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Sample records for dystrophin complex controls

  1. An alpha-catulin homologue controls neuromuscular function through localization of the dystrophin complex and BK channels in Caenorhabditis elegans.

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    Linu S Abraham

    2010-08-01

    Full Text Available The large conductance, voltage- and calcium-dependent potassium (BK channel serves as a major negative feedback regulator of calcium-mediated physiological processes and has been implicated in muscle dysfunction and neurological disorders. In addition to membrane depolarization, activation of the BK channel requires a rise in cytosolic calcium. Localization of the BK channel near calcium channels is therefore critical for its function. In a genetic screen designed to isolate novel regulators of the Caenorhabditis elegans BK channel, SLO-1, we identified ctn-1, which encodes an α-catulin homologue with homology to the cytoskeletal proteins α-catenin and vinculin. ctn-1 Mutants resemble slo-1 loss-of-function mutants, as well as mutants with a compromised dystrophin complex. We determined that CTN-1 uses two distinct mechanisms to localize SLO-1 in muscles and neurons. In muscles, CTN-1 utilizes the dystrophin complex to localize SLO-1 channels near L-type calcium channels. In neurons, CTN-1 is involved in localizing SLO-1 to a specific domain independent of the dystrophin complex. Our results demonstrate that CTN-1 ensures the localization of SLO-1 within calcium nanodomains, thereby playing a crucial role in muscles and neurons.

  2. Expression of dystrophin-glycoprotein complex at the skeletal muscle sarcolemma in Duchenne muscular dystrophy

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    Zhao, Lei; Chao-ping HU; Wang, Yi; Shui-zhen ZHOU; Shi, Yi-Yun; Xi-hua LI

    2015-01-01

    Background  Eccentric exercise or high tension exercise could cause damage to skeletal muscle structure, resulting in deficiency of dystrophin and secondary loss of dystrophin-glycoprotein complex (DGC) from the sarcolemma, which indicated that down-regulation of dystrophin was one of the key points of skeletal muscle injury from eccentric exercise. Duchenne muscular dystrophy (DMD) is caused by mutations of DMD gene, resulting in the absence of dystrophin, which means that skeletal muscles o...

  3. Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies

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    Caroline Perronnet

    2010-01-01

    Full Text Available Two decades of molecular, cellular, and functional studies considerably increased our understanding of dystrophins function and unveiled the complex etiology of the cognitive deficits in Duchenne muscular dystrophy (DMD, which involves altered expression of several dystrophin-gene products in brain. Dystrophins are normally part of critical cytoskeleton-associated membrane-bound molecular scaffolds involved in the clustering of receptors, ion channels, and signaling proteins that contribute to synapse physiology and blood-brain barrier function. The utrophin gene also drives brain expression of several paralogs proteins, which cellular expression and biological roles remain to be elucidated. Here we review the structural and functional properties of dystrophins and utrophins in brain, the consequences of dystrophins loss-of-function as revealed by numerous studies in mouse models of DMD, and we discuss future challenges and putative therapeutic strategies that may compensate for the cognitive impairment in DMD based on experimental manipulation of dystrophins and/or utrophins brain expression.

  4. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

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    Rafael Rodríguez-Muñoz

    Full Text Available The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f, during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV. By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60% and multipolar Glutamatergic (≤40% neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC: dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively, in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  5. Novel Nuclear Protein Complexes of Dystrophin 71 Isoforms in Rat Cultured Hippocampal GABAergic and Glutamatergic Neurons.

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    Rodríguez-Muñoz, Rafael; Cárdenas-Aguayo, María Del Carmen; Alemán, Víctor; Osorio, Beatriz; Chávez-González, Oscar; Rendon, Alvaro; Martínez-Rojas, Dalila; Meraz-Ríos, Marco Antonio

    2015-01-01

    The precise functional role of the dystrophin 71 in neurons is still elusive. Previously, we reported that dystrophin 71d and dystrophin 71f are present in nuclei from cultured neurons. In the present work, we performed a detailed analysis of the intranuclear distribution of dystrophin 71 isoforms (Dp71d and Dp71f), during the temporal course of 7-day postnatal rats hippocampal neurons culture for 1h, 2, 4, 10, 15 and 21 days in vitro (DIV). By immunofluorescence assays, we detected the highest level of nuclear expression of both dystrophin Dp71 isoforms at 10 DIV, during the temporal course of primary culture. Dp71d and Dp71f were detected mainly in bipolar GABAergic (≥60%) and multipolar Glutamatergic (≤40%) neurons, respectively. We also characterized the existence of two nuclear dystrophin-associated protein complexes (DAPC): dystrophin 71d or dystrophin 71f bound to β-dystroglycan, α1-, β-, α2-dystrobrevins, α-syntrophin, and syntrophin-associated protein nNOS (Dp71d-DAPC or Dp71f-DAPC, respectively), in the hippocampal neurons. Furthermore, both complexes were localized in interchromatin granule cluster structures (nuclear speckles) of neuronal nucleoskeleton preparations. The present study evinces that each Dp71's complexes differ slightly in dystrobrevins composition. The results demonstrated that Dp71d-DAPC was mainly localized in bipolar GABAergic and Dp71f-DAPC in multipolar Glutamatergic hippocampal neurons. Taken together, our results show that dystrophin 71d, dystrophin 71f and DAP integrate protein complexes, and both complexes were associated to nuclear speckles structures.

  6. Regional genomic instability predisposes to complex dystrophin gene rearrangements.

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    Oshima, Junko; Magner, Daniel B; Lee, Jennifer A; Breman, Amy M; Schmitt, Eric S; White, Lisa D; Crowe, Carol A; Merrill, Michelle; Jayakar, Parul; Rajadhyaksha, Aparna; Eng, Christine M; del Gaudio, Daniela

    2009-09-01

    Mutations in the dystrophin gene (DMD) cause Duchenne and Becker muscular dystrophies and the majority of cases are due to DMD gene rearrangements. Despite the high incidence of these aberrations, little is known about their causative molecular mechanism(s). We examined 792 DMD/BMD clinical samples by oligonucleotide array-CGH and report on the junction sequence analysis of 15 unique deletion cases and three complex intragenic rearrangements to elucidate potential underlying mechanism(s). Furthermore, we present three cases with intergenic rearrangements involving DMD and neighboring loci. The cases with intragenic rearrangements include an inversion with flanking deleted sequences; a duplicated segment inserted in direct orientation into a deleted region; and a splicing mutation adjacent to a deletion. Bioinformatic analysis demonstrated that 7 of 12 breakpoints combined among 3 complex cases aligned with repetitive sequences, as compared to 4 of 30 breakpoints for the 15 deletion cases. Moreover, the inversion/deletion case may involve a stem-loop structure that has contributed to the initiation of this rearrangement. For the duplication/deletion and splicing mutation/deletion cases, the presence of the first mutation, either a duplication or point mutation, may have elicited the deletion events in an attempt to correct preexisting mutations. While NHEJ is one potential mechanism for these complex rearrangements, the highly complex junction sequence of the inversion/deletion case suggests the involvement of a replication-based mechanism. Our results support the notion that regional genomic instability, aided by the presence of repetitive elements, a stem-loop structure, and possibly preexisting mutations, may elicit complex rearrangements of the DMD gene.

  7. Bortezomib (PS-341 treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

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    Karla P C Araujo

    Full Text Available Golden retriever muscular dystrophy (GRMD is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs with the proteasome inhibitor bortezomib, and three were control dogs (CD. Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity in whole blood after treatment and comparing it to that in CD. We performed immunohistochemical studies on muscle biopsy specimens to evaluate the rescue of dystrophin and dystrophin-associated proteins in the muscles of GRMD dogs treated with bortezomib. Skeletal tissue from TD had lower levels of connective tissue deposition and inflammatory cell infiltration than CD as determined by histology, collagen morphometry and ultrastructural analysis. The CD showed higher expression of phospho-NFκB and TGF-β1, suggesting a more pronounced activation of anti-apoptotic factors and inflammatory molecules and greater connective tissue deposition, respectively. Immunohistochemical analysis demonstrated that dystrophin was not present in the sarcoplasmic membrane of either group. However, bortezomib-TD showed higher expression of α- and β-dystroglycan, indicating an improved disease histopathology phenotype. Significant inhibition of 20S proteasome activity was observed 1 hour after bortezomib administration in the last cycle when the dose was higher. Proteasome inhibitors may thus improve the appearance of GRMD muscle fibers, lessen connective tissue deposition and reduce the infiltration of inflammatory cells. In addition, proteasome inhibitors may rescue some

  8. The sarcoglycan-sarcospan complex localization in mouse retina is independent from dystrophins

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    Fort, Patrice; Estrada, Francisco-Javier; Bordais, Agnès; Mornet, Dominique; Sahel, José-Alain; Picaud, Serge; Vargas, Haydeé Rosas; Coral-Vázquez, Ramón M.; Rendon, Alvaro

    2005-01-01

    The sarcoglycan–sarcospan (SG–SSPN) complex is part of the dystrophin-glycoprotein complex that has been extensively characterized in muscle. To establish the framework for functional studies of sarcoglycans in retina here, we quantified sarcoglycans mRNA levels with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and performed immunohistochemistry to determine their cellular and subcellular distribution. We showed that the β-, δ-, γ-, ε-sarcoglycans and sarcospan are expressed in mouse retina. They are localized predominantly in the outer and the inner limiting membranes, probably in the Müller cells and also in the ganglion cells axons where the expression of dystrophins have never been reported. We also investigated the status of the sarcoglycans in the retina of mdx3cv mutant mice for all Duchene Muscular Dystrophy (DMD) gene products. The absence of dystrophin did not produce any change in the sarcoglycan–sarcospan components expression and distribution. PMID:15993965

  9. Dystrophin insufficiency causes selective muscle histopathology and loss of dystrophin-glycoprotein complex assembly in pig skeletal muscle

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    Duchenne muscular dystrophy (DMD) is caused by a dystrophin deficiency while Becker muscular dystrophy (BMD) is caused by a dystrophin insufficiency or expression of a partially functional protein product. Both of these dystrophinopathies are most commonly studied using the mdx mouse and a golden r...

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

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    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.

  11. Platelet adhesion: structural and functional diversity of short dystrophin and utrophins in the formation of dystrophin-associated-protein complexes related to actin dynamics.

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    Cerecedo, Doris; Martínez-Rojas, Dalila; Chávez, Oscar; Martínez-Pérez, Francisco; García-Sierra, Francisco; Rendon, Alvaro; Mornet, Dominique; Mondragón, Ricardo

    2005-12-01

    Platelets are dynamic cell fragments that modify their shape during activation. Utrophin and dystrophins are minor actin-binding proteins present in muscle and non-muscle cytoskeleton. In the present study, we characterised the pattern of Dp71 isoforms and utrophin gene products by immunoblot in human platelets. Two new dystrophin isoforms were found, Dp71f and Dp71 d, as well as the Up71 isoform and the dystrophin-associated proteins, alpha and beta -dystrobrevins. Distribution of Dp71d/Dp71delta110m, Up400/Up71 and dystrophin-associated proteins in relation to the actin cytoskeleton was evaluated by confocal microscopy in both resting and platelets adhered on glass. Formation of two dystrophin-associated protein complexes (Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC) was demonstrated by co-immunoprecipitation and their distribution in relation to the actin cytoskeleton was characterised during platelet adhesion. The Dp71d/Dp71delta100m approximately DAPC is maintained mainly at the granulomere and is associated with dynamic structures during activation by adhesion to thrombin-coated surfaces. Participation of both Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC in the biological roles of the platelets is discussed.

  12. The Dystrophin-Glycoprotein Complex in the Prevention of Muscle Damage

    OpenAIRE

    2011-01-01

    Muscular dystrophies are genetically diverse but share common phenotypic features of muscle weakness, degeneration, and progressive decline in muscle function. Previous work has focused on understanding how disruptions in the dystrophin-glycoprotein complex result in muscular dystrophy, supporting a hypothesis that the muscle sarcolemma is fragile and susceptible to contraction-induced injury in multiple forms of dystrophy. Although benign in healthy muscle, contractions in dystrophic muscle ...

  13. Expression of dystrophin-glycoprotein complex at the skeletal muscle sarcolemma in Duchenne muscular dystrophy

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    Lei ZHAO

    2015-07-01

    Full Text Available Background  Eccentric exercise or high tension exercise could cause damage to skeletal muscle structure, resulting in deficiency of dystrophin and secondary loss of dystrophin-glycoprotein complex (DGC from the sarcolemma, which indicated that down-regulation of dystrophin was one of the key points of skeletal muscle injury from eccentric exercise. Duchenne muscular dystrophy (DMD is caused by mutations of DMD gene, resulting in the absence of dystrophin, which means that skeletal muscles of DMD patients after birth are in the natural state of actual path of force transmission which carried high tension from eccentric exercise. This paper investigated systematically whether expression of DGC is associated with progressive muscle weakness in natural history of DMD, and analyzed the expression of DGC at the sarcolemma of 197 confirmed DMD cases (9 days-12 years old.  Methods  The expression of α- and β-dystroglycan (DG, α-, β-, γ- and δ-sarcoglycan (SG and syntrophin at the sarcolemma of DMD patients was analyzed by immunofluorescent staining.  Results  The study showed that there was no relationship between lack of proteins and progressive muscle weakness with increasing age, although expression of α- and β-DG, α-, β-, γ- and δ-SG and syntrophin at the sarcolemma at different stages of 197 DMD patients (9 days-12 years old had different degrees of deficiency.  Conclusions  Deficiency of DGC may occur before birth and DMD patients were recommended to avoid further damage to skeletal muscles from eccentric exercise and high-resistance movement in activities of daily life and rehabilitation training. DOI: 10.3969/j.issn.1672-6731.2015.06.006

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

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    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.

  15. The Dystrophin-Glycoprotein Complex in the Prevention of Muscle Damage

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    Jessica D. Gumerson

    2011-01-01

    Full Text Available Muscular dystrophies are genetically diverse but share common phenotypic features of muscle weakness, degeneration, and progressive decline in muscle function. Previous work has focused on understanding how disruptions in the dystrophin-glycoprotein complex result in muscular dystrophy, supporting a hypothesis that the muscle sarcolemma is fragile and susceptible to contraction-induced injury in multiple forms of dystrophy. Although benign in healthy muscle, contractions in dystrophic muscle may contribute to a higher degree of muscle damage which eventually overwhelms muscle regeneration capacity. While increased susceptibility of muscle to mechanical injury is thought to be an important contributor to disease pathology, it is becoming clear that not all DGC-associated diseases share this supposed hallmark feature. This paper outlines experimental support for a function of the DGC in preventing muscle damage and examines the evidence that supports novel functions for this complex in muscle that when impaired, may contribute to the pathogenesis of muscular dystrophy.

  16. Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex.

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    Mariya M Kucherenko

    Full Text Available The Dystroglycan-Dystrophin (Dg-Dys complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-beta and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.

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

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    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

  18. Dystrophin Distribution and Expression in Human and Experimental Temporal Lobe Epilepsy

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    Hendriksen, Ruben G. F.; Schipper, Sandra; Hoogland, Govert; Schijns, Olaf E. M. G.; Dings, Jim T. A.; Aalbers, Marlien W.; Vles, Johan S. H.

    2016-01-01

    Objective: Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE). Method: Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats. Results: Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p < 0.05), whereas the level of the shorter Dp71 isoform did not differ. In contrast, AK animals showed similar dystrophin levels as controls. Conclusion: Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated

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

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    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.

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

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    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.

  1. Distribution of dystrophin- and utrophin-associated protein complexes (DAPC/UAPC) in human hematopoietic stem/progenitor cells.

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    Teniente-De Alba, Carmen; Martínez-Vieyra, Ivette; Vivanco-Calixto, Raúl; Galván, Iván J; Cisneros, Bulmaro; Cerecedo, Doris

    2011-10-01

    Hematopoietic stem cells (HSC) are defined by their cardinal properties, such as sustained proliferation, multilineage differentiation, and self-renewal, which give rise to a hierarchy of progenitor populations with more restricted potential lineage, ultimately leading to the production of all types of mature blood cells. HSC are anchored by cell adhesion molecules to their specific microenvironment, thus regulating their cell cycle, while cell migration is essentially required for seeding the HSC of the fetal bone marrow (BM) during development as well as in adult BM homeostasis. The dystrophin-associated protein complex (DAPC) is a large group of membrane-associated proteins linking the cytoskeleton to the extracellular matrix and exhibiting scaffolding, adhesion, and signaling roles in muscle and non-muscle cells including mature blood cells. Because adhesion and migration are mechanisms that influence the fate of the HSC, we explored the presence and the feasible role of DAPC. In this study, we characterized the pattern expression by immunoblot technique and, by confocal microscopy analysis, the cellular distribution of dystrophin and utrophin gene products, and the dystrophin-associated proteins (α-, β-dystroglycan, α-syntrophin, α-dystrobrevin) in relation to actin filaments in freshly isolated CD34+ cells from umbilical cord blood. Immunoprecipitation assays demonstrated the presence of Dp71d/Dp71Δ110m ∼DAPC and Up400/Up140∼DAPC. The subcellular distribution of the two DAPC in actin-based structures suggests their dynamic participation in adhesion and cell migration. In addition, the particular protein pattern expression found in hematopoietic stem/progenitor cells might be indicative of their feasible participation during differentiation.

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

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    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.

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

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    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.

  4. Distribution of components of basal lamina and dystrophin-dystroglycan complex in the rat pineal gland: differences from the brain tissue and between the subdivisions of the gland.

    Science.gov (United States)

    Bagyura, Zsolt; Pócsai, Károly; Kálmán, Mihály

    2010-01-01

    The pineal gland is an evagination of the brain tissue, a circumventricular neuroendocrine organ. Our immunohistochemical study investigates basal lamina components (laminin, agrin, perlecan, fibronectin), their receptor, the dystrophin-dystroglycan complex (beta-dystroglycan, dystrophin utrophin), aquaporins (-4,-9) and cellular markers (S100, neurofilament, GFAP, glutamine synthetase) in the adult rat corpus pineale. The aim was to compare the immunohistochemical features of the cerebral and pineal vessels and their environment, and to compare their features in the distal and proximal subdivisions of the so-called 'superficial pineal gland'. In contrast to the cerebral vessels, pineal vessels proved to be immunonegative to alpha1-dystrobrevin, but immunoreactive to laminin. An inner, dense, and an outer, loose layer of laminin as two basal laminae were present. The gap between them contained agrin and perlecan. Basal lamina components enmeshed the pinealocytes, too. Components of dystrophin-dystroglycan complex were also distributed along the vessels. Dystrophin, utrophin and agrin gave a 'patchy' distribution rather than a continuous one. The vessels were interconnected by wing-like structures, composed of basal lamina-components: a delicate network forming nests for cells. Cells immunostained with glutamine synthetase, S100-protein or neurofilament protein contacted the vessels, as well as GFAP- or aquaporin-immunostained astrocytes. Within the body a smaller, proximal, GFAP-and aquaporin-containing subdivision, and a larger, distal, GFAP-and aquaporin-free subdivision could be distinguished. The vascular localization of agrin and utrophin, as well as dystrophin, delineated vessels unequally, preferring the proximal or distal end of the body, respectively.

  5. Transcriptomic analysis of dystrophin RNAi knockdown reveals a central role for dystrophin in muscle differentiation and contractile apparatus organization

    Directory of Open Access Journals (Sweden)

    Graham Ian R

    2010-06-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. DMD has a complex and as yet incompletely defined molecular pathophysiology hindering development of effective ameliorative approaches. Transcriptomic studies so far conducted on dystrophic cells and tissues suffer from non-specific changes and background noise due to heterogeneous comparisons and secondary pathologies. A study design in which a perfectly matched control cell population is used as reference for transcriptomic studies will give a much more specific insight into the effects of dystrophin deficiency and DMD pathophysiology. Results Using RNA interference (RNAi to knock down dystrophin in myotubes from C57BL10 mice, we created a homogenous model to study the transcriptome of dystrophin-deficient myotubes. We noted significant differences in the global gene expression pattern between these myotubes and their matched control cultures. In particular, categorical analyses of the dysregulated genes demonstrated significant enrichment of molecules associated with the components of muscle cell contractile unit, ion channels, metabolic pathways and kinases. Additionally, some of the dysregulated genes could potentially explain conditions and endophenotypes associated with dystrophin deficiency, such as dysregulation of calcium homeostasis (Pvalb and Casq1, or cardiomyopathy (Obscurin, Tcap. In addition to be validated by qPCR, our data gains another level of validity by affirmatively reproducing several independent studies conducted previously at genes and/or protein levels in vivo and in vitro. Conclusion Our results suggest that in striated muscles, dystrophin is involved in orchestrating proper development and organization of myofibers as contractile units, depicting a novel pathophysiology for DMD where the absence of dystrophin results in maldeveloped myofibers prone to physical stress and damage

  6. Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion.

    Science.gov (United States)

    Cerna, Joel; Cerecedo, Doris; Ortega, Arturo; García-Sierra, Francisco; Centeno, Federico; Garrido, Efrain; Mornet, Dominique; Cisneros, Bulmaro

    2006-10-01

    Dystrophin Dp71 is the main product of the Duchenne muscular dystrophy gene in the brain; however, its function is unknown. To study the role of Dp71 in neuronal cells, we previously generated by antisense treatment PC12 neuronal cell clones with decreased Dp71 expression (antisense-Dp71 cells). PC12 cells express two different splicing isoforms of Dp71, a cytoplasmic variant called Dp71f and a nuclear isoform called Dp71d. We previously reported that antisense-Dp71 cells display deficient adhesion to substrate and reduced immunostaining of beta1-integrin in the cell area contacting the substrate. In this study, we isolated additional antisense-Dp71 clones to analyze in detail the potential involvement of Dp71f isoform with the beta1-integrin adhesion system of PC12 cells. Immunofluorescence analyses as well as immunoprecipitation assays demonstrated that the PC12 cell beta1-integrin adhesion complex is composed of beta1-integrin, talin, paxillin, alpha-actinin, FAK and actin. In addition, our results showed that Dp71f associates with most of the beta1-integrin complex components (beta1-integrin, FAK, alpha-actinin, talin and actin). In the antisense-Dp71 cells, the deficiency of Dp71 provokes a significant reduction of the beta1-integrin adhesion complex and, consequently, the deficient adhesion of these cells to laminin. In vitro binding experiments confirmed the interaction of Dp71f with FAK and beta1-integrin. Our data indicate that Dp71f is a structural component of the beta1-integrin adhesion complex of PC12 cells that modulates PC12 cell adhesion by conferring proper complex assembly and/or maintenance.

  7. 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 IK1, 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 IK1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that IK1 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.

  8. Dystrophin and utrophin influence fiber type composition and post-synaptic membrane structure.

    Science.gov (United States)

    Rafael, J A; Townsend, E R; Squire, S E; Potter, A C; Chamberlain, J S; Davies, K E

    2000-05-22

    The X-linked muscle wasting disease Duchenne muscular dystrophy is caused by the lack of dystrophin in muscle. Protein structure predictions, patient mutations, in vitro binding studies and transgenic and knockout mice suggest that dystrophin plays a mechanical role in skeletal muscle, linking the subsarcolemmal cytoskeleton with the extracellular matrix through its direct interaction with the dystrophin-associated protein complex (DAPC). Although a signaling role for dystrophin has been postulated, definitive data have been lacking. To identify potential non-mechanical roles of dystrophin, we tested the ability of various truncated dystrophin transgenes to prevent any of the skeletal muscle abnormalities associated with the double knockout mouse deficient for both dystrophin and the dystrophin-related protein utrophin. We show that restoration of the DAPC with Dp71 does not prevent the structural abnormalities of the post-synaptic membrane or the abnormal oxidative properties of utrophin/dystrophin-deficient muscle. In marked contrast, a dystrophin protein lacking the cysteine-rich domain, which is unable to prevent dystrophy in the mdx mouse, is able to ameliorate these abnormalities in utrophin/dystrophin-deficient mice. These experiments provide the first direct evidence that in addition to a mechanical role and relocalization of the DAPC, dystrophin and utrophin are able to alter both structural and biochemical properties of skeletal muscle. In addition, these mice provide unique insights into skeletal muscle fiber type composition.

  9. Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Meng, Jinhong; Counsell, John R; Reza, Mojgan; Laval, Steven H; Danos, Olivier; Thrasher, Adrian; Lochmüller, Hanns; Muntoni, Francesco; Morgan, Jennifer E

    2016-01-27

    Autologous stem cells that have been genetically modified to express dystrophin are a possible means of treating Duchenne Muscular Dystrophy (DMD). To maximize the therapeutic effect, dystrophin construct needs to contain as many functional motifs as possible, within the packaging capacity of the viral vector. Existing dystrophin constructs used for transduction of muscle stem cells do not contain the nNOS binding site, an important functional motif within the dystrophin gene. In this proof-of-concept study, using stem cells derived from skeletal muscle of a DMD patient (mdcs) transplanted into an immunodeficient mouse model of DMD, we report that two novel dystrophin constructs, C1 (ΔR3-R13) and C2 (ΔH2-R23), can be lentivirally transduced into mdcs and produce dystrophin. These dystrophin proteins were functional in vivo, as members of the dystrophin glycoprotein complex were restored in muscle fibres containing donor-derived dystrophin. In muscle fibres derived from cells that had been transduced with construct C1, the largest dystrophin construct packaged into a lentiviral system, nNOS was restored. The combination of autologous stem cells and a lentivirus expressing a novel dystrophin construct which optimally restores proteins of the dystrophin glycoprotein complex may have therapeutic application for all DMD patients, regardless of their dystrophin mutation.

  10. Dystrophin-Deficient Cardiomyopathy.

    Science.gov (United States)

    Kamdar, Forum; Garry, Daniel J

    2016-05-31

    Dystrophinopathies are a group of distinct neuromuscular diseases that result from mutations in the structural cytoskeletal Dystrophin gene. Dystrophinopathies include Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy, as well as DMD and BMD female carriers. The primary presenting symptom in most dystrophinopathies is skeletal muscle weakness. However, cardiac muscle is also a subtype of striated muscle and is similarly affected in many of the muscular dystrophies. Cardiomyopathies associated with dystrophinopathies are an increasingly recognized manifestation of these neuromuscular disorders and contribute significantly to their morbidity and mortality. Recent studies suggest that these patient populations would benefit from cardiovascular therapies, annual cardiovascular imaging studies, and close follow-up with cardiovascular specialists. Moreover, patients with DMD and BMD who develop end-stage heart failure may benefit from the use of advanced therapies. This review focuses on the pathophysiology, cardiac involvement, and treatment of cardiomyopathy in the dystrophic patient. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Role of dystrophins and utrophins in platelet adhesion process.

    Science.gov (United States)

    Cerecedo, Doris; Mondragón, Ricardo; Cisneros, Bulmaro; Martínez-Pérez, Francisco; Martínez-Rojas, Dalila; Rendón, Alvaro

    2006-07-01

    Platelets are crucial at the site of vascular injury, adhering to the sub-endothelial matrix through receptors on their surface, leading to cell activation and aggregation to form a haemostatic plug. Platelets display focal adhesions as well as stress fibres to contract and facilitate expulsion of growth and pro-coagulant factors contained in the granules and to constrict the clot. The interaction of F-actin with different actin-binding proteins determines the properties and composition of the focal adhesions. Recently, we demonstrated the presence of dystrophin-associated protein complex corresponding to short dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and Up71), which promote shape change, adhesion, aggregation, and granule centralisation. To elucidate participation of both complexes during the platelet adhesion process, their potential association with integrin beta-1 fraction and the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays. It was shown that the short dystrophin-associated protein complex participated in stress fibre assembly and in centralisation of cytoplasmic granules, while the utrophin-associated protein complex assembled and regulated focal adhesions. The simultaneous presence of dystrophin and utrophin complexes indicates complementary structural and signalling mechanisms to the actin network, improving the platelet haemostatic role.

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

    Science.gov (United States)

    Barnabei, Matthew S; Metzger, Joseph M

    2012-01-01

    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.

  13. 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.

  14. Muscle dysfunction and structural defects of dystrophin-null sapje mutant zebrafish larvae are rescued by ataluren treatment.

    Science.gov (United States)

    Li, Mei; Andersson-Lendahl, Monika; Sejersen, Thomas; Arner, Anders

    2014-04-01

    Sapje zebrafish carry a mutation in the dystrophin gene, which results in a premature stop codon, and a severe muscle phenotype. They display several of the structural characteristics of Duchenne muscular dystrophy (DMD). Ataluren (PTC124) is proposed to cause readthrough of premature stop codons and has been introduced as a potential treatment of genetic disorders. Clinical trials in DMD have shown promise, although with complex dose dependency. We have established physiology techniques, enabling high resolution of contractile function in skeletal muscle of zebrafish larvae. We aimed to provide a mechanical analysis of sapje larval muscle and examine effects of ataluren. Homozygous 5 d postfertilization (dpf) sapje larvae exhibited structural defects with 50% decrease in active tension. Ataluren (0.1-1 μM, 3-5 dpf) improved contractile function (~60% improvement of force at 0.5 μM) and dystrophin expression. Controls were not affected. Higher doses (5 μM, 35 μM) impaired contractile function, an effect also observed in controls, suggesting unspecific negative effects at high concentrations. In summary, Sapje larvae exhibit impaired contractile performance and provide a relevant DMD model for functional studies. Ataluren significantly improves skeletal muscle function in the sapje larvae, most likely reflecting an observed increase in dystrophin expression. The bell-shaped dose dependence in sapje resembles that previously reported in clinical DMD studies.

  15. Controllability of Complex Systems

    Science.gov (United States)

    Slotine, Jean-Jacques

    2013-03-01

    We review recent work on controllability of complex systems. We also discuss the interplay of our results with questions of synchronization, and point out key directions of future research. Work done in collaboration with Yang-Yu Liu, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University and Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Albert-László Barabási, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University; Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.

  16. Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice

    Directory of Open Access Journals (Sweden)

    Han Renzhi

    2011-12-01

    -null muscles, suggesting that dysferlin is required for the initial recovery from lengthening contraction-induced muscle injury of the dystrophin-glycoprotein complex-compromised muscles. Conclusions The results of our study suggest that dysferlin-mediated membrane repair helps to limit the dystrophic changes in dystrophin-deficient skeletal muscle. Dystrophin deficiency unmasks the function of dysferlin in membrane repair during lengthening contractions. Dystrophin/dysferlin-deficient mice provide a very useful model with which to evaluate the effectiveness of therapies designed to treat dysferlin deficiency.

  17. Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Yingyin Liang

    2015-05-01

    Full Text Available The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD and Becker (BMD muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD, spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC. On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD.

  18. Control of complex systems

    CERN Document Server

    Albertos, Pedro; Blanke, Mogens; Isidori, Alberto; Schaufelberger, Walter; Sanz, Ricardo

    2001-01-01

    The world of artificial systems is reaching complexity levels that es­ cape human understanding. Surface traffic, electricity distribution, air­ planes, mobile communications, etc. , are examples that demonstrate that we are running into problems that are beyond classical scientific or engi­ neering knowledge. There is an ongoing world-wide effort to understand these systems and develop models that can capture its behavior. The reason for this work is clear, if our lack of understanding deepens, we will lose our capability to control these systems and make they behave as we want. Researchers from many different fields are trying to understand and develop theories for complex man-made systems. This book presents re­ search from the perspective of control and systems theory. The book has grown out of activities in the research program Control of Complex Systems (COSY). The program has been sponsored by the Eu­ ropean Science Foundation (ESF) which for 25 years has been one of the leading players in stimula...

  19. 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.

  20. Control in Complex Organizations

    DEFF Research Database (Denmark)

    Rennstam, Jens; Kärreman, Dan

    The extant research on organizational control builds on the assumption of vertical control – managers are thought to develop orders, rules and norms to control the operating core. Yet it is claimed that work becomes increasingly “knowledge intensive” and that organizations rely heavily...... for their productivity on the knowledge and creativity of their work force. In this type of “knowledge work,” the strong focus on vertical control is insufficient as it fails to account for the important operative and horizontal interactions upon which many contemporary organizations depend. Drawing on practice theory...... and an ethnographic study of engineering work, this paper theorizes control as a form of work that does not only belong to formal management, but is dispersed among various work activities, including horizontal ones. The article introduces the idea of control work as a key practice in contemporary organizations...

  1. ON COMPLEX DYNAMIC CONTROL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    CHENG Daizhan

    2003-01-01

    This paper presents some recent works on the control of dynamic systems, which have certain complex properties caused by singularity of the nonlinear structures, structure-varyings, or evolution process etc. First, we consider the structure singularity of nonlinear control systems. It was revealed that the focus of researches on nonlinear control theory is shifting from regular systems to singular systems. The singularity of nonlinear systems causes certain complexity. Secondly, the switched systems are considered. For such systems the complexity is caused by the structure varying. We show that the switched systems have significant characteristics of complex systems. Finally, we investigate the evolution systems. The evolution structure makes complexity, and itself is a proper model for complex systems.

  2. 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.

  3. Control principles of complex systems

    Science.gov (United States)

    Liu, Yang-Yu; Barabási, Albert-László

    2016-07-01

    A reflection of our ultimate understanding of a complex system is our ability to control its behavior. Typically, control has multiple prerequisites: it requires an accurate map of the network that governs the interactions between the system's components, a quantitative description of the dynamical laws that govern the temporal behavior of each component, and an ability to influence the state and temporal behavior of a selected subset of the components. With deep roots in dynamical systems and control theory, notions of control and controllability have taken a new life recently in the study of complex networks, inspiring several fundamental questions: What are the control principles of complex systems? How do networks organize themselves to balance control with functionality? To address these questions here recent advances on the controllability and the control of complex networks are reviewed, exploring the intricate interplay between the network topology and dynamical laws. The pertinent mathematical results are matched with empirical findings and applications. Uncovering the control principles of complex systems can help us explore and ultimately understand the fundamental laws that govern their behavior.

  4. Physical controllability of complex networks

    Science.gov (United States)

    Wang, Le-Zhi; Chen, Yu-Zhong; Wang, Wen-Xu; Lai, Ying-Cheng

    2017-01-01

    A challenging problem in network science is to control complex networks. In existing frameworks of structural or exact controllability, the ability to steer a complex network toward any desired state is measured by the minimum number of required driver nodes. However, if we implement actual control by imposing input signals on the minimum set of driver nodes, an unexpected phenomenon arises: due to computational or experimental error there is a great probability that convergence to the final state cannot be achieved. In fact, the associated control cost can become unbearably large, effectively preventing actual control from being realized physically. The difficulty is particularly severe when the network is deemed controllable with a small number of drivers. Here we develop a physical controllability framework based on the probability of achieving actual control. Using a recently identified fundamental chain structure underlying the control energy, we offer strategies to turn physically uncontrollable networks into physically controllable ones by imposing slightly augmented set of input signals on properly chosen nodes. Our findings indicate that, although full control can be theoretically guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control cost to achieve physical control. PMID:28074900

  5. Physical controllability of complex networks

    Science.gov (United States)

    Wang, Le-Zhi; Chen, Yu-Zhong; Wang, Wen-Xu; Lai, Ying-Cheng

    2017-01-01

    A challenging problem in network science is to control complex networks. In existing frameworks of structural or exact controllability, the ability to steer a complex network toward any desired state is measured by the minimum number of required driver nodes. However, if we implement actual control by imposing input signals on the minimum set of driver nodes, an unexpected phenomenon arises: due to computational or experimental error there is a great probability that convergence to the final state cannot be achieved. In fact, the associated control cost can become unbearably large, effectively preventing actual control from being realized physically. The difficulty is particularly severe when the network is deemed controllable with a small number of drivers. Here we develop a physical controllability framework based on the probability of achieving actual control. Using a recently identified fundamental chain structure underlying the control energy, we offer strategies to turn physically uncontrollable networks into physically controllable ones by imposing slightly augmented set of input signals on properly chosen nodes. Our findings indicate that, although full control can be theoretically guaranteed by the prevailing structural controllability theory, it is necessary to balance the number of driver nodes and control cost to achieve physical control.

  6. Control efficacy of complex networks

    Science.gov (United States)

    Gao, Xin-Dong; Wang, Wen-Xu; Lai, Ying-Cheng

    2016-06-01

    Controlling complex networks has become a forefront research area in network science and engineering. Recent efforts have led to theoretical frameworks of controllability to fully control a network through steering a minimum set of driver nodes. However, in realistic situations not every node is accessible or can be externally driven, raising the fundamental issue of control efficacy: if driving signals are applied to an arbitrary subset of nodes, how many other nodes can be controlled? We develop a framework to determine the control efficacy for undirected networks of arbitrary topology. Mathematically, based on non-singular transformation, we prove a theorem to determine rigorously the control efficacy of the network and to identify the nodes that can be controlled for any given driver nodes. Physically, we develop the picture of diffusion that views the control process as a signal diffused from input signals to the set of controllable nodes. The combination of mathematical theory and physical reasoning allows us not only to determine the control efficacy for model complex networks and a large number of empirical networks, but also to uncover phenomena in network control, e.g., hub nodes in general possess lower control centrality than an average node in undirected networks.

  7. DMD transcript imbalance determines dystrophin levels.

    Science.gov (United States)

    Spitali, Pietro; van den Bergen, Janneke C; Verhaart, Ingrid E C; Wokke, Beatrijs; Janson, Anneke A M; van den Eijnde, Rani; den Dunnen, Johan T; Laros, Jeroen F J; Verschuuren, Jan J G M; 't Hoen, Peter A C; Aartsma-Rus, Annemieke

    2013-12-01

    Duchenne and Becker muscular dystrophies are caused by out-of-frame and in-frame mutations, respectively, in the dystrophin encoding DMD gene. Molecular therapies targeting the precursor-mRNA are in clinical trials and show promising results. These approaches will depend on the stability and expression levels of dystrophin mRNA in skeletal muscles and heart. We report that the DMD gene is more highly expressed in heart than in skeletal muscles, in mice and humans. The transcript mutated in the mdx mouse model shows a 5' to 3' imbalance compared with that of its wild-type counterpart and reading frame restoration via antisense-mediated exon skipping does not correct this event. We also report significant transcript instability in 22 patients with Becker dystrophy, clarifying the fact that transcript imbalance is not caused by premature nonsense mutations. Finally, we demonstrate that transcript stability, rather than transcriptional rate, is an important determinant of dystrophin protein levels in patients with Becker dystrophy. We suggest that the availability of the complete transcript is a key factor to determine protein abundance and thus will influence the outcome of mRNA-targeting therapies.

  8. Proteasome inhibitor (MG132 rescues Nav1.5 protein content and the cardiac sodium current in dystrophin-deficient mdx5cv mice

    Directory of Open Access Journals (Sweden)

    Jean-Sebastien eRougier

    2013-03-01

    Full Text Available The cardiac voltage-gated sodium channel, Nav1.5, plays a central role in cardiac excitability and impulse propagation and associates with the dystrophin multiprotein complex (DMC at the lateral membrane of cardiomyocytes. It was previously shown that Nav1.5 protein content and the sodium current (INa were both decreased in cardiomyocytes of dystrophin-deficient mdx5cv mice. In this study, wild-type (WT and mdx5cv mice were treated for 7 days with the proteasome inhibitor MG132 (10 µg/Kg/24 h using implanted osmotic mini pumps. MG132 rescued both the total amount of Nav1.5 protein and INa but, unlike in previous studies, de novo expression of dystrophin was not observed in skeletal or cardiac muscle. This study suggests that the reduced expression of Nav1.5 in dystrophin-deficient cells is dependent on proteasomal degradation.

  9. Coordination Control Of Complex Machines

    NARCIS (Netherlands)

    J.C.M. Baeten; B. van Beek; J. Markovski; L.J.A.M. Somers

    2015-01-01

    Control and coordination are important aspects of the development of complex machines due to an ever-increasing demand for better functionality, quality, and performance. In WP6 of the C4C project, we developed a synthesis-centric systems engineering framework suitable for supervisory coordination o

  10. 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…

  11. Complexity control in statistical learning

    Indian Academy of Sciences (India)

    Sameer M Jalnapurkar

    2006-04-01

    We consider the problem of determining a model for a given system on the basis of experimental data. The amount of data available is limited and, further, may be corrupted by noise. In this situation, it is important to control the complexity of the class of models from which we are to choose our model. In this paper, we first give a simplified overview of the principal features of learning theory. Then we describe how the method of regularization is used to control complexity in learning. We discuss two examples of regularization, one in which the function space used is finite dimensional, and another in which it is a reproducing kernel Hilbert space. Our exposition follows the formulation of Cucker and Smale. We give a new method of bounding the sample error in the regularization scenario, which avoids some difficulties in the derivation given by Cucker and Smale.

  12. 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

  13. Dystrophin/α1-syntrophin scaffold regulated PLC/PKC-dependent store-operated calcium entry in myotubes.

    Science.gov (United States)

    Sabourin, Jessica; Harisseh, Rania; Harnois, Thomas; Magaud, Christophe; Bourmeyster, Nicolas; Déliot, Nadine; Constantin, Bruno

    2012-12-01

    In skeletal muscles from patient suffering of Duchenne Muscular Dystrophy and from mdx mice, the absence of the cytoskeleton protein dystrophin has been shown to be essential for maintaining a normal calcium influx. We showed that a TRPC store-dependent cation influx is increased by loss of dystrophin or a scaffolding protein α1-syntrophin, however the mechanisms of this calcium mishandling are incompletely understood. First of all, we confirmed that TRPC1 but also STIM1 and Orai1 are supporting the store-operated cation entry which is enhanced in dystrophin-deficient myotubes. Next, we demonstrated that inhibition of PLC or PKC in dystrophin-deficient myotubes restores elevated cation entry to normal levels similarly to enforced minidystrophin expression. In addition, silencing α1-syntrophin also increased cation influx in a PLC/PKC dependent pathway. We also showed that α1-syntrophin and PLCβ are part of a same protein complex reinforcing the idea of their inter-relation in calcium influx regulation. This elevated cation entry was decreased to normal levels by chelating intracellular free calcium with BAPTA-AM. Double treatments with BAPTA-AM and PLC or PKC inhibitors suggested that the elevation of cation influx by PLC/PKC pathway is dependent on cytosolic calcium. All these results demonstrate an involvement in dystrophin-deficient myotubes of a specific calcium/PKC/PLC pathway in elevation of store-operated cation influx supported by the STIM1/Orai1/TRPC1 proteins, which is normally regulated by the α1-syntrophin/dystrophin scaffold.

  14. A marginal level of dystrophin partially ameliorates hindlimb muscle passive mechanical properties in dystrophin-null mice.

    Science.gov (United States)

    Hakim, Chady H; Duan, Dongsheng

    2012-12-01

    The goal of this study was to determine whether a minimal level of dystrophin expression improves the passive mechanical properties of skeletal muscle in the murine Duchenne muscular dystrophy model. We compared the elastic and viscous properties of the extensor digitorum longus muscle (EDL) in mdx3cv and mdx4cv mice at 6, 14, and 20 months of age. Both strains are on the C57Bl/6 background, and both lose the full-length dystrophin protein. Interestingly, mdx3cv mice express a near full-length dystrophin at ≈ 5% of the normal level. We found that the stress-strain profile and the stress relaxation rate of the EDL in mdx3cv mice were partially preserved in all age groups compared with age-matched mdx4cv mice. Our results suggest that a low level of dystrophin expression may treat muscle stiffness in Duchenne muscular dystrophy. Copyright © 2012 Wiley Periodicals, Inc.

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

    OpenAIRE

    2015-01-01

    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 exten...

  16. 免疫组织化学dystrophin染色诊断Duchenne型肌营养不良症的研究%Diagnosis of Duchenne muscular dystrophy through dystrophin expression detection by immunohistochemistry

    Institute of Scientific and Technical Information of China (English)

    刘鹏; 沈定国

    2008-01-01

    目的 探讨Duchenne型肌营养不良症(DMD)肌萎缩蛋白(dystrophin)表达规律和临床意义.方法 收集我院7例DMD患者作为试验组,7例非DMD患者为对照组.使用抗dystrophin杆状结构域单抗、免疫组织化学染色,观察肌膜dystrophin表达.结果 7例DMD患者肌细胞膜dystrophin阴性,7例非DMD患者dystrophin染色阳性.结论 证实DMD患者肌细胞膜dystrophin表达阴性,揭示dystrophin缺失是其发病机制,可以作为确诊DMD手段,对临床诊断DMD有实际意义.%Objective To study dystrophin expression in Duchenne muscular dystrophy (DMD) and non-DMD patients. Methods With immunohistochemistry method, using monoclonal antibody of dystrophin, expression of dystrophin was analyzed in 7 DMD patients (experimental group)and 7 non-DMD patients (control group). Results In 7 non-DMD patients, uniform and continuous dystrophin expression was found along the sarolemma, while not in 7 DMD patients. Conclusions Dystrophin expression in myocyte membrane is negative in DMD patients, which indicates that dystrophin loss may be involved in the pathogenesis of DMD. It can be used as a "gold standard" in diagnosing DMD.

  17. 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.

  18. Accurate Quantitation of Dystrophin Protein in Human Skeletal Muscle Using Mass Spectrometry

    OpenAIRE

    Brown, Kristy J; Marathi, Ramya; Fiorillo, Alyson A; Ciccimaro, Eugene F.; Sharma, Seema; Rowlands, David S.; Rayavarapu, Sree; Nagaraju, Kanneboyina; Eric P. Hoffman; Hathout, Yetrib

    2012-01-01

    Quantitation of human dystrophin protein in muscle biopsies is a clinically relevant endpoint for both diagnosis and response to dystrophin-replacement therapies for dystrophinopathies. A robust and accurate assay would enable the use of dystrophin as a surrogate biomarker, particularly in exploratory Phase 2 trials. Currently available methods to quantitate dystrophin rely on immunoblot or immunohistochemistry methods that are not considered robust. Here we present a mass spectrometry based ...

  19. Mathematical Control of Complex Systems 2013

    OpenAIRE

    Zidong Wang; Hamid Reza Karimi; Bo Shen; Jun Hu; Hongli Dong; Xiao He

    2014-01-01

    Mathematical control of complex systems have already become an ideal research area for control engineers, mathematicians, computer scientists, and biologists to understand, manage, analyze, and interpret functional information/dynamical behaviours from real-world complex dynamical systems, such as communication systems, process control, environmental systems, intelligent manufacturing systems, transportation systems, and structural systems. This special issue aims to bring together the latest...

  20. Concurrency Control Mechanism of Complex Objects

    Institute of Scientific and Technical Information of China (English)

    徐庆云; 王能斌

    1992-01-01

    A complex object is an abstraction and description of a complex entity of the real world.Many applications in such domains as CIMS,CAD and OA define and manipulate a complex object as a single unit.In this paper,a definition of the model of complex objects is given,and the concurrency control mechanism of complex objects in WHYMX object-oriented database system is described.

  1. The roles of dystrophin and dystrobrevin : in synaptic signaling in drosophila

    NARCIS (Netherlands)

    Potikanond, Saranyapin

    2012-01-01

    Duchenne muscular dystrophy (DMD) is a disease, characterized by progressive muscle wasting, caused by the lack of Dystrophin. A subset of DMD patients also have cognitive deficits likely due to the absence of Dystrophin from brain synapses where it is usually localized. Dystrophin and a number of o

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

    Directory of Open Access Journals (Sweden)

    Dejia Li

    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.

  3. Disodium cromoglycate protects dystrophin-deficient muscle fibers from leakiness.

    Science.gov (United States)

    Marques, Maria Julia; Ventura Machado, Rafael; Minatel, Elaine; Santo Neto, Humberto

    2008-01-01

    In dystrophin-deficient fibers of mdx mice and in Duchenne dystrophy, the lack of dystrophin leads to sarcolemma breakdown and muscle degeneration. We verified that cromolyn, a mast-cell stabilizer agent, stabilized dystrophic muscle fibers using Evans blue dye as a marker of sarcolemma leakiness. Mdx mice (n=8; 14 days of age) received daily intraperitoneal injections of cromolyn (50 mg/kg body weight) for 15 days. Untreated mdx mice (n=8) were injected with saline. Cryostat cross-sections of the sternomastoid, tibialis anterior, and diaphragm muscles were stained with hematoxylin and eosin. Cromolyn dramatically reduced Evans blue dye-positive fibers in all muscles (P<0.05; Student's t-test) and led to a significant increase in the percentage of fibers with peripheral nuclei. This study supports the protective effects of cromolyn in dystrophic muscles and further indicates its action against muscle fiber leakiness in muscles that are differently affected by the lack of dystrophin.

  4. Structural Dissection for Controlling Complex Networks

    CERN Document Server

    Wang, Wen-Xu; Zhao, Chen; Liu, Yang-Yu; Lai, Ying-Cheng

    2015-01-01

    Controlling complex networked systems has been a central goal in different fields and understanding controllability of complex networks has been at the forefront of contemporary science. Despite the recent progress in the development of controllability theories for complex networks, we continue to lack efficient tools to fully understand the effect of network topology and interaction strengths among nodes on controllability. Here we establish a framework to discern the significance of links and nodes for controlling general complex networks in a simple way based on local information. A dissection process is offered by the framework to probe and classify nodes and links completely, giving rise to a criterion for strong structural controllability. Analytical results indicate phase transitions associated with link and node categories, and strong structural controllability. Applying the tools to real networks demonstrate that real technological networks are strong structurally controllable, whereas most of real s...

  5. Controlling Congestion on Complex Networks

    CERN Document Server

    Buzna, Lubos

    2016-01-01

    From the Internet to road networks and the power grid, modern life depends on controlling flows on critical infrastructure networks that often operate in a congested state. Yet, we have a limited understanding of the relative performance of the control mechanisms available to manage congestion and of the interplay between network topology, path layout and congestion control algorithms. Here, we consider two flow algorithms (max-flow and uniform-flow), and two more realistic congestion control schemes (max-min fairness and proportional fairness). We analyse how the algorithms and network topology affect throughput, fairness and the location of bottleneck edges. Our results show that on large random networks a network operator can implement the trade-off (proportional fairness) instead of the fair allocation (max-min fairness) with little sacrifice in throughput. We illustrate how the previously studied uniform-flow approach leaves networks severely underutilised in comparison with congestion control algorithms...

