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Sample records for dystrophin complex controls

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

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

    2000-08-01

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

  2. 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.

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

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

    2009-07-17

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

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

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

    2003-01-01

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

  5. 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.

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

    2016-01-01

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

  7. 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

  8. 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.

  9. 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.

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

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

    2015-09-08

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

  11. 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.

  12. 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.

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

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

    2018-01-01

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

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

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

    2018-02-01

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

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

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

    2017-03-04

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

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

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

    2006-01-01

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

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

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    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.

  18. Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

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

    2017-01-01

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

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

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

    2011-12-01

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

  20. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

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

    2010-01-01

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

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

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    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.

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

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    Elena Bassi

    2012-01-01

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

  3. 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...

  4. A Cryo Complex Control

    CERN Document Server

    Alferov, V; Fedorchenko, V; Ivanova, N; Kholkin, A; Klimov, S; Krendelev, V; Kuznetsov, S; Lukyantsev, A; Lutchev, A; Milutkin, V; Sytin, A N; Vasilev, D

    2004-01-01

    A Cryogenic complex is being constructed to provide by liquid helium and nitrogen the RF-separator of kaons. About 500 parameters including temperature (1,8…300)K, liquid helium/nitrogen level, vacuum, 300 digital signals have to be measured, 70 commands generated, 20 closed loops activated. The paper describes controls electronics which includes home made I8051 compatible controllers connected by the CAN field bus to a bus controller and interface electronic modules for: - temperature measurements; - liquid Ni and He level measurements; - vacuum pumps current measurements; - analog and digital signals measurements and generations. The modules are tested together with signal imitators within a vertical slice of the Control System based on EPICS tools.

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kevin J Sonnemann

    2009-05-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  8. 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 ......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...

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

    Science.gov (United States)

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

    2015-03-01

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

  10. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    Science.gov (United States)

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

    2010-01-01

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

  11. Decentralized control of complex systems

    CERN Document Server

    Siljak, Dragoslav D

    2011-01-01

    Complex systems require fast control action in response to local input, and perturbations dictate the use of decentralized information and control structures. This much-cited reference book explores the approaches to synthesizing control laws under decentralized information structure constraints.Starting with a graph-theoretic framework for structural modeling of complex systems, the text presents results related to robust stabilization via decentralized state feedback. Subsequent chapters explore optimization, output feedback, the manipulative power of graphs, overlapping decompositions and t

  12. 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…

  13. Complexity control in statistical learning

    Indian Academy of Sciences (India)

    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.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  16. Advanced nuclear plant control complex

    International Nuclear Information System (INIS)

    Scarola, K.; Jamison, S.; Manazir, R.M.; Rescorl, R.L.; Harmon, D.L.

    1991-01-01

    An advanced control room complex for a nuclear power plant, including a discrete indicator and alarm system which is nuclear qualified for rapid response to changes in plant parameters and a component control system which together provide a discrete monitoring and control capability at a panel in the control room. A separate data processing system, which need not be nuclear qualified, provides integrated and overview information to the control room and to each panel, through CRTs and a large, overhead integrated process status overview board. The discrete indicator and alarm system and the data processing system receive inputs from common plant sensors and validate the sensor outputs to arrive at a representative value of the parameter for use by the operator during both normal and accidental conditions, thereby avoiding the need for him to assimilate data from each sensor individually. The integrated process status board is at the apex of an information hierarchy that extends through four levels and provides access at each panel to the full display hierarchy. The control room panels are preferably of a modular construction, permitting the definition of inputs and outputs, the man machine interface, and the plant specific algorithms, to proceed in parallel with the fabrication of the panels, the installation of the equipment and the generic testing thereof. (author)

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

    Indian Academy of Sciences (India)

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

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

    Science.gov (United States)

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

    2018-03-01

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

  19. 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.

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Dejia Li

    2010-12-01

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

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

    Science.gov (United States)

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

    2011-11-01

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

  3. Complexity control in statistical learning

    Indian Academy of Sciences (India)

    complexity of the class of models from which we are to choose our model. In this ... As is explained in §2, we use the concept of covering numbers to quantify the complexity of a class of ..... called structural risk minimization (SRM). Vapnik ...

  4. Model complexity control for hydrologic prediction

    NARCIS (Netherlands)

    Schoups, G.; Van de Giesen, N.C.; Savenije, H.H.G.

    2008-01-01

    A common concern in hydrologic modeling is overparameterization of complex models given limited and noisy data. This leads to problems of parameter nonuniqueness and equifinality, which may negatively affect prediction uncertainties. A systematic way of controlling model complexity is therefore

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  6. Identification of new dystroglycan complexes in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Eric K Johnson

    Full Text Available The dystroglycan complex contains the transmembrane protein β-dystroglycan and its interacting extracellular mucin-like protein α-dystroglycan. In skeletal muscle fibers, the dystroglycan complex plays an important structural role by linking the cytoskeletal protein dystrophin to laminin in the extracellular matrix. Mutations that affect any of the proteins involved in this structural axis lead to myofiber degeneration and are associated with muscular dystrophies and congenital myopathies. Because loss of dystrophin in Duchenne muscular dystrophy (DMD leads to an almost complete loss of dystroglycan complexes at the myofiber membrane, it is generally assumed that the vast majority of dystroglycan complexes within skeletal muscle fibers interact with dystrophin. The residual dystroglycan present in dystrophin-deficient muscle is thought to be preserved by utrophin, a structural homolog of dystrophin that is up-regulated in dystrophic muscles. However, we found that dystroglycan complexes are still present at the myofiber membrane in the absence of both dystrophin and utrophin. Our data show that only a minority of dystroglycan complexes associate with dystrophin in wild type muscle. Furthermore, we provide evidence for at least three separate pools of dystroglycan complexes within myofibers that differ in composition and are differentially affected by loss of dystrophin. Our findings indicate a more complex role of dystroglycan in muscle than currently recognized and may help explain differences in disease pathology and severity among myopathies linked to mutations in DAPC members.

  7. 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

  8. Predicting and Controlling Complex Networks

    Science.gov (United States)

    2015-06-22

    ubiquitous in nature and fundamental to evolution in ecosystems. However, a significant chal- lenge remains in understanding biodiversity since, by the...networks and control . . . . . . . . . . . . . . . . . . . 7 3.4 Pattern formation, synchronization and outbreak of biodiversity in cyclically...Ni, Y.-C. Lai, and C. Grebogi, “Pattern formation, synchronization and outbreak of biodiversity in cyclically competing games,” Physical Review E 83

  9. 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.

  10. Pinning impulsive control algorithms for complex network

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  11. Synchronizability on complex networks via pinning control

    Indian Academy of Sciences (India)

    Keywords. Complex network; the pinning synchronization; synchronizability. ... 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 ...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Batchelor, Clare L; Winder, Steve J

    2006-04-01

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

  14. 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.

  15. 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.

  16. 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.

  17. Spectrum of small mutations in the dystrophin coding region

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-07-01

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

  18. Subjective task complexity in the control room

    International Nuclear Information System (INIS)

    Braarud, Per Oeivind

    2000-05-01

    Understanding of what makes a control room situation difficult to handle is important when studying operator performance, both with respect to prediction as well as improvement of the human performance. Previous exploratory work on complexity showed a potential for prediction and explanation of operator performance. This report investigates in further detail the theoretical background and the structure of operator rated task complexity. The report complements the previous work on complexity to make a basis for development of operator performance analysis tools. The first part of the report outlines an approach for studying the complexity of the control room crew's work. The approach draws upon man-machine research as well as problem solving research. The approach identifies five complexity-shaping components: 'task work characteristics', 'teamwork characteristics', 'individual skill', 'teamwork skill', and 'interface and support systems'. The crew's work complexity is related to concepts of human performance quality and human error. The second part of the report is a post-hoc exploratory analysis of four empirical HRP studies, where operators' conception of the complexity of control room work is assessed by questionnaires. The analysis deals with the structure of complexity questionnaire ratings, and the relationship between complexity ratings and human performance measures. The main findings from the analysis of structure was the identification of three task work factors which were named Masking, Information load and Temporal demand, and in addition the identification of one interface factor which was named Navigation. Post-hoc analysis suggests that operator's subjective complexity, which was assessed by questionnaires, is related to workload, task and system performance, and operator's self-rated performance. (Author). 28 refs., 47 tabs

  19. Control of complex physically simulated robot groups

    Science.gov (United States)

    Brogan, David C.

    2001-10-01

    Actuated systems such as robots take many forms and sizes but each requires solving the difficult task of utilizing available control inputs to accomplish desired system performance. Coordinated groups of robots provide the opportunity to accomplish more complex tasks, to adapt to changing environmental conditions, and to survive individual failures. Similarly, groups of simulated robots, represented as graphical characters, can test the design of experimental scenarios and provide autonomous interactive counterparts for video games. The complexity of writing control algorithms for these groups currently hinders their use. A combination of biologically inspired heuristics, search strategies, and optimization techniques serve to reduce the complexity of controlling these real and simulated characters and to provide computationally feasible solutions.

  20. Controlling extreme events on complex networks

    Science.gov (United States)

    Chen, Yu-Zhong; Huang, Zi-Gang; Lai, Ying-Cheng

    2014-08-01

    Extreme events, a type of collective behavior in complex networked dynamical systems, often can have catastrophic consequences. To develop effective strategies to control extreme events is of fundamental importance and practical interest. Utilizing transportation dynamics on complex networks as a prototypical setting, we find that making the network ``mobile'' can effectively suppress extreme events. A striking, resonance-like phenomenon is uncovered, where an optimal degree of mobility exists for which the probability of extreme events is minimized. We derive an analytic theory to understand the mechanism of control at a detailed and quantitative level, and validate the theory numerically. Implications of our finding to current areas such as cybersecurity are discussed.

  1. Chaotification of complex networks with impulsive control.

    Science.gov (United States)

    Guan, Zhi-Hong; Liu, Feng; Li, Juan; Wang, Yan-Wu

    2012-06-01

    This paper investigates the chaotification problem of complex dynamical networks (CDN) with impulsive control. Both the discrete and continuous cases are studied. The method is presented to drive all states of every node in CDN to chaos. The proposed impulsive control strategy is effective for both the originally stable and unstable CDN. The upper bound of the impulse intervals for originally stable networks is derived. Finally, the effectiveness of the theoretical results is verified by numerical examples.

  2. Pinning impulsive control algorithms for complex network

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Wen [School of Information and Mathematics, Yangtze University, Jingzhou 434023 (China); Lü, Jinhu [Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190 (China); Chen, Shihua [College of Mathematics and Statistics, Wuhan University, Wuhan 430072 (China); Yu, Xinghuo [School of Electrical and Computer Engineering, RMIT University, Melbourne VIC 3001 (Australia)

    2014-03-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Sue Fletcher

    2012-01-01

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

  4. 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

  5. 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.

  6. 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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arpana Sali

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-11-01

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

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

    Science.gov (United States)

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

    2013-09-24

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

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

    Directory of Open Access Journals (Sweden)

    HaiFang Yin

    2013-01-01

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

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Jennifer England

    2017-07-01

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

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

    Science.gov (United States)

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

    2017-07-07

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Miller Jeffrey

    2005-04-01

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

  17. 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

    2016-10-11

    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.

  18. Assembly and control of large microtubule complexes

    Science.gov (United States)

    Korolev, Kirill; Ishihara, Keisuke; Mitchison, Timothy

    Motility, division, and other cellular processes require rapid assembly and disassembly of microtubule structures. We report a new mechanism for the formation of asters, radial microtubule complexes found in very large cells. The standard model of aster growth assumes elongation of a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we found evidence for microtubule nucleation away from centrosomes. By combining polymerization dynamics and auto-catalytic nucleation of microtubules, we developed a new biophysical model of aster growth. The model predicts an explosive transition from an aster with a steady-state radius to one that expands as a travelling wave. At the transition, microtubule density increases continuously, but aster growth rate discontinuously jumps to a nonzero value. We tested our model with biochemical perturbations in egg extract and confirmed main theoretical predictions including the jump in the growth rate. Our results show that asters can grow even though individual microtubules are short and unstable. The dynamic balance between microtubule collapse and nucleation could be a general framework for the assembly and control of large microtubule complexes. NIH GM39565; Simons Foundation 409704; Honjo International 486 Scholarship Foundation.

  19. Supervisory control for a complex robotic system

    International Nuclear Information System (INIS)

    Miller, D.J.

    1988-01-01

    The Robotic Radiation Survey and Analysis System investigates the use of advanced robotic technology for performing remote radiation surveys on nuclear waste shipping casks. Robotic systems have the potential for reducing personnel exposure to radiation and providing fast reliable throughput at future repository sites. A primary technology issue is the integrated control of distributed specialized hardware through a modular supervisory software system. Automated programming of robot trajectories based upon mathematical models of the cask and robot coupled with sensory feedback enables flexible operation of a commercial gantry robot with the reliability needed to perform autonomous operations in a hazardous environment. Complexity is managed using structured software engineering techniques resulting in the generation of reusable command primitives which contribute to a software parts catalog for a generalized robot programming language

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

    Science.gov (United States)

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

    2015-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  2. Control of multidimensional systems on complex network

    Science.gov (United States)

    Bagnoli, Franco; Battistelli, Giorgio; Chisci, Luigi; Fanelli, Duccio

    2017-01-01

    Multidimensional systems coupled via complex networks are widespread in nature and thus frequently invoked for a large plethora of interesting applications. From ecology to physics, individual entities in mutual interactions are grouped in families, homogeneous in kind. These latter interact selectively, through a sequence of self-consistently regulated steps, whose deeply rooted architecture is stored in the assigned matrix of connections. The asymptotic equilibrium eventually attained by the system, and its associated stability, can be assessed by employing standard nonlinear dynamics tools. For many practical applications, it is however important to externally drive the system towards a desired equilibrium, which is resilient, hence stable, to external perturbations. To this end we here consider a system made up of N interacting populations which evolve according to general rate equations, bearing attributes of universality. One species is added to the pool of interacting families and used as a dynamical controller to induce novel stable equilibria. Use can be made of the root locus method to shape the needed control, in terms of intrinsic reactivity and adopted protocol of injection. The proposed method is tested on both synthetic and real data, thus enabling to demonstrate its robustness and versatility. PMID:28892493

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

    Science.gov (United States)

    2016-09-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrea R. Durrant

    2012-06-01

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

  6. 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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Fernanda P Prado

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

  10. 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.

  11. 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.

  12. 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

  13. Adaptive control for a class of nonlinear complex dynamical systems with uncertain complex parameters and perturbations.

    Directory of Open Access Journals (Sweden)

    Jian Liu

    Full Text Available In this paper, adaptive control is extended from real space to complex space, resulting in a new control scheme for a class of n-dimensional time-dependent strict-feedback complex-variable chaotic (hyperchaotic systems (CVCSs in the presence of uncertain complex parameters and perturbations, which has not been previously reported in the literature. In detail, we have developed a unified framework for designing the adaptive complex scalar controller to ensure this type of CVCSs asymptotically stable and for selecting complex update laws to estimate unknown complex parameters. In particular, combining Lyapunov functions dependent on complex-valued vectors and back-stepping technique, sufficient criteria on stabilization of CVCSs are derived in the sense of Wirtinger calculus in complex space. Finally, numerical simulation is presented to validate our theoretical results.

  14. Adaptive control for a class of nonlinear complex dynamical systems with uncertain complex parameters and perturbations.

    Science.gov (United States)

    Liu, Jian; Liu, Kexin; Liu, Shutang

    2017-01-01

    In this paper, adaptive control is extended from real space to complex space, resulting in a new control scheme for a class of n-dimensional time-dependent strict-feedback complex-variable chaotic (hyperchaotic) systems (CVCSs) in the presence of uncertain complex parameters and perturbations, which has not been previously reported in the literature. In detail, we have developed a unified framework for designing the adaptive complex scalar controller to ensure this type of CVCSs asymptotically stable and for selecting complex update laws to estimate unknown complex parameters. In particular, combining Lyapunov functions dependent on complex-valued vectors and back-stepping technique, sufficient criteria on stabilization of CVCSs are derived in the sense of Wirtinger calculus in complex space. Finally, numerical simulation is presented to validate our theoretical results.

  15. 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.

  16. 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.

  17. 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

    1994-12-31

    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.

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-06-01

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

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

    Science.gov (United States)

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

    2018-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-06-01

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

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lluís Sánchez

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

  5. 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.

  6. Operational Assessment of Controller Complexity, Phase I

    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...

  7. 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...

  8. Complex Projective Synchronization in Drive-Response Stochastic Complex Networks by Impulsive Pinning Control

    Directory of Open Access Journals (Sweden)

    Xuefei Wu

    2014-01-01

    Full Text Available The complex projective synchronization in drive-response stochastic coupled networks with complex-variable systems is considered. The impulsive pinning control scheme is adopted to achieve complex projective synchronization and several simple and practical sufficient conditions are obtained in a general drive-response network. In addition, the adaptive feedback algorithms are proposed to adjust the control strength. Several numerical simulations are provided to show the effectiveness and feasibility of the proposed methods.

  9. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  11. 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...

  12. 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 ...

  13. 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

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

    Science.gov (United States)

    Eide, P K; Hansson, H-A

    2017-06-19

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

  15. Automated Diagnosis and Control of Complex Systems

    Science.gov (United States)

    Kurien, James; Plaunt, Christian; Cannon, Howard; Shirley, Mark; Taylor, Will; Nayak, P.; Hudson, Benoit; Bachmann, Andrew; Brownston, Lee; Hayden, Sandra; hide

    2007-01-01

    Livingstone2 is a reusable, artificial intelligence (AI) software system designed to assist spacecraft, life support systems, chemical plants, or other complex systems by operating with minimal human supervision, even in the face of hardware failures or unexpected events. The software diagnoses the current state of the spacecraft or other system, and recommends commands or repair actions that will allow the system to continue operation. Livingstone2 is an enhancement of the Livingstone diagnosis system that was flight-tested onboard the Deep Space One spacecraft in 1999. This version tracks multiple diagnostic hypotheses, rather than just a single hypothesis as in the previous version. It is also able to revise diagnostic decisions made in the past when additional observations become available. In such cases, Livingstone might arrive at an incorrect hypothesis. Re-architecting and re-implementing the system in C++ has increased performance. Usability has been improved by creating a set of development tools that is closely integrated with the Livingstone2 engine. In addition to the core diagnosis engine, Livingstone2 includes a compiler that translates diagnostic models written in a Java-like language into Livingstone2's language, and a broad set of graphical tools for model development.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Aziza Sbiti

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kane L Greer

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Susi Zatti

    2014-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

  1. Enabling Controlling Complex Networks with Local Topological Information.

    Science.gov (United States)

    Li, Guoqi; Deng, Lei; Xiao, Gaoxi; Tang, Pei; Wen, Changyun; Hu, Wuhua; Pei, Jing; Shi, Luping; Stanley, H Eugene

    2018-03-15

    Complex networks characterize the nature of internal/external interactions in real-world systems including social, economic, biological, ecological, and technological networks. Two issues keep as obstacles to fulfilling control of large-scale networks: structural controllability which describes the ability to guide a dynamical system from any initial state to any desired final state in finite time, with a suitable choice of inputs; and optimal control, which is a typical control approach to minimize the cost for driving the network to a predefined state with a given number of control inputs. For large complex networks without global information of network topology, both problems remain essentially open. Here we combine graph theory and control theory for tackling the two problems in one go, using only local network topology information. For the structural controllability problem, a distributed local-game matching method is proposed, where every node plays a simple Bayesian game with local information and local interactions with adjacent nodes, ensuring a suboptimal solution at a linear complexity. Starring from any structural controllability solution, a minimizing longest control path method can efficiently reach a good solution for the optimal control in large networks. Our results provide solutions for distributed complex network control and demonstrate a way to link the structural controllability and optimal control together.

  2. Practical synchronization on complex dynamical networks via optimal pinning control

    Science.gov (United States)

    Li, Kezan; Sun, Weigang; Small, Michael; Fu, Xinchu

    2015-07-01

    We consider practical synchronization on complex dynamical networks under linear feedback control designed by optimal control theory. The control goal is to minimize global synchronization error and control strength over a given finite time interval, and synchronization error at terminal time. By utilizing the Pontryagin's minimum principle, and based on a general complex dynamical network, we obtain an optimal system to achieve the control goal. The result is verified by performing some numerical simulations on Star networks, Watts-Strogatz networks, and Barabási-Albert networks. Moreover, by combining optimal control and traditional pinning control, we propose an optimal pinning control strategy which depends on the network's topological structure. Obtained results show that optimal pinning control is very effective for synchronization control in real applications.

  3. 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 ...

  4. 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

  5. A new main control room for the AGS complex

    International Nuclear Information System (INIS)

    Ingrassia, P.F.; Zaharatos, R.M.; Dyling, O.H.

    1991-01-01

    A new Main Control Room (MCR) has been built to control the accelerators of the AGS Complex. A new physical environment was produced to better control light, sound, temperature, and traffic. New control consoles were built around the work-stations that make up the distributed control system. Equipment placement within consoles and console placement within the room reflect attention to the ''human factors'' needs of the operator. 1 ref., 2 figs

  6. A new Main Control Room for the AGS complex

    International Nuclear Information System (INIS)

    Ingrassia, P.F.; Zaharatos, R.M.; Dyling, O.H.

    1991-01-01

    A new Main Control Room (MCR) has been built to control the accelerators of the AGS Complex. A new physical environment was produced to better control light, sound, temperature, and traffic. New control consoles were built around the work-stations that make up the distributed control system. Equipment placement within consoles and console placement within the room reflect attention to the 'human factors' needs of the operator

  7. Complex regulation controls Neurogenin3 proteolysis

    Directory of Open Access Journals (Sweden)

    Ryan Roark

    2012-10-01

    The ubiquitin proteasome system (UPS is known to be responsible for the rapid turnover of many transcription factors, where half-life is held to be critical for regulation of transcriptional activity. However, the stability of key transcriptional regulators of development is often very poorly characterised. Neurogenin 3 (Ngn3 is a basic helix–loop–helix transcription factor that plays a central role in specification and differentiation of endocrine cells of the pancreas and gut, as well as spermatogonia and regions of the brain. Here we demonstrate that Ngn3 protein stability is regulated by the ubiquitin proteasome system and that Ngn3 can be ubiquitylated on lysines, the N-terminus and, highly unusually, on non-canonical residues including cysteines and serines/threonines. Rapid turnover of Ngn3 is regulated both by binding to its heterodimeric partner E protein and by the presence of cdk inhibitors. We show that protein half-life does appear to regulate the activity of Ngn3 in vivo, but, unlike the related transcription factor c-myc, ubiquitylation on canonical sites is not a requirement for transcriptional activity of Ngn3. Hence, we characterise an important new level of Ngn3 post-translational control, which may regulate its transcriptional activity.

  8. ANS main control complex three-dimensional computer model development

    International Nuclear Information System (INIS)

    Cleaves, J.E.; Fletcher, W.M.

    1993-01-01

    A three-dimensional (3-D) computer model of the Advanced Neutron Source (ANS) main control complex is being developed. The main control complex includes the main control room, the technical support center, the materials irradiation control room, computer equipment rooms, communications equipment rooms, cable-spreading rooms, and some support offices and breakroom facilities. The model will be used to provide facility designers and operations personnel with capabilities for fit-up/interference analysis, visual ''walk-throughs'' for optimizing maintain-ability, and human factors and operability analyses. It will be used to determine performance design characteristics, to generate construction drawings, and to integrate control room layout, equipment mounting, grounding equipment, electrical cabling, and utility services into ANS building designs. This paper describes the development of the initial phase of the 3-D computer model for the ANS main control complex and plans for its development and use

  9. Mental Models and the Control of Actions in Complex Environments

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1987-01-01

    of human activities. The need for analysis of complex work scenarios is discussed, together with the necessity of considering several levels of cognitive control depending upon different kinds of internal representations. The development of mental representations during learning and adaptation...

  10. 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.

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

    Science.gov (United States)

    Nik-Ahd, Farnoosh; Bertoni, Carmen

    2014-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-05-10

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

  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. Finger functionality and joystick design for complex hand control

    NARCIS (Netherlands)

    Grinten, M.P. van der; Krause, F.

    2006-01-01

    Joysticks and similar multi-directional controls are increasingly applied in machines, instruments and consumer goods. Operational complexity rises through miniaturization and additional control functions on the joystick. With this the effort for the finger, hand and arm, and for the perceptive and

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

    Science.gov (United States)

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

    2017-10-31

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

  16. Optimal Control of Interdependent Epidemics in Complex Networks

    OpenAIRE

    Chen, Juntao; Zhang, Rui; Zhu, Quanyan

    2017-01-01

    Optimal control of interdependent epidemics spreading over complex networks is a critical issue. We first establish a framework to capture the coupling between two epidemics, and then analyze the system's equilibrium states by categorizing them into three classes, and deriving their stability conditions. The designed control strategy globally optimizes the trade-off between the control cost and the severity of epidemics in the network. A gradient descent algorithm based on a fixed point itera...

  17. Automated complex for research of electric drives control

    Science.gov (United States)

    Avlasko, P. V.; Antonenko, D. A.

    2018-05-01

    In the article, the automated complex intended for research of various control modes of electric motors including the inductor motor of double-way feed is described. As a basis of the created complex, the National Instruments platform is chosen. The operating controller built in a platform is delivered with an operating system of real-time for creation of systems of measurement and management. The software developed in the environment of LabVIEW consists of several connected modules which are in different elements of a complex. Besides the software for automated management by experimental installation, the program complex is developed for modelling of processes in the electric drive. As a result there is an opportunity to compare simulated and received experimentally transitional characteristics of the electric drive in various operating modes.

  18. 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/.

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

    Directory of Open Access Journals (Sweden)

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

    2014-04-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-02-01

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

  2. 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.

