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.

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

Science.gov (United States)

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

2011-12-01

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

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.

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

Use of Large Surface MicroChannel Plates for the Tagging of Intermediate Energy Exotic Beams

Energy Technology Data Exchange (ETDEWEB)

Lombardo, I., E-mail: ilombardo@lns.infn.it [Dipartimento di Fisica, Universita di Catania, Catania (Italy); INFN Laboratori Nazionali del Sud, Catania (Italy); Amorini, F. [INFN Laboratori Nazionali del Sud, Catania (Italy); Cardella, G. [INFN, Sezione di Catania, Catania (Italy); Cavallaro, S. [Dipartimento di Fisica, Universita di Catania, Catania (Italy); INFN Laboratori Nazionali del Sud, Catania (Italy); De Filippo, E. [INFN, Sezione di Catania, Catania (Italy); Geraci, E.; Grassi, L. [Dipartimento di Fisica, Universita di Catania, Catania (Italy); INFN, Sezione di Catania, Catania (Italy); La Guidara, E. [INFN, Sezione di Catania, Catania (Italy); Centro Siciliano di Fisica Nucleare e Struttura della Materia, Catania (Italy); Lanzalone, G. [INFN Laboratori Nazionali del Sud, Catania (Italy); Libera Universita Kore, Enna (Italy); Pagano, A.; Papa, M.; Pirrone, S. [INFN, Sezione di Catania, Catania (Italy); Politi, G. [Dipartimento di Fisica, Universita di Catania, Catania (Italy); INFN, Sezione di Catania, Catania (Italy); Porto, F.; Rizzo, F.; Russotto, P. [Dipartimento di Fisica, Universita di Catania, Catania (Italy); INFN Laboratori Nazionali del Sud, Catania (Italy); Verde, G. [INFN, Sezione di Catania, Catania (Italy); Vigilante, M. [INFN, Sezione di Napoli and Dipartimento di Fisica, Universita Federico II di Napoli (Italy)

2011-06-15

We show the properties of the tagging system for exotic beams coupled to the CHIMERA detector. In particular, the characteristics of a newly developed large surface MicroChannel Plate will be discussed. Timing and efficiency of this instrument have been investigated. Preliminary results of tests performed with radioactive beams and alpha sources are presented.

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.

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

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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.

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

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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.

Training warning flags

International Nuclear Information System (INIS)

Miller, Richard C.

2003-01-01

Problems in accredited training programmes at US nuclear stations have resulted in several programmes having their accreditation status designated as probationary. A limited probationary period allows time for problem resolution before the programmes are again reviewed by the National Nuclear Accrediting Board. A careful study of these problems has resulted in the identification of several 'Training Warning Flags' that singularly, or in concert, may indicate or predict degraded training programme effectiveness. These training warning flags have been used by several US nuclear stations as a framework for self-assessments, as a reference in making changes to training programmes, and as a tool in considering student and management feedback on training activities. Further analysis and consideration of the training warning flags has developed precursors for each of the training warning flags. Although more subjective than the training warning flags, the precursors may represent early indicators of factors that may lead to or contribute to degraded training programme effectiveness. Used as evaluative tools, the training warning flags and the precursors may help identify areas for improvements in training programmes and help prioritize training programme improvement efforts. (author)

Discovering "The Italian Flag" by Fernando Melani (1907-1985).

Science.gov (United States)

Carlesi, Serena; Bartolozzi, Giovanni; Cucci, Costanza; Marchiafava, Veronica; Picollo, Marcello; La Nasa, Jacopo; Di Girolamo, Francesca; Dilillo, Marialaura; Modugno, Francesca; Degano, Ilaria; Colombini, Maria Perla; Legnaioli, Stefano; Lorenzetti, Giulia; Palleschi, Vincenzo

2016-11-05

In the occasion of the celebrations for the 150th anniversary of the founding of Italy (1861-2011), it was decided to analyse the artwork "The Italian Flag" (La Bandiera Italiana) created by the artist Fernando Melani (Pistoia, 1907-1985), one of the precursors of the Poor Art artistic movement in Italy. This project is a follow-up to a previous study which was mainly focused on the pigments and dyes found in his home-studio. The main goal of this paper is to identify a correct diagnostic plan, based on the use of a combination of non-invasive and micro-invasive methodologies, in order to determine the state of preservation and define the best conservation procedures for a contemporary artwork. Visible, infrared and infrared false colour images as well as the Fibre Optic Reflectance Spectroscopy (FORS) technique were applied in situ to analyse The Italian Flag. Laser Induced Breakdown Spectroscopy (LIBS), Fourier Transform Infrared (FT-IR) and micro-Raman spectroscopies, Pyrolysis-Gas Chromatography/Mass Spectroscopy (Py-GC/MS), High Performance Liquid Chromatography with Diode Arrays Detection (HPLC-DAD) and Mass Spectrometric Detection (HPLC-ESI-Q-ToF) were all applied to three small samples detached from the three painted (green-blue, white and red-yellow, respectively) areas of the flag. The combination of the data obtained with all these techniques made possible a comprehensive understanding of both the chemical composition and physical behaviour of the materials used by the artist and supported curators in defining the preventive conservation of this artwork. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovering "The Italian Flag" by Fernando Melani (1907-1985)

Science.gov (United States)

Carlesi, Serena; Bartolozzi, Giovanni; Cucci, Costanza; Marchiafava, Veronica; Picollo, Marcello; La Nasa, Jacopo; Di Girolamo, Francesca; Dilillo, Marialaura; Modugno, Francesca; Degano, Ilaria; Colombini, Maria Perla; Legnaioli, Stefano; Lorenzetti, Giulia; Palleschi, Vincenzo

2016-11-01

In the occasion of the celebrations for the 150th anniversary of the founding of Italy (1861-2011), it was decided to analyse the artwork ;The Italian Flag; (La Bandiera Italiana) created by the artist Fernando Melani (Pistoia, 1907-1985), one of the precursors of the Poor Art artistic movement in Italy. This project is a follow-up to a previous study which was mainly focused on the pigments and dyes found in his home-studio. The main goal of this paper is to identify a correct diagnostic plan, based on the use of a combination of non-invasive and micro-invasive methodologies, in order to determine the state of preservation and define the best conservation procedures for a contemporary artwork. Visible, infrared and infrared false colour images as well as the Fibre Optic Reflectance Spectroscopy (FORS) technique were applied in situ to analyse The Italian Flag. Laser Induced Breakdown Spectroscopy (LIBS), Fourier Transform Infrared (FT-IR) and micro-Raman spectroscopies, Pyrolysis-Gas Chromatography/Mass Spectroscopy (Py-GC/MS), High Performance Liquid Chromatography with Diode Arrays Detection (HPLC-DAD) and Mass Spectrometric Detection (HPLC-ESI-Q-ToF) were all applied to three small samples detached from the three painted (green-blue, white and red-yellow, respectively) areas of the flag. The combination of the data obtained with all these techniques made possible a comprehensive understanding of both the chemical composition and physical behaviour of the materials used by the artist and supported curators in defining the preventive conservation of this artwork.

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…

Surgically Implanted JSATS Micro-Acoustic Transmitters Effects on Juvenile Chinook Salmon and Steelhead Tag Expulsion and Survival, 2010

Energy Technology Data Exchange (ETDEWEB)

Woodley, Christa M.; Carpenter, Scott M.; Carter, Kathleen M.; Wagner, Katie A.; Royer, Ida M.; Knox, Kasey M.; Kim, Jin A.; Gay, Marybeth E.; Weiland, Mark A.; Brown, Richard S.

2011-09-16

The purpose of this study was to evaluate survival model assumptions associated with a concurrent study - Acoustic Telemetry Evaluation of Dam Passage Survival and Associated Metrics at John Day, The Dalles, and Bonneville Dams, 2010 by Thomas Carlson and others in 2010 - in which the Juvenile Salmonid Acoustic Telemetry System (JSATS) was used to estimate the survival of yearling and subyearling Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) migrating through the Federal Columbia River Power System (FCRPS). The micro-acoustic transmitter used in these studies is the smallest acoustic transmitter model to date (12 mm long x 5 mm wide x 4 mm high, and weighing 0.43 g in air). This study and the 2010 study by Carlson and others were conducted by researchers from the Pacific Northwest National Laboratory and the University of Washington for the U.S. Army Corps of Engineers, Portland District, to meet requirements set forth by the 2008 FCRPS Biological Opinion. In 2010, we compared survival, tag burden, and tag expulsion in five spring groups of yearling Chinook salmon (YCH) and steelhead (STH) and five summer groups of subyearling Chinook salmon (SYC) to evaluate survival model assumptions described in the concurrent study. Each tagging group consisted of approximately 120 fish/species, which were collected and implanted on a weekly basis, yielding approximately 600 fish total/species. YCH and STH were collected and implanted from late April to late May (5 weeks) and SYC were collected and implanted from mid-June to mid-July (5 weeks) at the John Day Dam Smolt Monitoring Facility. The fish were collected once a week, separated by species, and assigned to one of three treatment groups: (1) Control (no surgical treatment), (2) Sham (surgical implantation of only a passive integrated transponder [PIT] tag), and (3) Tagged (surgical implantation of JSATS micro-acoustic transmitter [AT] and PIT tags). The test fish were held for 30 days in indoor

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.

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.

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.

Thermo-mechanical actuator-based miniature tagging module for localization in capsule endoscopy

Science.gov (United States)

Chandrappan, Jayakrishnan; Ruiqi, Lim; Su, Nandar; Yen Yi, Germaine Hoe; Vaidyanathan, Kripesh

2011-04-01

Capsule endoscopy is a frontline medical diagnostic tool for the gastro intestinal tract disorders. During diagnosis, efficient localization techniques are essential to specify a pathological area that may require further diagnosis or treatment. This paper presents the development of a miniature tagging module that relies on a novel concept to label the region of interest and has the potential to integrate with a capsule endoscope. The tagging module is a compact thermo-mechanical actuator loaded with a biocompatible micro tag. A low power microheater attached to the module serves as the thermal igniter for the mechanical actuator. At optimum temperature, the actuator releases the micro tag instantly and penetrates the mucosa layer of a GI tract, region of interest. Ex vivo animal trials are conducted to verify the feasibility of the tagging module concept. X-ray imaging is used to detect the location of the micro tag embedded in the GI tract wall. The method is successful, and radiopaque micro tags can provide valuable pre-operative position information on the infected area to facilitate further clinical procedures.

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.

FLIP for FLAG model visualization

Energy Technology Data Exchange (ETDEWEB)

Wooten, Hasani Omar [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-11-15

A graphical user interface has been developed for FLAG users. FLIP (FLAG Input deck Parser) provides users with an organized view of FLAG models and a means for efficiently and easily navigating and editing nodes, parameters, and variables.

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.

75 FR 34309 - Flag Day and National Flag Week, 2010

Science.gov (United States)

2010-06-16

... Nation to confront tyranny and oppression still flies today as an unequivocal emblem of freedom and... gatherings to private memorials, we gathered to salute our flag, and in doing so, renewed the eternal promise... recognize the American flag as a symbol of hope and inspiration to people at home and around the world--as a...

Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients

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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.

Romania's flag raised at CERN

CERN Multimedia

Corinne Pralavorio

2016-01-01

A ceremony was held for the raising of the Romanian flag alongside the flags of CERN’s 21 other Member States.   The Romanian flag is raised alongside the flags of CERN’s other Member States, in the presence of the Romanian President, CERN’s Director-General, the President of the CERN Council and a large Romanian delegation. (Image: Maximilien Brice/ Sophia Bennett/CERN) On Monday, 5 September, the Romanian flag was raised in front of CERN for the first time, marking the country’s accession to Membership of the Organization. The blue, yellow and red flag joined those of the other 21 Member States of CERN in a ceremony attended by the President of Romania, Klaus Iohannis, the Romanian Minister for Education and Scientific Research, Mircea Dumitru, and several other members of the President’s office, the government and academia in Romania. The country officially became a CERN Member State on 17 July 2016, after 25 years of collaboration between the...

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.

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

Science.gov (United States)

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

2017-03-04

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

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.

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.

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.

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.

46 CFR 282.11 - Ranking of flags.

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Ranking of flags. 282.11 Section 282.11 Shipping... COMMERCE OF THE UNITED STATES Foreign-Flag Competition § 282.11 Ranking of flags. The operators under each... priority of costs which are representative of the flag. For liner cargo vessels, the ranking of operators...

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

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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

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.

MicroRNA-486–dependent modulation of DOCK3/PTEN/AKT signaling pathways improves muscular dystrophy–associated symptoms

Science.gov (United States)

Alexander, Matthew S.; Casar, Juan Carlos; Motohashi, Norio; Vieira, Natássia M.; Eisenberg, Iris; Marshall, Jamie L.; Gasperini, Molly J.; Lek, Angela; Myers, Jennifer A.; Estrella, Elicia A.; Kang, Peter B.; Shapiro, Frederic; Rahimov, Fedik; Kawahara, Genri; Widrick, Jeffrey J.; Kunkel, Louis M.

2014-01-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, which results in dysfunctional signaling pathways within muscle. Previously, we identified microRNA-486 (miR-486) as a muscle-enriched microRNA that is markedly reduced in the muscles of dystrophin-deficient mice (Dmdmdx-5Cv mice) and in DMD patient muscles. Here, we determined that muscle-specific transgenic overexpression of miR-486 in muscle of Dmdmdx-5Cv mice results in reduced serum creatine kinase levels, improved sarcolemmal integrity, fewer centralized myonuclei, increased myofiber size, and improved muscle physiology and performance. Additionally, we identified dedicator of cytokinesis 3 (DOCK3) as a miR-486 target in skeletal muscle and determined that DOCK3 expression is induced in dystrophic muscles. DOCK3 overexpression in human myotubes modulated PTEN/AKT signaling, which regulates muscle hypertrophy and growth, and induced apoptosis. Furthermore, several components of the PTEN/AKT pathway were markedly modulated by miR-486 in dystrophin-deficient muscle. Skeletal muscle–specific miR-486 overexpression in Dmdmdx-5Cv animals decreased levels of DOCK3, reduced PTEN expression, and subsequently increased levels of phosphorylated AKT, which resulted in an overall beneficial effect. Together, these studies demonstrate that stable overexpression of miR-486 ameliorates the disease progression of dystrophin-deficient skeletal muscle. PMID:24789910

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.

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.

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.

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.

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

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.

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.

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

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

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

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...

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.

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

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.

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.

Isolation of microRNA targets using biotinylated synthetic microRNAs

DEFF Research Database (Denmark)

Ørom, Ulf Andersson; Lund, Anders H

2007-01-01

MicroRNAs are small regulatory RNAs found in multicellular organisms where they post-transcriptionally regulate gene expression. In animals, microRNAs bind mRNAs via incomplete base pairings making the identification of microRNA targets inherently difficult. Here, we present a detailed method...... for experimental identification of microRNA targets based on affinity purification of tagged microRNAs associated with their targets. Udgivelsesdato: 2007-Oct...

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.

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

Science.gov (United States)

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

2003-01-01

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

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/.

The International Atomic Energy Agency Flag Code

International Nuclear Information System (INIS)

1999-01-01

The document reproduces the text of the IAEA Flag Code which was promulgated by the Director General on 15 September 1999, pursuant to the decision of the Board of Governors on 10 June 1999 to adopt an Agency flag as described in document GOV/1999/41 and its use in accordance with a flag code to be promulgated by the Director General

The International Atomic Energy Agency Flag Code

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-11-17

The document reproduces the text of the IAEA Flag Code which was promulgated by the Director General on 15 September 1999, pursuant to the decision of the Board of Governors on 10 June 1999 to adopt an Agency flag as described in document GOV/1999/41 and its use in accordance with a flag code to be promulgated by the Director General.

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

A brief examination of optical tagging technologies.