  6. Control of Complex Multibody Spacecraft

    Science.gov (United States)

    1994-07-20

    Astronautical Sciences, vol. 40, no. 4, 1992, pp. 449-478. These results are of interest to JPL as a possible means to find unusual passively stable...Control, 1992. [43] M.E. Baraka , Optimal Control of Large Space Structures, Ph.D. Thesis, 1992 (Advisor: J.S. Baras) . [44] D.R. Augenstein, Parameter...Ph.D. dissertation of E1- Baraka (43) discusses his results on the problem of op- timal state feedback control for flexible structures using a spectral

  7. Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy.

    Science.gov (United States)

    Allen, David G; Whitehead, Nicholas P; Froehner, Stanley C

    2016-01-01

    Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca(2+)-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca(2+) entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease.

  8. Emergence of bimodality in controlling complex networks

    CERN Document Server

    Jia, Tao; Csóka, Endre; Pósfai, Márton; Slotine, Jean-Jacques; Barabási, Albert-László

    2015-01-01

    Our ability to control complex systems is a fundamental challenge of contemporary science. Recently introduced tools to identify the driver nodes, nodes through which we can achieve full control, predict the existence of multiple control configurations, prompting us to classify each node in a network based on their role in control. Accordingly a node is critical, intermittent or redundant if it acts as a driver node in all, some or none of the control configurations. Here we develop an analytical framework to identify the category of each node, leading to the discovery of two distinct control modes in complex systems: centralized vs distributed control. We predict the control mode for an arbitrary network and show that one can alter it through small structural perturbations. The uncovered bimodality has implications from network security to organizational research and offers new insights into the dynamics and control of complex systems.

  9. Pinning-controllability of complex networks

    OpenAIRE

    Sorrentino, Francesco; Di Bernardo, Mario; Garofalo, Franco; Chen, Guanrong

    2007-01-01

    We study the problem of controlling a general complex network towards an assigned synchronous evolution, by means of a pinning control strategy. We define the pinning-controllability of the network in terms of the spectral properties of an extended network topology. The roles of the control and coupling gains as well as of the number of pinned nodes are also discussed.

  10. Opinion control in complex networks

    Science.gov (United States)

    Masuda, Naoki

    2015-03-01

    In many political elections, the electorate appears to be a composite of partisan and independent voters. Given that partisans are not likely to convert to a different party, an important goal for a political party could be to mobilize independent voters toward the party with the help of strong leadership, mass media, partisans, and the effects of peer-to-peer influence. Based on the exact solution of classical voter model dynamics in the presence of perfectly partisan voters (i.e., zealots), we propose a computational method that uses pinning control strategy to maximize the share of a party in a social network of independent voters. The party, corresponding to the controller or zealots, optimizes the nodes to be controlled given the information about the connectivity of independent voters and the set of nodes that the opposing party controls. We show that controlling hubs is generally a good strategy, but the optimized strategy is even better. The superiority of the optimized strategy is particularly eminent when the independent voters are connected as directed (rather than undirected) networks.

  11. Opinion control in complex networks

    CERN Document Server

    Masuda, Naoki

    2014-01-01

    In many instances of election, the electorate appears to be a composite of partisan and independent voters. Given that partisans are not likely to convert to a different party, a main goal for a party could be to mobilize independent voters toward the party with the help of strong leadership, mass media, partisans, and effects of peer-to-peer influence. Based on the exact solution of the classical voter model dynamics in the presence of perfectly partisan voters (i.e., zealots), we propose a computational method to maximize the share of the party in a social network of independent voters by pinning control strategy. The party, corresponding to the controller or zealots, optimizes the nodes to be controlled given the information about the connectivity of independent voters and the set of nodes that the opponent party controls. We show that controlling hubs is generally a good strategy, whereas the optimized strategy is even better. The superiority of the optimized strategy is particularly eminent when the inde...

  12. Multistability and the control of complexity

    Energy Technology Data Exchange (ETDEWEB)

    Feudel, U.; Grebogi, C. [Institut fuer Physik, Universitaet Potsdam, PF 601553, D--14415 Potsdam (Germany)

    1997-12-01

    We show how multistability arises in nonlinear dynamics and discuss the properties of such a behavior. In particular, we show that most attractors are periodic in multistable systems, meaning that chaotic attractors are rare in such systems. After arguing that multistable systems have the general traits expected from a complex system, we pass to control them. Our controlling complexity ideas allow for both the stabilization and destabilization of any one of the coexisting states. The control of complexity differs from the standard control of chaos approach, an approach that makes use of the unstable periodic orbits embedded in an extended chaotic attractor. {copyright} {ital 1997 American Institute of Physics.}

  13. Predictive Approaches to Control of Complex Systems

    CERN Document Server

    Karer, Gorazd

    2013-01-01

    A predictive control algorithm uses a model of the controlled system to predict the system behavior for various input scenarios and determines the most appropriate inputs accordingly. Predictive controllers are suitable for a wide range of systems; therefore, their advantages are especially evident when dealing with relatively complex systems, such as nonlinear, constrained, hybrid, multivariate systems etc. However, designing a predictive control strategy for a complex system is generally a difficult task, because all relevant dynamical phenomena have to be considered. Establishing a suitable model of the system is an essential part of predictive control design. Classic modeling and identification approaches based on linear-systems theory are generally inappropriate for complex systems; hence, models that are able to appropriately consider complex dynamical properties have to be employed in a predictive control algorithm. This book first introduces some modeling frameworks, which can encompass the most frequ...

  14. Dystrophin, utrophin and {beta}-dystroglycan expression in skeletal muscle from patients with Becker muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Kawajiri, Masakazu; Mitsui, Takao; Kawai, Hisaomi [Univ. of Tokushima (Japan)] [and others

    1996-08-01

    The precise localization and semiquantitative correlation of dystrophin, utrophin and {beta}-dystroglycan expression on the sarcolemma of skeletal muscle cells obtained from patients with Becker muscular dystrophy (BMD) was studied using three types of double immunofluorescence. Staining intensity was measured using a confocal laser microscope. Each of these proteins was identified at the same locus on the sarcolemma. The staining intensities of dystrophin and utrophin were approximately reciprocal at sarcolemmal sites where dystrophin expression was obviously observed. The staining intensity of {beta}-dystroglycan was strong in areas where dystrophin staining was also strong and utrophin expression was weak. Quantitative analysis revealed that the staining intensity of {beta}-dystroglycan minus that of dystrophin approximated the staining intensity of utrophin, indicating that the sum of dystrophin and utrophin expression corresponds to that of {beta}-dystroglycan. These results suggest that utrophin may compensate for dystrophin deficiency found in BMD by binding to {beta}-dystroglycan. 35 refs., 3 figs., 1 tab.

  15. Controlling centrality in complex networks

    Science.gov (United States)

    Nicosia, V.; Criado, R.; Romance, M.; Russo, G.; Latora, V.

    2012-01-01

    Spectral centrality measures allow to identify influential individuals in social groups, to rank Web pages by popularity, and even to determine the impact of scientific researches. The centrality score of a node within a network crucially depends on the entire pattern of connections, so that the usual approach is to compute node centralities once the network structure is assigned. We face here with the inverse problem, that is, we study how to modify the centrality scores of the nodes by acting on the structure of a given network. We show that there exist particular subsets of nodes, called controlling sets, which can assign any prescribed set of centrality values to all the nodes of a graph, by cooperatively tuning the weights of their out-going links. We found that many large networks from the real world have surprisingly small controlling sets, containing even less than 5 – 10% of the nodes. PMID:22355732

  16. The dystrophin gene and cognitive function in the general population

    NARCIS (Netherlands)

    D. Vojinovic (Dina); H.H.H. Adams (Hieab); S. van der Lee (Sven); C.A. Ibrahim-Verbaas (Carla); R.W.W. Brouwer (Rutger); M.C.G.N. van den hout (Mirjam); E. Oole (Edwin); J. van Rooij (Jeroen); A.G. Uitterlinden (André); A. Hofman (Albert); W.F.J. van IJcken (Wilfred); A. Aartsma-Rus (Annemieke); G.-J.B. Van Ommen (Gert-Jan B.); M.A. Ikram (Arfan); C.M. van Duijn (Cornelia M.); N. Amin (Najaf)

    2015-01-01

    textabstractThe aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterd

  17. Synchronizability on complex networks via pinning control

    Indian Academy of Sciences (India)

    Yi Liang; Xingyuan Wang

    2013-04-01

    It is proved that the maximum eigenvalue sequence of the principal submatrices of coupling matrix is decreasing. The method of calculating the number of pinning nodes is given based on this theory. The findings reveal the relationship between the decreasing speed of maximum eigenvalue sequence of the principal submatrices for coupling matrix and the synchronizability on complex networks via pinning control. We discuss the synchronizability on some networks, such as scale-free networks and small-world networks. Numerical simulations show that different pinning strategies have different pinning synchronizability on the same complex network, and the synchronizability with pinning control is consistent with one without pinning control in various complex networks.

  18. Controlling centrality in complex networks

    CERN Document Server

    Nicosia, Vincenzo; Romance, Miguel; Russo, Giovanni; Latora, Vito

    2011-01-01

    Spectral centrality measures allow to identify influential individuals in social groups, to rank Web pages by their popularity, and even to determine the impact of scientific researches. The centrality score of a node within a network crucially depends on the entire pattern of connections, so that the usual approach is to compute the node centralities once the network structure is assigned. We face here with the inverse problem, that is, we study how to modify the centrality scores of the nodes by acting on the structure of a given network. We prove that there exist particular subsets of nodes, called controlling sets, which can assign any prescribed set of centrality values to all the nodes of a graph, by cooperatively tuning the weights of their out-going links. We show that many large networks from the real world have surprisingly small controlling sets, containing even less than 5-10% of the nodes. These results suggest that rankings obtained from spectral centrality measures have to be considered with ex...

  19. Multiplex ligation-dependent probe amplification for rapid detection of deletions and duplications in the dystrophin gene

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked disorders caused by mutations in the dystrophin gene. The majority of recognized mutations are copy number changes of individual exons. The objective of the present study was to assess the multiplex ligation-dependent probe amplification (MLPA) effects of detection of gene mutations. Methods: Samples of 20 control males and 80 males and their mothers referred to our diagnostic facility on the clinical suspicion of DMD or BMD were tested by MLPA and multiplex PCR. Results: The mean DQs for all peak of 20 control male samples was 1.02 (range from 0.83 to 1.21) by MLPA. Deletions or duplications were identified in 6 out of 31 families that had been previously tested as negative by multiplex PCR. One case of complex rearrangement involving a duplication of two regions: dupEX3-9 and dupEX 17-41 were found by MLPA. Conclusions: MLPA is a highly sensitive method and rapid alternative to multiplex PCR for detection of DMD and BMD.

  20. Control Complexity in Bucklin and Fallback Voting

    CERN Document Server

    Erdélyi, Gábor; Piras, Lena; Rothe, Jörg

    2011-01-01

    Electoral control models ways of changing the outcome of an election via such actions as adding/deleting/partitioning either candidates or voters. These actions modify an election's participation structure and aim at either making a favorite candidate win ("constructive control") or prevent a despised candidate from winning ("destructive control"). To protect elections from such control attempts, computational complexity has been used to show that electoral control, though not impossible, is computationally prohibitive. We show that fallback voting, an election system proposed by Brams and Sanver to combine Bucklin with approval voting, is resistant to each of the common types of control except to destructive control by either adding or deleting voters. Thus fallback voting displays the broadest control resistance currently known to hold among natural election systems with a polynomial-time winner problem. We also study the control complexity of Bucklin voting itself and show that it behaves almost as good (p...

  1. Pinning impulsive control algorithms for complex network.

    Science.gov (United States)

    Sun, Wen; Lü, Jinhu; Chen, Shihua; Yu, Xinghuo

    2014-03-01

    In this paper, we further investigate the synchronization of complex dynamical network via pinning control in which a selection of nodes are controlled at discrete times. Different from most existing work, the pinning control algorithms utilize only the impulsive signals at discrete time instants, which may greatly improve the communication channel efficiency and reduce control cost. Two classes of algorithms are designed, one for strongly connected complex network and another for non-strongly connected complex network. It is suggested that in the strongly connected network with suitable coupling strength, a single controller at any one of the network's nodes can always pin the network to its homogeneous solution. In the non-strongly connected case, the location and minimum number of nodes needed to pin the network are determined by the Frobenius normal form of the coupling matrix. In addition, the coupling matrix is not necessarily symmetric or irreducible. Illustrative examples are then given to validate the proposed pinning impulsive control algorithms.

  2. Constrained target controllability of complex networks

    Science.gov (United States)

    Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

    2017-06-01

    It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

  3. 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.

  4. Chimeric snRNA molecules carrying antisense sequences against the splice junctions of exon 51 of the dystrophin pre-mRNA induce exon skipping and restoration of a dystrophin synthesis in Δ48-50 DMD cells

    Science.gov (United States)

    De Angelis, Fernanda Gabriella; Sthandier, Olga; Berarducci, Barbara; Toso, Silvia; Galluzzi, Giuliana; Ricci, Enzo; Cossu, Giulio; Bozzoni, Irene

    2002-01-01

    Deletions and point mutations in the dystrophin gene cause either the severe progressive myopathy Duchenne muscular dystrophy (DMD) or the milder Becker muscular dystrophy, depending on whether the translational reading frame is lost or maintained. Because internal in-frame deletions in the protein produce only mild myopathic symptoms, it should be possible, by preventing the inclusion of specific mutated exon(s) in the mature dystrophin mRNA, to restore a partially corrected phenotype. Such control has been previously accomplished by the use of synthetic oligonucleotides; nevertheless, a significant drawback to this approach is caused by the fact that oligonucleotides would require periodic administrations. To circumvent this problem, we have produced several constructs able to express in vivo, in a stable fashion, large amounts of chimeric RNAs containing antisense sequences. In this paper we show that antisense molecules against exon 51 splice junctions are able to direct skipping of this exon in the human DMD deletion 48–50 and to rescue dystrophin synthesis. We also show that the highest skipping activity was found when antisense constructs against the 5′ and 3′ splice sites are coexpressed in the same cell. PMID:12077324

  5. Controlling complex networks with conformity behavior

    Science.gov (United States)

    Wang, Xu-Wen; Nie, Sen; Wang, Wen-Xu; Wang, Bing-Hong

    2015-09-01

    Controlling complex networks accompanied by common conformity behavior is a fundamental problem in social and physical science. Conformity behavior that individuals tend to follow the majority in their neighborhood is common in human society and animal communities. Despite recent progress in understanding controllability of complex networks, the existent controllability theories cannot be directly applied to networks associated with conformity. Here we propose a simple model to incorporate conformity-based decision making into the evolution of a network system, which allows us to employ the exact controllability theory to explore the controllability of such systems. We offer rigorous theoretical results of controllability for representative regular networks. We also explore real networks in different fields and some typical model networks, finding some interesting results that are different from the predictions of structural and exact controllability theory in the absence of conformity. We finally present an example of steering a real social network to some target states to further validate our controllability theory and tools. Our work offers a more realistic understanding of network controllability with conformity behavior and can have potential applications in networked evolutionary games, opinion dynamics and many other complex networked systems.

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

    Directory of Open Access Journals (Sweden)

    Sandra Murphy

    2015-09-01

    Full Text Available 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.

  7. Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

    Directory of Open Access Journals (Sweden)

    Sali Arpana

    2011-05-01

    Full Text Available Abstract Background Cardiomyopathy in Duchenne muscular dystrophy (DMD is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. Methods Three month old female mdx mice were exposed to the β1 receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188 (460 mg/kg/dose i.p. daily. Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD and picrosirius red staining. Results BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p Conclusions This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.

  8. Detection of an exon 53 polymorphism in the dystrophin gene.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Sedra, M S

    1993-10-01

    We utilized a heteroduplex method to screen for small mutations in Duchenne muscular dystrophy patients who did not have deletions or duplications. A dystrophin exon 53 heteroduplex band was identified in 14.4% of the affected patients. Direct sequencing of the amplified product from DNA producing the heteroduplex revealed the presence of a polymorphism in the coding region. The codon for asparagine was converted from AAT to AAC.

  9. 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.

  10. 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.

  11. 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.

  12. Spectrum of small mutations in the dystrophin coding region.

    Science.gov (United States)

    Prior, T W; Bartolo, C; Pearl, D K; Papp, A C; Snyder, P J; Sedra, M S; Burghes, A H; Mendell, J R

    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.

  13. Controlling complex Langevin dynamics at finite density

    Energy Technology Data Exchange (ETDEWEB)

    Aarts, Gert; Bongiovanni, Lorenzo [Swansea University, Department of Physics, College of Science, Swansea (United Kingdom); Seiler, Erhard [Max-Planck-Institut fuer Physik (Werner-Heisenberg-Institut), Muenchen (Germany); Sexty, Denes [Universitaet Heidelberg, Institut fuer Theoretische Physik, Heidelberg (Germany); Stamatescu, Ion-Olimpiu [Universitaet Heidelberg, Institut fuer Theoretische Physik, Heidelberg (Germany); FEST, Heidelberg (Germany)

    2013-07-15

    At nonzero chemical potential the numerical sign problem in lattice field theory limits the use of standard algorithms based on importance sampling. Complex Langevin dynamics provides a possible solution, but it has to be applied with care. In this review, we first summarise our current understanding of the approach, combining analytical and numerical insight. In the second part we study SL(N,C) gauge cooling, which was introduced recently as a tool to control complex Langevin dynamics in nonabelian gauge theories. We present new results in Polyakov chain models and in QCD with heavy quarks and compare various adaptive cooling implementations. (orig.)

  14. Controlling Complex Systems and Developing Dynamic Technology

    Science.gov (United States)

    Avizienis, Audrius Victor

    In complex systems, control and understanding become intertwined. Following Ilya Prigogine, we define complex systems as having control parameters which mediate transitions between distinct modes of dynamical behavior. From this perspective, determining the nature of control parameters and demonstrating the associated dynamical phase transitions are practically equivalent and fundamental to engaging with complexity. In the first part of this work, a control parameter is determined for a non-equilibrium electrochemical system by studying a transition in the morphology of structures produced by an electroless deposition reaction. Specifically, changing the size of copper posts used as the substrate for growing metallic silver structures by the reduction of Ag+ from solution under diffusion-limited reaction conditions causes a dynamical phase transition in the crystal growth process. For Cu posts with edge lengths on the order of one micron, local forces promoting anisotropic growth predominate, and the reaction produces interconnected networks of Ag nanowires. As the post size is increased above 10 microns, the local interfacial growth reaction dynamics couple with the macroscopic diffusion field, leading to spatially propagating instabilities in the electrochemical potential which induce periodic branching during crystal growth, producing dendritic deposits. This result is interesting both as an example of control and understanding in a complex system, and as a useful combination of top-down lithography with bottom-up electrochemical self-assembly. The second part of this work focuses on the technological development of devices fabricated using this non-equilibrium electrochemical process, towards a goal of integrating a complex network as a dynamic functional component in a neuromorphic computing device. Self-assembled networks of silver nanowires were reacted with sulfur to produce interfacial "atomic switches": silver-silver sulfide junctions, which exhibit

  15. Controlling edge dynamics in complex networks

    CERN Document Server

    Nepusz, Tamás

    2011-01-01

    The interaction of distinct units in physical, social, biological and technological systems naturally gives rise to complex network structures. Networks have constantly been in the focus of research for the last decade, with considerable advances in the description of their structural and dynamical properties. However, much less effort has been devoted to studying the controllability of the dynamics taking place on them. Here we introduce and evaluate a dynamical process defined on the edges of a network, and demonstrate that the controllability properties of this process significantly differ from simple nodal dynamics. Evaluation of real-world networks indicates that most of them are more controllable than their randomized counterparts. We also find that transcriptional regulatory networks are particularly easy to control. Analytic calculations show that networks with scale-free degree distributions have better controllability properties than uncorrelated networks, and positively correlated in- and out-degre...

  16. ADVANCED CONTROL OF A COMPLEX CHEMICAL PROCESS

    Directory of Open Access Journals (Sweden)

    Roxana Both

    Full Text Available Abstract Three phase catalytic hydrogenation reactors are important reactors with complex behavior due to the interaction among gas, solid and liquid phases with the kinetic, mass and heat transfer mechanisms. A nonlinear distributed parameter model was developed based on mass and energy conservation principles. It consists of balance equations for the gas and liquid phases, so that a system of partial differential equations is generated. Because detailed nonlinear mathematical models are not suitable for use in controller design, a simple linear mathematical model of the process, which describes its most important properties, was determined. Both developed mathematical models were validated using plant data. The control strategies proposed in this paper are a multivariable Smith Predictor PID controller and multivariable Smith Predictor structure in which the primary controllers are derived based on Internal Model Control. Set-point tracking and disturbance rejection tests are presented for both methods based on scenarios implemented in Matlab/SIMULINK.

  17. Robust Multiobjective Controllability of Complex Neuronal Networks.

    Science.gov (United States)

    Tang, Yang; Gao, Huijun; Du, Wei; Lu, Jianquan; Vasilakos, Athanasios V; Kurths, Jurgen

    2016-01-01

    This paper addresses robust multiobjective identification of driver nodes in the neuronal network of a cat's brain, in which uncertainties in determination of driver nodes and control gains are considered. A framework for robust multiobjective controllability is proposed by introducing interval uncertainties and optimization algorithms. By appropriate definitions of robust multiobjective controllability, a robust nondominated sorting adaptive differential evolution (NSJaDE) is presented by means of the nondominated sorting mechanism and the adaptive differential evolution (JaDE). The simulation experimental results illustrate the satisfactory performance of NSJaDE for robust multiobjective controllability, in comparison with six statistical methods and two multiobjective evolutionary algorithms (MOEAs): nondominated sorting genetic algorithms II (NSGA-II) and nondominated sorting composite differential evolution. It is revealed that the existence of uncertainties in choosing driver nodes and designing control gains heavily affects the controllability of neuronal networks. We also unveil that driver nodes play a more drastic role than control gains in robust controllability. The developed NSJaDE and obtained results will shed light on the understanding of robustness in controlling realistic complex networks such as transportation networks, power grid networks, biological networks, etc.

  18. 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 de

  19. Controlling edge dynamics in complex networks

    OpenAIRE

    Nepusz, Tamás; Vicsek, Tamás

    2012-01-01

    The interaction of distinct units in physical, social, biological and technological systems naturally gives rise to complex network structures. Networks have constantly been in the focus of research for the last decade, with considerable advances in the description of their structural and dynamical properties. However, much less effort has been devoted to studying the controllability of the dynamics taking place on them. Here we introduce and evaluate a dynamical process defined on the edges ...

  20. Polycomb repressive complex 1 controls uterine decidualization

    OpenAIRE

    Fenghua Bian; Fei Gao; Kartashov, Andrey V.; Jegga, Anil G; Artem Barski; Das, Sanjoy K.

    2016-01-01

    Uterine stromal cell decidualization is an essential part of the reproductive process. Decidual tissue development requires a highly regulated control of the extracellular tissue remodeling; however the mechanism of this regulation remains unknown. Through systematic expression studies, we detected that Cbx4/2, Rybp, and Ring1B [components of polycomb repressive complex 1 (PRC1)] are predominantly utilized in antimesometrial decidualization with polyploidy. Immunofluorescence analyses reveale...

  1. Parameterized Control Complexity in Fallback Voting

    CERN Document Server

    Erdélyi, Gábor

    2010-01-01

    We study the parameterized control complexity of fallback voting, a voting system that combines preference-based with approval voting. Electoral control is one of many different ways for an external agent to tamper with the outcome of an election. We show that adding and deleting candidates in fallback voting are W[2]-hard for both the constructive and destructive case, parameterized by the amount of action taken by the external agent. Furthermore, we show that adding and deleting voters in fallback voting are W[2]-hard for the constructive case, parameterized by the amount of action taken by the external agent, and are in FPT for the destructive case.

  2. 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.

  3. Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity.

    Science.gov (United States)

    Cox, G A; Cole, N M; Matsumura, K; Phelps, S F; Hauschka, S D; Campbell, K P; Faulkner, J A; Chamberlain, J S

    1993-08-19

    Duchenne and Becker muscular dystrophy (DMD and BMD) are X-linked recessive diseases caused by defective expression of dystrophin. The mdx mouse, an animal model for DMD, has a mutation that eliminates expression of the 427K muscle and brain isoforms of dystrophin. Although these animals do not display overt muscle weakness or impaired movement, the diaphragm muscle of the mdx mouse is severely affected and shows progressive myofibre degeneration and fibrosis which closely resembles the human disease. Here we explore the feasibility of gene therapy for DMD by examining the potential of a full-length dystrophin transgene to correct dystrophic symptoms in mdx mice. We find that expression of dystrophin in muscles of transgenic mdx mice eliminates the morphological and immunohistological symptoms of muscular dystrophy. In addition, overexpression of dystrophin prevents the development of the abnormal mechanical properties associated with dystrophic muscle without causing deleterious side effects. Our results provide functional evidence for the feasibility of gene therapy for DMD.

  4. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings

  5. Ultrastructural changes in the interstitial cells of Cajal and gastric dysrhythmias in mice lacking full-length dystrophin (mdx mice).

    Science.gov (United States)

    Vannucchi, Maria-Giuliana; Zizzo, Maria-Grazia; Zardo, Claudio; Pieri, Laura; Serio, Rosa; Mulè, Flavia; Faussone-Pellegrini, Maria-Simonetta

    2004-05-01

    At least two populations of c-kit positive interstitial cells of Cajal (ICC) lie in the gastric wall, one located at the myenteric plexus level has a pace-making function and the other located intramuscularly is intermediary in the neurotransmission and regenerates the slow waves. Both of these ICC sub-types express full-length dystrophin. Mdx mice, an animal model lacking in full-length dystrophin and used to study Duchenne muscular dystrophy (DMD), show gastric dismotilities. The aim of the present study was to verify in mdx mice whether: (i) gastric ICC undergo morphological changes, through immunohistochemical and ultrastructural analyses; and (ii) there are alterations in the electrical activity, using intracellular recording technique. In control mice, ICC sub-types showed heterogeneous ultrastructural features, either intramuscularly or at the myenteric plexus level. In mdx mice, all of the ICC sub-types underwent important changes: coated vesicles were significantly more numerous and caveolae significantly fewer than in control; moreover, cytoskeleton and smooth endoplasmic reticulum were reduced and mitochondria enlarged. c-Kit-positivity and integrity of the ICC networks were maintained. In the circular muscle of normal mice slow waves, which consisted of initial and secondary components, occurred with a regular frequency. In mdx mice, slow waves occurred in a highly dysrhythmic fashion and they lacked a secondary component. We conclude that the lack of the full-length dystrophin is associated with ultrastructural modifications of gastric ICC, most of which can be interpreted as signs of new membrane formation and altered Ca(2+) handling, and with defective generation and regeneration of slow wave activity.

  6. 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.

  7. 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

  8. Interactive formation control in complex environments.

    Science.gov (United States)

    Henry, Joseph; Shum, Hubert P H; Komura, Taku

    2014-02-01

    The degrees of freedom of a crowd is much higher than that provided by a standard user input device. Typically, crowd-control systems require multiple passes to design crowd movements by specifying waypoints, and then defining character trajectories and crowd formation. Such multi-pass control would spoil the responsiveness and excitement of real-time control systems. In this paper, we propose a single-pass algorithm to control a crowd in complex environments. We observe that low-level details in crowd movement are related to interactions between characters and the environment, such as diverging/merging at cross points, or climbing over obstacles. Therefore, we simplify the problem by representing the crowd with a deformable mesh, and allow the user, via multitouch input, to specify high-level movements and formations that are important for context delivery. To help prevent congestion, our system dynamically reassigns characters in the formation by employing a mass transport solver to minimize their overall movement. The solver uses a cost function to evaluate the impact from the environment, including obstacles and areas affecting movement speed. Experimental results show realistic crowd movement created with minimal high-level user inputs. Our algorithm is particularly useful for real-time applications including strategy games and interactive animation creation.

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

    Science.gov (United States)

    Li, Mei; Arner, Anders

    2015-01-01

    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.

  10. 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.

  11. Traffic Control Under Complex Weather Conditions in Suining Airport

    Institute of Scientific and Technical Information of China (English)

    吕维峰

    2014-01-01

    Complex weather conditions is meaning thunderstorm freezing turbulence wind-shear low visibility weather affect the flight safety. When confronted with complex weather conditions,the controllers should know the weather condition and trend weather,and notify the aircraft under your control zone.The controllers provide the required services to the pilots,help the pilots to avoid the complex weather.In this paper, through different complex weathers under different control command,get the different methods of control.

  12. Optimal control of complex atomic quantum systems

    Science.gov (United States)

    van Frank, S.; Bonneau, M.; Schmiedmayer, J.; Hild, S.; Gross, C.; Cheneau, M.; Bloch, I.; Pichler, T.; Negretti, A.; Calarco, T.; Montangero, S.

    2016-10-01

    Quantum technologies will ultimately require manipulating many-body quantum systems with high precision. Cold atom experiments represent a stepping stone in that direction: a high degree of control has been achieved on systems of increasing complexity. However, this control is still sub-optimal. In many scenarios, achieving a fast transformation is crucial to fight against decoherence and imperfection effects. Optimal control theory is believed to be the ideal candidate to bridge the gap between early stage proof-of-principle demonstrations and experimental protocols suitable for practical applications. Indeed, it can engineer protocols at the quantum speed limit – the fastest achievable timescale of the transformation. Here, we demonstrate such potential by computing theoretically and verifying experimentally the optimal transformations in two very different interacting systems: the coherent manipulation of motional states of an atomic Bose-Einstein condensate and the crossing of a quantum phase transition in small systems of cold atoms in optical lattices. We also show that such processes are robust with respect to perturbations, including temperature and atom number fluctuations.

  13. A defect in dystrophin causes a novel porcine stress syndrome

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2012-06-01

    Full Text Available Abstract Background Losses of slaughter-weight pigs due to transport stress are both welfare and economic concerns to pork producers. Historically, the HAL-1843 mutation in ryanodine receptor 1 was considered responsible for most of the losses; however, DNA testing has effectively eliminated this mutation from commercial herds. We identified two sibling barrows in the USMARC swine herd that died from apparent symptoms of a stress syndrome after transport at 12 weeks of age. The symptoms included open-mouth breathing, skin discoloration, vocalization and loss of mobility. Results We repeated the original mating along with sire-daughter matings to produce additional offspring. At 8 weeks of age, heart rate and electrocardiographs (ECG were monitored during isoflurane anesthesia challenge (3% for 3 min. Four males from the original sire-dam mating and two males from a sire-daughter mating died after one minute of anesthesia. Animals from additional litters were identified as having a stress response, sometimes resulting in death, during regular processing and weighing. Affected animals had elevated plasma creatine phosphokinase (CPK levels before and immediately after isoflurane challenge and cardiac arrhythmias. A pedigree containing 250 pigs, including 49 affected animals, was genotyped with the Illumina PorcineSNP60 Beadchip and only one chromosomal region, SSCX at 25.1-27.7 Mb over the dystrophin gene (DMD, was significantly associated with the syndrome. An arginine to tryptophan (R1958W polymorphism in exon 41 of DMD was the most significant marker associated with stress susceptibility. Immunoblots of affected heart and skeletal muscle showed a dramatic reduction of dystrophin protein and histopathology of affected hearts indicated muscle fiber degeneration. Conclusions A novel stress syndrome was characterized in pigs and the causative genetic factor most likely resides within DMD that results in less dystrophin protein and cardiac

  14. Analysis of dystrophin gene deletions by multiplex PCR in eastern India

    Directory of Open Access Journals (Sweden)

    Basak Jayasri

    2006-01-01

    Full Text Available The most common genetic neuromuscular disease of childhood, Duchenne and Becker muscular dystrophy (DMD/BMD is caused by deletion, duplication or point mutation of the dystrophin gene located at Xp 21.2. In the present study DNA from seventy unrelated patients clinically diagnosed as having DMD/BMD referred from different parts of West Bengal, a few other states and Bangladesh are analyzed using the multiplex polymerase chain reaction (m-PCR to screen for exon deletions and its distribution within the dystrophin gene. Out of seventy patients forty six (63% showed large intragenic deletion in the dystrophin gene. About 79% of these deletions are located in the hot spot region i.e., between exon 42 to 53. This is the first report of frequency and distribution of deletion in dystrophin gene in eastern Indian DMD/BMD population.

  15. Kolmogorov-Chaitin Complexity of Digital Controller Implementations

    Institute of Scientific and Technical Information of China (English)

    James F. Whidborne; John McKernan; Da-Wei Gu

    2006-01-01

    The complexity of linear, fixed-point arithmetic digital controllers is investigated from a Kolmogorov-Chaitin perspective. Based on the idea of Kolmogorov-Chaitin complexity, practical measures of complexity are developed for state-space realizations, parallel and cascade realizations, and for a newly proposed generalized implicit state-space realization.The complexity of solutions to a restricted complexity controller benchmark problem is investigated using this measure.The results show that from a Kolmogorov-Chaitin viewpoint, higher-order controllers with a shorter word-length may have lower complexity and better performance, than lower-order controllers with longer word-length.

  16. Toolkits Control Motion of Complex Robotics

    Science.gov (United States)

    2010-01-01

    That space is a hazardous environment for humans is common knowledge. Even beyond the obvious lack of air and gravity, the extreme temperatures and exposure to radiation make the human exploration of space a complicated and risky endeavor. The conditions of space and the space suits required to conduct extravehicular activities add layers of difficulty and danger even to tasks that would be simple on Earth (tightening a bolt, for example). For these reasons, the ability to scout distant celestial bodies and perform maintenance and construction in space without direct human involvement offers significant appeal. NASA has repeatedly turned to complex robotics for solutions to extend human presence deep into space at reduced risk and cost and to enhance space operations in low Earth orbit. At Johnson Space Center, engineers explore the potential applications of dexterous robots capable of performing tasks like those of an astronaut during extravehicular activities and even additional ones too delicate or dangerous for human participation. Johnson's Dexterous Robotics Laboratory experiments with a wide spectrum of robot manipulators, such as the Mitsubishi PA-10 and the Robotics Research K-1207i robotic arms. To simplify and enhance the use of these robotic systems, Johnson researchers sought generic control methods that could work effectively across every system.

  17. Electrotransfer of the full-length dog dystrophin into mouse and dystrophic dog muscles.

    Science.gov (United States)

    Pichavant, Christophe; Chapdelaine, Pierre; Cerri, Daniel G; Bizario, Joao C S; Tremblay, Jacques P

    2010-11-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by the absence of dystrophin (427 kDa). An approach to eventually restore this protein in patients with DMD is to introduce into their muscles a plasmid encoding dystrophin cDNA. Because the phenotype of the dystrophic dog is closer to the human phenotype than is the mdx mouse phenotype, we have studied the electrotransfer of a plasmid carrying the full-length dog dystrophin (FLDYS(dog)) in dystrophic dog muscle. To achieve this nonviral delivery, the FLDYS(dog) cDNA was cloned in two plasmids containing either a cytomegalovirus or a muscle creatine kinase promoter. In both cases, our results showed that the electrotransfer of these large plasmids (∼17 kb) into mouse muscle allowed FLDYS(dog) expression in the treated muscle. The electrotransfer of pCMV.FLDYS(dog) in a dystrophic dog muscle also led to the expression of dystrophin. In conclusion, introduction of the full-length dog dystrophin cDNA by electrotransfer into dystrophic dog muscle is a potential approach to restore dystrophin in patients with DMD. However, the electrotransfer procedure should be improved before applying it to humans.

  18. SWITCHING CONTROL:FROM SIMPLE RULES TO COMPLEX CHAOTIC SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    L(U) Jinhu

    2003-01-01

    This paper reviews and introduces some simple switching piecewise-linear controllers, which can generate complex chaotic behaviors from simple switching systems. The mechanism of simple switching rules creating complex chaotic behaviors is further investigated.

  19. 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

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

    Science.gov (United States)

    Legrand, Baptiste; Giudice, Emmanuel; Nicolas, Aurélie; Delalande, Olivier; Le Rumeur, Elisabeth

    2011-01-01

    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.

  1. 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.

  2. HEK293 cells express dystrophin Dp71 with nucleus-specific localization of Dp71ab.

    Science.gov (United States)

    Nishida, Atsushi; Yasuno, Sato; Takeuchi, Atsuko; Awano, Hiroyuki; Lee, Tomoko; Niba, Emma Tabe Eko; Fujimoto, Takahiro; Itoh, Kyoko; Takeshima, Yasuhiro; Nishio, Hisahide; Matsuo, Masafumi

    2016-09-01

    The dystrophin gene consists of 79 exons and encodes tissue-specific isoforms. Mutations in the dystrophin gene cause Duchenne muscular dystrophy, of which a substantial proportion of cases are complicated by non-progressive mental retardation. Abnormalities of Dp71, an isoform transcribed from a promoter in intron 62, are a suspected cause of mental retardation. However, the roles of Dp71 in human brain have not been fully elucidated. Here, we characterized dystrophin in human HEK293 cells with the neuronal lineage. Reverse transcription-PCR amplification of the full-length dystrophin transcript revealed the absence of fragments covering the 5' part of the dystrophin cDNA. In contrast, fragments covering exons 64-79 were present. The Dp71 promoter-specific exon G1 was shown spliced to exon 63. We demonstrated that the Dp71 transcript comprised two subisoforms: one lacking exon 78 (Dp71b) and the other lacking both exons 71 and 78 (Dp71ab). Western blotting of cell lysates using an antibody against the dystrophin C-terminal region revealed two bands, corresponding to Dp71b and Dp71ab. Immunohistochemical examination with the dystrophin antibody revealed scattered punctate signals in the cytoplasm and the nucleus. Western blotting revealed one band corresponding to Dp71b in the cytoplasm and two bands corresponding to Dp71b and Dp71ab in the nucleus, with Dp71b being predominant. These results indicated that Dp71ab is a nucleus-specific subisoform. We concluded that Dp71, comprising Dp71b and Dp71ab, was expressed exclusively in HEK293 cells and that Dp71ab was specifically localized to the nucleus. Our findings suggest that Dp71ab in the nucleus contributes to the diverse functions of HEK293 cells.

  3. Loss of dystrophin is associated with increased myocardial stiffness in a model of left ventricular hypertrophy.

    Science.gov (United States)

    Donato, Martín; Buchholz, Bruno; Morales, Celina; Valdez, Laura; Zaobornyj, Tamara; Baratta, Sergio; Paez, Diamela T; Matoso, Mirian; Vaccarino, Guillermo; Chejtman, Demian; Agüero, Oscar; Telayna, Juan; Navia, José; Hita, Alejandro; Boveris, Alberto; Gelpi, Ricardo J

    2017-08-01

    Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.

  4. Control system for the FFAG complex at KURRI

    Science.gov (United States)

    Tanigaki, M.; Takamiya, K.; Yoshino, H.; Abe, N.; Takeshita, T.; Osanai, A.

    2010-01-01

    A simple and convenient control system has been developed for the 150 MeV proton FFAG accelerator complex at Research Reactor Institute, Kyoto University. This control system is designed as a distributed control scheme and developed with simple and versatile tools, such as PLCs, LabVIEW and an IP based network, expecting applications in small accelerators, which are often operated by non-specialists in computer programming or in control systems. The control system for the FFAG accelerator complex has actually been developed by non-specialists, and the developed control system was successfully used for commissioning the FFAG complex.

  5. Code Samples Used for Complexity and Control

    Science.gov (United States)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    The following sections are included: * MathematicaⓇ Code * Generic Chaotic Simulator * Vector Differential Operators * NLS Explorer * 2C++ Code * C++ Lambda Functions for Real Calculus * Accelerometer Data Processor * Simple Predictor-Corrector Integrator * Solving the BVP with the Shooting Method * Linear Hyperbolic PDE Solver * Linear Elliptic PDE Solver * Method of Lines for a Set of the NLS Equations * C# Code * Iterative Equation Solver * Simulated Annealing: A Function Minimum * Simple Nonlinear Dynamics * Nonlinear Pendulum Simulator * Lagrangian Dynamics Simulator * Complex-Valued Crowd Attractor Dynamics * Freeform Fortran Code * Lorenz Attractor Simulator * Complex Lorenz Attractor * Simple SGE Soliton * Complex Signal Presentation * Gaussian Wave Packet * Hermitian Matrices * Euclidean L2-Norm * Vector/Matrix Operations * Plain C-Code: Levenberg-Marquardt Optimizer * Free Basic Code: 2D Crowd Dynamics with 3000 Agents

  6. Integrated pollution control for oil refinery complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kiperstok, A. [Bahia Univ., Salvador, BA (Brazil); Sharratt, P.N. [Manchester Univ. (United Kingdom). Inst. of Science and Technology

    1993-12-31

    Improving environmental performance of oil refineries is a complex task. Emission limits, operating constraints, available technologies, operating techniques, and local environment sensitivity must all be considered. This work describes efforts to build an interactive software to deal with this problem. 8 refs., 5 figs.

  7. Preservation of Muscle Force in Mdx3cv Mice Correlates with Low-Level Expression of a Near Full-Length Dystrophin Protein

    OpenAIRE

    2008-01-01

    The complete absence of dystrophin causes Duchenne muscular dystrophy. Its restoration by greater than 20% is needed to reduce muscle pathology and improve muscle force. Dystrophin levels lower than 20% are considered therapeutically irrelevant but are associated with a less severe phenotype in certain Becker muscular dystrophy patients. To understand the role of low-level dystrophin expression, we compared muscle force and pathology in mdx3cv and mdx4cv mice. Dystrophin was eliminated in mdx...

  8. 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.

  9. Monoclonal antibodies against the muscle-specific N-terminus of dystrophin: Characterization of dystrophin in a muscular dystrophy patient with a frameshift deletion of Exons 3-7

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, L. T.; Man, N. thi; Morris, G.E. (North East Wales Institute, Clwyd (United Kingdom)); Love, D.R.; Davies, K.E. (Institute of Molecular Medicine, John Radcliffe Hospital, Oxford (United Kingdom)); Helliwell, T.R. (Liverpool Univ. (United Kingdom))

    1993-07-01

    The first three exons of the human muscle dystrophin gene were expressed as a [beta]-galactosidase fusion protein. 1-his protein was then used to prepare two monoclonal antibodies (mAbs) which react with native dystrophin on frozen muscle sections and with denatured dystrophin on western blots but which do not cross-react with the distrophin-related protein, utrophin. Both mAbs recognized dystrophin in muscular dystrophy (MD) patients with deletions of exon 3, and further mapping with 11 overlapping synthetic peptides showed that they both recognize an epitope encoded by the muscle-specific exon 1. Neither mAb recognizes the brain dystrophin isoform, confirming the prediction from mRNA data that this has a different N-terminus. One Becker MD patient with a frameshift deletion of exons 3-7 is shown to produce dystrophin which reacts with the N-terminal mAbs, as well as with mAbs which bind on the C-terminal side of the deletion. The data suggest that transcription begins at the normal muscle dystrophin promoter and that the normal reading frame is restored after the deletion. A number of mechanisms have been proposed for restoration of the reading frame after deletion of exons 3-7, but those which predict dystrophin with an abnormal N-terminus do not appear to be major mechanisms in this patient. 27 refs., 6 figs.

  10. Communication and control for networked complex systems

    CERN Document Server

    Peng, Chen; Han, Qing-Long

    2015-01-01

    This book reports on the latest advances in the study of Networked Control Systems (NCSs). It highlights novel research concepts on NCSs; the analysis and synthesis of NCSs with special attention to their networked character; self- and event-triggered communication schemes for conserving limited network resources; and communication and control co-design for improving the efficiency of NCSs. The book will be of interest to university researchers, control and network engineers, and graduate students in the control engineering, communication and network sciences interested in learning the core principles, methods, algorithms and applications of NCSs.

  11. Analysis and control of complex dynamical systems robust bifurcation, dynamic attractors, and network complexity

    CERN Document Server

    Imura, Jun-ichi; Ueta, Tetsushi

    2015-01-01

    This book is the first to report on theoretical breakthroughs on control of complex dynamical systems developed by collaborative researchers in the two fields of dynamical systems theory and control theory. As well, its basic point of view is of three kinds of complexity: bifurcation phenomena subject to model uncertainty, complex behavior including periodic/quasi-periodic orbits as well as chaotic orbits, and network complexity emerging from dynamical interactions between subsystems. Analysis and Control of Complex Dynamical Systems offers a valuable resource for mathematicians, physicists, and biophysicists, as well as for researchers in nonlinear science and control engineering, allowing them to develop a better fundamental understanding of the analysis and control synthesis of such complex systems.

  12. 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.

  13. Is the human dystrophin gene's intron structure related to its intron instability?

    Institute of Scientific and Technical Information of China (English)

    盛文利; 陈江瑛; 朱良付; 刘焯霖

    2003-01-01

    Objective To study the human dystrophin gene molecular deletion mechanism, we analyzed breakpoint regions within junction fragments of deletion-type patients and investigated whether the dystrophin gene's intron structure might be related to intron instability.Methods Junction fragments corresponding to exon 46 and 51 deletions were cloned. The breakpoint regions were sequenced, and the features of introns with available Genebank sequences were analyzed.Results An analysis of junction fragment sequences corresponding to exon 46 and 51 deletions showed that all 5' and 3' breakpoints are located within repeat sequences. No small insertions, small deletions, or point mutations are located near the breakpoint junctions. By analyzing the secondary structure of the junction fragments, we demonstrated that all junction fragment breakpoints are located in non-matching regions of single-stranded hairpin loops. A high concentration of repetitive elements is found to be a key feature of many dystrophin introns. In total, 34.8% of the overall dystrophin intron sequences is composed of repeat sequences.Conclusion Repeat elements in many dystrophin gene introns are the key to their structural bases and reflect intron instability. As a result of the primary DNA sequences, single-stranded hairpin loops form, increasing the instability of the gene, and forming the base for breaks in the DNA. The formation of the single-stranded hairpins can result in reattachment of two different breakpoints, producing a deletion.

  14. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division.

    Science.gov (United States)

    Dumont, Nicolas A; Wang, Yu Xin; von Maltzahn, Julia; Pasut, Alessandra; Bentzinger, C Florian; Brun, Caroline E; Rudnicki, Michael A

    2015-12-01

    Dystrophin is expressed in differentiated myofibers, in which it is required for sarcolemmal integrity, and loss-of-function mutations in the gene that encodes it result in Duchenne muscular dystrophy (DMD), a disease characterized by progressive and severe skeletal muscle degeneration. Here we found that dystrophin is also highly expressed in activated muscle stem cells (also known as satellite cells), in which it associates with the serine-threonine kinase Mark2 (also known as Par1b), an important regulator of cell polarity. In the absence of dystrophin, expression of Mark2 protein is downregulated, resulting in the inability to localize the cell polarity regulator Pard3 to the opposite side of the cell. Consequently, the number of asymmetric divisions is strikingly reduced in dystrophin-deficient satellite cells, which also display a loss of polarity, abnormal division patterns (including centrosome amplification), impaired mitotic spindle orientation and prolonged cell divisions. Altogether, these intrinsic defects strongly reduce the generation of myogenic progenitors that are needed for proper muscle regeneration. Therefore, we conclude that dystrophin has an essential role in the regulation of satellite cell polarity and asymmetric division. Our findings indicate that muscle wasting in DMD not only is caused by myofiber fragility, but also is exacerbated by impaired regeneration owing to intrinsic satellite cell dysfunction.

  15. Parental source effect of inherited mutations in the dystrophin gene of mice and men

    Energy Technology Data Exchange (ETDEWEB)

    Kress, W.; Grimm, T.; Mueller, C.R. [Institute of Human Genetics, Wuerburg (Germany); Bittner, R. [Institute of Anatomy, Wein (Australia)

    1994-09-01

    Skewed X-inactivation has been suspected the genetic cause for some manifesting female carriers of BMD and DMD. To test whether a parental source effect on the protein expression of the dystrophin gene exists, we have set up backcrosses of mdx mice to wild type strains, enabling us to study the effect of the well-defined origin of the mutation on the dystrophin expression. In skeletal muscle sections the immunohistological staining patterns of dystrophin antibodies were showing a significant difference in the proportion of dystrophin positive versus negative fibers, suggesting a lower expression of paternally inherited mdx mutations. These data are in concordance with the pyruvate kinase (PK) levels in the serum: PK levels were much higher when the mutation was of maternal origin as compared to PK levels in paternally derived mutations. In order to test this {open_quotes}paternal source effect{close_quotes} in humans, we checked obligatory carriers of Becker muscular dystrophy (BMD) for the origin of their mutations. Creatin kinase (CK) levels in 21 carriers with maternally derived mutations were compared to CK values from 8 heterozygotes with mutations of paternal origin: CK (mat) = 140.3 IU/1 versus CK (pat) = 48.6 IU/I. The difference is statistically significant at the 5% level. These observations suggest either a differential X-inactivation or an imprinting of the dystrophin gene in mice and men.

  16. 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.

  17. ADVANCED CONTROL OF A COMPLEX CHEMICAL PROCESS

    OpenAIRE

    Roxana Both; Eva-Henrietta Dulf; Ana-Maria Cormos

    2016-01-01

    Abstract Three phase catalytic hydrogenation reactors are important reactors with complex behavior due to the interaction among gas, solid and liquid phases with the kinetic, mass and heat transfer mechanisms. A nonlinear distributed parameter model was developed based on mass and energy conservation principles. It consists of balance equations for the gas and liquid phases, so that a system of partial differential equations is generated. Because detailed nonlinear mathematical models are not...