  3. Effective control of complex turbulent dynamical systems through statistical functionals.

    Science.gov (United States)

    Majda, Andrew J; Qi, Di

    2017-05-30

    Turbulent dynamical systems characterized by both a high-dimensional phase space and a large number of instabilities are ubiquitous among complex systems in science and engineering, including climate, material, and neural science. Control of these complex systems is a grand challenge, for example, in mitigating the effects of climate change or safe design of technology with fully developed shear turbulence. Control of flows in the transition to turbulence, where there is a small dimension of instabilities about a basic mean state, is an important and successful discipline. In complex turbulent dynamical systems, it is impossible to track and control the large dimension of instabilities, which strongly interact and exchange energy, and new control strategies are needed. The goal of this paper is to propose an effective statistical control strategy for complex turbulent dynamical systems based on a recent statistical energy principle and statistical linear response theory. We illustrate the potential practical efficiency and verify this effective statistical control strategy on the 40D Lorenz 1996 model in forcing regimes with various types of fully turbulent dynamics with nearly one-half of the phase space unstable.

  4. 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.

  5. 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...

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

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

    OpenAIRE

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

    2003-01-01

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

  10. Natural enemy interactions constrain pest control in complex agricultural landscapes.

    Science.gov (United States)

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

    2013-04-02

    Biological control of pests by natural enemies is a major ecosystem service delivered to agriculture worldwide. Quantifying and predicting its effectiveness at large spatial scales is critical for increased sustainability of agricultural production. Landscape complexity is known to benefit natural enemies, but its effects on interactions between natural enemies and the consequences for crop damage and yield are unclear. Here, we show that pest control at the landscape scale is driven by differences in natural enemy interactions across landscapes, rather than by the effectiveness of individual natural enemy guilds. In a field exclusion experiment, pest control by flying insect enemies increased with landscape complexity. However, so did antagonistic interactions between flying insects and birds, which were neutral in simple landscapes and increasingly negative in complex landscapes. Negative natural enemy interactions thus constrained pest control in complex landscapes. These results show that, by altering natural enemy interactions, landscape complexity can provide ecosystem services as well as disservices. Careful handling of the tradeoffs among multiple ecosystem services, biodiversity, and societal concerns is thus crucial and depends on our ability to predict the functional consequences of landscape-scale changes in trophic interactions.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  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. 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

  18. 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...

  19. 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.

  20. 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 pa...... statistics and a control scheme. The algorithm also works well for scene change condition. Test results for coding interlaced video (720x576 PAL) are reported.......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...

  1. Scalable Harmonization of Complex Networks With Local Adaptive Controllers

    Czech Academy of Sciences Publication Activity Database

    Kárný, Miroslav; Herzallah, R.

    2017-01-01

    Roč. 47, č. 3 (2017), s. 394-404 ISSN 2168-2216 R&D Projects: GA ČR GA13-13502S Institutional support: RVO:67985556 Keywords : Adaptive control * Adaptive estimation * Bayes methods * Complex networks * Decentralized control * Fee dback * Fee dforward systems * Recursive estimation Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Statistics and probability Impact factor: 2.350, year: 2016 http://library.utia.cas.cz/separaty/2016/AS/karny-0457337.pdf

  2. Intelligent Transportation Control based on Proactive Complex Event Processing

    OpenAIRE

    Wang Yongheng; Geng Shaofeng; Li Qian

    2016-01-01

    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 p...

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  4. 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.

  5. Regularization and Complexity Control in Feed-forward Networks

    OpenAIRE

    Bishop, C. M.

    1995-01-01

    In this paper we consider four alternative approaches to complexity control in feed-forward networks based respectively on architecture selection, regularization, early stopping, and training with noise. We show that there are close similarities between these approaches and we argue that, for most practical applications, the technique of regularization should be the method of choice.

  6. The database for accelerator control in the CERN PS Complex

    International Nuclear Information System (INIS)

    Cuperus, J.H.

    1987-01-01

    The use of a database started 7 years ago and is an effort to separate logic from data so that programs and routines can do a larger number of operations on data structures without knowing a priori the contents of these structures. It is of great help in coping with the complexities of a system controlling many linked accelerators and storage rings

  7. 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: quote>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)...quote> 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.

  8. 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.

  9. 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...

  10. 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.

  11. Synchronizing and controlling hyperchaos in complex Lorentz-Haken systems

    Energy Technology Data Exchange (ETDEWEB)

    Jinqing, Fang [Academia Sinica, Beijing, BJ (China). Inst. of Atomic Energy

    1995-03-01

    Synchronizing hyperchaos is realized by the drive-response relationship in the complex Lorentz-Haken system and its higher-order cascading systems for the first time. Controlling hyperchaos is achieved by the intermittent proportional feedback to all of the drive (master) system variables. The complex Lorentz-Haken system describes the detuned single-mode laser and is taken as a typical example of hyperchaotic synchronization to clarify our ideas and results. The ideas and concepts could be extended to some nonlinear dynamical systems and have prospects for potential applications, for example. to laser, electronics, plasma, cryptography, communication, chemical and biological systems and so on. (8 figs., 2 tabs.).

  12. Controlling Magnetism of a Complex Metallic System Using Atomic Individualism

    Science.gov (United States)

    Mudryk, Y.; Paudyal, D.; Pecharsky, V. K.; Gschneidner, K. A., Jr.; Misra, S.; Miller, G. J.

    2010-08-01

    When the complexity of a metallic compound reaches a certain level, a specific location in the structure may be critically responsible for a given fundamental property of a material while other locations may not play as much of a role in determining such a property. The first-principles theory has pinpointed a critical location in the framework of a complex intermetallic compound—Gd5Ge4—that resulted in a controlled alteration of the magnetism of this compound using precise chemical tools.

  13. Synchronizing and controlling hyperchaos in complex Lorentz-Haken systems

    International Nuclear Information System (INIS)

    Fang Jinqing

    1995-03-01

    Synchronizing hyperchaos is realized by the drive-response relationship in the complex Lorentz-Haken system and its higher-order cascading systems for the first time. Controlling hyperchaos is achieved by the intermittent proportional feedback to all of the drive (master) system variables. The complex Lorentz-Haken system describes the detuned single-mode laser and is taken as a typical example of hyperchaotic synchronization to clarify our ideas and results. The ideas and concepts could be extended to some nonlinear dynamical systems and have prospects for potential applications, for example. to laser, electronics, plasma, cryptography, communication, chemical and biological systems and so on. (8 figs., 2 tabs.)

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  15. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  17. 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.

  18. Integrated health management and control of complex dynamical systems

    Science.gov (United States)

    Tolani, Devendra K.

    2005-11-01

    A comprehensive control and health management strategy for human-engineered complex dynamical systems is formulated for achieving high performance and reliability over a wide range of operation. Results from diverse research areas such as Probabilistic Robust Control (PRC), Damage Mitigating/Life Extending Control (DMC), Discrete Event Supervisory (DES) Control, Symbolic Time Series Analysis (STSA) and Health and Usage Monitoring System (HUMS) have been employed to achieve this goal. Continuous-domain control modules at the lower level are synthesized by PRC and DMC theories, whereas the upper-level supervision is based on DES control theory. In the PRC approach, by allowing different levels of risk under different flight conditions, the control system can achieve the desired trade off between stability robustness and nominal performance. In the DMC approach, component damage is incorporated in the control law to reduce the damage rate for enhanced structural durability. The DES controller monitors the system performance and, based on the mission requirements (e.g., performance metrics and level of damage mitigation), switches among various lower-level controllers. The core idea is to design a framework where the DES controller at the upper-level, mimics human intelligence and makes appropriate decisions to satisfy mission requirements, enhance system performance and structural durability. Recently developed tools in STSA have been used for anomaly detection and failure prognosis. The DMC deals with the usage monitoring or operational control part of health management, where as the issue of health monitoring is addressed by the anomaly detection tools. The proposed decision and control architecture has been validated on two test-beds, simulating the operations of rotorcraft dynamics and aircraft propulsion.

  19. Complexity of verifying nonblockingness in modular supervisory control

    Czech Academy of Sciences Publication Activity Database

    Masopust, Tomáš

    2018-01-01

    Roč. 63, č. 2 (2018), s. 602-607 ISSN 0018-9286 Institutional support: RVO:67985840 Keywords : nonblockingness * modular supervisory control * complexity Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 4.270, year: 2016 http://ieeexplore.ieee.org/document/7979596/

  20. 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.

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

    Science.gov (United States)

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

    2016-12-12

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

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

    Science.gov (United States)

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

    2018-04-01

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

  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 severity is linked to the structure of dystrophin.

    Science.gov (United States)

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

    2015-03-01

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

  6. 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.

  7. 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.

  8. 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...

  9. Improved safety in advanced control complexes, without side effects

    International Nuclear Information System (INIS)

    Harmon, D.L.

    1997-01-01

    If we only look for a moment at the world around us, it is obvious that advances in digital electronic equipment and Human-System Interface (HSI) technology are occurring at a phenomenal pace. This is evidenced from our home entertainment systems to the dashboard and computer-based operation of our new cars. Though the nuclear industry has less vigorously embraced these advances, their application is being implemented through individual upgrades to current generation nuclear plants and as plant-wide control complexes for advanced plants. In both venues modem technology possesses widely touted advantages for improving plant availability as well as safety. The well-documented safety benefits of digital Instrumentation and Controls (I ampersand C) include higher reliability resulting from redundancy and fault tolerance, inherent self-test and self-diagnostic capabilities which have replaced error-prone human tasks, resistance to setpoint drift increasing available operating margins, and the ability to run complex, real-time, computer-based algorithms directly supporting an operator's monitoring and control task requirements. 22 refs., 3 figs., 5 tabs

  10. Power systems control complex optimization in the new market conditions

    International Nuclear Information System (INIS)

    Krumm, L.; Kurrel, U.; Tauts, A.; Terno, O.; Zeidmanis, I.; Krisans, Z.

    2000-01-01

    A generalization and development of the theory and methods for complex optimisation of the performance and development control of an interconnected system (IPS) under new market conditions (mainly multicriterial and game approaches) is given considering the specifics of IPS at the international level in post-socialist countries and in particular in the Baltic states. Thereby the kernel of the mathematical apparatus of this theory the Generalized Reduced Gradient Method (GRGM) is further generalised and developed with the application of multicriterial and game methods to meet various market conditions. (author)

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

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakai

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Camilla Brolin

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xuan Guan

    2014-03-01

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

  15. Metformin selectively targets redox control of complex I energy transduction

    Directory of Open Access Journals (Sweden)

    Amy R. Cameron

    2018-04-01

    Full Text Available Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled. Keywords: Diabetes, Metformin, Mitochondria, NADH, NAD+

  16. 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.

  17. Calibration, monitoring, and control of complex detector systems

    International Nuclear Information System (INIS)

    Breidenbach, M.

    1981-01-01

    LEP detectors will probably be complex devices having tens of subsystems; some subsystems having perhaps tens of thousands of channels. Reasonable design goals for such a detector will include economic use of money and people, rapid and reliable calibration and monitoring of the detector, and simple control and operation of the device. The synchronous operation of an e + e - storage ring, coupled with its relatively low interaction rate, allow the design of simple circuits for time and charge measurements. These circuits, and more importantly, the basic detector channels, can usually be tested and calibrated by signal injection into the detector. Present detectors utilize semi-autonomous controllers which collect such calibration data and calculate statistics as well as control sparse data scans. Straightforward improvements in programming technology should move the entire calibration into these local controllers, so that calibration and testing time will be a constant independent of the number of channels in a system. Considerable programming effort may be saved by emphasizing the similarities of the subsystems, so that the subsystems can be described by a reasonable database and general purpose calibration and test routines can be used. Monitoring of the apparatus will probably continue to be of two classes: 'passive' histogramming of channel occupancies and other more complex combinations of the data; and 'active' injection of test patterns and calibration signals during a run. The relative importance of active monitoring will increase for the low data rates expected off resonances at high s. Experience at SPEAR and PEP is used to illustrate these approaches. (Auth.)

  18. Calibration, Monitoring, and Control of Complex Detector Systems

    Science.gov (United States)

    Breidenbach, M.

    1981-04-01

    LEP Detectors will probably be complex devices having tens of subsystems; some subsystems having perhaps tens of thousands of channels. Reasonable design goals for such a detector will include economic use of money and people, rapid and reliable calibration and monitoring of the detector, and simple control and operation of the device. The synchronous operation of an e+e- storage ring, coupled with its relatively low interaction rate, allow the design of simple circuits for time and charge measurements. These circuits, and more importantly, the basic detector channels, can usually be tested and calibrated by signal injection into the detector. Present detectors utilize semi-autonomous controllers which collect such calibration data and calculate statistics as well as control sparse data scans. Straightforward improvements in programming technology should move the entire calibration into these local controllers, so that calibration and testing time will be a constant independent of the number of channels in a system. Considerable programming effort may be saved by emphasizing the similarities of the subsystems, so that the subsystems can be described by a reasonable database and general purpose calibration and test routines can be used. Monitoring of the apparatus will probably continue to be of two classes: "passive" histogramming of channel occupancies and other more complex combinations of the data; and "active" injection of test patterns and calibration signals during a run. The relative importance of active monitoring will increase for the low data rates expected off resonances at high s. Experience at SPEAR and PEP is used to illustrate these approaches.

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2018-02-01

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

  2. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  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 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.

  5. Predictability, Force and (Anti-)Resonance in Complex Object Control.

    Science.gov (United States)

    Maurice, Pauline; Hogan, Neville; Sternad, Dagmar

    2018-04-18

    Manipulation of complex objects as in tool use is ubiquitous and has given humans an evolutionary advantage. This study examined the strategies humans choose when manipulating an object with underactuated internal dynamics, such as a cup of coffee. The object's dynamics renders the temporal evolution complex, possibly even chaotic, and difficult to predict. A cart-and-pendulum model, loosely mimicking coffee sloshing in a cup, was implemented in a virtual environment with a haptic interface. Participants rhythmically manipulated the virtual cup containing a rolling ball; they could choose the oscillation frequency, while the amplitude was prescribed. Three hypotheses were tested: 1) humans decrease interaction forces between hand and object; 2) humans increase the predictability of the object dynamics; 3) humans exploit the resonances of the coupled object-hand system. Analysis revealed that humans chose either a high-frequency strategy with anti-phase cup-and-ball movements or a low-frequency strategy with in-phase cup-and-ball movements. Counter Hypothesis 1, they did not decrease interaction force; instead, they increased the predictability of the interaction dynamics, quantified by mutual information, supporting Hypothesis 2. To address Hypothesis 3, frequency analysis of the coupled hand-object system revealed two resonance frequencies separated by an anti-resonance frequency. The low-frequency strategy exploited one resonance, while the high-frequency strategy afforded more choice, consistent with the frequency response of the coupled system; both strategies avoided the anti-resonance. Hence, humans did not prioritize interaction force, but rather strategies that rendered interactions predictable. These findings highlight that physical interactions with complex objects pose control challenges not present in unconstrained movements.

  6. Complex Formation Control of Large-Scale Intelligent Autonomous Vehicles

    Directory of Open Access Journals (Sweden)

    Ming Lei

    2012-01-01

    Full Text Available A new formation framework of large-scale intelligent autonomous vehicles is developed, which can realize complex formations while reducing data exchange. Using the proposed hierarchy formation method and the automatic dividing algorithm, vehicles are automatically divided into leaders and followers by exchanging information via wireless network at initial time. Then, leaders form formation geometric shape by global formation information and followers track their own virtual leaders to form line formation by local information. The formation control laws of leaders and followers are designed based on consensus algorithms. Moreover, collision-avoiding problems are considered and solved using artificial potential functions. Finally, a simulation example that consists of 25 vehicles shows the effectiveness of theory.

  7. Integrated circuit devices in control systems of coal mining complexes

    Energy Technology Data Exchange (ETDEWEB)

    1983-01-01

    Systems of automatic monitoring and control of coal mining complexes developed in the 1960's used electromagnetic relays, thyristors, and flip-flops on transistors of varying conductivity. The circuits' designers, devoted much attention to ensuring spark safety, lowering power consumption, and raising noise immunity and repairability of functional devices. The fast development of integrated circuitry led to the use of microelectronic components in most devices of mine automation. An analysis of specifications and experimental research into integrated circuits (IMS) shows that the series K 176 IMS components made by CMOS technology best meet mine conditions of operation. The use of IMS devices under mine conditions has demonstrated their high reliability. Further development of integrated circuitry involve using microprocessors and microcomputers. (SC)

  8. On synchronisation of a class of complex chaotic systems with complex unknown parameters via integral sliding mode control

    Science.gov (United States)

    Tirandaz, Hamed; Karami-Mollaee, Ali

    2018-06-01

    Chaotic systems demonstrate complex behaviour in their state variables and their parameters, which generate some challenges and consequences. This paper presents a new synchronisation scheme based on integral sliding mode control (ISMC) method on a class of complex chaotic systems with complex unknown parameters. Synchronisation between corresponding states of a class of complex chaotic systems and also convergence of the errors of the system parameters to zero point are studied. The designed feedback control vector and complex unknown parameter vector are analytically achieved based on the Lyapunov stability theory. Moreover, the effectiveness of the proposed methodology is verified by synchronisation of the Chen complex system and the Lorenz complex systems as the leader and the follower chaotic systems, respectively. In conclusion, some numerical simulations related to the synchronisation methodology is given to illustrate the effectiveness of the theoretical discussions.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-25

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-25

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

  11. 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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-12

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

  14. INTERPOLYELECTROLYTE COMPLEXES AS PROSPECTIVE CARRIERS FOR CONTROLLED DRUG DELIVERY

    OpenAIRE

    Kaur Jasmeet; Harikumar S.L.; Kaur Amanpreet

    2012-01-01

    In the current scenario, polymers as carriers have revolutionized the drug delivery system. A more successful approach, to exploit the different properties of polymers in a solitary system is the complexation of polymers to form polyelectrolyte complexes. These complexes circumvent the use of chemical crosslinking agents, thereby reducing the risk of toxicity. The complex formed is generally applied in different dosage forms for the formulation of stable aggregated macromolecules. There are t...

  15. Hydromorphological control of nutrient cycling in complex river floodplain systems

    Science.gov (United States)

    Hein, T.; Bondar-Kunze, E.; Felkl, M.; Habersack, H.; Mair, M.; Pinay, G.; Tritthart, M.; Welti, N.

    2009-04-01

    Riparian zones and floodplains are key components within river ecosystems controlling nutrient cycling by promoting transformation processes and thus, act as biogeochemical hot spots. The intensity of these processes depends on the exchange conditions (the connectivity) with the main channel and the morphological setting of the water bodies. At the landscape scale, three interrelated principles of hydromorphological dynamics can be formulated regarding the cycling and transfer of carbon and nutrients in large rivers ecosystems: a) The mode of carbon and nutrient delivery affects ecosystem functioning; b) Increasing residence time and contact area impact nutrient transformation; c) Floods and droughts are natural events that strongly influence pathways of carbon and nutrient cycling. These three principles of hydromorphological dynamics control the nutrient uptake and retention and are linked over different temporal and spatial scales. All three factors can be strongly affected by natural disturbances or anthropogenic impacts, through a change in either the water regime or the geomorphologic setting of the river valley. Any change in natural water regimes will affect the biogeochemistry of riparian zones and floodplains as well as their ability to cycle and mitigate nutrient fluxes originating from upstream and/or upslope. Especially these areas have been altered by river regulation and land use changes over the last 200 years leading to the deterioration of the functioning of these compartments within the riverine landscape. The resulting deficits have prompted rehabilitation and restoration measures aiming to increase the spatial heterogeneity, the complexity, of these ecosystems. Yet, a more integrated approach is needed considering the present status of nutrient dynamics and the effects of restoration measures at different scales. The present paper analyses the effects of river side-arm restoration on ecosystem functions within the side-arm and highlights

  16. 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.

  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. Sync in Complex Dynamical Networks: Stability, Evolution, Control, and Application

    OpenAIRE

    Li, Xiang

    2005-01-01

    In the past few years, the discoveries of small-world and scale-free properties of many natural and artificial complex networks have stimulated significant advances in better understanding the relationship between the topology and the collective dynamics of complex networks. This paper reports recent progresses in the literature of synchronization of complex dynamical networks including stability criteria, network synchronizability and uniform synchronous criticality in different topologies, ...

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

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, Morten; Vissing, John

    2011-01-01

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

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

    Science.gov (United States)

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

    2018-02-10

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-04-15

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

  2. Architecture of high reliable control systems using complex software

    International Nuclear Information System (INIS)

    Tallec, M.

    1990-01-01

    The problems involved by the use of complex softwares in control systems that must insure a very high level of safety are examined. The first part makes a brief description of the prototype of PROSPER system. PROSPER means protection system for nuclear reactor with high performances. It has been installed on a French nuclear power plant at the beginnning of 1987 and has been continually working since that time. This prototype is realized on a multi-processors system. The processors communicate between themselves using interruptions and protected shared memories. On each processor, one or more protection algorithms are implemented. Those algorithms use data coming directly from the plant and, eventually, data computed by the other protection algorithms. Each processor makes its own acquisitions from the process and sends warning messages if some operating anomaly is detected. All algorithms are activated concurrently on an asynchronous way. The results are presented and the safety related problems are detailed. - The second part is about measurements' validation. First, we describe how the sensors' measurements will be used in a protection system. Then, a proposal for a method based on the techniques of artificial intelligence (expert systems and neural networks) is presented. - The last part is about the problems of architectures of systems including hardware and software: the different types of redundancies used till now and a proposition of a multi-processors architecture which uses an operating system that is able to manage several tasks implemented on different processors, which verifies the good operating of each of those tasks and of the related processors and which allows to carry on the operation of the system, even in a degraded manner when a failure has been detected are detailed [fr

  3. 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......, IT systems, and business processes. In order to identify and eliminate complexity, several approaches are used, both by researchers and practitioners. The purpose of this thesis is to contribute to the existing knowledge of complexity management theory. This research focuses on the relationship between......Complexity tends to be arguably the biggest challenge of manufacturing companies. The motivation of further studying complexity is a combination between the existing literature and the practical experiences from the industry. Based on the latest trend companies are trying to supply a growing mix...

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

    OpenAIRE

    Smythe, Gayle M; White, Jason D

    2012-01-01

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

  5. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  7. Complexity and Automation Displays of Air Traffic Control: Literature Review and Analysis

    National Research Council Canada - National Science Library

    Xing, Jing; Manning, Carol A

    2005-01-01

    This report reviewed a number of measures of complexity associated with visual displays and analyzed the potential to apply these methods to assess the complexity of air traffic control (ATC) displays...

  8. Reaction-diffusion controlled growth of complex structures

    Science.gov (United States)

    Noorduin, Willem; Mahadevan, L.; Aizenberg, Joanna

    2013-03-01

    Understanding how the emergence of complex forms and shapes in biominerals came about is both of fundamental and practical interest. Although biomineralization processes and organization strategies to give higher order architectures have been studied extensively, synthetic approaches to mimic these self-assembled structures are highly complex and have been difficult to emulate, let alone replicate. The emergence of solution patterns has been found in reaction-diffusion systems such as Turing patterns and the BZ reaction. Intrigued by this spontaneous formation of complexity we explored if similar processes can lead to patterns in the solid state. We here identify a reaction-diffusion system in which the shape of the solidified products is a direct readout of the environmental conditions. Based on insights in the underlying mechanism, we developed a toolbox of engineering strategies to deterministically sculpt patterns and shapes, and combine different morphologies to create a landscape of hierarchical multi scale-complex tectonic architectures with unprecedented levels of complexity. These findings may hold profound implications for understanding, mimicking and ultimately expanding upon nature's morphogenesis strategies, allowing the synthesis of advanced highly complex microscale materials and devices. WLN acknowledges the Netherlands Organization for Scientific Research for financial support

  9. 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.

  10. 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...

  11. Programmable logic control applied to a coal preparation plant complex

    Energy Technology Data Exchange (ETDEWEB)

    Krahenbil, L W

    1979-02-01

    The programmable Logic Controller (PLC), at its present stage of evolution, is now considered as a mature control system. The PLC combines the solid-state reliability of hard-wired logic and computer control systems with the simplicity of a relay ladder logic. Relay symbolic programming through a function-oriented keyboard provides a means which plant personnel can easily become accoustomed to work with. In a large coal facility, it is shown that the control engineer can provide improved control flexibility with the advanced capabilities of the PLC.

  12. 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.

  13. Modulation of Protein Quality Control and Proteasome to Autophagy Switch in Immortalized Myoblasts from Duchenne Muscular Dystrophy Patients

    Directory of Open Access Journals (Sweden)

    Marion Wattin

    2018-01-01

    Full Text Available The maintenance of proteome integrity is of primary importance in post-mitotic tissues such as muscle cells; thus, protein quality control mechanisms must be carefully regulated to ensure their optimal efficiency, a failure of these processes being associated with various muscular disorders. Duchenne muscular dystrophy (DMD is one of the most common and severe forms of muscular dystrophies and is caused by mutations in the dystrophin gene. Protein quality control modulations have been diversely observed in degenerating muscles of patients suffering from DMD or in animal models of the disease. In this study, we investigated whether modulations of protein quality control mechanisms already pre-exist in undifferentiated myoblasts originating from DMD patients. We report for the first time that the absence of dystrophin in human myoblasts is associated with protein aggregation stress characterized by an increase of protein aggregates. This stress is combined with BAG1 to BAG3 switch, NFκB activation and up-regulation of BAG3/HSPB8 complexes that ensure preferential routing of misfolded/aggregated proteins to autophagy rather than to deficient 26S proteasome. In this context, restoration of pre-existing alterations of protein quality control processes might represent an alternative strategy for DMD therapies.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Chunli Zhao

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

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

    Science.gov (United States)

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

    2014-09-12

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

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

    Science.gov (United States)

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

    2003-11-01

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

  19. 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.

  20. Adaptive Missile Flight Control for Complex Aerodynamic Phenomena

    Science.gov (United States)

    2017-08-09

    roll damping and magnus stability coefficients for finned projectiles. J Spacecraft Rockets. 2016, accepted. 20. Burt JR. The effectiveness of canards...Performance degradation usually propagates into the pitch and yaw directions when these adverse roll control effects are encountered due to the coupling of... effect of control action (e.g., canard deflections) in the pitch and yaw planes is combined in an overall aerodynamic scaling and control amplitude

  1. 2706-T Complex Distributed Control System Tag and Setpoint List

    International Nuclear Information System (INIS)

    PRATT, D.A.