Energy Technology Data Exchange (ETDEWEB)

Ackermann, Mark R.; Cahill, Paul A. (Aspecular Optics, Dayton, OH); Drummond, Timothy J.; Wilcoxon, Jess Patrick

2003-07-01

Presented within this report are the results of a brief examination of optical tagging technologies funded by the Laboratory Directed Research and Development (LDRD) program at Sandia National Laboratories. The work was performed during the summer months of 2002 with total funding of $65k. The intent of the project was to briefly examine a broad range of approaches to optical tagging concentrating on the wavelength range between ultraviolet (UV) and the short wavelength infrared (SWIR, {lambda} < 2{micro}m). Tagging approaches considered include such things as simple combinations of reflective and absorptive materials closely spaced in wavelength to give a high contrast over a short range of wavelengths, rare-earth oxides in transparent binders to produce a narrow absorption line hyperspectral tag, and fluorescing materials such as phosphors, dies and chemically precipitated particles. One technical approach examined in slightly greater detail was the use of fluorescing nano particles of metals and semiconductor materials. The idea was to embed such nano particles in an oily film or transparent paint binder. When pumped with a SWIR laser such as that produced by laser diodes at {lambda}=1.54{micro}m, the particles would fluoresce at slightly longer wavelengths, thereby giving a unique signal. While it is believed that optical tags are important for military, intelligence and even law enforcement applications, as a business area, tags do not appear to represent a high on return investment. Other government agencies frequently shop for existing or mature tag technologies but rarely are interested enough to pay for development of an untried technical approach. It was hoped that through a relatively small investment of laboratory R&D funds, enough technologies could be identified that a potential customers requirements could be met with a minimum of additional development work. Only time will tell if this proves to be correct.

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.

RFI flagging implications for short-duration transients

Science.gov (United States)

Cendes, Y.; Prasad, P.; Rowlinson, A.; Wijers, R. A. M. J.; Swinbank, J. D.; Law, C. J.; van der Horst, A. J.; Carbone, D.; Broderick, J. W.; Staley, T. D.; Stewart, A. J.; Huizinga, F.; Molenaar, G.; Alexov, A.; Bell, M. E.; Coenen, T.; Corbel, S.; Eislöffel, J.; Fender, R.; Grießmeier, J.-M.; Jonker, P.; Kramer, M.; Kuniyoshi, M.; Pietka, M.; Stappers, B.; Wise, M.; Zarka, P.

2018-04-01

With their wide fields of view and often relatively long coverage of any position in the sky in imaging survey mode, modern radio telescopes provide a data stream that is naturally suited to searching for rare transients. However, Radio Frequency Interference (RFI) can show up in the data stream in similar ways to such transients, and thus the normal pre-treatment of filtering RFI (flagging) may also remove astrophysical transients from the data stream before imaging. In this paper we investigate how standard flagging affects the detectability of such transients by examining the case of transient detection in an observing mode used for Low Frequency Array (LOFAR; van Haarlem et al., 2013) surveys. We quantify the fluence range of transients that would be detected, and the reduction of their SNR due to partial flagging. We find that transients with a duration close to the integration sampling time, as well as bright transients with durations on the order of tens of seconds, are completely flagged. For longer transients on the order of several tens of seconds to minutes, the flagging effects are not as severe, although part of the signal is lost. For these transients, we present a modified flagging strategy which mitigates the effect of flagging on transient signals. We also present a script which uses the differences between the two strategies, and known differences between transient RFI and astrophysical transients, to notify the observer when a potential transient is in the data stream.

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.

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.

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.

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

Directory of Open Access Journals (Sweden)

Matthew S Barnabei

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

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.

Fcγ1 fragment of IgG1 as a powerful affinity tag in recombinant Fc-fusion proteins: immunological, biochemical and therapeutic properties.

Science.gov (United States)

Soleimanpour, Saman; Hassannia, Tahereh; Motiee, Mahdieh; Amini, Abbas Ali; Rezaee, S A R

2017-05-01

Affinity tags are vital tools for the production of high-throughput recombinant proteins. Several affinity tags, such as the hexahistidine tag, maltose-binding protein, streptavidin-binding peptide tag, calmodulin-binding peptide, c-Myc tag, glutathione S-transferase and FLAG tag, have been introduced for recombinant protein production. The fragment crystallizable (Fc) domain of the IgG1 antibody is one of the useful affinity tags that can facilitate detection, purification and localization of proteins and can improve the immunogenicity, modulatory effects, physicochemical and pharmaceutical properties of proteins. Fcγ recombinant forms a group of recombinant proteins called Fc-fusion proteins (FFPs). FFPs are widely used in drug discovery, drug delivery, vaccine design and experimental research on receptor-ligand interactions. These fusion proteins have become successful alternatives to monoclonal antibodies for drug developments. In this review, the physicochemical, biochemical, immunological, pharmaceutical and therapeutic properties of recombinant FFPs were discussed as a new generation of bioengineering strategies.

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.

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

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.

49 CFR 218.37 - Flag protection.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Flag protection. 218.37 Section 218.37..., DEPARTMENT OF TRANSPORTATION RAILROAD OPERATING PRACTICES Protection of Trains and Locomotives § 218.37 Flag protection. (a) After August 1, 1977, each railroad must have in effect an operating rule which complies with...

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.

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

Alterations in the muscle force transfer apparatus in aged rats during unloading and reloading: Impact of microRNA-31.

Science.gov (United States)

Hughes, David C; Marcotte, George R; Baehr, Leslie M; West, Daniel W D; Marshall, Andrea G; Ebert, Scott M; Davidyan, Arik; Adams, Christopher M; Bodine, Sue C; Baar, Keith

2018-05-03

Force transfer is integral for maintaining skeletal muscle structure and function. One important component is dystrophin. There is limited understanding of how force transfer is impacted by age and loading. Here, we investigate the force transfer apparatus in muscles of adult and old rats exposed to periods of disuse and reloading. Our results demonstrate an increase in dystrophin protein during the reloading phase in the adult TA muscle that is delayed in old. The consequence of this delay is an increased susceptibility towards contraction-induced muscle injury. Central to the lack of dystrophin protein is an increase in miR-31, a microRNA that inhibits dystrophin translation. In vivo electroporation with a miR-31 sponge led to increased dystrophin protein and decreased contraction-induced muscle injury in old skeletal muscle. Overall, our results detail the importance of the force transfer apparatus and provide new mechanisms for contraction-induced injury in aging skeletal muscle. In healthy muscle, the dystrophin-associated glycoprotein (DGC) and integrin/focal adhesion complexes, intermediate filaments, and Z-line proteins transmit force from the contractile proteins to the extracellular matrix. How loading and age affect these proteins is poorly understood. The experiments reported here sought to determine the effect of aging on the force transfer apparatus following muscle unloading and reloading. Adult (9 months) and old (29 months) rats were subjected to 14 days hindlimb unloading (HU) and 1, 3, 7 and 14 days of reloading (REL). The DGC complex, intermediate filament and z-line protein and mRNA levels, as well as dystrophin-targeting miRNAs (miR-31, -146b and -374) were examined in the tibialis anterior (TA) and medial gastrocnemius (MG) muscles at both ages. There was a significant increase in dystrophin protein levels (2.79-fold) upon 3 days of reloading in the adult TA muscle that did not occur in the old rats (p ≤ 0.05), and the rise in

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

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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.

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.

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

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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.

Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

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Takahashi, Hitoshi; Akazawa, Daisuke [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Kato, Takanobu; Date, Tomoko [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Shirakura, Masayuki [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Toray Industries, Inc., Kanagawa (Japan); Nakamura, Noriko; Mochizuki, Hidenori [Toray Industries, Inc., Kanagawa (Japan); Tanaka-Kaneko, Keiko; Sata, Tetsutaro [Department of Pathology, National Institute of Infectious Diseases, Tokyo (Japan); Tanaka, Yasuhito [Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medicine, Nagoya (Japan); Mizokami, Masashi [Research Center for Hepatitis and Immunology, Kohnodai Hospital, International Medical Center of Japan, Chiba (Japan); Suzuki, Tetsuro [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan); Wakita, Takaji, E-mail: wakita@nih.go.jp [Department of Virology II, National Institute of Infectious Diseases, Tokyo (Japan)

2010-05-14

To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

Biological properties of purified recombinant HCV particles with an epitope-tagged envelope

International Nuclear Information System (INIS)

Takahashi, Hitoshi; Akazawa, Daisuke; Kato, Takanobu; Date, Tomoko; Shirakura, Masayuki; Nakamura, Noriko; Mochizuki, Hidenori; Tanaka-Kaneko, Keiko; Sata, Tetsutaro; Tanaka, Yasuhito; Mizokami, Masashi; Suzuki, Tetsuro; Wakita, Takaji

2010-01-01

To establish a simple system for purification of recombinant infectious hepatitis C virus (HCV) particles, we designed a chimeric J6/JFH-1 virus with a FLAG (FL)-epitope-tagged sequence at the N-terminal region of the E2 hypervariable region-1 (HVR1) gene (J6/JFH-1/1FL). We found that introduction of an adaptive mutation at the potential N-glycosylation site (E2N151K) leads to efficient production of the chimeric virus. This finding suggests the involvement of glycosylation at Asn within the envelope protein(s) in HCV morphogenesis. To further analyze the biological properties of the purified recombinant HCV particles, we developed a strategy for large-scale production and purification of recombinant J6/JFH-1/1FL/E2N151K. Infectious particles were purified from the culture medium of J6/JFH-1/1FL/E2N151K-infected Huh-7 cells using anti-FLAG affinity chromatography in combination with ultrafiltration. Electron microscopy of the purified particles using negative staining showed spherical particle structures with a diameter of 40-60 nm and spike-like projections. Purified HCV particle-immunization induced both an anti-E2 and an anti-FLAG antibody response in immunized mice. This strategy may contribute to future detailed analysis of HCV particle structure and to HCV vaccine development.

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

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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.

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

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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.

76 FR 35087 - Flag Day and National Flag Week, 2011

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2011-06-15

... flag with thirteen stripes and thirteen stars to represent our Nation, one star for each of our founding colonies. The stars were set upon a blue field, in the words of the Congress's resolution, ``representing a new constellation'' in the night sky. What was then a fledgling democracy has flourished and...

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

QTL mapping of flag leaf-related traits in wheat (Triticum aestivum L.).

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Liu, Kaiye; Xu, Hao; Liu, Gang; Guan, Panfeng; Zhou, Xueyao; Peng, Huiru; Yao, Yingyin; Ni, Zhongfu; Sun, Qixin; Du, Jinkun

2018-04-01

QTL controlling flag leaf length, flag leaf width, flag leaf area and flag leaf angle were mapped in wheat. This study aimed to advance our understanding of the genetic mechanisms underlying morphological traits of the flag leaves of wheat (Triticum aestivum L.). A recombinant inbred line (RIL) population derived from ND3331 and the Tibetan semi-wild wheat Zang1817 was used to identify quantitative trait loci (QTLs) controlling flag leaf length (FLL), flag leaf width (FLW), flag leaf area (FLA), and flag leaf angle (FLANG). Using an available simple sequence repeat genetic linkage map, 23 putative QTLs for FLL, FLW, FLA, and FLANG were detected on chromosomes 1B, 2B, 3A, 3D, 4B, 5A, 6B, 7B, and 7D. Individual QTL explained 4.3-68.52% of the phenotypic variance in different environments. Four QTLs for FLL, two for FLW, four for FLA, and five for FLANG were detected in at least two environments. Positive alleles of 17 QTLs for flag leaf-related traits originated from ND3331 and 6 originated from Zang1817. QTLs with pleiotropic effects or multiple linked QTL were also identified on chromosomes 1B, 4B, and 5A; these are potential target regions for fine-mapping and marker-assisted selection in wheat breeding programs.

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.

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.

A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis

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Zheng Shuqiu

2012-08-01

Full Text Available Abstract Background Huntington’s disease (HD is an autosomal dominant neurodegenerative disease that is caused by the expansion of a polyglutamine (polyQ stretch within Huntingtin (htt, the protein product of the HD gene. Although studies in vitro have suggested that the mutant htt can act in a potentially dominant negative fashion by sequestering wild-type htt into insoluble protein aggregates, the role of the length of the normal htt polyQ stretch, and the adjacent proline-rich region (PRR in modulating HD mouse model pathogenesis is currently unknown. Results We describe the generation and characterization of a series of knock-in HD mouse models that express versions of the mouse HD gene (Hdh encoding N-terminal hemaglutinin (HA or 3xFlag epitope tagged full-length htt with different polyQ lengths (HA7Q-, 3xFlag7Q-, 3xFlag20Q-, and 3xFlag140Q-htt and substitution of the adjacent mouse PRR with the human PRR (3xFlag20Q- and 3xFlag140Q-htt. Using co-immunoprecipitation and immunohistochemistry analyses, we detect no significant interaction between soluble full-length normal 7Q- htt and mutant (140Q htt, but we do observe N-terminal fragments of epitope-tagged normal htt in mutant htt aggregates. When the sequences encoding normal mouse htt’s polyQ stretch and PRR are replaced with non-pathogenic human sequence in mice also expressing 140Q-htt, aggregation foci within the striatum, and the mean size of htt inclusions are increased, along with an increase in striatal lipofuscin and gliosis. Conclusion In mice, soluble full-length normal and mutant htt are predominantly monomeric. In heterozygous knock-in HD mouse models, substituting the normal mouse polyQ and PRR with normal human sequence can exacerbate some neuropathological phenotypes.

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

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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.

FIRE! A Red Flag Tap in Reclaiming Intervention

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Bodnar, Brian

2007-01-01

"Red Flag Interventions" address problems which are imported from elsewhere and acted out towards persons who are in effect innocent bystanders. This is commonly seen as students "carry in" problems from the home or street to school, or they "carry over" conflicts from one class to the next. A third variation of Red Flag intervention is when a…

Experimental investigation of flow field around the elastic flag flapping in periodic state

Science.gov (United States)

Jia, Yongxia; Jia, Lichao; Su, Zhuang; Yuan, Huijing

2018-05-01

The flapping of a flag in the wind is a classical fluid-structure problem that concerns the interaction of elastic bodies with ambient fluid. We focus on the desirable experimental results of the flow around the flapping flag. By immersing the elastic yet self-supporting heavy flag into water flow, we use particle image velocimetry (PIV) techniques to obtain the whole flow field around the midspan of the flag interacting with a fluid in periodic state. A unique PIV image processing method is used to measure near-wall flow velocities around a moving elastic flag. There exists a thin flow circulation region on the suction side of the flag in periodic state. This observation suggests that viscous flow models may be needed to improve the theoretical predictions of the flapping flag in periodic state, especially in a large amplitude.

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

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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.

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.

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.

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.

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

Science.gov (United States)

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

2009-07-17

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

Tag-elese or The Language of Tags

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Jan Simons

2008-01-01

Full Text Available The core "meme" of Web 2.0 from which almost all other memes radiated was: 'You control your own data' (O'Reilly, 2005, 3. Key instruments for this user control are tagging systems that allow users to freely assign keywords of their own choosing to Internet resources of their own making as well as to documents produced by others. Of course, freely chosen keywords tags do not necessarily follow prefixed taxonomies or classification systems. But going by the maxim that interaction creates similarity and similarity creates interaction, the idea - or hope - is, however, that the tagging practices of individual users will eventually converge into an emergent common vocabulary or folksonomy (Merholz, 2004; Shirky, 2005; Vander Wal, 2005b; Mika, 2007. It is far from clear, however, that free tagging systems will eventually yield controlled vocabularies, and there are many incentives for idiosyncratic, ambiguous, and inconsistent uses of tags. Left to themselves, free tagging systems seem to be too wild and too chaotic for any order to emerge. But are these free tagging systems really as "feral" as they seem to be, or do they only look uncontrolled because one has been looking for order in the wrong place? I have done a quick-and-dirty" analysis of Flickr's tag cloud. The concept was: if folksonomies encourage users to tap on their own vernacular, everyday natural language must somehow "guide" the tagging practices of users of tagging systems. Flickr's tag cloud has been choosen because it may teach us something about tagging systems and folksonomies, and not - or not primarily - because of what tags may tell us about pictures.