  18. Centralized Stochastic Optimal Control of Complex Systems

    Energy Technology Data Exchange (ETDEWEB)

    Malikopoulos, Andreas [ORNL

    2015-01-01

    In this paper we address the problem of online optimization of the supervisory power management control in parallel hybrid electric vehicles (HEVs). We model HEV operation as a controlled Markov chain using the long-run expected average cost per unit time criterion, and we show that the control policy yielding the Pareto optimal solution minimizes the average cost criterion online. The effectiveness of the proposed solution is validated through simulation and compared to the solution derived with dynamic programming using the average cost criterion.

  19. Complex systems relationships between control, communications and computing

    CERN Document Server

    2016-01-01

    This book gives a wide-ranging description of the many facets of complex dynamic networks and systems within an infrastructure provided by integrated control and supervision: envisioning, design, experimental exploration, and implementation. The theoretical contributions and the case studies presented can reach control goals beyond those of stabilization and output regulation or even of adaptive control. Reporting on work of the Control of Complex Systems (COSY) research program, Complex Systems follows from and expands upon an earlier collection: Control of Complex Systems by introducing novel theoretical techniques for hard-to-control networks and systems. The major common feature of all the superficially diverse contributions encompassed by this book is that of spotting and exploiting possible areas of mutual reinforcement between control, computing and communications. These help readers to achieve not only robust stable plant system operation but also properties such as collective adaptivity, integrity an...

  20. Dynamics Control of the Complex Systems via Nondifferentiability

    Directory of Open Access Journals (Sweden)

    Carmen Nejneru

    2013-01-01

    Full Text Available A new topic in the analyses of complex systems dynamics, considering that the movements of complex system entities take place on continuum but nondifferentiable curves, is proposed. In this way, some properties of complex systems (barotropic-type behaviour, self-similarity behaviour, chaoticity through turbulence and stochasticization, etc. are controlled through nondifferentiability of motion curves. These behaviours can simulate the standard properties of the complex systems (emergence, self-organization, adaptability, etc..

  1. Dynamics Control of the Complex Systems via Nondifferentiability

    OpenAIRE

    Carmen Nejneru; Anca Nicuţă; Boris Constantin; Liliana Rozemarie Manea; Mirela Teodorescu; Maricel Agop

    2013-01-01

    A new topic in the analyses of complex systems dynamics, considering that the movements of complex system entities take place on continuum but nondifferentiable curves, is proposed. In this way, some properties of complex systems (barotropic-type behaviour, self-similarity behaviour, chaoticity through turbulence and stochasticization, etc.) are controlled through nondifferentiability of motion curves. These behaviours can simulate the standard properties of the complex systems (emergence, se...

  2. Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs

    Directory of Open Access Journals (Sweden)

    Voit Thomas

    2011-04-01

    Full Text Available Abstract Background This study aimed to measure the gait abnormalities in GRMD (Golden retriever muscular dystrophy dogs during growth and disease progression using an ambulatory gait analyzer (3D-accelerometers as a possible tool to assess the effects of a therapeutic intervention. Methods Six healthy and twelve GRMD dogs were evaluated twice monthly, from the age of two to nine months. The evolution of each gait variable previously shown to be modified in control and dystrophin-deficient adults was assessed using two-ways variance analysis (age, clinical status with repeated measurements. A principal component analysis (PCA was applied to perfect multivariate data interpretation. Results Speed, stride length, total power and force significantly already decreased (p Conclusion The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials.

  3. Operational Assessment of Controller Complexity Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In today's operations, acceptable levels of controller workload are maintained by assigning sector capacities based on simple aircraft count and a capacity threshold...

  4. B Complex Test Control Center (TCC) #4210

    Data.gov (United States)

    Federal Laboratory Consortium — The TCC is a dual control room facility for the B-1 and B-2 Test Positions on the B-Stand. The TCC houses continually-updated, state-of-the-art Data Acquisition and...

  5. Complex systems and networks dynamics, controls and applications

    CERN Document Server

    Yu, Xinghuo; Chen, Guanrong; Yu, Wenwu

    2016-01-01

    This elementary book provides some state-of-the-art research results on broad disciplinary sciences on complex networks. It presents an in-depth study with detailed description of dynamics, controls and applications of complex networks. The contents of this book can be summarized as follows. First, the dynamics of complex networks, for example, the cluster dynamic analysis by using kernel spectral methods, community detection algorithms in bipartite networks, epidemiological modeling with demographics and epidemic spreading on multi-layer networks, are studied. Second, the controls of complex networks are investigated including topics like distributed finite-time cooperative control of multi-agent systems by applying homogenous-degree and Lyapunov methods, composite finite-time containment control for disturbed second-order multi-agent systems, fractional-order observer design of multi-agent systems, chaos control and anticontrol of complex systems via Parrondos game and many more. Third, the applications of ...

  6. Heteroduplex analysis of the dystrophin gene: application to point mutation and carrier detection.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Sedra, M S; Western, L M; Bartolo, C; Moxley, R T; Mendell, J R

    1994-03-01

    Approximately one-third of the 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, we 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. We conclude that the technique is not only ideal for mutation detection but is also useful for diagnostic testing.

  7. 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.

  8. Dystrophin expression in a Duchenne muscular dystrophy patient with a frame shift deletion.

    Science.gov (United States)

    Prior, T W; Bartolo, C; Papp, A C; Snyder, P J; Sedra, M S; Burghes, A H; Kissel, J T; Luquette, M H; Tsao, C Y; Mendell, J R

    1997-02-01

    The exon 45 deletion is a common dystrophin gene deletion. Although this is an out-of-frame deletion, which should not allow for protein synthesis, it has been observed in mildly affected patients. We describe a patient with an exon 45 deletion who produced protein, but still had a severe Duchenne muscular dystrophy phenotype. RT-PCR analysis and cDNA sequencing from the muscle biopsy sample revealed that the exon 45 deletion induced exon skipping of exon 44, which resulted in an in-frame deletion and the production of dystrophin. A conformational change in dystrophin induced by the deletion is proposed as being responsible for the severe phenotype in the patient. We feel that the variable clinical phenotype observed in patients with the exon 45 deletion is not due to exon splicing but may be the result of other environmental or genetic factors, or both.

  9. Controlling chaos to solutions with complex eigenvalues.

    Science.gov (United States)

    Kwon, Oh-Jong; Lee, Hoyun

    2003-02-01

    We derive formulas for parameter and variable perturbations to control chaos using linearized dynamics. They are available irrespective of the dimension of the system, the number of perturbed parameters or variables, and the kinds of eigenvalues of the linearized dynamics. We illustrate this using the two coupled Duffing oscillators and the two coupled standard maps.

  10. Managing Complexity of Control Software through Concurrency

    NARCIS (Netherlands)

    Hilderink, G.H.

    2005-01-01

    In this thesis, we are concerned with the development of concurrent software for embedded systems. The emphasis is on the development of control software. Embedded systems are concurrent systems whereby hardware and software communicate with the concurrent world. Concurrency is essential, which

  11. Differential expression of myosin heavy chain isoforms in the masticatory muscles of dystrophin-deficient mice.

    Science.gov (United States)

    Spassov, Alexander; Gredes, Tomasz; Gedrange, Tomasz; Lucke, Silke; Morgenstern, Sven; Pavlovic, Dragan; Kunert-Keil, Christiane

    2011-12-01

    The dystrophin-deficient mouse (mdx) is a homologue animal model of Duchenne muscular dystrophy (DMD) and is characterized by slowly progressive muscle weakness accompanied by changes in myosin heavy chain (MyHC) composition. It is likely that the masticatory muscles undergo similar changes. The aim of this study was to examine the masticatory muscles (masseter, temporal, tongue, and soleus) of 100-day-old mdx and control mice (n = 8-10), and the fibre type distribution (by immunohistochemistry) as well as the expression of the corresponding MyHC messenger RNA (mRNA) (protein and mRNA expression, using Western blot or quantitative real-time polymerase chain reaction (RT-PCR)). Immunohistochemistry and western blot analysis revealed that the masticatory muscles in the control and mdx mice consisted mainly of type 2 fibres, whereas soleus muscle consisted of both type 1 and 2 fibres. In the masseter muscle, the mRNA in mdx mice was not different from that found in the controls. However, the mRNA content of the MyHC-2b isoform in mdx mice was lower in comparison with the controls in the temporal muscle [11.9 versus 36.9 per cent; P muscle (65.7 versus 73.8 per cent; P muscle was lower than in the controls (25.9 versus 30.8 per cent; P muscles of mdx mice may lead to changed fibre type composition. The different MyHC gene expression in mdx mice masticatory muscles may be seen as an adaptive mechanism to muscular dystrophy.

  12. INFORMATION AND COMPLEXITY IN CONTROL SYSTEMS: A TUTORIAL

    Institute of Scientific and Technical Information of China (English)

    WANG Leyi

    2001-01-01

    This is a tutorial paper which presents schematically theconcepts of information, uncertainty, and complexity, and their relationships in their applications to control systems. By focusing on exact or lower bounds on achievable performance in the presence of uncertainties, studies of complexity in a control system can potentially reveal fundamentally limiting factors of the system, suggest beneficial modifications to system structures and hardware configurations to remove these limitations, provide benchmark values for evaluating a design and for quantifying rooms for performance improvement, and demonstrate intrinsic tradeoffs. Compared to its counterparts in communications (Shannon's information theory), computations (computational complexity and information-based complexity), and approximations (n-widths and Kolmogorov entropy), studies of information and complexity in control systems encounter further challenges, such as characterization of feedback robustness, interaction between identification and control, and co-existence of deterministic and stochastic uncertainties. Some of these issues are outlined and discussed.

  13. Exon exchange approach to repair Duchenne dystrophin transcripts.

    Directory of Open Access Journals (Sweden)

    Stéphanie Lorain

    Full Text Available BACKGROUND: Trans-splicing strategies for mRNA repair involve engineered transcripts designed to anneal target mRNAs in order to interfere with their natural splicing, giving rise to mRNA chimeras where endogenous mutated exons have been replaced by exogenous replacement sequences. A number of trans-splicing molecules have already been proposed for replacing either the 5' or the 3' part of transcripts to be repaired. Here, we show the feasibility of RNA surgery by using a double trans-splicing approach allowing the specific substitution of a given mutated exon. METHODOLOGY/PRINCIPAL FINDINGS: As a target we used a minigene encoding a fragment of the mdx dystrophin gene enclosing the mutated exon (exon 23. This minigene was cotransfected with a variety of exon exchange constructions, differing in their annealing domains. We obtained accurate and efficient replacement of exon 23 in the mRNA target. Adding up a downstream intronic splice enhancer DISE in the exon exchange molecule enhanced drastically its efficiency up to 25-45% of repair depending on the construction in use. CONCLUSIONS/SIGNIFICANCE: These results demonstrate the possibility to fix up mutated exons, refurbish deleted exons and introduce protein motifs, while keeping natural untranslated sequences, which are essential for mRNA stability and translation regulation. Conversely to the well-known exon skipping, exon exchange has the advantage to be compatible with almost any type of mutations and more generally to a wide range of genetic conditions. In particular, it allows addressing disorders caused by dominant mutations.

  14. Controlling defectiveness in a complex product

    Energy Technology Data Exchange (ETDEWEB)

    Harris, C.L.

    1976-09-01

    A common practice when measuring defectiveness in a complicated product is to assign ''demerit'' points to each defect in proportion to the seriousness of the fault. A plan is presented for monitoring defectives by using a modified demerit per unit control chart. The statistics presented are basic to control charts for demerits. What is different is the chart format which has the advantage of minimum effort for daily updates and independence from required sample sizes. Basically, the charts were designed for simplicity of use where product quantities are not large. Emphasis is placed on maintaining perspective between plotting data and completing the circle of defect reporting, analysis and corrective action feedback.

  15. Increased constitutive nitric oxide production by whole body periodic acceleration ameliorates alterations in cardiomyocytes associated with utrophin/dystrophin deficiency.

    Science.gov (United States)

    Lopez, Jose R; Kolster, Juan; Zhang, Rui; Adams, Jose

    2017-07-01

    Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn(-/-), or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age. Nitric oxide (NO) is an important signaling molecule involved in vital functions of regulating rhythm, contractility, and microcirculation of the heart, and constitutive NO production affects the function of proteins involved in excitation-contraction coupling. In this study, we explored the efficacy of enhancing NO production as a therapeutic strategy for treating DMD cardiomyopathy using the dKO mouse model of DMD. Specifically, NO production was induced via whole body periodic acceleration (pGz), a novel non-pharmacologic intervention which enhances NO synthase (NOS) activity through sinusoidal motion of the body in a headward-footward direction, introducing pulsatile shear stress to the vascular endothelium and cardiomyocyte plasma membrane. Male dKO mice were randomized at 8weeks of age to receive daily pGz (480cpm, Gz±3.0m/s(2), 1h/d) for 4weeks or no treatment, and a separate age-matched group of WT animals (pGz-treated and untreated) served as non-diseased controls. At the conclusion of the protocol, cardiomyocytes from untreated dKO animals had, respectively, 4.3-fold and 3.5-fold higher diastolic resting concentration of Ca(2+) ([Ca(2+)]d) and Na(+) ([Na(+)]d) compared to WT, while pGz treatment significantly reduced these levels. For dKO cardiomyocytes, pGz treatment also improved the depressed contractile function, decreased oxidative stress, blunted the elevation in calpain activity, and mitigated the abnormal increase in [Ca

  16. Synchronization of general complex networks via adaptive control schemes

    Indian Academy of Sciences (India)

    Ping He; Chun-Guo Jing; Chang-Zhong Chen; Tao Fan; Hassan Saberi Nik

    2014-03-01

    In this paper, the synchronization problem of general complex networks is investigated by using adaptive control schemes. Time-delay coupling, derivative coupling, nonlinear coupling etc. exist universally in real-world complex networks. The adaptive synchronization scheme is designed for the complex network with multiple class of coupling terms. A criterion guaranteeing synchronization of such complex networks is established by employing the Lyapunov stability theorem and adaptive control schemes. Finally, an illustrative example with numerical simulation is given to show the feasibility and efficiency of theoretical results.

  17. Low-complexity controllers for time-delay systems

    CERN Document Server

    Özbay, Hitay; Bonnet, Catherine; Mounier, Hugues

    2014-01-01

    This volume in the newly established series Advances in Delays and Dynamics (ADD@S) provides a collection of recent results on the design and analysis of Low Complexity Controllers for Time Delay Systems. A widely used indirect method to obtain low order controllers for time delay systems is to design a controller for the reduced order model of the plant. In the dual indirect approach, an infinite dimensional controller is designed first for the original plant model; then, the controller is approximated by keeping track of the degradation in performance and stability robustness measures. The present volume includes new techniques used at different stages of the indirect approach. It also includes new direct design methods for fixed structure and low order controllers. On the other hand, what is meant by low complexity controller is not necessarily low order controller. For example, Smith predictor or similar type of controllers include a copy of the plant internally in the controller, so they are technically ...

  18. A Multiobjective Optimization Framework for Stochastic Control of Complex Systems

    Energy Technology Data Exchange (ETDEWEB)

    Malikopoulos, Andreas [ORNL; Maroulas, Vasileios [ORNL; Xiong, Professor Jie [The University of Tennessee

    2015-01-01

    This paper addresses the problem of minimizing the long-run expected average cost of a complex system consisting of subsystems that interact with each other and the environment. We treat the stochastic control problem as a multiobjective optimization problem of the one-stage expected costs of the subsystems, and we show that the control policy yielding the Pareto optimal solution is an optimal control policy that minimizes the average cost criterion for the entire system. For practical situations with constraints consistent to those we study here, our results imply that the Pareto control policy may be of value in deriving online an optimal control policy in complex systems.

  19. 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.

  20. Optimizing controllability of complex networks by minimum structural perturbations.

    Science.gov (United States)

    Wang, Wen-Xu; Ni, Xuan; Lai, Ying-Cheng; Grebogi, Celso

    2012-02-01

    To drive a large, complex, networked dynamical system toward some desired state using as few external signals as possible is a fundamental issue in the emerging field of controlling complex networks. Optimal control is referred to the situation where such a network can be fully controlled using only one driving signal. We propose a general approach to optimizing the controllability of complex networks by judiciously perturbing the network structure. The principle of our perturbation method is validated theoretically and demonstrated numerically for homogeneous and heterogeneous random networks and for different types of real networks as well. The applicability of our method is discussed in terms of the relative costs of establishing links and imposing external controllers. Besides the practical usage of our approach, its implementation elucidates, interestingly, the intricate relationship between certain structural properties of the network and its controllability.

  1. Safety control program for complex system based on behavior science

    Institute of Scientific and Technical Information of China (English)

    LIANG Mei-jian; YANG Guang; CHEN Da-wei

    2008-01-01

    To control complex system's safety effectively,safety control program was supported based on the principles of behavioral science that shapes organizational behavior,and organizational behavior produced individual behavior.The program can be structured into a model that consists of three modules including individual behavior rectification,organization behavior diagnosis and model of safety culture.The research result not only reveals the deep cause of complex system accidents but also provides structural descriptions with the accidents cause.

  2. Safety control program for complex system based on behavior science

    Institute of Scientific and Technical Information of China (English)

    LIANG Mei-jian; YANG Guang; CHEN Da-wei

    2008-01-01

    To control complex system's safety effectively, safety control program was supported based on the principles of behavioral science that shapes organizational be-havior, and organizational behavior produced individual behavior. The program can be structured into a model that consists of three modules including individual behavior rectifi-cation, organization behavior diagnosis and model of safety culture. The research result not only reveals the deep cause of complex system accidents but also provides structural descriptions with the accidents cause.

  3. Computational Biomathematics: Toward Optimal Control of Complex Biological Systems

    Science.gov (United States)

    2016-09-26

    Computational Biomathematics: Toward Optimal Control Of Complex Biological Systems See attached. The views, opinions and/or findings contained in this... Control Of Complex Biological Systems Report Title See attached. (a) Papers published in peer-reviewed journals (N/A for none) Enter List of papers...substantially lowered. Since the equations depend on what information we are interested in, automatic conversion of agent-based models to systems of

  4. The Complex Network Synchronization via Chaos Control Nodes

    Directory of Open Access Journals (Sweden)

    Yin Li

    2013-01-01

    Full Text Available We investigate chaos control nodes of the complex network synchronization. The structure of the coupling functions between the connected nodes is obtained based on the chaos control method and Lyapunov stability theory. Moreover a complex network with nodes of the new unified Loren-Chen-Lü system, Coullet system, Chee-Lee system, and the New system is taken as an example; numerical simulations are used to verify the effectiveness of the method.

  5. Semiotic aspects of control and modeling relations in complex systems

    Energy Technology Data Exchange (ETDEWEB)

    Joslyn, C.

    1996-08-01

    A conceptual analysis of the semiotic nature of control is provided with the goal of elucidating its nature in complex systems. Control is identified as a canonical form of semiotic relation of a system to its environment. As a form of constraint between a system and its environment, its necessary and sufficient conditions are established, and the stabilities resulting from control are distinguished from other forms of stability. These result from the presence of semantic coding relations, and thus the class of control systems is hypothesized to be equivalent to that of semiotic systems. Control systems are contrasted with models, which, while they have the same measurement functions as control systems, do not necessarily require semantic relations because of the lack of the requirement of an interpreter. A hybrid construction of models in control systems is detailed. Towards the goal of considering the nature of control in complex systems, the possible relations among collections of control systems are considered. Powers arguments on conflict among control systems and the possible nature of control in social systems are reviewed, and reconsidered based on our observations about hierarchical control. Finally, we discuss the necessary semantic functions which must be present in complex systems for control in this sense to be present at all.

  6. Early manifestation of alteration in cardiac function in dystrophin deficient mdx mouse using 3D CMR tagging

    Directory of Open Access Journals (Sweden)

    Zhong Jia

    2009-10-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is caused by the absence of the cytoskeletal protein, dystrophin. In DMD patients, dilated cardiomyopathy leading to heart failure may occur during adolescence. However, early cardiac dysfunction is frequently undetected due to physical inactivity and generalized debilitation. The objective of this study is to determine the time course of cardiac functional alterations in mdx mouse, a mouse model of DMD, by evaluating regional ventricular function with CMR tagging. Methods In vivo myocardial function was evaluated by 3D CMR tagging in mdx mice at early (2 months, middle (7 months and late (10 months stages of disease development. Global cardiac function, regional myocardial wall strains, and ventricular torsion were quantified. Myocardial lesions were assessed with Masson's trichrome staining. Results Global contractile indexes were similar between mdx and C57BL/6 mice in each age group. Histology analysis showed that young mdx mice were free of myocardial lesions. Interstitial fibrosis was present in 7 month mdx mice, with further development into patches or transmural lesions at 10 months of age. As a result, 10 month mdx mice showed significantly reduced regional strain and torsion. However, young mdx mice showed an unexpected increase in regional strain and torsion, while 7 month mdx mice displayed similar regional ventricular function as the controls. Conclusion Despite normal global ventricular function, CMR tagging detected a biphasic change in myocardial wall strain and torsion, with an initial increase at young age followed by progressive decrease at older ages. These results suggest that CMR tagging can provide more sensitive measures of functional alterations than global functional indexes in dystrophin-related cardiomyopathies.

  7. 2′-O-Methyl RNA/Ethylene-Bridged Nucleic Acid Chimera Antisense Oligonucleotides to Induce Dystrophin Exon 45 Skipping

    Directory of Open Access Journals (Sweden)

    Tomoko Lee

    2017-02-01

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51, which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons. For improved clinical benefits, this strategy requires more studies of the delivery method and modification of nucleic acids. We studied a nucleotide with a 2′-O,4′-C-ethylene-bridged nucleic acid (ENA, which shows high nuclease resistance and high affinity for complementary RNA strands. Here, we describe the process of developing a 2′-O-methyl RNA(2′-OMeRNA/ENA chimera AO to induce dystrophin exon 45 skipping. One 18-mer 2′-OMeRNA/ENA chimera (AO85 had the most potent activity for inducing exon 45 skipping in cultured myotubes. AO85 was administered to mdx mice without significant side effects. AO85 transfection into cultured myotubes from 13 DMD patients induced exon 45 skipping in all samples at different levels and dystrophin expression in 11 patients. These results suggest the possible efficacy of AO-mediated exon skipping changes in individual patients and highlight the 2′-OMeRNA/ENA chimera AO as a potential fundamental treatment for DMD.

  8. 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...... of new potential therapeutic targets....

  9. Proteomic Profiling of the Dystrophin-Deficient mdx Phenocopy of Dystrophinopathy-Associated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ashling Holland

    2014-01-01

    Full Text Available Cardiorespiratory complications are frequent symptoms of Duchenne muscular dystrophy, a neuromuscular disorder caused by primary abnormalities in the dystrophin gene. Loss of cardiac dystrophin initially leads to changes in dystrophin-associated glycoproteins and subsequently triggers secondarily sarcolemmal disintegration, fibre necrosis, fibrosis, fatty tissue replacement, and interstitial inflammation. This results in progressive cardiac disease, which is the cause of death in a considerable number of patients afflicted with X-linked muscular dystrophy. In order to better define the molecular pathogenesis of this type of cardiomyopathy, several studies have applied mass spectrometry-based proteomics to determine proteome-wide alterations in dystrophinopathy-associated cardiomyopathy. Proteomic studies included both gel-based and label-free mass spectrometric surveys of dystrophin-deficient heart muscle from the established mdx animal model of dystrophinopathy. Comparative cardiac proteomics revealed novel changes in proteins associated with mitochondrial energy metabolism, glycolysis, signaling, iron binding, antibody response, fibre contraction, basal lamina stabilisation, and cytoskeletal organisation. This review summarizes the importance of studying cardiomyopathy within the field of muscular dystrophy research, outlines key features of the mdx heart and its suitability as a model system for studying cardiac pathogenesis, and discusses the impact of recent proteomic findings for exploring molecular and cellular aspects of cardiac abnormalities in inherited muscular dystrophies.

  10. 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.

  11. 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.

  12. Dystrophin and the two related genetic diseases, Duchenne and Becker muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Elisabeth Le Rumeur

    2015-07-01

    Full Text Available Mutations of the dystrophin DMD gene, essentially deletions of one or several exons, are the cause of two devastating and to date incurable diseases, Duchenne (DMD and Becker (BMD muscular dystrophies. Depending upon the preservation or not of the reading frame, dystrophin is completely absent in DMD, or present in either a mutated or a truncated form in BMD. DMD is a severe disease which leads to a premature death of the patients. Therapy approaches are evolving with the aim to transform the severe DMD in the BMD form of the disease by restoring the expression of a mutated or truncated dystrophin. These therapies are based on the assumption that BMD is a mild disease. However, this is not completely true as BMD patients are more or less severely affected and no molecular basis of this heterogeneity of the BMD form of the disease is yet understood. The aim of this review is to report for the correlation between dystrophin structures in BMD deletions in view of this heterogeneity and to emphasize that examining BMD patients in details is highly relevant to anticipate for DMD therapy effects.

  13. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue

    2012-01-01

    Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

  14. 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

  15. Complexity Control of Fast Motion Estimation in H.264/MPEG-4 AVC with Rate-Distortion-Complexity optimization

    DEFF Research Database (Denmark)

    Wu, Mo; Forchhammer, Søren; Aghito, Shankar Manuel

    2007-01-01

    A complexity control algorithm for H.264 advanced video coding is proposed. The algorithm can control the complexity of integer inter motion estimation for a given target complexity. The Rate-Distortion-Complexity performance is improved by a complexity prediction model, simple analysis of the past...

  16. Input graph: the hidden geometry in controlling complex networks

    Science.gov (United States)

    Zhang, Xizhe; Lv, Tianyang; Pu, Yuanyuan

    2016-11-01

    The ability to control a complex network towards a desired behavior relies on our understanding of the complex nature of these social and technological networks. The existence of numerous control schemes in a network promotes us to wonder: what is the underlying relationship of all possible input nodes? Here we introduce input graph, a simple geometry that reveals the complex relationship between all control schemes and input nodes. We prove that the node adjacent to an input node in the input graph will appear in another control scheme, and the connected nodes in input graph have the same type in control, which they are either all possible input nodes or not. Furthermore, we find that the giant components emerge in the input graphs of many real networks, which provides a clear topological explanation of bifurcation phenomenon emerging in dense networks and promotes us to design an efficient method to alter the node type in control. The findings provide an insight into control principles of complex networks and offer a general mechanism to design a suitable control scheme for different purposes.

  17. Novel Complex Polymers with Carbazole Functionality by Controlled Radical Polymerization

    Directory of Open Access Journals (Sweden)

    Kazuhiro Nakabayashi

    2012-01-01

    Full Text Available This review summarizes recent advances in the design and synthesis of novel complex polymers with carbazole moieties using controlled radical polymerization techniques. We focus on the polymeric architectures of block copolymers, star polymers, including star block copolymers and miktoarm star copolymers, comb-shaped copolymers, and hybrids. Controlled radical polymerization of N-vinylcarbazole (NVC and styrene and (methacrylate derivatives having carbazole moieties is well advanced, leading to the well-controlled synthesis of complex macromolecules. Characteristic optoelectronic properties, assembled structures, and three-dimensional architectures are briefly introduced.

  18. Unified Modeling of Complex Real-Time Control Systems

    CERN Document Server

    Hai, He; Chi-Lan, Cai

    2011-01-01

    Complex real-time control system is a software dense and algorithms dense system, which needs modern software engineering techniques to design. UML is an object-oriented industrial standard modeling language, used more and more in real-time domain. This paper first analyses the advantages and problems of using UML for real-time control systems design. Then, it proposes an extension of UML-RT to support time-continuous subsystems modeling. So we can unify modeling of complex real-time control systems on UML-RT platform, from requirement analysis, model design, simulation, until generation code.

  19. Strategy optimization for controlled Markov process with descriptive complexity constraint

    Institute of Scientific and Technical Information of China (English)

    JIA QingShan; ZHAO QianChuan

    2009-01-01

    Due to various advantages in storage and Implementation,simple strategies are usually preferred than complex strategies when the performances are close.Strategy optimization for controlled Markov process with descriptive complexity constraint provides a general framework for many such problems.In this paper,we first show by examples that the descriptive complexity and the performance of a strategy could be Independent,and use the F-matrix in the No-Free-Lunch Theorem to show the risk that approximating complex strategies may lead to simple strategies that are unboundedly worse in cardinal performance than the original complex strategies.We then develop a method that handles the descriptive complexity constraint directly,which describes simple strategies exactly and only approximates complex strategies during the optimization.The ordinal performance difference between the resulting strategies of this selective approximation method and the global optimum is quantified.Numerical examples on an engine maintenance problem show how this method Improves the solution quality.We hope this work sheds some insights to solving general strategy optimization for controlled Markov procase with descriptive complexity constraint.

  20. Adaptive Missile Flight Control for Complex Aerodynamic Phenomena

    Science.gov (United States)

    2017-08-09

    e.g., top -right fin at beginning of animation while the vehicle is at a high angle of attack). These data illustrate these complex aerodynamic...optimal controllers. The poor roll control performance of the optimal controller means that the airframe flies at those aerodynamic angles while spinning ...corrected spinning projectile. J Spacecraft Rockets. 1975;12(12):733–738. 2. Chandgadkar S, Costello M, Dano B, Liburdy J, Pence D. Performance of a

  1. Design of Low Complexity Model Reference Adaptive Controllers

    Science.gov (United States)

    Hanson, Curt; Schaefer, Jacob; Johnson, Marcus; Nguyen, Nhan

    2012-01-01

    Flight research experiments have demonstrated that adaptive flight controls can be an effective technology for improving aircraft safety in the event of failures or damage. However, the nonlinear, timevarying nature of adaptive algorithms continues to challenge traditional methods for the verification and validation testing of safety-critical flight control systems. Increasingly complex adaptive control theories and designs are emerging, but only make testing challenges more difficult. A potential first step toward the acceptance of adaptive flight controllers by aircraft manufacturers, operators, and certification authorities is a very simple design that operates as an augmentation to a non-adaptive baseline controller. Three such controllers were developed as part of a National Aeronautics and Space Administration flight research experiment to determine the appropriate level of complexity required to restore acceptable handling qualities to an aircraft that has suffered failures or damage. The controllers consist of the same basic design, but incorporate incrementally-increasing levels of complexity. Derivations of the controllers and their adaptive parameter update laws are presented along with details of the controllers implementations.

  2. Control capability analysis for complex spacecraft thruster configurations

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The set of forces and moments that can be generated by thrusters of a spacecraft is called the"control capability"with respect to the thruster configuration.If the control capability of a thruster configuration is adequate to fulfill a given space mission,we say this configuration is a feasible one with respect to the task.This study proposed a new way to analyze the control capability of the complex thruster configuration.Precise mathematical definitions of feasibility were proposed,based on which a criterion to judge the feasibility of the thruster configuration was presented through calculating the shortest distance to the boundary of the controllable region as a function of the thruster configuration.Finally,control capability analysis for the complex thruster configuration based on its feasibility with respect to the space mission was given followed by a 2-D thruster configuration example to demonstrate its validity.

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

    National Research Council Canada - National Science Library

    Finkel, Richard S; Flanigan, Kevin M; Wong, Brenda; Bönnemann, Carsten; Sampson, Jacinda; Sweeney, H Lee; Reha, Allen; Northcutt, Valerie J; Elfring, Gary; Barth, Jay; Peltz, Stuart W

    2013-01-01

    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...

  4. Modelling, Estimation and Control of Networked Complex Systems

    CERN Document Server

    Chiuso, Alessandro; Frasca, Mattia; Rizzo, Alessandro; Schenato, Luca; Zampieri, Sandro

    2009-01-01

    The paradigm of complexity is pervading both science and engineering, leading to the emergence of novel approaches oriented at the development of a systemic view of the phenomena under study; the definition of powerful tools for modelling, estimation, and control; and the cross-fertilization of different disciplines and approaches. This book is devoted to networked systems which are one of the most promising paradigms of complexity. It is demonstrated that complex, dynamical networks are powerful tools to model, estimate, and control many interesting phenomena, like agent coordination, synchronization, social and economics events, networks of critical infrastructures, resources allocation, information processing, or control over communication networks. Moreover, it is shown how the recent technological advances in wireless communication and decreasing in cost and size of electronic devices are promoting the appearance of large inexpensive interconnected systems, each with computational, sensing and mobile cap...

  5. Pinning control of clustered complex networks with different size

    Science.gov (United States)

    Fu, Chenbo; Wang, Jinbao; Xiang, Yun; Wu, Zhefu; Yu, Li; Xuan, Qi

    2017-08-01

    In pinning control of complex networks, it is found that, with the same pinning effort, the network can be better controlled by pinning the large-degree nodes. But in the clustered complex networks, this preferential pinning (PP) strategy is losing its effectiveness. In this paper, we demonstrate that in the clustered complex networks, especially when the clusters have different size, the random pinning (RP) strategy performs much better than the PP strategy. Then, we propose a new pinning strategy based on cluster degree. It is revealed that the new cluster pinning strategy behaves better than RP strategy when there are only a smaller number of pinning nodes. The mechanism is studied by using eigenvalue and eigenvector analysis, and the simulations of coupled chaotic oscillators are given to verify the theoretical results. These findings could be beneficial for the design of control schemes in some practical systems.

  6. Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

    Science.gov (United States)

    Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

    2017-01-01

    The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity. PMID:28218249

  7. Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

    Science.gov (United States)

    Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

    2017-02-01

    The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.

  8. Qualitative analysis and control of complex neural networks with delays

    CERN Document Server

    Wang, Zhanshan; Zheng, Chengde

    2016-01-01

    This book focuses on the stability of the dynamical neural system, synchronization of the coupling neural system and their applications in automation control and electrical engineering. The redefined concept of stability, synchronization and consensus are adopted to provide a better explanation of the complex neural network. Researchers in the fields of dynamical systems, computer science, electrical engineering and mathematics will benefit from the discussions on complex systems. The book will also help readers to better understand the theory behind the control technique and its design.

  9. Controlling Uncertainty Decision Making and Learning in Complex Worlds

    CERN Document Server

    Osman, Magda

    2010-01-01

    Controlling Uncertainty: Decision Making and Learning in Complex Worlds reviews and discusses the most current research relating to the ways we can control the uncertain world around us.: Features reviews and discussions of the most current research in a number of fields relevant to controlling uncertainty, such as psychology, neuroscience, computer science and engineering; Presents a new framework that is designed to integrate a variety of disparate fields of research; Represents the first book of its kind to provide a general overview of work related to understanding control

  10. Rate control algorithm based on frame complexity estimation for MVC

    Science.gov (United States)

    Yan, Tao; An, Ping; Shen, Liquan; Zhang, Zhaoyang

    2010-07-01

    Rate control has not been well studied for multi-view video coding (MVC). In this paper, we propose an efficient rate control algorithm for MVC by improving the quadratic rate-distortion (R-D) model, which reasonably allocate bit-rate among views based on correlation analysis. The proposed algorithm consists of four levels for rate bits control more accurately, of which the frame layer allocates bits according to frame complexity and temporal activity. Extensive experiments show that the proposed algorithm can efficiently implement bit allocation and rate control according to coding parameters.

  11. A new topology for the control of complex interferometers

    Energy Technology Data Exchange (ETDEWEB)

    Rabeling, David S; Gossler, Stefan; Cumpston, Jeffrey; Gray, Malcolm B; McClelland, David E [Centre for Gravitational Physics, Faculty of Science, Australian National University, Canberra, 0200 (Australia)

    2006-04-21

    We discuss a new control topology which will generate control signals for the output optics of complex interferometers operating on a pure dark fringe. Our system, which involves the injection of a modulated control field through the output port of the interferometer, is also compatible with the use of squeezed light. We discuss this topology in the context of the control of an interferometer featuring a variable reflectivity signal recycling mirror and present results from a coupled cavity geometry to demonstrate some of the features.

  12. The semiotics of control and modeling relations in complex systems.

    Science.gov (United States)

    Joslyn, C

    2001-01-01

    We provide a conceptual analysis of ideas and principles from the systems theory discourse which underlie Pattee's semantic or semiotic closure, which is itself foundational for a school of theoretical biology derived from systems theory and cybernetics, and is now being related to biological semiotics and explicated in the relational biological school of Rashevsky and Rosen. Atomic control systems and models are described as the canonical forms of semiotic organization, sharing measurement relations, but differing topologically in that control systems are circularly and models linearly related to their environments. Computation in control systems is introduced, motivating hierarchical decomposition, hybrid modeling and control systems, and anticipatory or model-based control. The semiotic relations in complex control systems are described in terms of relational constraints, and rules and laws are distinguished as contingent and necessary functional entailments, respectively. Finally, selection as a meta-level of constraint is introduced as the necessary condition for semantic relations in control systems and models.

  13. Efficient target control of complex networks based on preferential matching

    CERN Document Server

    Zhang, Xizhe; Lv, Tianyang

    2016-01-01

    Controlling a complex network towards a desire state is of great importance in many applications. Existing works present an approximate algorithm to find the driver nodes used to control partial nodes of the network. However, the driver nodes obtained by this algorithm depend on the matching order of nodes and cannot get the optimum results. Here we present a novel algorithm to find the driver nodes for target control based on preferential matching. The algorithm elaborately arrange the matching order of nodes in order to minimize the size of the driver nodes set. The results on both synthetic and real networks indicate that the performance of proposed algorithm are better than the previous one. The algorithm may have various application in controlling complex networks.

  14. Complex envelope control of pulsed accelerating fields in superconducting cavities

    CERN Document Server

    Czarski, T

    2010-01-01

    A digital control system for superconducting cavities of a linear accelerator is presented in this work. FPGA (Field Programmable Gate Arrays) based controller, managed by MATLAB, was developed to investigate a novel firmware implementation. The LLRF - Low Level Radio Frequency system for FLASH project in DESY is introduced. Essential modeling of a cavity resonator with signal and power analysis is considered as a key approach to the control methods. An electrical model is represented by the non-stationary state space equation for the complex envelope of the cavity voltage driven by the current generator and the beam loading. The electromechanical model of the superconducting cavity resonator including the Lorentz force detuning has been developed for a simulation purpose. The digital signal processing is proposed for the field vector detection. The field vector sum control is considered for multiple cavities driven by one klystron. An algebraic, complex domain model is proposed for the system analysis. The c...

  15. Connecting core percolation and controllability of complex networks.

    Science.gov (United States)

    Jia, Tao; Pósfai, Márton

    2014-06-20

    Core percolation is a fundamental structural transition in complex networks related to a wide range of important problems. Recent advances have provided us an analytical framework of core percolation in uncorrelated random networks with arbitrary degree distributions. Here we apply the tools in analysis of network controllability. We confirm analytically that the emergence of the bifurcation in control coincides with the formation of the core and the structure of the core determines the control mode of the network. We also derive the analytical expression related to the controllability robustness by extending the deduction in core percolation. These findings help us better understand the interesting interplay between the structural and dynamical properties of complex networks.

  16. Edge orientation for optimizing controllability of complex networks.

    Science.gov (United States)

    Xiao, Yan-Dong; Lao, Song-Yang; Hou, Lv-Lin; Bai, Liang

    2014-10-01

    Recently, as the controllability of complex networks attracts much attention, how to design and optimize the controllability of networks has become a common and urgent problem in the field of controlling complex networks. Previous work focused on the structural perturbation and neglected the role of edge direction to optimize the network controllability. In a recent work [Phys. Rev. Lett. 103, 228702 (2009)], the authors proposed a simple method to enhance the synchronizability of networks by assignment of link direction while keeping network topology unchanged. However, the controllability is fundamentally different from synchronization. In this work, we systematically propose the definition of assigning direction to optimize controllability, which is called the edge orientation for optimal controllability problem (EOOC). To solve the EOOC problem, we construct a switching network and transfer the EOOC problem to find the maximum independent set of the switching network. We prove that the principle of our optimization method meets the sense of unambiguity and optimum simultaneously. Furthermore, the relationship between the degree-degree correlations and EOOC are investigated by experiments. The results show that the disassortativity pattern could weaken the orientation for optimal controllability, while the assortativity pattern has no correlation with EOOC. All the experimental results of this work verify that the network structure determines the network controllability and the optimization effects.

  17. A dynamic epidemic control model on uncorrelated complex networks

    Institute of Scientific and Technical Information of China (English)

    Pei Wei-Dong; Chen Zeng-Qiang; Yuan Zhu-Zhi

    2008-01-01

    In this paper,a dynamic epidemic control model on the uncorrelated complex networks is proposed.By means of theoretical analysis,we found that the new model has a similar epidemic threshold as that of the susceptible-infectedrecovered (SIR) model on the above networks,but it can reduce the prevalence of the infected individuals remarkably.This result may help us understand epidemic spreading phenomena on real networks and design appropriate strategies to control infections.

  18. Quantum Sensing of Noisy and Complex Systems under Dynamical Control

    Directory of Open Access Journals (Sweden)

    Gershon Kurizki

    2016-12-01

    Full Text Available We review our unified optimized approach to the dynamical control of quantum-probe interactions with noisy and complex systems viewed as thermal baths. We show that this control, in conjunction with tools of quantum estimation theory, may be used for inferring the spectral and spatial characteristics of such baths with high precision. This approach constitutes a new avenue in quantum sensing, dubbed quantum noise spectroscopy.

  19. 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/.

  20. 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.

  1. A missense mutation in the dystrophin gene in a Duchenne muscular dystrophy patient.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Burghes, A H; Bartolo, C; Sedra, M S; Western, L M; Mendell, J R

    1993-08-01

    About two thirds of Duchenne muscular dystrophy (DMD) patients have either gene deletions or duplications. The other DMD cases are most likely the result of point mutations that cannot be easily identified by current strategies. Utilizing a heteroduplex technique and direct sequencing of amplified products, we screened our nondeletion/duplication DMD population for point mutations. We now describe what we believe to be the first dystrophin missense mutation in a DMD patient. The mutation results in the substitution of an evolutionarily conserved leucine to arginine in the actin-binding domain. The patient makes a dystrophin protein which is properly localized and is present at a higher level than is observed in DMD patients. This suggests that an intact actin-binding domain is necessary for protein stability and essential for function.

  2. Intelligent Transportation Control based on Proactive Complex Event Processing

    Directory of Open Access Journals (Sweden)

    Wang Yongheng

    2016-01-01

    Full Text Available Complex Event Processing (CEP has become the key part of Internet of Things (IoT. Proactive CEP can predict future system states and execute some actions to avoid unwanted states which brings new hope to intelligent transportation control. In this paper, we propose a proactive CEP architecture and method for intelligent transportation control. Based on basic CEP technology and predictive analytic technology, a networked distributed Markov decision processes model with predicting states is proposed as sequential decision model. A Q-learning method is proposed for this model. The experimental evaluations show that this method works well when used to control congestion in in intelligent transportation systems.

  3. Controller Design of Complex System Based on Nonlinear Strength

    Directory of Open Access Journals (Sweden)

    Rongjun Mu

    2015-01-01

    Full Text Available This paper presents a new idea of controller design for complex systems. The nonlinearity index method was first developed for error propagation of nonlinear system. The nonlinearity indices access the boundary between the strong and the weak nonlinearities of the system model. The algorithm of nonlinearity index according to engineering application is first proposed in this paper. Applying this method on nonlinear systems is an effective way to measure the nonlinear strength of dynamics model over the full flight envelope. The nonlinearity indices access the boundary between the strong and the weak nonlinearities of system model. According to the different nonlinear strength of dynamical model, the control system is designed. The simulation time of dynamical complex system is selected by the maximum value of dynamic nonlinearity indices. Take a missile as example; dynamical system and control characteristic of missile are simulated. The simulation results show that the method is correct and appropriate.

  4. Variable structure control of complex systems analysis and design

    CERN Document Server

    Yan, Xing-Gang; Edwards, Christopher

    2017-01-01

    This book systematizes recent research work on variable-structure control. It is self-contained, presenting necessary mathematical preliminaries so that the theoretical developments can be easily understood by a broad readership. The text begins with an introduction to the fundamental ideas of variable-structure control pertinent to their application in complex nonlinear systems. In the core of the book, the authors lay out an approach, suitable for a large class of systems, that deals with system uncertainties with nonlinear bounds. Its treatment of complex systems in which limited measurement information is available makes the results developed convenient to implement. Various case-study applications are described, from aerospace, through power systems to river pollution control with supporting simulations to aid the transition from mathematical theory to engineering practicalities. The book addresses systems with nonlinearities, time delays and interconnections and considers issues such as stabilization, o...

  5. Reliability Architecture for Collaborative Robot Control Systems in Complex Environments

    Directory of Open Access Journals (Sweden)

    Liang Tang

    2016-02-01

    Full Text Available Many different kinds of robot systems have been successfully deployed in complex environments, while research into collaborative control systems between different robots, which can be seen as a hybrid internetware safety-critical system, has become essential. This paper discusses ways to construct robust and secure reliability architecture for collaborative robot control systems in complex environments. First, the indication system for evaluating the realtime reliability of hybrid internetware systems is established. Next, a dynamic collaborative reliability model for components of hybrid internetware systems is proposed. Then, a reliable, adaptive and evolutionary computation method for hybrid internetware systems is proposed, and a timing consistency verification solution for collaborative robot control internetware applications is studied. Finally, a multi-level security model supporting dynamic resource allocation is established.

  6. Antisense oligonucleotide induced exon skipping and the dystrophin gene transcript: cocktails and chemistries

    Directory of Open Access Journals (Sweden)

    Fletcher Sue

    2007-07-01

    Full Text Available Abstract Background Antisense oligonucleotides (AOs can interfere with exon recognition and intron removal during pre-mRNA processing, and induce excision of a targeted exon from the mature gene transcript. AOs have been used in vitro and in vivo to redirect dystrophin pre-mRNA processing in human and animal cells. Targeted exon skipping of selected exons in the dystrophin gene transcript can remove nonsense or frame-shifting mutations that would otherwise have lead to Duchenne Muscular Dystrophy, the most common childhood form of muscle wasting. Results Although many dystrophin exons can be excised using a single AO, several exons require two motifs to be masked for efficient or specific exon skipping. Some AOs were inactive when applied individually, yet pronounced exon excision was induced in transfected cells when the AOs were used in select combinations, clearly indicating synergistic rather than cumulative effects on splicing. The necessity for AO cocktails to induce efficient exon removal was observed with 2 different chemistries, 2'-O-methyl modified bases on a phosphorothioate backbone and phosphorodiamidate morpholino oligomers. Similarly, other trends in exon skipping, as a consequence of 2'-O-methyl AO action, such as removal of additional flanking exons or variations in exon skipping efficiency with overlapping AOs, were also seen when the corresponding sequences were prepared as phosphorodiamidate morpholino oligomers. Conclusion The combination of 2 AOs, directed at appropriate motifs in target exons was found to induce very efficient targeted exon skipping during processing of the dystrophin pre-mRNA. This combinatorial effect is clearly synergistic and is not influenced by the chemistry of the AOs used to induce exon excision. A hierarchy in exon skipping efficiency, observed with overlapping AOs composed of 2'-O-methyl modified bases, was also observed when these same sequences were evaluated as phosphorodiamidate morpholino

  7. 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.

  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

    , and suggested that significant changes in mdx/ADAM12 muscle might occur post-transcriptionally. Indeed, by immunostaining and immunoblotting we found an approximately 2-fold increase in expression, and distinct extrasynaptic localization, of alpha 7B integrin and utrophin, the functional homolog of dystrophin....... The expression of the dystrophin-associated glycoproteins was also increased. In conclusion, these results demonstrate a novel way to alleviate dystrophin deficiency in mice, and may stimulate the development of new approaches to compensate for dystrophin deficiency in animals and humans....

  9. Optimal control of complex networks based on matrix differentiation

    Science.gov (United States)

    Li, Guoqi; Ding, Jie; Wen, Changyun; Pei, Jing

    2016-09-01

    Finding the key node set to be connected to external control sources so as to minimize the energy for controlling a complex network, known as the minimum-energy control problem, is of critical importance but remains open. We address this critical problem where matrix differentiation is involved. To this end, the differentiation of energy/cost function with respect to the input matrix is obtained based on tensor analysis, and the Hessian matrix is compressed from a fourth-order tensor. Normalized projected gradient method (NPGM) normalized projected trust-region method (NPTM) are proposed with established convergence property. We show that NPGM is more computationally efficient than NPTM. Simulation results demonstrate satisfactory performance of the algorithms, and reveal important insights as well. Two interesting phenomena are observed. One is that the key node set tends to divide elementary paths equally. The other is that the low-degree nodes may be more important than hubs from a control point of view, indicating that controlling hub nodes does not help to lower the control energy. These results suggest a way of achieving optimal control of complex networks, and provide meaningful insights for future researches.

  10. In silico analyses of dystrophin Dp40 cellular distribution, nuclear export signals and structure modeling

    Directory of Open Access Journals (Sweden)

    Alejandro Martínez-Herrera

    2015-09-01

    Full Text Available Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular dystrophy gene. This protein is unique since it lacks the C-terminal end of dystrophins. In this data article, we describe the subcellular localization, nuclear export signals and the three-dimensional structure modeling of putative Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear. Changes L93P and L170P are involved in the nuclear localization of Dp40n4 protein. A close analysis of Dp40 protein scored that amino acids 93LEQEHNNLV101 and 168LLLHDSIQI176 could function as NES sequences and the scores are lost in Dp40n4. In addition, the changes L93/170P modify the tertiary structure of putative Dp40 mutants. The analysis showed that changes of residues 93 and 170 from leucine to proline allow the nuclear localization of Dp40 proteins. The data described here are related to the research article entitled “EF-hand domains are involved in the differential cellular distribution of dystrophin Dp40” (J. Aragón et al. Neurosci. Lett. 600 (2015 115–120 [1].

