinetic equation. The governing equation for ZMFs in the presence of nonlinear advection force of the DWs is obtained from the parallel component of the electron momentum equation and the Faraday law. Standard techniques are used to derive a nonlinear dispersion relation, which depicts instability via which ZMFs are excited in plasmas. ZMFs may inhibit the turbulent cross-field particle and energy transport in a nonuniform magnetoplasma.

  11. Impact of Flexibility Options on Grid Economic Carrying Capacity of Solar and Wind: Three Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Denholm, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Novacheck, Joshua [National Renewable Energy Lab. (NREL), Golden, CO (United States); Jorgenson, Jennie [National Renewable Energy Lab. (NREL), Golden, CO (United States); O' Connell, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-12-01

    In this study, we attempt to quantify the benefits of various options of grid flexibility by measuring their impact on two measures: economic carrying capacity and system costs. Flexibility can increase ECC and reduce overall system costs. In some cases, options that provide a limited increase in ECC can provide significant operational savings, thus demonstrating the need to evaluate flexibility options using multiple metrics. The value of flexibility options varies regionally due to different generation mixes and types of renewables. The more rapid decline in PV value compared to wind makes PV more dependent on adding flexibility options, including transmission and energy storage.

  12. Forces on a current-carrying wire in a magnetic field: the macro-micro connection

    DEFF Research Database (Denmark)

    Avelar Sotomaior Karam, Ricardo; Kneubil, Fabiana; Robilotta, Manoel

    2017-01-01

    The classic problem of determining the force on a current-carrying wire in a magnetic field is critically analysed. A common explanation found in many introductory textbooks is to represent the force on the wire as the sum of the forces on charge carriers. In this approach neither the nature...... of the forces involved nor their application points are fully discussed. In this paper we provide an alternative microscopic explanation that is suitable for introductory electromagnetism courses at university level. By considering the wire as a superposition of a positive and a negative cylindrical charge...

  13. Larval traits carry over to affect post-settlement behaviour in a common coral reef fish.

    Science.gov (United States)

    Dingeldein, Andrea L; White, J Wilson

    2016-07-01

    Most reef fishes begin life as planktonic larvae before settling to the reef, metamorphosing and entering the benthic adult population. Different selective forces determine survival in the planktonic and benthic life stages, but traits established in the larval stage may carry over to affect post-settlement performance. We tested the hypothesis that larval traits affect two key post-settlement fish behaviours: social group-joining and foraging. Certain larval traits of reef fishes are permanently recorded in the rings in their otoliths. In the bluehead wrasse (Thalassoma bifasciatum), prior work has shown that key larval traits recorded in otoliths (growth rate, energetic condition at settlement) carry over to affect post-settlement survival on the reef, with higher-larval-condition fish experiencing less post-settlement mortality. We hypothesized that this selective mortality is mediated by carry-over effects on post-settlement antipredator behaviours. We predicted that better-condition fish would forage less and be more likely to join groups, both behaviours that would reduce predation risk. We collected 550 recently settled bluehead wrasse (Thalassoma bifasciatum) from three reef sites off St. Croix (USVI) and performed two analyses. First, we compared each settler's larval traits to the size of its social group to determine whether larval traits influenced group-joining behaviour. Secondly, we observed foraging behaviour in a subset of grouped and solitary fish (n = 14) for 1-4 days post-settlement. We then collected the fish and tested whether larval traits influenced the proportion of time spent foraging. Body length at settlement, but not condition, affected group-joining behaviour; smaller fish were more likely to remain solitary or in smaller groups. However, both greater length and better condition were associated with greater proportions of time spent foraging over four consecutive days post-settlement. Larval traits carry over to affect post

  14. Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain.

    Science.gov (United States)

    Iwaniuk, Daniel P; Whetmore, Eric D; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C; Roepe, Paul D; Wolf, Christian

    2009-09-15

    We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain.