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...

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.

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.

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.

A Rotational Crofton Formula for Flagged Intrinsic Volumes of Sets of Positive Reach

DEFF Research Database (Denmark)

Auneau, Jeremy Michel

A rotational Crofton formula is derived relating the flagged intrinsic volumes of a compact set of positive reach with the flagged intrinsic volumes measured on sections passing through a fixed point. In particular cases, the flagged intrinsic volumes defined in the present paper are identical...

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.

Support for the Confederate Battle Flag in the Southern United States: Racism or Southern Pride?

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Joshua D. Wright

2017-05-01

Full Text Available Supporters of the Confederate battle flag often argue that their support is driven by pride in the South, not negative racial attitudes. Opponents of the Confederate battle flag often argue that the flag represents racism, and that support for the flag is an expression of racism and an attempt to maintain oppression of Blacks in the Southern United States. We evaluate these two competing views in explaining attitudes toward the Confederate battle flag in the Southern United States through a survey of 526 Southerners. In the aggregate, our latent variable model suggests that White support for the flag is driven by Southern pride, political conservatism, and blatant negative racial attitudes toward Blacks. Using cluster-analysis we were able to distinguish four distinct sub-groups of White Southerners: Cosmopolitans, New Southerners, Traditionalists, and Supremacists. The greatest support for the Confederate battle flag is seen among Traditionalists and Supremacists; however, Traditionalists do not display blatant negative racial attitudes toward Blacks, while Supremacists do. Traditionalists make up the majority of Confederate battle flag supporters in our sample, weakening the claim that supporters of the flag are generally being driven by negative racial attitudes toward Blacks.

Exposure to the American flag polarizes democratic-republican ideologies.

Science.gov (United States)

Chan, Eugene Y

2017-12-01

Some prior research has suggested that exposure to the American flag tilts Americans towards Republicanism, while others have proffered that it brings outs a common 'together' perspective instead. We explore a third possibility - that it may actually polarize Americans' political ideology. It is generally accepted that exposure to an environmental cue can shift attitudes and behaviours, at least partly or temporarily, in a manner that is consistent with that cue. Yet, the same cue can mean different things to different people. In the same vein, given how national identity and political ideology are intertwined in the United States, we hypothesize that the American flag should heighten different political beliefs depending on individuals' political ideology. To Democrats, being American is to support Democratic values, but to Republicans, being American is to support Republican values. The American flag thus should heighten Democrats of their Democratic identity, and it should heighten Republicans of their Republican one. The results of an experiment with 752 American respondents who were representative of the US population supported this polarizing effect of the American flag. The theoretical and policy implications of the findings are offered. © 2017 The British Psychological Society.

Flags of the night sky when astronomy meets national pride

CERN Document Server

Bordeleau, André G

2014-01-01

Many national flags display astronomical features–Sun, Moon, stars–but are they really based on existing astronomical objects? The United States flag sports 50 stars, one for each state, however none of them are linked to real stars. Further, the lunar crescent is often shaped like the Sun being eclipsed by the Moon. At times, stars are seen right next to the crescent, where the darkened disc of the moon should be! This book will present true astronomical objects and patterns highlighted on national flags and link informative capsules about these objects to the political reasons why they were chosen to adorn such an important symbol.

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....

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

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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.

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.

High explosive programmed burn in the FLAG code

Energy Technology Data Exchange (ETDEWEB)

Mandell, D.; Burton, D.; Lund, C.

1998-02-01

The models used to calculate the programmed burn high-explosive lighting times for two- and three-dimensions in the FLAG code are described. FLAG uses an unstructured polyhedra grid. The calculations were compared to exact solutions for a square in two dimensions and for a cube in three dimensions. The maximum error was 3.95 percent in two dimensions and 4.84 percent in three dimensions. The high explosive lighting time model described has the advantage that only one cell at a time needs to be considered.

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

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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

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

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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.

76 FR 39885 - Risk-Based Targeting of Foreign Flagged Mobile Offshore Drilling Units (MODUs)

Science.gov (United States)

2011-07-07

... Foreign Flagged Mobile Offshore Drilling Units (MODUs) AGENCY: Coast Guard, DHS. ACTION: Notice of... 11-06, Risk-Based Targeting of Foreign Flagged Mobile Offshore Drilling Units (MODUs). This policy... applicable regulations, every foreign-flagged mobile offshore drilling unit (MODU) must undergo a Coast Guard...

Artist's rendering of astronaut Neil Armstrong planting U.S. flag on Moon

Science.gov (United States)

1969-01-01

Artist's Concept: Apollo 11 astronaut Neil Armstrong, after stepping onto the lunar surface, will plant the United States flag in its soil. The flag will be made of nylone, size 3- by 5 feet on a staff 8 feet long. During flight it will be stowed in two 4-foot sections strapped to the Lunar Module ladder. Armstrong's first assignment after stepping off the ladder is to pull a 'D' ring to start a television camera. The second assignment is to erect the U.S. flag. The flag will appear to be flying in a breeze. This is done with a spring-loaded wire in the nylon cloth. With everything is working normally, this will be observed on live television.

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.

[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.

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.

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.

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

Pseudo-Kaehler quantization on flag manifolds

International Nuclear Information System (INIS)

Karabegov, A.V.

1997-07-01

A unified approach to geometric, symbol and deformation quantizations on a generalized flag manifold endowed with an invariant pseudo-Kaehler structure is proposed. In particular cases we arrive at Berezin's quantization via covariant and contravariant symbols. (author). 16 refs

A magnetic particle micro-trap for large trapping surfaces

KAUST Repository

Gooneratne, Chinthaka P.

2012-01-08

Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

A magnetic particle micro-trap for large trapping surfaces

KAUST Repository

Gooneratne, Chinthaka P.; Liang, Cai; Giouroudi, Ioanna; Kosel, Jü rgen

2012-01-01

Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

Tag questions Tag questions

Directory of Open Access Journals (Sweden)

David Brazil

2008-04-01

Full Text Available The so-called 'tag' structures of English have received a lot of attention in language teaching programmes, attention that is not hard to justify when one considers the problems and anxiety they can occasion for many foreign learners. Most teachers one speaks to seem fairly willing to agree, however, that traditional treatments of the topic leave much to be desired. It happens, also, that, when considered collectively, the tags and some related phenomena have a special heoretical interest. For they constitute a field in which it seems essential to bring together insights that derive from the study of several aspects of linguistic organisation, aspects which in some recent work have been held to need distinctive kinds of descriptive category to handle. Traditional treatments have found it necessary to recognise different syntactic types (e.g. 'same polarity' and 'reversed polarity' tags and ifferent intonational treatments ("falling'and 'rising' tag; while the way the communicative significance of the various permutations is described normally requires reference to the expectations they signal regarding the immediately following behaviour of the other party (in the common phrase, 'What kind of answer they expect'. This last consideration places the matter squarely in the arena of recent work on the analysis of interactive discourse. The so-called 'tag' structures of English have received a lot of attention in language teaching programmes, attention that is not hard to justify when one considers the problems and anxiety they can occasion for many foreign learners. Most teachers one speaks to seem fairly willing to agree, however, that traditional treatments of the topic leave much to be desired. It happens, also, that, when considered collectively, the tags and some related phenomena have a special heoretical interest. For they constitute a field in which it seems essential to bring together insights that derive from the study of several aspects

Tempting To Tag: An Experimental Comparison Of Four Tagging Input Mechanisms

Directory of Open Access Journals (Sweden)

Mark Melenhorst

2010-01-01

Full Text Available Tagging helps achieve improved indexing and recommendation of resources (e.g., videos or pictures in large data collections. In order to reap the benefits of tagging, people must be persuaded to label the resources they consume. This paper reports on a study in which four different tagging input mechanisms and their effect on users' motivation to tag were compared. The mechanisms consisted of a standard tag input box, a chatbot-like environment, a bookmarking mechanism, and a "tag and vote" game. The results of our experiment show that the use of the nonstandard tagging input mechanisms does not affect users' motivation to tag. In some instances tagging mechanisms were found to distract users from their primary task: consuming resources. Persuading people to tag might be accomplished more effectively by using other motivating tagging mechanisms (e.g., tagging games, or motivation could be created by explaining the usefulness of tagging.

The iconography of the flags of Charles V: examples and documents

Directory of Open Access Journals (Sweden)

Jesús F. Pascual Molina

2017-03-01

Full Text Available The Emperor Charles V formed an important group of arms and armor in his armory at Valladolid. In 1556, during his last journey to Spain, new pieces were sent to this royal armory; after his death they passed to Philip II, who sent them to Madrid, where he ordered a new building especially for the collection. Among these pieces was an important group of flags linked to major episodes of the Emperor’s life. The author describes the flags and their iconography, providing as well unpublished archival materials, which permit a better understanding of the flags used in times of Caesar Charles and their meanings.

Cyber Flag: A Realistic Cyberspace Training Construct

National Research Council Canada - National Science Library

Hansen, Andrew P

2008-01-01

.... Red Flag provides dominant training within the air domain and now with the evolution of cyberspace, a comprehensive training environment is necessary to meet this growing and broadening threat...

FlagHouse Forum: You Say "Tomato"... and I Use a Communicator

Science.gov (United States)

Exceptional Parent, 2011

2011-01-01

This month's "FlagHouse Forum" focuses on how to choose the communicator best-suited to a child's special need. FlagHouse--a premier global supplier of resources for special needs, education, physical activity and recreation--is pleased to partner with "Exceptional Parent" to bring its readers this informational forum. Humans communicate with each…

Anomalous Hydrodynamic Drafting of Interacting Flapping Flags

Science.gov (United States)

Ristroph, Leif; Zhang, Jun

2008-11-01

In aggregates of objects moving through a fluid, bodies downstream of a leader generally experience reduced drag force. This conventional drafting holds for objects of fixed shape, but interactions of deformable bodies in a flow are poorly understood, as in schools of fish. In our experiments on “schooling” flapping flags, we find that it is the leader of a group who enjoys a significant drag reduction (of up to 50%), while the downstream flag suffers a drag increase. This counterintuitive inverted drag relationship is rationalized by dissecting the mutual influence of shape and flow in determining drag. Inverted drafting has never been observed with rigid bodies, apparently due to the inability to deform in response to the altered flow field of neighbors.

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.

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.

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.

46 CFR 252.22 - Substantiality and extent of foreign-flag competition.

Science.gov (United States)

2010-10-01

... January 1 of the subsidized year, by surveying a data file known as “Merchant Fleets of the World” that is... total tonnage in the range. (e) Largest foreign flag not competitor. In the event that the Board... competitor of any particular operator, the Board may determine the foreign-flag competition in a manner that...

The use of external electronic tags on fish: an evaluation of tag retention and tagging effects

DEFF Research Database (Denmark)

Jepsen, Niels; Thorstad, Eva B.; Havn, Torgeir

2015-01-01

External tagging of fish with electronic tags has been used for decades for a wide range of marine and freshwater species. In the early years of fish telemetry research, it was the most commonly used attachment method, but later internal implants became preferred. Recently, the number of telemetry...... unsuitable for surgical implantation, or when using tags with sensors recording the external environment. The most commonly reported problems with external tags are tissue damage, premature tag loss, and decreased swimming capacity, but the effects are highly context dependent and species specific. Reduced......, but particularly there are few studies on predation risk, social interactions, and studies distinguishing capture and handling effects from tagging effects. For PSATs, especially those that are large relative to fish size, there are particular problems with a high proportion of premature tag losses, reduced...

Billfish Tagging

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The SWFSC's constituent-based Billfish Tagging Program began in 1963 and since that time has provided conventional spaghetti type tags and tagging supplies to...

Construction and characterization of 3A-epitope-tagged foot-and-mouth disease virus.

Science.gov (United States)

Ma, Xueqing; Li, Pinghua; Sun, Pu; Bai, Xingwen; Bao, Huifang; Lu, Zengjun; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

2015-04-01

Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids (aa) in most FMDVs examined to date. Specific deletion in the FMDV 3A protein has been associated with the inability of FMDV to grow in primary bovine cells and cause disease in cattle. However, the aa residues playing key roles in these processes are poorly understood. In this study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9 aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues 94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses stably maintained and expressed the foreign epitopes even after 10 serial passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties and plaque phenotypes similar to those of the parental virus in BHK-21 cells. However, the epitope-tagged viruses exhibited lower growth rates and smaller plaque size phenotypes than those of the parental virus in primary fetal bovine kidney (FBK) cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the decreased ability of FMDV to replicate in primary bovine cells was not associated with the length of 3A, and the genetic determinant thought to play key role in decreased ability to replicate in primary bovine cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101 in 3A protein. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Laura Graciotti

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

Yellow flag scores in a compensable New Zealand cohort suffering acute low back pain

Directory of Open Access Journals (Sweden)

Karen Grimmer-Somers

2008-12-01

Full Text Available Karen Grimmer-Somers1, Mathew Prior1, Jim Robertson21Centre for Allied Health Evidence, University of South Australia, City East Campus, North Tce, Adelaide, South Australia, Australia; 2New Zealand Accident Compensation Corporation, Auckland, New ZealandBackground: Despite its high prevalence, most acute low back pain (ALBP is nonspecific, self-limiting with no definable pathology. Recurrence is prevalent, as is resultant chronicity. Psychosocial factors (yellow flags comprising depression and anxiety, negative pain beliefs, job dissatisfaction are associated with the development of chronic LBP.Methods: A national insurer (Accident Compensation Corporation, New Zealand [NZ], in conjunction with a NZ primary health organization, piloted a strategy for more effective management of patients with ALBP, by following the NZ ALBP Guideline. The guidelines recommend the use of a psychosocial screening instrument (Yellow Flags Screening Instrument, a derivative of Örebro Musculoskeletal Pain Questionnaire. This instrument was recommended for administration on the second visit to a general medical practitioner (GP. This paper tests whether published cut-points of yellow flag scores to predict LBP claims length and costs were valid in this cohort.Results: Data was available for 902 claimants appropriately enrolled into the pilot. 25% claimants consulted the GP once only, and thus were not requested to provide a yellow flag score. Yellow flag scores were provided by 48% claimants who consumed two or more GP services. Approximately 60% LBP presentations resolved within five GP visits. Yellow flag scores were significantly and positively associated with treatment costs and service use, although the association was nonlinear. Claimants with moderate yellow flag scores were similarly likely to incur lengthy claims as claimants with at-risk scores.Discussion: Capturing data on psychosocial factors for compensable patients with ALBP has merit in predicting

Effects of Cd2+ on chlorophyll content in flag and grain yield of wheats

International Nuclear Information System (INIS)

Zhu Zhiyong; Li Youjun; Liu Yingjie; Duan Youqiang; Li Qiang; Hao Yufen; Guo Jia

2011-01-01

A field experiment was conducted with wheat cultivars Luohan 6 and Yumai 18 to investigate the effects of Cd 2+ stress on chlorophyll contents in flag leaves, flag leave area, thousand kernel weight, kernel filling velocity and yield of wheat. Results indicated that, under low Cd 2+ stress (10 mg/kg), the average contents of chlorophyll a + b of Luohan 6 reduced by 1.6%, however, its average area of flag leave and yield increased by 3.8% and 1.6%, respectively. At the same time, the average content of chlorophyll a + b, area of flag leave yield of Yumai 18 reduced 8.0%, 9.6% and 5.4%. Under high Cd 2+ stress (100 mg/kg), the average contents of chlorophyll a + b, areas of flag leaves and yields of Luohan 6 and Yumai 18 reduced by 29.2% and 30.5%, 6.3% and 17.4%, 16.7% and 36.7%, respectively. The results demonstrated that Cd 2+ restrained synthesis and accumulation of chlorophyll and its components. This study even showed that within a range of Cd 2+ concentration could promote the growth of flag leaves, and it also had an equal positive effect on yield of wheat if the Cd 2+ concentration in grains were not out of limit. The growth of flag leave and yield of wheat would be limited when Cd 2+ concentration exceed that range. Overall, Yumai 18 bore more poison from Cd 2+ than Luohan 6. (authors)

Extracting Tag Hierarchies

Science.gov (United States)

Tibély, Gergely; Pollner, Péter; Vicsek, Tamás; Palla, Gergely

2013-01-01

Tagging items with descriptive annotations or keywords is a very natural way to compress and highlight information about the properties of the given entity. Over the years several methods have been proposed for extracting a hierarchy between the tags for systems with a "flat", egalitarian organization of the tags, which is very common when the tags correspond to free words given by numerous independent people. Here we present a complete framework for automated tag hierarchy extraction based on tag occurrence statistics. Along with proposing new algorithms, we are also introducing different quality measures enabling the detailed comparison of competing approaches from different aspects. Furthermore, we set up a synthetic, computer generated benchmark providing a versatile tool for testing, with a couple of tunable parameters capable of generating a wide range of test beds. Beside the computer generated input we also use real data in our studies, including a biological example with a pre-defined hierarchy between the tags. The encouraging similarity between the pre-defined and reconstructed hierarchy, as well as the seemingly meaningful hierarchies obtained for other real systems indicate that tag hierarchy extraction is a very promising direction for further research with a great potential for practical applications. Tags have become very prevalent nowadays in various online platforms ranging from blogs through scientific publications to protein databases. Furthermore, tagging systems dedicated for voluntary tagging of photos, films, books, etc. with free words are also becoming popular. The emerging large collections of tags associated with different objects are often referred to as folksonomies, highlighting their collaborative origin and the “flat” organization of the tags opposed to traditional hierarchical categorization. Adding a tag hierarchy corresponding to a given folksonomy can very effectively help narrowing or broadening the scope of search

Extracting tag hierarchies.