  11. 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.

  12. 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.

  13. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9.

    Science.gov (United States)

    Chen, Yongchang; Zheng, Yinghui; Kang, Yu; Yang, Weili; Niu, Yuyu; Guo, Xiangyu; Tu, Zhuchi; Si, Chenyang; Wang, Hong; Xing, Ruxiao; Pu, Xiuqiong; Yang, Shang-Hsun; Li, Shihua; Ji, Weizhi; Li, Xiao-Jiang

    2015-07-01

    CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy.

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

    Science.gov (United States)

    Robinson-Hamm, Jacqueline N; Gersbach, Charles A

    2016-09-01

    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.

  15. 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.

  16. 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.

  17. Complexity and Control: Towards a Rigorous Behavioral Theory of Complex Dynamical Systems

    Science.gov (United States)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    We introduce our motive for writing this book on complexity and control with a popular "complexity myth," which seems to be quite wide spread among chaos and complexity theory fashionistas: Low-dimensional systems usually exhibit complex behaviours (which we know fromMay's studies of the Logisticmap), while high-dimensional systems usually exhibit simple behaviours (which we know from synchronisation studies of the Kuramoto model)... We admit that this naive view on complex (e.g., human) systems versus simple (e.g., physical) systems might seem compelling to various technocratic managers and politicians; indeed, the idea makes for appealing sound-bites. However, it is enough to see both in the equations and computer simulations of pendula of various degree - (i) a single pendulum, (ii) a double pendulum, and (iii) a triple pendulum - that this popular myth is plain nonsense. The only thing that we can learn from it is what every tyrant already knows: by using force as a strong means of control, it is possible to effectively synchronise even hundreds of millions of people, at least for a while.

  18. Complex-Vector Time-Delay Control of Power Converters

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Loh, P. C.; Tang, Y.;

    2008-01-01

    Precise controlling of current produced by power converters is an important topic that has attracted interests over the last few decades. With the recent proliferation of grid-tied converters where the control of power flow is indirectly governed by the accuracy of current tracking, motivation...... to develop dynamically fast and accurate current controllers is even more intensive with more features expected to be embedded within a single control module. Believing in its continual importance, this paper contributes by proposing a complex-vector time-delay control scheme that can achieve high tracking...... precision and disturbance rejection. In principle, the proposed scheme can either be implemented solely in the stationary frame or in a "mixed" stationary and synchronous frame, termed as mixed frame in the paper. Regardless of the frame orientation chosen, the scheme always exhibits ease of implementation...

  19. Mitotic Exit Control as an Evolved Complex System

    Energy Technology Data Exchange (ETDEWEB)

    Bosl, W; Li, R

    2005-04-25

    The exit from mitosis is the last critical decision a cell has to make during a division cycle. A complex regulatory system has evolved to evaluate the success of mitotic events and control this decision. Whereas outstanding genetic work in yeast has led to rapid discovery of a large number of interacting genes involved in the control of mitotic exit, it has also become increasingly difficult to comprehend the logic and mechanistic features embedded in the complex molecular network. Our view is that this difficulty stems in part from the attempt to explain mitotic exit control using concepts from traditional top-down engineering design, and that exciting new results from evolutionary engineering design applied to networks and electronic circuits may lend better insights. We focus on four particularly intriguing features of the mitotic exit control system: the two-stepped release of Cdc14; the self-activating nature of Tem1 GTPase; the spatial sensor associated with the spindle pole body; and the extensive redundancy in the mitotic exit network. We attempt to examine these design features from the perspective of evolutionary design and complex system engineering.

  20. Complex collaborative problem-solving processes in mission control.

    Science.gov (United States)

    Fiore, Stephen M; Wiltshire, Travis J; Oglesby, James M; O'Keefe, William S; Salas, Eduardo

    2014-04-01

    NASA's Mission Control Center (MCC) is responsible for control of the International Space Station (ISS), which includes responding to problems that obstruct the functioning of the ISS and that may pose a threat to the health and well-being of the flight crew. These problems are often complex, requiring individuals, teams, and multiteam systems, to work collaboratively. Research is warranted to examine individual and collaborative problem-solving processes in this context. Specifically, focus is placed on how Mission Control personnel-each with their own skills and responsibilities-exchange information to gain a shared understanding of the problem. The Macrocognition in Teams Model describes the processes that individuals and teams undertake in order to solve problems and may be applicable to Mission Control teams. Semistructured interviews centering on a recent complex problem were conducted with seven MCC professionals. In order to assess collaborative problem-solving processes in MCC with those predicted by the Macrocognition in Teams Model, a coding scheme was developed to analyze the interview transcriptions. Findings are supported with excerpts from participant transcriptions and suggest that team knowledge-building processes accounted for approximately 50% of all coded data and are essential for successful collaborative problem solving in mission control. Support for the internalized and externalized team knowledge was also found (19% and 20%, respectively). The Macrocognition in Teams Model was shown to be a useful depiction of collaborative problem solving in mission control and further research with this as a guiding framework is warranted.

  1. Ecological Complexity and the Success of Fungal Biological Control Agents

    Directory of Open Access Journals (Sweden)

    Guy R. Knudsen

    2014-01-01

    Full Text Available Fungal biological control agents against plant pathogens, especially those in soil, operate within physically, biologically, and spatially complex systems by means of a variety of trophic and nontrophic interspecific interactions. However, the biocontrol agents themselves are also subject to the same types of interactions, which may reduce or in some cases enhance their efficacy against target plant pathogens. Characterization of these ecologically complex systems is challenging, but a number of tools are available to help unravel this complexity. Several of these tools are described here, including the use of molecular biology to generate biocontrol agents with useful marker genes and then to quantify these agents in natural systems, epifluorescence and confocal laser scanning microscopy to observe their presence and activity in situ, and spatial statistics and computer simulation modeling to evaluate and predict these activities in heterogeneous soil habitats.

  2. 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.

  3. Absence of Dystrophin Related Protein-2 disrupts Cajal bands in a patient with Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Brennan, Kathryn M; Bai, Yunhong; Pisciotta, Chiara; Wang, Suola; Feely, Shawna M E; Hoegger, Mark; Gutmann, Laurie; Moore, Steven A; Gonzalez, Michael; Sherman, Diane L; Brophy, Peter J; Züchner, Stephan; Shy, Michael E

    2015-10-01

    Using exome sequencing in an individual with Charcot-Marie-Tooth disease (CMT) we have identified a mutation in the X-linked dystrophin-related protein 2 (DRP2) gene. A 60-year-old gentleman presented to our clinic and underwent clinical, electrophysiological and skin biopsy studies. The patient had clinical features of a length dependent sensorimotor neuropathy with an age of onset of 50 years. Neurophysiology revealed prolonged latencies with intermediate conduction velocities but no conduction block or temporal dispersion. A panel of 23 disease causing genes was sequenced and ultimately was uninformative. Whole exome sequencing revealed a stop mutation in DRP2, c.805C>T (Q269*). DRP2 interacts with periaxin and dystroglycan to form the periaxin-DRP2-dystroglycan complex which plays a role in the maintenance of the well-characterized Cajal bands of myelinating Schwann cells. Skin biopsies from our patient revealed a lack of DRP2 in myelinated dermal nerves by immunofluorescence. Furthermore electron microscopy failed to identify Cajal bands in the patient's dermal myelinated axons in keeping with ultrastructural pathology seen in the Drp2 knockout mouse. Both the electrophysiologic and dermal nerve twig pathology support the interpretation that this patient's DRP2 mutation causes characteristic morphological abnormalities recapitulating the Drp2 knockout model and potentially represents a novel genetic cause of CMT. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The mTOR Complex Controls HIV Latency.

    Science.gov (United States)

    Besnard, Emilie; Hakre, Shweta; Kampmann, Martin; Lim, Hyung W; Hosmane, Nina N; Martin, Alyssa; Bassik, Michael C; Verschueren, Erik; Battivelli, Emilie; Chan, Jonathan; Svensson, J Peter; Gramatica, Andrea; Conrad, Ryan J; Ott, Melanie; Greene, Warner C; Krogan, Nevan J; Siliciano, Robert F; Weissman, Jonathan S; Verdin, Eric

    2016-12-14

    A population of CD4 T lymphocytes harboring latent HIV genomes can persist in patients on antiretroviral therapy, posing a barrier to HIV eradication. To examine cellular complexes controlling HIV latency, we conducted a genome-wide screen with a pooled ultracomplex shRNA library and in vitro system modeling HIV latency and identified the mTOR complex as a modulator of HIV latency. Knockdown of mTOR complex subunits or pharmacological inhibition of mTOR activity suppresses reversal of latency in various HIV-1 latency models and HIV-infected patient cells. mTOR inhibitors suppress HIV transcription both through the viral transactivator Tat and via Tat-independent mechanisms. This inhibition occurs at least in part via blocking the phosphorylation of CDK9, a p-TEFb complex member that serves as a cofactor for Tat-mediated transcription. The control of HIV latency by mTOR signaling identifies a pathway that may have significant therapeutic opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pinning control of a generalized complex dynamical network model

    Institute of Scientific and Technical Information of China (English)

    Huizhong YANG; Li SHENG

    2009-01-01

    This paper investigates the local and global synchronization of a generalized complex dynamical network model with constant and delayed coupling.Without assuming symmetry of the couplings,we proved that a single controller can pin the generalized complex network to a homogenous solution.Some previous synchronization results are generalized.In this paper,we first discuss how to pin an array of delayed neural networks to the synchronous solution by adding only one controller.Next,by using the Lyapunov functional method,some sufficient conditions are derived for the local and global synchronization of the coupled systems.The obtained results are expressed in terms of LMIs,which can be efficiently checked by the Matlab LMI toolbox.Finally,an example is given to illustrate the theoretical results.

  6. Control of complex dynamics and chaos in distributed parameter systems

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarti, S.; Marek, M.; Ray, W.H. [Univ. of Wisconsin, Madison, WI (United States)

    1995-12-31

    This paper discusses a methodology for controlling complex dynamics and chaos in distributed parameter systems. The reaction-diffusion system with Brusselator kinetics, where the torus-doubling or quasi-periodic (two characteristic incommensurate frequencies) route to chaos exists in a defined range of parameter values, is used as an example. Poincare maps are used for characterization of quasi-periodic and chaotic attractors. The dominant modes or topos, which are inherent properties of the system, are identified by means of the Singular Value Decomposition. Tested modal feedback control schemas based on identified dominant spatial modes confirm the possibility of stabilization of simple quasi-periodic trajectories in the complex quasi-periodic or chaotic spatiotemporal patterns.

  7. Nucleic Acid-Peptide Complex Phase Controlled by DNA Hybridization

    Science.gov (United States)

    Vieregg, Jeffrey; Lueckheide, Michael; Leon, Lorraine; Marciel, Amanda; Tirrell, Matthew

    When polyanions and polycations are mixed, counterion release drives formation of polymer-rich complexes that can either be solid (precipitates) or liquid (coacervates) depending on the properties of the polyelectrolytes. These complexes are important in many fields, from encapsulation of industrial polymers to membrane-free segregation of biomolecules such as nucleic acids and proteins. Condensation of long double-stranded DNA has been studied for several decades, but comparatively little attention has been paid to the polyelectrolyte behavior of oligonucleotides. We report here studies of DNA oligonucleotides (10 - 88 nt) complexed with polylysine (10 - 100 aa). Unexpectedly, we find that the phase of the resulting complexes is controlled by the hybridization state of the nucleic acid, with double-stranded DNA forming precipitates and single-stranded DNA forming coacervates. Stability increases with polyelectrolyte length and decreases with solution salt concentration, with complexes of the longer double-stranded polymers undergoing precipitate/coacervate/soluble transitions as ionic strength is increased. Mixing coacervates formed by complementary single-stranded oligonucleotides results in precipitate formation, raising the possibility of stimulus-responsive material design.

  8. Spatially-controlled complex molecules and their applications

    CERN Document Server

    Chang, Yuan-Pin; Trippel, Sebastian; Küpper, Jochen

    2015-01-01

    The understanding of molecular structure and function is at the very heart of the chemical and molecular sciences. Experiments that allow for the creation of structurally pure samples and the investigation of their molecular dynamics and chemical function have developed tremendeously over the last few decades, although "there's plenty of room at the bottom" for better control as well as further applications. Here, we describe the use of inhomogeneous electric fields for the manipulation of neutral molecules in the gas-phase, \\ie, for the separation of complex molecules according to size, structural isomer, and quantum state. Current applications of these controlled samples are summarized and interesting future applications discussed.

  9. Control of State Transitions in Complex and Biophysical Networks

    Science.gov (United States)

    Motter, Adilson; Wells, Daniel; Kath, William

    Noise is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a desired cell state. Here I will present a scalable, quantitative method based on the Freidlin-Wentzell action to predict and control noise-induced switching between different states in genetic networks that, conveniently, can also control transitions between stable states in the absence of noise. I will discuss applications of this methodology to predict control interventions that can induce lineage changes and to identify new candidate strategies for cancer therapy. This framework offers a systems approach to identifying the key factors for rationally manipulating network dynamics, and should also find use in controlling other classes of complex networks exhibiting multi-stability. Reference: D. K. Wells, W. L. Kath, and A. E. Motter, Phys. Rev. X 5, 031036 (2015). Work funded by CBC, NCI, NIGMS, and NSF.

  10. Structure-based control of complex networks with nonlinear dynamics

    CERN Document Server

    Zañudo, Jorge G T; Albert, Réka

    2016-01-01

    Given the network of interactions underlying a complex system, what can we learn about controlling such a system solely from its structure? Over a century of research in control theory has given us tools to answer this question, which were widely applied in science and engineering. Yet the current tools do not always consider the inherently nonlinear dynamics of real systems and the naturally occurring system states in their definition of "control", a term whose interpretation varies across disciplines. Here we use a new mathematical framework for structure-based control of networks governed by a broad class of nonlinear dynamics that includes the major dynamic models of biological, technological, and social processes. This framework provides realizable node overrides that steer a system towards any of its natural long term dynamic behaviors and which are guaranteed to be effective regardless of the dynamic details and parameters of the underlying system. We use this framework on several real networks, compar...

  11. The Similar Structures and Control Problems of Complex Systems

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    In this paper, the naturally evolving complex systems, such as biotic and social ones, are considered. Focusing on their structures, a feature is noteworthy, i.e., the similarity in structures. The relations between the functions and behaviors of these systems and their similar structures will be studied. Owing to the management of social systems and the course of evolution of biotic systems may be regarded as control processes, the researches will be within the scope of control problems. Moreover, since it is difficult to model for biotic and social systems, it will start with the control problems of complex systems, possessing similar structures, in engineering.The obtained results show that for either linear or nonlinear systems and for a lot of control problemssimilar structures lead to a series of simplifications. In general, the original system may be decomposed into reduced amount of subsystems with lower dimensions and simpler structures. By virtue of such subsystems, the control problems of original system can be solved more simply.At last, it turns round to observe the biotic and social systems and some analyses are given.

  12. A Japanese boy with myalgia and cramps has a novel in-frame deletion of the dystrophin gene.

    Science.gov (United States)

    Ishigaki, C; Patria, S Y; Nishio, H; Yabe, M; Matsuo, M

    1996-05-01

    We report a Japanese Becker muscular dystrophy (BMD) patient with occasional myalgia and cramps during normal activity that developed at the age of 28 months. His family history was negative for neuromuscular diseases. Muscle biopsy analyses, including dystrophin immunostaining, disclosed no clinically relevant findings. The diagnosis of BMD was initially made at the age of 10 years, when indications of persistent high serum levels of CK prompted us to screen deletions in the dystrophin gene by amplification of 19 deletion-prone exons from the genomic DNA by the polymerase chain reaction (PCR). Among the exons examined, exons 13 and 17 were deleted. To clarify the size of the deletion, the dystrophin transcript was analyzed by reverse transcription PCR. The determined nucleotide sequence of the amplified product encompassing exons 10 to 20 disclosed that the entire segment corresponding to exons 13 to 18 (810 bp) was absent, a deletion that would be expected to cause the production of a dystrophin protein lacking 270 amino acids from the rod domain. This result indicates that occasional myalgia and cramps could be early clinical manifestations of mild BMD, especially in patients who have a deletion in the rod domain, and that deletion screening of the dystrophin gene might be the only reliable method to diagnose such cases.

  13. Becker Muscular Dystrophy (BMD) caused by duplication of exons 3-6 of the dystrophin gene presenting as dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, A.C.; Allingham-Hawkins, D.J.; Becker, L. [Univ. of Toronto, Ontario (Canada)] [and others

    1994-09-01

    X-linked dilated cardiomyopathy (XLCM) is a progressive myocardial disease presenting with congestive heart failure in teenage males without clinical signs of skeletal myopathy. Tight linkage of XLCM to the DMD locus has been demonstrated; it has been suggested that, at least in some families, XLCM is a {open_quotes}dystrophinopathy.{close_quotes} We report a 14-year-old boy who presented with acute heart failure due to dilated cardiomyopathy. He had no history of muscle weakness, but physical examination revealed pseudohypertrophy of the calf muscles. He subsequently received a heart transplantation. Family history was negative. Serum CK level at the time of diagnosis was 10,416. Myocardial biopsy showed no evidence of carditis. Dystrophin staining of cardiac and skeletal muscle with anti-sera to COOH and NH{sub 2}termini showed a patchy distribution of positivity suggestive of Becker muscular dystrophy. Analysis of 18 of the 79 dystrophin exons detected a duplication that included exons 3-6. The proband`s mother has an elevated serum CK and was confirmed to be a carrier of the same duplication. A mutation in the muscle promotor region of the dystrophin gene has been implicated in the etiology of SLCM. However, Towbin et al. (1991) argued that other 5{prime} mutations in the dystrophin gene could cause selective cardiomyopathy. The findings in our patient support the latter hypothesis. This suggests that there are multiple regions in the dystrophin gene which, when disrupted, can cause isolated dilated cardiomyopathy.

  14. 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.

  15. Complex system modelling and control through intelligent soft computations

    CERN Document Server

    Azar, Ahmad

    2015-01-01

    The book offers a snapshot of the theories and applications of soft computing in the area of complex systems modeling and control. It presents the most important findings discussed during the 5th International Conference on Modelling, Identification and Control, held in Cairo, from August 31-September 2, 2013. The book consists of twenty-nine selected contributions, which have been thoroughly reviewed and extended before their inclusion in the volume. The different chapters, written by active researchers in the field, report on both current theories and important applications of soft-computing. Besides providing the readers with soft-computing fundamentals, and soft-computing based inductive methodologies/algorithms, the book also discusses key industrial soft-computing applications, as well as multidisciplinary solutions developed for a variety of purposes, like windup control, waste management, security issues, biomedical applications and many others. It is a perfect reference guide for graduate students, r...

  16. CERN Proton Synchrotron Complex High-Level Controls Renovation

    CERN Document Server

    Deghaye, S; Garcia Quintas, D; Gourber-Pace, M; Kruk, G; Kulikova, O; Lezhebokov, V; Pasinelli, S; Peryt, M; Roderick, C; Roux, E; Sobczak, M; Steerenberg, R; Wozniak, J; Zaharieva, Z

    2009-01-01

    After a detailed study of the Proton Synchrotron (PS) complex requirements by experts of CERN controls & operation groups, a proposal to develop a new system, called Injector Controls Architecture (InCA), was presented to and accepted by the management late 2007. Aiming at the homogenisation of the control systems across CERN accelerators, InCA is based on components developed for the Large Hadron Collider (LHC) but also new components required to fulfil operation needs. In 2008, the project was in its elaboration phase and we successfully validated its architecture and critical use-cases during several machine development sessions. After description of the architecture put in place and the components used, this paper describes the planning approach taken combining iterative development phases with deployment in operation for validation sessions.

  17. Self-Controlled Feedback for a Complex Motor Task

    Directory of Open Access Journals (Sweden)

    Wolf Peter

    2011-12-01

    Full Text Available Self-controlled augmented feedback enhances learning of simple motor tasks. Thereby, learners tend to request feedback after trials that were rated as good by themselves. Feedback after good trials promotes positive reinforcement, which enhances motor learning. The goal of this study was to investigate when naïve learners request terminal visual feedback in a complex motor task, as conclusions drawn on simple tasks can hardly be transferred to complex tasks. Indeed, seven of nine learners stated to have intended to request feedback predominantly after good trials, but in contrast to their intention, kinematic analysis showed that feedback was rather requested randomly (23% after good, 44% after intermediate, 33% after bad trials. Moreover, requesting feedback after good trials did not correlate with learning success. It seems that self-estimation of performance in complex tasks is challenging. As a consequence, learners might have focused on certain movement aspects rather than on the overall movement. Further studies should assess the current focus of the learner in detail to gain more insight in self-estimation capabilities during complex motor task learning.

  18. Levels of control and closure in complex semiotic systems

    Science.gov (United States)

    Joslyn

    2000-01-01

    It is natural to advance closures as atomic processes of universal evolution, and to analyze this concept specifically. Real complex systems like organisms and complex mechanisms cannot exist at either extreme of complete closure or lack of closure, nevertheless we should consider the properties of closures in general, the introduction of boundaries, a corresponding stability, the establishment of system autonomy and identity, and thereby the introduction of emergent new system of potentially new types. Our focus should move from simple physical closure of common objects and classical self-organizing systems to semiotically closed systems that maintain cyclic relations of perception, interpretation, decision, and action with their environments. Thus, issues arise concerning the use and interpretation of symbols, representations, and/or internal models (whether explicit or implicit) by the system; and the syntactic, semantic, and pragmatic relations among the sign tokens, their interpretations, and their use or function for the systems in question. Primitive semiotic closures are hypothesized as equivalent to simple control systems, and in turn equivalent to simple organisms. This leads us directly to the grand hierarchical control theories of Turchin, Powers, and Albus, which provide an explicit mechanism for the formation of new levels within complex semiotically closed systems.

  19. Supramolecular control of a mononuclear biomimetic copper(II) center: bowl complexes vs funnel complexes.

    Science.gov (United States)

    Gout, Jérôme; Višnjevac, Aleksandar; Rat, Stéphanie; Parrot, Arnaud; Hessani, Assia; Bistri, Olivia; Le Poul, Nicolas; Le Mest, Yves; Reinaud, Olivia

    2014-06-16

    Modeling the mononuclear site of copper enzymes is important for a better understanding of the factors controlling the reactivity of the metal center. A major difficulty stems from the difficult control of the nuclearity while maintaining free sites open to coordination of exogenous ligands. A supramolecular approach consists in associating a hydrophobic cavity to a tripodal ligand that will define the coordination spheres as well as access to the metal ion. Here, we describe the synthesis of a bowl Cu(II) complex based on the resorcinarene scaffold. This study supplements a previous work on Cu(I) coordination. It provides a complete picture of the cavity-copper system in its two oxidation states. The first XRD structure of such a bowl complex was obtained, evidencing a 5-coordinate Cu(II) ion with the three imidazole donors bound to the metal (two in the base of the pyramid, one in the apical position) and with an acetate anion, completing the base of the pyramid, and deeply included in the bowl. Solution studies conducted by EPR and UV-vis absorption spectroscopies as well as cyclic voltammetry highlighted interaction with coordinating solvents, various carboxylates that can sit either in the endo or in the exo position depending on their size as well as possible stabilization of hydroxo species in a mononuclear state. A comparison of the binding and redox properties of the bowl complex with funnel complexes based on the calix[6]arene core further highlights the importance of supramolecular features defining the first, second, and third coordination sphere for control of the metal ion.

  20. Controlling congestion on complex networks: fairness, efficiency and network structure.

    Science.gov (United States)

    Buzna, Ľuboš; Carvalho, Rui

    2017-08-22

    We consider two elementary (max-flow and uniform-flow) and two realistic (max-min fairness and proportional fairness) congestion control schemes, and analyse how the algorithms and network structure affect throughput, the fairness of flow allocation, and the location of bottleneck edges. The more realistic proportional fairness and max-min fairness algorithms have similar throughput, but path flow allocations are more unequal in scale-free than in random regular networks. Scale-free networks have lower throughput than their random regular counterparts in the uniform-flow algorithm, which is favoured in the complex networks literature. We show, however, that this relation is reversed on all other congestion control algorithms for a region of the parameter space given by the degree exponent γ and average degree 〈k〉. Moreover, the uniform-flow algorithm severely underestimates the network throughput of congested networks, and a rich phenomenology of path flow allocations is only present in the more realistic α-fair family of algorithms. Finally, we show that the number of paths passing through an edge characterises the location of a wide range of bottleneck edges in these algorithms. Such identification of bottlenecks could provide a bridge between the two fields of complex networks and congestion control.

  1. MULTILEVEL RECURRENT MODEL FOR HIERARCHICAL CONTROL OF COMPLEX REGIONAL SECURITY

    Directory of Open Access Journals (Sweden)

    Andrey V. Masloboev

    2014-11-01

    Full Text Available Subject of research. The research goal and scope are development of methods and software for mathematical and computer modeling of the regional security information support systems as multilevel hierarchical systems. Such systems are characterized by loosely formalization, multiple-aspect of descendent system processes and their interconnectivity, high level dynamics and uncertainty. The research methodology is based on functional-target approach and principles of multilevel hierarchical system theory. The work considers analysis and structural-algorithmic synthesis problem-solving of the multilevel computer-aided systems intended for management and decision-making information support in the field of regional security. Main results. A hierarchical control multilevel model of regional socio-economic system complex security has been developed. The model is based on functional-target approach and provides both formal statement and solving, and practical implementation of the automated information system structure and control algorithms synthesis problems of regional security management optimal in terms of specified criteria. An approach for intralevel and interlevel coordination problem-solving in the multilevel hierarchical systems has been proposed on the basis of model application. The coordination is provided at the expense of interconnection requirements satisfaction between the functioning quality indexes (objective functions, which are optimized by the different elements of multilevel systems. That gives the possibility for sufficient coherence reaching of the local decisions, being made on the different control levels, under decentralized decision-making and external environment high dynamics. Recurrent model application provides security control mathematical models formation of regional socioeconomic systems, functioning under uncertainty. Practical relevance. The model implementation makes it possible to automate synthesis realization of

  2. 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.

  3. Cell division control by the Chromosomal Passenger Complex

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Maike S. van der; Hengeveld, Rutger C.C.; Horst, Armando van der; Lens, Susanne M.A., E-mail: s.m.a.lens@umcutrecht.nl

    2012-07-15

    The Chromosomal Passenger Complex (CPC) consisting of Aurora B kinase, INCENP, Survivin and Borealin, is essential for genomic stability by controlling multiple processes during both nuclear and cytoplasmic division. In mitosis it ensures accurate segregation of the duplicated chromosomes by regulating the mitotic checkpoint, destabilizing incorrectly attached spindle microtubules and by promoting the axial shortening of chromosomal arms in anaphase. During cytokinesis the CPC most likely prevents chromosome damage by imposing an abscission delay when a chromosome bridge connects the two daughter cells. Moreover, by controlling proper cytoplasmic division, the CPC averts tetraploidization. This review describes recent insights on how the CPC is capable of conducting its various functions in the dividing cell to ensure chromosomal stability.

  4. 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.

  5. Becker muscular dystrophy in Indian patients: Analysis of dystrophin gene deletion patterns

    Directory of Open Access Journals (Sweden)

    Dastur Rashna

    2008-01-01

    Full Text Available Background: Becker muscular dystrophy (BMD is caused by mutations in the dystrophin gene with variable phenotypes. Becker muscular dystrophy patients have low levels of nearly full-length dystrophin and carry in-frame mutations, which allow partial functioning of the protein. Aim: To study the deletion patterns of BMD and to correlate the same with reading frame rule and different phenotypes. Setting: A tertiary care teaching hospital. Design: This is a prospective hospital-based study. Materials and Methods: Thirty-two exons spanning different "hot spot" regions using Multiplex PCR techniques were studied in 347 patients. Two hundred and twenty-two showed deletions in one or more of the 32 exons. Out of these, 46 diagnosed as BMD patients were analyzed. Results: Forty-six BMD patients showed deletions in both regions of the dystrophin gene. Out of these 89.1% (41/46 were in-frame deletions. Deletions starting with Exon 45 were found in 76.1% (35/46 of the cases. Mutations in the majority of cases i.e. 39/46 (84.8% were seen in 3′ downstream region (Exon 45-55, distal rod domain. Few, i.e. 5/46 (10.8% showed deletions in 5′ upstream region (Exons 3-20, N-terminus and proximal rod domain of the gene, while in 2/46 (4.4% large mutations (>40 bp spanning both regions (Exons 3-55 were detected. Conclusion: This significant gene deletion analysis has been carried out for BMD patients particularly from Western India using 32 exons.

  6. Visual control of foot placement when walking over complex terrain.

    Science.gov (United States)

    Matthis, Jonathan S; Fajen, Brett R

    2014-02-01

    The aim of this study was to investigate the role of visual information in the control of walking over complex terrain with irregularly spaced obstacles. We developed an experimental paradigm to measure how far along the future path people need to see in order to maintain forward progress and avoid stepping on obstacles. Participants walked over an array of randomly distributed virtual obstacles that were projected onto the floor by an LCD projector while their movements were tracked by a full-body motion capture system. Walking behavior in a full-vision control condition was compared with behavior in a number of other visibility conditions in which obstacles did not appear until they fell within a window of visibility centered on the moving observer. Collisions with obstacles were more frequent and, for some participants, walking speed was slower when the visibility window constrained vision to less than two step lengths ahead. When window sizes were greater than two step lengths, the frequency of collisions and walking speed were weakly affected or unaffected. We conclude that visual information from at least two step lengths ahead is needed to guide foot placement when walking over complex terrain. When placed in the context of recent research on the biomechanics of walking, the findings suggest that two step lengths of visual information may be needed because it allows walkers to exploit the passive mechanical forces inherent to bipedal locomotion, thereby avoiding obstacles while maximizing energetic efficiency. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  7. On Market Economies: How Controllable Constructs Become Complex

    Directory of Open Access Journals (Sweden)

    C-René DOMINIQUE

    2014-11-01

    Full Text Available Since Lėon Walras neoclassical economists hold an inalterable belief in a unique and stable equilibrium for the economic system which however remains to this day unobservable. Yet that belief is the corner stone of other theories such as the ‘Effi-cient Market Hypothesis’ as well as the philosophy of neo-liberalism, whose out-comes are also shown to be flawed by recent events. A modern market economy is obviously an input/output nonlinear controllable construct. However, this paper examines four such models of increasing complexity, including the affine nonline-ar feedback H-control, to show that the ‘data requirement’ precludes all attempts at the empirical verification of the existence of a stable equilibrium. If equilibria of complex nonlinear deterministic systems are most likely unstable, multiple or deterministically chaotic depending on their parameter values and uncertainties, then society should impose limits on the state space and focus on endurable pat-terns thrown-off by such systems.

  8. Role of mental retardation-associated dystrophin-gene product Dp71 in excitatory synapse organization, synaptic plasticity and behavioral functions.

    Directory of Open Access Journals (Sweden)

    Fatma Daoud

    Full Text Available BACKGROUND: Duchenne muscular dystrophy (DMD is caused by deficient expression of the cytoskeletal protein, dystrophin. One third of DMD patients also have mental retardation (MR, likely due to mutations preventing expression of dystrophin and other brain products of the DMD gene expressed from distinct internal promoters. Loss of Dp71, the major DMD-gene product in brain, is thought to contribute to the severity of MR; however, the specific function of Dp71 is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Complementary approaches were used to explore the role of Dp71 in neuronal function and identify mechanisms by which Dp71 loss may impair neuronal and cognitive functions. Besides the normal expression of Dp71 in a subpopulation of astrocytes, we found that a pool of Dp71 colocalizes with synaptic proteins in cultured neurons and is expressed in synaptic subcellular fractions in adult brains. We report that Dp71-associated protein complexes interact with specialized modular scaffolds of proteins that cluster glutamate receptors and organize signaling in postsynaptic densities. We then undertook the first functional examination of the brain and cognitive alterations in the Dp71-null mice. We found that these mice display abnormal synapse organization and maturation in vitro, altered synapse density in the adult brain, enhanced glutamatergic transmission and reduced synaptic plasticity in CA1 hippocampus. Dp71-null mice show selective behavioral disturbances characterized by reduced exploratory and novelty-seeking behavior, mild retention deficits in inhibitory avoidance, and impairments in spatial learning and memory. CONCLUSIONS/SIGNIFICANCE: Results suggest that Dp71 expression in neurons play a regulatory role in glutamatergic synapse organization and function, which provides a new mechanism by which inactivation of Dp71 in association with that of other DMD-gene products may lead to increased severity of MR.

  9. Backbone of complex networks of corporations: The flow of control

    Science.gov (United States)

    Glattfelder, J. B.; Battiston, S.

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

  10. Backbone of complex networks of corporations: the flow of control.

    Science.gov (United States)

    Glattfelder, J B; Battiston, S

    2009-09-01

    We present a methodology to extract the backbone of complex networks based on the weight and direction of links, as well as on nontopological properties of nodes. We show how the methodology can be applied in general to networks in which mass or energy is flowing along the links. In particular, the procedure enables us to address important questions in economics, namely, how control and wealth are structured and concentrated across national markets. We report on the first cross-country investigation of ownership networks, focusing on the stock markets of 48 countries around the world. On the one hand, our analysis confirms results expected on the basis of the literature on corporate control, namely, that in Anglo-Saxon countries control tends to be dispersed among numerous shareholders. On the other hand, it also reveals that in the same countries, control is found to be highly concentrated at the global level, namely, lying in the hands of very few important shareholders. Interestingly, the exact opposite is observed for European countries. These results have previously not been reported as they are not observable without the kind of network analysis developed here.

  11. A complex control system based on the fuzzy PID control and state predictor feedback control

    Institute of Scientific and Technical Information of China (English)

    Zhengxi Li; Jie Liu; Dehui Sun; Rentao Zhao

    2004-01-01

    A multi-mode adaptive controller was proposed. The controller features in the combination of Bang-bang and Fuzzy PID controls with state predictor. When large error exists, the controller operates in Bang-bang mode, otherwise it works as a fuzzy PID controller. For only few parameters to be adjusted, the real time controlled system achieveed good stability and fast response. Furthermore, the introduction of state observer was also discussed to extend the capability of the proposed controller to the plant with time-delay factors. The classical PID controller and the multi-mode controller were applied to the same second-order system successively. By comparison of the simulation results, the effectiveness of the controller were shown. At last, on electric-wire production line, this approach was practiced to control electric-wire diameter with an additive random disturbance signal. The test result further proved the effectiveness of the multi-mode controller.

  12. Control of Future Air Traffic Systems via Complexity Bound Management

    Science.gov (United States)

    Alexandrov, Natalia

    2013-01-01

    The complexity of the present system for managing air traffic has led to "discreteness" in approaches to creating new concepts: new concepts are created as point designs, based on experience, expertise, and creativity of the proposer. Discrete point designs may be highly successful but they are difficult to substantiate in the face of equally strong substantiation of competing concepts, as well as the state of the art in concept evaluation via simulations. Hybrid concepts may present a compromise - the golden middle. Yet a hybrid of sometimes in principle incompatible concepts forms another point design that faces the challenge of substantiation and validation. We are faced with the need to re-design the air transportation system ab initio. This is a daunting task, especially considering the problem of transitioning from the present system to any fundamentally new system. However, design from scratch is also an opportunity to reconsider approaches to new concept development. In this position paper we propose an approach, Optimized Parametric Functional Design, for systematic development of concepts for management and control of airspace systems, based on optimization formulations in terms of required system functions and states. This reasoning framework, realizable in the context of ab initio system design, offers an approach to deriving substantiated airspace management and control concepts. With growing computational power, we hope that the approach will also yield a methodology for actual dynamic control of airspace

  13. Early right ventricular fibrosis and reduction in biventricular cardiac reserve in the dystrophin-deficient mdx heart.

    Science.gov (United States)

    Meyers, Tatyana A; Townsend, DeWayne

    2015-02-15

    Duchenne muscular dystrophy (DMD) is a progressive disease of striated muscle deterioration. Respiratory and cardiac muscle dysfunction are particularly clinically relevant because they result in the leading causes of death in DMD patients. Despite the clinical and physiological significance of these systems, little has been done to understand the cardiorespiratory interaction in DMD. We show here that prior to the onset of global cardiac dysfunction, dystrophin-deficient mdx mice have increased cardiac fibrosis with the right ventricle being particularly affected. Using a novel biventricular cardiac catheterization technique coupled with cardiac stress testing, we demonstrate that both the right and left ventricles have significant reductions in both systolic and diastolic function in response to dobutamine. Unstimulated cardiac function is relatively normal except for a significant reduction in the ventricular pressure transient duration compared with controls. These biventricular analyses also reveal the absence of a dobutamine-induced increase in isovolumic relaxation in the right ventricle of control hearts. Simultaneous assessment of biventricular pressure demonstrates a dobutamine-dependent enhancement of coupling between the ventricles in control mice, which is absent in mdx mice. Furthermore, studies probing the passive-extension properties of the left ventricle demonstrate that the mdx heart is significantly more compliant compared with age-matched C57BL/10 hearts, which have an age-dependent stiffening that is completely absent from dystrophic hearts. These new results indicate that right ventricular fibrosis is an early indicator of the development of dystrophic cardiomyopathy, suggesting a mechanism by which respiratory insufficiency may accelerate the development of heart failure in DMD.

  14. Non-equilibrium control of complex solids by nonlinear phononics

    Science.gov (United States)

    Mankowsky, Roman; Först, Michael; Cavalleri, Andrea

    2016-06-01

    We review some recent advances in the use of optical fields at terahertz frequencies to drive the lattice of complex materials. We will focus on the control of low energy collective properties of solids, which emerge on average when a high frequency vibration is driven and a new crystal structure induced. We first discuss the fundamentals of these lattice rearrangements, based on how anharmonic mode coupling transforms an oscillatory motion into a quasi-static deformation of the crystal structure. We then discuss experiments, in which selectively changing a bond angle turns an insulator into a metal, accompanied by changes in charge, orbital and magnetic order. We then address the case of light induced non-equilibrium superconductivity, a mysterious phenomenon observed in some cuprates and molecular materials when certain lattice vibrations are driven. Finally, we show that the dynamics of electronic and magnetic phase transitions in complex-oxide heterostructures follow distinctly new physical pathways in case of the resonant excitation of a substrate vibrational mode.

  15. 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.

  16. Current understanding of dystrophin-related muscular dystrophy and therapeutic challenges ahead

    Institute of Scientific and Technical Information of China (English)

    ZHOU Guang-qian; XIE Hui-qi; ZHANG Su-zhen; YANG Zhi-ming

    2006-01-01

    Objective To review the recent research progress in dystrophin-related muscular dystrophy includes X-linked hereditary Duchenne and Becker muscular dystrophies (DMD and BMD).Data sources Information included in this article was identified by searches of PUBMED and other online resources using the key terms DMD, dystrophin, mutations, animal models, pathophysiology, gene expression, stem cells, gene therapy, cell therapy, and pharmacological.Study selection Mainly original milestone articles and timely reviews written by major pioneer investigators of the field were selected.Results The key issues related to the genetic basis and pathophysiological factors of the diseases were critically addressed. The availabilities and advantages of various animal models for the diseases were described. Major molecular and cellular therapeutic approaches were also discussed, many of which have indeed exhibited some success in pre-clinical studies but at the same time encountered a number of technical hurdles, including the efficient and systemic delivery of a functional gene and myogenic precursor/stem cells to repair genetic defects.Conclusions Further understanding of pathophysiological mechanisms at molecular levels and regenerative properites of myogenic precursor/stem cells will promote the development of multiple therapeutic strategies. The combined use of multiple strategies may represent the major challenge as well as the greatest hope for the therapy of these diseases in coming years.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Thibaut Larcher

    Full Text Available 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.

  19. 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.

  20. Characterization of 65 epitope-specific dystrophin monoclonal antibodies in canine and murine models of duchenne muscular dystrophy by immunostaining and western blot.

    Science.gov (United States)

    Kodippili, Kasun; Vince, Lauren; Shin, Jin-Hong; Yue, Yongping; Morris, Glenn E; McIntosh, Mark A; Duan, Dongsheng

    2014-01-01

    Epitope-specific monoclonal antibodies can provide unique insights for studying cellular proteins. Dystrophin is one of the largest cytoskeleton proteins encoded by 79 exons. The absence of dystrophin results in Duchenne muscular dystrophy (DMD). Over the last two decades, dozens of exon-specific human dystrophin monoclonal antibodies have been developed and successfully used for DMD diagnosis. Unfortunately, the majority of these antibodies have not been thoroughly characterized in dystrophin-deficient dogs, an outstanding large animal model for translational research. To fill the gap, we performed a comprehensive study on 65 dystrophin monoclonal antibodies in normal and dystrophic dogs (heart and skeletal muscle) by immunofluorescence staining and western blot. For comparison, we also included striated muscles from normal BL10 and dystrophin-null mdx mice. Our analysis revealed distinctive species, tissue and assay-dependent recognition patterns of different antibodies. Importantly, we identified 15 antibodies that can consistently detect full-length canine dystrophin in both immunostaining and western blot. Our results will serve as an important reference for studying DMD in the canine model.

  1. 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.

  2. A case of Becker muscular dystrophy resulting from the skipping of four contiguous exons (71-74) of the dystrophin gene during mRNA maturation.

    Science.gov (United States)

    Patria, S Y; Alimsardjono, H; Nishio, H; Takeshima, Y; Nakamura, H; Matsuo, M

    1996-07-01

    The mutations in one-third of both Duchenne and Becker muscular dystrophy patients remain unknown because they do not involve gross rearrangements of the dystrophin gene. Here we report the first example of multiple exon skipping during the splicing of dystrophin mRNA precursor encoded by an apparently normal dystrophin gene. A 9-year-old Japanese boy exhibiting excessive fatigue and high serum creatine kinase activity was examined for dystrophinopathy. An immunohistochemical study of muscle tissue biopsy disclosed faint and discontinuous staining of the N-terminal and rod domains of dystrophin but no staining at all of the C-terminal domain of dystrophin. The dystrophin transcript from muscle tissue was analyzed by the reverse transcriptase polymerase chain reaction. An amplified product encompassing exons 67-79 of dystrophin cDNA was found to be smaller than that of the wild-type product. Sequence analysis of this fragment showed that the 3' end of exon 70 was directly connected to the 5' end of exon 75 and, thus, that exons 71-74 were completely absent. As a result, a truncated dystrophin protein lacking 110 amino acids from the C-terminal domain should result from translation of this truncated mRNA, and the patient was diagnosed as having Becker muscular dystrophy at the molecular level. Genomic DNA was analyzed to identify the cause of the disappearance of these exons. Every exon-encompassing region could be amplified from genomic DNA, indicating that the dystrophin gene is intact. Furthermore, sequencing of these amplified products did not disclose any particular nucleotide change that could be responsible for the multiple exon skipping observed. Considering that exons 71-74 are spliced out alternatively in some tissue-specific isoforms, to suppose that the alternative splicing machinery is present in the muscle tissue of the index case and that it is activated by an undetermined mechanism is reasonable. These results illustrate a novel genetic anomaly that

  3. Understanding and controlling complex states arising from magnetic frustration

    Energy Technology Data Exchange (ETDEWEB)

    Zapf, Vivien [Los Alamos National Laboratory

    2012-06-01

    Much of our national security relies on capabilities made possible by magnetism, in particular the ability to compute and store huge bodies of information as well as to move things and sense the world. Most of these technologies exploit ferromagnetism, i.e. the global parallel alignment of magnetic spins as seen in a bar magnet. Recent advances in computing technologies, such as spintronics and MRAM, take advantage of antiferromagnetism where the magnetic spins alternate from one to the next. In certain crystal structures, however, the spins take on even more complex arrangements. These are often created by frustration, where the interactions between spins cannot be satisfied locally or globally within the material resulting in complex and often non-coplanar spin textures. Frustration also leads to the close proximity of many different magnetic states, which can be selected by small perturbations in parameters like magnetic fields, temperature and pressure. It is this tunability that makes frustrated systems fundamentally interesting and highly desirable for applications. We move beyond frustration in insulators to itinerant systems where the interaction between mobile electrons and the non-coplanar magnetic states lead to quantum magneto-electric amplification. Here a small external field is amplified by many orders of magnitude by non-coplanar frustrated states. This greatly enhances their sensitivity and opens broader fields for applications. Our objective is to pioneer a new direction for condensed matter science at the Laboratory as well as for international community by discovering, understanding and controlling states that emerge from the coupling of itinerant charges to frustrated spin textures.

  4. 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 BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00264888.

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

    Science.gov (United States)

    Finkel, Richard S; Flanigan, Kevin M; Wong, Brenda; Bönnemann, Carsten; Sampson, Jacinda; Sweeney, H Lee; Reha, Allen; Northcutt, Valerie J; Elfring, Gary; Barth, Jay; Peltz, Stuart W

    2013-01-01

    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.

  6. Structural controllability of complex networks based on preferential matching.

    Science.gov (United States)

    Zhang, Xizhe; Lv, Tianyang; Yang, XueYing; Zhang, Bin

    2014-01-01

    Minimum driver node sets (MDSs) play an important role in studying the structural controllability of complex networks. Recent research has shown that MDSs tend to avoid high-degree nodes. However, this observation is based on the analysis of a small number of MDSs, because enumerating all of the MDSs of a network is a #P problem. Therefore, past research has not been sufficient to arrive at a convincing conclusion. In this paper, first, we propose a preferential matching algorithm to find MDSs that have a specific degree property. Then, we show that the MDSs obtained by preferential matching can be composed of high- and medium-degree nodes. Moreover, the experimental results also show that the average degree of the MDSs of some networks tends to be greater than that of the overall network, even when the MDSs are obtained using previous research method. Further analysis shows that whether the driver nodes tend to be high-degree nodes or not is closely related to the edge direction of the network.

  7. Regulation and controlled synchronization for complex dynamical systems

    NARCIS (Netherlands)

    Huijberts, H.J.C.; Nijmeijer, Henk; Willems, R.M.A.

    2000-01-01

    In this paper we investigate the problem of controlled synchronization as a regulator problem. In controlled synchronization one is given autonomous transmitter dynamics and controlled receiver dynamics. The question is to find a (output) feedback controller that achieves matching between

  8. Complexity Management - A multiple case study analysis on control and reduction of complexity costs

    DEFF Research Database (Denmark)

    Myrodia, Anna

    of products, with features more custom-made to cover individual needs, both regarding characteristics of products and support services. This necessity leads to a considerable increase of the complexity in the company, which affects the product portfolio, production and supply chain, market segments...... product and process complexity. The possible factors for describing this correlation are identified and defined as complexity cost factors (CCFs). By identifying the CCFs this research intends to analyze the most relevant processes where the complexity and cost are directly related to the complexity...

  9. 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.

  10. 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

    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....

  11. Early cardiac failure in a child with Becker muscular dystrophy is due to an abnormally low amount of dystrophin transcript lacking exon 13.

    Science.gov (United States)

    Ishigaki, C; Patria, S Y; Nishio, H; Yoshioka, A; Matsuo, M

    1997-12-01

    Two Japanese brothers with Becker muscular dystrophy were shown by polymerase chain reaction (PCR) and cDNA sequence analysis to produce a dystrophin gene transcript lacking a single exon: that is, number 13. Despite having the same deletion mutation, the brothers showed clearly different clinical phenotypes: the younger brother developed cardiac failure at the age of nine, while the elder brother was asymptomatic. As alternative splicing was not responsible for this clinical difference, the amount of dystrophin transcript was examined by using reverse transcription semi-nested and parallel PCR. The results showed that the amount of the dystrophin transcript in the younger brother was 20% of that of the elder brother. This finding suggested that lesser amount of dystrophin transcript in the younger brother was responsible for the early onset of cardiac failure. This would represent a novel molecular mechanism for dystrophinopathy.

  12. 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.

  13. A Novel Evolutionary-Fuzzy Control Algorithm for Complex Systems

    Institute of Scientific and Technical Information of China (English)

    王攀; 徐承志; 冯珊; 徐爱华

    2002-01-01

    This paper presents an adaptive fuzzy control scheme based on modified genetic algorithm. In the control scheme, genetic algorithm is used to optimze the nonlinear quantization functions of the controller and some key parameters of the adaptive control algorithm. Simulation results show that this control scheme has satisfactory performance in MIMO systems, chaotic systems and delay systems.

  14. Handling Qualities of Model Reference Adaptive Controllers with Varying Complexity for Pitch-Roll Coupled Failures

    Science.gov (United States)

    Schaefer, Jacob; Hanson, Curt; Johnson, Marcus A.; Nguyen, Nhan

    2011-01-01

    Three model reference adaptive controllers (MRAC) with varying levels of complexity were evaluated on a high performance jet aircraft and compared along with a baseline nonlinear dynamic inversion controller. The handling qualities and performance of the controllers were examined during failure conditions that induce coupling between the pitch and roll axes. Results from flight tests showed with a roll to pitch input coupling failure, the handling qualities went from Level 2 with the baseline controller to Level 1 with the most complex MRAC tested. A failure scenario with the left stabilator frozen also showed improvement with the MRAC. Improvement in performance and handling qualities was generally seen as complexity was incrementally added; however, added complexity usually corresponds to increased verification and validation effort required for certification. The tradeoff between complexity and performance is thus important to a controls system designer when implementing an adaptive controller on an aircraft. This paper investigates this relation through flight testing of several controllers of vary complexity.

  15. 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.

  16. Dual chirality control of palladium(II) complexes bearing tropos biphenyl diamine ligands.

    Science.gov (United States)

    Aikawa, Kohsuke; Mikami, Koichi

    2005-12-14

    Axial and center chirality of Pd complexes with tropos biphenyl secondary diamine ligands is shown to be controlled by chiral amide (R)-DABNTf, which can efficiently discriminate between two enantiomeric Pd complexes.