    1999-01-01

    The 2706-T Distributed Control System (DCS) interfaces with field equipment through analog and digital input and output signals that are terminated at a programmable logic controller (PLC). The Tag names and addresses of the input and output signals are listed in this document as well as setpoint values assigned to fixed inputs

  2. Control board and utility system for cell complex

    International Nuclear Information System (INIS)

    Almeida, G.L. de; Silva, A.C.; Souza, A.S.F. de; Souza, M.L.M. de; Rautenberg, F.A.

    1986-01-01

    To attend necessities of hot cells operation and process control for isotope production in IEN cyclotron (Brazilian-CNEN) a utility system, such as, electricity, water, vacuum, air, and gas, and control board was constructed, which advantages are presented. (M.C.K.)

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

    Science.gov (United States)

    Zañudo, Jorge Gomez Tejeda; Yang, Gang; Albert, Réka

    2017-07-11

    What can we learn about controlling a system solely from its underlying network structure? Here we adapt a recently developed framework for control of networks governed by a broad class of nonlinear dynamics that includes the major dynamic models of biological, technological, and social processes. This feedback-based framework provides realizable node overrides that steer a system toward any of its natural long-term dynamic behaviors, regardless of the specific functional forms and system parameters. We use this framework on several real networks, identify the topological characteristics that underlie the predicted node overrides, and compare its predictions to those of structural controllability in control theory. Finally, we demonstrate this framework's applicability in dynamic models of gene regulatory networks and identify nodes whose override is necessary for control in the general case but not in specific model instances.

  4. Exploring the complexity of quantum control optimization trajectories.

    Science.gov (United States)

    Nanduri, Arun; Shir, Ofer M; Donovan, Ashley; Ho, Tak-San; Rabitz, Herschel

    2015-01-07

    The control of quantum system dynamics is generally performed by seeking a suitable applied field. The physical objective as a functional of the field forms the quantum control landscape, whose topology, under certain conditions, has been shown to contain no critical point suboptimal traps, thereby enabling effective searches for fields that give the global maximum of the objective. This paper addresses the structure of the landscape as a complement to topological critical point features. Recent work showed that landscape structure is highly favorable for optimization of state-to-state transition probabilities, in that gradient-based control trajectories to the global maximum value are nearly straight paths. The landscape structure is codified in the metric R ≥ 1.0, defined as the ratio of the length of the control trajectory to the Euclidean distance between the initial and optimal controls. A value of R = 1 would indicate an exactly straight trajectory to the optimal observable value. This paper extends the state-to-state transition probability results to the quantum ensemble and unitary transformation control landscapes. Again, nearly straight trajectories predominate, and we demonstrate that R can take values approaching 1.0 with high precision. However, the interplay of optimization trajectories with critical saddle submanifolds is found to influence landscape structure. A fundamental relationship necessary for perfectly straight gradient-based control trajectories is derived, wherein the gradient on the quantum control landscape must be an eigenfunction of the Hessian. This relation is an indicator of landscape structure and may provide a means to identify physical conditions when control trajectories can achieve perfect linearity. The collective favorable landscape topology and structure provide a foundation to understand why optimal quantum control can be readily achieved.

  5. IPAD Paperless Work Control for Test Complex Facilities Management

    Data.gov (United States)

    National Aeronautics and Space Administration — The purpose of this project was to identify a way to improve the work control processes used at Stennis Space Center that are traditionally done via paper by...

  6. 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...

  7. Complex optimization of radiometric control and measurement systems

    International Nuclear Information System (INIS)

    Onishchenko, A.M.

    1995-01-01

    Fundamentals of a new approach to increase in the accuracy of radiometric systems of control and measurements are presented in succession. Block diagram of the new concept of radiometric system optimization is provided. The approach involving radical increase in accuracy and envisages ascertaining of controlled parameter by the totality of two intelligence signals closely correlated with each other. The new concept makes use of system analysis as a unified one-piece object, permitting euristic synthesis of the system. 4 refs., 3 figs

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

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

  9. Automatic control in multidrive electrotechnical complexes with semiconductor converters

    Science.gov (United States)

    Vasilev, B. U.; Mardashov, D. V.

    2017-01-01

    The frequency convertor and the automatic control system, which can be used in the multi-drive electromechanical system with a few induction motions, are considered. The paper presents the structure of existing modern multi-drive electric drives inverters, namely, electric drives with a total frequency converter and few electric motions, and an electric drive, in which the converter is used for power supply and control of the independent frequency. It was shown that such technical solutions of frequency converters possess a number of drawbacks. The drawbacks are given. It was shown that the control of technological processes using the electric drive of this structure may be provided under very limited conditions, as the energy efficiency and the level of electromagnetic compatibility of electric drives is low. The authors proposed using a multi-inverter structure with an active rectifier in multidrive electric drives with induction motors frequency converters. The application of such frequency converter may solve the problem of electromagnetic compatibility, namely, consumption of sinusoidal currents from the network and the maintenance of a sinusoidal voltage and energy compatibility, namely, consumption of practically active energy from the network. Also, the paper proposes the use of the automatic control system, which by means of a multi-inverter frequency converter provides separate control of drive machines and flexible regulation of technological processes. The authors present oscillograms, which confirm the described characteristics of the developed electrical drive. The possible subsequent ways to improve the multi-motor drives are also described.

  10. 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...... since only a small amount of memory space for storing time-delayed values and simple arithmetic computations are needed for its physical realization. In addition to that, other advantages of the scheme include its abilities to compensate for negative-sequence, load and grid harmonic components using...

  11. 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

  12. Methylene Diphosphonate Chemical and Biological control of MDP complex

    International Nuclear Information System (INIS)

    Aungurarat, Angkanan; Ngamprayad, Tippanan

    2000-01-01

    Technetium-9 9m MDP easy prepared from MDP kits which different sources such as OAP (In house), SIGMA. The resulting Tc 9 9m -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

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

    Science.gov (United States)

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

    2014-01-01

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

  14. 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.

  15. Human as the chief controller in the complex system

    International Nuclear Information System (INIS)

    Jung, Yeonsub

    2012-01-01

    Due to accuracy of measurement and improvement of control logic, human beings are freed from time consuming and repeated task. When there are situations where the control logic cannot calculate the next state of system, human beings interrupt the system and steer the system manually. The most scope of human factors is focused on this interruption, and economists are concern how to present information cognitively and reliably. Fukushima nuclear accident has considered the role of human beings again. Human beings are forced to do something without proper knowledge, procedure, and process information. Thus post Fukushima actions should include how for human beings to be trained and how to get real time information. Finally because safety culture can determine behaviors of human beings, the method to cultivate safety culture should be considered

  16. 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.

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

    Science.gov (United States)

    2016-09-26

    SECURITY CLASSIFICATION OF: 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE 13. SUPPLEMENTARY NOTES 12. DISTRIBUTION AVAILIBILITY STATEMENT 6. AUTHORS...neighbor or bi-linear interpolation). The following paper is in preparation: Scaling methods and heuristic algorithms for agent-based models. Matt...The actual method of control used is in the form of heuristic algorithms. In general, these algorithms search through a virtually infinite set of

  18. Automation of program model developing for complex structure control objects

    International Nuclear Information System (INIS)

    Ivanov, A.P.; Sizova, T.B.; Mikhejkina, N.D.; Sankovskij, G.A.; Tyufyagin, A.N.

    1991-01-01

    A brief description of software for automated developing the models of integrating modular programming system, program module generator and program module library providing thermal-hydraulic calcualtion of process dynamics in power unit equipment components and on-line control system operation simulation is given. Technical recommendations for model development are based on experience in creation of concrete models of NPP power units. 8 refs., 1 tab., 4 figs

  19. Bactrocera dorsalis complex and its problem in control

    International Nuclear Information System (INIS)

    Tan, Keng-Hong

    2003-01-01

    Eight species of fifty-two in the Bactrocera dorsalis complex are serious pests in the Asia-Pacific region. Of these, all except one are attracted to methyl eugenol. Four of these pests B. carambolae, B. dorsalis, B. papayae and B. philippinesis are polyphagous species and infest 75, 117, 195 and 18 fruit host species respectively. Common names for B. carambalae and B. papayae (sympatric species) have caused confusion. Both species can interbreed and produce viable offspring; and their natural hybrids have been collected. Bactrocera dorsalis and B. papayae can interbreed readily and produce viable offspring in the laboratory as males produce identical booster sex and aggregation pheromonal components after consuming methyl eugenol. The DNA sequences of one of their respective allelic introns of the actin gene are also identical which suggests that they are not distinct genetic species. Protein bait application and male annihilation techniques have been successful in the management of fruit flies in many cases but they have to compete with natural sources of lures. SIT is amenable for non-methyl engenol species; but for methyl eugenol sensitive species, sterile makes should be allowed to consume methyl eugenol before release to have an equal mating competitiveness with wild males. (author)

  20. Dissection of combinatorial control by the Met4 transcriptional complex.

    Science.gov (United States)

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  1. Ketosis, ketogenic diet and food intake control: a complex relationship.

    Science.gov (United States)

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

  2. Generation of clusters in complex dynamical networks via pinning control

    International Nuclear Information System (INIS)

    Li Kezan; Fu Xinchu; Small, Michael

    2008-01-01

    Many real-world networks show community structure, i.e., groups (or clusters) of nodes that have a high density of links within them but with a lower density of links between them. In this paper, by applying feedback injections to a fraction of network nodes, various clusters are synchronized independently according to the community structure generated by the group partition of the network (cluster synchronization). This control is achieved by pinning (i.e. applying linear feedback control) to a subset of the network nodes. Those pinned nodes are selected not randomly but according to the topological structure of communities of a given network. Specifically, for a given group partition of a network, those nodes with direct connections between groups must be pinned in order to achieve cluster synchronization. Both the local stability and global stability of cluster synchronization are investigated. Taking the tree-shaped network and the most modular network as two particular examples, we illustrate in detail how the pinning strategy influences the generation of clusters. The simulations verify the efficiency of the pinning schemes used in this paper

  3. Ketosis, ketogenic diet and food intake control: a complex relationship

    Directory of Open Access Journals (Sweden)

    Antonio ePaoli

    2015-02-01

    Full Text Available Though the hunger-reduction phenomenon reported during ketogenic diets is well known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK release while reducing orexigenic signals e.g. via ghrelin. However ketone bodies (KB seem to be able to increase food intake through AMP-activated protein kinase (AMPK phosphorylation, gamma-aminobutyric acid (GABA and the release and production of adiponectin. The aim of this review is to provide an overview of our current knowledge of the effects of ketogenic diet (KD on food control in an effort to unify the apparently contradictory data into a coherent picture.

  4. Ketosis, ketogenic diet and food intake control: a complex relationship

    Science.gov (United States)

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

  5. 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

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

    Science.gov (United States)

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

    2017-10-03

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

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

    Science.gov (United States)

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

    2017-01-01

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

  9. 100-fold but not 50-fold dystrophin overexpression aggravates electrocardiographic defects in the mdx model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Yongping Yue

    2016-01-01

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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Vanessa Borges Pires

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

  12. Criteria for the design of the control room complex for a nuclear power generating station

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This Standard addresses the central control room of a nuclear power generating station and the overall complex in which this room is housed. It is not intended to cover special or normally unattended control rooms, such as those provided for radioactive waste handling or for emergency shutdown operations. The nuclear power generating station control room complex provides a protective envelope for plant operating personnel and for instrument and control equipment vital to the operation of the plant during normal and abnormal conditions. In this capacity, the control room complex must be designed and constructed to meet the following criteria contained in Appendix A of 10CFR50, General Design criteria for Nuclear Power Plants: (1) Criterion 2: design bases for protection against natural phenomena; (2) Criterion 3: fire protection; (3) Criterion 4: environmental and missile design bases; (4) Criterion 5: sharing of structures, systems and components (multiunit stations only); and (5) Criterion 19: control room

  13. Using the calculational simulating complexes when making the computer process control systems for NPP

    International Nuclear Information System (INIS)

    Zimakov, V.N.; Chernykh, V.P.

    1998-01-01

    The problems on creating calculational-simulating (CSC) and their application by developing the program and program-technical means for computer-aided process control systems at NPP are considered. The abo- ve complex is based on the all-mode real time mathematical model, functioning at a special complex of computerized means

  14. Dynamic behavior and chaos control in a complex Riccati-type map ...

    African Journals Online (AJOL)

    This paper is devoted to analyze the dynamic behavior of a Riccati- type map with complex variables and complex parameters. Fixed points and their asymptotic stability are studied. Lyapunov exponent is computed to indicate chaos. Bifurcation and chaos are discussed. Chaotic behavior of the map has been controlled by ...

  15. 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.

  16. 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».

  17. Complexity control algorithm based on adaptive mode selection for interframe coding in high efficiency video coding

    Science.gov (United States)

    Chen, Gang; Yang, Bing; Zhang, Xiaoyun; Gao, Zhiyong

    2017-07-01

    The latest high efficiency video coding (HEVC) standard significantly increases the encoding complexity for improving its coding efficiency. Due to the limited computational capability of handheld devices, complexity constrained video coding has drawn great attention in recent years. A complexity control algorithm based on adaptive mode selection is proposed for interframe coding in HEVC. Considering the direct proportionality between encoding time and computational complexity, the computational complexity is measured in terms of encoding time. First, complexity is mapped to a target in terms of prediction modes. Then, an adaptive mode selection algorithm is proposed for the mode decision process. Specifically, the optimal mode combination scheme that is chosen through offline statistics is developed at low complexity. If the complexity budget has not been used up, an adaptive mode sorting method is employed to further improve coding efficiency. The experimental results show that the proposed algorithm achieves a very large complexity control range (as low as 10%) for the HEVC encoder while maintaining good rate-distortion performance. For the lowdelayP condition, compared with the direct resource allocation method and the state-of-the-art method, an average gain of 0.63 and 0.17 dB in BDPSNR is observed for 18 sequences when the target complexity is around 40%.

  18. 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.

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

    Science.gov (United States)

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

    1995-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  1. 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.

  2. 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.

  3. Design process and philosophy of TVA's latest advance control room complex

    International Nuclear Information System (INIS)

    Owens, G.R.; Masters, D.W.

    1979-01-01

    TVA's latest nuclear power plant control room design includes a greater emphasis on human factors as compared to their earlier plant designs. This emphasis has resulted in changes in the overall design philosophy and design process. This paper discusses some of the prominent design features of both the control room and the surrounding control room complex. In addition, it also presents some of the important activities involved in the process of developing the advanced control room design

  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. Novel pinning control strategies for synchronisation of complex networks with nonlinear coupling dynamics

    International Nuclear Information System (INIS)

    Zhao-Bing, Liu; Hua-Guang, Zhang; Qiu-Ye, Sun

    2010-01-01

    This paper considers the global stability of controlling an uncertain complex network to a homogeneous trajectory of the uncoupled system by a local pinning control strategy. Several sufficient conditions are derived to guarantee the network synchronisation by investigating the relationship among pinning synchronisation, network topology, and coupling strength. Also, some fundamental and yet challenging problems in the pinning control of complex networks are discussed: (1) what nodes should be selected as pinned candidates? (2) How many nodes are needed to be pinned for a fixed coupling strength? Furthermore, an adaptive pinning control scheme is developed. In order to achieve synchronisation of an uncertain complex network, the adaptive tuning strategy of either the coupling strength or the control gain is utilised. As an illustrative example, a network with the Lorenz system as node self-dynamics is simulated to verify the efficacy of theoretical results. (general)

  6. 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.

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

    Science.gov (United States)

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

    2012-08-01

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

  8. Controlling Uncertainty: A Review of Human Behavior in Complex Dynamic Environments

    Science.gov (United States)

    Osman, Magda

    2010-01-01

    Complex dynamic control (CDC) tasks are a type of problem-solving environment used for examining many cognitive activities (e.g., attention, control, decision making, hypothesis testing, implicit learning, memory, monitoring, planning, and problem solving). Because of their popularity, there have been many findings from diverse domains of research…

  9. A design control structure for architectural firms in a highly complex and uncertain situation

    NARCIS (Netherlands)

    Schijlen, J.T.H.A.M.; Otter, den A.F.H.J.; Pels, H.J.

    2011-01-01

    A large architectural firm in a highly complex and uncertain production situation asked to improve its existing ?production control? system for design projects. To that account a research and design project of nine months at the spot was defined. The production control in the organization was based

  10. Architecture of built-in microcontrollers in the U-70 complex control system

    International Nuclear Information System (INIS)

    Balakin, S.I.; Voevodin, V.P.; Inchagov, A.A.; Komarov, V.V.

    2000-01-01

    The distributed system of built-in microcontrollers (BMS) for functional control of supply sources of magnetooptical elements is created within the frames of works on modernization of the U-70 control complex. The BMS architecture and functional diagram of one of them are presented. The microcontrollers operation algorithm is based on the eventuation principle. The BMS basic parameters are presented [ru

  11. Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-09-01

    Full Text Available Duchenne muscular dystrophy (DMD, Becker muscular dystrophy (BMD, and X-linked dilated cardiomyopathy (XL-DCM consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts.

  12. Design and implementation of the control system for nuclear plant VVER-1000. Instrumentation (program technical complexes)

    International Nuclear Information System (INIS)

    Siora, A.; Tokarev, V.; Bakhmach, E.

    2004-01-01

    Program-technical complexes (PTC) are designed as control and protection systems in water-moderated atomic reactors, including emergency and preventive systems, automatic control, unloading, reactor capacity limitation and accelerated preventive protection systems. Utilization of programmable logic integrated circuits from world leading manufacturers makes the complexes simple in structure, compact, with low energy demands and mutually independent for key and supporting functions The results of PTC assessment and implementation in Ukraine are outlined. Opportunities for a future development of RADIJ company in the area of control and protection systems for VVER reactors are also discussed

  13. 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.

  14. Optimal Control of Complex Systems Based on Improved Dual Heuristic Dynamic Programming Algorithm

    Directory of Open Access Journals (Sweden)

    Hui Li

    2017-01-01

    Full Text Available When applied to solving the data modeling and optimal control problems of complex systems, the dual heuristic dynamic programming (DHP technique, which is based on the BP neural network algorithm (BP-DHP, has difficulty in prediction accuracy, slow convergence speed, poor stability, and so forth. In this paper, a dual DHP technique based on Extreme Learning Machine (ELM algorithm (ELM-DHP was proposed. Through constructing three kinds of network structures, the paper gives the detailed realization process of the DHP technique in the ELM. The controller designed upon the ELM-DHP algorithm controlled a molecular distillation system with complex features, such as multivariability, strong coupling, and nonlinearity. Finally, the effectiveness of the algorithm is verified by the simulation that compares DHP and HDP algorithms based on ELM and BP neural network. The algorithm can also be applied to solve the data modeling and optimal control problems of similar complex systems.

  15. Control system for a heavy-ion accelerator complex K4 - K10

    International Nuclear Information System (INIS)

    Kotov, V.M.; Pose, R.

    1992-01-01

    Control systems for newly created accelerators, perhaps for the first time, may be designed almost only around international standards for communication and control techniques. This is also true for the project of a control system for the accelerator complex K4-K10 at the Joint Institute for Nuclear Research Dubna. Nevertheless, open systems architecture with construction principles being essential for modern systems of such big devices as particle accelerators leaves designers enough possibilities for solving even very sophisticated problems. (author)

  16. The Control Based on Internal Average Kinetic Energy in Complex Environment for Multi-robot System

    Science.gov (United States)

    Yang, Mao; Tian, Yantao; Yin, Xianghua

    In this paper, reference trajectory is designed according to minimum energy consumed for multi-robot system, which nonlinear programming and cubic spline interpolation are adopted. The control strategy is composed of two levels, which lower-level is simple PD control and the upper-level is based on the internal average kinetic energy for multi-robot system in the complex environment with velocity damping. Simulation tests verify the effectiveness of this control strategy.

  17. Chaos synchronization and chaotization of complex chaotic systems in series form by optimal control

    International Nuclear Information System (INIS)

    Ge Zhengming; Yang, C.-H.

    2009-01-01

    By the method of quadratic optimum control, a quadratic optimal regulator is used for synchronizing two complex chaotic systems in series form. By this method the least error with less control energy is achieved, and the optimization on both energy and error is realized synthetically. The simulation results of two Quantum-CNN chaos systems in series form prove the effectiveness of this method. Finally, chaotization of the system is given by optimal control.

  18. 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...... Unmanned Aerial Vehicle (UAV) has been constructed and used to develop an attitude controller based on Model Predictive Control (MPC). The MPC controller has been compared to an existing open source Proportional Integral Derivative (PID) attitude controller. This thesis contributes to the discipline...

  19. 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.

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

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, Morten; Vissing, John

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-07-26

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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Christopher F Spurney

    2010-01-01

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

  4. Coherent operation of detector systems and their readout electronics in a complex experiment control environment

    Energy Technology Data Exchange (ETDEWEB)

    Koestner, Stefan [CERN (Switzerland)], E-mail: koestner@mpi-halle.mpg.de

    2009-09-11

    With the increasing size and degree of complexity of today's experiments in high energy physics the required amount of work and complexity to integrate a complete subdetector into an experiment control system is often underestimated. We report here on the layered software structure and protocols used by the LHCb experiment to control its detectors and readout boards. The experiment control system of LHCb is based on the commercial SCADA system PVSS II. Readout boards which are outside the radiation area are accessed via embedded credit card sized PCs which are connected to a large local area network. The SPECS protocol is used for control of the front end electronics. Finite state machines are introduced to facilitate the control of a large number of electronic devices and to model the whole experiment at the level of an expert system.

  5. Exponential synchronization of complex delayed dynamical networks via pinning periodically intermittent control

    Energy Technology Data Exchange (ETDEWEB)

    Cai Shuiming, E-mail: caishuiming2008@yahoo.com.c [Department of Mathematics, Shanghai University, Shanghai 200444 (China); Institute of System Biology, Shanghai University, Shanghai 200444 (China); Hao Junjun [Institute of System Biology, Shanghai University, Shanghai 200444 (China); He, Qinbin [Department of Mathematics, Taizhou University, Linhai 317000 (China); Institute of System Biology, Shanghai University, Shanghai 200444 (China); Liu Zengrong, E-mail: zrongliu@126.co [Department of Mathematics, Shanghai University, Shanghai 200444 (China) and Institute of System Biology, Shanghai University, Shanghai 200444 (China)

    2011-05-09

    The problem of synchronization for a class of complex delayed dynamical networks via pinning periodically intermittent control is considered in this Letter. Some novel and useful exponential synchronization criteria are obtained by utilizing the methods which are different from the techniques employed in the existing works, and the derived results are less conservative. Especially, the traditional assumptions on control width and time delays are released in our results. Moreover, a pinning scheme deciding what nodes should be chosen as pinned candidates and how many nodes are needed to be pinned for a fixed coupling strength is provided. A Barabasi-Albert network example is finally given to illustrate the effectiveness of the theoretical results. - Highlights: Pinning control problem of complex networks via intermittent control is investigated. The traditional assumptions on control width and time delays are removed. A scheme deciding what nodes should be chosen as pinned candidates is proposed. A scheme deciding how many nodes are needed to be pinned is provided.

  6. The method of measurement and synchronization control for large-scale complex loading system

    International Nuclear Information System (INIS)

    Liao Min; Li Pengyuan; Hou Binglin; Chi Chengfang; Zhang Bo

    2012-01-01

    With the development of modern industrial technology, measurement and control system was widely used in high precision, complex industrial control equipment and large-tonnage loading device. The measurement and control system is often used to analyze the distribution of stress and displacement in the complex bearing load or the complex nature of the mechanical structure itself. In ITER GS mock-up with 5 flexible plates, for each load combination, detect and measure potential slippage between the central flexible plate and the neighboring spacers is necessary as well as the potential slippage between each pre-stressing bar and its neighboring plate. The measurement and control system consists of seven sets of EDC controller and board, computer system, 16-channel quasi-dynamic strain gauge, 25 sets of displacement sensors, 7 sets of load and displacement sensors in the cylinders. This paper demonstrates the principles and methods of EDC220 digital controller to achieve synchronization control, and R and D process of multi-channel loading control software and measurement software. (authors)

  7. Complex motion of a vehicle through a series of signals controlled by power-law phase

    Science.gov (United States)

    Nagatani, Takashi

    2017-07-01

    We study the dynamic motion of a vehicle moving through the series of traffic signals controlled by the position-dependent phase of power law. All signals are controlled by both cycle time and position-dependent phase. The dynamic model of the vehicular motion is described in terms of the nonlinear map. The vehicular motion varies in a complex manner by varying cycle time for various values of the power of the position-dependent phase. The vehicle displays the periodic motion with a long cycle for the integer power of the phase, while the vehicular motion exhibits the very complex behavior for the non-integer power of the phase.

  8. Verification and Validation Challenges for Adaptive Flight Control of Complex Autonomous Systems

    Science.gov (United States)

    Nguyen, Nhan T.

    2018-01-01

    Autonomy of aerospace systems requires the ability for flight control systems to be able to adapt to complex uncertain dynamic environment. In spite of the five decades of research in adaptive control, the fact still remains that currently no adaptive control system has ever been deployed on any safety-critical or human-rated production systems such as passenger transport aircraft. The problem lies in the difficulty with the certification of adaptive control systems since existing certification methods cannot readily be used for nonlinear adaptive control systems. Research to address the notion of metrics for adaptive control began to appear in the recent years. These metrics, if accepted, could pave a path towards certification that would potentially lead to the adoption of adaptive control as a future control technology for safety-critical and human-rated production systems. Development of certifiable adaptive control systems represents a major challenge to overcome. Adaptive control systems with learning algorithms will never become part of the future unless it can be proven that they are highly safe and reliable. Rigorous methods for adaptive control software verification and validation must therefore be developed to ensure that adaptive control system software failures will not occur, to verify that the adaptive control system functions as required, to eliminate unintended functionality, and to demonstrate that certification requirements imposed by regulatory bodies such as the Federal Aviation Administration (FAA) can be satisfied. This presentation will discuss some of the technical issues with adaptive flight control and related V&V challenges.