Directory of Open Access Journals (Sweden)

Gergely Tibély

Full Text Available Tagging items with descriptive annotations or keywords is a very natural way to compress and highlight information about the properties of the given entity. Over the years several methods have been proposed for extracting a hierarchy between the tags for systems with a "flat", egalitarian organization of the tags, which is very common when the tags correspond to free words given by numerous independent people. Here we present a complete framework for automated tag hierarchy extraction based on tag occurrence statistics. Along with proposing new algorithms, we are also introducing different quality measures enabling the detailed comparison of competing approaches from different aspects. Furthermore, we set up a synthetic, computer generated benchmark providing a versatile tool for testing, with a couple of tunable parameters capable of generating a wide range of test beds. Beside the computer generated input we also use real data in our studies, including a biological example with a pre-defined hierarchy between the tags. The encouraging similarity between the pre-defined and reconstructed hierarchy, as well as the seemingly meaningful hierarchies obtained for other real systems indicate that tag hierarchy extraction is a very promising direction for further research with a great potential for practical applications. Tags have become very prevalent nowadays in various online platforms ranging from blogs through scientific publications to protein databases. Furthermore, tagging systems dedicated for voluntary tagging of photos, films, books, etc. with free words are also becoming popular. The emerging large collections of tags associated with different objects are often referred to as folksonomies, highlighting their collaborative origin and the "flat" organization of the tags opposed to traditional hierarchical categorization. Adding a tag hierarchy corresponding to a given folksonomy can very effectively help narrowing or broadening the scope of

Extracting tag hierarchies.

Science.gov (United States)

Tibély, Gergely; Pollner, Péter; Vicsek, Tamás; Palla, Gergely

2013-01-01

Tagging items with descriptive annotations or keywords is a very natural way to compress and highlight information about the properties of the given entity. Over the years several methods have been proposed for extracting a hierarchy between the tags for systems with a "flat", egalitarian organization of the tags, which is very common when the tags correspond to free words given by numerous independent people. Here we present a complete framework for automated tag hierarchy extraction based on tag occurrence statistics. Along with proposing new algorithms, we are also introducing different quality measures enabling the detailed comparison of competing approaches from different aspects. Furthermore, we set up a synthetic, computer generated benchmark providing a versatile tool for testing, with a couple of tunable parameters capable of generating a wide range of test beds. Beside the computer generated input we also use real data in our studies, including a biological example with a pre-defined hierarchy between the tags. The encouraging similarity between the pre-defined and reconstructed hierarchy, as well as the seemingly meaningful hierarchies obtained for other real systems indicate that tag hierarchy extraction is a very promising direction for further research with a great potential for practical applications. Tags have become very prevalent nowadays in various online platforms ranging from blogs through scientific publications to protein databases. Furthermore, tagging systems dedicated for voluntary tagging of photos, films, books, etc. with free words are also becoming popular. The emerging large collections of tags associated with different objects are often referred to as folksonomies, highlighting their collaborative origin and the "flat" organization of the tags opposed to traditional hierarchical categorization. Adding a tag hierarchy corresponding to a given folksonomy can very effectively help narrowing or broadening the scope of search. Moreover

Quantum tagging for tags containing secret classical data

International Nuclear Information System (INIS)

Kent, Adrian

2011-01-01

Various authors have considered schemes for quantum tagging, that is, authenticating the classical location of a classical tagging device by sending and receiving quantum signals from suitably located distant sites, in an environment controlled by an adversary whose quantum information processing and transmitting power is potentially unbounded. All of the schemes proposed elsewhere in the literature assume that the adversary is able to inspect the interior of the tagging device. All of these schemes have been shown to be breakable if the adversary has unbounded predistributed entanglement. We consider here the case in which the tagging device contains a finite key string shared with distant sites but kept secret from the adversary, and show this allows the location of the tagging device to be authenticated securely and indefinitely. Our protocol relies on quantum key distribution between the tagging device and at least one distant site, and demonstrates a new practical application of quantum key distribution. It also illustrates that the attainable security in position-based cryptography can depend crucially on apparently subtle details in the security scenario considered.

Pseudo-Kähler Quantization on Flag Manifolds

Science.gov (United States)

Karabegov, Alexander V.

A unified approach to geometric, symbol and deformation quantizations on a generalized flag manifold endowed with an invariant pseudo-Kähler structure is proposed. In particular cases we arrive at Berezin's quantization via covariant and contravariant symbols.

Comparative Performance of Acoustic-tagged and PIT-tagged Juvenile Salmonids

Energy Technology Data Exchange (ETDEWEB)

Hockersmith, Eric E.; Brown, Richard S.; Liedtke, Theresa L.

2008-02-01

Numerous research tools and technologies are currently being used to evaluate fish passage and survival to determine the impacts of the Federal Columbia River Power System (FCRPS) on endangered and threatened juvenile salmonids, including PIT tags, balloon tags, hydroacoustic evaluations, radio telemetry, and acoustic telemetry. Each has advantages and disadvantages, but options are restricted in some situations because of limited capabilities of a specific technology, lack of detection capability downstream, or availability of adequate numbers of fish. However, there remains concern about the comparative effects of the tag or the tagging procedure on fish performance. The recently developed Juvenile Salmonid Acoustic Telemetry System (JSATS) acoustic transmitter is the smallest active acoustic tag currently available. The goal of this study was to determine whether fish tagged with the JSATS acoustic-telemetry tag can provide unbiased estimates of passage behavior and survival within the performance life of the tag. We conducted both field and laboratory studies to assess tag effects. For the field evaluation we released a total of 996 acoustic-tagged fish in conjunction with 21,026 PIT-tagged fish into the tailrace of Lower Granite Dam on 6 and 13 May. Travel times between release and downstream dams were not significantly different for the majority of the reaches between acoustic-tagged and PIT-tagged fish. In addition to the field evaluation, a series of laboratory experiments were conducted to determine if growth and survival of juvenile Chinook salmon surgically implanted with acoustic transmitters is different than untagged or PIT tagged juvenile Chinook salmon. Only yearling fish with integrated and non-integrated transmitters experienced mortalities, and these were low (<4.5%). Mortality among sub-yearling control and PIT-tag treatments ranged up to 7.7% while integrated and non-integrated treatments had slightly higher rates (up to 8.3% and 7

Tagging the European eel Anguilla anguilla (L.) with coded wire tags

DEFF Research Database (Denmark)

Thomassen, S.; Pedersen, Michael Ingemann; Holdensgaard, G.

2000-01-01

The coded wire tag (CWT) system was examined as a possible tool for tagging European eels (Anguilla anguilla). Two size groups of eels (3.8 and 10.2 g) were tagged with CWTs in the dorsal musculature, Tag loss 28 days after tagging was 3.1% for the small and 0.7% for the large groups of eels...

Tempting to Tag : An Experimental Comparison of Four Tagging Input Mechanisms

OpenAIRE

Melenhorst, Mark; van Velsen, Lex

2010-01-01

Tagging helps achieve improved indexing and recommendation of resources (e.g., videos or pictures) in large data collections. In order to reap the benefits of tagging, people must be persuaded to label the resources they consume. This paper reports on a study in which four different tagging input mechanisms and their effect on users' motivation to tag were compared. The mechanisms consisted of a standard tag input box, a chatbot-like environment, a bookmarking mechanism, and a "tag and v...

The Full Kostant-Toda Hierarchy on the Positive Flag Variety

Science.gov (United States)

Kodama, Yuji; Williams, Lauren

2015-04-01

We study some geometric and combinatorial aspects of the solution to the full Kostant-Toda (f-KT) hierarchy, when the initial data is given by an arbitrary point on the totally non-negative (tnn) flag variety of . The f-KT flows on the tnn flag variety are complete, and we show that their asymptotics are completely determined by the cell decomposition of the tnn flag variety given by Rietsch (Total positivity and real flag varieties. Ph.D. Thesis, Massachusetts Institute of Technology, Cambridge, 1998). Our results represent the first results on the asymptotics of the f-KT hierarchy (and even the f-KT lattice); moreover, our results are not confined to the generic flow, but cover non-generic flows as well. We define the f-KT flow on the weight space via the moment map, and show that the closure of each f-KT flow forms an interesting convex polytope which we call a Bruhat interval polytope. In particular, the Bruhat interval polytope for the generic flow is the permutohedron of the symmetric group . We also prove analogous results for the full symmetric Toda hierarchy, by mapping our f-KT solutions to those of the full symmetric Toda hierarchy. In the appendix we show that Bruhat interval polytopes are generalized permutohedra, in the sense of Postnikov (Int. Math. Res. Not. IMRN (6):1026-1106, 2009).

Swedish Seafarers' Commitment to Work in Times of Flagging out

Directory of Open Access Journals (Sweden)

C. Hult

2014-03-01

Full Text Available This study takes its departure in the difficulties to recruit and retain qualified senior seafarers in the Swedish shipping sector. The study focus is on seafarers' motivation at work for the specific shipping company (organizational commitment, and seafarers' motivation towards their occupation (occupational commitment, in times of flagging out. It was hypothesized that the youngest seafarers and the oldest may be most sensitive to foreign registration of ships. Statistical analyses were employed, using a survey material of 1,309 Swedish seafarers randomly collected in 2010 from a national register of seafarers. The results of the analyses show that flagging-out imposes a significant decline in organizational commitment for all seafarers. This decline is related to the perception of the social composition of crew. In addition, the oldest seafarers (age 55+ demonstrate diminished occupational commitment under a foreign flag. This decline is related to the degree of satisfaction with the social security structure. Occupational commitment among the youngest seafarers (age 19-30 is not affected by the nationality of flag. However, this type of commitment is decreasing by the time served on the same ship. This effect is partly related to a decline in satisfaction with the work content. In the concluding discussion, the findings are discussed in more details and recommendations are put forward.

Using atypical symptoms and red flags to identify non-demyelinating disease.

LENUS (Irish Health Repository)

Kelly, Siobhan B

2012-01-01

Red flags and atypical symptoms have been described as being useful in suggesting alternative diagnoses to multiple sclerosis (MS) and clinically isolated syndrome (CIS); however, their diagnostic utility has not been assessed. The aim of this study was to establish the predictive value of red flags and the typicality\\/atypicality of symptoms at presentation in relation to the final diagnosis of patients referred with suspected MS.

Frobenius splitting of thick flag manifolds of Kac-Moody algebras

OpenAIRE

Kato, Syu

2017-01-01

We explain that the Pl\\"ucker relations provide the defining equations of the thick flag manifold associated to a Kac-Moody algebra. This naturally transplant the result of Kumar-Mathieu-Schwede about the Frobenius splitting of thin flag manifolds to the thick case. As a consequence, we provide a description of the global sections of line bundles of a thick Schubert variety as conjectured in Kashiwara-Shimozono [Duke Math. J. 148 (2009)]. This also yields the existence of a compatible basis o...

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.

3D micro-crack propagation simulation at enamel/adhesive interface using FE submodeling and element death techniques.

Science.gov (United States)

Liu, Heng-Liang; Lin, Chun-Li; Sun, Ming-Tsung; Chang, Yen-Hsiang

2010-06-01

This study investigates micro-crack propagation at the enamel/adhesive interface using finite element (FE) submodeling and element death techniques. A three-dimensional (3D) FE macro-model of the enamel/adhesive/ceramic subjected to shear bond testing was generated and analyzed. A 3D micro-model with interfacial bonding structure was constructed at the upper enamel/adhesive interface where the stress concentration was found from the macro-model results. The morphology of this interfacial bonding structure (i.e., resin tag) was assigned based on resin tag geometry and enamel rod arrangement from a scanning electron microscopy micrograph. The boundary conditions for the micro-model were determined from the macro-model results. A custom iterative code combined with the element death technique was used to calculate the micro-crack propagation. Parallel experiments were performed to validate this FE simulation. The stress concentration within the adhesive occurred mainly at the upper corner near the enamel/adhesive interface and the resin tag base. A simulated fracture path was found at the resin tag base along the enamel/adhesive interface. A morphological observation of the fracture patterns obtained from in vitro testing corresponded with the simulation results. This study shows that the FE submodeling and element death techniques could be used to simulate the 3D micro-stress pattern and the crack propagation noted at the enamel/adhesive interface.

Red flags in detecting credit cooperative fraud: the perceptions of internal auditors

Directory of Open Access Journals (Sweden)

Cristian Baú Dal Magro

2017-07-01

Full Text Available Purpose – Red flags are mechanisms that can be used by internal auditors for early detection of possible fraud. In this context, the aim of this study was to identify the relevance credit unions’ internal auditors attribute to red flags in assessing fraud risk. Design/methodology/approach – This article is characterized as descriptive concerning its goals, as a survey as to is procedures, and as quantitative in reference to its approach to the problem. The sample onsists of 51 internal auditors working in Credit Union Centers in southern Brazil. Findings – Results indicate that, in the assessment of fraud risk, internal auditors attribute greater importance to red flags referring to operational activities and internal control procedures. In addition, it is suggested that internal auditors are not impartial concerning their perception of relevance of most of the warning signs of the possibility of fraud. Originality/value – The findings contribute by demonstrating to internal auditors the need for greater attention to the use of red flags as auditing tools.