  17. 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

  18. Controlling Halo-chaos Complexity for Nuclear Power System and Managing High Technology Field

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Variability is one of most important features of complexity in the complex systems because of itssensitivities to small perturbation. Various possible competing behaviors in the systems provide greatflexibility in controlling dynamical complexity and can manage/select a desired behavior for applicationsin real world. In many high-tech fields, how to control or manage complexity is of significant andchallenge issue. Taking as a typical example, accelerator driven clean nuclear power system (ADS) is one

  19. Function complex for automated system of coke machinery remote control

    Energy Technology Data Exchange (ETDEWEB)

    Simonov, N.F.; Pankrat' ev, O.N.; Bannikov, L.S.; Slatin, E.I.; Parfenov, G.I.

    1979-05-01

    this paper discusses a functional control system for remote control of coking plants introduced at the KBAiM of the Giprokoks. The control block allows for three modes of operation: fully automatic, by predesignated program according to oven design and technology; semi-automatic, in which individual programs perform automatically, checked and initiated by the operator; and remote, in which the operator controls each operation from the control console. The functions of selecting the location for the coke machinery, signal transmission and control selection have been incorporated as three autonomous but interfacing systems. (In Russian)

  20. Controllable subspace of edge dynamics in complex networks

    Science.gov (United States)

    Pang, Shao-Peng; Hao, Fei

    2017-09-01

    For the edge dynamics in some real networks, it may be neither feasible nor necessary to be fully controlled. An accompanying issue is that, when the external signal is applied to a few nodes or even a single node, how many edges can be controlled? In this paper, for the edge dynamics system, we propose a theoretical framework to determine the controllable subspace and calculate its generic dimension based on the integer linear programming. This framework allows us not only to analyze the control centrality, i.e., the ability of a node to control, but also to uncover the controllable centrality, i.e., the propensity of an edge to be controllable. The simulation results and analytic calculation show that dense and homogeneous networks tend to have larger control centrality of nodes and controllable centrality of edges, but the negatively correlated in- and out-degrees of nodes or edges can reduce the two centrality. The positive correlation between the control centrality of node and its out-degree leads to that the distribution of control centrality, instead of that of controllable centrality, is encoded by the out-degree distribution of networks. Meanwhile, the positive correlation indicates that the nodes with high out-degree tend to play more important roles in control.

  1. Identification of two point mutations and a one base deletion in exon 19 of the dystrophin gene by heteroduplex formation.

    Science.gov (United States)

    Prior, T W; Papp, A C; Snyder, P J; Burghes, A H; Sedra, M S; Western, L M; Bartello, C; Mendell, J R

    1993-03-01

    Two thirds of the Duchenne muscular dystrophy population have either gene deletions or duplications. The nondeletion/duplication cases are most likely the result of point mutations or small deletions and duplications that cannot be easily identified by current strategies. The major obstacle in identifying small mutations is due to the large size of the dystrophin gene. We selectively screened 5 DMD exons containing CpG dinucleotides in 110 DMD patients without detectable deletions or duplications. Nonsenses mutations are frequently due to a C- to -T transition within a CG dinucleotide pair. To screen for the nonsense mutations, we used the heteroduplex method. Utilizing this approach, we identified 2 different nonsense mutations and a single base deletion all occurring in exon 19. This is the first report of a clustering of small mutations in the dystrophin gene.

  2. Application study of complex control algorithm for regenerative furnace temperature

    Institute of Scientific and Technical Information of China (English)

    Lusheng GE

    2004-01-01

    Altemative switch combustion mode of air and gas is adopted on the two sides of the regenerative furnace, its temperature is in uncontrolled state in the switching process and the switch period is generally 3 ~ 5 min. Thus, the conventional bi-cross limited combustion control method is no longer applicable to the object. This paper makes use of neutral network algorithm to adjust the static operating point. On this basis, fuzzy control strategy is used for the furnace temperature control. The actual application result shows that the control strategy is effective to solve the problem of the combustion control for regenerative furnace.

  3. Novel hybrid adaptive controller for manipulation in complex perturbation environments.

    Directory of Open Access Journals (Sweden)

    Alex M C Smith

    Full Text Available In this paper we present a hybrid control scheme, combining the advantages of task-space and joint-space control. The controller is based on a human-like adaptive design, which minimises both control effort and tracking error. Our novel hybrid adaptive controller has been tested in extensive simulations, in a scenario where a Baxter robot manipulator is affected by external disturbances in the form of interaction with the environment and tool-like end-effector perturbations. The results demonstrated improved performance in the hybrid controller over both of its component parts. In addition, we introduce a novel method for online adaptation of learning parameters, using the fuzzy control formalism to utilise expert knowledge from the experimenter. This mechanism of meta-learning induces further improvement in performance and avoids the need for tuning through trial testing.

  4. Novel Hybrid Adaptive Controller for Manipulation in Complex Perturbation Environments

    Science.gov (United States)

    Smith, Alex M. C.; Yang, Chenguang; Ma, Hongbin; Culverhouse, Phil; Cangelosi, Angelo; Burdet, Etienne

    2015-01-01

    In this paper we present a hybrid control scheme, combining the advantages of task-space and joint-space control. The controller is based on a human-like adaptive design, which minimises both control effort and tracking error. Our novel hybrid adaptive controller has been tested in extensive simulations, in a scenario where a Baxter robot manipulator is affected by external disturbances in the form of interaction with the environment and tool-like end-effector perturbations. The results demonstrated improved performance in the hybrid controller over both of its component parts. In addition, we introduce a novel method for online adaptation of learning parameters, using the fuzzy control formalism to utilise expert knowledge from the experimenter. This mechanism of meta-learning induces further improvement in performance and avoids the need for tuning through trial testing. PMID:26029916

  5. Diagnosis for Control and Decision Support in Complex Systems

    DEFF Research Database (Denmark)

    Blanke, Mogens; Hansen, Søren; Blas, Morten Rufus

    2011-01-01

    with complex and nonlinear systems have matured and even though there are many un-solved problems, methodology and associated tools have become available in the form of theory and software for design. Genuine industrial cases have also become available. Analysis of system topology, referred to as structural...... for on-line prognosis and diagnosis. For complex systems, results from non-Gaussian detection theory have been employed with convincing results. The paper presents the theoretical foundation for design methodologies that now appear as enabling technology for a new area of design of systems...

  6. Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Bengtsson, Niclas E; Hall, John K; Odom, Guy L; Phelps, Michael P; Andrus, Colin R; Hawkins, R David; Hauschka, Stephen D; Chamberlain, Joel R; Chamberlain, Jeffrey S

    2017-02-14

    Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx(4cv) mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders.

  7. Localization and quantitation of the chromosome 6-encoded dystrophin-related protein in normal and pathological human muscle.

    Science.gov (United States)

    Karpati, G; Carpenter, S; Morris, G E; Davies, K E; Guerin, C; Holland, P

    1993-03-01

    A dystrophin-related protein (DRP) encoded by a gene on chromosome 6 was studied in 14 normal and 79 pathological human skeletal muscle biopsies, as well as in cultured myotubes by light microscopic immunocytochemistry and quantitative immunoblots. In normal muscle immunoreactive DRP was present at the postjunctional surface membrane, at the surface of satellite cells, in the walls of blood vessels, in Schwann cells and in perineurium of intramuscular nerves. All of this produced a weak signal on immunoblots. In Duchenne/Becker dystrophy (DMD/BMD) and in polymyositis (PM) or dermatomyositis (DM) DRP was present throughout the extrajunctional surface membrane of extra- and intrafusal muscle fibers, particularly regenerating ones. This produced a 15-17-fold increase of DRP over normal in DMD/BMD and 4-10-fold increase over normal in PM and DM on immunoblots. In other pathological muscles, DRP localization pattern and quantity was about the same as in normals. Dystrophin-related protein was present in about the same amounts and distribution in normal and DMD cultured myoblasts and myotubes. The molecular stimulus for the marked upregulation of DRP in DMD/BMD and in the inflammatory myopathies is not known. In DMD/BMD the diffuse sarcolemmal DRP may partially compensate for dystrophin deficiency.

  8. 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.

  9. The integrated manual and automatic control of complex flight systems

    Science.gov (United States)

    Schmidt, David K.

    1991-01-01

    Research dealt with the general area of optimal flight control synthesis for manned flight vehicles. The work was generic; no specific vehicle was the focus of study. However, the class of vehicles generally considered were those for which high authority, multivariable control systems might be considered, for the purpose of stabilization and the achievement of optimal handling characteristics. Within this scope, the topics of study included several optimal control synthesis techniques, control-theoretic modeling of the human operator in flight control tasks, and the development of possible handling qualities metrics and/or measures of merit. Basic contributions were made in all these topics, including human operator (pilot) models for multi-loop tasks, optimal output feedback flight control synthesis techniques; experimental validations of the methods developed, and fundamental modeling studies of the air-to-air tracking and flared landing tasks.

  10. 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.

  11. Vibra-Sensors PXI-Based Test Complex Controlled by Labview

    Directory of Open Access Journals (Sweden)

    Borisov Alexey

    2016-01-01

    Full Text Available The article devoted to construction of an automated test complex for parametric and functional control of vibra-sensors ICs (such as integrated accelerometers and MEMS-generators. The test complex based on PXI-standard measurement devices and controlled by LabVIEW soft. The complex’s characteristics was confirmed by calibration service and been certified.

  12. Wind Turbine Converter Control Interaction with Complex Wind Farm Systems

    DEFF Research Database (Denmark)

    Kocewiak, Lukasz Hubert; Hjerrild, Jesper; Bak, Claus Leth

    2013-01-01

    in this study. It is shown that wind farm components, such as long high-voltage alternating current cables and park transformers, can introduce significant low-frequency series resonances seen from the wind turbine terminals that can affect wind turbine control system operation and overall wind farm stability......This study presents wind turbine converter stability analysis of wind farms in frequency domain. The interaction between the wind turbine control system and the wind farm structure in wind farms is deeply investigated. Two wind farms (i.e. Horns Rev II and Karnice) are taken into consideration....... The same wind turbine converter control strategy is evaluated in two different wind farms. It is emphasised that the grid-side converter controller should be characterised by sufficient harmonic/noise rejection and adjusted depending on wind farms to which it is connected. Various stability indices...

  13. Wind Turbine Converter Control Interaction with Complex Wind Farm Systems

    DEFF Research Database (Denmark)

    Kocewiak, Lukasz Hubert; Hjerrild, Jesper; Bak, Claus Leth

    2013-01-01

    . The same wind turbine converter control strategy is evaluated in two different wind farms. It is emphasised that the grid-side converter controller should be characterised by sufficient harmonic/noise rejection and adjusted depending on wind farms to which it is connected. Various stability indices......This study presents wind turbine converter stability analysis of wind farms in frequency domain. The interaction between the wind turbine control system and the wind farm structure in wind farms is deeply investigated. Two wind farms (i.e. Horns Rev II and Karnice) are taken into consideration...... in this study. It is shown that wind farm components, such as long high-voltage alternating current cables and park transformers, can introduce significant low-frequency series resonances seen from the wind turbine terminals that can affect wind turbine control system operation and overall wind farm stability...

  14. IPAD Paperless Work Control for Test Complex Facilities Management Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This project created a pilot version of the software tool work control system to run on a tablet by modifying the existing template and beginning an initial...

  15. Shear-stress-controlled dynamics of nematic complex fluids.

    Science.gov (United States)

    Klapp, Sabine H L; Hess, Siegfried

    2010-05-01

    Based on a mesoscopic theory we investigate the nonequilibrium dynamics of a sheared nematic liquid, with the control parameter being the shear stress σ xy (rather than the usual shear rate, γ). To this end we supplement the equations of motion for the orientational order parameters by an equation for γ, which then becomes time dependent. Shearing the system from an isotropic state, the stress-controlled flow properties turn out to be essentially identical to those at fixed γ. Pronounced differences occur when the equilibrium state is nematic. Here, shearing at controlled γ yields several nonequilibrium transitions between different dynamic states, including chaotic regimes. The corresponding stress-controlled system has only one transition from a regular periodic into a stationary (shear-aligned) state. The position of this transition in the σ xy-γ plane turns out to be tunable by the delay time entering our control scheme for σ xy. Moreover, a sudden change in the control method can stabilize the chaotic states appearing at fixed γ.

  16. Controlling Chaos with Rectificative Feedback Injections in 2D Coupled Complex Ginzburg-Landau Oscillators

    Institute of Scientific and Technical Information of China (English)

    GAOJi-Hua; ZHENGZhi-Gang; TANGJiao-Ning; PENGJian-Hua

    2003-01-01

    A model of two-dimensional coupled complex Ginzburg-Landau oscillators driven by a rectificative feedback controller is used to study controlling spatiotemporal chaos without gradient force items. By properly selecting the signal injecting position with considering the maximum gap between signals and targets, and adjusting the control time interval,we have finally obtained the efficient chaos control via numerical simulations.

  17. Optimal pinning controllability of complex networks: dependence on network structure.

    Science.gov (United States)

    Jalili, Mahdi; Askari Sichani, Omid; Yu, Xinghuo

    2015-01-01

    Controlling networked structures has many applications in science and engineering. In this paper, we consider the problem of pinning control (pinning the dynamics into the reference state), and optimally placing the driver nodes, i.e., the nodes to which the control signal is fed. Considering the local controllability concept, a metric based on the eigenvalues of the Laplacian matrix is taken into account as a measure of controllability. We show that the proposed optimal placement strategy considerably outperforms heuristic methods including choosing hub nodes with high degree or betweenness centrality as drivers. We also study properties of optimal drivers in terms of various centrality measures including degree, betweenness, closeness, and clustering coefficient. The profile of these centrality values depends on the network structure. For homogeneous networks such as random small-world networks, the optimal driver nodes have almost the mean centrality value of the population (much lower than the centrality value of hub nodes), whereas the centrality value of optimal drivers in heterogeneous networks such as scale-free ones is much higher than the average and close to that of hub nodes. However, as the degree of heterogeneity decreases in such networks, the profile of centrality approaches the population mean.

  18. 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.

  19. 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.

  20. Optimal Control and Forecasting of Complex Dynamical Systems

    CERN Document Server

    Grigorenko, Ilya

    2006-01-01

    This important book reviews applications of optimization and optimal control theory to modern problems in physics, nano-science and finance. The theory presented here can be efficiently applied to various problems, such as the determination of the optimal shape of a laser pulse to induce certain excitations in quantum systems, the optimal design of nanostructured materials and devices, or the control of chaotic systems and minimization of the forecast error for a given forecasting model (for example, artificial neural networks). Starting from a brief review of the history of variational calcul

  1. Pinning controllability of complex networks with community structure.

    Science.gov (United States)

    Miao, Qingying; Tang, Yang; Kurths, Jürgen; Fang, Jian-an; Wong, W K

    2013-09-01

    In this paper, we study the controllability of networks with different numbers of communities and various strengths of community structure. By means of simulations, we show that the degree descending pinning scheme performs best among several considered pinning schemes under a small number of pinned nodes, while the degree ascending pinning scheme is becoming more powerful by increasing the number of pinned nodes. It is found that increasing the number of communities or reducing the strength of community structure is beneficial for the enhancement of the controllability. Moreover, it is revealed that the pinning scheme with evenly distributed pinned nodes among communities outperforms other kinds of considered pinning schemes.

  2. Controlling hyperchaotic complex systems with unknown parameters based on adaptive passive method

    Institute of Scientific and Technical Information of China (English)

    Gamal M.Mahmoud; Emad E.Mahmoud; Ayman A.Arafa

    2013-01-01

    The aim of this paper is to study the control of hyperchaotic complex nonlinear systems with unknown parameters using passive control theory.An approach is stated to design the passive controller and estimate the unknown parameters based on the property of the passive system.The feasibility and effectiveness of the proposed approach is demonstrated through its application to the hyperchaotic complex Lü system,as an example.The estimated values of the unknown parameters are calculated.The analytical form of the complex controller is derived and used in the numerical simulation to control the hyperchaotic attractors of this example.Block diagrams of this example using Matlab/Simulink are constructed after and before the control to ensure the validity of the analytical results.Other examples of hyperchaotic complex nonlinear systems can be similarly treated.

  3. Methylene Diphosphonate Chemical and Biological control of MDP complex

    CERN Document Server

    Aungurarat, A

    2000-01-01

    Technetium-9 sup 9 sup m MDP easy prepared from MDP kits which different sources such as OAP (In house), SIGMA. The resulting Tc 9 sup 9 sup m -MDP preparations were controlled in chemical and biological tests to compare the different results in these cases: radiochemical purity, the quantity of starting material and biodistribution result.

  4. Cognitive Complexity and Attentional Control in the Bilingual Mind.

    Science.gov (United States)

    Bialystok, Ellen

    1999-01-01

    Investigated in preschoolers whether the bilingual advantage in cognitive control or selective attention could be found in a nonverbal task, the dimensional change card sort, requiring minimal demands for analysis or representation. Found that bilingual children were more advanced than monolinguals in solving problems requiring high levels of…

  5. Structural analysis of complex ecological economic optimal control problems

    NARCIS (Netherlands)

    Kiseleva, T.

    2011-01-01

    This thesis demonstrates the importance and effectiveness of methods of bifurcation theory applied to studying non-convex optimal control problems. It opens up a new methodological approach to investigation of parameterized economic models. While standard analytical methods are not efficient and

  6. Controlled synchronization of complex network with different kinds of nodes

    Institute of Scientific and Technical Information of China (English)

    Zhengquan YANG; Zhongxin LIU; Zengqiang CHEN; Zhuzhi YUAN

    2008-01-01

    In this paper, a new dynamical network model is introduced, in which the nodes of the network are different. It is shown that by the designed controllers, the state of the network can exponentially synchronize onto a homogeneous stationary state. Some criteria are derived and some examples are presented. The numerical simulations coincide with theoretical analysis.

  7. Realization of a Complex Control & Diagnosis System on Simplified Hardware

    Science.gov (United States)

    Stetter, R.; Swamy Prasad, M.

    2015-11-01

    Energy is an important factor in today's industrial environment. Pump systems account for about 20% of the total industrial electrical energy consumption. Several studies show that with proper monitoring, control and maintenance, the efficiency of pump systems can be increased. Controlling pump systems with intelligent systems can help to reduce a pump's energy consumption by up to one third of its original consumption. The research in this paper was carried out in the scope of a research project which involves modelling and simulation of pump systems. This paper focuses on the future implementation of modelling capabilities in PLCs (programmable logic controllers). The whole project aims to use a pump itself as the sensor rather than introducing external sensors into the system, which would increase the cost considerably. One promising approach for an economic and robust industrial implementation of this intelligence is the use of PLCs. PLCs can be simulated in multiple ways; in this project, Codesys was chosen for several reasons which are explained in this paper. The first part of this paper explains the modelling of a pump itself, the process load of the asynchronous motor with a control system, and the simulation possibilities of the motor in Codesys. The second part describes the simulation and testing of a system realized. The third part elaborates the Codesys system structure and interfacing of the system with external files. The final part consists of comparing the result with an earlier Matlab/SIMULINK model and original test data.

  8. Physiological complexity and system adaptability: evidence from postural control dynamics of older adults.

    Science.gov (United States)

    Manor, Brad; Costa, Madalena D; Hu, Kun; Newton, Elizabeth; Starobinets, Olga; Kang, Hyun Gu; Peng, C K; Novak, Vera; Lipsitz, Lewis A

    2010-12-01

    The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.

  9. Light fields in complex media: Mesoscopic scattering meets wave control

    Science.gov (United States)

    Rotter, Stefan; Gigan, Sylvain

    2017-01-01

    The newly emerging field of wave front shaping in complex media has recently seen enormous progress. The driving force behind these advances has been the experimental accessibility of the information stored in the scattering matrix of a disordered medium, which can nowadays routinely be exploited to focus light as well as to image or to transmit information even across highly turbid scattering samples. An overview of these new techniques, their experimental implementations, and the underlying theoretical concepts following from mesoscopic scattering theory is provided. In particular, the intimate connections between quantum transport phenomena and the scattering of light fields in disordered media, which can both be described by the same theoretical concepts, are highlighted. Particular emphasis is put on how these topics relate to application-oriented research fields such as optical imaging, sensing, and communication.

  10. Nanoparticle Controlled Soft Complex Structures with Topological Defects

    Science.gov (United States)

    2013-10-01

    4) Soft Matter 9, 3956-3964 (2013); 5) Adv. Cond. Matter Phys. 2013, 505219-1-505219-10 (2013); 6) J. Phys.: Condens. Matter, Special Issue on...Curvature control of valence on nematic shells, Soft Matter 7, 670 (2011). [14] F.C. MacKintosh, T.C. Lubensky, Orientational order, topology, and...Zidansek, Different modulated structures of topological defects stabilized by adaptive targeting nanoparticles, Soft Matter 9, 3956 (2013). [20

  11. Control and acquisition software complex for TBTS experiments

    CERN Document Server

    Dubrovskiy, Alexey

    2010-01-01

    The Two-beam Test-stand (TBTS) is a test area in the CLIC Test Facility (CTF3) to demonstrate the high power RF extraction and acceleration at a high accelerating gradient, which are feasibility issues for the Compact Linear Collider (CLIC) project. In order to achieve an efficient data collection, an acquisition and logging software system was developed. All year round these systems store the main parameters such as beam position, beam current, vacuum level, pulse length etc. For predefined events they also gather and store all information about the last several pulses and the machine status. A GUI interface allows from anywhere to plot many logged characteristics at a maximum of 10 minutes delay, to go though all events and to extract any logged data. A control interface configures actions and long-term control procedures for conditioning accelerating structures. The flexible configuration of the logging, the acquisition and the control systems are integrated into the same GUI. After two years operation the...

  12. Complex conditional control by pigeons in a continuous virtual environment.

    Science.gov (United States)

    Qadri, Muhammad A J; Reid, Sean; Cook, Robert G

    2016-01-01

    We tested two pigeons in a continuously streaming digital environment. Using animation software that constantly presented a dynamic, three-dimensional (3D) environment, the animals were tested with a conditional object identification task. The correct object at a given time depended on the virtual context currently streaming in front of the pigeon. Pigeons were required to accurately peck correct target objects in the environment for food reward, while suppressing any pecks to intermixed distractor objects which delayed the next object's presentation. Experiment 1 established that the pigeons' discrimination of two objects could be controlled by the surface material of the digital terrain. Experiment 2 established that the pigeons' discrimination of four objects could be conjunctively controlled by both the surface material and topography of the streaming environment. These experiments indicate that pigeons can simultaneously process and use at least two context cues from a streaming environment to control their identification behavior of passing objects. These results add to the promise of testing interactive digital environments with animals to advance our understanding of cognition and behavior.

  13. Quantification of the mechanical behavior of carotid arteries from wild-type, dystrophin-deficient, and sarcoglycan-δ knockout mice

    Science.gov (United States)

    Gleason, Rudolph L.; Dye, Wendy W.; Wilson, Emily; Humphrey, Jay D.

    2008-01-01

    As patients with muscular dystrophy live longer because of improved clinical care, they will become increasingly susceptible to many of the cardiovascular diseases that affect the general population. There is, therefore, a pressing need to better understand both the biology and the mechanics of the arterial wall in these patients. In this paper, we use nonlinear constitutive relations to model, for the first time, the biaxial mechanical behavior of carotid arteries from two common mouse models of muscular dystrophy (dystrophin deficient and sarcoglycan-delta null) and wild-type controls. It is shown that a structurally motivated four-fiber family stress-strain relation describes the passive behavior of all three genotypes better than does a commonly used phenomenological exponential model, and that a Rachev-Hayashi model describes the mechanical contribution of smooth muscle contraction under basal tone. Because structurally motivated constitutive relations can be extended easily to model adaptations to altered hemodynamics, results from this study represent an important step toward the ultimate goal of understanding better the mechanobiology and pathophysiology of arteries in muscular dystrophy. PMID:18842267

  14. Automatically Finding the Control Variables for Complex System Behavior

    Science.gov (United States)

    Gay, Gregory; Menzies, Tim; Davies, Misty; Gundy-Burlet, Karen

    2010-01-01

    Testing large-scale systems is expensive in terms of both time and money. Running simulations early in the process is a proven method of finding the design faults likely to lead to critical system failures, but determining the exact cause of those errors is still time-consuming and requires access to a limited number of domain experts. It is desirable to find an automated method that explores the large number of combinations and is able to isolate likely fault points. Treatment learning is a subset of minimal contrast-set learning that, rather than classifying data into distinct categories, focuses on finding the unique factors that lead to a particular classification. That is, they find the smallest change to the data that causes the largest change in the class distribution. These treatments, when imposed, are able to identify the factors most likely to cause a mission-critical failure. The goal of this research is to comparatively assess treatment learning against state-of-the-art numerical optimization techniques. To achieve this, this paper benchmarks the TAR3 and TAR4.1 treatment learners against optimization techniques across three complex systems, including two projects from the Robust Software Engineering (RSE) group within the National Aeronautics and Space Administration (NASA) Ames Research Center. The results clearly show that treatment learning is both faster and more accurate than traditional optimization methods.

  15. Control of Complex Systems Using Bayesian Networks and Genetic Algorithm

    CERN Document Server

    Marwala, Tshilidzi

    2007-01-01

    A method based on Bayesian neural networks and genetic algorithm is proposed to control the fermentation process. The relationship between input and output variables is modelled using Bayesian neural network that is trained using hybrid Monte Carlo method. A feedback loop based on genetic algorithm is used to change input variables so that the output variables are as close to the desired target as possible without the loss of confidence level on the prediction that the neural network gives. The proposed procedure is found to reduce the distance between the desired target and measured outputs significantly.

  16. Multi-goal Control of Chaotic Connected Complex Networks

    Institute of Scientific and Technical Information of China (English)

    FANG Jin-Qing; LIU Qiang; LU Xin-Biao; WANG Xiao-Fan; LI Yong

    2008-01-01

    Beam transport network (BTN) with small world (SW) (so-called BTN-SW) and Lorenz chaotic connected network with scale-free (SF) are taken as two typical examples, we proposed a global linear coupling and combined with local error feedback methods in sub-networks to realize multi-goal control method of halo and chaos in two networks above. The simulation results show that the methods above is effective for any chaotic connected networks and has a potential of applications in based-halo-chaos secure communication.

  17. Optimizing controllability of edge dynamics in complex networks by perturbing network structure

    Science.gov (United States)

    Pang, Shaopeng; Hao, Fei

    2017-03-01

    Using the minimum input signals to drive the dynamics in complex networks toward some desired state is a fundamental issue in the field of network controllability. For a complex network with the dynamical process defined on its edges, the controllability of this network is optimal if it can be fully controlled by applying one input signal to an arbitrary non-isolated vertex of it. In this paper, the adding-edge strategy and turning-edge strategy are proposed to optimize the controllability by minimum structural perturbations. Simulations and analyses indicate that the minimum number of adding-edges required for the optimal controllability is equal to the minimum number of turning-edges, and networks with positively correlated in- and out-degrees are easier to achieve optimal controllability. Furthermore, both the strategies have the capacity to reveal the relationship between certain structural properties of a complex network and its controllability of edge dynamics.

  18. Transcranial magnetic stimulation reveals complex cognitive control representations in the rostral frontal cortex.

    Science.gov (United States)

    Bahlmann, J; Beckmann, I; Kuhlemann, I; Schweikard, A; Münte, T F

    2015-08-06

    Convergent evidence suggests that the lateral frontal cortex is at the heart of a brain network subserving cognitive control. Recent theories assume a functional segregation along the rostro-caudal axis of the lateral frontal cortex based on differences in the degree of complexity of cognitive control. However, the functional contribution of specific rostral and caudal sub-regions remains elusive. Here we investigate the impact of disrupting rostral and caudal target regions on cognitive control processes, using Transcranial Magnetic Stimulation (TMS). Participants performed three different task-switching conditions that assessed differences in the degree of complexity of cognitive control processes, after temporally disrupting rostral, or caudal target regions, or a control region. Disrupting the rostral lateral frontal region specifically impaired behavioral performance of the most complex task-switching condition, in comparison to the caudal target region and the control region. These novel findings shed light on the neuroanatomical architecture supporting control over goal-directed behavior.

  19. Controlling Combinatorial Complexity in Software and Malware Behavior Computation

    Energy Technology Data Exchange (ETDEWEB)

    Pleszkoch, Mark G [ORNL; Linger, Richard C [ORNL

    2015-01-01

    Virtually all software is out of intellectual control in that no one knows its full behavior. Software Behavior Computation (SBC) is a new technology for understanding everything software does. SBC applies the mathematics of denotational semantics implemented by function composition in Functional Trace Tables (FTTs) to compute the behavior of programs, expressed as disjoint cases of conditional concurrent assignments. In some circumstances, combinatorial explosions in the number of cases can occur when calculating the behavior of sequences of multiple branching structures. This paper describes computational methods that avoid combinatorial explosions. The predicates that control branching structures such as ifthenelses can be organized into three categories: 1) Independent, resulting in no behavior case explosion, 2) Coordinated, resulting in two behavior cases, or 3) Goaloriented, with potential exponential growth in the number of cases. Traditional FTT-based behavior computation can be augmented by two additional computational methods, namely, Single-Value Function Abstractions (SVFAs) and, introduced in this paper, Relational Trace Tables (RTTs). These methods can be applied to the three predicate categories to avoid combinatorial growth in behavior cases while maintaining mathematical correctness.

  20. Pest control of aphids depends on landscape complexity and natural enemy interactions

    Directory of Open Access Journals (Sweden)

    Emily A. Martin

    2015-07-01

    Full Text Available Aphids are a major concern in agricultural crops worldwide, and control by natural enemies is an essential component of the ecological intensification of agriculture. Although the complexity of agricultural landscapes is known to influence natural enemies of pests, few studies have measured the degree of pest control by different enemy guilds across gradients in landscape complexity. Here, we use multiple natural-enemy exclosures replicated in 18 fields across a gradient in landscape complexity to investigate (1 the strength of natural pest control across landscapes, measured as the difference between pest pressure in the presence and in the absence of natural enemies; (2 the differential contributions of natural enemy guilds to pest control, and the nature of their interactions across landscapes. We show that natural pest control of aphids increased up to six-fold from simple to complex landscapes. In the absence of pest control, aphid population growth was higher in complex than simple landscapes, but was reduced by natural enemies to similar growth rates across all landscapes. The effects of enemy guilds were landscape-dependent. Particularly in complex landscapes, total pest control was supplied by the combined contribution of flying insects and ground-dwellers. Birds had little overall impact on aphid control. Despite evidence for intraguild predation of flying insects by ground-dwellers and birds, the overall effect of enemy guilds on aphid control was complementary. Understanding pest control services at large spatial scales is critical to increase the success of ecological intensification schemes. Our results suggest that, where aphids are the main pest of concern, interactions between natural enemies are largely complementary and lead to a strongly positive effect of landscape complexity on pest control. Increasing the availability of seminatural habitats in agricultural landscapes may thus benefit not only natural enemies, but also the

  1. Pest control of aphids depends on landscape complexity and natural enemy interactions.

    Science.gov (United States)

    Martin, Emily A; Reineking, Björn; Seo, Bumsuk; Steffan-Dewenter, Ingolf

    2015-01-01

    Aphids are a major concern in agricultural crops worldwide, and control by natural enemies is an essential component of the ecological intensification of agriculture. Although the complexity of agricultural landscapes is known to influence natural enemies of pests, few studies have measured the degree of pest control by different enemy guilds across gradients in landscape complexity. Here, we use multiple natural-enemy exclosures replicated in 18 fields across a gradient in landscape complexity to investigate (1) the strength of natural pest control across landscapes, measured as the difference between pest pressure in the presence and in the absence of natural enemies; (2) the differential contributions of natural enemy guilds to pest control, and the nature of their interactions across landscapes. We show that natural pest control of aphids increased up to six-fold from simple to complex landscapes. In the absence of pest control, aphid population growth was higher in complex than simple landscapes, but was reduced by natural enemies to similar growth rates across all landscapes. The effects of enemy guilds were landscape-dependent. Particularly in complex landscapes, total pest control was supplied by the combined contribution of flying insects and ground-dwellers. Birds had little overall impact on aphid control. Despite evidence for intraguild predation of flying insects by ground-dwellers and birds, the overall effect of enemy guilds on aphid control was complementary. Understanding pest control services at large spatial scales is critical to increase the success of ecological intensification schemes. Our results suggest that, where aphids are the main pest of concern, interactions between natural enemies are largely complementary and lead to a strongly positive effect of landscape complexity on pest control. Increasing the availability of seminatural habitats in agricultural landscapes may thus benefit not only natural enemies, but also the effectiveness of

  2. Mathematical Foundations for Efficient Structural Controllability and Observability Analysis of Complex Systems

    Directory of Open Access Journals (Sweden)

    Pedro J. Zufiria

    2014-01-01

    Full Text Available The relationship between structural controllability and observability of complex systems is studied. Algebraic and graph theoretic tools are combined to prove the extent of some controller/observer duality results. Two types of control design problems are addressed and some fundamental theoretical results are provided. In addition new algorithms are presented to compute optimal solutions for monitoring large scale real networks.

  3. Controlling Chaos with Rectificative Feedback Injections in 2D Coupled Complex Ginzburg-Landau Oscillators

    Institute of Scientific and Technical Information of China (English)

    GAO Ji-Hua; ZHENG Zhi-Gang; TANG Jiao-Ning; PENG Jian-Hua

    2003-01-01

    A model of two-dimensional coupled complex Ginzburg-Landau oscillators driven by a rectificative feedbackcontroller is used to study controlling spatiotemporal chaos without gradient force items. By properly selecting the signalinjecting position with considering the maximum gap between signals and targets, and adjusting the control time interval,we have finally obtained the efficient chaos control via numerical simulations.

  4. Complexity

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  5. Pinning Lur’e Complex Networks via Output Feedback Control

    Directory of Open Access Journals (Sweden)

    Fang Liu

    2014-01-01

    Full Text Available Without requiring the full-state information of network nodes, this paper studies the pinning synchronization in a network of Lur’e dynamical systems based on the output feedback control strategy. Some simple pinning conditions are established for both undirected and directed Lur’e networks by using M-matrix theory and S-procedure technique. With the derived stability criteria, the pinning synchronization problem of large-scale Lur’e networks can be transformed to the test of a low-dimensional linear matrix inequality. Some remarks are further given to address the selection of pinned nodes and the design of pinning feedback gains. Numerical results are provided to demonstrate the effectiveness of the theoretical analysis.

  6. Pinning control of complex networked systems synchronization, consensus and flocking of networked systems via pinning

    CERN Document Server

    Su, Housheng

    2013-01-01

    Synchronization, consensus and flocking are ubiquitous requirements in networked systems. Pinning Control of Complex Networked Systems investigates these requirements by using the pinning control strategy, which aims to control the whole dynamical network with huge numbers of nodes by imposing controllers for only a fraction of the nodes. As the direct control of every node in a dynamical network with huge numbers of nodes might be impossible or unnecessary, it’s then very important to use the pinning control strategy for the synchronization of complex dynamical networks. The research on pinning control strategy in consensus and flocking of multi-agent systems can not only help us to better understand the mechanisms of natural collective phenomena, but also benefit applications in mobile sensor/robot networks. This book offers a valuable resource for researchers and engineers working in the fields of control theory and control engineering.   Housheng Su is an Associate Professor at the Department of Contro...

  7. A Two-amino Acid Mutation Encountered in Duchenne Muscular Dystrophy Decreases Stability of the Rod Domain 23 (R23) Spectrin-like Repeat of Dystrophin.

    Science.gov (United States)

    Legardinier, Sébastien; Legrand, Baptiste; Raguénès-Nicol, Céline; Bondon, Arnaud; Hardy, Serge; Tascon, Christophe; Le Rumeur, Elisabeth; Hubert, Jean-François

    2009-03-27

    Lack of functional dystrophin causes severe Duchenne muscular dystrophy. The subsarcolemmal location of dystrophin, as well as its association with both cytoskeleton and membrane, suggests a role in the mechanical regulation of muscular membrane stress. In particular, phenotype rescue in a Duchenne muscular dystrophy mice model has shown that some parts of the central rod domain of dystrophin, constituted by 24 spectrin-like repeats, are essential. In this study, we made use of rare missense pathogenic mutations in the dystrophin gene and analyzed the biochemical properties of the isolated repeat 23 bearing single or double mutations E2910V and N2912D found in muscle dystrophy with severity grading. No dramatic effect on secondary and tertiary structure of the repeat was found in mutants compared with wild type as revealed by circular dichroism and NMR. Thermal and chemical unfolding data from circular dichroism and tryptophan fluorescence show significant decrease of stability for the mutants, and stopped-flow spectroscopy shows decreased refolding rates. The most deleterious single mutation is the N2912D replacement, although we observe additive effects of the two mutations on repeat stability. Based on three-dimensional structures built by homology molecular modeling, we discuss the modifications of the mutation-induced repeat stability. We conclude that the main forces involved in repeat stability are electrostatic inter-helix interactions that are disrupted following mutations. This study represents the first analysis at the protein level of the consequences of missense mutations in the human dystrophin rod domain. Our results suggest that it may participate in mechanical weakening of dystrophin-deficient muscle.

  8. Nestin expression in end-stage disease in dystrophin-deficient heart: implications for regeneration from endogenous cardiac stem cells.

    Science.gov (United States)

    Berry, Suzanne E; Andruszkiewicz, Peter; Chun, Ju Lan; Hong, Jun

    2013-11-01

    Nestin(+) cardiac stem cells differentiate into striated cells following myocardial infarct. Transplantation of exogenous stem cells into myocardium of a murine model for Duchenne muscular dystrophy (DMD) increased proliferation of endogenous nestin(+) stem cells and resulted in the appearance of nestin(+) striated cells. This correlated with, and may be responsible for, prevention of dilated cardiomyopathy. We examined nestin(+) stem cells in the myocardium of dystrophin/utrophin-deficient (mdx/utrn(-/-)) mice, a model for DMD. We found that 92% of nestin(+) interstitial cells expressed Flk-1, a marker present on cardiac progenitor cells that differentiate into the cardiac lineage, and that a subset expressed Sca-1, present on adult cardiac cells that become cardiomyocytes. Nestin(+) interstitial cells maintained expression of Flk-1 but lost Sca-1 expression with age and were present in lower numbers in dystrophin-deficient heart than in wild-type heart. Unexpectedly, large clusters of nestin(+) striated cells ranging in size from 20 to 250 cells and extending up to 500 μm were present in mdx/utrn(-/-) heart near the end stage of disease. These cells were also present in dystrophin-deficient mdx/utrn(+/-) and mdx heart but not wild-type heart. Nestin(+) striated cells expressed cardiac troponin I, desmin, and Connexin 43 and correlated with proinflammatory CD68(+) macrophages. Elongated nestin(+) interstitial cells with striations were observed that did not express Flk-1 or the late cardiac marker cardiac troponin I but strongly expressed the early cardiac marker desmin. Nestin was also detected in endothelial and smooth muscle cells. These data indicate that new cardiomyocytes form in dystrophic heart, and nestin(+) interstitial cells may generate them in addition to other cells of the cardiac lineage.

  9. Optimization of controllability and robustness of complex networks by edge directionality

    Science.gov (United States)

    Liang, Man; Jin, Suoqin; Wang, Dingjie; Zou, Xiufen

    2016-09-01

    Recently, controllability of complex networks has attracted enormous attention in various fields of science and engineering. How to optimize structural controllability has also become a significant issue. Previous studies have shown that an appropriate directional assignment can improve structural controllability; however, the evolution of the structural controllability of complex networks under attacks and cascading has always been ignored. To address this problem, this study proposes a new edge orientation method (NEOM) based on residual degree that changes the link direction while conserving topology and directionality. By comparing the results with those of previous methods in two random graph models and several realistic networks, our proposed approach is demonstrated to be an effective and competitive method for improving the structural controllability of complex networks. Moreover, numerical simulations show that our method is near-optimal in optimizing structural controllability. Strikingly, compared to the original network, our method maintains the structural controllability of the network under attacks and cascading, indicating that the NEOM can also enhance the robustness of controllability of networks. These results alter the view of the nature of controllability in complex networks, change the understanding of structural controllability and affect the design of network models to control such networks.

  10. Extreme events in multilayer, interdependent complex networks and control

    Science.gov (United States)

    Chen, Yu-Zhong; Huang, Zi-Gang; Zhang, Hai-Feng; Eisenberg, Daniel; Seager, Thomas P.; Lai, Ying-Cheng

    2015-11-01

    We investigate the emergence of extreme events in interdependent networks. We introduce an inter-layer traffic resource competing mechanism to account for the limited capacity associated with distinct network layers. A striking finding is that, when the number of network layers and/or the overlap among the layers are increased, extreme events can emerge in a cascading manner on a global scale. Asymptotically, there are two stable absorption states: a state free of extreme events and a state of full of extreme events, and the transition between them is abrupt. Our results indicate that internal interactions in the multiplex system can yield qualitatively distinct phenomena associated with extreme events that do not occur for independent network layers. An implication is that, e.g., public resource competitions among different service providers can lead to a higher resource requirement than naively expected. We derive an analytical theory to understand the emergence of global-scale extreme events based on the concept of effective betweenness. We also articulate a cost-effective control scheme through increasing the capacity of very few hubs to suppress the cascading process of extreme events so as to protect the entire multi-layer infrastructure against global-scale breakdown.

  11. Mathematical and computer tools of discrete dynamic modeling and analysis of complex systems in control loop

    CERN Document Server

    Bagdasaryan, Armen

    2008-01-01

    We present a method of discrete modeling and analysis of multilevel dynamics of complex large-scale hierarchical dynamic systems subject to external dynamic control mechanism. Architectural model of information system supporting simulation and analysis of dynamic processes and development scenarios (strategies) of complex large-scale hierarchical systems is also proposed.

  12. Influences of Sentence Length and Syntactic Complexity on the Speech Motor Control of Children Who Stutter

    Science.gov (United States)

    MacPherson, Megan K.; Smith, Anne

    2013-01-01

    Purpose: To investigate the potential effects of increased sentence length and syntactic complexity on the speech motor control of children who stutter (CWS). Method: Participants repeated sentences of varied length and syntactic complexity. Kinematic measures of articulatory coordination variability and movement duration during perceptually…

  13. Multiscale entropy identifies differences in complexity in postural control in women with multiple sclerosis.

    Science.gov (United States)

    Busa, Michael A; Jones, Stephanie L; Hamill, Joseph; van Emmerik, Richard E A

    2016-03-01

    Loss of postural center-of-pressure complexity (COP complexity) has been associated with reduced adaptability that accompanies disease and aging. The aim of this study was to identify if COP complexity is reduced: (1) in those with Multiple Sclerosis (MS) compared to controls; (2) when vision is limited compared to remaining intact; and (3) during more demanding postural conditions compared to quiet standing. Additionally, we explored the relationship between the COP complexity and disease severity, fatigue, cutaneous sensation and central motor drive. Twelve women with MS and 12 age-matched controls were tested under quiet standing and postural maximal lean conditions with normal and limited vision. The key dependent variable was the complexity index (CI) of the center of pressure. We observed a lower CI in the MS group compared to controls in both anterior-posterior (AP) and medio-lateral (ML) directions (p's0.05) was observed, indicating that limiting vision did not impact COP complexity differently in the two groups. Decreased cutaneous sensitivity was associated with lower CI values in the AP direction among those with MS (r(2)=0.57); all other measures did not exhibit significant relationships. The findings reported here suggest that (1) MS is associated with diminished COP complexity under both normal and challenging postures, and (2) complexity is strongly correlated with cutaneous sensitivity, suggesting the unique contribution of impaired somatosensation on postural control deficits in persons with MS.

  14. Influences of Sentence Length and Syntactic Complexity on the Speech Motor Control of Children Who Stutter

    Science.gov (United States)

    MacPherson, Megan K.; Smith, Anne

    2013-01-01

    Purpose: To investigate the potential effects of increased sentence length and syntactic complexity on the speech motor control of children who stutter (CWS). Method: Participants repeated sentences of varied length and syntactic complexity. Kinematic measures of articulatory coordination variability and movement duration during perceptually…

  15. CONTROLLING AS A MECHANISM TO INCREASE THE EFFICIENCY OF MANAGEMENT ENTERPRISES OF FUEL-ENERGY COMPLEX

    Directory of Open Access Journals (Sweden)

    M. A. Ostashkin

    2013-01-01

    Full Text Available This article discusses the possibility of application of controlling as mechanism of increasing the efficiency of management of enterprises of fuel- energy complex. The research was conducted on the materials of the JSC «Gazprom».

  16. Complexity of the transcriptional network controlling secondary wall biosynthesis.

    Science.gov (United States)

    Zhong, Ruiqin; Ye, Zheng-Hua

    2014-12-01

    Secondary walls in the form of wood and fibers are the most abundant biomass produced by vascular plants, and are important raw materials for many industrial uses. Understanding how secondary walls are constructed is of significance in basic plant biology and also has far-reaching implications in genetic engineering of plant biomass better suited for various end uses, such as biofuel production. Secondary walls are composed of three major biopolymers, i.e., cellulose, hemicelluloses and lignin, the biosynthesis of which requires the coordinated transcriptional regulation of all their biosynthesis genes. Genomic and molecular studies have identified a number of transcription factors, whose expression is associated with secondary wall biosynthesis. We comprehensively review how these secondary wall-associated transcription factors function together to turn on the secondary wall biosynthetic program, which leads to secondary wall deposition in vascular plants. The transcriptional network regulating secondary wall biosynthesis employs a multi-leveled feed-forward loop regulatory structure, in which the top-level secondary wall NAC (NAM, ATAF1/2 and CUC2) master switches activate the second-level MYB master switches and they together induce the expression of downstream transcription factors and secondary wall biosynthesis genes. Secondary wall NAC master switches and secondary wall MYB master switches bind to and activate the SNBE (secondary wall NAC binding element) and SMRE (secondary wall MYB-responsive element) sites, respectively, in their target gene promoters. Further investigation of what and how developmental signals trigger the transcriptional network to regulate secondary wall biosynthesis and how different secondary wall-associated transcription factors function cooperatively in activating secondary wall biosynthetic pathways will lead to a better understanding of the molecular mechanisms underlying the transcriptional control of secondary wall biosynthesis.

  17. Disruption of action potential and calcium signaling properties in malformed myofibers from dystrophin-deficient mice.

    Science.gov (United States)

    Hernández-Ochoa, Erick O; Pratt, Stephen J P; Garcia-Pelagio, Karla P; Schneider, Martin F; Lovering, Richard M

    2015-04-01

    Duchenne muscular dystrophy (DMD), the most common and severe muscular dystrophy, is caused by the absence of dystrophin. Muscle weakness and fragility (i.e., increased susceptibility to damage) are presumably due to structural instability of the myofiber cytoskeleton, but recent studies suggest that the increased presence of malformed/branched myofibers in dystrophic muscle may also play a role. We have previously studied myofiber morphology in healthy wild-type (WT) and dystrophic (MDX) skeletal muscle. Here, we examined myofiber excitability using high-speed confocal microscopy and the voltage-sensitive indicator di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) to assess the action potential (AP) properties. We also examined AP-induced Ca(2+) transients using high-speed confocal microscopy with rhod-2, and assessed sarcolemma fragility using elastimetry. AP recordings showed an increased width and time to peak in malformed MDX myofibers compared to normal myofibers from both WT and MDX, but no significant change in AP amplitude. Malformed MDX myofibers also exhibited reduced AP-induced Ca(2+) transients, with a further Ca(2+) transient reduction in the branches of malformed MDX myofibers. Mechanical studies indicated an increased sarcolemma deformability and instability in malformed MDX myofibers. The data suggest that malformed myofibers are functionally different from myofibers with normal morphology. The differences seen in AP properties and Ca(2+) signals suggest changes in excitability and remodeling of the global Ca(2+) signal, both of which could underlie reported weakness in dystrophic muscle. The biomechanical changes in the sarcolemma support the notion that malformed myofibers are more susceptible to damage. The high prevalence of malformed myofibers in dystrophic muscle may contribute to the progressive strength loss and fragility seen in dystrophic muscles. © 2015 The Authors. Physiological Reports published by Wiley

  18. Screening the dystrophin gene suggests a high rate of polymorphism in general but no exonic deletions in schizophrenics

    Energy Technology Data Exchange (ETDEWEB)

    Lindor, N.M.; Sobell, J.L.; Thibodeau, S.N. [Mayo Clinic/Foundation, Rochester, MN (United States)] [and others

    1994-03-15

    The dystrophin gene, located at chromosome Xp21, was evaluated as a candidate gene in chronic schizophrenia in response to the report of a large family in which schizophrenia cosegregated with Becker muscular dystrophy. Genomic DNA from 94 men with chronic schizophrenia was evaluated by Southern blot analysis using cDNA probes that span exons 1-59. No exonic deletions were identified. An unexpectedly high rate of polymorphism was calculated in this study and two novel polymorphisms were found, demonstrating the usefulness of the candidate gene approach even when results of the original study are negative. 41 refs., 1 fig., 4 tabs.

  19. 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.

  20. Dia2 controls transcription by mediating assembly of the RSC complex.

    Directory of Open Access Journals (Sweden)

    Edward J Andress

    Full Text Available BACKGROUND: Dia2 is an F-box protein found in the budding yeast, S. cerevisiae. Together with Skp1 and Cul1, Dia2 forms the substrate-determining part of an E3 ubiquitin ligase complex, otherwise known as the SCF. Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex. PRINCIPAL FINDINGS: We identified components of the RSC chromatin remodelling complex as genetic interactors with Dia2, suggesting an additional role for Dia2 in the regulation of transcription. We show that Dia2 is involved in controlling assembly of the RSC complex. RSC belongs to a group of ATP-dependent nucleosome-remodelling complexes that controls the repositioning of nucleosomes. The RSC complex is expressed abundantly and its 17 subunits are recruited to chromatin in response to both transcription activation and repression. In the absence of Dia2, RSC-mediated transcription regulation was impaired, with concomitant abnormalities in nucleosome positioning. CONCLUSIONS: Our findings imply that Dia2 is required for the correct assembly and function of the RSC complex. Dia2, by controlling the RSC chromatin remodeller, fine-tunes transcription by controlling nucleosome positioning during transcriptional activation and repression.