  9. Distributed Low-Complexity Controller for Wind Power Plant in Derated Operation

    DEFF Research Database (Denmark)

    Biegel, Benjamin; Madjidian, Daria; Spudic, Vedrana

    2013-01-01

    We consider a wind power plant of megawatt wind turbines operating in derated mode. When operating in this mode, the wind power plant controller is free to distribute power set-points to the individual turbines, as long as the total power demand is met. In this work, we design a controller...... that exploits this freedom to reduce the fatigue on the turbines in the wind power plant. We show that the controller can be designed in a decentralized manner, such that each wind turbine is equipped with a local low-complexity controller relying only on few measurements and little communication. As a basis...... for the controller design, a linear wind turbine model is constructed and verified in an operational wind power plant of megawatt turbines. Due to limitations of the wind power plant available for tests, it is not possible to implement the developed controller; instead the final distributed controller is evaluated...

  10. Outer synchronization of complex networks with internal delay and coupling delay via aperiodically intermittent pinning control

    Science.gov (United States)

    Zhang, Chuan; Wang, Xingyuan; Wang, Chunpeng; Xia, Zhiqiu

    This paper concerns the outer synchronization problem between two complex delayed networks via the method of aperiodically intermittent pinning control. Apart from previous works, internal delay and coupling delay are both involved in this model, and the designed intermittent controllers can be aperiodic. The main work in this paper can be summarized as follows: First, two cases of aperiodically intermittent control with constant gain and adaptive gain are implemented, respectively. The intermittent control and pinning control are combined to reduce consumptions further. Then, based on the Lyapunov stability theory, synchronization protocols are given by strict derivation. Especially, the designed controllers are indeed simple and valid in application of theory to practice. Finally, numerical examples put the proposed control methods to the test.

  11. 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.

  12. The impulsive control synchronization of the drive-response complex system

    International Nuclear Information System (INIS)

    Zhao Yanhong; Yang Yongqing

    2008-01-01

    This Letter investigates projective synchronization between the drive system and response complex dynamical system. An impulsive control scheme is adapted to synchronize the drive-response dynamical system to a desired scalar factor. By using the stability theory of the impulsive differential equation, the criteria for the projective synchronization are derived. The feasibility of the impulsive control of the projective synchronization is demonstrated in the drive-response dynamical system

  13. Complexity and dynamics of switched human balance control during quiet standing.

    Science.gov (United States)

    Nema, Salam; Kowalczyk, Piotr; Loram, Ian

    2015-10-01

    In this paper, we use a combination of numerical simulations, time series analysis, and complexity measures to investigate the dynamics of switched systems with noise, which are often used as models of human balance control during quiet standing. We link the results with complexity measures found in experimental data of human sway motion during quiet standing. The control model ensuring balance, which we use, is based on an act-and-wait control concept, that is, a human controller is switched on when a certain sway angle is reached. Otherwise, there is no active control present. Given a time series data, we determine how does it look a typical pattern of control strategy in our model system. We detect the switched nonlinearity in the system using a frequency analysis method in the absence of noise. We also analyse the effect of time delay on the existence of limit cycles in the system in the absence of noise. We perform the entropy and detrended fluctuation analyses in view of linking the switchings (and the dead zone) with the occurrences of complexity in the model system in the presence of noise. Finally, we perform the entropy and detrended fluctuation analyses on experimental data and link the results with numerical findings in our model example.

  14. Distance-Based Behaviors for Low-Complexity Control in Multiagent Robotics

    Science.gov (United States)

    Pierpaoli, Pietro

    Several biological examples show that living organisms cooperate to collectively accomplish tasks impossible for single individuals. More importantly, this coordination is often achieved with a very limited set of information. Inspired by these observations, research on autonomous systems has focused on the development of distributed control techniques for control and guidance of groups of autonomous mobile agents, or robots. From an engineering perspective, when coordination and cooperation is sought in large ensembles of robotic vehicles, a reduction in hardware and algorithms' complexity becomes mandatory from the very early stages of the project design. The research for solutions capable of lowering power consumption, cost and increasing reliability are thus worth investigating. In this work, we studied low-complexity techniques to achieve cohesion and control on swarms of autonomous robots. Starting from an inspiring example with two-agents, we introduced effects of neighbors' relative positions on control of an autonomous agent. The extension of this intuition addressed the control of large ensembles of autonomous vehicles, and was applied in the form of a herding-like technique. To this end, a low-complexity distance-based aggregation protocol was defined. We first showed that our protocol produced a cohesion aggregation among the agent while avoiding inter-agent collisions. Then, a feedback leader-follower architecture was introduced for the control of the swarm. We also described how proximity measures and probability of collisions with neighbors can also be used as source of information in highly populated environments.

  15. 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.

  16. The effect of a priori probability and complexity on decision making in a supervisory control task

    NARCIS (Netherlands)

    Kerstholt, J.H.; Passenier, P.O.; Houttuin, K.; Schuffel, H.

    1996-01-01

    In the present study we investigated how monitoring and fault management in a ship control task are affected by complexity and a priori probability of disturbances. Partici-pants were required to supervise four independent shipping subsystems and to adjust the subsystems whenever deviations

  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. 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)

    1994-12-31

    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.

  19. Analysis and Control of Epidemics: A survey of spreading processes on complex networks

    OpenAIRE

    Nowzari, Cameron; Preciado, Victor M.; Pappas, George J.

    2015-01-01

    This article reviews and presents various solved and open problems in the development, analysis, and control of epidemic models. We are interested in presenting a relatively concise report for new engineers looking to enter the field of spreading processes on complex networks.

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

    Science.gov (United States)

    Dowling, Paul; Culligan, Kevin; Ohlendieck, Kay

    2002-02-01

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

  1. Quantum control with noisy fields: computational complexity versus sensitivity to noise

    International Nuclear Information System (INIS)

    Kallush, S; Khasin, M; Kosloff, R

    2014-01-01

    A closed quantum system is defined as completely controllable if an arbitrary unitary transformation can be executed using the available controls. In practice, control fields are a source of unavoidable noise, which has to be suppressed to retain controllability. Can one design control fields such that the effect of noise is negligible on the time-scale of the transformation? This question is intimately related to the fundamental problem of a connection between the computational complexity of the control problem and the sensitivity of the controlled system to noise. The present study considers a paradigm of control, where the Lie-algebraic structure of the control Hamiltonian is fixed, while the size of the system increases with the dimension of the Hilbert space representation of the algebra. We find two types of control tasks, easy and hard. Easy tasks are characterized by a small variance of the evolving state with respect to the operators of the control operators. They are relatively immune to noise and the control field is easy to find. Hard tasks have a large variance, are sensitive to noise and the control field is hard to find. The influence of noise increases with the size of the system, which is measured by the scaling factor N of the largest weight of the representation. For fixed time and control field the ability to control degrades as O(N) for easy tasks and as O(N 2 ) for hard tasks. As a consequence, even in the most favorable estimate, for large quantum systems, generic noise in the controls dominates for a typical class of target transformations, i.e. complete controllability is destroyed by noise. (paper)

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Gemma L Walmsley

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-29

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  6. Complex fluid network optimization and control integrative design based on nonlinear dynamic model

    International Nuclear Information System (INIS)

    Sui, Jinxue; Yang, Li; Hu, Yunan

    2016-01-01

    In view of distribution according to complex fluid network’s needs, this paper proposed one optimization computation method of the nonlinear programming mathematical model based on genetic algorithm. The simulation result shows that the overall energy consumption of the optimized fluid network has a decrease obviously. The control model of the fluid network is established based on nonlinear dynamics. We design the control law based on feedback linearization, take the optimal value by genetic algorithm as the simulation data, can also solve the branch resistance under the optimal value. These resistances can provide technical support and reference for fluid network design and construction, so can realize complex fluid network optimization and control integration design.

  7. Adaptive Synchronization of Fractional Order Complex-Variable Dynamical Networks via Pinning Control

    Science.gov (United States)

    Ding, Da-Wei; Yan, Jie; Wang, Nian; Liang, Dong

    2017-09-01

    In this paper, the synchronization of fractional order complex-variable dynamical networks is studied using an adaptive pinning control strategy based on close center degree. Some effective criteria for global synchronization of fractional order complex-variable dynamical networks are derived based on the Lyapunov stability theory. From the theoretical analysis, one concludes that under appropriate conditions, the complex-variable dynamical networks can realize the global synchronization by using the proper adaptive pinning control method. Meanwhile, we succeed in solving the problem about how much coupling strength should be applied to ensure the synchronization of the fractional order complex networks. Therefore, compared with the existing results, the synchronization method in this paper is more general and convenient. This result extends the synchronization condition of the real-variable dynamical networks to the complex-valued field, which makes our research more practical. Finally, two simulation examples show that the derived theoretical results are valid and the proposed adaptive pinning method is effective. Supported by National Natural Science Foundation of China under Grant No. 61201227, National Natural Science Foundation of China Guangdong Joint Fund under Grant No. U1201255, the Natural Science Foundation of Anhui Province under Grant No. 1208085MF93, 211 Innovation Team of Anhui University under Grant Nos. KJTD007A and KJTD001B, and also supported by Chinese Scholarship Council

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

    Science.gov (United States)

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

    2015-01-13

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

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

    Directory of Open Access Journals (Sweden)

    Yusuke Echigoya

    2015-01-01

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

  10. The impact of treatment complexity and computer-control delivery technology on treatment delivery errors

    International Nuclear Information System (INIS)

    Fraass, Benedick A.; Lash, Kathy L.; Matrone, Gwynne M.; Volkman, Susan K.; McShan, Daniel L.; Kessler, Marc L.; Lichter, Allen S.

    1998-01-01

    Purpose: To analyze treatment delivery errors for three-dimensional (3D) conformal therapy performed at various levels of treatment delivery automation and complexity, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system (CCRS). Methods and Materials: All treatment delivery errors which occurred in our department during a 15-month period were analyzed. Approximately 34,000 treatment sessions (114,000 individual treatment segments [ports]) on four treatment machines were studied. All treatment delivery errors logged by treatment therapists or quality assurance reviews (152 in all) were analyzed. Machines 'M1' and 'M2' were operated in a standard manual setup mode, with no record and verify system (R/V). MLC machines 'M3' and 'M4' treated patients under the control of the CCRS system, which (1) downloads the treatment delivery plan from the planning system; (2) performs some (or all) of the machine set up and treatment delivery for each field; (3) monitors treatment delivery; (4) records all treatment parameters; and (5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3; therefore, it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments, nonaxial and noncoplanar plans, multisegment intensity modulation, and pseudoisocentric treatments studied for a 6-month period (505 patients) concurrent with the period in which the delivery errors were obtained. Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines; therefore, this analysis does not depend on fixed therapist staff on particular

  11. 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

    In vector-controlled AC drives, the design of current controller is usually based on a machine model defined in synchronous frame coordinate, where the drive performance may be degraded by both the variation of the machine parameters and the cross-coupling between the d- and q-axes components...... 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...... 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....

  12. Interactions between default mode and control networks as a function of increasing cognitive reasoning complexity.

    Science.gov (United States)

    Hearne, Luke; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

    2015-07-01

    Successful performance of challenging cognitive tasks depends on a consistent functional segregation of activity within the default-mode network, on the one hand, and control networks encompassing frontoparietal and cingulo-opercular areas on the other. Recent work, however, has suggested that in some cognitive control contexts nodes within the default-mode and control networks may actually cooperate to achieve optimal task performance. Here, we used functional magnetic resonance imaging to examine whether the ability to relate variables while solving a cognitive reasoning problem involves transient increases in connectivity between default-mode and control regions. Participants performed a modified version of the classic Wason selection task, in which the number of variables to be related is systematically varied across trials. As expected, areas within the default-mode network showed a parametric deactivation with increases in relational complexity, compared with neural activity in null trials. Critically, some of these areas also showed enhanced connectivity with task-positive control regions. Specifically, task-based connectivity between the striatum and the angular gyri, and between the thalamus and right temporal pole, increased as a function of relational complexity. These findings challenge the notion that functional segregation between regions within default-mode and control networks invariably support cognitive task performance, and reveal previously unknown roles for the striatum and thalamus in managing network dynamics during cognitive reasoning. © 2015 Wiley Periodicals, Inc.

  13. Muscle synergies and complexity of neuromuscular control during gait in cerebral palsy.

    Science.gov (United States)

    Steele, Katherine M; Rozumalski, Adam; Schwartz, Michael H

    2015-12-01

    Individuals with cerebral palsy (CP) have impaired movement due to a brain injury near birth. Understanding how neuromuscular control is altered in CP can provide insight into pathological movement. We sought to determine if individuals with CP demonstrate reduced complexity of neuromuscular control during gait compared with unimpaired individuals and if changes in control are related to functional ability. Muscle synergies during gait were retrospectively analyzed for 633 individuals (age range 3.9-70y): 549 with CP (hemiplegia, n=122; diplegia, n=266; triplegia, n=73; quadriplegia, n=88) and 84 unimpaired individuals. Synergies were calculated using non-negative matrix factorization from surface electromyography collected during previous clinical gait analyses. Synergy complexity during gait was compared with diagnosis subtype, functional ability, and clinical examination measures. Fewer synergies were required to describe muscle activity during gait in individuals with CP compared with unimpaired individuals. Changes in synergies were related to functional impairment and clinical examination measures including selective motor control, strength, and spasticity. Individuals with CP use a simplified control strategy during gait compared with unimpaired individuals. These results were similar to synergies during walking among adult stroke survivors, suggesting similar neuromuscular control strategies between these clinical populations. © 2015 Mac Keith Press.

  14. Effect of interaction strength on robustness of controlling edge dynamics in complex networks

    Science.gov (United States)

    Pang, Shao-Peng; Hao, Fei

    2018-05-01

    Robustness plays a critical role in the controllability of complex networks to withstand failures and perturbations. Recent advances in the edge controllability show that the interaction strength among edges plays a more important role than network structure. Therefore, we focus on the effect of interaction strength on the robustness of edge controllability. Using three categories of all edges to quantify the robustness, we develop a universal framework to evaluate and analyze the robustness in complex networks with arbitrary structures and interaction strengths. Applying our framework to a large number of model and real-world networks, we find that the interaction strength is a dominant factor for the robustness in undirected networks. Meanwhile, the strongest robustness and the optimal edge controllability in undirected networks can be achieved simultaneously. Different from the case of undirected networks, the robustness in directed networks is determined jointly by the interaction strength and the network's degree distribution. Moreover, a stronger robustness is usually associated with a larger number of driver nodes required to maintain full control in directed networks. This prompts us to provide an optimization method by adjusting the interaction strength to optimize the robustness of edge controllability.

  15. Controls of multi-modal wave conditions in a complex coastal setting

    Science.gov (United States)

    Hegermiller, Christie; Rueda, Ana C.; Erikson, Li H.; Barnard, Patrick L.; Antolinez, J.A.A.; Mendez, Fernando J.

    2017-01-01

    Coastal hazards emerge from the combined effect of wave conditions and sea level anomalies associated with storms or low-frequency atmosphere-ocean oscillations. Rigorous characterization of wave climate is limited by the availability of spectral wave observations, the computational cost of dynamical simulations, and the ability to link wave-generating atmospheric patterns with coastal conditions. We present a hybrid statistical-dynamical approach to simulating nearshore wave climate in complex coastal settings, demonstrated in the Southern California Bight, where waves arriving from distant, disparate locations are refracted over complex bathymetry and shadowed by offshore islands. Contributions of wave families and large-scale atmospheric drivers to nearshore wave energy flux are analyzed. Results highlight the variability of influences controlling wave conditions along neighboring coastlines. The universal method demonstrated here can be applied to complex coastal settings worldwide, facilitating analysis of the effects of climate change on nearshore wave climate.

  16. SCIENTIFIC METHODOLOGICAL APPROACHES TO CREATION OF COMPLEX CONTROL SYSTEM MODEL FOR THE STREAMS OF BUILDING WASTE

    Directory of Open Access Journals (Sweden)

    Tskhovrebov Eduard Stanislavovich

    2015-09-01

    Full Text Available In 2011 in Russia a Strategy of Production Development of Construction Materials and Industrial Housing Construction for the period up to 2020 was approved as one of strategic documents in the sphere of construction. In the process of this strategy development all the needs of construction complex were taken into account in all the spheres of economy, including transport system. The strategy also underlined, that the construction industry is a great basis for use and application in secondary economic turnover of dangerous waste from different production branches. This gives possibility to produce construction products of recycled materials and at the same time to solve the problem of environmental protection. The article considers and analyzes scientific methodological approaches to creation of a model of a complex control system for the streams of building waste in frames of organizing uniform ecologically safe and economically effective complex system of waste treatment in country regions.

  17. Pinning-controlled synchronization of complex networks with bounded or unbounded synchronized regions

    International Nuclear Information System (INIS)

    Yan-Li, Zou; Guan-Rong, Chen

    2009-01-01

    This paper studies pinning-controlled synchronization of complex networks with bounded or unbounded synchronized regions. To study a state-feedback pinning-controlled network with N nodes, it first converts the controlled network to an extended network of N+1 nodes without controls. It is shown that the controlled synchronizability of the given network is determined by the real part of the smallest nonzero eigenvalue of the coupling matrix of its extended network when the synchronized region is unbounded; but it is determined by the ratio of the real parts of the largest and the smallest nonzero eigenvalues of the coupling matrix when the synchronized region is bounded. Both theoretical analysis and numerical simulation show that the portion of controlled nodes has no critical values when the synchronized region is unbounded, but it has a critical value when the synchronized region is bounded. In the former case, therefore, it is possible to control the network to achieve synchronization by pinning only one node. In the latter case, the network can achieve controlled synchronization only when the portion of controlled nodes is larger than the critical value. (general)

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  19. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Adaptive control of structural balance for complex dynamical networks based on dynamic coupling of nodes

    Science.gov (United States)

    Gao, Zilin; Wang, Yinhe; Zhang, Lili

    2018-02-01

    In the existing research results of the complex dynamical networks controlled, the controllers are mainly used to guarantee the synchronization or stabilization of the nodes’ state, and the terms coupled with connection relationships may affect the behaviors of nodes, this obviously ignores the dynamic common behavior of the connection relationships between the nodes. In fact, from the point of view of large-scale system, a complex dynamical network can be regarded to be composed of two time-varying dynamic subsystems, which can be called the nodes subsystem and the connection relationships subsystem, respectively. Similar to the synchronization or stabilization of the nodes subsystem, some characteristic phenomena can be also emerged in the connection relationships subsystem. For example, the structural balance in the social networks and the synaptic facilitation in the biological neural networks. This paper focuses on the structural balance in dynamic complex networks. Generally speaking, the state of the connection relationships subsystem is difficult to be measured accurately in practical applications, and thus it is not easy to implant the controller directly into the connection relationships subsystem. It is noted that the nodes subsystem and the relationships subsystem are mutually coupled, which implies that the state of the connection relationships subsystem can be affected by the controllable state of nodes subsystem. Inspired by this observation, by using the structural balance theory of triad, the controller with the parameter adaptive law is proposed for the nodes subsystem in this paper, which may ensure the connection relationship matrix to approximate a given structural balance matrix in the sense of the uniformly ultimately bounded (UUB). That is, the structural balance may be obtained by employing the controlling state of the nodes subsystem. Finally, the simulations are used to show the validity of the method in this paper.

  1. 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.

  2. Complex dynamics of a Holling type II prey-predator system with state feedback control

    International Nuclear Information System (INIS)

    Jiang Guirong; Lu Qishao; Qian Linning

    2007-01-01

    The complex dynamics of a Holling type II prey-predator system with impulsive state feedback control is studied in both theoretical and numerical ways. The sufficient conditions for the existence and stability of semi-trivial and positive periodic solutions are obtained by using the Poincare map and the analogue of the Poincare criterion. The qualitative analysis shows that the positive periodic solution bifurcates from the semi-trivial solution through a fold bifurcation. The bifurcation diagrams, Lyapunov exponents, and phase portraits are illustrated by an example, in which the chaotic solutions appear via a cascade of period-doubling bifurcations. The superiority of the state feedback control strategy is also discussed

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

    International Nuclear Information System (INIS)

    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.

    1994-01-01

    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. ((orig.))

  4. Fabrication of advanced Bragg gratings with complex apodization profiles by use of the polarization control method

    DEFF Research Database (Denmark)

    Deyerl, Hans-Jürgen; Plougmann, Nikolai; Jensen, Jesper Bo Damm

    2004-01-01

    The polarization control method offers a flexible, robust, and low-cost route for the parallel fabrication of gratings with complex apodization profiles including several discrete phase shifts and chirp. The performance of several test gratings is evaluated in terms of their spectral response...... and compared with theoretical predictions. Short gratings with sidelobe-suppression levels in excess of 32 dB and transmission dips lower than 80 dB have been realized. Finally, most of the devices fabricated by the polarization control method show comparable quality to gratings manufactured by far more...

  5. Lower extremity fatigue increases complexity of postural control during a single-legged stance

    Directory of Open Access Journals (Sweden)

    Bailey Jerry J

    2011-08-01

    Full Text Available Abstract Background Non-linear approaches to assessment of postural control can provide insight that compliment linear approaches. Control entropy (CE is a recently developed statistical tool from non-linear dynamical systems used to assess the complexity of non-stationary signals. We have previously used CE of high resolution accelerometry in running to show decreased complexity with exhaustive exercise. The purpose of this study was to determine if complexity of postural control decreases following fatiguing exercise using CE. Methods Ten subjects (5 M/5 F; 25 ± 3 yr; 169.4 ± 11.7 cm; 79.0 ± 16.9 kg consented to participation approved by Western Oregon University IRB and completed two trials separated by 2-7 days. Trials consisted of two single-legged balance tests separated by two Wingate anaerobic tests (WAnT; PreFat/PostFat, or rest period (PreRest/PostRest. Balance tests consisted of a series of five single-legged stances, separated by 30 s rest, performed while standing on the dominant leg for 15-s with the participant crossing the arms over the chest and flexing the non-dominant knee to 90 degrees. High resolution accelerometers (HRA were fixed superficial to L3/L4 at the approximate center of mass (COM. Triaxial signals from the HRA were streamed in real time at 625 Hz. COM accelerations were recorded in g's for vertical (VT, medial/lateral (ML, and anterior/posterior (AP axes. A newly developed statistic (R-test was applied to group response shapes generated by Karhunen Loeve (KL transform modes resulting from Control Entropy (CE analysis. Results R-tests showed a significant mean vector difference (p p p p Conclusions These data indicate that fatiguing exercise eliminates the differential complexity response between axes, but increases complexity in all axes compared to the non-fatigued condition. This has implications with regard to the effects of fatigue on strategies of the control system to maintain postural control.

  6. Effective algorithm for solving complex problems of production control and of material flows control of industrial enterprise

    Science.gov (United States)

    Mezentsev, Yu A.; Baranova, N. V.

    2018-05-01

    A universal economical and mathematical model designed for determination of optimal strategies for managing subsystems (components of subsystems) of production and logistics of enterprises is considered. Declared universality allows taking into account on the system level both production components, including limitations on the ways of converting raw materials and components into sold goods, as well as resource and logical restrictions on input and output material flows. The presented model and generated control problems are developed within the framework of the unified approach that allows one to implement logical conditions of any complexity and to define corresponding formal optimization tasks. Conceptual meaning of used criteria and limitations are explained. The belonging of the generated tasks of the mixed programming with the class of NP is shown. An approximate polynomial algorithm for solving the posed optimization tasks for mixed programming of real dimension with high computational complexity is proposed. Results of testing the algorithm on the tasks in a wide range of dimensions are presented.

  7. 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.

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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

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

    Science.gov (United States)

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

    2017-10-27

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

  14. Assisted reproductive techniques and risk of exstrophy-epispadias complex: a German case-control study.

    Science.gov (United States)

    Zwink, Nadine; Jenetzky, Ekkehart; Hirsch, Karin; Reifferscheid, Peter; Schmiedeke, Eberhard; Schmidt, Dominik; Reckin, Sabrina; Obermayr, Florian; Boemers, Thomas M; Stein, Raimund; Reutter, Heiko; Rösch, Wolfgang H; Brenner, Hermann; Ebert, Anne-Karoline

    2013-04-01

    We assessed the risk of exstrophy-epispadias complex in children conceived by in vitro fertilization or intracytoplasmic sperm injection. Data from the German Network for Congenital Uro-REctal malformations were compared to nationwide data from the German In Vitro Fertilization Register and the German Federal Statistical Office. Odds ratios (95% CI) were determined to quantify associations using logistic regression. A total of 123 patients with exstrophy-epispadias complex born in Germany between 1997 and 2011 were recruited through participating departments of pediatric urology and pediatric surgery throughout the country as well as the German self-help organizations Blasenekstrophie/Epispadie e.V. and Kloakenekstrophie. All German live births (10,069,986) between 1997 and 2010 comprised the controls. Overall, 12 subjects (10%) and 129,982 controls (1%) were conceived by in vitro fertilization or intracytoplasmic sperm injection. Conception by assisted reproductive technique was associated with a more than eightfold increased risk of exstrophy-epispadias complex compared to spontaneous conception (OR 8.3, 95% CI 4.6-15.0, p risk of exstrophy-epispadias complex in children conceived by in vitro fertilization (OR 14.0, 95% CI 6.5-30.0, p study provides evidence that assisted reproductive techniques such as in vitro fertilization and intracytoplasmic sperm injection are associated with a markedly increased risk of having a child born with exstrophy-epispadias complex. However, it remains unclear whether this finding may be due to assisted reproduction per se and/or underlying infertility/subfertility etiology or parent characteristics. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Smythe, Gayle M; White, Jason D

    2011-12-18

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

  16. 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.