Ontologies and tag-statistics

Science.gov (United States)

Tibély, Gergely; Pollner, Péter; Vicsek, Tamás; Palla, Gergely

2012-05-01

Due to the increasing popularity of collaborative tagging systems, the research on tagged networks, hypergraphs, ontologies, folksonomies and other related concepts is becoming an important interdisciplinary area with great potential and relevance for practical applications. In most collaborative tagging systems the tagging by the users is completely ‘flat’, while in some cases they are allowed to define a shallow hierarchy for their own tags. However, usually no overall hierarchical organization of the tags is given, and one of the interesting challenges of this area is to provide an algorithm generating the ontology of the tags from the available data. In contrast, there are also other types of tagged networks available for research, where the tags are already organized into a directed acyclic graph (DAG), encapsulating the ‘is a sub-category of’ type of hierarchy between each other. In this paper, we study how this DAG affects the statistical distribution of tags on the nodes marked by the tags in various real networks. The motivation for this research was the fact that understanding the tagging based on a known hierarchy can help in revealing the hidden hierarchy of tags in collaborative tagging systems. We analyse the relation between the tag-frequency and the position of the tag in the DAG in two large sub-networks of the English Wikipedia and a protein-protein interaction network. We also study the tag co-occurrence statistics by introducing a two-dimensional (2D) tag-distance distribution preserving both the difference in the levels and the absolute distance in the DAG for the co-occurring pairs of tags. Our most interesting finding is that the local relevance of tags in the DAG (i.e. their rank or significance as characterized by, e.g., the length of the branches starting from them) is much more important than their global distance from the root. Furthermore, we also introduce a simple tagging model based on random walks on the DAG, capable of

Ontologies and tag-statistics

International Nuclear Information System (INIS)

Tibély, Gergely; Vicsek, Tamás; Pollner, Péter; Palla, Gergely

2012-01-01

Due to the increasing popularity of collaborative tagging systems, the research on tagged networks, hypergraphs, ontologies, folksonomies and other related concepts is becoming an important interdisciplinary area with great potential and relevance for practical applications. In most collaborative tagging systems the tagging by the users is completely ‘flat’, while in some cases they are allowed to define a shallow hierarchy for their own tags. However, usually no overall hierarchical organization of the tags is given, and one of the interesting challenges of this area is to provide an algorithm generating the ontology of the tags from the available data. In contrast, there are also other types of tagged networks available for research, where the tags are already organized into a directed acyclic graph (DAG), encapsulating the ‘is a sub-category of’ type of hierarchy between each other. In this paper, we study how this DAG affects the statistical distribution of tags on the nodes marked by the tags in various real networks. The motivation for this research was the fact that understanding the tagging based on a known hierarchy can help in revealing the hidden hierarchy of tags in collaborative tagging systems. We analyse the relation between the tag-frequency and the position of the tag in the DAG in two large sub-networks of the English Wikipedia and a protein-protein interaction network. We also study the tag co-occurrence statistics by introducing a two-dimensional (2D) tag-distance distribution preserving both the difference in the levels and the absolute distance in the DAG for the co-occurring pairs of tags. Our most interesting finding is that the local relevance of tags in the DAG (i.e. their rank or significance as characterized by, e.g., the length of the branches starting from them) is much more important than their global distance from the root. Furthermore, we also introduce a simple tagging model based on random walks on the DAG, capable of

75 FR 66125 - Federal Land Managers' Air Quality Related Values Work Group (FLAG)

Science.gov (United States)

2010-10-27

... pollutants that could affect the health and status of resources in areas managed by the three agencies... Work Group (FLAG) AGENCY: National Park Service, Interior. ACTION: Notice of availability of final... Public Comments document. The Federal Land Managers' Air Quality Related Values Work Group (FLAG) was...

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

Science.gov (United States)

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Narinder Janghra

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

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.

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.

Reliance communications' flag telecom to provide ethernet link between CERN and TIFR

CERN Multimedia

2007-01-01

"Flag Telecom Group Limited (Flag), the undersea cable network arm of Anil Ambani-le Reliance Communications, has announced a landmark deal with CERn (Conseil Européen pour la Recheche Nucléaire), the European organisation for nuclear research based in Geneva, Switzerland and the Tata institute of Fundamental Research (TIFR) in Mumbai to provide gigabit Ethernet connectivity between the two." (1 page)

An algorithm for applying flagged Sysmex XE-2100 absolute neutrophil counts in clinical practice

DEFF Research Database (Denmark)

Friis-Hansen, Lennart; Saelsen, Lone; Abildstrøm, Steen Z

2008-01-01

BACKGROUND: Even though most differential leukocyte counts are performed by automated hematology platforms, turn-around time is often prolonged as flagging of test results trigger additional confirmatory manual procedures. However, frequently only the absolute neutrophil count (ANC) is needed. We...... therefore examined if an algorithm could be developed to identify samples in which the automated ANC is valid despite flagged test results. METHODS: During a 3-wk period, a training set consisting of 1448 consecutive flagged test-results from the Sysmex XE-2100 system and associated manual differential...... counts was collected. The training set was used to determine which alarms were associated with valid ANCs. The algorithm was then tested on a new set of 1371 test results collected during a later 3-wk period. RESULTS: Analysis of the training set data revealed that the ANC from test results flagged...

DNA-tagged Microparticles for Tracing Water Flows and Travel Times in Natural Systems: The First results from Controlled Laboratory Experiments

Science.gov (United States)

Bogaard, T.; Bandyopadhyay, S.; Foppen, J. W.

2017-12-01

Societal demand for water safety is continuously increasing, being it resilient against flood/droughts, clean water for ecosystems, recreation or safe drinking water. Robust methods to measure temporal and spatial patterns of water and contaminant pathways are still lacking. Our research project aims to develop and apply (1) innovative, robust, and environmental-friendly silica-protected iron oxide micro-particles tagged with artificial DNA to trace contaminant movement and travel times of water in natural systems and (2) an innovative coupled model approach to capture dynamics in hydrological pathways and their effects on water quality. The exceptional property of DNA-tagging is the infinite number of unique tracers that can be produced and their detectability at extreme low concentrations. The advantage of the iron-core of the particle is the magnetic harvesting of the particles from water-samples. Such tracers are thought to give the water sector a unique tool for in-situ mapping of transport of contaminants and pathogenic microorganisms in water systems. However, the characteristics of the particle like magnetic property of the iron-core and surface potential of the silica layer, are of key importance for the behaviour of the particle in surface water and in soils. Furthermore, the application of such micro-particles requires strict protocols for the experiment, sampling and laboratory handling which are currently not available. We used two different types of silica-protected DNA-tagged micro-particles. We performed batch, column and flow experiments to assess the behaviour of the particles. We will present the first results of the controlled laboratory experiments for hydrological tracing. We will discuss the results and link it to the differences in particles design. Furthermore, we will draw conclusions and discuss knowledge gaps for future application of silica-protected DNA-tagged micro-particles in hydrological research.

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 ...

Testing ALE code FLAG with analytical self-similar solutions of 2D magnetized implosion

Energy Technology Data Exchange (ETDEWEB)

Bereznyak, Andrey [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gianakon, Thomas Arthur [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rousculp, Christopher L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cooley, James Hamilton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Giuliani, John [Naval Research Lab. (NRL), Washington, DC (United States)

2018-01-04

The goal of this collaboration was to provide a mechanism to verify the MHD implementation in FLAG and improve the FLAG MHD packages as need to meet broader LANL institutional goals. These three Magnetic Noh problems are proving immensely useful.

New Dystrophin/Dystroglycan interactors control neuron behavior in Drosophila eye

Directory of Open Access Journals (Sweden)

Rishko Valentyna M

2011-09-01

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

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.

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.

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.

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.

Race Discourse and the US Confederate Flag

Science.gov (United States)

Holyfield, Lori; Moltz, Matthew Ryan; Bradley, Mindy S.

2009-01-01

Research reveals that racial hierarchies and "color-blind" racism is maintained through discourse. The current study utilizes exploratory data from focus groups in a predominantly white southern university in the United States to examine race talk, the Confederate Flag, and the construction of southern white identity. Drawing from…

Customization of Advia 120 thresholds for canine erythrocyte volume and hemoglobin concentration, and effects on morphology flagging results.

Science.gov (United States)

Grimes, Carolyn N; Fry, Michael M

2014-12-01

This study sought to develop customized morphology flagging thresholds for canine erythrocyte volume and hemoglobin concentration [Hgb] on the ADVIA 120 hematology analyzer; compare automated morphology flagging with results of microscopic blood smear evaluation; and examine effects of customized thresholds on morphology flagging results. Customized thresholds were determined using data from 52 clinically healthy dogs. Blood smear evaluation and automated morphology flagging results were correlated with mean cell volume (MCV) and cellular hemoglobin concentration mean (CHCM) in 26 dogs. Customized thresholds were applied retroactively to complete blood (cell) count (CBC) data from 5 groups of dogs, including a reference sample group, clinical cases, and animals with experimentally induced iron deficiency anemia. Automated morphology flagging correlated more highly with MCV or CHCM than did blood smear evaluation; correlation with MCV was highest using customized thresholds. Customized morphology flagging thresholds resulted in more sensitive detection of microcytosis, macrocytosis, and hypochromasia than default thresholds.

Flag-dipole and flagpole spinor fluid flows in Kerr spacetimes

Energy Technology Data Exchange (ETDEWEB)

Rocha, Roldão da, E-mail: roldao.rocha@ufabc.edu.br [Universidade Federal do ABC, CMCC (Brazil); Cavalcanti, R. T., E-mail: rogerio.cavalcanti@ufabc.edu.br [Universidade Federal do ABC, CCNH (Brazil)

2017-03-15

Flagpole and flag-dipole spinors are particular classes of spinor fields that has been recently used in different branches of theoretical physics. In this paper, we study the possibility and consequences of these spinor fields to induce an underlying fluid flow structure in the background of Kerr spacetimes. We show that flag-dipole spinor fields are solutions of the equations of motion in this context. To our knowledge, this is the second time that this class of spinor field appears as a physical solution, the first one occurring as a solution of the Dirac equation in ESK gravities.

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

Directory of Open Access Journals (Sweden)

Elena Bassi

2012-01-01

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

PIT Tagging Anurans

Science.gov (United States)

McCreary, Brome

2008-01-01

The following video demonstrates a procedure to insert a passive integrated transponder (PIT) tag under the skin of an anuran (frog or toad) for research and monitoring purposes. Typically, a 12.5 mm tag (0.5 in.) is used to uniquely identify individual anurans as smal as 40 mm (1.6 in.) in length from snout to vent. Smaller tags are also available and allow smaller anurans to be tagged. The procedure does not differ for other sizes of tages or other sizes of anurans. Anyone using this procedure should ensure that the tag is small enough to fit easily behind the sacral hump of the anuran, as shown in this video.

Cutaneous skin tag

Science.gov (United States)

Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

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

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.

Monitoring System for Slope Stability under Rainfall by using MEMS Acceleration Sensor IC tags

International Nuclear Information System (INIS)

Murakami, S; Dairaku, A; Komine, H; Saito, O; Sakai, N; Isizawa, T; Maruyama, I

2013-01-01

Real-time warning system for slope failure under rainfall is available to disaster prevention and mitigation. Monitoring of multi-point and wireless measurements is effective because it is difficult to conclude the most dangerous part in a slope. The purpose of this study is to propose a method of monitoring system with multi-point and wireless measurements for a slope stability using MEMS acceleration sensor IC tags. MEMS acceleration sensor IC tag is an acceleration sensor microminiaturized by a technology of Micro Electro Mechanical Systems on board IC tag. Especially, low cost of the sensor will yield to the realization of the system. In order to investigate the applicability of the proposed system, a large-scale model test of artificial slope subjected to rainfall has been performed. MEMS acceleration sensor IC tags has been located on the slope and ground acceleration caused by forced vibration has been measured until the model slope collapses. The experimental results show that the MEMS acceleration sensor IC tag is comfortably available under rainfall, the characteristics of ground accelerations varies with changing the condition of the slope subjected to rainfall, and the proposed method can be applied to a real-time monitoring system for slope failure under rainfall.

Phloem Transport of Arsenic Species from Flag Leaf to Grain During Grain Filling

Energy Technology Data Exchange (ETDEWEB)

A Carey; G Norton; C Deacon; K Scheckel; E Lombi; T Punshon; M Guerinot; A Lanzirotti; M Newville; et al.

2011-12-31

Strategies to reduce arsenic (As) in rice grain, below concentrations that represent a serious human health concern, require that the mechanisms of As accumulation within grain be established. Therefore, retranslocation of As species from flag leaves into filling rice grain was investigated. Arsenic species were delivered through cut flag leaves during grain fill. Spatial unloading within grains was investigated using synchrotron X-ray fluorescence (SXRF) microtomography. Additionally, the effect of germanic acid (a silicic acid analog) on grain As accumulation in arsenite-treated panicles was examined. Dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) were extremely efficiently retranslocated from flag leaves to rice grain; arsenate was poorly retranslocated, and was rapidly reduced to arsenite within flag leaves; arsenite displayed no retranslocation. Within grains, DMA rapidly dispersed while MMA and inorganic As remained close to the entry point. Germanic acid addition did not affect grain As in arsenite-treated panicles. Three-dimensional SXRF microtomography gave further information on arsenite localization in the ovular vascular trace (OVT) of rice grains. These results demonstrate that inorganic As is poorly remobilized, while organic species are readily remobilized, from leaves to grain. Stem translocation of inorganic As may not rely solely on silicic acid transporters.

Phloem transport of arsenic species from flag leaf to grain during grain filling

Energy Technology Data Exchange (ETDEWEB)

Carey, Anne-Marie; Norton, Gareth J.; Deacon, Claire; Scheckel, Kirk G.; Lombi, Enzo; Punshon, Tracy; Guerinot, Mary Lou; Lanzirotti, Antonio; Newville, Matt; Choi, Yongseong; Price, Adam H.; Meharg, Andrew A. (EPA); (U. South Australia); (Aberdeen); (UC); (Dartmouth)

2011-09-20

Strategies to reduce arsenic (As) in rice grain, below concentrations that represent a serious human health concern, require that the mechanisms of As accumulation within grain be established. Therefore, retranslocation of As species from flag leaves into filling rice grain was investigated. Arsenic species were delivered through cut flag leaves during grain fill. Spatial unloading within grains was investigated using synchrotron X-ray fluorescence (SXRF) microtomography. Additionally, the effect of germanic acid (a silicic acid analog) on grain As accumulation in arsenite-treated panicles was examined. Dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) were extremely efficiently retranslocated from flag leaves to rice grain; arsenate was poorly retranslocated, and was rapidly reduced to arsenite within flag leaves; arsenite displayed no retranslocation. Within grains, DMA rapidly dispersed while MMA and inorganic As remained close to the entry point. Germanic acid addition did not affect grain As in arsenite-treated panicles. Three-dimensional SXRF microtomography gave further information on arsenite localization in the ovular vascular trace (OVT) of rice grains. These results demonstrate that inorganic As is poorly remobilized, while organic species are readily remobilized, from leaves to grain. Stem translocation of inorganic As may not rely solely on silicic acid transporters.

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.

Field evidence of social influence in the expression of political preferences: the case of secessionists flags in Barcelona.

Science.gov (United States)

Parravano, Antonio; Noguera, José A; Hermida, Paula; Tena-Sánchez, Jordi

2015-01-01

Models of social influence have explored the dynamics of social contagion, imitation, and diffusion of different types of traits, opinions, and conducts. However, few behavioral data indicating social influence dynamics have been obtained from direct observation in "natural" social contexts. The present research provides that kind of evidence in the case of the public expression of political preferences in the city of Barcelona, where thousands of citizens supporting the secession of Catalonia from Spain have placed a Catalan flag in their balconies and windows. Here we present two different studies. 1) During July 2013 we registered the number of flags in 26% of the electoral districts in the city of Barcelona. We find that there is a large dispersion in the density of flags in districts with similar density of pro-independence voters. However, by comparing the moving average to the global mean we find that the density of flags tends to be fostered in electoral districts where there is a clear majority of pro-independence vote, while it is inhibited in the opposite cases. We also show that the distribution of flags in the observed districts deviates significantly from that of an equivalent random distribution. 2) During 17 days around Catalonia's 2013 national holiday we observed the position at balcony resolution of the flags displayed in the facades of a sub-sample of 82 blocks. We compare the 'clustering index' of flags on the facades observed each day to thousands of equivalent random distributions. Again we provide evidence that successive hangings of flags are not independent events but that a local influence mechanism is favoring their clustering. We also find that except for the national holiday day the density of flags tends to be fostered in facades located in electoral districts where there is a clear majority of pro-independence vote.