  1. Synthesis of Titanium Dioxide Nanocrystals with Controlled Crystal- and Micro-structures from Titanium Complexes

    OpenAIRE

    Makoto Kobayashi; Hideki Kato; Masato Kakihana

    2013-01-01

    Selective synthesis of titanium dioxide (TiO2) polymorphs including anatase, rutile, brookite and TiO2(B) by solvothermal treatment of water-soluble titanium complexes is described with a special focus on their morphological control. The utilization of water-soluble titanium complexes as a raw material allowed us to employ various additives in the synthesis of TiO2. As a result, the selective synthesis of the polymorphs, as well as diverse morphological control, was achieved.

  2. Finite-Time Chaos Control of a Complex Permanent Magnet Synchronous Motor System

    Directory of Open Access Journals (Sweden)

    Xiaobing Zhou

    2014-01-01

    Full Text Available This paper investigates the finite-time chaos control of a permanent magnet synchronous motor system with complex variables. Based on the finite-time stability theory, two control strategies are proposed to realize stabilization of the complex permanent magnet synchronous motor system in a finite time. Two numerical simulations have been conducted to demonstrate the validity and feasibility of the theoretical analysis.

  3. Complex

    African Journals Online (AJOL)

    CLEMENT O BEWAJI

    Schiff bases and their complex compounds have been studied for their .... establishing coordination of the N–(2 – hydroxybenzyl) - L - α - valine Schiff base ..... (1967); “Spectrophotometric Identification of Organic Compounds”, Willey, New.

  4. A Probabilistic Approach to Control of Complex Systems and Its Application to Real-Time Pricing

    Directory of Open Access Journals (Sweden)

    Koichi Kobayashi

    2014-01-01

    Full Text Available Control of complex systems is one of the fundamental problems in control theory. In this paper, a control method for complex systems modeled by a probabilistic Boolean network (PBN is studied. A PBN is widely used as a model of complex systems such as gene regulatory networks. For a PBN, the structural control problem is newly formulated. In this problem, a discrete probability distribution appeared in a PBN is controlled by the continuous-valued input. For this problem, an approximate solution method using a matrix-based representation for a PBN is proposed. Then, the problem is approximated by a linear programming problem. Furthermore, the proposed method is applied to design of real-time pricing systems of electricity. Electricity conservation is achieved by appropriately determining the electricity price over time. The effectiveness of the proposed method is presented by a numerical example on real-time pricing systems.

  5. Realistic and verifiable coherent control of excitonic states in a light harvesting complex

    CERN Document Server

    Hoyer, Stephan; Montangero, Simone; Sarovar, Mohan; Calarco, Tommaso; Plenio, Martin B; Whaley, K Birgitta

    2013-01-01

    We explore the feasibility of coherent control of excitonic dynamics in light harvesting complexes despite the open nature of these quantum systems. We establish feasible targets for phase and phase/amplitude control of the electronically excited state populations in the Fenna-Mathews-Olson (FMO) complex and analyze the robustness of this control. We further present two possible routes to verification of the control target, with simulations for the FMO complex showing that steering of the excited state is experimentally verifiable either by extending excitonic coherence or by producing novel states in a pump-probe setup. Our results provide a first step toward coherent control of these systems in an ultrafast spectroscopy setup.

  6. Complex state variable- and disturbance observer-based current controllers for AC drives

    DEFF Research Database (Denmark)

    Dal, Mehmet; Teodorescu, Remus; Blaabjerg, Frede

    2013-01-01

    , extracted by a disturbance observer and then injected into the current controller. In this study, a revised version of a disturbance observer-based controller and a well known complex variable model-based design with a single set of complex pole are compared in terms of design aspects and performance...... of the parameter and the cross-coupling effect. Moreover, it provides a better performance, smooth and low noisy operation with respect to the complex variable controller....... of the stator current. In order to improve the current control performance an alternative current control strategy was proposed previously aiming to avoid the undesired cross-coupling and non-linearities between the state variables. These effects are assumed as disturbances arisen in the closed-loop path...

  7. Control of two-photon quantum walk in a complex multimode system by wavefront shaping

    CERN Document Server

    Defienne, Hugo; Walmsley, Ian A; Smith, Brian J; Gigan, Sylvain

    2015-01-01

    Multi-photon interferences in complex multimode structures - quantum walks - are of both funda- mental and technological interest. They rely on the ability to design the complex network where the walk occurs. Here, we demonstrate the control of quantum walks of two indistinguishable photons in a complex linear system - a highly multimode fiber - by means of wavefront shaping techniques. Using the measured transmission matrix of the fiber, we demonstrate the ability to address arbitrary output modes of the two-photon speckle pattern, and simultaneous control of the quantum inter- ferences. This work provides a reconfigurable platform for multi-photon, multimode interference experiments and a route to high-dimensional quantum systems.

  8. Dynamic control of the lumbopelvic complex; lack of reliability of established test procedures

    DEFF Research Database (Denmark)

    Henriksen, Marius; Lund, Hans; Bliddal, Henning

    2007-01-01

    Impairment of the dynamic control of the lumbopelvic complex in LBP has gained increased focus both clinically and experimentally. The objectives of this study were to determine the reliability of inclinometry as a measure of dynamic lumbopelvic control. Lumbopelvic reposition accuracy during pel...

  9. Efficient Restoration of the Dystrophin Gene Reading Frame and Protein Structure in DMD Myoblasts Using the CinDel Method

    Directory of Open Access Journals (Sweden)

    Jean-Paul Iyombe-Engembe

    2016-01-01

    Full Text Available The CRISPR/Cas9 system is a great revolution in biology. This technology allows the modification of genes in vitro and in vivo in a wide variety of living organisms. In most Duchenne muscular dystrophy (DMD patients, expression of dystrophin (DYS protein is disrupted because exon deletions result in a frame shift. We present here the CRISPR-induced deletion (CinDel, a new promising genome-editing technology to correct the DMD gene. This strategy is based on the use of two gRNAs targeting specifically exons that precede and follow the patient deletion in the DMD gene. This pair of gRNAs induced a precise large additional deletion leading to fusion of the targeted exons. Using an adequate pair of gRNAs, the deletion of parts of these exons and the intron separating them restored the DMD reading frame in 62% of the hybrid exons in vitro in DMD myoblasts and in vivo in electroporated hDMD/mdx mice. Moreover, adequate pairs of gRNAs also restored the normal spectrin-like repeat of the dystrophin rod domain; such restoration is not obtained by exon skipping or deletion of complete exons. The expression of an internally deleted DYS protein was detected following the formation of myotubes by the unselected, treated DMD myoblasts. Given that CinDel induces permanent reparation of the DMD gene, this treatment would not have to be repeated as it is the case for exon skipping induced by oligonucleotides.

  10. Proteomic Profiling of the Dystrophin-Deficient MDX Heart Reveals Drastically Altered Levels of Key Metabolic and Contractile Proteins

    Directory of Open Access Journals (Sweden)

    Caroline Lewis

    2010-01-01

    Full Text Available Although Duchenne muscular dystrophy is primarily classified as a neuromuscular disease, cardiac complications play an important role in the course of this X-linked inherited disorder. The pathobiochemical steps causing a progressive decline in the dystrophic heart are not well understood. We therefore carried out a fluorescence difference in-gel electrophoretic analysis of 9-month-old dystrophin-deficient versus age-matched normal heart, using the established MDX mouse model of muscular dystrophy-related cardiomyopathy. Out of 2,509 detectable protein spots, 79 2D-spots showed a drastic differential expression pattern, with the concentration of 3 proteins being increased, including nucleoside diphosphate kinase and lamin-A/C, and of 26 protein species being decreased, including ATP synthase, fatty acid binding-protein, isocitrate dehydrogenase, NADH dehydrogenase, porin, peroxiredoxin, adenylate kinase, tropomyosin, actin, and myosin light chains. Hence, the lack of cardiac dystrophin appears to trigger a generally perturbed protein expression pattern in the MDX heart, affecting especially energy metabolism and contractile proteins.

  11. 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.

  12. Deletion analysis of the dystrophin gene in Duchenne and Becker muscular dystrophy patients: Use in carrier diagnosis

    Directory of Open Access Journals (Sweden)

    Kumari D

    2003-04-01

    Full Text Available The dystrophin gene was analyzed in 8 Duchenne muscular dystrophy (DMD and 10 Becker muscular dystrophy (BMD unrelated families (22 subjects: 18 index cases and 4 sibs for the presence of deletions by multiplex polymerase chain reaction (mPCR; 27 exons and Southern hybridization using 8 cDMD probes. Deletions were identified in 5 DMD and 7 BMD patients (6 index cases and 1 sib. The concordance between the clinical phenotype and 'reading frame hypothesis' was observed in 11/12 patients (92%. The female relatives of DMD/BMD patients with identifiable deletions were examined by quantitative mPCR. Carriers were identified in 7 families. We also describe a variation in the HindIII pattern with cDNA probe 8 and 11-14. Molecular characterization of the dystrophin gene in this study has been helpful in advising the patients concerning the inheritance of the condition, and carrier diagnosis of female relatives, and should also prove useful for prenatal diagnosis.

  13. Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy*

    Science.gov (United States)

    Turk, Rolf; Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Pospisil, Tyler C.; Jones, Kayla S.; Campbell, Kevin P.; Wright, Michael E.

    2016-01-01

    Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

  14. Managerial span of control: a pilot study comparing departmental complexity and number of direct reports.

    Science.gov (United States)

    Merrill, Katreena Collette; Pepper, Ginette; Blegen, Mary

    2013-09-01

    Nurse managers play pivotal roles in hospitals. However, restructuring has resulted in nurse managers having wider span of control and reduced visibility. The purpose of this pilot study was to compare two methods of measuring span of control: departmental complexity and number of direct reports. Forty-one nurse managers across nine hospitals completed The Ottawa Hospital Clinical Manager Span of Control Tool (TOH-SOC) and a demographic survey. A moderate positive relationship between number of direct reports and departmental complexity score was identified (r=.49, p=managers' responsibility. Copyright © 2013 Longwoods Publishing.

  15. Model-Based Development and Evaluation of Control for Complex Multi-Domain Systems

    DEFF Research Database (Denmark)

    Grujic, Ivan; Nilsson, Rene

    A Cyber-Physical System (CPS) incorporates sensing, actuating, computing and communicative capabilities, which are often combined to control the system. The development of CPSs poses a challenge, since the complexity of the physical system dynamics must be taken into account when designing...... the control application. The physical system dynamics are often defined within mechanical and electrical engineering domains, with the control application residing in software and control engineering domains. Therefore, such a system can be considered multi-domain. With the constant increase in the complexity...... of such systems, caused by technological advances in all domains, new ways of approaching multi- domain system development are needed. One methodology, which excels in complexity management, is model-based development. Multidomain systems require collaborative modeling, where the physical system dynamics...

  16. A structurally controlled fan-delta complex at the southern margin of the peninsular range forearc basin complex (Baja California)

    Energy Technology Data Exchange (ETDEWEB)

    Morris, W.R.; Busby-Spera, C. (Univ. of California, Santa Barbara (USA))

    1990-05-01

    A confined trunk fan delta and its structurally controlled tributary fan deltas are extremely well exposed along the southern margin of the Rosario embayment. This fan-delta complex consists of nonmarine to deep marine deposits almost continuously exposed for over 20 km in the down-paleoslope direction. Facies and stratal patterns in the fan-delta complex were controlled by local faulting, climatic variation, and eustasy, resulting in relative sea level fluctuations. Basin bathymetry and drainage patterns were controlled by a series of half-grabens that formed along north-south-trending faults that lay along the northern margin of an east-west-trending depression. Breccias were initially shed into the north-south-trending half-grabens; axial drainage systems were later established within the grabens, making up the tributary fan deltas. These tributary fan deltas fed a voluminous trunk fan delta confined to the east-west-trending depression. The trunk and tributary fan delta deposits show two major progradational to retrogradational cycles that record relative sea level fluctuations. Progradation in the shallow-marine environment is represented by conglomerate channels cut into ripple-laminated or bioturbated siltstone and HCS sandstones, overlain by conglomerate mouth bar deposits interstratified with nearshore sandstone deposits. Retrogradation in the shallow marine environment is recorded by either a vertical clastic facies transition or a clastic-carbonate facies transition. The clastic facies transition consists of nearshore sandstone deposits overlain by offshore bioturbated siltstones. The clastic-carbonate facies transition consists of the development of red algal patch reefs and rhodoliths on top of fan-delta conglomeratic lobes, mudstone and sandstone bank channel margins, or paleobasement highs. The clastic-carbonate facies transition reflects low sediment supply controlled by climatic conditions.

  17. Proficiency and Linguistic Complexity Influence Speech Motor Control and Performance in Spanish Language Learners.

    Science.gov (United States)

    Nip, Ignatius S B; Blumenfeld, Henrike K

    2015-06-01

    Second-language (L2) production requires greater cognitive resources to inhibit the native language and to retrieve less robust lexical representations. The current investigation identifies how proficiency and linguistic complexity, specifically syntactic and lexical factors, influence speech motor control and performance. Speech movements of 29 native English speakers with low or high proficiency in Spanish were recorded while producing simple and syntactically complex sentences in English and Spanish. Sentences were loaded with cognate (e.g., baby-bebé) or noncognate (e.g., dog-perro) words. Effects of proficiency, lexicality (cognate vs. noncognate), and syntactic complexity on maximum speed, range of movement, duration, and speech movement variability were examined. In general, speakers with lower L2 proficiency differed in their speech motor control and performance from speakers with higher L2 proficiency. Speakers with higher L2 proficiency generally had less speech movement variability, shorter phrase durations, greater maximum speeds, and greater ranges of movement. In addition, lexicality and syntactic complexity affected speech motor control and performance. L2 proficiency, lexicality, and syntactic complexity influence speech motor control and performance in adult L2 learners. Information about relationships between speech motor control, language proficiency, and cognitive-linguistic demands may be used to assess and treat bilingual clients and language learners.

  18. 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.

  19. 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.

  20. 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.

  1. Outer Synchronization of Complex Networks with Nondelayed and Time-Varying Delayed Couplings via Pinning Control or Impulsive Control

    Directory of Open Access Journals (Sweden)

    Jianwen Feng

    2015-01-01

    synchronization between two complex networks. Secondly, impulsive control is added to the nodes of corresponding response network. Based on the generalized inequality about time-varying delayed different equation, the sufficient conditions for outer synchronization are derived. Finally, some examples are presented to demonstrate the effectiveness and feasibility of the results obtained in this paper.

  2. A mixed-signal architecture for high complexity CMOS fuzzy controlers

    OpenAIRE

    1999-01-01

    Analog circuits provide better area/power efficiency than their digital counterparts for low-medium precision requirements. This limit in precision, as well as the lack of design tools when compared to the digital approach, imposes a limit of complexity, hence fuzzy analog controllers are usually oriented to fast low-power systems with low-medium complexity. This paper presents a strategy to preserve most of the advantages of an analog implementation, while allowing a notorious increment of t...

  3. Extraocular muscle is spared despite the absence of an intact sarcoglycan complex in gamma- or delta-sarcoglycan-deficient mice.

    Science.gov (United States)

    Porter, J D; Merriam, A P; Hack, A A; Andrade, F H; McNally, E M

    2001-03-01

    Models of the dystrophin-glycoprotein complex do not reconcile the novel sparing of extraocular muscle in muscular dystrophy. Extraocular muscle sparing in Duchenne muscular dystrophy implies the existence of adaptive properties in these muscles that may extend protection to other neuromuscular diseases. We studied the extraocular muscle morphology and dystrophin-glycoprotein complex organization in murine targeted deletion of the gamma-sarcoglycan (gsg(-/-)) and delta-sarcoglycan (dsg(-/-)) genes, two models of autosomal recessive limb girdle muscular dystrophy. In contrast to limb and diaphragm, the principal extraocular muscles were intact in gsg(-/-) and dsg(-/-) mice. However, central nucleated, presumptive regenerative, fibers were seen in the accessory extraocular muscles (retractor bulbi, levator palpebrae superioris) of both strains. Skeletal muscles of gsg(-/-) mice exhibited in vivo Evans Blue dye permeability, while the principal extraocular muscles did not. Disruption of gamma-sarcoglycan produced secondary displacement of alpha- and beta-sarcoglycans in the extraocular muscles. The intensity of immunofluorescence for dystrophin and alpha- and beta-dystroglycan also appeared to be slightly reduced. Utrophin localization was unchanged. The finding that sarcoglycan disruption was insufficient to elicit alterations in extraocular muscle suggests that loss of mechanical stability and increased sarcolemmal permeability are not inevitable consequences of mutations that disrupt the dystrophin-glycoprotein complex organization and must be accounted for in models of muscular dystrophy.

  4. Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

    Science.gov (United States)

    Cabiddu, Ramona; Trimer, Renata; Borghi-Silva, Audrey; Migliorini, Matteo; Mendes, Renata G; Oliveira, Antonio D; Costa, Fernando S M; Bianchi, Anna M

    2015-01-01

    Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV) signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.

  5. Are Complexity Metrics Reliable in Assessing HRV Control in Obese Patients During Sleep?

    Directory of Open Access Journals (Sweden)

    Ramona Cabiddu

    Full Text Available Obesity is associated with cardiovascular mortality. Linear methods, including time domain and frequency domain analysis, are normally applied on the heart rate variability (HRV signal to investigate autonomic cardiovascular control, whose imbalance might promote cardiovascular disease in these patients. However, given the cardiac activity non-linearities, non-linear methods might provide better insight. HRV complexity was hereby analyzed during wakefulness and different sleep stages in healthy and obese subjects. Given the short duration of each sleep stage, complexity measures, normally extracted from long-period signals, needed be calculated on short-term signals. Sample entropy, Lempel-Ziv complexity and detrended fluctuation analysis were evaluated and results showed no significant differences among the values calculated over ten-minute signals and longer durations, confirming the reliability of such analysis when performed on short-term signals. Complexity parameters were extracted from ten-minute signal portions selected during wakefulness and different sleep stages on HRV signals obtained from eighteen obese patients and twenty controls. The obese group presented significantly reduced complexity during light and deep sleep, suggesting a deficiency in the control mechanisms integration during these sleep stages. To our knowledge, this study reports for the first time on how the HRV complexity changes in obesity during wakefulness and sleep. Further investigation is needed to quantify altered HRV impact on cardiovascular mortality in obesity.

  6. Control and learning for intelligent mobility of unmanned ground vehicles in complex terrains

    Science.gov (United States)

    Trentini, M.; Beckman, B.; Digney, B.

    2005-05-01

    The Autonomous Intelligent Systems program at Defence R&D Canada-Suffield envisions autonomous systems contributing to decisive operations in the urban battle space. Creating effective intelligence for these systems demands advances in perception, world representation, navigation, and learning. In the land environment, these scientific areas have garnered much attention, while largely ignoring the problem of locomotion in complex terrain. This is a gap in robotics research, where sophisticated algorithms are needed to coordinate and control robotic locomotion in unknown, highly complex environments. Unlike traditional control problems, intuitive and systematic control tools for robotic locomotion do not readily exist thus limiting their practical application. This paper addresses the mobility problem for unmanned ground vehicles, defined here as the autonomous maneuverability of unmanned ground vehicles in unknown, highly complex environments. It discusses the progress and future direction of intelligent mobility research at Defence R&D Canada-Suffield and presents the research tools, topics and plans to address this critical research gap.

  7. Controlled Release of Doxorubicin from Doxorubicin/γ-Polyglutamic Acid Ionic Complex

    Directory of Open Access Journals (Sweden)

    Bhavik Manocha

    2010-01-01

    Full Text Available Formation of drug/polymer complexes through ionic interactions has proven to be very effective for the controlled release of drugs. The stability of such drug/polymer ionic complexes can be greatly influenced by solution pH and ionic strength. The aim of the current work was to evaluate the potential of γ-polyglutamic acid (γ-PGA as a carrier for the anticancer drug, Doxorubicin (DOX. We investigated the formation of ionic complexes between γ-PGA and DOX using scanning electron microscopy, spectroscopy, thermal analysis, and X-ray diffraction. Our studies demonstrate that DOX specifically interacts with γ-PGA forming random colloidal aggregates and results in almost 100% complexation efficiency. In vitro drug release studies illustrated that these complexes were relatively stable at neutral pH but dissociates slowly under acidic pH environments, facilitating a pH-triggered release of DOX from the complex. Hydrolytic degradation of γ-PGA and DOX/γ-PGA complex was also evaluated in physiological buffer. In conclusion, these studies clearly showed the feasibility of γ-PGA to associate cationic drug such as DOX and that is may serve as a new drug carrier for the controlled release of DOX in malignant tissues.

  8. 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.

  9. Nodal dynamics, not degree distributions, determine the structural controllability of complex networks.

    Directory of Open Access Journals (Sweden)

    Noah J Cowan

    Full Text Available Structural controllability has been proposed as an analytical framework for making predictions regarding the control of complex networks across myriad disciplines in the physical and life sciences (Liu et al., Nature:473(7346:167-173, 2011. Although the integration of control theory and network analysis is important, we argue that the application of the structural controllability framework to most if not all real-world networks leads to the conclusion that a single control input, applied to the power dominating set, is all that is needed for structural controllability. This result is consistent with the well-known fact that controllability and its dual observability are generic properties of systems. We argue that more important than issues of structural controllability are the questions of whether a system is almost uncontrollable, whether it is almost unobservable, and whether it possesses almost pole-zero cancellations.

  10. Geotechnical approaches to coal ash content control in mining of complex structure deposits

    Science.gov (United States)

    Batugin, SA; Gavrilov, VL; Khoyutanov, EA

    2017-02-01

    Coal deposits having complex structure and nonuniform quality coal reserves require improved processes of production quality control. The paper proposes a method to present coal ash content as components of natural and technological dilution. It is chosen to carry out studies on the western site of Elginsk coal deposit, composed of four coal beds of complex structure. The reported estimates of coal ash content in the beds with respect to five components point at the need to account for such data in confirmation exploration, mine planning and actual mining. Basic means of analysis and control of overall ash content and its components are discussed.

  11. Including inputs and control within equation-free architectures for complex systems

    Science.gov (United States)

    Proctor, Joshua L.; Brunton, Steven L.; Kutz, J. Nathan

    2016-11-01

    The increasing ubiquity of complex systems that require control is a challenge for existing methodologies in characterization and controller design when the system is high-dimensional, nonlinear, and without physics-based governing equations. We review standard model reduction techniques such as Proper Orthogonal Decomposition (POD) with Galerkin projection and Balanced POD (BPOD). Further, we discuss the link between these equation-based methods and recently developed equation-free methods such as the Dynamic Mode Decomposition and Koopman operator theory. These data-driven methods can mitigate the challenge of not having a well-characterized set of governing equations. We illustrate that this equation-free approach that is being applied to measurement data from complex systems can be extended to include inputs and control. Three specific research examples are presented that extend current equation-free architectures toward the characterization and control of complex systems. These examples motivate a potentially revolutionary shift in the characterization of complex systems and subsequent design of objective-based controllers for data-driven models.

  12. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release.

    Science.gov (United States)

    Lu, Z; Chen, W; Hamman, J H

    2007-10-01

    A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.

  13. Impulsive Controller Design for Complex Nonlinear Singular Networked Systems with Packet Dropouts

    Directory of Open Access Journals (Sweden)

    Xian-Lin Zhao

    2013-01-01

    Full Text Available Globally exponential stability of Complex (with coupling Nonlinear Singular Impulsive Networked Control Systems (CNSINCS with packet dropouts and time-delay is investigated. Firstly, the mathematic model of CNSINCS is established. Then, by employing the method of Lyapunov functional, exponential stability criteria are obtained and the impulsive controller design method is given. Finally, some simulation results are provided to demonstrate the effectiveness of the proposed method.

  14. Optimal control of transient dynamics in balanced networks supports generation of complex movements.

    Science.gov (United States)

    Hennequin, Guillaume; Vogels, Tim P; Gerstner, Wulfram

    2014-06-18

    Populations of neurons in motor cortex engage in complex transient dynamics of large amplitude during the execution of limb movements. Traditional network models with stochastically assigned synapses cannot reproduce this behavior. Here we introduce a class of cortical architectures with strong and random excitatory recurrence that is stabilized by intricate, fine-tuned inhibition, optimized from a control theory perspective. Such networks transiently amplify specific activity states and can be used to reliably execute multidimensional movement patterns. Similar to the experimental observations, these transients must be preceded by a steady-state initialization phase from which the network relaxes back into the background state by way of complex internal dynamics. In our networks, excitation and inhibition are as tightly balanced as recently reported in experiments across several brain areas, suggesting inhibitory control of complex excitatory recurrence as a generic organizational principle in cortex. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Low complexity power control approach based on MMSE detection for V-BLAST

    Institute of Scientific and Technical Information of China (English)

    Zhao Kun; Qiu Ling; Zhu Jinkang

    2006-01-01

    A low complexity Per-Antenna Power Control (PAPC) approach based on Minimum Mean Squared Error (MMSE) detection for V-BLAST is proposed in this paper. The PAPC approach is developed for minimizing the Bit Error Rate (BER) averaged over all substreams when the data throughput and the total transmit power keep constant over time. Simulation results show that the Power-controlled V-BLAST (P-BLAST) outperforms the conventional V-BLAST in terms of BER performance with MMSE detector, especially in presence of high spatial correlation between antennas. However, the additional complexity for P-BLAST is not high. When MMSE detector is adopted, the P-BLAST can achieve a comparable BER performance to that of conventional V-BLAST with Maximum Likelihood (ML) detector but with low complexity.

  16. Source pollution control program at the Camacari Petrochemical Complex: overall and individual improvements

    Energy Technology Data Exchange (ETDEWEB)

    Freire, P.A.; Neto, D.B.; Carvalho, D.M. [CETREL S.A., Camacari, BA (Brazil)

    1993-12-31

    Along with the technical progress experienced by the Camacari Petrochemical Complex in the last few years, new policies, following new worldwide trends, in pollution control and prevention became mandatory. This work describes some of these experiences as well as future perspectives. 3 refs., 2 fig., 13 tabs.

  17. Instructional Control of Cognitive Load in the Design of Complex Learning Environments

    NARCIS (Netherlands)

    Kester, Liesbeth; Paas, Fred; Van Merriënboer, Jeroen

    2010-01-01

    Kester, L., Paas, F., & Van Merriënboer, J. J. G. (2010). Instructional control of cognitive load in the design of complex learning environments. In J. L. Plass, R. Moreno, & Roland Brünken (Eds.), Cognitive Load Theory (pp. 109-130). New York: Cambridge University Press.

  18. Proficiency and Linguistic Complexity Influence Speech Motor Control and Performance in Spanish Language Learners

    Science.gov (United States)

    Nip, Ignatius S. B.; Blumenfeld, Henrike K.

    2015-01-01

    Purpose: Second-language (L2) production requires greater cognitive resources to inhibit the native language and to retrieve less robust lexical representations. The current investigation identifies how proficiency and linguistic complexity, specifically syntactic and lexical factors, influence speech motor control and performance. Method: Speech…

  19. "Operationalizing C2 agility”. Coping with complexity in command and control

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2012-06-01

    Full Text Available Combat presents a complex system that requires effective management to ensure successful completion of missions. Management of own forces and other assets in the pursuit of mission objectives is performed by the Command and Control (C2) system...

  20. Proficiency and Linguistic Complexity Influence Speech Motor Control and Performance in Spanish Language Learners

    Science.gov (United States)

    Nip, Ignatius S. B.; Blumenfeld, Henrike K.

    2015-01-01

    Purpose: Second-language (L2) production requires greater cognitive resources to inhibit the native language and to retrieve less robust lexical representations. The current investigation identifies how proficiency and linguistic complexity, specifically syntactic and lexical factors, influence speech motor control and performance. Method: Speech…

  1. Often Ignored Facts about the Control of the 2-Oxoglutarate Dehydrogenase Complex

    Science.gov (United States)

    Strumilo, Slawomir

    2005-01-01

    Information about the control of the activity of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme in the citric acid cycle, is not well covered in the biochemical education literature, especially as it concerns the allosteric regulation of OGDHC by adenine nucleotide and ortophosphate. From experimental work published during the last…

  2. Often Ignored Facts about the Control of the 2-Oxoglutarate Dehydrogenase Complex

    Science.gov (United States)

    Strumilo, Slawomir

    2005-01-01

    Information about the control of the activity of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key enzyme in the citric acid cycle, is not well covered in the biochemical education literature, especially as it concerns the allosteric regulation of OGDHC by adenine nucleotide and ortophosphate. From experimental work published during the last…

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

    Indian Academy of Sciences (India)

    MARYAM HAGHSHENAS; MOHAMMAD TAGHI AKBARI; SHOHREH ZARE KARIZI; FARAVAREH KHORDADPOOR DEILAMANI; SHAHRIAR NAFISSI; ZIVAR SALEHI

    2016-06-01

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

  4. 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.

  5. 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

    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...... 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...... showed dystrophic changes. He had comorbidity with dystonia, slight mental retardation, low stature and neuropathy. The brother of the proband's mother came to medical attention when he was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+ hip extention palsy and a discrete...

  6. 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

    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...... 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...... showed dystrophic changes. He had comorbidity with dystonia, slight mental retardation, low stature and neuropathy. The brother of the proband's mother came to medical attention when he was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+ hip extention palsy and a discrete...

  7. Effect of edge pruning on structural controllability and observability of complex networks.

    Science.gov (United States)

    Mengiste, Simachew Abebe; Aertsen, Ad; Kumar, Arvind

    2015-12-17

    Controllability and observability of complex systems are vital concepts in many fields of science. The network structure of the system plays a crucial role in determining its controllability and observability. Because most naturally occurring complex systems show dynamic changes in their network connectivity, it is important to understand how perturbations in the connectivity affect the controllability of the system. To this end, we studied the control structure of different types of artificial, social and biological neuronal networks (BNN) as their connections were progressively pruned using four different pruning strategies. We show that the BNNs are more similar to scale-free networks than to small-world networks, when comparing the robustness of their control structure to structural perturbations. We introduce a new graph descriptor, 'the cardinality curve', to quantify the robustness of the control structure of a network to progressive edge pruning. Knowing the susceptibility of control structures to different pruning methods could help design strategies to destroy the control structures of dangerous networks such as epidemic networks. On the other hand, it could help make useful networks more resistant to edge attacks.

  8. Pinning weighted complex networks with heterogeneous delays by a small number of feedback controllers

    Institute of Scientific and Technical Information of China (English)

    XIANG LinYing; LIU ZhongXin; CHEN ZengQiang; YUAN ZhuZhi

    2008-01-01

    Weighted complex dynamical networks with heterogeneous delays in both con-tinuous-time and discrete-time domains are controlled by applying local feedback injections to a small fraction of network nodes. Some generic stability criteria en-suring delay-independent stability are derived for such controlled networks in terms of linear matrix inequalities (LMIs), which guarantee that by placing a small number of feedback controllers on some nodes the whole network can be pinned to some desired homogenous states. In some particular cases, a single controller can achieve the control objective. It is found that stabilization of such pinned networks is completely determined by the dynamics of the individual uncoupled node, the overall coupling strength, the inner-coupling matrix, and the smallest eigenvalue of the coupling and control matrix. Numerical simulations of a weighted network composing of a 3-dimensional nonlinear system are finally given for illustration and verification.

  9. Fuzzy Approximation-Based Global Pinning Synchronization Control of Uncertain Complex Dynamical Networks.

    Science.gov (United States)

    Li, Xiao-Jian; Yang, Guang-Hong

    2017-04-01

    This paper is concerned with the global pinning synchronization problem of uncertain complex dynamical networks with communication constraints. First, an adaptive fuzzy controller is designed within a given compact set. In addition, a robust controller is introduced outside the compact set to pull back the system states. Then, a new pinning control scheme is given such that the global synchronization can be ensured. Moreover, via the Lyapunov theory and graph theory, the synchronization errors are proved to be asymptotically convergent. Especially, in an uncertainty-free environment, the proposed control scheme includes two easy-to-implement pinning control strategies as special cases, which improve the existing results from the view point of reducing the number of feedback controllers. Finally, two simulation examples are provided to validate the theoretical results.

  10. Design and control strategies for CELSS - Integrating mechanistic paradigms and biological complexities

    Science.gov (United States)

    Moore, B., III; Kaufmann, R.; Reinhold, C.

    1981-01-01

    Systems analysis and control theory consideration are given to simulations of both individual components and total systems, in order to develop a reliable control strategy for a Controlled Ecological Life Support System (CELSS) which includes complex biological components. Because of the numerous nonlinearities and tight coupling within the biological component, classical control theory may be inadequate and the statistical analysis of factorial experiments more useful. The range in control characteristics of particular species may simplify the overall task by providing an appropriate balance of stability and controllability to match species function in the overall design. The ultimate goal of this research is the coordination of biological and mechanical subsystems in order to achieve a self-supporting environment.

  11. Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system.

    Science.gov (United States)

    Ricotti, Valeria; Jägle, Herbert; Theodorou, Maria; Moore, Anthony T; Muntoni, Francesco; Thompson, Dorothy A

    2016-04-01

    Multiple isoforms of dystrophin (Dp427, Dp260, Dp140, Dp71) are expressed differentially in the central nervous system (CNS) including the retinal layers. Disruption of these protein products is responsible for cognitive dysfunction, electroretinogram (ERG) abnormalities and behavioural disorders in Duchenne muscular dystrophy (DMD). We studied the ocular characteristics and neuropsychiatric profile of 16 DMD boys. The ISCEV standard, full-field flash ERGs were assessed. Intellectual ability and behavioural disturbances were measured. All genotypes were associated with mildly abnormal photopic ERG a:b-wave amplitude ratios. In addition, we identified the following genotype/phenotype correlations: boys with mutations upstream of exon 30 (ie, isolated Dp427 altered expression) showed normal scotopic a:b ratios, abnormal photopic oscillatory potential OP2 and normal scotopic OP2. Conversely, all boys with DMD mutations downstream of exon 30 showed profoundly 'negative' scotopic ERGs (a:b ratios >1). In these patients, the involvement of Dp260 isoform resulted in the absence of slow rod pathway signalling in15 Hz scotopic flicker ERGs. These boys had abnormal scotopic OP2 and normal photopic OP2. Finally, children with mutations also affecting Dp71 were associated with more pronounced electronegative ERGs. When correlating ERGs to neurodevelopmental outcome, we found a positive correlation between negative scotopic ERGs and neurodevelopmental disturbances, and the most severe findings were in boys with Dp71 disruption. These findings suggest a strong association between DMD mutations affecting different DMD isoforms with characteristically abnormal scotopic ERGs and severe neurodevelopmental problems. The role of the ERG as a potential biomarker for dystrophin function in the CNS and response to novel genetic therapies warrants further exploration.

  12. 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

    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.

  13. 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.

  14. Complex shape product tolerance and accuracy control method for virtual assembly

    Science.gov (United States)

    Ma, Huiping; Jin, Yuanqiang; Zhang, Xiaoguang; Zhou, Hai

    2015-02-01

    The simulation of virtual assembly process for engineering design lacks of accuracy in the software of three-dimension CAD at present. Product modeling technology with tolerance, assembly precision preanalysis technique and precision control method are developed. To solve the problem of lack of precision information transmission in CAD, tolerance mathematical model of Small Displacement Torsor (SDT) is presented, which can bring about technology transfer and establishment of digital control function for geometric elements from the definition, description, specification to the actual inspection and evaluation process. Current tolerance optimization design methods for complex shape product are proposed for optimization of machining technology, effective cost control and assembly quality of the products.

  15. Partial control of complex systems with application to the Fluidized Catalytic Cracker

    Energy Technology Data Exchange (ETDEWEB)

    Rinard, I.H.; Shinnar, R.

    1996-12-31

    The research deals with the control of complex nonlinear system with a limited number of manipulated variables. In many chemical processes the number of variables that make up the specifications and constraints exceeds the number of manipulated variables available. Furthermore, model information is limited. The goal of this work is to study the design of the control system and the conditions required to achieve adequate control for such cases. A Fluid Catalytic Cracker was chosen to illustrate and test the approach. This paper presents a short overview and summary of the approach and results.

  16. Pinning synchronization of two general complex networks with periodically intermittent control

    Directory of Open Access Journals (Sweden)

    Meng Fanyu

    2015-12-01

    Full Text Available In this paper, the method of periodically pinning intermittent control is introduced to solve the problem of outer synchronization between two complex networks. Based on the Lyapunov stability theory, differential inequality method and adaptive technique, some simple synchronous criteria have been derived analytically. At last, both the theoretical and numerical analysis illustrate the effectiveness of the proposed control methodology. This method not only reduces the conservatism of control gain but also saves the cost of production.These advantages make this method having a large application scope in the real production process.

  17. Decentralized adaptive robust controller design for complex system based on partition of unity

    Institute of Scientific and Technical Information of China (English)

    WANG Wenqing; HAN Chongzhao

    2007-01-01

    A new method for designing decentralized adaptive robust controllers was proposed which focuses on a class of more general uncertain complex systems,using the concept of the partition of unity in differential geometry to deal with system uncertainties.In this method the uncertainty of the system to be controlled was normalized firstly,and then the partition of unity that was subordinated to an open covering of state variables compact set was constructed.Subsequently the approximation was realized by using its property that can approximate nonlinear continuous function with arbitrary precision,and then the decentralized adaptive robust controller of complex systems and adaptive laws of approximate parameter estimation were designed.Compared to existing methods,the proposed algorithm requires simpler assumed conditions and no complicated computations.Simulation result shows that the method is valid.

  18. Efficient polarization insensitive complex wavefront control using Huygens' metasurfaces based on dielectric resonant meta-atoms

    CERN Document Server

    Chong, Katie E; Staude, Isabelle; James, Anthony; Dominguez, Jason; Liu, Sheng; Subramania, Ganapathi S; Decker, Manuel; Neshev, Dragomir N; Brener, Igal; Kivshar, Yuri S

    2016-01-01

    Subwavelength-thin metasurfaces have shown great promises for the control of optical wavefronts, thus opening new pathways for the development of efficient flat optics. In particular, Huygens' metasurfaces based on all-dielectric resonant meta-atoms have already shown a huge potential for practical applications with their polarization insensitivity and high transmittance efficiency. Here, we experimentally demonstrate a polarization insensitive holographic Huygens' metasurface based on dielectric resonant meta-atoms capable of complex wavefront control at telecom wavelengths. Our metasurface produces a hologram image in the far-field with 82% transmittance efficiency and 40% imaging efficiency. Such efficient complex wavefront control shows that Huygens' metasurfaces based on resonant dielectric meta-atoms are a big step towards practical applications of metasurfaces in wavefront design related technologies, including computer-generated holograms, ultra-thin optics, security and data storage devices.

  19. Complexity and simplicity of optimal control theory pulses shaped for controlling vibrational qubits.

    Science.gov (United States)

    Shyshlov, Dmytro; Babikov, Dmitri

    2012-11-21

    In the context of molecular quantum computation the optimal control theory (OCT) is used to obtain shaped laser pulses for high-fidelity control of vibrational qubits. Optimization is done in time domain and the OCT algorithm varies values of electric field in each time step independently, tuning hundreds of thousands of parameters to find one optimal solution. Such flexibility is not available in experiments, where pulse shaping is done in frequency domain and the number of "tuning knobs" is much smaller. The question of possible experimental interpretations of theoretically found OCT solutions arises. In this work we analyze very accurate optimal pulse that we obtained for implementing quantum gate CNOT for the two-qubit system encoded into the exited vibrational states of thiophosgene molecule. Next, we try to alter this pulse by reducing the number of available frequency channels and intentionally introducing systematic and random errors (in frequency domain, by modifying the values of amplitudes and phases of different frequency components). We conclude that a very limited number of frequency components (only 32 in the model of thiophosgene) are really necessary for accurate control of the vibrational two-qubit system, and such pulses can be readily constructed using OCT. If the amplitude and phase errors of different frequency components do not exceed ±3% of the optimal values, one can still achieve accurate transformations of the vibrational two-qubit system, with gate fidelity of CNOT exceeding 0.99.

  20. The operative treatment of complex pilon fractures: A strategy of soft tissue control

    Directory of Open Access Journals (Sweden)

    Xianfeng He

    2013-01-01

    Full Text Available Background: Pilon fractures are challenging to manage because of the complexity of the injury pattern and the risk of significant complications. The soft tissue injury and handling of the soft tissue envelope are crucial in pilon fracture outcomes. The purpose of this study was to evaluate the early rate of complications using the strategy of "soft tissue control" for operative treatment of complex pilon fractures. Materials and Methods: 36 complex pilon fractures were treated with the "soft tissue control" strategy. Patients followed the standard staged protocol, anterolateral approach to the distal tibia, the "no-touch" technique and incisional negative pressure wound therapy for pilon fractures. Patients were examined clinically at 2-3 weeks and then 8 weeks for complications associated with the surgical technique. Results: All fractures were AO/OTA (Orthopaedic Trauma Association type C fractures (61% C3, 22% C2 and 16% C1. Only one patient developed superficial infection and resolved with antibiotics and local wound care. None developed deep infection. Conclusions: The strategy of soft tissue control for treatment of pilon fractures resulted in relatively low incidence of early wound complications in patients with complex pilon fractures.

  1. Description and control of dissociation channels in gas-phase protein complexes

    Science.gov (United States)

    Thachuk, Mark; Fegan, Sarah K.; Raheem, Nigare

    2016-08-01

    Using molecular dynamics simulations of a coarse-grained model of the charged apo-hemoglobin protein complex, this work expands upon our initial report [S. K. Fegan and M. Thachuk, J. Am. Soc. Mass Spectrom. 25, 722-728 (2014)] about control of dissociation channels in the gas phase using specially designed charge tags. Employing a charge hopping algorithm and a range of temperatures, a variety of dissociation channels are found for activated gas-phase protein complexes. At low temperatures, a single monomer unfolds and becomes charge enriched. At higher temperatures, two additional channels open: (i) two monomers unfold and charge enrich and (ii) two monomers compete for unfolding with one eventually dominating and the other reattaching to the complex. At even higher temperatures, other more complex dissociation channels open with three or more monomers competing for unfolding. A model charge tag with five sites is specially designed to either attract or exclude charges. By attaching this tag to the N-terminus of specific monomers, the unfolding of those monomers can be decidedly enhanced or suppressed. In other words, using charge tags to direct the motion of charges in a protein complex provides a mechanism for controlling dissociation. This technique could be used in mass spectrometry experiments to direct forces at specific attachment points in a protein complex, and hence increase the diversity of product channels available for quantitative analysis. In turn, this could provide insight into the function of the protein complex in its native biological environment. From a dynamics perspective, this system provides an interesting example of cooperative behaviour involving motions with differing time scales.

  2. Amylose-lipid complexes as controlled lipid release agents during starch gelatinization and pasting.

    Science.gov (United States)

    Gelders, Greta G; Goesaert, Hans; Delcour, Jan A

    2006-02-22

    The effect of amylose-lipid (AM-L) complexes consisting of amylose populations with different peak degrees of polymerization (DP) and complexed with glyceryl monostearate (GMS) or docosanoic acid (C22) on the pasting properties of wheat and rice starches was evaluated with a rapid visco analyzer (RVA). AM-L complexes were formed by both (i) addition of lipids to amylose fractions with peak DP 20, 60, 400, or 950 at 60 degrees C or (ii) potato phosphorylase-catalyzed amylose synthesis in the presence of lipids. All AM-L complexes affected pasting properties in line with their dissociation characteristics. AM-L complexes therefore have potential as "controlled lipid release agents" with effects markedly different from those observable with emulsifier addition in starch pasting. More in particular, short chain AM-L complexes resulted in a starch pasting behavior comparable to that of cross-linked starch, as evidenced by reduced granule swelling, good viscosity stability in conditions of high temperature and shear, and a stable cold paste viscosity.

  3. A new yeast poly(A polymerase complex involved in RNA quality control.

    Directory of Open Access Journals (Sweden)

    Stepánka Vanácová

    2005-06-01

    Full Text Available Eukaryotic cells contain several unconventional poly(A polymerases in addition to the canonical enzymes responsible for the synthesis of poly(A tails of nuclear messenger RNA precursors. The yeast protein Trf4p has been implicated in a quality control pathway that leads to the polyadenylation and subsequent exosome-mediated degradation of hypomethylated initiator tRNAMet (tRNAiMet. Here we show that Trf4p is the catalytic subunit of a new poly(A polymerase complex that contains Air1p or Air2p as potential RNA-binding subunits, as well as the putative RNA helicase Mtr4p. Comparison of native tRNAiMet with its in vitro transcribed unmodified counterpart revealed that the unmodified RNA was preferentially polyadenylated by affinity-purified Trf4 complex from yeast, as well as by complexes reconstituted from recombinant components. These results and additional experiments with other tRNA substrates suggested that the Trf4 complex can discriminate between native tRNAs and molecules that are incorrectly folded. Moreover, the polyadenylation activity of the Trf4 complex stimulated the degradation of unmodified tRNAiMet by nuclear exosome fractions in vitro. Degradation was most efficient when coupled to the polyadenylation activity of the Trf4 complex, indicating that the poly(A tails serve as signals for the recruitment of the exosome. This polyadenylation-mediated RNA surveillance resembles the role of polyadenylation in bacterial RNA turnover.

  4. A New Yeast Poly(A Polymerase Complex Involved in RNA Quality Control

    Directory of Open Access Journals (Sweden)

    Vanácová Stepánka

    2005-01-01

    Full Text Available Eukaryotic cells contain several unconventional poly(A polymerases in addition to the canonical enzymes responsible for the synthesis of poly(A tails of nuclear messenger RNA precursors. The yeast protein Trf4p has been implicated in a quality control pathway that leads to the polyadenylation and subsequent exosome-mediated degradation of hypomethylated initiator tRNAMet (tRNAiMet. Here we show that Trf4p is the catalytic subunit of a new poly(A polymerase complex that contains Air1p or Air2p as potential RNA-binding subunits, as well as the putative RNA helicase Mtr4p. Comparison of native tRNAiMet with its in vitro transcribed unmodified counterpart revealed that the unmodified RNA was preferentially polyadenylated by affinity-purified Trf4 complex from yeast, as well as by complexes reconstituted from recombinant components. These results and additional experiments with other tRNA substrates suggested that the Trf4 complex can discriminate between native tRNAs and molecules that are incorrectly folded. Moreover, the polyadenylation activity of the Trf4 complex stimulated the degradation of unmodified tRNAiMet by nuclear exosome fractions in vitro. Degradation was most efficient when coupled to the polyadenylation activity of the Trf4 complex, indicating that the poly(A tails serve as signals for the recruitment of the exosome. This polyadenylation-mediated RNA surveillance resembles the role of polyadenylation in bacterial RNA turnover.

  5. Tie-Line Bias Control Applicability to Load Frequency Control for Multi-Area Interconnected Power Systems of Complex Topology

    Directory of Open Access Journals (Sweden)

    Chunyu Chen

    2017-01-01

    Full Text Available The tie-line bias control (TBC method has been widely used in the load frequency control (LFC of multi-area interconnected systems. However, it should be questioned whether the conventional TBC can still apply to LFC when considering the complication of structures of power systems. LFC, in essence, is to stabilize system frequency/tie-line power by controlling controlled outputs’ area control error (ACE. In this paper, relations between LFC control variables and controlled outputs are expressed as a system of equations, based on which an exemplary ring network is studied. Sufficient and necessary conditions for TBC applicability is presented, and a novel LFC mode is proposed for a general ring network where TBC cannot work. Finally, TBC applicability to multi-area systems with general topology is studied, and a general LFC mode is proposed for systems where TBC is not definitely applicable, thus rendering routines that may guide LFC design of future power systems with more complex topologies.

  6. Robust H∞ observer-based control for synchronization of a class of complex dynamical networks

    Institute of Scientific and Technical Information of China (English)

    Zheng Hai-Qing; Jing Yuan-Wei

    2011-01-01

    This paper is concerned with the robust H∞ synchronization problem for a class of complex dynamical networks by applying the observer-based control. The proposed feedback control scheme is developed to ensure the asymptotic stability of the augmented system, to reconstruct the non-measurable state variables of each node and to improve the H∞ performance related to the synchronization error and observation error despite the external disturbance. Based on the Lyapunov stability theory, a synchronization criterion is obtained under which the controlled network can be robustly stabilized onto a desired state with a guaranteed H∞ performance. The controller and the observer gains can be given by the feasible solutions of a set of linear matrix inequalities (LMIs). The effectiveness of the proposed control scheme is demonstrated by a numerical example through simulation.