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

    Science.gov (United States)

    Vaseashta, Ashok

    2005-03-01

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

  18. 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 [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, SCIB, UMR-E3 CEA-UJF, INAC, CEA-Grenoble (France); Kefalidis, Christos E.; Maron, Laurent [LPCNO, CNRS et INSA, UPS, Universite de Toulouse (France)

    2013-07-01

    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. Such compounds may be useful precursors to uranium ceramics relevant for catalysis and the storage of spent nuclear fuel. (Copyright copyright 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. The alternative complement pathway control protein H binds to immune complexes and serves their detection

    International Nuclear Information System (INIS)

    Nydegger, U.E.; Corvetta, A.; Spaeth, P.J.; Spycher, M.

    1983-01-01

    During solubilization of immune complexes C3b becomes fixed to the immunoglobulin part and serves as a receptor for the alternative complement pathway control protein H. The H-C3b immune complex interaction can be made detectable using 4% polyethyleneglycol to separate free from bound 125 I-H. Tetanus toxoid (Te)/anti-Te complexes kept soluble with fresh serum and containing 125 IU of specific antibody bound 18% of 125 I-H; when fresh serum was chelated with 10 mM EDTA, 125 I-H binding was only 5%. On sucrose density gradients, the H-binding material sedimented in the range of 12 to 30 S. In 36 serum samples from rheumatoid arthritis (RA) patients and in 12 serum samples from patients with systemic lupus erythematosus (SLE), 125 I-H binding was significantly elevated to 9.5 +/- 4.7% (mean +/- 1 SD) and 13.3 +/- 5.6%, respectively, while 125 I-H binding by 36 normal human sera was 4 +/- 2%. RA samples (17/36, 47%) and SLE samples (9/12, 75%) had H-binding values increased by more than 2 SD above the normal mean. The serum samples were also assessed for conglutinin- and C1q-binding activities; a significant correlation between H and C1q binding was observed (P less than 0.001); there was no correlation between H and conglutinin binding. Although binding to immune complexes through its interaction with C3b, H clearly detects a population of complexes other than conglutinin, thus expanding the possibilities of further characterizing pathological complexes

  20. Complex dynamics and bifurcation analysis of host–parasitoid models with impulsive control strategy

    International Nuclear Information System (INIS)

    Yang, Jin; Tang, Sanyi; Tan, Yuanshun

    2016-01-01

    Highlights: • We develop novel host-parasitoid models with impulsive control strategy. • The effects of key parameters on the successful control have been addressed. • The complex dynamics and related biological significance are investigated. • The results between two types of host-parasitoid models have been discussed. - Abstract: In this paper, we propose and analyse two type host–parasitoid models with integrated pest management (IPM) interventions as impulsive control strategies. For fixed pulsed model, the threshold condition for the global stability of the host-eradication periodic solution is provided, and the effects of key parameters including the impulsive period, proportionate killing rate, instantaneous search rate, releasing constant, survival rate and the proportionate release rate on the threshold condition are discussed. Then latin hypercube sampling /partial rank correlation coefficients are used to carry out sensitivity analyses to determine the significance of each parameters. Further, bifurcation analyses are presented and the results show that coexistence of attractors existed for a wide range of parameters, and the switch-like transitions among these attractors indicate that varying dosages and frequencies of insecticide applications and numbers of parasitoid released are crucial for IPM strategy. For unfixed pulsed model, the results show that this model exists very complex dynamics and the host population can be controlled below ET, and it implies that the modelling methods are helpful for improving optimal strategies to design appropriate IPM.

  1. 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.

  2. Controlled molecular self-assembly of complex three-dimensional structures in soft materials.

    Science.gov (United States)

    Huang, Changjin; Quinn, David; Suresh, Subra; Hsia, K Jimmy

    2018-01-02

    Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications. Copyright © 2017 the Author(s). Published by PNAS.

  3. 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.

  4. 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.

  5. The disruptive effects of pain on complex cognitive performance and executive control.

    Science.gov (United States)

    Keogh, Edmund; Moore, David J; Duggan, Geoffrey B; Payne, Stephen J; Eccleston, Christopher

    2013-01-01

    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.

  6. The structure of control and data transfer management system for the GAMMA-400 scientific complex

    International Nuclear Information System (INIS)

    Arkhangelskiy, A I; Bobkov, S G; Serdin, O V; Gorbunov, M S; Topchiev, N P

    2016-01-01

    A description of the control and data transfer management system for scientific instrumentation involved in the GAMMA-400 space project is given. The technical capabilities of all specialized equipment to provide the functioning of the scientific instrumentation and satellite support systems are unified in a single structure. Control of the scientific instruments is maintained using one-time pulse radio commands, as well as program commands in the form of 16-bit code words, which are transmitted via onboard control system and scientific data acquisition system. Up to 100 GByte of data per day can be transferred to the ground segment of the project. The correctness of the proposed and implemented structure, engineering solutions and electronic elemental base selection has been verified by the experimental working-off of the prototype of the GAMMA-400 scientific complex in laboratory conditions. (paper)

  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. 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.

  9. Modified gum Arabic hydrogels as matrices for controlled release of curcumin supramolecular complexes

    International Nuclear Information System (INIS)

    Gerola, Adriana P.; Silva, Danielle C.; Rubira, Adley F.; Muniz, Edvani C.

    2015-01-01

    Modified gum Arabic (GA) hydrogels show a pH-responsive behavior making them excellent matrices to be used for oral administration of drugs. Our goal is to study the behavior of those matrices in simulated gastric and intestinal fluids. In this work we will present how the methacrylation degree of GA, by using glycidyl methacrylate, can affect the properties of these hydrogels for controlled release. The drug used in this work is the curcumin (Cur). Cur is associated with numerous pharmacological activities, but their application is limited by the low water solubility. We will present some studies involving the formation of host-guest complexes between Cur and natural cyclodextrins. Both modified GA and hydrogels were characterized by different techniques. The kinetics release of Cur complex-containing modified GA hydrogels was studied to have an insight on the release mechanism and rate constants. Toxicity studies on undifferentiated and differentiated Caco-2 were also carried out. (author)

  10. Distributed Recurrent Neural Forward Models with Neural Control for Complex Locomotion in Walking Robots

    DEFF Research Database (Denmark)

    Dasgupta, Sakyasingha; Goldschmidt, Dennis; Wörgötter, Florentin

    2015-01-01

    here, an artificial bio-inspired walking system which effectively combines biomechanics (in terms of the body and leg structures) with the underlying neural mechanisms. The neural mechanisms consist of (1) central pattern generator based control for generating basic rhythmic patterns and coordinated......Walking animals, like stick insects, cockroaches or ants, demonstrate a fascinating range of locomotive abilities and complex behaviors. The locomotive behaviors can consist of a variety of walking patterns along with adaptation that allow the animals to deal with changes in environmental...... conditions, like uneven terrains, gaps, obstacles etc. Biological study has revealed that such complex behaviors are a result of a combination of biomechanics and neural mechanism thus representing the true nature of embodied interactions. While the biomechanics helps maintain flexibility and sustain...

  11. 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.

  12. 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.

  13. Constructing Asymmetric Polyion Complex Vesicles via Template Assembling Strategy: Formulation Control and Tunable Permeability

    Directory of Open Access Journals (Sweden)

    Junbo Li

    2017-11-01

    Full Text Available A strategy for constructing polyion complex vesicles (PICsomes with asymmetric structure is described. Poly(methylacrylic acid-block-poly(N-isopropylacrylamide modified gold nanoparticles (PMAA-b-PNIPAm-@-Au NPs were prepared and then assembled with poly(ethylene glycol-block-poly[1-methyl-3-(2-methacryloyloxy propylimidazolium bromine] (PEG-b-PMMPImB via polyion complex of PMMA and PMMPImB. After removing the Au NPs template, asymmetric PICsomes composed of a PNIPAm inner-shell, PIC wall, and PEG outer-corona were obtained. These PICsomes have low protein absorption and thermally tunable permeability, provided by the PEG outer-corona and the PNIPAm inner-shell, respectively. Moreover, PICsome size can be tailored by using templates of predetermined sizes. This novel strategy for constructing asymmetric PICsomes with well-defined properties and controllable size is valuable for applications such as drug delivery, catalysis and monitoring of chemical reactions, and biomimetics.

  14. 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.

  15. Advances in complexity of beam halo-chaos and its control methods for beam transport networks

    International Nuclear Information System (INIS)

    Fang Jinqing

    2004-11-01

    The complexity theory of beam halo-chaos in beam transport networks and its control methods for a new subject of high-tech field is discussed. It is pointed that in recent years, there has been growing interest in proton beams of high power linear accelerator due to its attractive features in possible breakthrough applications in national defense and industry. In particular, high-current accelerator driven clean activity nuclear power systems for various applications as energy resources has been one of the most focusing issues in the current research, because it provides a safer, cleaner and cheaper nuclear energy resource. However, halo-chaos in high-current beam transport networks become a key concerned issue because it can generate excessive radioactivity therefore significantly limits its applications. It is very important to study the complexity properties of beam halo-chaos and to understand the basic physical mechanisms for halo chaos formation as well as to develop effective control methods for its suppression. These are very challenging subjects for the current research. The main research advances in the subjects, including experimental investigation and the oretical research, especially some very efficient control methods developed through many years of efforts of authors are reviewed and summarized. Finally, some research outlooks are given. (author)

  16. 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.

  17. 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.

  18. Phase dynamics of complex-valued neural networks and its application to traffic signal control.

    Science.gov (United States)

    Nishikawa, Ikuko; Iritani, Takeshi; Sakakibara, Kazutoshi; Kuroe, Yasuaki

    2005-01-01

    Complex-valued Hopfield networks which possess the energy function are analyzed. The dynamics of the network with certain forms of an activation function is de-composable into the dynamics of the amplitude and phase of each neuron. Then the phase dynamics is described as a coupled system of phase oscillators with a pair-wise sinusoidal interaction. Therefore its phase synchronization mechanism is useful for the area-wide offset control of the traffic signals. The computer simulations show the effectiveness under the various traffic conditions.

  19. A Lean Framework for Production Control in Complex and Constrained Construction Projects (PC4P)

    DEFF Research Database (Denmark)

    Lindhard, Søren Munch; Wandahl, Søren

    2014-01-01

    Production conditions in construction are different than in themanufacturing industry. First of all, construction is rooted in place and conducted as on-site manufacturing. Secondly, every construction project is unique and a one-of-a-kind production, managed by a temporary organization consisting...... and constrained construction project. Even though several tools have attempted to add structure and to create order, to the complex, dynamic, and uncertain context in which constructions is conducted, none has yet fully succeeded in providing a robust production control system. With outset in the lean tool Last...

  20. 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.

  1. Design of complex bone internal structure using topology optimization with perimeter control.

    Science.gov (United States)

    Park, Jaejong; Sutradhar, Alok; Shah, Jami J; Paulino, Glaucio H

    2018-03-01

    Large facial bone loss usually requires patient-specific bone implants to restore the structural integrity and functionality that also affects the appearance of each patient. Titanium alloys (e.g., Ti-6Al-4V) are typically used in the interfacial porous coatings between the implant and the surrounding bone to promote stability. There exists a property mismatch between the two that in general leads to complications such as stress-shielding. This biomechanical discrepancy is a hurdle in the design of bone replacements. To alleviate the mismatch, the internal structure of the bone replacements should match that of the bone. Topology optimization has proven to be a good technique for designing bone replacements. However, the complex internal structure of the bone is difficult to mimic using conventional topology optimization methods without additional restrictions. In this work, the complex bone internal structure is recovered using a perimeter control based topology optimization approach. By restricting the solution space by means of the perimeter, the intricate design complexity of bones can be achieved. Three different bone regions with well-known physiological loadings are selected to illustrate the method. Additionally, we found that the target perimeter value and the pattern of the initial distribution play a vital role in obtaining the natural curvatures in the bone internal structures as well as avoiding excessive island patterns. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

    Science.gov (United States)

    Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

    2016-08-31

    Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

  3. The CD control improvement by using CDSEM 2D measurement of complex OPC patterns

    Science.gov (United States)

    Chou, William; Cheng, Jeffrey; Lee, Adder; Cheng, James; Tzeng, Alex C.; Lu, Colbert; Yang, Ray; Lee, Hong Jen; Bandoh, Hideaki; Santo, Izumi; Zhang, Hao; Chen, Chien Kang

    2016-10-01

    As the process node becomes more advanced, the accuracy and precision in OPC pattern CD are required in mask manufacturing. CD SEM is an essential tool to confirm the mask quality such as CD control, CD uniformity and CD mean to target (MTT). Unfortunately, in some cases of arbitrary enclosed patterns or aggressive OPC patterns, for instance, line with tiny jogs and curvilinear SRAF, CD variation depending on region of interest (ROI) is a very serious problem in mask CD control, even it decreases the wafer yield. For overcoming this situation, the 2-dimensional (2D) method by Holon is adopted. In this paper, we summarize the comparisons of error budget between conventional (1D) and 2D data using CD SEM and the CD performance between mask and wafer by complex OPC patterns including ILT features.

  4. 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.

  5. Future directions in controlling the LAMPF-PSR Accelerator Complex at Los Alamos National Laboratory

    International Nuclear Information System (INIS)

    Stuewe, R.; Schaller, S.; Bjorklund, E.; Burns, M.; Callaway, T.; Carr, G.; Cohen, S.; Kubicek, D.; Harrington, M.; Poore, R.; Schultz, D.

    1991-01-01

    Four interrelated projects are underway whose purpose is to migrate the LAMPF-PSR Accelerator Complex control systems to a system with a common set of hardware and software components. Project goals address problems in performance, maintenance and growth potential. Front-end hardware, operator interface hardware and software, computer systems, network systems and data system software are being simultaneously upgraded as part of these efforts. The efforts are being coordinated to provide for a smooth and timely migration to a client-sever model-based data acquisition and control system. An increased use of the distributed intelligence at both the front-end and operator interface is a key element of the projects. 2 refs., 2 figs

  6. Future directions in controlling the LAMPF-PSR accelerator complex at Los Alamos National Laboratory

    International Nuclear Information System (INIS)

    Stuewe, R.; Schaller, S.; Bjorklund, E.

    1992-01-01

    Four interrelated projects are underway whose purpose is to migrate the LAMPF-PSR Accelerator Complex control systems to a system with a common set of hardware and software components. Project goals address problems in performance, maintenance and growth potential. Front-end hardware, operator interface hardware and software, computer systems, network systems and data system software are being simultaneously upgraded as part of these efforts. The efforts are being coordinated to provide for a smooth and timely migration to a client-server model-based data acquisition and control system. An increased use of distributed intelligence at both the front-end and the operator interface is a key element of the projects. (author)

  7. 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.

  8. Trade-offs between driving nodes and time-to-control in complex networks

    Science.gov (United States)

    Pequito, Sérgio; Preciado, Victor M.; Barabási, Albert-László; Pappas, George J.

    2017-01-01

    Recent advances in control theory provide us with efficient tools to determine the minimum number of driving (or driven) nodes to steer a complex network towards a desired state. Furthermore, we often need to do it within a given time window, so it is of practical importance to understand the trade-offs between the minimum number of driving/driven nodes and the minimum time required to reach a desired state. Therefore, we introduce the notion of actuation spectrum to capture such trade-offs, which we used to find that in many complex networks only a small fraction of driving (or driven) nodes is required to steer the network to a desired state within a relatively small time window. Furthermore, our empirical studies reveal that, even though synthetic network models are designed to present structural properties similar to those observed in real networks, their actuation spectra can be dramatically different. Thus, it supports the need to develop new synthetic network models able to replicate controllability properties of real-world networks.

  9. Experimental control versus realism: methodological solutions for simulator studies in complex operating environments

    Energy Technology Data Exchange (ETDEWEB)

    Skraaning, Gyrd Jr.

    2004-03-15

    This report is a reprint of a dr.philos. thesis written by Gyrd Skraaning Jr. The text was submitted and accepted by the Norwegian University of Science and Technology in 2003 (ISBN 82-471-5237-1). The thesis suggests a nonlinear model of the theoretical relationship between experimental control and realism, claiming that high degrees of realism and experimental control can be obtained simultaneously if the experimental methods are utilized strategically and developed further. This is in opposition to the conventional opinion that realism and experimental control are mutually excluding objectives. The thesis debates the impact of the operating task on human performance during simulator studies in HAMMLAB, and suggests how task variation can be experimentally controlled. In a within subject design, every subject is tested under all experimental conditions, and the presentation order of the conditions is counterbalanced to compensate for order effects. In realistic settings, it is essential that the experimental design imposes few artificial constrains on the research environment. At the same time, the design should be able to uncover experimental effects in situations where the number of participants is low. Within-subject design represents a reasonable compromise between these aspirations. In this respect, an alternative counterbalancing method is proposed (dis-ORDER). A theoretical analysis of the human performance concept and a discussion about performance measurement in complex operating environments, are followed by a debate on the shortcomings of traditional performance indicators. Two specialized operator performance assessment techniques are then presented and evaluated (OPAS and ORT). (Author)

  10. Experimental control versus realism: methodological solutions for simulator studies in complex operating environments

    International Nuclear Information System (INIS)

    Skraaning, Gyrd Jr.

    2004-03-01

    This report is a reprint of a dr.philos. thesis written by Gyrd Skraaning Jr. The text was submitted and accepted by the Norwegian University of Science and Technology in 2003 (ISBN 82-471-5237-1). The thesis suggests a nonlinear model of the theoretical relationship between experimental control and realism, claiming that high degrees of realism and experimental control can be obtained simultaneously if the experimental methods are utilized strategically and developed further. This is in opposition to the conventional opinion that realism and experimental control are mutually excluding objectives. The thesis debates the impact of the operating task on human performance during simulator studies in HAMMLAB, and suggests how task variation can be experimentally controlled. In a within subject design, every subject is tested under all experimental conditions, and the presentation order of the conditions is counterbalanced to compensate for order effects. In realistic settings, it is essential that the experimental design imposes few artificial constrains on the research environment. At the same time, the design should be able to uncover experimental effects in situations where the number of participants is low. Within-subject design represents a reasonable compromise between these aspirations. In this respect, an alternative counterbalancing method is proposed (dis-ORDER). A theoretical analysis of the human performance concept and a discussion about performance measurement in complex operating environments, are followed by a debate on the shortcomings of traditional performance indicators. Two specialized operator performance assessment techniques are then presented and evaluated (OPAS and ORT). (Author)

  11. Biology, ecology and control of the Penthaleus species complex (Acari: Penthaleidae).

    Science.gov (United States)

    Umina, Paul A; Hoffmann, Ary A; Weeks, Andrew R

    2004-01-01

    Blue oat mites, Penthaleus spp. (Acari: Penthaleidae), are major agricultural pests in southern Australia and other parts of the world, attacking various pasture, vegetable and crop plants. Management of these mites has been complicated by the recent discovery of three cryptic pest species of Penthaleus, whereas prior research had assumed a single species. The taxonomy, population genetics, ecology, biology and control of the Penthaleus spp. complex are reviewed. Adult Penthaleus have a dark blue-black body approximately 1 mm in length, and eight red-orange legs. Within Australia, they are winter pests completing two or three generations a season, depending on conditions. The summer is passed as diapausing eggs, when long-distance dispersal is thought to occur. The Penthaleus spp. reproduce by thelytokous parthenogenesis, with populations comprising clones that differ ecologically. The three pest Penthaleus spp. differ markedly in their distributions, plant hosts, timing of diapause egg production and response to pesticides, highlighting the need to develop control strategies that consider each species separately. Chemicals are the main weapons used in current control programs, however research continues into alternative more sustainable management options. Host plant resistance, crop rotations, conservation of natural enemies, and improved timing of pesticide application would improve the management of these pests. The most cost-effective and environmentally acceptable means of control will result from the integration of these practices combined with the development of a simple field-based kit to distinguish the different mite species.

  12. 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.

  13. Dynamic complexities in a pest control model with birth pulse and harvesting

    International Nuclear Information System (INIS)

    Goel, A.; Gakkhar, S.

    2016-01-01

    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.

  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. From trees to forest: relational complexity network and workload of air traffic controllers.

    Science.gov (United States)

    Zhang, Jingyu; Yang, Jiazhong; Wu, Changxu

    2015-01-01

    In this paper, we propose a relational complexity (RC) network framework based on RC metric and network theory to model controllers' workload in conflict detection and resolution. We suggest that, at the sector level, air traffic showing a centralised network pattern can provide cognitive benefits in visual search and resolution decision which will in turn result in lower workload. We found that the network centralisation index can account for more variance in predicting perceived workload and task completion time in both a static conflict detection task (Study 1) and a dynamic one (Study 2) in addition to other aircraft-level and pair-level factors. This finding suggests that linear combination of aircraft-level or dyad-level information may not be adequate and the global-pattern-based index is necessary. Theoretical and practical implications of using this framework to improve future workload modelling and management are discussed. We propose a RC network framework to model the workload of air traffic controllers. The effect of network centralisation was examined in both a static conflict detection task and a dynamic one. Network centralisation was predictive of perceived workload and task completion time over and above other control variables.

  16. 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. © 2016. Published by The Company of Biologists Ltd.

  17. 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.

  18. RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

    Science.gov (United States)

    Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

    2018-05-01

    RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

  19. Control of GABARAP-mediated autophagy by the Golgi complex, centrosome and centriolar satellites.

    Science.gov (United States)

    Joachim, Justin; Tooze, Sharon A

    2018-01-01

    Within minutes of induction of autophagy by amino-acid starvation in mammalian cells, multiple autophagosomes form throughout the cell cytoplasm. During their formation, the autophagosomes sequester cytoplasmic material and deliver it to lysosomes for degradation. How these organelles can be so rapidly formed and how their formation is acutely regulated are major questions in the autophagy field. Protein and lipid trafficking from diverse cell compartments contribute membrane to, or regulate the formation of the autophagosome. In addition, recruitment of Atg8 (in yeast), and the ATG8-family members (in mammalian cells) to autophagosomes is required for efficient autophagy. Recently, it was discovered that the centrosome and centriolar satellites regulate autophagosome formation by delivery of an ATG8-family member, GABARAP, to the forming autophagosome membrane, the phagophore. We propose that GABARAP regulates phagophore expansion by activating the ULK complex, the amino-acid controlled initiator complex. This finding reveals a previously unknown link between the centrosome, centriolar satellites and autophagy. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  20. PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs.

    Science.gov (United States)

    Zhu, Zhexin; Li, Chunliang; Zeng, Yanwu; Ding, Jianyi; Qu, Zepeng; Gu, Junjie; Ge, Laixiang; Tang, Fan; Huang, Xin; Zhou, Chenlin; Wang, Ping; Zheng, Deyou; Jin, Ying

    2017-02-02

    The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of α-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Shifting effects in randomised controlled trials of complex interventions: a new kind of performance bias?

    Science.gov (United States)

    Gold, C; Erkkilä, J; Crawford, M J

    2012-11-01

    Randomised controlled trials (RCTs) aim to provide unbiased estimates of treatment effects. However, the process of implementing trial procedures may have an impact on the performance of complex interventions that rely strongly on the intuition and confidence of therapists. We aimed to examine whether shifting effects over the recruitment period can be observed that might indicate such impact. Three RCTs investigating music therapy vs. standard care were included. The intervention was performed by experienced therapists and based on established methods. We examined outcomes of participants graphically, analysed cumulative effects and tested for differences between first vs. later participants. We tested for potential confounding population shifts through multiple regression models. Cumulative differences suggested trends over the recruitment period. Effect sizes tended to be less favourable among the first participants than later participants. In one study, effects even changed direction. Age, gender and baseline severity did not account for these shifting effects. Some trials of complex interventions have shifting effects over the recruitment period that cannot be explained by therapist experience or shifting demographics. Replication and further research should aim to find out which interventions and trial designs are most vulnerable to this new kind of performance bias. © 2012 John Wiley & Sons A/S.

  2. Dysfunction of Protein Quality Control in Parkinsonism–Dementia Complex of Guam

    Directory of Open Access Journals (Sweden)

    Bert M. Verheijen

    2018-03-01

    Full Text Available Guam parkinsonism–dementia complex (G-PDC is an enigmatic neurodegenerative disease that is endemic to the Pacific island of Guam. G-PDC patients are clinically characterized by progressive cognitive impairment and parkinsonism. Neuropathologically, G-PDC is characterized by abundant neurofibrillary tangles, which are composed of hyperphosphorylated tau, marked deposition of 43-kDa TAR DNA-binding protein, and neuronal loss. Although both genetic and environmental factors have been implicated, the etiology and pathogenesis of G-PDC remain unknown. Recent neuropathological studies have provided new clues about the pathomechanisms involved in G-PDC. For example, deposition of abnormal components of the protein quality control system in brains of G-PDC patients indicates a role for proteostasis imbalance in the disease. This opens up promising avenues for new research on G-PDC and could have important implications for the study of other neurodegenerative disorders.

  3. The development of controls for pulse-to-pulse modulation at the Brookhaven AGS complex

    International Nuclear Information System (INIS)

    Barton, D.S.

    1989-01-01

    Operation of the AGS Complex, comprising a 200 MeV Linac, the 1.5 GeV Booster (400 MeV/amu heavy ions) which is under construction, and the AGS, requires service of multiple uses with different beam requirements. Local Linac users, Booster commissioning with protons and heavy ions, and the AGS physics program and accelerator studies must run concurrently in various combinations. A new timing system is being built which will distribute serially encoded events derived from real-time and magnetic field clocks to each accelerator. The master timing of the supercycle will be managed centrally with encoded reset events determining the assigned user for each pulse. Operational aspects of the design of this system will be described, along with the principal control system modifications necessary to implement this mode of operation. 4 refs., 3 figs

  4. RFID card based access control system with counter for Indus Complex

    International Nuclear Information System (INIS)

    Jathar, M.R.; Vikas, Meshram; Patidar, S.C.