  15. Emissions from heavy current carrying high density plasma and their diagnostics

    International Nuclear Information System (INIS)

    Hirano, Katsumi

    1987-06-01

    Workshop on ''Emissions from heavy current carrying high density plasma and diagnostics'' was held at Institute of Plasma Physics, Nagoya University on 3. and 4. December 1986 under a collaborating research Program. The workshop was attended by 43 researchers from 19 labolatories. A total of 22 papers were submitted and are presented in these proceedings. The largest group of papers was that on soft X-ray emission. It seems this topic is a foremost interest for groups which engaged in research of the Z pinch and the plasma focus. A variety of problems in pinched dense plasmas, namely spectroscopy, diagnostics, pinch dynamics, and related engineering aspects were also discussed. (author)

  16. Goiania radiation accident: activities carried out and lessons learned based on personal experience

    International Nuclear Information System (INIS)

    Silva, F.C.A. da

    2017-01-01

    Goiânia Radiological Accident, on September 13, 1987, with a radioactive source of cesium-137 with 50.9 TBq, used in radiotherapy, is one of the most important accidents in the scientific area, representing a milestone for all workers in the areas of radiation protection and radiological emergency that worked during the event. A personal view of the Goiânia Radiological Accident is presented, showing some activities carried out in contaminated areas and lessons learned based on own experience during the event

  17. Special training for drivers of vehicles carrying radioactive materials in Germany

    International Nuclear Information System (INIS)

    Ridder, K.

    1993-01-01

    In Germany drivers of vehicles carrying radioactive materials have to undergo special training since midyear 1991. Training is organized in a modular system, which means that the driver can customize his dangerous goods training programme by combining several modules. The contents of the training programme, its organization and supervision as well as the means for checking the successful completion of the programme can be seen from the slides. This paper will close with an outlook on the European development, considering the framework set by the regulations of the Economic Commission for Europe (ECE) and the European Community (EC). (J.P.N.)

  18. Studies on esterase isozymes and mycelium growth speed of ganoderma lucidum carried by Shenzhou spaceship

    International Nuclear Information System (INIS)

    Qi Jianjun; Chen Xiangdong; Lan Jin

    2002-01-01

    The esterase isozymes and mycelium growth speed of four Ganoderma lucidum strains carried by Shenzhou spaceship were studied. The results showed that different effects occurred to esterase and mycelium growth speed. The SX, S3 esterase band had changed compared with their control CX, C3, respectively, but there were no differences between SH and CH, S4 and C4. The growth speed of S4 strain was faster than its control C4, SX strain lower than its control CX, and there were no difference between SH and CH, S3 and C3

  19. Research on the behaviour of pressure suppression containment systems carried out at the University of Pisa

    International Nuclear Information System (INIS)

    Bigi, R.; Bovalini, R.; Mazzini, M.; Micheletti, E.

    1978-01-01

    A research programme has been carried out at the University of Pisa to study the thermo-hydraulic transient in pressure suppression containment systems during a LOCA. In the first series of experimental tests remarkable oscillations of pressure were observed both in dry and in wet-well. In order to describe these dynamic phenomena, a mathematical model has been set up; the main out-lines of this model are briefly described and the comparison between the calculated and experimental results is reported. (author)

  20. Eddy current quality control of soldered current-carrying busbar splices of superconducting magnets

    CERN Document Server

    Kogan, L; Savary, F; Principe, R; Datskov, V; Rozenfel'd, E; Khudjakov, B

    2015-01-01

    The eddy current technique associated with a U-shaped transducer is studied for the quality control of soldered joints between superconducting busbars ('splices'). Two other quality control techniques, based on X-rays and direct measurement of the electrical resistance, are also studied for comparison. A comparative analysis of the advantages and disadvantages of these three methods in relation to the quality control of soldered superconducting busbar cables enclosed in copper shells is used for benchmarking. The results of inspections with the U-shaped eddy current transducer carried out on several sample joints presenting different types of soldering defects show the potential of this type of nondestructive (ND) quality control technique.