  7. Multi-agent based control of large-scale complex systems employing distributed dynamic inference engine

    Science.gov (United States)

    Zhang, Daili

    Increasing societal demand for automation has led to considerable efforts to control large-scale complex systems, especially in the area of autonomous intelligent control methods. The control system of a large-scale complex system needs to satisfy four system level requirements: robustness, flexibility, reusability, and scalability. Corresponding to the four system level requirements, there arise four major challenges. First, it is difficult to get accurate and complete information. Second, the system may be physically highly distributed. Third, the system evolves very quickly. Fourth, emergent global behaviors of the system can be caused by small disturbances at the component level. The Multi-Agent Based Control (MABC) method as an implementation of distributed intelligent control has been the focus of research since the 1970s, in an effort to solve the above-mentioned problems in controlling large-scale complex systems. However, to the author's best knowledge, all MABC systems for large-scale complex systems with significant uncertainties are problem-specific and thus difficult to extend to other domains or larger systems. This situation is partly due to the control architecture of multiple agents being determined by agent to agent coupling and interaction mechanisms. Therefore, the research objective of this dissertation is to develop a comprehensive, generalized framework for the control system design of general large-scale complex systems with significant uncertainties, with the focus on distributed control architecture design and distributed inference engine design. A Hybrid Multi-Agent Based Control (HyMABC) architecture is proposed by combining hierarchical control architecture and module control architecture with logical replication rings. First, it decomposes a complex system hierarchically; second, it combines the components in the same level as a module, and then designs common interfaces for all of the components in the same module; third, replications

  8. Rapid Synthesis of Size-controlled Gold Nanoparticles by Complex Intramolecular Photoreduction

    Institute of Scientific and Technical Information of China (English)

    DONG Shou-an; YANG Sheng-chun; TANG Chun

    2007-01-01

    A rapid synthesis of size-controlled gold nanoparticles was proposed. The method is based on the sensitive intramolecular photoreduction reaction of Fe( Ⅲ )-EDTA complex in chloroacetic acid-sodium acetate buffer solution,where Fe(Ⅱ)-EDTA complex generated by photo-promotion acts as a reductant of AuCl4- ions. Gold nanoparticles formed were stabilized by EDTA ligand or other protective agents added. As a result, well-dispersed gold nanoparticles with an average diameter range of 6.7 to 50. 9 nm were obtained. According to the characterizations by the UV spectrum and TEM, the intramolecular charge transfer of the excited states of complex Fe(Ⅲ) -EDTA and the mechanism of forming gold nanoparticles were discussed in detail.

  9. The spectrum of mutations controlling complex traits and the genetics of fitness in plants.

    Science.gov (United States)

    Falke, K Christin; Glander, Shirin; He, Fei; Hu, Jinyong; de Meaux, Juliette; Schmitz, Gregor

    2013-12-01

    Elucidating the molecular basis of natural variation in complex traits is the key for their effective management in crops or natural systems. This review focuses on plant variation. It will first, show that genetic modifications causing major alterations in polygenic phenotypes often hit targets within an array of 'candidate genes', second, present new methods that include mutations of all effect sizes, and help exhaustively describe the molecular systems underlying complex traits, and third, discuss recent findings regarding the role of epigenetic variants, which in plants are often maintained through both mitosis and meiosis. Exploring the whole spectrum of mutations controlling complex traits is made possible by the combination of genetic, genomic and epigenomic approaches.

  10. Control of size in losartan/copper(II) coordination complex hydrophobic precipitate.

    Science.gov (United States)

    Denadai, Ângelo M L; Da Silva, Jeferson G; Guimarães, Pedro P G; Gomes, Leonardo Bertolini S; Mangrich, Antonio S; de Rezende, Edivaltrys I P; Daniel, Izabela M P; Beraldo, Heloísa; Sinisterra, Rubén D

    2013-10-01

    Reaction of highly soluble orally active, non-peptide antihypertensive drug losartan with copper(II) leads to the spontaneous formation of a very insoluble 2:1 covalent complex, which self assembles in a hydrophobic supramolecular structure of nanometric dimensions. Thermal analysis showed that Los/Cu(II) complex presents intermediate stability in comparison with its precursors KLos and Cu(OAc)2·H2O. Isothermal titration calorimetry indicated complexation to be a stepwise process, driven by enthalpy and entropy. Zeta potential and DLS measurements showed that it is possible to control the size and charge of nanoprecipitates by adjusting the relative concentration of Los(-) and Cu(II). Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Formation of ternary complexes between a macrotricyclic host and hetero-guest pairs: an acid-base controlled selective complexation process.

    Science.gov (United States)

    Han, Tao; Chen, Chuan-Feng

    2007-10-11

    A triptycene-based cylindrical macrotricyclic host can include diquat and electron-rich aromatics simultaneously to form stable ternary complexes, which is stabilized not only by a charge-transfer (CT) interaction between electron-rich and electron-deficient guests but also by the face to face pi-stacking interactions between the host and the guests. Moreover, a selective complexation process between a ternary complex containing benzidine and a binary complex can be effectively controlled by the use of acid and base.

  12. Controlling collective dynamics in complex, minority-game resource-allocation systems

    CERN Document Server

    Zhang, Ji-Qiang; Huang, Zi-Gang; Huang, Liang; Huang, Tie-Qiao; Lai, Ying-Cheng

    2013-01-01

    Resource allocation takes place in various kinds of real-world complex systems, such as the traffic systems, social services institutions or organizations, or even the ecosystems. The fundamental principle underlying complex resource-allocation dynamics is Boolean interactions associated with minority games, as resources are generally limited and agents tend to choose the least used resource based on available information. A common but harmful dynamical behavior in resource-allocation systems is herding, where there are time intervals during which a large majority of the agents compete for a few resources, leaving many other resources unused. Ac- companying the herd behavior is thus strong fluctuations with time in the number of resources being used. In this paper, we articulate and establish that an intuitive control strategy, namely pinning control, is effective at harnessing the herding dynamics. In particular, by fixing the choices of resources for a few agents while leaving majority of the agents free, h...

  13. Simulation of complex glazing products; from optical data measurements to model based predictive controls

    Energy Technology Data Exchange (ETDEWEB)

    Kohler, Christian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-04-01

    Complex glazing systems such as venetian blinds, fritted glass and woven shades require more detailed optical and thermal input data for their components than specular non light-redirecting glazing systems. Various methods for measuring these data sets are described in this paper. These data sets are used in multiple simulation tools to model the thermal and optical properties of complex glazing systems. The output from these tools can be used to generate simplified rating values or as an input to other simulation tools such as whole building annual energy programs, or lighting analysis tools. I also describe some of the challenges of creating a rating system for these products and which factors affect this rating. A potential future direction of simulation and building operations is model based predictive controls, where detailed computer models are run in real-time, receiving data for an actual building and providing control input to building elements such as shades.

  14. Engineering a large application software project: the controls of the CERN PS accelerator complex

    Energy Technology Data Exchange (ETDEWEB)

    Benincasa, G.P.; Daneels, A.; Heymans, P.; Serre, Ch.

    1985-10-01

    The CERN PS accelerator complex has been progressively converted to full computer controls without interrupting its full-time operation (more than 6000 hours per year with on average not more than 1% of the total down-time due to controls). The application software amounts to 120 man-years and 450'000 instructions: it compares with other large software projects, also outside the accelerator world: e.g. Skylab's ground support software. This paper outlines the application software structure which takes into account technical requirements and constraints (resulting from the complexity of the process and its operation) and economical and managerial ones. It presents the engineering and management techniques used to promote implementation, testing and commissioning within budget, manpower and time constraints and concludes with experience gained.

  15. SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    LI Hong; ZHOU Zhiyuan; DAI Rongyang; LUO Bo; ZHENG Xiaoli; YANG Wenli; HE Tao; WU Minglu

    2004-01-01

    In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as "signal scattering", "positive feedback", "negative feedback" and "B-Raf shunt". Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

  16. What qualitative research can contribute to a randomized controlled trial of a complex community intervention.

    Science.gov (United States)

    Nelson, Geoffrey; Macnaughton, Eric; Goering, Paula

    2015-11-01

    Using the case of a large-scale, multi-site Canadian Housing First research demonstration project for homeless people with mental illness, At Home/Chez Soi, we illustrate the value of qualitative methods in a randomized controlled trial (RCT) of a complex community intervention. We argue that quantitative RCT research can neither capture the complexity nor tell the full story of a complex community intervention. We conceptualize complex community interventions as having multiple phases and dimensions that require both RCT and qualitative research components. Rather than assume that qualitative research and RCTs are incommensurate, a more pragmatic mixed methods approach was used, which included using both qualitative and quantitative methods to understand program implementation and outcomes. At the same time, qualitative research was used to examine aspects of the intervention that could not be understood through the RCT, such as its conception, planning, sustainability, and policy impacts. Through this example, we show how qualitative research can tell a more complete story about complex community interventions.

  17. Unraveling the CHIP:Hsp70 complex as an information processor for protein quality control.

    Science.gov (United States)

    VanPelt, Jamie; Page, Richard C

    2017-02-01

    The CHIP:Hsp70 complex stands at the crossroads of the cellular protein quality control system. Hsp70 facilitates active refolding of misfolded client proteins, while CHIP directs ubiquitination of misfolded client proteins bound to Hsp70. The direct competition between CHIP and Hsp70 for the fate of misfolded proteins leads to the question: how does the CHIP:Hsp70 complex execute triage decisions that direct misfolded proteins for either refolding or degradation? The current body of literature points toward action of the CHIP:Hsp70 complex as an information processor that takes inputs in the form of client folding state, dynamics, and posttranslational modifications, then outputs either refolded or ubiquitinated client proteins. Herein we examine the CHIP:Hsp70 complex beginning with the structure and function of CHIP and Hsp70, followed by an examination of recent studies of the interactions and dynamics of the CHIP:Hsp70 complex. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Complex Dynamical Network Control for Trajectory Tracking Using Delayed Recurrent Neural Networks

    Directory of Open Access Journals (Sweden)

    Jose P. Perez

    2014-01-01

    Full Text Available In this paper, the problem of trajectory tracking is studied. Based on the V-stability and Lyapunov theory, a control law that achieves the global asymptotic stability of the tracking error between a delayed recurrent neural network and a complex dynamical network is obtained. To illustrate the analytic results, we present a tracking simulation of a dynamical network with each node being just one Lorenz’s dynamical system and three identical Chen’s dynamical systems.

  19. Optimal Control of Transient Dynamics in Balanced Networks Supports Generation of Complex Movements

    OpenAIRE

    Hennequin, Guillaume; Vogels, Tim; Gerstner, Wulfram

    2014-01-01

    Populations of neurons in motor cortex engage in complex transient dynamics of large amplitude during the execution of limb movements. Traditional network models with stochastically assigned synapses cannot reproduce this behavior. Here we introduce a class of cortical architectures with strong and random excitatory recurrence that is stabilized by intricate, fine-tuned inhibition, optimized from a control theory perspective. Such networks transiently amplify specific activity states and can ...

  20. Polyelectrolyte complexes : Preparation, characterization, and use for control of wet and dry adhesion between surfaces

    OpenAIRE

    Ankerfors, Caroline

    2012-01-01

    This thesis examines polyelectrolyte complex (PEC) preparation, adsorption behaviour, and potential use for control of wet and dry adhesion between surfaces. PEC formation was studied using a jet-mixing method not previously used for mixing polyelectrolytes. The PECs were formed using various mixing times, and the results were compared with those for PECs formed using the conventional polyelectrolyte titration method. The results indicated that using the jet mixer allowed the size of the form...

  1. Complexity Theory of Beam Halo-Chaos and Its Control Methods With Prospective Applications

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This article offers an overview and comprehensive survey of the complexity theory of beamhalo-chaos and its control methods with prospective applications. In recent years, there has been growinginterest in proton beams of high power linear accelerator due to its attractive features in possiblebreakthrough applications, such as production of nuclear materials (e.g., tritium, transforming 232Th to233U), transmutation of radioactive wastes, productions of radioactive isotopes for medical use, heavy ion

  2. MODELING OF OPERATION MODES OF SHIP POWER PLANT OF COMBINED PROPULSION COMPLEX WITH CONTROL SYSTEM BASED ON ELECTRONIC CONTROLLERS

    Directory of Open Access Journals (Sweden)

    E. A. Yushkov

    2016-12-01

    Full Text Available Purpose. Designing of diagrams to optimize mathematic model of the ship power plant (SPP combined propulsion complexes (CPC for decreasing operational loss and increasing fuel efficiency with simultaneous load limiting on medium revolutions diesel generator (MRDG by criterion reducing of wear and increasing operation time between repairs. Methodology. After analyzing of ship power plant modes of CPC proposed diagrams to optimize mathematic model of the above mentioned complex. The model based on using of electronic controllers in automatic regulation and control systems for diesel and thruster which allow to actualize more complicated control algorithm with viewpoint of increasing working efficiency of ship power plant at normal and emergency modes. Results. Determined suitability of comparative computer modeling in MatLab Simulink for building of imitation model objects based on it block diagrams and mathematic descriptions. Actualized diagrams to optimize mathematic model of the ship’s power plant (SPP combined propulsion complexes (CPC with Azipod system in MatLab Simulink software package Ships_CPC for decreasing operational loss and increasing fuel efficiency with simultaneous load limiting on medium revolutions diesel generator (MRDG by criterion reducing of wear and increasing operation time between repairs. The function blocks of proposed complex are the main structural units which allow to investigate it normal and emergency modes. Originality. This model represents a set of functional blocks of the components SPP CPC, built on the principle of «input-output». For example, the function boxes outputs of PID-regulators of MRDG depends from set excitation voltage and rotating frequency that in turn depends from power-station load and respond that is a ship moving or dynamically positioning, and come on input (inputs of thruster rotating frequency PID-regulator models. Practical value. The results of researches planned to use in

  3. Droop Control with an Adjustable Complex Virtual Impedance Loop based on Cloud Model Theory

    DEFF Research Database (Denmark)

    Li, Yan; Shuai, Zhikang; Xu, Qinming

    2016-01-01

    not only can avoid the active/reactive power coupling, but also it may reduce the output voltage drop of the PCC voltage. The proposed adjustable complex virtual impedance loop is putted into the conventional P/Q droop control to overcome the difficulty of getting the line impedance, which may change...... sometimes. The cloud model theory is applied to get online the changing line impedance value, which relies on the relevance of the reactive power responding the changing line impedance. The verification of the proposed control strategy is done according to the simulation in a low voltage microgrid in Matlab....

  4. Control protocol: large scale implementation at the CERN PS complex - a first assessment

    Energy Technology Data Exchange (ETDEWEB)

    Abie, H. (CERN, 1211, Geneva 23 (Switzerland)); Benincasa, G. (CERN, 1211, Geneva 23 (Switzerland)); Coudert, G. (CERN, 1211, Geneva 23 (Switzerland)); Davydenko, Y. (CERN, 1211, Geneva 23 (Switzerland)); Dehavay, C. (CERN, 1211, Geneva 23 (Switzerland)); Gavaggio, R. (CERN, 1211, Geneva 23 (Switzerland)); Gelato, G. (CERN, 1211, Geneva 23 (Switzerland)); Heinze, W. (CERN, 1211, Geneva 23 (Switzerland)); Legras, M. (CERN, 1211, Geneva 23 (Switzerland)); Lustig, H. (CERN, 1211, Geneva 23 (Switzerland)); Merard, L. (CERN, 1211, Geneva 23 (Switzerland)); Pearson, T. (CERN, 1211, Geneva 23 (Switzerland)); Strubin, P. (CERN, 1211, Geneva 23 (Switzerland)); Tedesco, J. (CERN, 1211, Geneva 23 (Switzerland))

    1994-12-15

    The Control Protocol is a model-based, uniform access procedure from a control system to accelerator equipment. It was proposed at CERN about 5 years ago and prototypes were developed in the following years. More recently, this procedure has been finalized and implemented at a large scale in the PS Complex. More than 300 pieces of equipment are now using this protocol in normal operation and another 300 are under implementation. These include power converters, vacuum systems, beam instrumentation devices, RF equipment, etc. This paper describes how the single general procedure is applied to the different kinds of equipment. The advantages obtained are also discussed. ((orig.))

  5. Control protocol: large scale implementation at the CERN PS complex — a first assessment

    Science.gov (United States)

    Abie, H.; Benincasa, G.; Coudert, G.; Davydenko, Y.; Dehavay, C.; Gavaggio, R.; Gelato, G.; Heinze, W.; Legras, M.; Lustig, H.; Merard, L.; Pearson, T.; Strubin, P.; Tedesco, J.

    1994-12-01

    The Control Protocol is a model-based, uniform access procedure from a control system to accelerator equipment. It was proposed at CERN about 5 years ago and prototypes were developed in the following years. More recently, this procedure has been finalized and implemented at a large scale in the PS Complex. More than 300 pieces of equipment are now using this protocol in normal operation and another 300 are under implementation. These include power converters, vacuum systems, beam instrumentation devices, RF equipment, etc. This paper describes how the single general procedure is applied to the different kinds of equipment. The advantages obtained are also discussed.

  6. Automated information and control complex of hydro-gas endogenous mine processes

    Science.gov (United States)

    Davkaev, K. S.; Lyakhovets, M. V.; Gulevich, T. M.; Zolin, K. A.

    2017-09-01

    The automated information and control complex designed to prevent accidents, related to aerological situation in the underground workings, accounting of the received and handed over individual devices, transmission and display of measurement data, and the formation of preemptive solutions is considered. Examples for the automated workplace of an airgas control operator by individual means are given. The statistical characteristics of field data characterizing the aerological situation in the mine are obtained. The conducted studies of statistical characteristics confirm the feasibility of creating a subsystem of controlled gas distribution with an adaptive arrangement of points for gas control. The adaptive (multivariant) algorithm for processing measuring information of continuous multidimensional quantities and influencing factors has been developed.

  7. Distributed optimization-based control of multi-agent networks in complex environments

    CERN Document Server

    Zhu, Minghui

    2015-01-01

    This book offers a concise and in-depth exposition of specific algorithmic solutions for distributed optimization based control of multi-agent networks and their performance analysis. It synthesizes and analyzes distributed strategies for three collaborative tasks: distributed cooperative optimization, mobile sensor deployment and multi-vehicle formation control. The book integrates miscellaneous ideas and tools from dynamic systems, control theory, graph theory, optimization, game theory and Markov chains to address the particular challenges introduced by such complexities in the environment as topological dynamics, environmental uncertainties, and potential cyber-attack by human adversaries. The book is written for first- or second-year graduate students in a variety of engineering disciplines, including control, robotics, decision-making, optimization and algorithms and with backgrounds in aerospace engineering, computer science, electrical engineering, mechanical engineering and operations research. Resea...

  8. Direct Control of Spin Distribution and Anisotropy in Cu-Dithiolene Complex Anions by Light

    Directory of Open Access Journals (Sweden)

    Hiroki Noma

    2016-03-01

    Full Text Available Electrical and magnetic properties are dominated by the (delocalization and the anisotropy in the distribution of unpaired electrons in solids. In molecular materials, these properties have been indirectly controlled through crystal structures using various chemical modifications to affect molecular structures and arrangements. In the molecular crystals, since the energy band structures can be semi-quantitatively known using band calculations and solid state spectra, one can anticipate the (delocalization of unpaired electrons in particular bands/levels, as well as interactions with other electrons. Thus, direct control of anisotropy and localization of unpaired electrons by locating them in selected energy bands/levels would realize more efficient control of electrical and magnetic properties. In this work, it has been found that the unpaired electrons on Cu(II-complex anions can be optically controlled to behave as anisotropically-delocalized electrons (under dark or isotropically-localized electrons like free electrons (under UV, the latter of which has hardly been observed in the ground states of Cu(II-complexes by any chemical modifications. Although the compounds examined in this work did not switch between conductors and magnets, these findings indicate that optical excitation in the [Cu(dmit2]2− salts should be an effective method to control spin distribution and anisotropy.

  9. 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

    Full Text Available BACKGROUND: 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". METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  10. Multiscale entropy:A tool for understanding the complexity of postural control

    Institute of Scientific and Technical Information of China (English)

    Michael A. Busa; Richard E.A. van Emmerik

    2016-01-01

    Clinical disorders often are characterized by a breakdown in dynamical processes that contribute to the control of upright standing. Disruption to a large number of physiological processes operating at different time scales can lead to alterations in postural center of pressure (CoP) fluctuations. Multiscale entropy (MSE) has been used to identify differences in fluctuations of postural CoP time series between groups with and without known physiological impairments at multiple time scales. The purpose of this paper is to: 1) review basic elements and current developments in entropy techniques used to assess physiological complexity;and 2) identify how MSE can provide insights into the complexity of physiological systems operating at multiple time scales that underlie the control of posture. We review and synthesize evidence from the literature providing support for MSE as a valuable tool to evaluate the breakdown in the physiological processes that accompany changes due to aging and disease in postural control. This evidence emerges from observed lower MSE values in individuals with multiple sclerosis, idiopathic scoliosis, and in older individuals with sensory impairments. Finally, we suggest some future applications of MSE that will allow for further insight into how physiological deficits impact the complexity of postural fluctuations;this information may improve the development and evaluation of new therapeutic interventions.

  11. LOW COMPLEXITY LMMSE TURBO EQUALIZATION FOR COMBINED ERROR CONTROL CODED AND LINEARLY PRECODED OFDM

    Institute of Scientific and Technical Information of China (English)

    Qu Daiming; Zhu Guangxi

    2006-01-01

    The turbo equalization approach is studied for Orthogonal Frequency Division Multiplexing (OFDM) system with combined error control coding and linear precoding. While previous literatures employed linear precoder of small size for complexity reasons, this paper proposes to use a linear precoder of size larger than or equal to the maximum length of the equivalent discrete-time channel in order to achieve full frequency diversity and reduce complexities of the error control coder/decoder. Also a low complexity Linear Minimum Mean Square Error (LMMSE) turbo equalizer is derived for the receiver. Through simulation and performance analysis, it is shown that the performance of the proposed scheme over frequency selective fading channel reaches the matched filter bound; compared with the same coded OFDM without linear precoding, the proposed scheme shows an Signal-to-Noise Ratio (SNR) improvement of at least 6dB at a bit error rate of 10-6 over a multipath channel with exponential power delay profile. Convergence behavior of the proposed scheme with turbo equalization using various type of linear precoder/transformer, various interleaver size and error control coder of various constraint length is also investigated.

  12. Complex Event Processing Approach To Automated Monitoring Of Particle Accelerator And Its Control System

    Directory of Open Access Journals (Sweden)

    Karol Grzegorczyk

    2014-01-01

    Full Text Available This article presents the design and implementation of a software component for automated monitoring and diagnostic information analysis of a particle accelerator and its control system. The information that is analyzed can be seen as streams of events. A Complex Event Processing (CEP approach to event processing was selected. The main advantage of this approach is the ability to continuously query data coming from several streams. The presented software component is based on Esper, the most popular open-source implementation of CEP. As a test bed, the control system of the accelerator complex located at CERN, the European Organization for Nuclear Research, was chosen. The complex includes the Large Hadron Collider, the world’s most powerful accelerator. The main contribution to knowledge is by showing that the CEP approach can successfully address many of the challenges associated with automated monitoring of the accelerator and its control system that were previously unsolved. Test results, performance analysis, and a proposal for further works are also presented.

  13. Investigating the Complexity of Transitioning Separation Assurance Tools into NextGen Air Traffic Control

    Science.gov (United States)

    Gomez, Ashley Nicole; Martin, Lynne Hazel; Homola, Jeffrey; Morey, Susan; Cabrall, Christopher; Mercer, Joey; Prevot, Thomas

    2013-01-01

    In a study, that introduced ground-based separation assurance automation through a series of envisioned transitional phases of concept maturity, it was found that subjective responses to scales of workload, situation awareness, and acceptability in a post run questionnaire revealed as-predicted results for three of the four study conditions but not for the third, Moderate condition. The trend continued for losses of separation (LOS) where the number of LOS events were far greater than expected in the Moderate condition. To offer an account of why the Moderate condition was perceived to be more difficult to manage than predicted, researchers examined the increase in amount and complexity of traffic, increase in communication load, and increased complexities as a result of the simulation's mix of aircraft equipage. Further analysis compared the tools presented through the phases, finding that controllers took advantage of the informational properties of the tools presented but shied away from using their decision support capabilities. Taking into account similar findings from other studies, it is suggested that the Moderate condition represented the first step into a "shared control" environment, which requires the controller to use the automation as a decision making partner rather than just a provider of information. Viewed in this light, the combination of tools offered in the Moderate condition was reviewed and some tradeoffs that may offset the identified complexities were suggested.

  14. Stoichiometry control of complex oxides by sequential pulsed-laser deposition from binary-oxide targets

    Energy Technology Data Exchange (ETDEWEB)

    Herklotz, A. [ORNL, Materials Science and Technology Division, Bethel Valley Road, Oak Ridge, Tennessee 37831-6056 (United States); Martin Luther University Halle-Wittenberg, Institute for Physics, Von-Danckelmann-Platz 3, 06120 Halle (Germany); Dörr, K. [Martin Luther University Halle-Wittenberg, Institute for Physics, Von-Danckelmann-Platz 3, 06120 Halle (Germany); Ward, T. Z.; Eres, G. [ORNL, Materials Science and Technology Division, Bethel Valley Road, Oak Ridge, Tennessee 37831-6056 (United States); Christen, H. M.; Biegalski, M. D. [ORNL, Center for Nanophase Materials Sciences, Bethel Valley Road, Oak Ridge, Tennessee 37831-6496 (United States)

    2015-03-30

    To have precise atomic layer control over interfaces, we examine the growth of complex oxides through the sequential deposition from binary targets by pulsed laser deposition. In situ reflection high-energy electron diffraction (RHEED) is used to control the growth and achieve films with excellent structural quality. The growth from binary oxide targets is fundamentally different from single target growth modes and shows more similarities to shuttered growth by molecular beam epitaxy. The RHEED intensity oscillations of non-stoichiometric growth are consistent with a model of island growth and accumulation of excess material on the surface that can be utilized to determine the correct stoichiometry for growth. Correct monolayer doses can be determined through an envelope frequency in the RHEED intensity oscillations. In order to demonstrate the ability of this growth technique to create complex heterostructures, the artificial n = 2 and 3 Sr{sub n+1}Ti{sub n}O{sub 3n+1} Ruddlesden-Popper phases are grown with good long-range order. This method enables the precise unit-cell level control over the structure of perovskite-type oxides, and thus the growth of complex materials with improved structural quality and electronic functionality.

  15. Periodic reference tracking control approach for smart material actuators with complex hysteretic characteristics

    Science.gov (United States)

    Sun, Zhiyong; Hao, Lina; Song, Bo; Yang, Ruiguo; Cao, Ruimin; Cheng, Yu

    2016-10-01

    Micro/nano positioning technologies have been attractive for decades for their various applications in both industrial and scientific fields. The actuators employed in these technologies are typically smart material actuators, which possess inherent hysteresis that may cause systems behave unexpectedly. Periodic reference tracking capability is fundamental for apparatuses such as scanning probe microscope, which employs smart material actuators to generate periodic scanning motion. However, traditional controller such as PID method cannot guarantee accurate fast periodic scanning motion. To tackle this problem and to conduct practical implementation in digital devices, this paper proposes a novel control method named discrete extended unparallel Prandtl-Ishlinskii model based internal model (d-EUPI-IM) control approach. To tackle modeling uncertainties, the robust d-EUPI-IM control approach is investigated, and the associated sufficient stabilizing conditions are derived. The advantages of the proposed controller are: it is designed and represented in discrete form, thus practical for digital devices implementation; the extended unparallel Prandtl-Ishlinskii model can precisely represent forward/inverse complex hysteretic characteristics, thus can reduce modeling uncertainties and benefits controllers design; in addition, the internal model principle based control module can be utilized as a natural oscillator for tackling periodic references tracking problem. The proposed controller was verified through comparative experiments on a piezoelectric actuator platform, and convincing results have been achieved.

  16. Effects of Edge Directions on the Structural Controllability of Complex Networks.

    Directory of Open Access Journals (Sweden)

    Yandong Xiao

    Full Text Available Recent advances indicate that assigning or reversing edge direction can significantly improve the structural controllability of complex networks. For directed networks, approaching the optimal structural controllability can be achieved by detecting and reversing certain "inappropriate" edge directions. However, the existence of multiple sets of "inappropriate" edge directions suggests that different edges have different effects on optimal controllability-that is, different combinations of edges can be reversed to achieve the same structural controllability. Therefore, we classify edges into three categories based on their direction: critical, redundant and intermittent. We then investigate the effects of changing these edge directions on network controllability, and demonstrate that the existence of more critical edge directions implies not only a lower cost of modifying inappropriate edges but also better controllability. Motivated by this finding, we present a simple edge orientation method aimed at producing more critical edge directions-utilizing only local information-which achieves near optimal controllability. Furthermore, we explore the effects of edge direction on the controllability of several real networks.

  17. Effects of Edge Directions on the Structural Controllability of Complex Networks.

    Science.gov (United States)

    Xiao, Yandong; Lao, Songyang; Hou, Lvlin; Small, Michael; Bai, Liang

    2015-01-01

    Recent advances indicate that assigning or reversing edge direction can significantly improve the structural controllability of complex networks. For directed networks, approaching the optimal structural controllability can be achieved by detecting and reversing certain "inappropriate" edge directions. However, the existence of multiple sets of "inappropriate" edge directions suggests that different edges have different effects on optimal controllability-that is, different combinations of edges can be reversed to achieve the same structural controllability. Therefore, we classify edges into three categories based on their direction: critical, redundant and intermittent. We then investigate the effects of changing these edge directions on network controllability, and demonstrate that the existence of more critical edge directions implies not only a lower cost of modifying inappropriate edges but also better controllability. Motivated by this finding, we present a simple edge orientation method aimed at producing more critical edge directions-utilizing only local information-which achieves near optimal controllability. Furthermore, we explore the effects of edge direction on the controllability of several real networks.

  18. Deficiency of syntrophin, dystroglycan, and merosin in a female infant with a congenital muscular dystrophy phenotype lacking cysteine-rich and C-terminal domains of dystrophin.

    Science.gov (United States)

    Tachi, N; Ohya, K; Chiba, S; Matsuo, M; Patria, S Y; Matsumura, K

    1997-08-01

    Primary deficiency of merosin is the cause of the classic form of congenital muscular dystrophy (CMD) accompanied by brain white matter abnormalities. We report a female infant with dystrophinopathy who was deficient in merosin in skeletal muscle. The patient had a phenotype of typical CMD and white matter abnormalities on brain MRI. Merosin was greatly reduced in the biopsied skeletal muscle. However, the expression of dystroglycan and syntrophin was also greatly reduced, and the immunoreactivity for the antibodies against the cysteine-rich/C-terminal domains of dystrophin was absent in the sarcolemma. Reverse transcriptase polymerase chain reaction analysis of the dystrophin gene revealed a complete lack of exons 71 through 74. In skeletal muscle, only the mutant gene was expressed. These results suggest that the patient is a symptomatic Duchenne muscular dystrophy carrier with skewed X-inactivation. This patient illustrates for the first time that a dystrophin abnormality can cause a secondary deficiency of merosin in dystrophinopathy. The reduction of merosin may account for the clinical phenotype of CMD and correlate with the white matter abnormalities in our patient.

  19. Up-regulation of miR-31 in human atrial fibrillation begets the arrhythmia by depleting dystrophin and neuronal nitric oxide synthase

    Science.gov (United States)

    Carnicer, Ricardo; Recalde, Alice; Muszkiewicz, Anna; Jayaram, Raja; Carena, Maria Cristina; Wijesurendra, Rohan; Stefanini, Matilde; Surdo, Nicoletta C.; Lomas, Oliver; Ratnatunga, Chandana; Sayeed, Rana; Krasopoulos, George; Rajakumar, Timothy; Bueno-Orovio, Alfonso; Verheule, Sander; Fulga, Tudor A.; Rodriguez, Blanca; Schotten, Ulrich

    2016-01-01

    Atrial fibrillation (AF) is a growing public health burden, and its treatment remains a challenge. AF leads to electrical remodeling of the atria, which in turn promotes AF maintenance and resistance to treatment. Although remodeling has long been a therapeutic target in AF, its causes remain poorly understood. We show that atrial-specific up-regulation of microRNA-31 (miR-31) in goat and human AF depletes neuronal nitric oxide synthase (nNOS) by accelerating mRNA decay and alters nNOS subcellular localization by repressing dystrophin translation. By shortening action potential duration and abolishing rate-dependent adaptation of the action potential duration, miR-31 overexpression and/or disruption of nNOS signaling recapitulates features of AF-induced remodeling and significantly increases AF inducibility in mice in vivo. By contrast, silencing miR-31 in atrial myocytes from patients with AF restores dystrophin and nNOS and normalizes action potential duration and its rate dependency. These findings identify atrial-specific up-regulation of miR-31 in human AF as a key mechanism causing atrial dystrophin and nNOS depletion, which in turn contributes to the atrial phenotype begetting this arrhythmia. miR-31 may therefore represent a potential therapeutic target in AF. PMID:27225184

  20. Precise Correction of the Dystrophin Gene in Duchenne Muscular Dystrophy Patient Induced Pluripotent Stem Cells by TALEN and CRISPR-Cas9

    Directory of Open Access Journals (Sweden)

    Hongmei Lisa Li

    2015-01-01

    Full Text Available 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.

  1. Critical Nodes Identification of Power Systems Based on Controllability of Complex Networks

    Directory of Open Access Journals (Sweden)

    Yu-Shuai Li

    2015-09-01

    Full Text Available This paper proposes a new method for assessing the vulnerability of power systems based on the controllability theories of complex networks. A novel controllability index is established, taking into consideration the full controllability of the power systems, for identifying critical nodes. The network controllability model is used to calculate the minimum number of driver nodes (ND, which can solve the computable problems of the controllability of power systems. The proposed approach firstly applies the network controllability theories to research the power systems' vulnerability, which can not only effectively reveal the important nodes but also maintain full control of the power systems. Meanwhile, the method can also overcome the limitation of the hypothesis that the weight of each link or transmission line must be known compared with the existing literature. In addition, the power system is considered as a directed network and the power system model is also redefined. The proposed methodology is then used to identify critical nodes of the IEEE 118 and 300 bus system. The results show that the failure of the critical nodes can clearly increase ND and lead a significant driver node shift. Thus, the rationality and validity are verified.

  2. Effects of Edge Directions on the Structural Controllability of Complex Networks

    Science.gov (United States)

    Xiao, Yandong; Lao, Songyang; Hou, Lvlin; Small, Michael; Bai, Liang

    2015-01-01

    Recent advances indicate that assigning or reversing edge direction can significantly improve the structural controllability of complex networks. For directed networks, approaching the optimal structural controllability can be achieved by detecting and reversing certain “inappropriate” edge directions. However, the existence of multiple sets of “inappropriate” edge directions suggests that different edges have different effects on optimal controllability—that is, different combinations of edges can be reversed to achieve the same structural controllability. Therefore, we classify edges into three categories based on their direction: critical, redundant and intermittent. We then investigate the effects of changing these edge directions on network controllability, and demonstrate that the existence of more critical edge directions implies not only a lower cost of modifying inappropriate edges but also better controllability. Motivated by this finding, we present a simple edge orientation method aimed at producing more critical edge directions—utilizing only local information—which achieves near optimal controllability. Furthermore, we explore the effects of edge direction on the controllability of several real networks. PMID:26281042

  3. Can Rehabilitation Influence the Efficiency of Control Signals in Complex Motion Strategies?

    Directory of Open Access Journals (Sweden)

    Joanna Cholewa

    2017-01-01

    Full Text Available The factor determining quality of life in Parkinson’s disease (PD is the worsening of a patient’s walking ability. The use of external stimuli can improve gait when performing complex motor patterns. The aim of this study was to evaluate the effect of rehabilitation on the effectiveness of control signals in people with PD. The study was performed on 42 people with idiopathic PD in the third stage of disease. The control group consisted of 19 patients who did not participate in rehabilitation activities. The experimental group was systematically participating in rehabilitation activities twice a week (60 minutes for 9 months. Gait speed, mean step length, and step frequency were calculated on the basis of the obtained results. These parameters were compared in both groups by single factor variance analyses. The best results were obtained using rhythmic external auditory signals. The group with patients actively participating in rehabilitation showed statistically significant improvement in gait speed (12.35%, mean step length (18.00%, and frequency step (2.40% compared to the control group. The presented research showed the positive effect of rehabilitation and was based on the performance of complex motion patterns, using external control signals for their effectiveness in new motion tasks.

  4. Low order modelling for feedback control of fluid flows around complex geometries

    Science.gov (United States)

    Dellar, Oliver; Jones, Bryn; Department of Automatic Control; Systems Engineering Collaboration

    2015-11-01

    The majority of goods transportation vehicles' power is consumed in overcoming aerodynamic drag. Reduction in pressure drag via feedback control could have significant economic and environmental effects on CO2 emissions, and reduce fatigue on the body by suppressing vortex shedding. The difficulty in designing such controllers lies in obtaining models suited to modern control design methods, which are necessarily of much lesser complexity than typical Computational Fluid Dynamics (CFD) models, or models derived from immediate spatial discretisation of the Navier-Stokes equations. This work develops an approach for modelling fluid flows using frequency response data generated for individual computational node sub-systems that result from a CFD type spatial discretisation of the governing equations. Input-to-sensor frequency response data for the overall system are then computed by forming interconnections between adjacent nodes via a Redheffer Star Product operation, from which one typically observes low-order dynamics. With this data, a low-order model can be identified and used for controller design. This method avoids manipulating large matrices and is therefore computationally efficient and numerically well-conditioned. It can be readily applied to complex geometry flows.

  5. Final LDRD report human interaction with complex systems: advances in hybrid reachability and control.

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Meeko M.

    2006-08-01

    This document describes new advances in hybrid reachability techniques accomplished during the course of a one-year Truman Postdoctoral Fellowship. These techniques provide guarantees of safety in complex systems, which is especially important in high-risk, expensive, or safety-critical systems. My work focused on new approaches to two specific problems motivated by real-world issues in complex systems: (1) multi-objective controller synthesis, and (2) control for recovery from error. Regarding the first problem, a novel application of reachability analysis allowed controller synthesis in a single step to achieve (a) safety, (b) stability, and (c) prevent input saturation. By extending the state to include the input parameters, constraints for stability, saturation, and envelope protection are incorporated into a single reachability analysis. Regarding the second problem, a new approach to the problem of recovery provides (a) states from which recovery is possible, and (b) controllers to guide the system during a recovery maneuver from an error state to a safe state in minimal time. Results are computed in both problems on nonlinear models of single longitudinal aircraft dynamics and two-aircraft lateral collision avoidance dynamics.

  6. Chitosan green tea polyphenol complex as a released control compound for wound healing

    Institute of Scientific and Technical Information of China (English)

    QIN Yao; WANG Hong-wei; Thirupathi Karuppanapandian; Wook Kim

    2010-01-01

    Objective: In recent years, oxidative stress has been implicated in a variety °enerative pro-cess and diseases, including acute and chronic inflamma-tory conditions such as wound healing.Green tea polyphe-nols have shown anti-oxidant property.The present study discussed the application of chitosan green tea polyphenol complex on the wound healing.Methods: The wound healing effect ofchitosan green tea polyphenol complex was studied in ten-week-old healthy male Sherman rats weighing 150-180 g by two wound models.The rats were randomly chosen and divided into four groups (n=5), administered with distilled water in Group A as con-trol group, epigallocatechin-3-gallate (EGCG) in Group B, chitosan-EGCG complex in Group C and chitosan-green tea polyphenols complex in Group D, respectively.In rats'incision wound model, two straight paravertebral inci-sions were made and skin tensile strength was measured using continuous water flow technology on the 10th day.In rats'excision wound model, wound contraction and pe-riod of epithelization were measured.The polyphenols re-lease from the complex was continuously monitored by an elution technique in aqueous solution at different pH val-ues (pH=4, 5, 6, 7).Results: The treatment groups showed significantly enhanced the breaking strength in incision wound (328±4.5) g and (421±18.5) g compared with control (264±16.7) g.In the excision wound model, the wound contraction percentage in treatment groups was relatively increased during the re-covery period.Respectively, the percentage of wound contraction ranged from 47.60%±2.15% on day 4 to 107.98% ±1.26% on day 16 compared with control group (8.46%±5.42% to 59.80%±4.47%).The complex demonstrated a gradual in-crease in the release rate from the initial stage and slow increase at different pH values.The release rate approxi-mated 0.6-0.7 in the complex and remained stable 6 hours after injury, which may be the end of the release process.Conclusions: In our study, chitosan

  7. Discomfort glare with complex fenestration systems and the impact on energy use when using daylighting control

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Sabine; McNeil, Andrew; Lee, Eleanor S.; Kalyanam, Raghuram

    2015-11-03

    Glare is a frequent issue in highly glazed buildings. A modelling approach is presented that uses discomfort glare probability and discomfort glare index as metrics to determine occupants’ behaviour. A glare control algorithm that actuated an interior shade for glare protection based on the predicted perception was implemented in a building simulation program. A reference case with a state-of-the-art base glazing was compared to the same glazing but with five different complex fenestration systems, i.e., exterior shades. The windows with exterior shades showed significant variations in glare frequencies. Energy use intensity in a prototypical office building with daylighting controls was greatly influenced for the systems with frequent glare occurrence. While the base glazing could benefit from glare control, some of the exterior shades showed significantly greater energy use when discomfort glare-based operation of interior shades was considered.

  8. Optimal control of an SIVRS epidemic spreading model with virus variation based on complex networks

    Science.gov (United States)

    Xu, Degang; Xu, Xiyang; Xie, Yongfang; Yang, Chunhua

    2017-07-01

    A novel SIVRS mathematical model for infectious diseases spreading is proposed and investigated in this paper. In this model virus variation factors are considered in the process of epidemic spreading based on complex networks, which can describe different contact status for different agents including the susceptible, the infectious, the variant and the recovered in a network. An optimal control problem is formulated to maximize the recovered agents with the limited resource allocation and optimal control strategies over the susceptible, the infected and the variant are investigated. Then the existence of a solution to the optimal control problem is given based on Pontryagin's Minimum Principle and modified forward backward sweep technique. Numerical simulations are provided to illustrate obtained theoretical results.

  9. Baseline scheme for polarization preservation and control in the MEIC ion complex

    Energy Technology Data Exchange (ETDEWEB)

    Derbenev, Yaroslav S. [Jefferson Lab, Newport News, VA (United States); Lin, Fanglei [Jefferson Lab, Newport News, VA (United States); Morozov, Vasiliy [Jefferson Lab, Newport News, VA (United States); Zhang, Yuhong [Jefferson Lab, Newport News, VA (United States); Kondratenko, Anatoliy [Science and Technique Laboratory Zaryad, Novosibirsk (Russian Federation); Kondratenko, M. A. [Science and Technique Laboratory Zaryad, Novosibirsk (Russian Federation); Filatov, Yury [MIPT, Dolgoprudny, Moscow (Russian Federation)

    2015-09-01

    The scheme for preservation and control of the ion polarization in the Medium-energy Electron-Ion Collider (MEIC) has been under active development in recent years. The figure-8 configuration of the ion rings provides a unique capability to control the polarization of any ion species including deuterons by means of "weak" solenoids rotating the particle spins by small angles. Insertion of "weak" solenoids into the magnetic lattices of the booster and collider rings solves the problem of polarization preservation during acceleration of the ion beam. Universal 3D spin rotators designed on the basis of "weak" solenoids allow one to obtain any polarization orientation at an interaction point of MEIC. This paper presents the baseline scheme for polarization preservation and control in the MEIC ion complex.

  10. Complexity Analysis of a Master-Slave Oligopoly Model and Chaos Control

    Directory of Open Access Journals (Sweden)

    Junhai Ma

    2014-01-01

    Full Text Available We establish a master-slave oligopoly game model with an upstream monopoly whose output is considered and two downstream oligopolies whose prices are considered. The existence and the local stable region of the Nash equilibrium point are investigated. The complex dynamic properties, such as bifurcation and chaos, are analyzed using bifurcation diagrams, the largest Lyapunov exponent diagrams, and the strange attractor graph. We further analyze the long-run average profit of the three firms and find that they are all optimal in the stable region. In addition, delay feedback control method and limiter control method are used in nondelayed model to control chaos. Furthermore, a delayed master-slave oligopoly game model is considered, and the three firms’ profit in various conditions is analyzed. We find that suitable delayed parameters are important for eliminating chaos and maximizing the profit of the players.

  11. Morphostructure Control Towards the Development of Mahawu Volcanic Complex, North Sulawesi

    Directory of Open Access Journals (Sweden)

    S. Poedjoprajitno

    2014-06-01

    Full Text Available DOI: 10.17014/ijog.v7i1.134The studied area, situated in northeastern part of North Sulawesi Arm, is dominantly occupied by the Mahawu, Linau, Tompusu, and Kasurutan volcanic rocks. Using remote sensing data, such as landsat image, black and white panchromatic aerial photograph, and IFSAR image, morphology-origin unit and morphology lineament can be interpreted. Four morphology-origin units, those are Mahawu Volcano Complex, Intra-montane Plain structure, Linau Volcano Complex, and Lacustrine Plain are recognized. Furthermore, morphological lineament pattern was statistically processed to find out the general stress direction in the area to determine the probability of the structural morphology occurrence in the Mahawu Volcano Complex. The result shows that generally the development pattern of volcanic cones are irregular, except the Mahawu Volcano Complex showing a linear pattern. This lineament pattern is interpreted as a NW - SE fault pattern controlling the rise of magma. At least, two tectonic and two eruption periods occurred regularly at different time from the Quaternary age till the present.

  12. The migrating motor complex: control mechanisms and its role in health and disease.

    Science.gov (United States)

    Deloose, Eveline; Janssen, Pieter; Depoortere, Inge; Tack, Jan

    2012-03-27

    The migrating motor complex (MMC) is a cyclic, recurring motility pattern that occurs in the stomach and small bowel during fasting; it is interrupted by feeding. The MMC is present in the gastrointestinal tract of many species, including humans. The complex can be subdivided into four phases, of which phase III is the most active, with a burst of contractions originating from the antrum or duodenum and migrating distally. Control of the MMC is complex. Phase III of the MMC with an antral origin can be induced in humans through intravenous administration of motilin, erythromycin or ghrelin, whereas administration of serotonin or somatostatin induces phase III activity with duodenal origin. The role of the vagus nerve in control of the MMC seems to be restricted to the stomach, as vagotomy abolishes the motor activity in the stomach, but leaves the periodic activity in the small bowel intact. The physiological role of the MMC is incompletely understood, but its absence has been associated with gastroparesis, intestinal pseudo-obstruction and small intestinal bacterial overgrowth. Measuring the motility of the gastrointestinal tract can be important for the diagnosis of gastrointestinal disorders. In this Review we summarize current knowledge of the MMC, especially its role in health and disease.

  13. The plant cell cycle: Pre-Replication complex formation and controls.

    Science.gov (United States)

    Brasil, Juliana Nogueira; Costa, Carinne N Monteiro; Cabral, Luiz Mors; Ferreira, Paulo C G; Hemerly, Adriana S

    2017-01-01

    The multiplication of cells in all living organisms requires a tight regulation of DNA replication. Several mechanisms take place to ensure that the DNA is replicated faithfully and just once per cell cycle in order to originate through mitoses two new daughter cells that contain exactly the same information from the previous one. A key control mechanism that occurs before cells enter S phase is the formation of a pre-replication complex (pre-RC) that is assembled at replication origins by the sequential association of the origin recognition complex, followed by Cdt1, Cdc6 and finally MCMs, licensing DNA to start replication. The identification of pre-RC members in all animal and plant species shows that this complex is conserved in eukaryotes and, more importantly, the differences between kingdoms might reflect their divergence in strategies on cell cycle regulation, as it must be integrated and adapted to the niche, ecosystem, and the organism peculiarities. Here, we provide an overview of the knowledge generated so far on the formation and the developmental controls of the pre-RC mechanism in plants, analyzing some particular aspects in comparison to other eukaryotes.

  14. Effect of the Postural Challenge on the Dependence of the Cardiovascular Control Complexity on Age

    Directory of Open Access Journals (Sweden)

    Aparecida M. Catai

    2014-12-01

    Full Text Available Short-term complexity of heart period (HP and systolic arterial pressure (SAP was computed to detect age and gender influences over cardiovascular control in resting supine condition (REST and during standing (STAND. Healthy subjects (n = 110, men = 55 were equally divided into five groups (21–30; 31–40; 41–50; 51–60; and 61–70 years of age. HP and SAP series were recorded for 15 min at REST and during STAND. A normalized complexity index (NCI based on conditional entropy was assessed. At REST we found that both NCIHP and NCISAP decreased with age in the overall population, but only women were responsible for this trend. During STAND we observed that both NCIHP and NCISAP were unrelated to age in the overall population, even when divided by gender. When the variation of NCI in response to STAND (ΔNCI = NCI at REST-NCI during STAND was computed individually, we found that ΔNCIHP progressively decreased with age in the overall population, and women were again responsible for this trend. Conversely, ΔNCISAP was unrelated to age and gender. This study stresses that the complexity of cardiovascular control and its ability to respond to stressors are more importantly lost with age in women than in men.

  15. The disruptive effects of pain on complex cognitive performance and executive control.

    Directory of Open Access Journals (Sweden)

    Edmund Keogh

    Full Text Available Pain interferes and disrupts attention. What is less clear is how pain affects performance on complex tasks, and the strategies used to ensure optimal outcomes. The aim of the current study was to examine the effect of pain on higher-order executive control processes involved in managing complex tasks. Sixty-two adult volunteers (40 female completed two computer-based tasks: a breakfast making task and a word generation puzzle. Both were complex, involving executive control functions, including goal-directed planning and switching. Half of those recruited performed the tasks under conditions of thermal heat pain, and half with no accompanying pain. Whilst pain did not affect central performance on either task, it did have indirect effects. For the breakfast task, pain resulted in a decreased ability to multitask, with performance decrements found on the secondary task. However, no effects of pain were found on the processes thought to underpin this task. For the word generation puzzle, pain did not affect task performance, but did alter subjective accounts of the processes used to complete the task; pain affected the perceived allocation of time to the task, as well as switching perceptions. Sex differences were also found. When studying higher-order cognitive processes, pain-related interference effects are varied, and may result in subtle or indirect changes in cognition.