    2015-01-01

    As per norms of the Atomic energy regulatory board (AERB) to operate a facility in round the clock which has a potential of radiation exposure, radiation safety rules are to be followed. Indus -1 and Indus-2 are synchrotron radiation sources which are open for various users round the clock. To monitor the persons inside the defined zone at any given time, a system is setup consisting of RF ID cards and their readers along with dedicated software. Software is developed in Visual Basic and uses UDP network protocol for receiving data from readers installed at various locations and connected to local area network. The paper describes the access control scheme followed in Indus Accelerator Complex. (author)

  5. Design and control of the precise tracking bed based on complex electromechanical design theory

    Science.gov (United States)

    Ren, Changzhi; Liu, Zhao; Wu, Liao; Chen, Ken

    2010-05-01

    The precise tracking technology is wide used in astronomical instruments, satellite tracking and aeronautic test bed. However, the precise ultra low speed tracking drive system is one high integrated electromechanical system, which one complexly electromechanical design method is adopted to improve the efficiency, reliability and quality of the system during the design and manufacture circle. The precise Tracking Bed is one ultra-exact, ultra-low speed, high precision and huge inertial instrument, which some kind of mechanism and environment of the ultra low speed is different from general technology. This paper explores the design process based on complex electromechanical optimizing design theory, one non-PID with a CMAC forward feedback control method is used in the servo system of the precise tracking bed and some simulation results are discussed.

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

    Directory of Open Access Journals (Sweden)

    Nayereh Nouri

    2014-01-01

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

  7. Geologic and climatic controls on streamflow generation processes in a complex eogenetic karst basin

    Science.gov (United States)

    Vibhava, F.; Graham, W. D.; Maxwell, R. M.

    2012-12-01

    Streamflow at any given location and time is representative of surface and subsurface contributions from various sources. The ability to fully identify the factors controlling these contributions is key to successfully understanding the transport of contaminants through the system. In this study we developed a fully integrated 3D surface water-groundwater-land surface model, PARFLOW, to evaluate geologic and climatic controls on streamflow generation processes in a complex eogenetic karst basin in North Central Florida. In addition to traditional model evaluation criterion, such as comparing field observations to model simulated streamflow and groundwater elevations, we quantitatively evaluated the model's predictions of surface-groundwater interactions over space and time using a suite of binary end-member mixing models that were developed using observed specific conductivity differences among surface and groundwater sources throughout the domain. Analysis of model predictions showed that geologic heterogeneity exerts a strong control on both streamflow generation processes and land atmospheric fluxes in this watershed. In the upper basin, where the karst aquifer is overlain by a thick confining layer, approximately 92% of streamflow is "young" event flow, produced by near stream rainfall. Throughout the upper basin the confining layer produces a persistent high surficial water table which results in high evapotranspiration, low groundwater recharge and thus negligible "inter-event" streamflow. In the lower basin, where the karst aquifer is unconfined, deeper water tables result in less evapotranspiration. Thus, over 80% of the streamflow is "old" subsurface flow produced by diffuse infiltration through the epikarst throughout the lower basin, and all surface contributions to streamflow originate in the upper confined basin. Climatic variability provides a secondary control on surface-subsurface and land-atmosphere fluxes, producing significant seasonal and

  8. The Effect of Visual Stimuli on Stability and Complexity of Postural Control

    Directory of Open Access Journals (Sweden)

    Haizhen Luo

    2018-02-01

    Full Text Available Visual input could benefit balance control or increase postural sway, and it is far from fully understanding the effect of visual stimuli on postural stability and its underlying mechanism. In this study, the effect of different visual inputs on stability and complexity of postural control was examined by analyzing the mean velocity (MV, SD, and fuzzy approximate entropy (fApEn of the center of pressure (COP signal during quiet upright standing. We designed five visual exposure conditions: eyes-closed, eyes-open (EO, and three virtual reality (VR scenes (VR1–VR3. The VR scenes were a limited field view of an optokinetic drum rotating around yaw (VR1, pitch (VR2, and roll (VR3 axes, respectively. Sixteen healthy subjects were involved in the experiment, and their COP trajectories were assessed from the force plate data. MV, SD, and fApEn of the COP in anterior–posterior (AP, medial–lateral (ML directions were calculated. Two-way analysis of variance with repeated measures was conducted to test the statistical significance. We found that all the three parameters obtained the lowest values in the EO condition, and highest in the VR3 condition. We also found that the active neuromuscular intervention, indicated by fApEn, in response to changing the visual exposure conditions were more adaptive in AP direction, and the stability, indicated by SD, in ML direction reflected the changes of visual scenes. MV was found to capture both instability and active neuromuscular control dynamics. It seemed that the three parameters provided compensatory information about the postural control in the immersive virtual environment.

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

    Directory of Open Access Journals (Sweden)

    Chicoine Louis G

    2007-09-01

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

  10. Protein complexes and cholesterol in the control of late endosomal dynamicsCholesterol and multi-protein complexes in the control of late endosomal dynamics

    NARCIS (Netherlands)

    Kant, Rik Henricus Nicolaas van der

    2013-01-01

    Late endosomal transport is disrupted in several diseases such as Niemann-Pick type C, ARC syndrome and Alzheimer’s disease. This thesis describes the regulation of late endosomal dynamics by cholesterol and multi-protein complexes. We find that cholesterol acts as a cellular tomtom that steers the

  11. Automatic Generation of Complex Spatial Trajectories of the UAV and Synthesis of Control

    Directory of Open Access Journals (Sweden)

    S. B. Tkachev

    2015-01-01

    Full Text Available In this paper, we propose a new method and algorithms that allow us to design complex spatial trajectories for an unmanned aerial vehicle (UAV passing through a given sequence of waypoints in the three-dimensional space.The nonlinear six-dimensional model of the UAV center-of-mass motion given in the trajectory frame is used for calculations. The state vector includes the altitude, the along-track deviation, the cross-track position, the velocity, the flight-path angle and the heading angle. The longitudinal and transverse overloads and the angle between the cross overload vector and vertical plane are considered as controls. This angle is often named as the roll angle.The feature of the problem is that both positions at waypoints and additional conditions are given. These conditions determine orientation of the velocity vector at each point (using the flight path angle and the heading angle. We also set either the point-visiting time or the pointvisiting velocity. The full state vector and controls are fixed at the starting waypoint.To construct a spatial trajectory, the concept of inverse dynamics problems is applied, as well as modern results of mathematical control theory of nonlinear dynamical systems. The introduction of new virtual controls allows us to represent the original system as an affine (linear in control system. Then, the designed system is converted into the regular canonical form.When we set flight times between any two waypoints, the corresponding segments of the trajectory are designed using time-dependent polynomials of the fifth degree. These polynomials specify the altitude variation, the variation of the along-track deviation and that of the cross-track position. If the point-visiting times are not fixed, the transition to a new independent variable (the normalized mechanical energy of the system is used. This transition is possible if the energy varies monotonically. In this case, the spatial trajectory is defined as a

  12. Automation of multi-agent control for complex dynamic systems in heterogeneous computational network

    Science.gov (United States)

    Oparin, Gennady; Feoktistov, Alexander; Bogdanova, Vera; Sidorov, Ivan

    2017-01-01

    The rapid progress of high-performance computing entails new challenges related to solving large scientific problems for various subject domains in a heterogeneous distributed computing environment (e.g., a network, Grid system, or Cloud infrastructure). The specialists in the field of parallel and distributed computing give the special attention to a scalability of applications for problem solving. An effective management of the scalable application in the heterogeneous distributed computing environment is still a non-trivial issue. Control systems that operate in networks, especially relate to this issue. We propose a new approach to the multi-agent management for the scalable applications in the heterogeneous computational network. The fundamentals of our approach are the integrated use of conceptual programming, simulation modeling, network monitoring, multi-agent management, and service-oriented programming. We developed a special framework for an automation of the problem solving. Advantages of the proposed approach are demonstrated on the parametric synthesis example of the static linear regulator for complex dynamic systems. Benefits of the scalable application for solving this problem include automation of the multi-agent control for the systems in a parallel mode with various degrees of its detailed elaboration.

  13. Material control and accounting in the Department of Energy's nuclear fuel complex

    Energy Technology Data Exchange (ETDEWEB)

    None

    1989-01-01

    Material control and accounting takes place within an envelope of activities related to safeguards and security, as well as to safety, health, and environment, all of which need to be managed to assure that the entire nuclear fuel complex can operate in a societally accepted manner. Within this envelope the committee was directed to carry out the following scope of work: (1) Review the MCandA systems in use at selected DOE facilities that are processing special nuclear material (SNM) in various physical and chemical forms. (2) Design and convene a workshop for senior representatives from each of DOE's facilities on the flows and inventories of nuclear materials. (3) Plan and conduct a series of site visits to each of the facilities to observe first hand the processing operations and the related MCandA systems. (4) Review the potential improvement in overall safeguard systems effectiveness, as measured by expected reduction in inventory difference control limits and inventory differences for materials balance accounts and facilities, or other criteria as appropriate. Indicate how this affects the relative degree of uncertainty in the system. (5) Review the efficiency of operating the MCandA system with and without the upgrading options and assess whether upgrading will contribute further efficiencies in operation, which may reduce many of the current operations costs. Determine if the current system is cost-effective. (6) Recommend the most promising technical approaches for further development by DOE and further study as warranted.

  14. Non-neural Muscle Weakness Has Limited Influence on Complexity of Motor Control during Gait

    Directory of Open Access Journals (Sweden)

    Marije Goudriaan

    2018-01-01

    Full Text Available Cerebral palsy (CP and Duchenne muscular dystrophy (DMD are neuromuscular disorders characterized by muscle weakness. Weakness in CP has neural and non-neural components, whereas in DMD, weakness can be considered as a predominantly non-neural problem. Despite the different underlying causes, weakness is a constraint for the central nervous system when controlling gait. CP demonstrates decreased complexity of motor control during gait from muscle synergy analysis, which is reflected by a higher total variance accounted for by one synergy (tVAF1. However, it remains unclear if weakness directly contributes to higher tVAF1 in CP, or whether altered tVAF1 reflects mainly neural impairments. If muscle weakness directly contributes to higher tVAF1, then tVAF1 should also be increased in DMD. To examine the etiology of increased tVAF1, muscle activity data of gluteus medius, rectus femoris, medial hamstrings, medial gastrocnemius, and tibialis anterior were measured at self-selected walking speed, and strength data from knee extensors, knee flexors, dorsiflexors and plantar flexors, were analyzed in 15 children with CP [median (IQR age: 8.9 (2.2], 15 boys with DMD [8.7 (3.1], and 15 typical developing (TD children [8.6 (2.7]. We computed tVAF1 from 10 concatenated steps with non-negative matrix factorization, and compared tVAF1 between the three groups with a Mann-Whiney U-test. Spearman's rank correlation coefficients were used to determine if weakness in specific muscle groups contributed to altered tVAF1. No significant differences in tVAF1 were found between DMD [tVAF1: 0.60 (0.07] and TD children [0.65 (0.07], while tVAF1 was significantly higher in CP [(0.74 (0.09] than in the other groups (both p < 0.005. In CP, weakness in the plantar flexors was related to higher tVAF1 (r = −0.72. In DMD, knee extensor weakness related to increased tVAF1 (r = −0.50. These results suggest that the non-neural weakness in DMD had limited influence on

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

    Directory of Open Access Journals (Sweden)

    Alberto Malerba

    2012-01-01

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

  16. Composite Scaffold of Poly(Vinyl Alcohol) and Interfacial Polyelectrolyte Complexation Fibers for Controlled Biomolecule Delivery

    Science.gov (United States)

    Cutiongco, Marie Francene A.; Choo, Royden K. T.; Shen, Nathaniel J. X.; Chua, Bryan M. X.; Sju, Ervi; Choo, Amanda W. L.; Le Visage, Catherine; Yim, Evelyn K. F.

    2015-01-01

    Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC) fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor, and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol) hydrogel (PVA). Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight. Next, IPC fibers were incorporated in between layers of PVA to produce PVA–IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA–IPC composite grafts exhibited dependence on molecular weight, with lysozyme showing near-linear release for 1 month. Angiogenic factors were also incorporated into the PVA–IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA–IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release, and bioinertness, PVA–IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft tissue

  17. Composite scaffold of poly(vinyl alcohol) and interfacial polyelectrolyte complexation fibers for controlled biomolecule delivery.

    Science.gov (United States)

    Cutiongco, Marie Francene A; Choo, Royden K T; Shen, Nathaniel J X; Chua, Bryan M X; Sju, Ervi; Choo, Amanda W L; Le Visage, Catherine; Yim, Evelyn K F

    2015-01-01

    Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC) fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor, and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol) hydrogel (PVA). Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight. Next, IPC fibers were incorporated in between layers of PVA to produce PVA-IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA-IPC composite grafts exhibited dependence on molecular weight, with lysozyme showing near-linear release for 1 month. Angiogenic factors were also incorporated into the PVA-IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA-IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release, and bioinertness, PVA-IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft tissue engineering.

  18. RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

    Directory of Open Access Journals (Sweden)

    Uta Meyer Zum Büschenfelde

    2018-05-01

    Full Text Available RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1 as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

  19. A Model of Human Decision Making in Complex Systems and its Use for Design of System Control Strategies

    DEFF Research Database (Denmark)

    Rasmussen, Jens; Lind, Morten

    The paper describes a model of operators' decision making in complex system control, based on studies of event reports and performance in control rooms. This study shows how operators base their decisions on knowledge of system properties at different levels of abstraction depending on their perc...... representation of system properties in a multilevel flow model is described to provide a basis for an integrated control system design.......The paper describes a model of operators' decision making in complex system control, based on studies of event reports and performance in control rooms. This study shows how operators base their decisions on knowledge of system properties at different levels of abstraction depending...... on their perception of the system's immediate control requirements. These levels correspond to the abstraction hierarchy including system purpose, functions, and physical details, which is generally used to describe a formal design process. In emergency situations the task of the operator is to design a suitable...

  20. Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G. Cutroneo

    2015-06-01

    Full Text Available The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

  1. Complexity and Pilot Workload Metrics for the Evaluation of Adaptive Flight Controls on a Full Scale Piloted Aircraft

    Science.gov (United States)

    Hanson, Curt; Schaefer, Jacob; Burken, John J.; Larson, David; Johnson, Marcus

    2014-01-01

    Flight research has shown the effectiveness of adaptive flight controls for improving aircraft safety and performance in the presence of uncertainties. The National Aeronautics and Space Administration's (NASA)'s Integrated Resilient Aircraft Control (IRAC) project designed and conducted a series of flight experiments to study the impact of variations in adaptive controller design complexity on performance and handling qualities. A novel complexity metric was devised to compare the degrees of simplicity achieved in three variations of a model reference adaptive controller (MRAC) for NASA's F-18 (McDonnell Douglas, now The Boeing Company, Chicago, Illinois) Full-Scale Advanced Systems Testbed (Gen-2A) aircraft. The complexity measures of these controllers are also compared to that of an earlier MRAC design for NASA's Intelligent Flight Control System (IFCS) project and flown on a highly modified F-15 aircraft (McDonnell Douglas, now The Boeing Company, Chicago, Illinois). Pilot comments during the IRAC research flights pointed to the importance of workload on handling qualities ratings for failure and damage scenarios. Modifications to existing pilot aggressiveness and duty cycle metrics are presented and applied to the IRAC controllers. Finally, while adaptive controllers may alleviate the effects of failures or damage on an aircraft's handling qualities, they also have the potential to introduce annoying changes to the flight dynamics or to the operation of aircraft systems. A nuisance rating scale is presented for the categorization of nuisance side-effects of adaptive controllers.

  2. Models and synchronization of time-delayed complex dynamical networks with multi-links based on adaptive control

    International Nuclear Information System (INIS)

    Peng Haipeng; Wei Nan; Li Lixiang; Xie Weisheng; Yang Yixian

    2010-01-01

    In this Letter, time-delay has been introduced in to split the networks, upon which a model of complex dynamical networks with multi-links has been constructed. Moreover, based on Lyapunov stability theory and some hypotheses, we achieve synchronization between two complex networks with different structures by designing effective controllers. The validity of the results was proved through numerical simulations of this Letter.

  3. Heterobimetallic porphyrin complexes displaying triple dynamics: coupled metal motions controlled by constitutional evolution.

    Science.gov (United States)

    Le Gac, Stéphane; Fusaro, Luca; Roisnel, Thierry; Boitrel, Bernard

    2014-05-07

    A bis-strap porphyrin ligand (1), with an overhanging carboxylic acid group on each side of the macrocycle, has been investigated toward the formation of dynamic libraries of bimetallic complexes with Hg(II), Cd(II), and Pb(II). Highly heteroselective metalation processes occurred in the presence of Pb(II), with Hg(II) or Cd(II) bound out-of-plane to the N-core and "PbOAc" bound to a carboxylate group of a strap on the opposite side. The resulting complexes, 1(Hg)·PbOAc and 1(Cd)·PbOAc, display three levels of dynamics. The first is strap-level (interactional dynamics), where the PbOAc moiety swings between the left and right side of the strap owing to a second sphere of coordination with lateral amide functions. The second is ligand-level (motional dynamics), where 1(Hg)·PbOAc and 1(Cd)·PbOAc exist as two degenerate states in equilibrium controlled by a chemical effector (AcO(-)). The process corresponds to a double translocation of the metal ions according to an intramolecular migration of Hg(II) or Cd(II) through the N-core, oscillating between the two equivalent overhanging carbonyl groups, coupled to an intermolecular pathway for PbOAc exchanging between the two equivalent overhanging carboxylate groups (N-core(up) ⇆ N-core(down) coupled to strap(down) ⇆ strap(up), i.e., coupled motion #1 in the abstract graphic). The third is library-level (constitutional dynamics), where a dynamic constitutional evolution of the system was achieved by the successive addition of two chemical effectors (DMAP and then AcO(-)). It allowed shifting equilibrium forward and backward between 1(Hg)·PbOAc and the corresponding homobimetallic complexes 1(Hg2)·DMAP and 1(Pb)·PbOAc. The latter displays a different ligand-level dynamics, in the form of an intraligand coupled migration of the Pb(II) ions (N-core(up) ⇆ strap(up) coupled to strap(down) ⇆ N-core(down), i.e., coupled motion #2 in the abstract graphic). In addition, the neutral "bridged" complexes 1HgPb and 1Cd

  4. Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and α7 integrin

    Science.gov (United States)

    Marshall, Jamie L.; Oh, Jennifer; Chou, Eric; Lee, Joy A.; Holmberg, Johan; Burkin, Dean J.; Crosbie-Watson, Rachelle H.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene that result in loss of the dystrophin–glycoprotein complex, a laminin receptor that connects the myofiber to its surrounding extracellular matrix. Utrophin, a dystrophin ortholog that is normally localized to the neuromuscular junction, is naturally upregulated in DMD muscle, which partially compensates for the loss of dystrophin. Transgenic overexpression of utrophin causes broad sarcolemma localization of utrophin, restoration of laminin binding and amelioration of disease in the mdx mouse model of DMD. We previously demonstrated that overexpression of sarcospan, a dystrophin- and utrophin-binding protein, ameliorates mdx muscular dystrophy. Sarcospan boosts levels of utrophin to therapeutic levels at the sarcolemma, where attachment to laminin is restored. However, understanding the compensatory mechanism is complicated by concomitant upregulation of α7β1 integrin, which also binds laminin. Similar to the effects of utrophin, transgenic overexpression of α7 integrin prevents DMD disease in mice and is accompanied by increased abundance of utrophin around the extra-synaptic sarcolemma. In order to investigate the mechanisms underlying sarcospan ‘rescue’ of muscular dystrophy, we created double-knockout mice to test the contributions of utrophin or α7 integrin. We show that sarcospan-mediated amelioration of muscular dystrophy in DMD mice is dependent on the presence of both utrophin and α7β1 integrin, even when they are individually expressed at therapeutic levels. Furthermore, we found that association of sarcospan into laminin-binding complexes is dependent on utrophin and α7β1 integrin. PMID:25504048

  5. Redox control of electric melters with complex feed compositions. Part I: analytical methods and models

    International Nuclear Information System (INIS)

    Bickford, D.F.; Diemer, R.B. Jr.

    1985-01-01

    The redox state of glass from electric melters with complex feed compositions is determined by balance between gases above the melt, and transition metals and organic compounds in the feed. Part I discusses experimental and computational methods of relating flowrates and other melter operating conditions to the redox state of glass, and composition of the melter offgas. Computerized thermodynamic computational methods are useful in predicting the sequence and products of redox reactions and in assessing individual process variations. Melter redox state can be predicted by combining monitoring of melter operating conditions, redox measurement of fused melter feed samples, and periodic redox measurement of product. Mossbauer spectroscopy, and other methods which measure Fe(II)/Fe(III) in glass, can be used to measure melter redox state. Part II develops preliminary operating limits for the vitrification of High-Level Radioactive Waste. Limits on reducing potential to preclude the accumulation of combustible gases, accumulation of sulfides and selenides, and degradation of melter components are the most critical. Problems associated with excessively oxidizing conditions, such as glass foaming and potential ruthenium volatility, are controlled when sufficient formic acid is added to adjust melter feed rheology

  6. Balancing Control and Complexity in Field Studies of Neonicotinoids and Honey Bee Health

    Science.gov (United States)

    Suryanarayanan, Sainath

    2013-01-01

    Amidst ongoing declines in honey bee health, the contributory role of the newer systemic insecticides continues to be intensely debated. Scores of toxicological field experiments, which bee scientists and regulators in the United States have looked to for definitive causal evidence, indicate a lack of support. This paper analyzes the methodological norms that shape the design and interpretation of field toxicological studies. I argue that contemporary field studies of honey bees and pesticides are underpinned by a “control-oriented” approach, which precludes a serious investigation of the indirect and multifactorial ways in which pesticides could drive declines in honey bee health. I trace the historical rise to prominence of this approach in honey bee toxicology to the development of entomology as a science of insecticide development in the United States. Drawing on “complexity-oriented” knowledge practices in ecology, epidemiology, beekeeping and sociology, I suggest an alternative socio-ecological systems approach, which would entail in situ studies that are less concerned with isolating individual factors and more attentive to the interactive and place-based mix of factors affecting honey bee health. PMID:26466800

  7. MET receptor tyrosine kinase controls dendritic complexity, spine morphogenesis, and glutamatergic synapse maturation in the hippocampus.

    Science.gov (United States)

    Qiu, Shenfeng; Lu, Zhongming; Levitt, Pat

    2014-12-03

    The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk. Copyright © 2014 the authors 0270-6474/14/3416166-14$15.00/0.

  8. Efficiency Control in Iridium Complex-Based Phosphorescent Light-Emitting Diodes

    Directory of Open Access Journals (Sweden)

    Boucar Diouf

    2012-01-01

    Full Text Available Key factors to control the efficiency in iridium doped red and green phosphorescent light emitting diodes (PhOLEDs are discussed in this review: exciton confinement, charge trapping, dopant concentration and dopant molecular structure. They are not independent from each other but we attempt to present each of them in a situation where its specific effects are predominant. A good efficiency in PhOLEDs requires the triplet energy of host molecules to be sufficiently high to confine the triplet excitons within the emitting layer (EML. Furthermore, triplet excitons must be retained within the EML and should not drift into the nonradiative levels of the electron or hole transport layer (resp., ETL or HTL; this is achieved by carefully choosing the EML’s adjacent layers. We prove how reducing charge trapping results in higher efficiency in PhOLEDs. We show that there is an ideal concentration for a maximum efficiency of PhOLEDs. Finally, we present the effects of molecular structure on the efficiency of PhOLEDs using red iridium complex dopant with different modifications on the ligand to tune its highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO energies.

  9. In-flight simulation of high agility through active control: Taming complexity by design

    Science.gov (United States)

    Padfield, Gareth D.; Bradley, Roy

    1993-01-01

    The motivation for research into helicopter agility stems from the realization that marked improvements relative to current operational types are possible, yet there is a dearth of useful criteria for flying qualities at high performance levels. Several research laboratories are currently investing resources in developing second generation airborne rotorcraft simulators. The UK's focus has been the exploitation of agility through active control technology (ACT); this paper reviews the results of studies conducted to date. The conflict between safety and performance in flight research is highlighted and the various forms of safety net to protect against system failures are described. The role of the safety pilot, and the use of actuator and flight envelope limiting are discussed. It is argued that the deep complexity of a research ACT system can only be tamed through a requirement specification assembled using design principles and cast in an operational simulation form. Work along these lines conducted at DRA is described, including the use of the Jackson System Development method and associated Ada simulation.

  10. A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

    Science.gov (United States)

    Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

    2016-12-22

    In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy 1-3 . Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S 44 > S 60 > S 40 > S 29 ). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study 4 , we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

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

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1995-09-01

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

  12. Controlled acrylate insertion regioselectivity in diazaphospholidine- sulfonato palladium(II) complexes

    KAUST Repository

    Wucher, Philipp

    2012-12-24

    Diazaphospholidine-sulfonato Pd(II) complexes [{κ2-P,O-(N- Ar2C2H4N2P)C6H 4SO3}PdMe(L)] 1-L (L = dmso, pyridine, lutidine, or μ-LiCl(solvent); 1a: Ar = Ph, 1b: Ar = 2-MeC6H4, 1c: Ar = 2-MeOC6H4, 1d: Ar = 2,4,6-Me3C 6H2, 1e: Ar = 2,6-iPr2C6H 3, 1f: Ar = 2,6-(p-tolyl)2C6H3) were prepared and structurally characterized. The regioselectivity of methyl acrylate (MA) insertion into the Pd-Me bond is entirely inverted from >93% 1,2-insertion for bulky substituents (1d-f, yielding the insertion products [(P̂O)Pd{κ2-C,O-CH2CHMeC(O)OMe], 12) to the usual electronically controlled 2,1-insertion (>95%) for the less bulky Ar = Ph (1a, yielding the insertion product [(P̂O)Pd{κ2-C,O- CHEtC(O)OMe], 11, and β-H elimination product methyl crotonate). DFT studies underline that this is due to a more favorable insertion transition state (2,1- favored by 12 kJ mol-1 over 1,2- for 1a) vs destabilization of the 2,1-insertion transition state in 1d,e. By contrast, MA insertion into the novel isolated and structurally characterized hydride and deuteride complexes [{κ2-P,O-(N-Ar2C 2H4N2P)C6H4SO 3}PdR(lutidine)] (Ar = 2,6-iPr2C6H3; 9e: R = H, 10e: R = D) occurs 2,1-selectively. This is due to the insertion occurring from the isomer with the P-donor and the olefin in trans arrangement, rather than the insertion into the alkyl from the cis isomer in which the olefin is in proximity to the bulky diazaphospholidine. 1a-f are precursors to active catalysts for ethylene polymerization to highly linear polyethylene with M n up to 35 000 g mol-1. In copolymerization experiments, norbornene was incorporated in up to 6.1 mol % into the polyethylene backbone. © 2012 American Chemical Society.