The epidemiology of injuries in contact flag football.

Science.gov (United States)

Kaplan, Yonatan; Myklebust, Grethe; Nyska, Meir; Palmanovich, Ezequiel; Victor, Jan; Witvrouw, Erik

2013-01-01

To characterize the epidemiology of injuries in post-high school male and female athletes in the rapidly growing international sport of contact flag football. Prospective injury-observational study. Kraft Stadium, Jerusalem, Israel. A total of 1492 players, consisting of men (n = 1252, mean age, 20.49 ± 5.11) and women (n = 240, mean age, 21.32 ± 8.95 years), participated in 1028 games over a 2-season period (2007-2009). All time-loss injuries sustained in game sessions were recorded by the off-the-field medical personnel and followed up by a more detailed phone injury surveillance questionnaire. One hundred sixty-three injuries were reported, comprising 1 533 776 athletic exposures (AEs). The incidence rate was 0.11 [95% confidence interval (CI), 0.09-0.12] per 1000 AEs, and incidence proportion was 10.66% (95% CI, 9.10-12.22). Seventy-six percent of the injuries were extrinsic in nature. Thirty percent of the injuries were to the fingers, thumb, and wrist, 17% to the knee, 17% to the head/face, 13% to the ankle, and 11% to the shoulder. Contact flag football results in a significant amount of moderate to severe injuries. These data may be used in the development of a formal American flag football injury database and in the development and implementation of a high-quality, randomized, prospective injury prevention study. This study should include the enforcement of the no-pocket rule, appropriate headgear, self-fitting mouth guards, the use of ankle braces, and changing the blocking rules of the game.

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

Tags on healthcare information websites

DEFF Research Database (Denmark)

Lykke, Marianne; Ådland, Marit Kristine

2018-01-01

This paper explores tags and tagging behaviour on health information websites using an empirical, user-oriented, exploratory case study. Taggers and editors were interviewed about tags and tagging, while taggers solved tasks that included applying tags to a website. This qualitative data...... articles, request information, and value article content. Some of these show that tags are not only not only topical descriptions, but communicative by intent. This result can potentially inform the design of tagging features....

Tag-to-Tag Interference Suppression Technique Based on Time Division for RFID

Directory of Open Access Journals (Sweden)

Grishma Khadka

2017-01-01

Full Text Available Radio-frequency identification (RFID is a tracking technology that enables immediate automatic object identification and rapid data sharing for a wide variety of modern applications using radio waves for data transmission from a tag to a reader. RFID is already well established in technical areas, and many companies have developed corresponding standards and measurement techniques. In the construction industry, effective monitoring of materials and equipment is an important task, and RFID helps to improve monitoring and controlling capabilities, in addition to enabling automation for construction projects. However, on construction sites, there are many tagged objects and multiple RFID tags that may interfere with each other’s communications. This reduces the reliability and efficiency of the RFID system. In this paper, we propose an anti-collision algorithm for communication between multiple tags and a reader. In order to suppress interference signals from multiple neighboring tags, the proposed algorithm employs the time-division (TD technique, where tags in the interrogation zone are assigned a specific time slot so that at every instance in time, a reader communicates with tags using the specific time slot. We present representative computer simulation examples to illustrate the performance of the proposed anti-collision technique for multiple RFID tags.

Photon-tagged and B-meson-tagged b-jet production at the LHC

Directory of Open Access Journals (Sweden)

Jinrui Huang

2015-11-01

Full Text Available Tagged jet measurements in high energy hadronic and nuclear reactions provide constraints on the energy and parton flavor origin of the parton shower that recoils against the tagging particle. Such additional insight can be especially beneficial in illuminating the mechanisms of heavy flavor production in proton–proton collisions at the LHC and their modification in the heavy ion environment, which are not fully understood. With this motivation, we present theoretical results for isolated-photon-tagged and B-meson-tagged b-jet production at sNN=5.1 TeV for comparison to the upcoming lead–lead data. We find that photon-tagged b-jets exhibit smaller momentum imbalance shift in nuclear matter, and correspondingly smaller energy loss, than photon-tagged light flavor jets. Our results show that B-meson tagging is most effective in ensuring that the dominant fraction of recoiling jets originate from prompt b-quarks. Interestingly, in this channel the large suppression of the cross section is not accompanied by a significant momentum imbalance shift.

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...

To tag or not to tag: animal welfare, conservation and stakeholder considerations in fish tracking studies that use electronic tags

Energy Technology Data Exchange (ETDEWEB)

Cooke, Steven J.; Nguyen, Vivian M.; Murchie, Karen J.; Thiem, Jason D.; Donaldson, Michael R.; Hinch, Scott G.; Brown, Richard S.; Fisk, Aaron

2013-11-01

The advent and widespread adoption of electronic tags (including biotelemetry and biologging devices) for tracking animals has provided unprecedented information on the biology, management, and conservation of fish in the world’s oceans and inland waters. However, use of these tools is not without controversy. Even when scientific and management objectives may best be achieved using electronic tags, it is increasingly important to further consider other factors such as the welfare of tagged animals (i.e., the role of training and science-based surgical guidelines, anesthetic use, inability to maintain sterile conditions in field environments), the ethics of tagging threatened species vs. using surrogates, stakeholder perspectives on tagging (including aboriginals), as well as use of data emanating from such studies (e.g., by fishers to facilitate exploitation). Failure to do so will have the potential to create conflict and undermine scientific, management and public confidence in the use of this powerful tool. Indeed, there are already a number of examples of where tracking studies using electronic tags have been halted based on concerns raised by researchers, authorities, or stakeholders. Here we present a candid evaluation of several factors that should be considered when determining when to tag or not to tag fish with electronic devices. It is not our objective to judge the merit of previous studies. Rather, we hope to stimulate debate and discussion regarding the use of electronic tags to study fish. Relatedly, there is a need for more research to address these questions (e.g., what level of cleanliness is needed when conducting surgeries, what type of training should be required for fish surgery) including human dimensions studies to understand perspectives of different actors including society as a whole with respect to tagging and tracking studies.

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.

Equivelar toroids with few flag-orbits

OpenAIRE

Collins, José; Montero, Antonio

2018-01-01

An $(n+1)$-toroid is a quotient of a tessellation of the $n$-dimensional Euclidean space with a lattice group. Toroids are generalizations of maps in the torus on higher dimensions and also provide examples of abstract polytopes. Equivelar toroids are those that are induced by regular tessellations. In this paper we present a classification of equivelar $(n+1)$-toroids with at most $n$ flag-orbits; in particular, we discuss a classification of $2$-orbit toroids of arbitrary dimension.

Yellowtail Tagging Data (MRDBS)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Yellowtail Flounder Tagging Program began in 2003 and works with commercial fishermen to tag and release yellowtaiI flounder with pink and yellow disc tags or...

Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

Directory of Open Access Journals (Sweden)

Lauren G Holinka

Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

Understanding why users tag: A survey of tagging motivation literature and results from an empirical study.

Science.gov (United States)

Strohmaier, Markus; Körner, Christian; Kern, Roman

2012-12-01

While recent progress has been achieved in understanding the structure and dynamics of social tagging systems, we know little about the underlying user motivations for tagging, and how they influence resulting folksonomies and tags. This paper addresses three issues related to this question. (1) What distinctions of user motivations are identified by previous research, and in what ways are the motivations of users amenable to quantitative analysis? (2) To what extent does tagging motivation vary across different social tagging systems? (3) How does variability in user motivation influence resulting tags and folksonomies? In this paper, we present measures to detect whether a tagger is primarily motivated by categorizing or describing resources, and apply these measures to datasets from seven different tagging systems. Our results show that (a) users' motivation for tagging varies not only across, but also within tagging systems, and that (b) tag agreement among users who are motivated by categorizing resources is significantly lower than among users who are motivated by describing resources . Our findings are relevant for (1) the development of tag-based user interfaces, (2) the analysis of tag semantics and (3) the design of search algorithms for social tagging systems.

A conformation-induced fluorescence method for microRNA detection

DEFF Research Database (Denmark)

Aw, Sherry S; Tang, Melissa Xm; Teo, Yin Nah

2016-01-01

and quantify microRNAs may aid research into novel aspects of microRNA biology and contribute to the development of diagnostics. By introducing an additional stem loop into the fluorescent RNA Spinach and altering its 3' and 5' ends, we have generated a new RNA, Pandan, that functions as the basis for a micro......MicroRNAs play important roles in a large variety of biological systems and processes through their regulation of target mRNA expression, and show promise as clinical biomarkers. However, their small size presents challenges for tagging or direct detection. Innovation in techniques to sense......RNA sensor. Pandan contains two sequence-variable stem loops that encode complementary sequence for a target microRNA of interest. In its sensor form, it requires the binding of a target microRNA in order to reconstitute the RNA scaffold for fluorophore binding and fluorescence. Binding of the target micro...

And another thing - flags of convenience

International Nuclear Information System (INIS)

Flatern, R. von

2002-01-01

Crude oil being shipped around the world, when spilled, is a threat to the environment unlike any other commodity, save perhaps for radioactive materials. Therefore, if the oil industry expects to be taken seriously in its role of protecting the environment, it must assume responsibility for its product from wellhead to consumer. Whilst there are many operators paying considerable attention to transportation issues - the largest of them using their own double-hulled tanker fleets - there still too many using ships unsuitable for the purpose, either because of age or the fact that they are single hulled vessels. These derelicts are kept in business by owners who have registered them in country's where inspections are a local joke, registration requires only a fraction of the fee charged by more conscientious nations, and taxes are low. Ships flying flags of convenience have no ties to any country, including the ones in which they are registered. The author says that it is up to the oil industry to clean up their act, for instance they could refuse to use ships that sail under a flag of convenience or single hulled vessels to move their product. The major and large independent companies learned some time ago that taking care of the environment is very much in their interest, and further that only they can do it effectively

Tagged at first listen: an examination of social tagging practices in a music recommender system

Directory of Open Access Journals (Sweden)

Audrey Laplante

2015-01-01

Full Text Available http://dx.doi.org/10.5007/1518-2924.2015v20nesp1p33 Social tagging has become a very common way to index different types of resources on the web. Less prevalent in music than in other domains, social tagging is nevertheless used in a popular recommender system, Last.fm. Although the number of publications on tagging and folksonomies has exploded in the last few years, music tagging is still not well studied. In this paper, we present a study of tagging practices of Last.fm users. We examine the social tagging of songs during the first three months after their release. Our analysis shows that the release of a song triggers a burst in tagging activity that lasts two weeks, after what it decreases sharply and then remains fairly constant for the next ten weeks. We also find that a majority of songs do not get tagged during the first week and that tagging was positively related to popularity. Finally, we find that tags that have been frequently applied to a given song are more likely to be genre related, shorter in length, and relatively objective than tags that have been applied only once.

Multi-Threaded DNA Tag/Anti-Tag Library Generator for Multi-Core Platforms

Science.gov (United States)

2009-05-01

base pair)  Watson ‐ Crick  strand pairs that bind perfectly within pairs, but poorly across pairs. A variety  of  DNA  strand hybridization metrics...AFRL-RI-RS-TR-2009-131 Final Technical Report May 2009 MULTI-THREADED DNA TAG/ANTI-TAG LIBRARY GENERATOR FOR MULTI-CORE PLATFORMS...TYPE Final 3. DATES COVERED (From - To) Jun 08 – Feb 09 4. TITLE AND SUBTITLE MULTI-THREADED DNA TAG/ANTI-TAG LIBRARY GENERATOR FOR MULTI-CORE

Progress toward an enhanced vaccine: Eight marked attenuated viruses to porcine reproductive and respiratory disease virus.

Science.gov (United States)

Spear, Allyn; Wang, Feng-Xue; Kappes, Matthew A; Das, Phani B; Faaberg, Kay S

2018-03-01

Recombinant viruses of strain Ingelvac® PRRS porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus vaccine were produced with two individual small in-frame deletions in nonstructural protein 2 (nsp2; Δ23 and Δ87) and also the same deletions supplanted with foreign tags (Δ23-V5, Δ23-FLAG, Δ23-S, Δ87-V5, Δ87-FLAG, Δ87-S). The viruses, but one (Δ87-FLAG), were stable for 10 passages and showed minimal effects on in vitro growth. Northern hybridization showed that the Δ23-tagged probe detected intracellular viral genome RNA as well as shorter RNAs that may represent heteroclite species, while the Δ87-tagged probe detected predominantly only genome length RNAs. When the tagged viruses were used to probe nsp2 protein in infected cells, perinuclear localization similar to native nsp2 was seen. Dual infection of Δ23-S and Δ87-S viruses allowed some discrimination of individual tagged nsp2 protein, facilitating future research. The mutants could potentially also be used to differentiate infected from vaccinated animals. Published by Elsevier Inc.

Low back pain and physiotherapy use of red flags: the evidence from Scotland.

Science.gov (United States)

Ferguson, Fraser; Holdsworth, Lesley; Rafferty, Danny

2010-12-01

Red flags are recognised as indicators of possible serious spinal pathology, and their use is indicated by numerous guidelines. Similar to other countries worldwide, Scotland lacked a national view about the overall quality of the physiotherapy management of low back pain and the use of red flags. Anecdotal evidence suggested that practice varied considerably. To improve the use and documentation of red flags by physiotherapists during the assessment and management of low back pain. Prospective, multicentred, national data collection and improvement initiative. National Health Service (NHS) health boards in Scotland (n=14) plus two private provider sites. One hundred and eighty-six individual NHS provider sites and two private provider sites, with in excess of 360 physiotherapists providing services to low back pain patients. Measurement of documented practice in line with evidence- and consensus-based recommendations from guidelines collected via a web-based tool over two 5-week audit cycles interspersed with an improvement phase over 1 year (2008-2009). Data from 2147 patients showed improvement in the documentation of all red flags assessed from 33% (n=709) to 65% (n=1396), and improvement in the documentation of cauda equina syndrome from 60% (n=1288) to 84% (n=1804) over the two cycles. Only two regions provided evidence of 100% documentation of all components of cauda equina syndrome, with wide variation across the country. This national initiative resulted in considerable improvement in the documentation of red flags. Despite this, however, one in five patients did not receive optimal management as recommended by guidance. This has significant implications for patient safety and highlights the need for ongoing education of physiotherapists in this area. Copyright © 2010 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The flagellar protein FLAG1/SMP1 is a candidate for Leishmania-sand fly interaction.

Science.gov (United States)

Di-Blasi, Tatiana; Lobo, Amanda R; Nascimento, Luanda M; Córdova-Rojas, Jose L; Pestana, Karen; Marín-Villa, Marcel; Tempone, Antonio J; Telleria, Erich L; Ramalho-Ortigão, Marcelo; McMahon-Pratt, Diane; Traub-Csekö, Yara M

2015-03-01

Leishmaniasis is a serious problem that affects mostly poor countries. Various species of Leishmania are the agents of the disease, which take different clinical manifestations. The parasite is transmitted by sandflies, predominantly from the Phlebotomus genus in the Old World and Lutzomyia in the New World. During development in the gut, Leishmania must survive various challenges, which include avoiding being expelled with blood remnants after digestion. It is believed that attachment to the gut epithelium is a necessary step for vector infection, and molecules from parasites and sand flies have been implicated in this attachment. In previous work, monoclonal antibodies were produced against Leishmania. Among these an antibody was obtained against Leishmania braziliensis flagella, which blocked the attachment of Leishmania panamensis flagella to Phlebotomus papatasi guts. The protein recognized by this antibody was identified and named FLAG1, and the complete FLAG1 gene sequence was obtained. This protein was later independently identified as a small, myristoylated protein and called SMP1, so from now on it will be denominated FLAG1/SMP1. The FLAG1/SMP1 gene is expressed in all developmental stages of the parasite, but has higher expression in promastigotes. The anti-FLAG1/SMP1 antibody recognized the flagellum of all Leishmania species tested and generated the expected band by western blots. This antibody was used in attachment and infection blocking experiments. Using the New World vector Lutzomyia longipalpis and Leishmania infantum chagasi, no inhibition of attachment ex vivo or infection in vivo was seen. On the other hand, when the Old World vectors P. papatasi and Leishmania major were used, a significant decrease of both attachment and infection were seen in the presence of the antibody. We propose that FLAG1/SMP1 is involved in the attachment/infection of Leishmania in the strict vector P. papatasi and not the permissive vector L. longipalpis.