  16. Miniaturized Swimming Soft Robot with Complex Movement Actuated and Controlled by Remote Light Signals

    Science.gov (United States)

    Huang, Chaolei; Lv, Jiu-An; Tian, Xiaojun; Wang, Yuechao; Yu, Yanlei; Liu, Jie

    2015-12-01

    Powering and communication with micro robots to enable complex functions is a long-standing challenge as the size of robots continues to shrink. Physical connection of wires or components needed for wireless communication are complex and limited by the size of electronic and energy storage devices, making miniaturization of robots difficult. To explore an alternative solution, we designed and fabricated a micro soft swimming robot with both powering and controlling functions provided by remote light, which does not carry any electronic devices and batteries. In this approach, a polymer film containing azobenzene chromophore which is sensitive to ultra-violet (UV) light works as “motor”, and the UV light and visible light work as “power and signal lines”. Periodically flashing UV light and white light drives the robot flagellum periodically to swing to eventually push forward the robot in the glass tube filled with liquid. The gripper on robot head can be opened or closed by lights to grab and carry the load. This kind of remotely light-driven approach realizes complex driving and controlling of micro robotic structures, making it possible to design and fabricate even smaller robots. It will have great potential among applications in the micro machine and robot fields.

  17. Chemical Control for Host-Parasitoid Model within the Parasitism Season and Its Complex Dynamics

    Directory of Open Access Journals (Sweden)

    Tao Wang

    2016-01-01

    Full Text Available In the present paper, we develop a host-parasitoid model with Holling type II functional response function and chemical control, which can be applied at any time of each parasitism season or pest generation, and focus on addressing the importance of the timing of application pesticide during the parasitism season or pest generation in successful pest control. Firstly, the existence and stability of both the host and parasitoid populations extinction equilibrium and parasitoid-free equilibrium have been investigated. Secondly, the effects of key parameters on the threshold conditions have been discussed in more detail, which shows the importance of pesticide application times on the pest control. Thirdly, the complex dynamics including multiple attractors coexistence, chaotic behavior, and initial sensitivity have been studied by using numerical bifurcation analyses. Finally, the uncertainty and sensitivity of all the parameters on the solutions of both the host and parasitoid populations are investigated, which can help us to determine the key parameters in designing the pest control strategy. The present research can help us to further understand the importance of timings of pesticide application in the pest control and to improve the classical chemical control and to make management decisions.

  18. The critical phase for visual control of human walking over complex terrain

    Science.gov (United States)

    Matthis, Jonathan Samir; Barton, Sean L.; Fajen, Brett R.

    2017-01-01

    To walk efficiently over complex terrain, humans must use vision to tailor their gait to the upcoming ground surface without interfering with the exploitation of passive mechanical forces. We propose that walkers use visual information to initialize the mechanical state of the body before the beginning of each step so the resulting ballistic trajectory of the walker’s center-of-mass will facilitate stepping on target footholds. Using a precision stepping task and synchronizing target visibility to the gait cycle, we empirically validated two predictions derived from this strategy: (1) Walkers must have information about upcoming footholds during the second half of the preceding step, and (2) foot placement is guided by information about the position of the target foothold relative to the preceding base of support. We conclude that active and passive modes of control work synergistically to allow walkers to negotiate complex terrain with efficiency, stability, and precision. PMID:28739912

  19. Cancer control through principles of systems science, complexity, and chaos theory: a model.

    Science.gov (United States)

    Janecka, Ivo P

    2007-06-05

    Cancer is a significant medical and societal problem. This reality arises from the fact that an exponential and an unrestricted cellular growth destabilizes human body as a system. From this perspective, cancer is a manifestation of a system-in-failing.A model of normal and abnormal cell cycle oscillations has been developed incorporating systems science, complexity, and chaos theories. Using this model, cancer expresses a failing subsystem and is characterized by a positive exponential growth taking place in the outer edge of chaos. The overall survival of human body as a system is threatened. This model suggests, however, that cancer's exponential cellular growth and disorganized complexity could be controlled through the process of induction of differentiation of cancer stem cells into cells of low and basic functionality. This concept would imply reorientation of current treatment principles from cellular killing (cyto-toxic therapies) to cellular retraining (cyto-education).

  20. The critical phase for visual control of human walking over complex terrain.

    Science.gov (United States)

    Matthis, Jonathan Samir; Barton, Sean L; Fajen, Brett R

    2017-08-08

    To walk efficiently over complex terrain, humans must use vision to tailor their gait to the upcoming ground surface without interfering with the exploitation of passive mechanical forces. We propose that walkers use visual information to initialize the mechanical state of the body before the beginning of each step so the resulting ballistic trajectory of the walker's center-of-mass will facilitate stepping on target footholds. Using a precision stepping task and synchronizing target visibility to the gait cycle, we empirically validated two predictions derived from this strategy: (1) Walkers must have information about upcoming footholds during the second half of the preceding step, and (2) foot placement is guided by information about the position of the target foothold relative to the preceding base of support. We conclude that active and passive modes of control work synergistically to allow walkers to negotiate complex terrain with efficiency, stability, and precision.

  1. Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly.

    Science.gov (United States)

    Munson, M; Chen, X; Cocina, A E; Schultz, S M; Hughson, F M

    2000-10-01

    In the eukaryotic secretory and endocytic pathways, transport vesicles shuttle cargo among intracellular organelles and to and from the plasma membrane. Cargo delivery entails fusion of the transport vesicle with its target, a process thought to be mediated by membrane bridging SNARE protein complexes. Temporal and spatial control of intracellular trafficking depends in part on regulating the assembly of these complexes. In vitro, SNARE assembly is inhibited by the closed conformation adopted by the syntaxin family of SNAREs. To visualize this closed conformation directly, the X-ray crystal structure of a yeast syntaxin, Sso1p, has been determined and refined to 2.1 A resolution. Mutants designed to destabilize the closed conformation exhibit accelerated rates of SNARE assembly. Our results provide insight into the mechanism of SNARE assembly and its intramolecular and intermolecular regulation.

  2. Failure of Arm Movement Control in Stroke Patients, Characterized by Loss of Complexity.

    Science.gov (United States)

    Goh, Segun; Han, Kyungreem; Ryu, Jehkwang; Kim, Seonjin; Choi, MooYoung

    2015-01-01

    We study the mechanism of human arm-posture control by means of nonlinear dynamics and quantitative time series analysis methods. Utilizing linear and nonlinear measures in combination, we find that pathological tremors emerge in patient dynamics and serve as a main feature discriminating between normal and patient groups. The deterministic structure accompanied with loss of complexity inherent in the tremor dynamics is also revealed. To probe the underlying mechanism of the arm-posture dynamics, we further analyze the coupling patterns between joints and components, and discuss their roles in breaking of the organization structure. As a result, we elucidate the mechanisms in the arm-posture dynamics of normal subjects responding to the gravitational force and for the reduction of the dynamic degrees of freedom in the patient dynamics. This study provides an integrated framework for the origin of the loss of complexity in the dynamics of patients as well as the coupling structure in the arm-posture dynamics.

  3. Geomorphic controls of soil spatial complexity in a primeval mountain forest in the Czech Republic

    Science.gov (United States)

    Daněk, Pavel; Šamonil, Pavel; Phillips, Jonathan D.

    2016-11-01

    Soil diversity and complexity is influenced by a variety of factors, and much recent research has been focused on interpreting or modeling complexity based on soil-topography relationships, and effects of biogeomorphic processes. We aimed to (i) describe local soil diversity in one of the oldest forest reserves in Europe, (ii) employ existing graph theory concepts in pedocomplexity calculation and extend them by a novel approach based on hypothesis testing and an index measuring graph sequentiality (the extent to which soils have gradual vs. abrupt variations in underlying soil factors), and (iii) reveal the main sources of pedocomplexity, with a particular focus on geomorphic controls. A total of 954 soil profiles were described and classified to soil taxonomic units (STU) within a 46 ha area. We analyzed soil diversity using the Shannon index, and soil complexity using a novel graph theory approach. Pairwise tests of observed adjacencies, spectral radius and a newly proposed sequentiality index were used to describe and quantify the complexity of the spatial pattern of STUs. This was then decomposed into the contributions of three soil factor sequences (SFS), (i) degree of weathering and leaching processes, (ii) hydromorphology, and (iii) proportion of rock fragments. Six Reference Soil Groups and 37 second-level soil units were found. A significant portion of pedocomplexity occurred at distances shorter than the 22 m spacing of neighbouring soil profiles. The spectral radius (an index of complexity) of the pattern of soil spatial adjacency was 14.73, to which the individual SFS accounted for values of 2.0, 8.0 and 3.5, respectively. Significant sequentiality was found for degree of weathering and hydromorphology. Exceptional overall pedocomplexity was particularly caused by enormous spatial variability of soil wetness, representing a crucial soil factor sequence in the primeval forest. Moreover, the soil wetness gradient was partly spatially correlated with the

  4. Robust reconstitution of active cell-cycle control complexes from co-expressed proteins in bacteria

    Directory of Open Access Journals (Sweden)

    Harashima Hirofumi

    2012-06-01

    Full Text Available Abstract Background Cell proliferation is an important determinant of plant growth and development. In addition, modulation of cell-division rate is an important mechanism of plant plasticity and is key in adapting of plants to environmental conditions. One of the greatest challenges in understanding the cell cycle of flowering plants is the large families of CDKs and cyclins that have the potential to form many different complexes. However, it is largely unclear which complexes are active. In addition, there are many CDK- and cyclin-related proteins whose biological role is still unclear, i.e. whether they have indeed enzymatic activity. Thus, a biochemical characterization of these proteins is of key importance for the understanding of their function. Results Here we present a straightforward system to systematically express and purify active CDK-cyclin complexes from E. coli extracts. Our method relies on the concomitant production of a CDK activating kinase, which catalyzes the T-loop phosphorylation necessary for kinase activity. Taking the examples of the G1-phase cyclin CYCLIN D3;1 (CYCD3;1, the mitotic cyclin CYCLIN B1;2 (CYCB1;2 and the atypical meiotic cyclin SOLO DANCERS (SDS in conjunction with A-, B1- and B2-type CDKs, we show that different CDKs can interact with various cyclins in vitro but only a few specific complexes have high levels of kinase activity. Conclusions Our work shows that both the cyclin as well as the CDK partner contribute to substrate specificity in plants. These findings refine the interaction networks in cell-cycle control and pinpoint to particular complexes for modulating cell proliferation activity in breeding.

  5. Controlling collective dynamics in complex minority-game resource-allocation systems.

    Science.gov (United States)

    Zhang, Ji-Qiang; Huang, Zi-Gang; Dong, Jia-Qi; Huang, Liang; Lai, Ying-Cheng

    2013-05-01

    Resource allocation takes place in various kinds of real-world complex systems, such as traffic systems, social services institutions or organizations, or even ecosystems. The fundamental principle underlying complex resource-allocation dynamics is Boolean interactions associated with minority games, as resources are generally limited and agents tend to choose the least used resource based on available information. A common but harmful dynamical behavior in resource-allocation systems is herding, where there are time intervals during which a large majority of the agents compete for a few resources, leaving many other resources unused. Accompanying the herd behavior is thus strong fluctuations with time in the number of resources being used. In this paper, we articulate and establish that an intuitive control strategy, namely pinning control, is effective at harnessing the herding dynamics. In particular, by fixing the choices of resources for a few agents while leaving the majority of the agents free, herding can be eliminated completely. Our investigation is systematic in that we consider random and targeted pinning and a variety of network topologies, and we carry out a comprehensive analysis in the framework of mean-field theory to understand the working of control. The basic philosophy is then that, when a few agents waive their freedom to choose resources by receiving sufficient incentives, the majority of the agents benefit in that they will make fair, efficient, and effective use of the available resources. Our work represents a basic and general framework to address the fundamental issue of fluctuations in complex dynamical systems with significant applications to social, economical, and political systems.

  6. Algorithms and Complexity Analyses for Control of Singleton Attractors in Boolean Networks

    Directory of Open Access Journals (Sweden)

    Wai-Ki Ching

    2008-09-01

    Full Text Available A Boolean network (BN is a mathematical model of genetic networks. We propose several algorithms for control of singleton attractors in BN. We theoretically estimate the average-case time complexities of the proposed algorithms, and confirm them by computer experiments. The results suggest the importance of gene ordering. Especially, setting internal nodes ahead yields shorter computational time than setting external nodes ahead in various types of algorithms. We also present a heuristic algorithm which does not look for the optimal solution but for the solution whose computational time is shorter than that of the exact algorithms.

  7. Self-Reference as a Problem in the Control of Complex Systems

    DEFF Research Database (Denmark)

    Hollnagel, Erik; Lind, Morten

    1982-01-01

    Argues that it is necessary that control systems for complex processes be self-referencing. A system is described as self-referencing when it uses a model of itself as a basis for communication and interaction with other systems, and it is suggested that human–machine systems should be looked upo...... philosophers and psychologists are encouraged to cooperate in the study of this issue, which touches on the analysis of induction concerning reflectivity both in human beings and in data processing systems....

  8. Technology improvement of chromium on steel parts electrodeposition using complex command and control systems

    Science.gov (United States)

    Stănescu, A.; Alecusan, A. M.; Dimitescu, A.

    2016-08-01

    The paper aims to provide improved technological process of electrochemical deposition of chromium on steel for decorative parts for corrosion protection but also to improve mechanical properties. The proposed idea is perfectly suited to be grafted onto existing electrodeposition installations, but it can be applied successfully in the development of new such plants. Complex command and control systems are designed to operate in high aggressive environmental conditions specific to these types of installations. The theoretical part completes the experimental results obtained on a laboratory facility.

  9. Dynamic nonlinear feedback for temperature control of continuous stirred reactor with complex behavior

    Directory of Open Access Journals (Sweden)

    Pablo A. López Pérez

    2009-08-01

    Full Text Available The main objective of this work is to present an alternative methodology for the design of a class of integral high order slidingmodecontroller applied to a class of continuous chemical reactor with complex behavior for temperature tracking purposes.The proposed design is based on the differential geometry framework, where the named reaching trajectory contains a highorder sliding mode term in order to diminish chattering. Considering that the proposed technique is model based, an observerbaseduncertainty estimator is coupled, which provides robustness against model uncertainties and noisy measurements.Numerical simulations are performed in order to show the capacities of the proposed controller, which is compared with othernonlinear methodologies.

  10. Spatiotemporal chaos control with a target wave in the complex Ginzburg-Landau equation system.

    Science.gov (United States)

    Jiang, Minxi; Wang, Xiaonan; Ouyang, Qi; Zhang, Hong

    2004-05-01

    An effective method for controlling spiral turbulence in spatially extended systems is realized by introducing a spatially localized inhomogeneity into a two-dimensional system described by the complex Ginzburg-Landau equation. Our numerical simulations show that with the introduction of the inhomogeneity, a target wave can be produced, which will sweep all spiral defects out of the boundary of the system. The effects exist in certain parameter regions where the spiral waves are absolutely unstable. A theoretical explanation is given to reveal the underlying mechanism.

  11. 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.

  12. 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.

  13. Failure mechanism and stability control technology of rock surrounding a roadway in complex stress conditions

    Institute of Scientific and Technical Information of China (English)

    Yu Yang; Bai Jianbiao; Chen Ke; Wang Xiangyu; Xiao Tongqiang; Chen Yong

    2011-01-01

    To solve the problem of supporting three downhill coal structures in the Yongan Coal Mine of Shanxi Jincheng,we studied the regular development of stress and plastic zones and characteristics of deformation of rock surrounding roadway groups after a period of roadway driving,mining one side as well as mining both sides,we used FLAC3D for our numerical and theoretical analyses.Field test were carried out,where we revealed the deformation mechanism of roadways and its coal pillars in complex stress conditions.We proposed a roadway stability control technology using backwall grouting with high-water rapid hardening material and combined support with bolt and cable anchoring after mining both sides.Our field practices showed that deformation of rock surrounding roadways can be controlled with this technology.

  14. Adaptive Output Feedback Sliding Mode Control for Complex Interconnected Time-Delay Systems

    Directory of Open Access Journals (Sweden)

    Van Van Huynh

    2015-01-01

    Full Text Available We extend the decentralized output feedback sliding mode control (SMC scheme to stabilize a class of complex interconnected time-delay systems. First, sufficient conditions in terms of linear matrix inequalities are derived such that the equivalent reduced-order system in the sliding mode is asymptotically stable. Second, based on a new lemma, a decentralized adaptive sliding mode controller is designed to guarantee the finite time reachability of the system states by using output feedback only. The advantage of the proposed method is that two major assumptions, which are required in most existing SMC approaches, are both released. These assumptions are (1 disturbances are bounded by a known function of outputs and (2 the sliding matrix satisfies a matrix equation that guarantees the sliding mode. Finally, a numerical example is used to demonstrate the efficacy of the method.

  15. Preparation and characterization of controlled release matrices based on novel seaweed interpolyelectrolyte complexes.

    Science.gov (United States)

    Prado, Héctor J; Matulewicz, María C; Bonelli, Pablo R; Cukierman, Ana L

    2012-06-15

    Novel interpolyelectrolyte complexes (IPECs) between naturally sulfated polysaccharides of the seaweed Polysiphonia nigrescens (PN) and cationized agaroses (CAG) and Eudragit E (EE) were prepared using an organic solvent free process, characterized, and explored for controlled drug release. Tablets containing model drug ibuprofen and IPECs were prepared by direct compression. Drug release in acid medium was low owing to the low solubility of ibuprofen in that condition and to the matrix action. Zero order drug release was determined in the buffer stage (pH=6.8), with Fickian diffusion predominating over relaxation during the initial phases. Relaxation appears to increase along the release process and even overcomes diffusion for some systems. Drug release profiles could be controlled by varying the content of IPECs in the tablets. Also, the change in molecular weight and the degree of substitution of the components allowed altering the release profiles.

  16. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    DEFF Research Database (Denmark)

    Hoof, Ilka; Kesmir, Can; Lund, Ole;

    2008-01-01

    Background: Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia...... and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...

  17. Controlled synthesis of titania using water-soluble titanium complexes: A review

    Science.gov (United States)

    Truong, Quang Duc; Dien, Luong Xuan; Vo, Dai-Viet N.; Le, Thanh Son

    2017-07-01

    The development of human society has led to the increase in energy and resources consumption as well as the arising problems of environmental damage and the toxicity to the human health. The development of novel synthesis method which tolerates utilization of toxic solvents and chemicals would fulfill the demand of the society for safer, softer, and environmental friendly technologies. For the past decades, a remarkable progress has been attained in the development of new water-soluble titanium complexes (WSTC) and their use for the synthesis of nanocrystalline titanium dioxide materials by aqueous solution-based approaches. The progress of synthesis of nanocrystalline titanium dioxide using such WSTCs is reviewed in this work. The key structural features responsible for the successfully controlled synthesis of TiO2 are discussed to provide guidelines for the morphology-controlled synthesis. Finally, this review ends with a summary and some perspectives on the challenges as well as new directions in this fascinating research.

  18. Formation of oxygen complexes in controlled atmosphere at surface of doped glassy carbon

    Indian Academy of Sciences (India)

    Aleksandra A Perić-Grujić; Tatjana M Vasiljević; Olivera M Nešković; Miomir V Veljković; Zoran V Laušević; Mila D Laušević

    2006-10-01

    The effects of boron and phosphorus incorporation in phenolic resin precursor to the oxidation resistance of glassy carbon have been studied. In order to reveal the nature and composition of the oxygen complexes formed at the surface of doped glassy carbon, under controlled atmosphere, the surface of the samples was cleaned under vacuum up to 1273 K. Specific functional groups, subsequently formed under dry CO2 or O2 atmosphere on the surface of boron-doped and phosphorus-doped glassy carbon samples, were examined using the temperature-programmed desorption method combined with mass spectrometric analysis. Characterization of surface properties of undoped and doped samples has shown that in the presence of either boron or phosphorus heteroatoms, a lower amount of oxygen complexes formed after CO2 exposure, while, typically, higher amount of oxygen complexes formed after O2 exposure. It has been concluded that the surface of undoped glassy carbon has a greater affinity towards CO2, while in the presence of either boron or phosphorus heteroatoms, the glassy carbon surface affinity becomes greater towards O2, under experimental conditions.

  19. [Ecological control effects of Litchi chinensis-Desmodium intortum complex plant ecosystem on litchi pests].

    Science.gov (United States)

    Ouyang, Gecheng; Yang, Yueping; Liu, Deguang; Xiong, Jinjun; Huang, Mingdu

    2006-01-01

    An investigation on the community structure and dynamics of litchi pests and their natural enemies in constructed Litchi chinensis-Desmodium intortum complex plant ecosystem and single L. chinensis ecosystem showed that the total amount of litchi pests in the complex plant ecosystem was 61.27% of that in the single ecosystem in whole year, and only 50.45% in May, the key time for fruit development, which suggested that there was an interaction between D. intortum and L. chinensis. D. intortum and L. chinensis had a few common pests, but many common natural enemies. D. intortum florescence in winter provided shelter and substitutive food for the natural enemies of pests to survive in the extreme environmental conditions in winter. L. chinensis florescence was on the heel of D. intortum florescence, which provided better conditions for the natural enemies to survive and multiply. During florescence and fruit development stages of L. chinensis (from March to June), the predator/prey ratio in complex plant system was 4.22, 2.34, 2.2 and 20.63 times of that in single plant system in March, April, May and June, respectively, indicating the good control effect on pests of L. chinensis.

  20. A Whi7-anchored loop controls the G1 Cdk-cyclin complex at start.

    Science.gov (United States)

    Yahya, Galal; Parisi, Eva; Flores, Alba; Gallego, Carme; Aldea, Martí

    2014-01-09

    Cells commit to a new cell cycle at Start by activation of the G1 Cdk-cyclin complex which, in turn, triggers a genome-wide transcriptional wave that executes the G1/S transition. In budding yeast, the Cdc28-Cln3 complex is regulated by an ER-retention mechanism that is important for proper cell size control. We have isolated small-cell-size CDC28 mutants showing impaired retention at the ER and premature accumulation of the Cln3 cyclin in the nucleus. The differential interactome of a quintuple Cdc28(wee) mutant pinpointed Whi7, a Whi5 paralog targeted by Cdc28 that associates to the ER in a phosphorylation-dependent manner. Our results demonstrate that the Cln3 cyclin and Whi7 act in a positive feedback loop to release the G1 Cdk-cyclin complex and trigger Start once a critical size has been reached, thus uncovering a key nonlinear mechanism at the earliest known events of cell-cycle entry.

  1. Complex Outcomes from Insect and Weed Control with Transgenic Plants: Ecological Surprises?

    Directory of Open Access Journals (Sweden)

    Thomas Bøhn

    2017-09-01

    Full Text Available Agriculture is fundamental for human survival through food production and is performed in ecosystems that, while simplified, still operate along ecological principles and retain complexity. Agricultural plants are thus part of ecological systems, and interact in complex ways with the surrounding terrestrial, soil, and aquatic habitats. We discuss three case studies that demonstrate how agricultural solutions to pest and weed control, if they overlook important ecological and evolutionary factors, cause “surprises”: (i the fast emergence of resistance against the crop-inserted Bt-toxin in South Africa, (ii the ecological changes generated by Bt-cotton landscapes in China, and (iii the decline of the monarch butterfly, Danaus plexippus, in North America. The recognition that we work with complex systems is in itself important, as it should limit the belief in reductionist solutions. Agricultural practices lacking eco-evolutionary understanding result in “surprises” like resistance evolution both in weeds and pest insects, risking the reappearance of the “pesticide treadmill”—with increased use of toxic pesticides as the follow-up. We recommend prioritization of research that counteracts the tendencies of reductionist approaches. These may be beneficial on a short term, but with trade-off costs on a medium- to long-term. Such costs include loss of biodiversity, ecosystem services, long-term soil productivity, pollution, and reduced food quality.

  2. Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study.

    Science.gov (United States)

    Lewin, Simon; Glenton, Claire; Oxman, Andrew D

    2009-09-10

    To examine the use of qualitative approaches alongside randomised trials of complex healthcare interventions. Review of randomised controlled trials of interventions to change professional practice or the organisation of care. Systematic sample of 100 trials published in English from the register of the Cochrane Effective Practice and Organisation of Care Review Group. Published and unpublished qualitative studies linked to the randomised controlled trials were identified through database searches and contact with authors. Data were extracted from each study by two reviewers using a standard form. We extracted data describing the randomised controlled trials and qualitative studies, the quality of these studies, and how, if at all, the qualitative and quantitative findings were combined. A narrative synthesis of the findings was done. 30 of the 100 trials had associated qualitative work and 19 of these were published studies. 14 qualitative studies were done before the trial, nine during the trial, and four after the trial. 13 studies reported an explicit theoretical basis and 11 specified their methodological approach. Approaches to sampling and data analysis were poorly described. For most cases (n=20) we found no indication of integration of qualitative and quantitative findings at the level of either analysis or interpretation. The quality of the qualitative studies was highly variable. Qualitative studies alongside randomised controlled trials remain uncommon, even where relatively complex interventions are being evaluated. Most of the qualitative studies were carried out before or during the trials with few studies used to explain trial results. The findings of the qualitative studies seemed to be poorly integrated with those of the trials and often had major methodological shortcomings.

  3. A solvent-controlled switch of manganese complex assemblies with a beta-diketonate-based ligand.

    Science.gov (United States)

    Aromí, Guillem; Gamez, Patrick; Roubeau, Olivier; Berzal, Paula Carrero; Kooijman, Huub; Spek, Anthony L; Driessen, Willem L; Reedijk, Jan

    2002-07-15

    The coordination properties of the new polynucleating ligand H(3)L1 (1,3-bis(3-oxo-3-phenylpropionyl)-2-hydroxy-5-methylbenzene) with Mn(II/III) are described. Depending on the solvent used, the reaction of H(3)L1 with Mn(OAc)(2) yields either of the two new multinuclear assemblies [Mn(2)(HL1)(2)(py)(4)] (1) and [Mn(3)(HL1)(3)] (2), as revealed by X-ray crystallography. The structure of 2 is remarkable in that it shows a unique asymmetric triple-stranded helicate. Complexes 1 and 2 can be interconverted by controlling the solvent of the reaction system, and therefore, this ensemble constitutes an interesting externally addressable switch. In the presence of Mn(III)/pyridine, partial degradation of H(3)L1 occurs via oxidative cleavage, and the new complex [Mn(2)(L2)(2)(py)(4)] (3) is formed. The crystal structure of this complex has shown the fully deprotonated form of the new donor H(3)L2 (3-(3-oxo-3-phenylpropionyl)-5-methylsalicylic acid). From the same reaction, the Mn(II) complex 1 is also obtained. A rational synthesis of H(3)L2 is reported, and this has been used to prepare 3 in high yields, directly from its components. Variable-temperature magnetic susceptibility (chi(m)) measurements were performed on complexes 1-3 under a magnetic field of 1 kG. The data for each complex were fit to the appropriate chi(m) vs T theoretical equation, respectively. In 1, the Mn(II) ions are uncoupled, with g = 2.01. The data from 2 were fit by assuming the presence of an exchange coupled Mn(II)...Mn(II) pair next to a magnetically isolated Mn(II) center. The fit gave J = -2.75 cm(-1), g(12) = 1.97, and g(3) = 1.92, respectively. In 3, two models fit the experimental data. In the most satisfactory, the Mn(III) ions are coupled antiferromagnetically with J = -1.48 cm(-1) and g = 1.98 and a term for weak ferromagnetic intermolecular exchange is included with zJ' = 0.39 cm(-1). The other model contemplates the presence of two uncoupled zero field split Mn(III) ions.

  4. APC/C-CCS52A complexes control meristem maintenance in the Arabidopsis root.

    Science.gov (United States)

    Vanstraelen, Marleen; Baloban, Mikhail; Da Ines, Olivier; Cultrone, Antonietta; Lammens, Tim; Boudolf, Véronique; Brown, Spencer C; De Veylder, Lieven; Mergaert, Peter; Kondorosi, Eva

    2009-07-14

    Plant organs originate from meristems where stem cells are maintained to produce continuously daughter cells that are the source of different cell types. The cell cycle switch gene CCS52A, a substrate specific activator of the anaphase promoting complex/cyclosome (APC/C), controls the mitotic arrest and the transition of mitotic cycles to endoreduplication (ER) cycles as part of cell differentiation. Arabidopsis, unlike other organisms, contains 2 CCS52A isoforms. Here, we show that both of them are active and regulate meristem maintenance in the root tip, although through different mechanisms. The CCS52A1 activity in the elongation zone of the root stimulates ER and mitotic exit, and contributes to the border delineation between dividing and expanding cells. In contrast, CCS52A2 acts directly in the distal region of the root meristem to control identity of the quiescent center (QC) cells and stem cell maintenance. Cell proliferation assays in roots suggest that this control involves CCS52A2 mediated repression of mitotic activity in the QC cells. The data indicate that the CCS52A genes favor a low mitotic state in different cell types of the root tip that is required for meristem maintenance, and reveal a previously undescribed mechanism for APC/C mediated control in plant development.

  5. Controlling the Self-organizing Dynamics in a Sandpile Model on Complex Networks by Failure Tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Qi, J.; Pfenninger, S.

    2015-08-01

    In this paper, we propose a strategy to control the self-organizing dynamics of the Bak-Tang-Wiesenfeld (BTW) sandpile model on complex networks by allowing some degree of failure tolerance for the nodes and introducing additional active dissipation while taking the risk of possible node damage. We show that the probability for large cascades significantly increases or decreases respectively when the risk for node damage outweighs the active dissipation and when the active dissipation outweighs the risk for node damage. By considering the potential additional risk from node damage, a non-trivial optimal active dissipation control strategy which minimizes the total cost in the system can be obtained. Under some conditions the introduced control strategy can decrease the total cost in the system compared to the uncontrolled model. Moreover, when the probability of damaging a node experiencing failure tolerance is greater than the critical value, then no matter how successful the active dissipation control is, the total cost of the system will have to increase. This critical damage probability can be used as an indicator of the robustness of a network or system. Copyright (C) EPLA, 2015

  6. The evolution of the dystroglycan complex, a major mediator of muscle integrity

    Directory of Open Access Journals (Sweden)

    Josephine C. Adams

    2015-09-01

    Full Text Available Basement membrane (BM extracellular matrices are crucial for the coordination of different tissue layers. A matrix adhesion receptor that is important for BM function and stability in many mammalian tissues is the dystroglycan (DG complex. This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and the transmembrane β-DG, that interacts principally with dystrophin to connect to the actin cytoskeleton. Mutations in dystrophin, DG, or several enzymes that glycosylate α-DG underlie severe forms of human muscular dystrophy. Nonwithstanding the pathophysiological importance of the DG complex and its fundamental interest as a non-integrin system of cell-ECM adhesion, the evolution of DG and its interacting proteins is not understood. We analysed the phylogenetic distribution of DG, its proximal binding partners and key processing enzymes in extant metazoan and relevant outgroups. We identify that DG originated after the divergence of ctenophores from porifera and eumetazoa. The C-terminal half of the DG core protein is highly-conserved, yet the N-terminal region, that includes the laminin-binding region, has undergone major lineage-specific divergences. Phylogenetic analysis based on the C-terminal IG2_MAT_NU region identified three distinct clades corresponding to deuterostomes, arthropods, and mollusks/early-diverging metazoans. Whereas the glycosyltransferases that modify α-DG are also present in choanoflagellates, the DG-binding proteins dystrophin and laminin originated at the base of the metazoa, and DG-associated sarcoglycan is restricted to cnidarians and bilaterians. These findings implicate extensive functional diversification of DG within invertebrate lineages and identify the laminin-DG-dystrophin axis as a conserved adhesion system that evolved subsequent to integrin-ECM adhesion, likely to enhance the functional complexity of cell-BM interactions in early metazoans.

  7. The evolution of the dystroglycan complex, a major mediator of muscle integrity.

    Science.gov (United States)

    Adams, Josephine C; Brancaccio, Andrea

    2015-08-28

    Basement membrane (BM) extracellular matrices are crucial for the coordination of different tissue layers. A matrix adhesion receptor that is important for BM function and stability in many mammalian tissues is the dystroglycan (DG) complex. This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and the transmembrane β-DG, that interacts principally with dystrophin to connect to the actin cytoskeleton. Mutations in dystrophin, DG, or several enzymes that glycosylate α-DG underlie severe forms of human muscular dystrophy. Nonwithstanding the pathophysiological importance of the DG complex and its fundamental interest as a non-integrin system of cell-ECM adhesion, the evolution of DG and its interacting proteins is not understood. We analysed the phylogenetic distribution of DG, its proximal binding partners and key processing enzymes in extant metazoan and relevant outgroups. We identify that DG originated after the divergence of ctenophores from porifera and eumetazoa. The C-terminal half of the DG core protein is highly-conserved, yet the N-terminal region, that includes the laminin-binding region, has undergone major lineage-specific divergences. Phylogenetic analysis based on the C-terminal IG2_MAT_NU region identified three distinct clades corresponding to deuterostomes, arthropods, and mollusks/early-diverging metazoans. Whereas the glycosyltransferases that modify α-DG are also present in choanoflagellates, the DG-binding proteins dystrophin and laminin originated at the base of the metazoa, and DG-associated sarcoglycan is restricted to cnidarians and bilaterians. These findings implicate extensive functional diversification of DG within invertebrate lineages and identify the laminin-DG-dystrophin axis as a conserved adhesion system that evolved subsequent to integrin-ECM adhesion, likely to enhance the functional complexity of cell-BM interactions in early metazoans.

  8. Controlled thermolysis of uranium (alkoxy)siloxy complexes. A route to polymetallic complexes of low-valent uranium

    Energy Technology Data Exchange (ETDEWEB)

    Camp, Clement; Pecaut, Jacques; Mazzanti, Marinella [CEA-Grenoble (France). Lab. de Reconnaissance Ionique et Chimie de Coordination; Kefalidis, Christos E.; Maron, Laurent [Toulouse Univ. (France). LPCNO, CNRS et INSA, UPS

    2013-11-25

    Decomposition into higher species: Intramolecular U{sup III}-mediated homolytic C-O bond cleavage in U{sup III} (alkoxy)siloxy complexes at low temperature and subsequent reduction with KC{sub 8} led to unprecedented polymetallic complexes containing siloxy, silanediolate, and silanetriolate ligands (see example: U green, Si yellow, K blue, O red). Such compounds may be useful precursors to uranium ceramics relevant for catalysis and the storage of spent nuclear fuel. [German] Zerfall in hoehere Spezies: Die intramolekulare U{sup III}-vermittelte homolytische C-O-Spaltung in U{sup III}-(Alkoxy)siloxy-Komplexen bei tiefer Temperatur mit nachfolgender Reduktion mit KC{sub 8} fuehrte zu ungewoehnlichen Polymetallkomplexen mit Siloxy-, Silandiolat- und Silantriolatliganden (siehe Beispiel: U gruen, Si gelb, K blau, O rot). Solche Verbindungen sind nuetzliche Vorstufen von Urankeramiken, die fuer die Katalyse und fuer die Speicherung verbrauchter Kernbrennstoffe wichtig sind.

  9. A Localized Complex of Two Protein Oligomers Controls the Orientation of Cell Polarity.

    Science.gov (United States)

    Perez, Adam M; Mann, Thomas H; Lasker, Keren; Ahrens, Daniel G; Eckart, Michael R; Shapiro, Lucy

    2017-02-28

    Signaling hubs at bacterial cell poles establish cell polarity in the absence of membrane-bound compartments. In the asymmetrically dividing bacterium Caulobacter crescentus, cell polarity stems from the cell cycle-regulated localization and turnover of signaling protein complexes in these hubs, and yet the mechanisms that establish the identity of the two cell poles have not been established. Here, we recapitulate the tripartite assembly of a cell fate signaling complex that forms during the G1-S transition. Using in vivo and in vitro analyses of dynamic polar protein complex formation, we show that a polymeric cell polarity protein, SpmX, serves as a direct bridge between the PopZ polymeric network and the cell fate-directing DivJ histidine kinase. We demonstrate the direct binding between these three proteins and show that a polar microdomain spontaneously assembles when the three proteins are coexpressed heterologously in an Escherichia coli test system. The relative copy numbers of these proteins are essential for complex formation, as overexpression of SpmX in Caulobacter reorganizes the polarity of the cell, generating ectopic cell poles containing PopZ and DivJ. Hierarchical formation of higher-order SpmX oligomers nucleates new PopZ microdomain assemblies at the incipient lateral cell poles, driving localized outgrowth. By comparison to self-assembling protein networks and polar cell growth mechanisms in other bacterial species, we suggest that the cooligomeric PopZ-SpmX protein complex in Caulobacter illustrates a paradigm for coupling cell cycle progression to the controlled geometry of cell pole establishment.IMPORTANCE Lacking internal membrane-bound compartments, bacteria achieve subcellular organization by establishing self-assembling protein-based microdomains. The asymmetrically dividing bacterium Caulobacter crescentus uses one such microdomain to link cell cycle progression to morphogenesis, but the mechanism for the generation of this

  10. Hand-held tools with complex kinematics are efficiently incorporated into movement planning and online control.

    Science.gov (United States)

    Baugh, Lee A; Hoe, Erica; Flanagan, J Randall

    2012-10-01

    Certain hand-held tools alter the mapping between hand motion and motion of the tool end point that must be controlled in order to perform a task. For example, when using a pool cue, the motion of the cue tip is reversed relative to the hand. Previous studies have shown that the time required to initiate a reaching movement (Fernandez-Ruiz J, Wong W, Armstrong IT, Flanagan JR. Behav Brain Res 219: 8-14, 2011), or correct an ongoing reaching movement (Gritsenko V, Kalaska JF. J Neurophysiol 104: 3084-3104, 2010), is prolonged when the mapping between hand motion and motion of a cursor controlled by the hand is reversed. Here we show that these time costs can be significantly reduced when the reversal is instantiated by a virtual hand-held tool. Participants grasped the near end of a virtual tool, consisting of a rod connecting two circles, and moved the end point to displayed targets. In the reversal condition, the rod translated through, and rotated about, a pivot point such that there was a left-right reversal between hand and end point motion. In the nonreversal control, the tool translated with the hand. As expected, when only the two circles were presented, movement initiation and correction times were much longer in the reversal condition. However, when full vision of the tool was provided, the reaction time cost was almost eliminated. These results indicate that tools with complex kinematics can be efficiently incorporated into sensorimotor control mechanisms used in movement planning and online control.

  11. Anticipatory Monitoring and Control of Complex Systems using a Fuzzy based Fusion of Support Vector Regressors

    Energy Technology Data Exchange (ETDEWEB)

    Miltiadis Alamaniotis; Vivek Agarwal

    2014-10-01

    This paper places itself in the realm of anticipatory systems and envisions monitoring and control methods being capable of making predictions over system critical parameters. Anticipatory systems allow intelligent control of complex systems by predicting their future state. In the current work, an intelligent model aimed at implementing anticipatory monitoring and control in energy industry is presented and tested. More particularly, a set of support vector regressors (SVRs) are trained using both historical and observed data. The trained SVRs are used to predict the future value of the system based on current operational system parameter. The predicted values are then inputted to a fuzzy logic based module where the values are fused to obtain a single value, i.e., final system output prediction. The methodology is tested on real turbine degradation datasets. The outcome of the approach presented in this paper highlights the superiority over single support vector regressors. In addition, it is shown that appropriate selection of fuzzy sets and fuzzy rules plays an important role in improving system performance.

  12. TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis.

    Science.gov (United States)

    Baker, Karen; Kirkham, Sara; Halova, Lenka; Atkin, Jane; Franz-Wachtel, Mirita; Cobley, David; Krug, Karsten; Maček, Boris; Mulvihill, Daniel P; Petersen, Janni

    2016-07-01

    The timing of cell division is controlled by the coupled regulation of growth and division. The target of rapamycin (TOR) signalling network synchronises these processes with the environmental setting. Here, we describe a novel interaction of the fission yeast TOR complex 2 (TORC2) with the cytokinetic actomyosin ring (CAR), and a novel role for TORC2 in regulating the timing and fidelity of cytokinesis. Disruption of TORC2 or its localisation results in defects in CAR morphology and constriction. We provide evidence that the myosin II protein Myp2 and the myosin V protein Myo51 play roles in recruiting TORC2 to the CAR. We show that Myp2 and TORC2 are co-dependent upon each other for their normal localisation to the cytokinetic machinery. We go on to show that TORC2-dependent phosphorylation of actin-capping protein 1 (Acp1, a known regulator of cytokinesis) controls CAR stability, modulates Acp1-Acp2 (the equivalent of the mammalian CAPZA-CAPZB) heterodimer formation and is essential for survival upon stress. Thus, TORC2 localisation to the CAR, and TORC2-dependent Acp1 phosphorylation contributes to timely control and the fidelity of cytokinesis and cell division.

  13. Dynamic complexities in a pest control model with birth pulse and harvesting

    Energy Technology Data Exchange (ETDEWEB)

    Goel, A., E-mail: goelanju23@gmail.com; Gakkhar, S., E-mail: sungkfma@iitr.ernet.in [Department of Mathematics, Indian Institute of Technology, Roorkee, Uttarakhand 247667 (India)

    2016-04-06

    In this paper, an impulsive model is discussed for an integrated pest management approach comprising of chemical and mechanical controls. The pesticides and harvesting are used to control the stage-structured pest population. The mature pest give birth to immature pest in pulses at regular intervals. The pest is controlled by spraying chemical pesticides affecting immature as well as mature pest. The harvesting of both immature and mature pest further reduce the pest population. The discrete dynamical system obtained from stroboscopic map is analyzed. The threshold conditions for stability of pest-free state as well as non-trivial period-1 solution is obtained. The effect of pesticide spray timing and harvesting on immature as well as mature pest are shown. Finally, by numerical simulation with MATLAB, the dynamical behaviors of the model is found to be complex. Above the threshold level there is a characteristic sequence of bifurcations leading to chaotic dynamics. Route to chaos is found to be period-doubling. Period halving bifurcations are also observed.

  14. Congestion Control for a Fair Packet Delivery in WSN: From a Complex System Perspective

    Directory of Open Access Journals (Sweden)

    Daniela Aguirre-Guerrero

    2014-01-01

    Full Text Available In this work, we propose that packets travelling across a wireless sensor network (WSN can be seen as the active agents that make up a complex system, just like a bird flock or a fish school, for instance. From this perspective, the tools and models that have been developed to study this kind of systems have been applied. This is in order to create a distributed congestion control based on a set of simple rules programmed at the nodes of the WSN. Our results show that it is possible to adapt the carried traffic to the network capacity, even under stressing conditions. Also, the network performance shows a smooth degradation when the traffic goes beyond a threshold which is settled by the proposed self-organized control. In contrast, without any control, the network collapses before this threshold. The use of the proposed solution provides an effective strategy to address some of the common problems found in WSN deployment by providing a fair packet delivery. In addition, the network congestion is mitigated using adaptive traffic mechanisms based on a satisfaction parameter assessed by each packet which has impact on the global satisfaction of the traffic carried by the WSN.

  15. AIR POLLUTION INVESTIGATION AND PROVIDING SYSTEM OF CONTROL IN KHORASAN STEEL COMPLEX

    Directory of Open Access Journals (Sweden)

    J. Nouri

    1999-12-01

    Full Text Available The most important environmental pollutant in steel industry is air pollution due to the process of its products. Optimise sitting for this industry, in a great extend will prevent pollutants and emissions. Khorasan Steel Company is located near some populous villages and three rivers. It is necessary to perform an investigation for providing abatement and control of air pollution, in time of planning and manufacturing of control instruments. The manufacturing company has determined air pollution reduction instruments in this site, according to the emission suspended particulate and its climatic conditions. The air pollution reducer's instruments were used back-fither. But, this offer was not agreed by the Department of the Environment of Iran. Perhaps, this disagreement was announced just for another original problem, which was the site selection of plants. This research was on the filtration which has been offered by the manufacturing company, if this selection can improve the future regional air pollution. These figures, of course, were obtained from the present data and plume rise particulate, considering Gausian distribution mode for all the rural population and rivers rounding to the site, up to 5 km. The results showed that the produced particulates were less than permissible limit and the proposed methods will improve the complex air pollution difficulties So, the proposed methods were provided for increasing the control and operating the system for conducting of cyclone before input of particulate to the back-filter.

  16. Congestion control for a fair packet delivery in WSN: from a complex system perspective.

    Science.gov (United States)

    Aguirre-Guerrero, Daniela; Marcelín-Jiménez, Ricardo; Rodriguez-Colina, Enrique; Pascoe-Chalke, Michael

    2014-01-01

    In this work, we propose that packets travelling across a wireless sensor network (WSN) can be seen as the active agents that make up a complex system, just like a bird flock or a fish school, for instance. From this perspective, the tools and models that have been developed to study this kind of systems have been applied. This is in order to create a distributed congestion control based on a set of simple rules programmed at the nodes of the WSN. Our results show that it is possible to adapt the carried traffic to the network capacity, even under stressing conditions. Also, the network performance shows a smooth degradation when the traffic goes beyond a threshold which is settled by the proposed self-organized control. In contrast, without any control, the network collapses before this threshold. The use of the proposed solution provides an effective strategy to address some of the common problems found in WSN deployment by providing a fair packet delivery. In addition, the network congestion is mitigated using adaptive traffic mechanisms based on a satisfaction parameter assessed by each packet which has impact on the global satisfaction of the traffic carried by the WSN.

  17. Dynamic complexities in a pest control model with birth pulse and harvesting

    Science.gov (United States)

    Goel, A.; Gakkhar, S.

    2016-04-01

    In this paper, an impulsive model is discussed for an integrated pest management approach comprising of chemical and mechanical controls. The pesticides and harvesting are used to control the stage-structured pest population. The mature pest give birth to immature pest in pulses at regular intervals. The pest is controlled by spraying chemical pesticides affecting immature as well as mature pest. The harvesting of both immature and mature pest further reduce the pest population. The discrete dynamical system obtained from stroboscopic map is analyzed. The threshold conditions for stability of pest-free state as well as non-trivial period-1 solution is obtained. The effect of pesticide spray timing and harvesting on immature as well as mature pest are shown. Finally, by numerical simulation with MATLAB, the dynamical behaviors of the model is found to be complex. Above the threshold level there is a characteristic sequence of bifurcations leading to chaotic dynamics. Route to chaos is found to be period-doubling. Period halving bifurcations are also observed.

  18. Rapid characterization and quality control of complex cell culture media solutions using raman spectroscopy and chemometrics.

    Science.gov (United States)

    Li, Boyan; Ryan, Paul W; Ray, Bryan H; Leister, Kirk J; Sirimuthu, Narayana M S; Ryder, Alan G

    2010-10-01

    The use of Raman spectroscopy coupled with chemometrics for the rapid identification, characterization, and quality assessment of complex cell culture media components used for industrial mammalian cell culture was investigated. Raman spectroscopy offers significant advantages for the analysis of complex, aqueous-based materials used in biotechnology because there is no need for sample preparation and water is a weak Raman scatterer. We demonstrate the efficacy of the method for the routine analysis of dilute aqueous solution of five different chemically defined (CD) commercial media components used in a Chinese Hamster Ovary (CHO) cell manufacturing process for recombinant proteins.The chemometric processing of the Raman spectral data is the key factor in developing robust methods. Here, we discuss the optimum methods for eliminating baseline drift, background fluctuations, and other instrumentation artifacts to generate reproducible spectral data. Principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA) were then employed in the development of a robust routine for both identification and quality evaluation of the five different media components. These methods have the potential to be extremely useful in an industrial context for "in-house" sample handling, tracking, and quality control.

  19. FROM MANUFACTURING SCHEDULING TO SUPPLY CHAIN COORDINATION:THE CONTROL OF COMPLEXITY AND UNCERTAINTY

    Institute of Scientific and Technical Information of China (English)

    Peter B. LUH; Weidong FENG

    2003-01-01

    With time-based competition and rapid technology advancements, effective manufacturing scheduling and supply chain coordination are critical to quickly respond to changing market conditions. These problems, however, are difficult in view of inherent complexity and various uncertainties involved. Based on a series of results by the authors, decomposition and coordination by using Lagrangian relaxation is identified in this paper as an effective way to control complexity and uncertainty. A manufacturing scheduling problem is first formulated within the job shop context with uncertain order arrivals, processing times, due dates, and part priorities as a separable optimization problem. A solution methodology that combines Lagrangian relaxation, stochastic dynamic programming, and heuristics is developed. Method improvements to effectively solve large problems are also highlighted. To extend manufacturing scheduling within a factory to coordinate autonomic members across chains of suppliers, a decentralized supply chain model is established in the second half of this paper. By relaxing cross-member constraints, the model is decomposed into member-wise subproblems, and a nested optimization structure is developed based on the job shop scheduling results. Coordination is performed through the iterative updating of cross-member prices without accessing other members' private information or intruding their decision-making authorities, either with or without a coordinator. Two examples are presented to demonstrate the effectiveness of the method. Future prospects to overcome problem inseparability and improve computing efficiency are then discussed.

  20. The Anaphase-Promoting Complex/Cyclosome in Control of Plant Development

    Institute of Scientific and Technical Information of China (English)

    Jefri Heyman; Lieven De Veylder

    2012-01-01

    Temporal controlled degradation of key cell division proteins ensures a correct onset of the different cell cycle phases and exit from the cell division program.In light of the cell cycle,the Anaphase-Promoting Complex/Cyclosome (APC/C) is an important conserved multi-subunit ubiquitin ligase,marking targets for degradation by the 26S proteasome.However,whereas the APC/C has been studied extensively in yeast and mammals,only in the last decade has the plant APC/C started to unveil its secrets.Research results have shown the importance of the APC/C core complex and its activators during gametogenesis,growth,hormone signaling,symbiotic interactions,and endoreduplication onset.In addition,recently,the first plant APC/C inhibitors have been reported,allowing a fine-tuning of APC/C activity during the cell cycle.Together with the identification of the first APC/C targets,a picture emerges of APC/C activity being essential for many different developmental processes.