  13. Towards controlled innovation of complex objects.: A sociotechnical approach to describing ship design

    OpenAIRE

    van Bruinessen, T.M.

    2016-01-01

    Within the ship design industry, and in particular in the development of large, complex and innovative vessels experienced ship designers play an important role in organizing and structuring the design process. How this actually happens within projects that develop such large, complex and innovative vessels for a single client is not clear. This observation lead to a broad, initial research question as the starting point for further research. How are innovative, large and complex vessels deve...

  14. Design and Simulation of the Robust ABS and ESP Fuzzy Logic Controller on the Complex Braking Maneuvers

    Directory of Open Access Journals (Sweden)

    Andrei Aksjonov

    2016-11-01

    Full Text Available Automotive driving safety systems such as an anti-lock braking system (ABS and an electronic stability program (ESP assist drivers in controlling the vehicle to avoid road accidents. In this paper, ABS and the ESP, based on the fuzzy logic theory, are integrated for vehicle stability control in complex braking maneuvers. The proposed control algorithm is implemented for a sport utility vehicle (SUV and investigated for braking on different surfaces. The results obtained for the vehicle software simulator confirm the robustness of the developed control strategy for a variety of road profiles and surfaces.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-06-01

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

  17. Dose prescription complexity versus tumor control probability in biologically conformal radiotherapy

    International Nuclear Information System (INIS)

    South, C. P.; Evans, P. M.; Partridge, M.

    2009-01-01

    The technical feasibility and potential benefits of voxel-based nonuniform dose prescriptions for biologically heterogeneous tumors have been widely demonstrated. In some cases, an ''ideal'' dose prescription has been generated by individualizing the dose to every voxel within the target, but often this voxel-based prescription has been discretized into a small number of compartments. The number of dose levels utilized and the methods used for prescribing doses and assigning tumor voxels to different dose compartments have varied significantly. The authors present an investigation into the relationship between the complexity of the dose prescription and the tumor control probability (TCP) for a number of these methods. The linear quadratic model of cell killing was used in conjunction with a number of modeled tumors heterogeneous in clonogen density, oxygenation, or proliferation. Models based on simple mathematical functions, published biological data, and biological image data were investigated. Target voxels were assigned to dose compartments using (i) simple rules based on the initial biological distribution, (ii) iterative methods designed to maximize the achievable TCP, or (iii) methods based on an ideal dose prescription. The relative performance of the simple rules was found to depend on the form of heterogeneity of the tumor, while the iterative and ideal dose methods performed comparably for all models investigated. In all cases the maximum achievable TCP was approached within the first few (typically two to five) compartments. Results suggest that irrespective of the pattern of heterogeneity, the optimal dose prescription can be well approximated using only a few dose levels but only if both the compartment boundaries and prescribed dose levels are well chosen.

  18. The role of risk analysis in control of complex plant safe operation

    International Nuclear Information System (INIS)

    Dumitrescu, Maria; Preda, Irina Aida; Lazar, Roxana Elena; Carcadea, Elena

    1999-01-01

    The problem of risk estimation assessment and control is necessary to be discussed in every decision making level of an activity. Performances of a system, action or technology, by indicating the possible consequences on environment, people or property should be qualitatively assessed. The paper presents methodologies of risk assessment successful applied on isotopic separation plants. The quantitative methodologies presented, use fault tree and event tree to determine the accident states frequency, physical models to analyse the dispersion in atmosphere of dangerous substances. The qualitative methodologies use the fuzzy models for the multicriterial decision making, models based on risk matrix build on the base of combination between the severity and the probability of maximum admissible consequence. These methodologies present the following steps for applying: familiarising with the activity in study, establishing the adequate method of risk assessment, building the model of risk assessment for the activity or objective in study, developing the applications of the proposed model. Applying this methodology to isotopic separation plants have led to: analysis of operation events and establishing of principal types of events potentially dangerous, analysis of human error in these plant operations and operating experience assessment, technical specifications for optimisation by probabilistic safety assessment, reliability analysis and development of reliability and exploitation of events database, post accident events analysis (releases, fires, explosions) and mathematical modelling of dispersion in atmosphere of dangerous substances. The risk concept being complex and with multiple implications, is not the case of a rigid approaching neither of existence of some methods universally valid. Because of these reasons, choosing of the most appropriate method for the risk assessment of an activity, leads to a solution in useful time, of some problems with economic, social

  19. The role of risk analysis in control of complex plants' safety operation

    International Nuclear Information System (INIS)

    Dumitrescu, Maria; Preda, Irina Aida; Lazar, Roxana Elena; Carcadea, Elena

    1999-01-01

    The problem of risk estimation, assessment and control is necessary to be discussed at every decision level of an activity. In this way the performances of a system, action or technology are qualitatively assessed by indicating the possible consequences on environmental, people or property. The paper presents methodologies of risk assessment successfully applied on isotopic separation plants. The quantitative methodologies presented use fault tree and event tree to determine the accident states frequency and physical models to analyse the dispersion in atmosphere of dangerous substances. The qualitative methodologies use fuzzy models for the multi-criteria decision making, models based on risk matrix built on the basis of a combination between severity and probability of maximum admissible consequence. These methodologies present the following steps for applying: familiarising with the activity in study, establishing the adequate method of risk assessment, realising of the model of risk assessment for the activity or objective in study, developing of application of the proposed model. Applying this methodology to isotopic separation plants has led to: analysis of operation events and establishing of principal types of events potentially dangerous, analysis of human error in these plants operation and operating experience assessment, technical specifications optimisation by probabilistic safety assessment, reliability analysis and development of reliability and exploitation events database, post accident events analysis (releases, fires, explosions) and mathematical modelling of dispersion in atmosphere of dangerous substances. The risk concept being complex and with multiple implications, it is not the case of a rigid approaching neither of existence of some methods universally valid. Because of these reasons choosing of the most appropriate method for the risk assessment of an activity, leads to solution in due time, of some problems with economic, social

  20. Towards controlled innovation of complex objects. : A sociotechnical approach to describing ship design

    NARCIS (Netherlands)

    van Bruinessen, T.M.

    2016-01-01

    Within the ship design industry, and in particular in the development of large, complex and innovative vessels experienced ship designers play an important role in organizing and structuring the design process. How this actually happens within projects that develop such large, complex and

  1. Copolymers containing phosphorescent iridium(III) complexes obtained by free and controlled radical polymerization techniques

    NARCIS (Netherlands)

    Ulbricht, C.; Becer, C.R.; Winter, A.; Veldman, D.; Schubert, U.S.

    2008-01-01

    A methacrylate-functionalized phosphorescent Ir(III)-complex has been synthesized, characterized, and applied as a monomer in radical copolymerizations. Together with methyl methacrylate, the complex has been copolymerized under free radical polymerization conditions. Aiming for host-guest-systems,

  2. Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Assenholt, Jannie; Mouaikel, John; Saguez, Cyril

    2011-01-01

    RNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits...

  3. Ubiquitin-SUMO Circuitry Controls Activated Fanconi Anemia ID Complex Dosage in Response to DNA Damage

    DEFF Research Database (Denmark)

    Gibbs-Seymour, Ian; Oka, Yasuyoshi; Rajendra, Eeson

    2015-01-01

    We show that central components of the Fanconi anemia (FA) DNA repair pathway, the tumor suppressor proteins FANCI and FANCD2 (the ID complex), are SUMOylated in response to replication fork stalling. The ID complex is SUMOylated in a manner that depends on the ATR kinase, the FA ubiquitin ligase...

  4. Complexation with dissolved organic matter and solubility control of heavy metals in sandy soil

    NARCIS (Netherlands)

    Weng, L.; Temminghoff, E.J.M.; Lofts, S.; Tipping, E.; Riemsdijk, van W.H.

    2002-01-01

    The complexation of heavy metals with dissolved organic matter (DOM) in the environment influences the solubility and mobility of these metals. In this paper, we measured the complexation of Cu, Cd, Zn, Ni, and Pb with DOM in the soil solution at pH 3.7-6.1 using a Donnan membrane technique. The

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

    Directory of Open Access Journals (Sweden)

    Michelle Wehling-Henricks

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

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

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  8. A model of human decision making in complex systems and its use for design of system control strategies

    International Nuclear Information System (INIS)

    Rasmussen, J.; Lind, M.

    1982-04-01

    The paper describes a model of operators' decision making in complex system control, based on studies of event reports and performance in control rooms. This study shows how operators base their decisions on knowledge of system properties at different levels of abstraction depending on their preception of the system's immediate control requirements. These levels correspond to the abstraction hierarchy including system purpose, functions, and physical details, which is generally used to describe a formal design process. In emergency situations the task of the operator is to design a suitabel control strategy for systems recovery, and the control systems designer should provide a man-machine interface, supporting the operator in identification of his task and in communication with the system at the level of abstraction corresponding to the immedite control requirement. A formalized representation of system properties in a multilevel flow model is described to provide a basis for an integrated control system design. (author)

  9. Preparation of a novel breviscapine-loaded halloysite nanotubes complex for controlled release of breviscapine

    Science.gov (United States)

    Gao, Min; Lu, Liqian; Wang, Xiaoyue; Lin, Houke; Zhou, Qingsong

    2017-11-01

    For sustain the release rate and prolong half-life of breviscapine in vivo, the breviscapine-loaded halloysite nanotubes complex was prepared. The breviscapine was encapsulated into halloysite nanotubes (HNTs) using a vacuum process. The complex were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy(FT-IR). The formation of breviscapine-loaded HNTs complex was proved by the test results of SEM, DSC, TEM and IR analysise. The results confirmed that breviscapine was successfully loaded in the halloysite nanotubes. Additionally, the in vitro drug release of breviscapine from breviscapine-loaded HNTs complex was investigated, the result indicated this complex has apparent sustained-release effect.

  10. Optimal Design of Complex Passive-Damping Systems for Vibration Control of Large Structures: An Energy-to-Peak Approach

    Directory of Open Access Journals (Sweden)

    Francisco Palacios-Quiñonero

    2014-01-01

    Full Text Available We present a new design strategy that makes it possible to synthesize decentralized output-feedback controllers by solving two successive optimization problems with linear matrix inequality (LMI constraints. In the initial LMI optimization problem, two auxiliary elements are computed: a standard state-feedback controller, which can be taken as a reference in the performance assessment, and a matrix that facilitates a proper definition of the main LMI optimization problem. Next, by solving the second optimization problem, the output-feedback controller is obtained. The proposed strategy extends recent results in static output-feedback control and can be applied to design complex passive-damping systems for vibrational control of large structures. More precisely, by taking advantages of the existing link between fully decentralized velocity-feedback controllers and passive linear dampers, advanced active feedback control strategies can be used to design complex passive-damping systems, which combine the simplicity and robustness of passive control systems with the efficiency of active feedback control. To demonstrate the effectiveness of the proposed approach, a passive-damping system for the seismic protection of a five-story building is designed with excellent results.

  11. DNA-directed control of enzyme-inhibitor complex formation: a modular approach to reversibly switch enzyme activity

    NARCIS (Netherlands)

    Janssen, B.M.G.; Engelen, W.; Merkx, M.

    2015-01-01

    DNA-templated reversible assembly of an enzyme–inhibitor complex is presented as a new and highly modular approach to control enzyme activity. TEM1-ß-lactamase and its inhibitor protein BLIP were conjugated to different oligonucleotides, resulting in enzyme inhibition in the presence of template

  12. Single conversion audio amplifier and DC-AC converters with high performance and low complexity control scheme

    DEFF Research Database (Denmark)

    Poulsen, Søren; Andersen, Michael Andreas E.

    2004-01-01

    This paper proposes a novel control topology for a mains isolated single conversion audio amplifier and DC-AC converters. The topology is made for use in audio applications, and differs from prior art in terms of significantly reduced distortion as well as lower system complexity. The topology can...

  13. Synchronization of coupled stochastic complex-valued dynamical networks with time-varying delays via aperiodically intermittent adaptive control

    Science.gov (United States)

    Wang, Pengfei; Jin, Wei; Su, Huan

    2018-04-01

    This paper deals with the synchronization problem of a class of coupled stochastic complex-valued drive-response networks with time-varying delays via aperiodically intermittent adaptive control. Different from the previous works, the intermittent control is aperiodic and adaptive, and the restrictions on the control width and time delay are removed, which lead to a larger application scope for this control strategy. Then, based on the Lyapunov method and Kirchhoff's Matrix Tree Theorem as well as differential inequality techniques, several novel synchronization conditions are derived for the considered model. Specially, impulsive control is also considered, which can be seen as a special case of the aperiodically intermittent control when the control width tends to zero. And the corresponding synchronization criteria are given as well. As an application of the theoretical results, a class of stochastic complex-valued coupled oscillators with time-varying delays is studied, and the numerical simulations are also given to demonstrate the effectiveness of the control strategies.

  14. FAA Air Traffic Control Operations Concepts. Volume 5. ATCT/TCCC (airport Traffic Control Tower/Tower Control Computer Complex) Tower Controllers

    Science.gov (United States)

    1988-07-29

    Departure List. T1.1.4.13 RESEQUENCE FOE MANUALLY 3.7.2.2.1.1.2.2-00 ARRIVAL LIST 457 3.7.2.2.1,1.2.2-11 b. Ordering - In manual ordering , the 457 a...3.7.2.2.1.1.2.3-12 b. Ordering - In manual ordering , the 457 controller shall have the capability to put a new FOE in the appropriate place in a sublist...3.7.2.2.1.1.2.2-00 ARRIVAL LIST 457 3.7.2.2.1.1.2.2-11 b. Ordering - In manual ordering , the 457 controller snall have the capability to put a new FOE in

  15. Complex emergencies in the Eastern Mediterranean Region: Impact on tuberculosis control

    Directory of Open Access Journals (Sweden)

    Akihiro Seita

    2016-01-01

    Conclusion: Complex emergencies pose a significant negative impact on tuberculosis in the EMR. This issue should be raised in the global health and political arena. This is a time bomb for tuberculosis.

  16. Border control: selectivity of chloroplast protein import and regulation at the TOC-complex.

    Science.gov (United States)

    Demarsy, Emilie; Lakshmanan, Ashok M; Kessler, Felix

    2014-01-01

    Plants have evolved complex and sophisticated molecular mechanisms to regulate their development and adapt to their surrounding environment. Particularly the development of their specific organelles, chloroplasts and other plastid-types, is finely tuned in accordance with the metabolic needs of the cell. The normal development and functioning of plastids require import of particular subsets of nuclear encoded proteins. Most preproteins contain a cleavable sequence at their N terminal (transit peptide) serving as a signal for targeting to the organelle and recognition by the translocation machinery TOC-TIC (translocon of outer membrane complex-translocon of inner membrane complex) spanning the dual membrane envelope. The plastid proteome needs constant remodeling in response to developmental and environmental factors. Therefore selective regulation of preprotein import plays a crucial role in plant development. In this review we describe the diversity of transit peptides and TOC receptor complexes, and summarize the current knowledge and potential directions for future research concerning regulation of the different Toc isoforms.

  17. How to elucidate and control the redox sequence in vinylbenzoate and vinylpyridine bridged diruthenium complexes

    Czech Academy of Sciences Publication Activity Database

    Pevny, F.; Winter, R. F.; Sarkar, B.; Záliš, Stanislav

    2010-01-01

    Roč. 39, č. 34 (2010), s. 8000-8011 ISSN 1477-9226 R&D Projects: GA AV ČR KAN100400702; GA MŠk 1P05OC068; GA MŠk OC09043 Institutional research plan: CEZ:AV0Z40400503 Keywords : vinylbenzoate-bridged diruthenium complexes * electrochemistry * vinylpyridine-bridged diruthenium complexes Subject RIV: CG - Electrochemistry Impact factor: 3.647, year: 2010

  18. Managing expectations: cognitive authority and experienced control in complex healthcare processes.

    Science.gov (United States)

    Hunt, Katherine J; May, Carl R

    2017-07-05

    Balancing the normative expectations of others (accountabilities) against the personal and distributed resources available to meet them (capacity) is a ubiquitous feature of social relations in many settings. This is an important problem in the management of long-term conditions, because of widespread problems of non-adherence to treatment regimens. Using long-term conditions as an example, we set out middle range theory of this balancing work. A middle-range theory was constructed four stages. First, a qualitative elicitation study of men with heart failure was used to develop general propositions about patient and care giver experience, and about the ways that the organisation and delivery of care affected this. Second, these propositions were developed and confirmed through a systematic review of qualitative research literature. Third, theoretical propositions and constructs were built, refined and presented as a logic model associated with two main theoretical propositions. Finally, a construct validation exercise was undertaken, in which construct definitions informed reanalysis of a set of systematic reviews of studies of patient and caregiver experiences of heart failure that had been included in an earlier meta-review. Cognitive Authority Theory identifies, characterises and explains negotiation processes in in which people manage their relations with the expectations of normative systems - like those encountered in the management of long-term conditions. Here, their cognitive authority is the product of an assessment of competence, trustworthiness and credibility made about a person by other participants in a healthcare process; and their experienced control is a function of the degree to which they successfully manage the external process-specific limiting factors that make it difficult to otherwise perform in their role. Cognitive Authority Theory assists in explaining how participants in complex social processes manage important relational aspects of

  19. Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential

    Directory of Open Access Journals (Sweden)

    Akinaga Sonoda

    2010-07-01

    Full Text Available Akinaga Sonoda1, Norihisa Nitta1, Ayumi Nitta-Seko1, Shinich Ohta1, Shigeyuki Takamatsu2, Yoshio Ikehata3, Isamu Nagano3, Jun-ichiro Jo4, Yasuhiko Tabata4, Masashi Takahashi1, Osamu Matsui3, Kiyoshi Murata11Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 520-2192, Japan; 2Department of Radiology, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa Ishikawa, 920-8641, Japan; 3Department of Natural Science and Technology, Graduate School of Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Shogoin kawara-machi 53, Sakyo-ku 606-8507, Kyoto, JapanAbstract: We developed a dextran-magnetite conjugated cisplatin (DM-Cis complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron. The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip and placed magnets subcutaneously (sc. In group 2 we injected saline (ip and placed magnets (sc. In group 3 we injected DM-Cis (ip and placed a sc incision (sham. The control (group 4 received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (µm2 were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 µg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05 in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a

  20. A novel instrumented multipeg running wheel system, Step-Wheel, for monitoring and controlling complex sequential stepping in mice.

    Science.gov (United States)

    Kitsukawa, Takashi; Nagata, Masatoshi; Yanagihara, Dai; Tomioka, Ryohei; Utsumi, Hideko; Kubota, Yasuo; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo

    2011-07-01

    Motor control is critical in daily life as well as in artistic and athletic performance and thus is the subject of intense interest in neuroscience. Mouse models of movement disorders have proven valuable for many aspects of investigation, but adequate methods for analyzing complex motor control in mouse models have not been fully established. Here, we report the development of a novel running-wheel system that can be used to evoke simple and complex stepping patterns in mice. The stepping patterns are controlled by spatially organized pegs, which serve as footholds that can be arranged in adjustable, ladder-like configurations. The mice run as they drink water from a spout, providing reward, while the wheel turns at a constant speed. The stepping patterns of the mice can thus be controlled not only spatially, but also temporally. A voltage sensor to detect paw touches is attached to each peg, allowing precise registration of footfalls. We show that this device can be used to analyze patterns of complex motor coordination in mice. We further demonstrate that it is possible to measure patterns of neural activity with chronically implanted tetrodes as the mice engage in vigorous running bouts. We suggest that this instrumented multipeg running wheel (which we name the Step-Wheel System) can serve as an important tool in analyzing motor control and motor learning in mice.

  1. Neurochemical Architecture of the Central Complex Related to Its Function in the Control of Grasshopper Acoustic Communication

    Science.gov (United States)

    Kunst, Michael; Pförtner, Ramona; Aschenbrenner, Katja; Heinrich, Ralf

    2011-01-01

    The central complex selects and coordinates the species- and situation-specific song production in acoustically communicating grasshoppers. Control of sound production is mediated by several neurotransmitters and modulators, their receptors and intracellular signaling pathways. It has previously been shown that muscarinic cholinergic excitation in the central complex promotes sound production whereas both GABA and nitric oxide/cyclic GMP signaling suppress its performance. The present immunocytochemical and pharmacological study investigates the question whether GABA and nitric oxide mediate inhibition of sound production independently. Muscarinic ACh receptors are expressed by columnar output neurons of the central complex that innervate the lower division of the central body and terminate in the lateral accessory lobes. GABAergic tangential neurons that innervate the lower division of the central body arborize in close proximity of columnar neurons and thus may directly inhibit these central complex output neurons. A subset of these GABAergic tangential neurons accumulates cyclic GMP following the release of nitric oxide from neurites in the upper division of the central body. While sound production stimulated by muscarine injection into the central complex is suppressed by co-application of sodium nitroprusside, picrotoxin-stimulated singing was not affected by co-application of this nitric oxide donor, indicating that nitric oxide mediated inhibition requires functional GABA signaling. Hence, grasshopper sound production is controlled by processing of information in the lower division of the central body which is subject to modulation by nitric oxide released from neurons in the upper division. PMID:21980504

  2. Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes.

    Science.gov (United States)

    Vlachou, Marilena; Papamichael, Marianna; Siamidi, Angeliki; Fragouli, Irene; Afroudakis, Pandelis A; Kompogennitaki, Rodanthi; Dotsikas, Yannis

    2017-07-28

    A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

  3. Synthesis quality control and biodistribution of technetium-99m triamcinolone (99mTc-TA) complex: An inflammation tracer agent

    International Nuclear Information System (INIS)

    Rizvii, Faheem Askari; Naqvi, Syed Ali Raza; Mehdi, Muhammad; Roohi, Samina; Zahoor, Ameer Fawad; Khan, Zulfiqar Ali; Sohaib, Muhammad; Rasheed, Rashid

    2017-01-01

    In present study synthesis of 99m Tc-triamcinolone acetonide ( 99m Tc-TA) complex and its stability using set of quality control parameters such as ligand concentration, reducing agent concentration, pH, temperature and reaction time was assessed. 99m Tc-TA complex was characterized in terms of percent (%) yield, stability in saline and serum using chromatographic procedures. Radiochemically the 99m Tc-TA complex was found quite stable in saline and serum. After 30 min of reaction the complex showed maximum radiochemical yield of 96.32% which decreased to 96.25 % after 4 h incubation period. In serum, the % yield of radiochemical was remained same up to 2 h which decreased to 93.5% at 24 h time point. Normal biodistribution pattern in Sprague-Dawley rats revealed liver, stomach and kidneys as areas of high 99m Tc-TA complex uptake (8.44 ±1.32, 8.75 ± 1.03 and 12.67 ± 1.21%, respectively) at 1 h post injection time point. Scintigraphy of 99m Tc-TA in rabbits showed similar eco as observed in biodistribution study. Based on the promising results obtained in context of in vitro and in vivo stability and biodistribution, 99m Tc-TA complex could be further studied to identify the inflammation based diseases

  4. Decentralized H-infinity control of complex systems with delayed feedback

    Czech Academy of Sciences Publication Activity Database

    Bakule, Lubomír; Rehák, Branislav; Papík, Martin

    2016-01-01

    Roč. 67, č. 1 (2016), s. 127-131 ISSN 0005-1098 R&D Projects: GA ČR GA13-02149S Institutional support: RVO:67985556 Keywords : decentralized control * H-infinity control * large-scale systems * Fault-tolerant systems Subject RIV: BC - Control Systems Theory Impact factor: 5.451, year: 2016

  5. Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

    Science.gov (United States)

    Maple, Jodi; Møller, Simon G

    2007-10-01

    Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

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

    Directory of Open Access Journals (Sweden)

    Aoife Gowran

    2018-04-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

  8. The strategic control of prospective memory monitoring in response to complex and probabilistic contextual cues.

    Science.gov (United States)

    Bugg, Julie M; Ball, B Hunter

    2017-07-01

    Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets ("tor" syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring-namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue.

  9. A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

    Science.gov (United States)

    Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

    2018-01-19

    The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the

  10. Tissue-Specific Control of the Endocycle by the Anaphase Promoting Complex/Cyclosome Inhibitors UVI4 and DEL1.

    Science.gov (United States)

    Heyman, Jefri; Polyn, Stefanie; Eekhout, Thomas; De Veylder, Lieven

    2017-09-01

    The endocycle represents a modified mitotic cell cycle that in plants is often coupled to cell enlargement and differentiation. Endocycle onset is controlled by activity of the Anaphase Promoting Complex/Cyclosome (APC/C), a multisubunit E3 ubiquitin ligase targeting cell-cycle factors for destruction. CELL CYCLE SWITCH52 (CCS52) proteins represent rate-limiting activator subunits of the APC/C. In Arabidopsis ( Arabidopsis thaliana ), mutations in either CCS52A1 or CCS52A2 activators result in a delayed endocycle onset, whereas their overexpression triggers increased DNA ploidy levels. Here, the relative contribution of the APC/C CCS52A1 and APC/C CCS52A2 complexes to different developmental processes was studied through analysis of their negative regulators, being the ULTRAVIOLET-B-INSENSITIVE4 protein and the DP-E2F-Like1 transcriptional repressor, respectively. Our data illustrate cooperative activity of the APC/C CCS52A1 and APC/C CCS52A2 complexes during root and trichome development, but functional interdependency during leaf development. Furthermore, we found APC/C CCS52A1 activity to control CCS52A2 expression. We conclude that interdependency of CCS52A-controlled APC/C activity is controlled in a tissue-specific manner. © 2017 American Society of Plant Biologists. All Rights Reserved.