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-04-29

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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.

Towards Universal Semantic Tagging

NARCIS (Netherlands)

Abzianidze, Lasha; Bos, Johan

2017-01-01

The paper proposes the task of universal semantic tagging---tagging word tokens with language-neutral, semantically informative tags. We argue that the task, with its independent nature, contributes to better semantic analysis for wide-coverage multilingual text. We present the initial version of

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.

Sensor-based material tagging system

International Nuclear Information System (INIS)

Vercellotti, L.C.; Cox, R.W.; Ravas, R.J.; Schlotterer, J.C.

1991-01-01

Electronic identification tags are being developed for tracking material and personnel. In applying electronic identification tags to radioactive materials safeguards, it is important to measure attributes of the material to ensure that the tag remains with the material. The addition of a microcontroller with an on-board analog-to-digital converter to an electronic identification tag application-specific integrated-circuit has been demonstrated as means to provide the tag with sensor data. Each tag is assembled into a housing, which serves as a scale for measuring the weight of a paint-can-sized container and its contents. Temperature rise of the can above ambient is also measured, and a piezoelectric detector detects disturbances and immediately puts the tag into its alarm and beacon mode. Radiation measurement was also considered, but the background from nearby containers was found to be excessive. The sensor-based tagging system allows tracking of the material in cans as it is stored in vaults or is moved through the manufacturing process. The paper presents details of the sensor-based material tagging system and describes a demonstration system

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.

Antenna for passive RFID tags

Science.gov (United States)

Schiopu, Paul; Manea, Adrian; Cristea, Ionica; Grosu, Neculai; Vladescu, Marian; Craciun, Anca-Ileana; Craciun, Alexandru

2015-02-01

Minuscule devices, called RFID tags are attached to objects and persons and emit information which positioned readers may capture wirelessly. Many methods of identification have been used, but that of most common is to use a unique serial number for identification of person or object. RFID tags can be characterized as either active or passive [1,2]. Traditional passive tags are typically in "sleep" state until awakened by the reader's emitted field. In passive tags, the reader's field acts to charge the capacitor that powers the badge and this can be a combination of antenna and barcodes obtained with SAW( Surface Acoustic Wave) devices [1,2,3] . The antenna in an RFID tag is a conductive element that permits the tag to exchange data with the reader. The paper contribution are targeted to antenna for passive RFID tags. The electromagnetic field generated by the reader is somehow oriented by the reader antenna and power is induced in the tag only if the orientation of the tag antenna is appropriate. A tag placed orthogonal to the reader yield field will not be read. This is the reason that guided manufacturers to build circular polarized antenna capable of propagating a field that is alternatively polarized on all planes passing on the diffusion axis. Passive RFID tags are operated at the UHF frequencies of 868MHz (Europe) and 915MHz (USA) and at the microwave frequencies of 2,45 GHz and 5,8 GHz . Because the tags are small dimensions, in paper, we present the possibility to use circular polarization microstrip antenna with fractal edge [2].

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.

48 CFR 47.403-1 - Availability and unavailability of U.S.-flag air carrier service.

Science.gov (United States)

2010-10-01

... farthest interchange point on a usually traveled route. (2) When an origin or interchange point is not... interchange point on a usually traveled route to connect with U.S.-flag air carrier service. (3) When a U.S... travel by a foreign-flag air carrier. (e) For travel between two points outside the United States, the...

Tagging vs. Controlled Vocabulary

DEFF Research Database (Denmark)

Bogers, Toine; Petras, Vivien

2015-01-01

The popularity of social tagging has sparked a great deal of debate on whether tags could replace or improve upon professional metadata as descriptors of books and other information objects. In this paper we present a large-scale empirical comparison of the contributions of individual information...... that tags and controlled vocabulary terms do not actually outperform each other consistently, but seem to provide complementary contributions: some information needs are best addressed using controlled vocabulary terms whereas other are best addressed using tags....

Improving Recommendations in Tag-based Systems with Spectral Clustering of Tag Neighbors

DEFF Research Database (Denmark)

Pan, Rong; Xu, Guandong; Dolog, Peter

2012-01-01

Tag as a useful metadata reflects the collaborative and conceptual features of documents in social collaborative annotation systems. In this paper, we propose a collaborative approach for expanding tag neighbors and investigate the spectral clustering algorithm to filter out noisy tag neighbors...... in order to get appropriate recommendation for users. The preliminary experiments have been conducted on MovieLens dataset to compare our proposed approach with the traditional collaborative filtering recommendation approach and naive tag neighbors expansion approach in terms of precision, and the result...... demonstrates that our approach could considerably improve the performance of recommendations....

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...

Strep-Tagged Protein Purification.

Science.gov (United States)

Maertens, Barbara; Spriestersbach, Anne; Kubicek, Jan; Schäfer, Frank

2015-01-01

The Strep-tag system can be used to purify recombinant proteins from any expression system. Here, protocols for lysis and affinity purification of Strep-tagged proteins from E. coli, baculovirus-infected insect cells, and transfected mammalian cells are given. Depending on the amount of Strep-tagged protein in the lysate, a protocol for batch binding and subsequent washing and eluting by gravity flow can be used. Agarose-based matrices with the coupled Strep-Tactin ligand are the resins of choice, with a binding capacity of up to 9 mg ml(-1). For purification of lower amounts of Strep-tagged proteins, the use of Strep-Tactin magnetic beads is suitable. In addition, Strep-tagged protein purification can also be automated using prepacked columns for FPLC or other liquid-handling chromatography instrumentation, but automated purification is not discussed in this protocol. The protocols described here can be regarded as an update of the Strep-Tag Protein Handbook (Qiagen, 2009). © 2015 Elsevier Inc. All rights reserved.

Marine Mammal Necropsy: An Introductory Guide for Stranding Responders and Field Biologists

Science.gov (United States)

2007-09-01

increasing friction we have found that the easiest to hardest surfaces are as follows: wet slab rock such as basalt , cobble, slick mud, gravel, sand...Flagging tape, biodegradable Laundry tags- www.golps.com,Daily Delivery Tag, 1-Ply fiber ; Label tape- www.VWR.com Tyveck tags-www.LSS.com; Blank tags

WebTag: Web browsing into sensor tags over NFC.

Science.gov (United States)

Echevarria, Juan Jose; Ruiz-de-Garibay, Jonathan; Legarda, Jon; Alvarez, Maite; Ayerbe, Ana; Vazquez, Juan Ignacio

2012-01-01

Information and Communication Technologies (ICTs) continue to overcome many of the challenges related to wireless sensor monitoring, such as for example the design of smarter embedded processors, the improvement of the network architectures, the development of efficient communication protocols or the maximization of the life cycle autonomy. This work tries to improve the communication link of the data transmission in wireless sensor monitoring. The upstream communication link is usually based on standard IP technologies, but the downstream side is always masked with the proprietary protocols used for the wireless link (like ZigBee, Bluetooth, RFID, etc.). This work presents a novel solution (WebTag) for a direct IP based access to a sensor tag over the Near Field Communication (NFC) technology for secure applications. WebTag allows a direct web access to the sensor tag by means of a standard web browser, it reads the sensor data, configures the sampling rate and implements IP based security policies. It is, definitely, a new step towards the evolution of the Internet of Things paradigm.

Fluid-structure-interaction of a flag in a channel flow

Science.gov (United States)

Liu, Yingzheng; Yu, Yuelong; Zhou, Wenwu; Wang, Weizhe

2017-11-01

The unsteady flow field and flapping dynamics of an inverted flag in water channel are investigated using time resolved particle image velocimetry (TR-PIV) measurements. The dynamically deformed profiles of the inverted flag are determined by a novel algorithm that combines morphological image processing and principle component analysis. Instantaneous flow field, phase averaged vorticity, time-mean flow field and turbulent kinematic energy are addressed for the flow. Four modes are discovered as the dimensionless bending stiffness decreases, i.e., the straight mode, the biased mode, the flapping mode and the deflected mode. Among all modes, the flapping mode is characterized by large flapping amplitude and the reverse von Kármán vortex street wake, which is potential to enhance heat transfer remarkably. National Natural Science Foundation of China.

Extracting Usage Patterns and the Analysis of Tag Connection Dynamics within Collaborative Tagging Systems

Directory of Open Access Journals (Sweden)

Daniel MICAN

2013-01-01

Full Text Available Collaborative tagging has become a very popular way of annotation, thanks to the fact that any entity may be labeled by any individual based on his own reason. In this paper we present the results of the case study carried out on the basis of data gathered at different time intervals from the social tagging system developed and implemented on Întelepciune.ro. Analyzing collective data referring to the way in which community members associate different tags, we have observed that between tags, links are formed which become increasingly stable with the passing of time. Following the application of methodology specific to network analysis, we have managed to extract information referring to tag popularity, their influence within the network and the degree to which a tag depends upon another. As such, we have succeeded in determining different semantic structures within the collective tagging system and see their evolution at different stages in time. Furthermore, we have pictured the way in which tag rec-ommendations can be executed and that they can be integrated within recommendation sys-tems. Thus, we will be able to identify experts and trustworthy content based on different cat-egories of interest.

Editorial Tag Endogeneity for News Websites

OpenAIRE

Bruno Ribeiro; Ricardo Morla; Amílcar Correia

2013-01-01

Editors and journalists at some news websites label their articles with structure and content-related editorial tags. Each article can have more than one tag and each tag can be used in more than one article. A network of tags can be defined whose edges are all possible pairs of tags in each article. Because editorial tags relate to structure and content rather than individual articles, the analysis of a network of editorial tags could assist editorial decisions to prioritize types of content...

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

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.

Quantum cohomology of flag manifolds and Toda lattices

International Nuclear Information System (INIS)

Givental, A.; Kim, B.

1995-01-01

We discuss relations of Vafa's quantum cohomology with Floer's homology theory, introduce equivariant quantum cohomology, formulate some conjectures about its general properties and, on the basis of these conjectures, compute quantum cohomology algebras of the flag manifolds. The answer turns out to coincide with the algebra of regular functions on an invariant lagrangian variety of a Toda lattice. (orig.)

Gillnet Tag Program

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Certain fishery management programs require vessels to obtain gillnet tags to be used with their gillnet gear. Gillnet tag data is a collection of requests and...

Structure of anti-FLAG M2 Fab domain and its use in the stabilization of engineered membrane proteins

International Nuclear Information System (INIS)

Roosild, Tarmo P.; Castronovo, Samantha; Choe, Senyon

2006-01-01

The X-ray crystallographic analysis of anti-FLAG M2 Fab is reported and the implications of the structure on FLAG epitope binding are described as a first step in the development of a tool for the structural and biophysical study of membrane proteins. The inherent difficulties of stabilizing detergent-solubilized integral membrane proteins for biophysical or structural analysis demand the development of new methodologies to improve success rates. One proven strategy is the use of antibody fragments to increase the ‘soluble’ portion of any membrane protein, but this approach is limited by the difficulties and expense associated with producing monoclonal antibodies to an appropriate exposed epitope on the target protein. Here, the stabilization of a detergent-solubilized K + channel protein, KvPae, by engineering a FLAG-binding epitope into a known loop region of the protein and creating a complex with Fab fragments from commercially available anti-FLAG M2 monoclonal antibodies is reported. Although well diffracting crystals of the complex have not yet been obtained, during the course of crystallization trials the structure of the anti-FLAG M2 Fab domain was solved to 1.86 Å resolution. This structure, which should aid future structure-determination efforts using this approach by facilitating molecular-replacement phasing, reveals that the binding pocket appears to be specific only for the first four amino acids of the traditional FLAG epitope, namely DYKD. Thus, the use of antibody fragments for improving the stability of target proteins can be rapidly applied to the study of membrane-protein structure by placing the short DKYD motif within a predicted peripheral loop of that protein and utilizing commercially available anti-FLAG M2 antibody fragments

Vortex dynamics and heat transfer behind self-oscillating inverted flags of various lengths in channel flow

Science.gov (United States)

Yu, Yuelong; Liu, Yingzheng; Chen, Yujia

2018-04-01

The influence of an inverted flag's length-to-channel-width ratio (C* = L/W) on its oscillating behavior in a channel flow and the resultant vortex dynamics and heat transfer are determined experimentally. Three systems with C* values of 0.125, 0.250, and 0.375 were chosen for comparison. The interaction of highly unsteady flow with the inverted flag is measured with time-resolved particle image velocimetry. Variations in the underlying flow physics are discussed in terms of the statistical flow quantities, flag displacement, phase-averaged flow field, and vortex dynamics. The results show that the increase in C* shifts the occurrence of the flapping regime at high dimensionless bending stiffness. With the flag in the flapping region, three distinct vortex dynamics—the von Kármán vortex street, the G mode, and the singular mode—are identified at C* values of 0.375, 0.250, and 0.125, respectively. Finally, the heat transfer enhancement from the self-oscillating inverted flag is measured to serve as complementary information to quantify the cause-and-effect relationship between vortex dynamics and wall heat transfer. The increase in C* strongly promotes wall heat removal because disruption of the boundary layer by the energetic vortices is substantially intensified. Among all systems, wall heat transfer removal is most efficient at the intermediate C* value of 0.250.

Social Tagging of Mission Data

Science.gov (United States)

Norris, Jeffrey S.; Wallick, Michael N.; Joswig, Joseph C.; Powell, Mark W.; Torres, Recaredo J.; Mittman, David S.; Abramyan, Lucy; Crockett, Thomas M.; Shams, Khawaja S.; Fox, Jason M.;

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.

THE STATE PRESIDENT'S FLAG SINCE 4 SEPTEMBER 1984

African Journals Online (AJOL)

The heraldic description of the flag reads as follows: a rectangular tricolour, ratio three by two, with three triangular fields (top to bottom) in orange, white and blue. The white charged in the hoist with the coat of arms of the Republic of. South Africa. Above the coat of arms the letter. 'SP' are ensigned in gold with black ...

A Preliminary Assessment of the SURF Reactive Burn Model Implementation in FLAG

Energy Technology Data Exchange (ETDEWEB)

Johnson, Carl Edward [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McCombe, Ryan Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Carver, Kyle [United States Air Force, Washington, DC (United States)

2017-09-18

Properly validated and calibrated reactive burn models (RBM) can be useful engineering tools for assessing high explosive performance and safety. Experiments with high explosives are expensive. Inexpensive RBM calculations are increasingly relied on for predictive analysis for performance and safety. This report discusses the validation of Menikoff and Shaw’s SURF reactive burn model, which has recently been implemented in the FLAG code. The LANL Gapstick experiment is discussed as is its’ utility in reactive burn model validation. Data obtained from pRad for the LT-63 series is also presented along with FLAG simulations using SURF for both PBX 9501 and PBX 9502. Calibration parameters for both explosives are presented.

Analysis of historical and recent PBX 9404 cylinder tests using FLAG

Energy Technology Data Exchange (ETDEWEB)

Wooten, Hasani Omar [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Whitley, Von Howard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-01-31

Cylinder test experiments using aged PBX-9404 were recently conducted. When compared to similar historical tests using the same materials, but different diagnostics, the data indicate that PBX 9404 imparts less energy to surrounding copper. The purpose of this work was to simulate historical and recent cylinder tests using the Lagrangian hydrodynamics code, FLAG, and identify any differences in the energetic behavior of the material. Nine experiments spanning approximately 4.5 decades were simulated, and radial wall expansions and velocities were compared. Equation-of-state parameters were adjusted to obtain reasonable matches with experimental data. Pressure-volume isentropes were integrated, and resultant energies at specific volume expansions were compared. FLAG simulations matched to experimental data indicate energetic changes of approximately -0.57% to -0.78% per decade.