  11. Optical angular constancy is maintained as a navigational control strategy when pursuing robots moving along complex pathways.

    Science.gov (United States)

    Wang, Wei; McBeath, Michael K; Sugar, Thomas G

    2015-03-24

    The optical navigational control strategy used to intercept moving targets was explored using a real-world object that travels along complex, evasive pathways. Fielders ran across a gymnasium attempting to catch a moving robot that varied in speed and direction, while ongoing position was measured using an infrared motion-capture system. Fielder running paths were compared with the predictions of three lateral control models, each based on maintaining a particular optical angle relative to the robotic target: (a) constant alignment angle (CAA), (b) constant eccentricity angle (CEA), and (c) linear optical trajectory (LOT). Findings reveal that running pathways were most consistent with maintenance of LOT and least consistent with CEA. This supports that fielders use the same optical control strategy of maintaining angular constancy using a LOT when navigating toward targets moving along complex pathways as when intercepting simple ballistic trajectories. In those cases in which a target dramatically deviates from its optical path, fielders appear to simply reset LOT parameters using a new constant angle value. Maintenance of such optical angular constancy has now been shown to work well with ballistic, complex, and evasive moving targets, confirming the LOT strategy as a robust, general-purpose optical control mechanism for navigating to intercept catchable targets, both airborne and ground based. © 2015 ARVO.

  12. Nonlinear Decoupling Control With ANFIS-Based Unmodeled Dynamics Compensation for a Class of Complex Industrial Processes.

    Science.gov (United States)

    Zhang, Yajun; Chai, Tianyou; Wang, Hong; Wang, Dianhui; Chen, Xinkai

    2018-06-01

    Complex industrial processes are multivariable and generally exhibit strong coupling among their control loops with heavy nonlinear nature. These make it very difficult to obtain an accurate model. As a result, the conventional and data-driven control methods are difficult to apply. Using a twin-tank level control system as an example, a novel multivariable decoupling control algorithm with adaptive neural-fuzzy inference system (ANFIS)-based unmodeled dynamics (UD) compensation is proposed in this paper for a class of complex industrial processes. At first, a nonlinear multivariable decoupling controller with UD compensation is introduced. Different from the existing methods, the decomposition estimation algorithm using ANFIS is employed to estimate the UD, and the desired estimating and decoupling control effects are achieved. Second, the proposed method does not require the complicated switching mechanism which has been commonly used in the literature. This significantly simplifies the obtained decoupling algorithm and its realization. Third, based on some new lemmas and theorems, the conditions on the stability and convergence of the closed-loop system are analyzed to show the uniform boundedness of all the variables. This is then followed by the summary on experimental tests on a heavily coupled nonlinear twin-tank system that demonstrates the effectiveness and the practicability of the proposed method.

  13. Parameterization and Sensitivity Analysis of a Complex Simulation Model for Mosquito Population Dynamics, Dengue Transmission, and Their Control

    Science.gov (United States)

    Ellis, Alicia M.; Garcia, Andres J.; Focks, Dana A.; Morrison, Amy C.; Scott, Thomas W.

    2011-01-01

    Models can be useful tools for understanding the dynamics and control of mosquito-borne disease. More detailed models may be more realistic and better suited for understanding local disease dynamics; however, evaluating model suitability, accuracy, and performance becomes increasingly difficult with greater model complexity. Sensitivity analysis is a technique that permits exploration of complex models by evaluating the sensitivity of the model to changes in parameters. Here, we present results of sensitivity analyses of two interrelated complex simulation models of mosquito population dynamics and dengue transmission. We found that dengue transmission may be influenced most by survival in each life stage of the mosquito, mosquito biting behavior, and duration of the infectious period in humans. The importance of these biological processes for vector-borne disease models and the overwhelming lack of knowledge about them make acquisition of relevant field data on these biological processes a top research priority. PMID:21813844

  14. Fuzzy control for optimal operation of complex chilling systems; Betriebsoptimierung von komplexen Kaelteanlagen mit Fuzzy-Control

    Energy Technology Data Exchange (ETDEWEB)

    Talebi-Daryani, R. [Fachhochschule Koeln (Germany). Lehrgebiet und Lab. fuer Regelungs- und Gebaeudeleittechnik; Luther, C. [JCI Regelungstechnik GmbH, Koeln (Germany)

    1998-05-01

    The optimization potentials for the operation of chilling systems within the building supervisory control systems are limited to abilities of PLC functions with their binary logic. The aim of this project is to replace inefficient PLC-solutions for the operation of chilling system by a Fuzzy control system. Optimal operation means: reducing operation time and operation costs of the system, reducing cooling energy generation- and consumption costs. Analysis of the thermal behaviour of the building and the chilling system is necessary, in order to find the current efficient cooling potentials and cooling methods during the operation. Three different Fuzzy controller have been developed with a total rule number of just 70. This realized Fuzzy control system is able to forecast the maximum cooling power of the building, but also to determine the cooling potential of the out door air. This new Fuzzy control system has been successfully commissioned, and remarkable improvement of the system behaviour is reached. Comparison of the system behaviour before and after the implementation of Fuzzy control system proved the benefits of the Fuzzy logic based operation system realized here. The system described here is a joint project between the University of applied sciences Cologne, and Johnson Controls International Cologne. The Fuzzy software tool used here (SUCO soft Fuzzy TECH 4.0), was provided by Kloeckner Moeller Bonn. (orig.) [Deutsch] Die Betriebsoptimierung von Kaelteanlagen innerhalb von Gebaeudeleitsystemen ist auf die Faehigkeiten von logischen Steuerverknuepfungen der Digitaltechnik begrenzt. In diesem Zusammenhang kann nur ein geringer Anteil der Information ueber das thermische Speicherverhalten des jeweiligen Gebaeudes herangezogen werden. Ziel des vorliegenden Projektes war es, die unzureichenden logischen Steuerverknuepfungen durch ein Fuzzy-Control-System zu ersetzen, um die Arbeitsweise der Kaelteanlage zu optimieren. Die Optimierungskriterien dieses

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

    Directory of Open Access Journals (Sweden)

    Surinder M Singh

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

  16. Supramolecular Control of Oligothienylenevinylene-Fullerene Interactions: Evidence for a Ground-State EDA Complex

    NARCIS (Netherlands)

    McClenaghan, N.D.; Grote, Z.; Darriet, K.; Zimine, M.Y.; Williams, R.M.; De Cola, L.; Bassani, D.M.

    2005-01-01

    Complementary hydrogen-bonding interactions between a barbituric acid-substituted fullerene derivative (1) and corresponding receptor (2) bearing thienylenevinylene units are used to assemble a 1:1 supramolecular complex ( K ) 5500 M-1). Due to the close proximity of the redox-active moieties within

  17. Complex rupture mechanism and topography control symmetry of mass - wasting pattern, 2010 Haiti earthquake

    NARCIS (Netherlands)

    Gorum, T.; van Westen, C.J.; Korup, Oliver; van der Meijde, M.; Fan, Xuanmei; van der Meer, F.D.

    2013-01-01

    The 12 January 2010 Mw 7.0 Haiti earthquake occurred in a complex deformation zone at the boundary between the North American and Caribbean plates. Combined geodetic, geological and seismological data posited that surface deformation was driven by rupture on the Léogâne blind thrust fault, while

  18. Managing Epileptic Seizures by Controlling the Brain Driver Nodes: A Complex Network View

    Energy Technology Data Exchange (ETDEWEB)

    Bakouie, Fatemeh, E-mail: fbakouie@aut.ac.ir [Neural and Cognitive Sciences Laboratory, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Cybernetics and Modeling of Biological Systems Laboratory, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Gharibzadeh, Shahriar, E-mail: fbakouie@aut.ac.ir [Neural and Cognitive Sciences Laboratory, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Towhidkhah, Farzad [Cybernetics and Modeling of Biological Systems Laboratory, Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of)

    2013-12-12

    The brain is a complex biological organization. In its hierarchy, different components, from neurons to functional cognitive circuits are interacting with each other. As a result of cooperation between neurons in the lower levels of this hierarchy, high level cognitive functions emerge (Stam and Reijneveld, 2007). In order to uncover the complexity of these higher functions, understanding the interaction rules in the lower level may be useful. In this level, there are lots of components which connect to each other (with a special structure) and exchange their information (in a specific manner). In this regard, complex network approach will be an influential way to study brain organization. The brain connectivity structure is suggested as a basis for emergence of its complex functions (Rubinov et al., 2009). For example, brain network analysis shows that its connectivity has the “small-worldness” feature, i.e., low characteristic path length and high clustering coefficient (Sporns et al., 2004). It has been seen that “synchronization” (as a collective dynamical behavior) occurs more rapidly in networks with small-world structure (Watts and Strogatz, 1998). Hence, we are able to use structural information (i.e., the pattern of connectivity between elements of the system) for understanding the functional pattern of the organization. Moreover, it is suggested that synchronization is the main mechanism for information exchange between different brain regions (Womelsdorf et al.,).

  19. Managing Epileptic Seizures by Controlling the Brain Driver Nodes: A Complex Network View

    International Nuclear Information System (INIS)

    Bakouie, Fatemeh; Gharibzadeh, Shahriar; Towhidkhah, Farzad

    2013-01-01

    The brain is a complex biological organization. In its hierarchy, different components, from neurons to functional cognitive circuits are interacting with each other. As a result of cooperation between neurons in the lower levels of this hierarchy, high level cognitive functions emerge (Stam and Reijneveld, 2007). In order to uncover the complexity of these higher functions, understanding the interaction rules in the lower level may be useful. In this level, there are lots of components which connect to each other (with a special structure) and exchange their information (in a specific manner). In this regard, complex network approach will be an influential way to study brain organization. The brain connectivity structure is suggested as a basis for emergence of its complex functions (Rubinov et al., 2009). For example, brain network analysis shows that its connectivity has the “small-worldness” feature, i.e., low characteristic path length and high clustering coefficient (Sporns et al., 2004). It has been seen that “synchronization” (as a collective dynamical behavior) occurs more rapidly in networks with small-world structure (Watts and Strogatz, 1998). Hence, we are able to use structural information (i.e., the pattern of connectivity between elements of the system) for understanding the functional pattern of the organization. Moreover, it is suggested that synchronization is the main mechanism for information exchange between different brain regions (Womelsdorf et al.,).

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

    CSIR Research Space (South Africa)

    Oosthuizen, R

    2012-06-01

    Full Text Available . The trend of modern combat is to move away from conventional warfare, increasing the occurrence of “messy” and “wicked” problems. Modern C2 systems require new frameworks and designs to cope with the increase in complexity experienced in warfare. Despite...

  1. Using remote substituents to control solution structure and anion binding in lanthanide complexes

    DEFF Research Database (Denmark)

    Tropiano, Manuel; Blackburn, Octavia A.; Tilney, James A.

    2013-01-01

    A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery ...

  2. Complex realities : community engagement for a paediatric randomized controlled malaria vaccine trial in Kilifi, Kenya

    NARCIS (Netherlands)

    Angwenyi, Vibian; Kamuya, Dorcas; Mwachiro, Dorothy; Kalama, Betty; Marsh, Vicki; Njuguna, Patricia; Molyneux, Sassy

    2014-01-01

    BACKGROUND: Community engagement (CE) is increasingly promoted for biomedical research conducted in resource poor settings for both intrinsic and instrumental purposes. Given the potential importance of CE, but also complexities and possibility of unexpected negative outcomes, there is need for more

  3. The System of Automatic Control of Complexity Work Evaluation in Assembly

    Directory of Open Access Journals (Sweden)

    Ivo HLAVATÝ

    2011-06-01

    Full Text Available The article is about a task of creating of an automated system for the evaluation of the complexity and the prediction of labour input of fitting and assembly operations, which used for manufacturing of machine-building item.

  4. Dimensional Control and Morphological Transformations of Supramolecular Polymeric Nanofibers Based on Cofacially-Stacked Planar Amphiphilic Platinum(II) Complexes.

    Science.gov (United States)

    Robinson, Matthew E; Nazemi, Ali; Lunn, David J; Hayward, Dominic W; Boott, Charlotte E; Hsiao, Ming-Siao; Harniman, Robert L; Davis, Sean A; Whittell, George R; Richardson, Robert M; De Cola, Luisa; Manners, Ian

    2017-09-26

    Square-planar platinum(II) complexes often stack cofacially to yield supramolecular fiber-like structures with interesting photophysical properties. However, control over fiber dimensions and the resulting colloidal stability is limited. We report the self-assembly of amphiphilic Pt(II) complexes with solubilizing ancillary ligands based on polyethylene glycol [PEG n , where n = 16, 12, 7]. The complex with the longest solubilizing PEG ligand, Pt-PEG 16 , self-assembled to form polydisperse one-dimensional (1D) nanofibers (diameters fibers of length up to ca. 400 nm. The fiber lengths were dependent on the Pt-PEG 16 complex to seed mass ratio in a manner analogous to a living covalent polymerization of molecular monomers. Moreover, the fiber lengths were unchanged in solution after 1 week and were therefore "static" with respect to interfiber exchange processes on this time scale. In contrast, similarly formed near-uniform fibers of Pt-PEG 12 exhibited dynamic behavior that led to broadening of the length distribution within 48 h. After aging for 4 weeks in solution, Pt-PEG 12 fibers partially evolved into 2D platelets. Furthermore, self-assembly of Pt-PEG 7 yielded only transient fibers which rapidly evolved into 2D platelets. On addition of further fiber-forming Pt complex (Pt-PEG 16 ), the platelets formed assemblies via the growth of fibers selectively from their short edges. Our studies demonstrate that when interfiber dynamic exchange is suppressed, dimensional control and hierarchical structure formation are possible for supramolecular polymers through the use of kinetically controlled seeded growth methods.

  5. Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication

    Directory of Open Access Journals (Sweden)

    Yasushi Shiomi

    2017-01-01

    Full Text Available During cell division, genome integrity is maintained by faithful DNA replication during S phase, followed by accurate segregation in mitosis. Many DNA metabolic events linked with DNA replication are also regulated throughout the cell cycle. In eukaryotes, the DNA sliding clamp, proliferating cell nuclear antigen (PCNA, acts on chromatin as a processivity factor for DNA polymerases. Since its discovery, many other PCNA binding partners have been identified that function during DNA replication, repair, recombination, chromatin remodeling, cohesion, and proteolysis in cell-cycle progression. PCNA not only recruits the proteins involved in such events, but it also actively controls their function as chromatin assembles. Therefore, control of PCNA-loading onto chromatin is fundamental for various replication-coupled reactions. PCNA is loaded onto chromatin by PCNA-loading replication factor C (RFC complexes. Both RFC1-RFC and Ctf18-RFC fundamentally function as PCNA loaders. On the other hand, after DNA synthesis, PCNA must be removed from chromatin by Elg1-RFC. Functional defects in RFC complexes lead to chromosomal abnormalities. In this review, we summarize the structural and functional relationships among RFC complexes, and describe how the regulation of PCNA loading/unloading by RFC complexes contributes to maintaining genome integrity.

  6. General algebraic method applied to control analysis of complex engine types

    Science.gov (United States)

    Boksenbom, Aaron S; Hood, Richard

    1950-01-01

    A general algebraic method of attack on the problem of controlling gas-turbine engines having any number of independent variables was utilized employing operational functions to describe the assumed linear characteristics for the engine, the control, and the other units in the system. Matrices were used to describe the various units of the system, to form a combined system showing all effects, and to form a single condensed matrix showing the principal effects. This method directly led to the conditions on the control system for noninteraction so that any setting disturbance would affect only its corresponding controlled variable. The response-action characteristics were expressed in terms of the control system and the engine characteristics. The ideal control-system characteristics were explicitly determined in terms of any desired response action.

  7. Master-slave exponential synchronization of delayed complex-valued memristor-based neural networks via impulsive control.

    Science.gov (United States)

    Li, Xiaofan; Fang, Jian-An; Li, Huiyuan

    2017-09-01

    This paper investigates master-slave exponential synchronization for a class of complex-valued memristor-based neural networks with time-varying delays via discontinuous impulsive control. Firstly, the master and slave complex-valued memristor-based neural networks with time-varying delays are translated to two real-valued memristor-based neural networks. Secondly, an impulsive control law is constructed and utilized to guarantee master-slave exponential synchronization of the neural networks. Thirdly, the master-slave synchronization problems are transformed into the stability problems of the master-slave error system. By employing linear matrix inequality (LMI) technique and constructing an appropriate Lyapunov-Krasovskii functional, some sufficient synchronization criteria are derived. Finally, a numerical simulation is provided to illustrate the effectiveness of the obtained theoretical results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The use of picture cues to establish self-control in the preparation of complex meals by mentally retarded adults.

    Science.gov (United States)

    Martin, J E; Rusch, F R; James, V L; Decker, P J; Trtol, K A

    1982-01-01

    This investigation examined the effectiveness of picture cues in establishing self-control in the completion of complex meals by mildly and moderately retarded adults. Three participants, who lived in nonsheltered residential settings, were trained to prepare five complex meals. Following a training baseline comprised of pre-instruction, instructional feedback, and trainers' presence, picture recipe cards were introduced in a multiple-baseline fashion. Rapid improvement in the ability of each participant to independently complete each meal when the picture recipe cards were used occurred. A return to baseline for one of the participants demonstrated further self-directed antecedent stimulus control of the picture recipe cards as an effective treatment procedure. A discussion of future areas of research is included.

  9. Reservoir-based Online Adaptive Forward Models with Neural Control for Complex Locomotion in a Hexapod Robot

    DEFF Research Database (Denmark)

    Manoonpong, Poramate; Dasgupta, Sakyasingha; Goldschmidt, Dennis

    2014-01-01

    Walking animals show fascinating locomotor abilities and complex behaviors. Biological study has revealed that such complex behaviors is a result of a combination of biomechanics and neural mechanisms. While biomechanics allows for flexibility and a variety of movements, neural mechanisms generate...... locomotion, make predictions, and provide adaptation. Inspired by this finding, we present here an artificial bio-inspired walking system which combines biomechanics (in terms of its body and leg structures) and neural mechanisms. The neural mechanisms consist of 1) central pattern generator-based control...... for generating basic rhythmic patterns and coordinated movements, 2) reservoir-based adaptive forward models with efference copies for sensory prediction as well as state estimation, and 3) searching and elevation control for adapting the movement of an individual leg to deal with different environmental...

  10. Buildings 104 and 142 Complex Physical Protection and Material Control and Accounting Upgrades at the Mayak Production Association

    International Nuclear Information System (INIS)

    Aichele, Walter T.; Dwyer, Gregory M.; Larsen, R.; Malone, Tim

    2004-01-01

    The Federal State Unitary Enterprise Mayak Production Association (Mayak) and the U.S. Material Protection, Control and Accounting (MPC and A) United States Project Team (USPT) have worked together for a number of years as part of the U.S. national Nuclear Security Administration's (NNSA) MPC and A program to implement both Physical Protection (PP) and Material Control and Accounting (MC and A) upgrades within the Buildings 104 and 142 Complex, a long-term storage area for uranium and plutonium oxide located within Mayak's RT-1 Spent Fuel Reprocessing Plant. This paper focuses on the successes and areas for improvement in the analysis, planning, construction, implementation, and completion of a complex and labor-intensive project aimed at the refurbishment of two existing, in service, long-term special nuclear material (SNM) storage buildings within a Russian SNM production facility

  11. Department of Energy Nuclear Material Protection, Control, and Accounting Program at the Mangyshlak Atomic Energy Complex, Aktau, Republic of Kazakhstan

    International Nuclear Information System (INIS)

    Case, R.; Berry, R.B.; Eras, A.

    1998-01-01

    As part of the Cooperative Threat Reduction Nuclear Material Protection, Control, and Accounting (MPC and A) Program, the US Department of Energy and Mangyshlak Atomic Energy Complex (MAEC), Aktau, Republic of Kazakstan have cooperated to enhance existing MAEC MPC and A features at the BN-350 liquid-metal fast-breeder reactor. This paper describes the methodology of the enhancement activities and provides representative examples of the MPC and A augmentation implemented at the MAEC

  12. Cdk1 and Okadaic Acid-sensitive Phosphatases Control Assembly of Nuclear Pore Complexes in Drosophila EmbryosV⃞

    OpenAIRE

    Onischenko, Evgeny A.; Gubanova, Natalia V.; Kiseleva, Elena V.; Hallberg, Einar

    2005-01-01

    Disassembly and reassembly of the nuclear pore complexes (NPCs) is one of the major events during open mitosis in higher eukaryotes. However, how this process is controlled by the mitotic machinery is not clear. To investigate this we developed a novel in vivo model system based on syncytial Drosophila embryos. We microinjected different mitotic effectors into the embryonic cytoplasm and monitored the dynamics of disassembly/reassembly of NPCs in live embryos using fluorescently labeled wheat...

  13. IMPROVING THE EFFICIENCY OF THE STATE FINANCIAL CONTROL IN THE SPHERE OF HIGH-TECH MILITARY-INDUSTRIAL COMPLEX

    Directory of Open Access Journals (Sweden)

    Anzhela Zakhitovna Namitulina

    2016-01-01

    Full Text Available The presented research topic is particularly relevant due to the high value and the need to strengthen fi nancial control for the development of the military-industrial complex (MIC, to ensure the country's economic security, preservation and development of scientifi c and technical potential. The urgency of acquiring those aspects of economic relations which are connected with the supply the export of high-tech military products in a limited budget funding State should have levers of infl uence on the functioning of the military-industrial complex, the ability to pursue an independent foreign military-technical policy. In the new economic conditions, it became necessary to address the problems of fi nancial security of the defense-industrial complex, in order to strengthen the independence and security of Russia, as well as the need to give priority nature of the measures of state control in the economy related to the implementation of the defense order, ie, in the sphere of military-industrial complex. At the present stage of economic development of Russia, the rate of growth of the national economy largely depends on what the situation is in the military-industrial complex (MIC. This is due to the fact that the defense industry is the most high-quality, high-tech economy. It concentrated the largest part of the Russian potential, the best staff of scientists and experts. Products and DIC technology widely used in other industries. The modern military-industrial complex produces a signifi cant part of civil production. DIC integration with civilian industries – it is also a technological basis for solving the basic problems currently facing the Russian economy, and, above all, the basis of the formation of a new technological basis for the development of high technology and competitive products, which determines the pace of scientifi c and technological progress and the growth of the national economy. Objectives. The aim of the paper is the

  14. AC field effect flow control of EOF in complex microfluidic systems with integrated electrodes

    NARCIS (Netherlands)

    van der Wouden, E.J.; Pennathur, S.; van den Berg, Albert; Locascio, L.E.; Gaitan, M.; Paegel, B.M.; Ross, D.J.; Vreeland, W.N.

    2008-01-01

    In this work, we demonstrate that positive net flow can be induced and controlled with relatively low potential due to the parallel alignment of the integrated channel electrodes. Therefore, we present a novel method to exquisitely control Electro Osmotic Flow (EOF) by using integrated electrodes

  15. High level language for measurement complex control based on the computer E-100I

    Science.gov (United States)

    Zubkov, B. V.

    1980-01-01

    A high level language was designed to control the process of conducting an experiment using the computer "Elektrinika-1001". Program examples are given to control the measuring and actuating devices. The procedure of including these programs in the suggested high level language is described.

  16. The politics of control : New dynamics of agrarian change in Bolivia's Soy Complex

    NARCIS (Netherlands)

    B. McKay (Ben)

    2017-01-01

    markdownabstractAround the world, plantation economies are on the rise. Increasing concerns over food, energy, and financial security combined with a geopolitical restructuring of the global agro-food system have led to a new wave and rush to secure control over resources. Corporate-controlled

  17. The Complex Relationship between Parental Divorce and the Sense of Control

    Science.gov (United States)

    Kim, Joongbaeck; Woo, Hyeyoung

    2011-01-01

    How does parental divorce influence the sense of control in adult offspring? Numerous studies have examined the implications of parental divorce on adult psychological well-being. However, little attention has been paid to the long-term consequences of parental divorce for adult sense of control. Using data from the Survey of Aging, Status, and…

  18. Control of cell fate by the formation of an architecturally complex bacterial community.

    Science.gov (United States)

    Vlamakis, Hera; Aguilar, Claudio; Losick, Richard; Kolter, Roberto

    2008-04-01

    Bacteria form architecturally complex communities known as biofilms in which cells are held together by an extracellular matrix. Biofilms harbor multiple cell types, and it has been proposed that within biofilms individual cells follow different developmental pathways, resulting in heterogeneous populations. Here we demonstrate cellular differentiation within biofilms of the spore-forming bacterium Bacillus subtilis, and present evidence that formation of the biofilm governs differentiation. We show that motile, matrix-producing, and sporulating cells localize to distinct regions within the biofilm, and that the localization and percentage of each cell type is dynamic throughout development of the community. Importantly, mutants that do not produce extracellular matrix form unstructured biofilms that are deficient in sporulation. We propose that sporulation is a culminating feature of biofilm formation, and that spore formation is coupled to the formation of an architecturally complex community of cells.

  19. Advances in statistical monitoring of complex multivariate processes with applications in industrial process control

    CERN Document Server

    Kruger, Uwe

    2012-01-01

    The development and application of multivariate statistical techniques in process monitoring has gained substantial interest over the past two decades in academia and industry alike.  Initially developed for monitoring and fault diagnosis in complex systems, such techniques have been refined and applied in various engineering areas, for example mechanical and manufacturing, chemical, electrical and electronic, and power engineering.  The recipe for the tremendous interest in multivariate statistical techniques lies in its simplicity and adaptability for developing monitoring applica

  20. Output-Feedback Control for Discrete-Time Spreading Models in Complex Networks

    Directory of Open Access Journals (Sweden)

    Luis A. Alarcón Ramos

    2018-03-01

    Full Text Available The problem of stabilizing the spreading process to a prescribed probability distribution over a complex network is considered, where the dynamics of the nodes in the network is given by discrete-time Markov-chain processes. Conditions for the positioning and identification of actuators and sensors are provided, and sufficient conditions for the exponential stability of the desired distribution are derived. Simulations results for a network of N = 10 6 corroborate our theoretical findings.