14 CFR 1221.106 - Establishment of the NASA Flag.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Establishment of the NASA Flag. 1221.106 Section 1221.106 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA...

14 CFR 1221.113 - Use of the NASA Flags.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Use of the NASA Flags. 1221.113 Section 1221.113 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL AND OTHER DEVICES, AND THE CONGRESSIONAL SPACE MEDAL OF HONOR NASA Seal, NASA Insignia, NASA Logotype, NASA Program...

Gas tagging system development in Japan

International Nuclear Information System (INIS)

Sekiguchi, N.; Rindo, H.; Akiyama, T.; Miyazawa, T.; Heki, H.

1981-05-01

The Gas tagging method has been considered to be most desirable for a failed fuel location system for the fast breeder reactor, regarding the component reduction in the reactor vessel and rapid location during reactor operation. The gas tagging system has been designed by referring to R and D results obtained in Japan and other countries. The designed system is comprised of tag gas filling pins, cover gas sampling system, tag gas recovery and enrichment system, tag gas analyzer and system control and data handling computers. The main specifications for this system have been decided as follows; 1) Main function is location of failed fuels in core and a part of blanket region, 2) Identification capability is each subassembly, 3) Time for identification is within a few days, 4) Continuous operation with automatic start at fuel failure, 5) Detection sensitivity must cover both gas leak and pin burst. In designing the gas tagging system, the following R and D items were selected; 1) System design study, 2) Tag gas capsule development, 3) Modeling the tag gas behavior in reactor primary cooling system, 4) Tag gas recovery and enrichment system, 5) Computer code development for tag gas isotope ratio change estimation. Details of the Japanese gas tagging system development appear in this paper. (author)

Knowledge and Utilization of Red Flags by Physiotherapists in the ...

African Journals Online (AJOL)

DR. BASHIR BELLO

majority of the physiotherapists 44 (88%) had knowledge of red flags but only 14 (28%) ... documented, while medical history of cancer, HIV status, as well as history of fever were .... The main objective of this study was to determine the level.

75 FR 13645 - Inventory of U.S.-Flag Launch Barges

Science.gov (United States)

2010-03-22

... Qualified Launch Barges, the Interim Final Rule requires that the Maritime Administration publish a notice... DEPARTMENT OF TRANSPORTATION Maritime Administration [Docket No. MARAD-2010 0023] Inventory of U.S.-Flag Launch Barges AGENCY: Maritime Administration, Department of Transportation. ACTION: Inventory of...

76 FR 20080 - Inventory of U.S.-Flag Launch Barges

Science.gov (United States)

2011-04-11

... Administration publish a notice in the Federal Register requesting that owners or operators (or potential owners... DEPARTMENT OF TRANSPORTATION Maritime Administration [Docket Number MARAD 2011 0030] Inventory of U.S.-Flag Launch Barges AGENCY: Maritime Administration, Department of Transportation. ACTION...

Integrative Genomic Analysis of In Vivo Muscle Regeneration After Severe Trauma

Science.gov (United States)

2015-11-30

muscular dystrophy and aging. The cis-regulatory networks that orchestrate in-vivo muscle repair and regeneration after traumatic injury have only been...modulates dystrophin expression: new implications for Duchenne muscular dystrophy therapy. EMBO Rep. 12, 136-141 (2011). 46. Cachiarelli, D., Martone...I. MicroRNAs involved in molecular circuitries relevant for the Duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS

50 CFR 216.46 - U.S. citizens on foreign flag vessels operating under the International Dolphin Conservation...

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false U.S. citizens on foreign flag vessels operating under the International Dolphin Conservation Program. 216.46 Section 216.46 Wildlife and Fisheries....46 U.S. citizens on foreign flag vessels operating under the International Dolphin Conservation...

Topical tags vs non-topical tags : Towards a bipartite classification?

NARCIS (Netherlands)

Basile, Valerio; Peroni, Silvio; Tamburini, Fabio; Vitali, Fabio

2015-01-01

In this paper we investigate whether it is possible to create a computational approach that allows us to distinguish topical tags (i.e. talking about the topic of a resource) and non-topical tags (i.e. describing aspects of a resource that are not related to its topic) in folksonomies, in a way that

The role of tag suggestions in folksonomies

NARCIS (Netherlands)

Bollen, D.G.F.M.; Halpin, H.

2009-01-01

Most tagging systems support the user in the tag selection process by providing tag suggestions, or recommendations, based on a popularity measurement of tags other users provided when tagging the same resource. The majority of theories and mathematical models of tagging found in the literature

Air Quality Flags Program, U.S., 2017, EPA/OAR/OAQPS/OID

Data.gov (United States)

U.S. Environmental Protection Agency — This map service contains participants in EPA's Air Quality Flags Program. The map service also includes the current day's AQI forecast for each participant in the...

Flag varieties an interplay of geometry, combinatorics, and representation theory

CERN Document Server

Lakshmibai, V

2009-01-01

Flag varieties are important geometric objects and their study involves an interplay of geometry, combinatorics, and representation theory. This book is detailed account of this interplay. In the area of representation theory, the book presents a discussion of complex semisimple Lie algebras and of semisimple algebraic groups; in addition, the representation theory of symmetric groups is also discussed. In the area of algebraic geometry, the book gives a detailed account of the Grassmannian varieties, flag varieties, and their Schubert subvarieties. Because of the connections with root systems, many of the geometric results admit elegant combinatorial description, a typical example being the description of the singular locus of a Schubert variety. This is shown to be a consequence of standard monomial theory (abbreviated SMT). Thus the book includes SMT and some important applications - singular loci of Schubert varieties, toric degenerations of Schubert varieties, and the relationship between Schubert variet...

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.

Red Flags for Low Back Pain Are Not Always Really Red: A Prospective Evaluation of the Clinical Utility of Commonly Used Screening Questions for Low Back Pain.

Science.gov (United States)

Premkumar, Ajay; Godfrey, William; Gottschalk, Michael B; Boden, Scott D

2018-03-07

Low back pain has a high prevalence and morbidity, and is a source of substantial health-care spending. Numerous published guidelines support the use of so-called red flag questions to screen for serious pathology in patients with low back pain. This paper examines the effectiveness of red flag questions as a screening tool for patients presenting with low back pain to a multidisciplinary academic spine center. We conducted a retrospective review of the cases of 9,940 patients with a chief complaint of low back pain. The patients completed a questionnaire that included several red flag questions during their first physician visit. Diagnostic data for the same clinical episode were collected from medical records and were corroborated with imaging reports. Patients who were diagnosed as having a vertebral fracture, malignancy, infection, or cauda equina syndrome were classified as having a red flag diagnosis. Specific individual red flags and combinations of red flags were associated with an increased probability of underlying serious spinal pathology, e.g., recent trauma and an age of >50 years were associated with vertebral fracture. The presence or absence of other red flags, such as night pain, was unrelated to any particular diagnosis. For instance, for patients with no recent history of infection and no fever, chills, or sweating, the presence of night pain was a false-positive finding for infection >96% of the time. In general, the absence of red flag responses did not meaningfully decrease the likelihood of a red flag diagnosis; 64% of patients with spinal malignancy had no associated red flags. While a positive response to a red flag question may indicate the presence of serious disease, a negative response to 1 or 2 red flag questions does not meaningfully decrease the likelihood of a red flag diagnosis. Clinicians should use caution when utilizing red flag questions as screening tools.

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.

FLAG Simulations of the Elasticity Test Problem of Gavrilyuk et al.

Energy Technology Data Exchange (ETDEWEB)

Kamm, James R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Runnels, Scott R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Canfield, Thomas R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Carney, Theodore C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2014-04-23

This report contains a description of the impact problem used to compare hypoelastic and hyperelastic material models, as described by Gavrilyuk, Favrie & Saurel. That description is used to set up hypoelastic simulations in the FLAG hydrocode.

General and Flag Officer Careers: Consequences of Increased Tenure

National Research Council Canada - National Science Library

Thie, Harry

2001-01-01

.... As a result of these concerns, Congress asked the Secretary of Defense to review the career patterns of flag-rank officers. It requested specific data about average time-in-grade both when selected and when promoted as well as the length of tours. It also asked the Secretary to assess the appropriateness of mandatory retirement at 35 years.

Buddy Tag CONOPS and Requirements.

Energy Technology Data Exchange (ETDEWEB)

Brotz, Jay Kristoffer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Deland, Sharon M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-12-01

This document defines the concept of operations (CONOPS) and the requirements for the Buddy Tag, which is conceived and designed in collaboration between Sandia National Laboratories and Princeton University under the Department of State Key VerificationAssets Fund. The CONOPS describe how the tags are used to support verification of treaty limitations and is only defined to the extent necessary to support a tag design. The requirements define the necessary functions and desired non-functional features of the Buddy Tag at a high level

Potential synergy between the Ionospheric Disturbance Flag and NeQuick-G for single frequency users

Science.gov (United States)

Aragon-Angel, Angela; Fortuny, Joaquim

2016-04-01

The document describing the particular ionospheric model developed for the Galileo satellite navigation system has been very recently released, the official Ionospheric Correction Algorithm for Galileo Single Frequency Users document (from here on-wards named Galileo-Iono), available at www.gsc-europa.eu/system/files/galileo_documents/Galileo_Ionospheric_Model.pdf. This publication allows GNSS receiver manufacturers to start the implementation of the specific algorithm targeted for their Galileo related products in order to be compliant with the Galileo system. As indicated in the Galileo OS SIS ICD, among the parameters that are broadcast in the Galileo navigation message, parameters that are sent within both F/NAV and I/NAV, one can find five Ionospheric Disturbance Flags for Regions 1 to 5 (SF1, SF2, SF3, SF4 and SF5). Nevertheless, in the current version of the model presented in the Galileo-Iono document, the Ionospheric Disturbance flags are "not used" within the Galileo ionospheric correction calculation. In this work, a potential approach to account for this information is being investigated. This plan includes the update of the Galileo ionospheric, NeQuick-G, correction model by specifying the use of these flags. Hence a customized version of the NeQuick-G model has been developed and tested. Specific scenarios will be considered to test whether this approach of considering the added value information of the Ionospheric Disturbance Flags is translated into the positioning domain. In order to assess the improvement obtained using the proposed approach five stations displaced in the five regions are used. Different days of data have been collected in nominal and disturbed conditions; the evaluation is carried out comparing the performance of the proposed approach with respect to the classical approach. The benefits of the use of the disturbance flags information are evaluated comparing the performance in similar geometry conditions.

Flavour tagging performance in LHCb

International Nuclear Information System (INIS)

Grabalosa Gandara, Marc

2009-01-01

To do precise CP violation measurements, the best possible determination of the flavour of the B-meson is necessary. This report summarizes the flavour tagging performances for the LHCb experiment. The flavour tagging is obtained through a combination of several methods, based on different signatures. The use of control channels, which are decays to flavour-specific final states, will allow to determine the wrong tag fraction ω (the probability of a tag to be wrong), which can be used as an input for the determination of CKM unitarity triangle angles.

Cooperative Tagging Center (CTC)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Cooperative Tagging Center (CTC) began as the Cooperative Game Fish Tagging Program (GTP) at Woods Hole Oceanographic Institute (WHOI) in 1954. The GTP was...

Secure passive RFID tag with seal

Science.gov (United States)

Nekoogar, Faranak; Reynolds, Matthew; Lefton, Scott; Dowla, Farid; Twogood, Richard

2017-11-14

A secure passive RFID tag system comprises at least one base station and at least one passive RFID tag. The tag includes a fiber optic cable with the cable ends sealed within the tag and the middle portion forming an external loop. The loop may be secured to at least portions of an object. The tag transmits and receives an optical signal through the fiber optic cable, and the cable is configured to be damaged or broken in response to removal or tampering attempts, wherein the optical signal is significantly altered if the cable is damaged or broken. The tag transmits the optical signal in response to receiving a radio signal from the base station and compares the transmitted optical signal to the received optical signal. If the transmitted optical signal and the received optical signal are identical, the tag transmits an affirmative radio signal to the base station.

North Pacific Albacore Tagging

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conventional tagging data are available from 1971 to 1996. Electronic tagging data are available from 2000 to present. The data are managed by SWFSC in Access...

Modifying Flag Football for Gender Equitable Engagement in Secondary Schools

Science.gov (United States)

Kahan, David

2008-01-01

Flag or touch football is a popular activity unit in American secondary physical education curricula. However, unlike other sports its stigmatization as a masculine-typed activity and frequent inequitable distribution of game play opportunities at the skill positions (e.g., receiver, quarterback) results in the marginalization of female…

EnTagRec : an enhanced tag recommendation system for software information sites

NARCIS (Netherlands)

Wang, S.; Lo, D.; Vasilescu, B.N.; Serebrenik, A.

2014-01-01

Software engineers share experiences with modern technologies by means of software information sites, such as STACK OVERFLOW. These sites allow developers to label posted content, referred to as software objects, with short descriptions, known as tags. However, tags assigned to objects tend to be

Smart-tag Based Data Dissemination

DEFF Research Database (Denmark)

Bonnet, Philippe; Beaufour, Allan; Leopold, Martin

2002-01-01

Monitoring wide, hostile areas requires disseminating data between fixed, disconnected clusters of sensor nodes. It is not always possible to install long-range radios in order to cover the whole area. We propose to leverage the movement of mobile individuals, equipped with smart-tags, to dissemi......-tag based data dissemination. We use simulation to study the characteristics of the model we propose. Finally, we present an implementation based on Bluetooth smart-tags.......Monitoring wide, hostile areas requires disseminating data between fixed, disconnected clusters of sensor nodes. It is not always possible to install long-range radios in order to cover the whole area. We propose to leverage the movement of mobile individuals, equipped with smart......-tags, to disseminate data across disconnected static nodes spread across a wide area. Static nodes and mobile smart-tags exchange data when they are in the vicinity of each other; smart-tags disseminate data as they move around. In this paper, we propose an algorithm for update propagation and a model for smart...

Comparing the hierarchy of author given tags and repository given tags in a large document archive

Science.gov (United States)

Tibély, Gergely; Pollner, Péter; Palla, Gergely

2016-10-01

Folksonomies - large databases arising from collaborative tagging of items by independent users - are becoming an increasingly important way of categorizing information. In these systems users can tag items with free words, resulting in a tripartite item-tag-user network. Although there are no prescribed relations between tags, the way users think about the different categories presumably has some built in hierarchy, in which more special concepts are descendants of some more general categories. Several applications would benefit from the knowledge of this hierarchy. Here we apply a recent method to check the differences and similarities of hierarchies resulting from tags given by independent individuals and from tags given by a centrally managed repository system. The results from our method showed substantial differences between the lower part of the hierarchies, and in contrast, a relatively high similarity at the top of the hierarchies.

Compliance with McDonald criteria and red flag recognition in a general neurology practice in Ireland.

LENUS (Irish Health Repository)

Albertyn, Christine

2012-02-01

BACKGROUND: The revised McDonald criteria aim to simplify and speed the diagnosis of multiple sclerosis (MS). An important principle of the criteria holds there should be no better explanation for the clinical presentation. In Miller et al.\\'s consensus statement on the differential diagnosis of MS, red flags are identified that may suggest a non-MS diagnosis. OBJECTIVE: All new patients with a practice diagnosis of MS were assessed for compliance with McDonald criteria. The group of patients not fulfilling criteria was followed up to assess compliance over time. At the end of the follow-up period, red flags were sought in the group of patients who remained McDonald criteria negative. METHODS: Clinical notes and paraclinical tests were examined retrospectively for compliance with McDonald criteria and for the presence of red flags. RESULTS: Sixty-two patients were identified, with two lost to follow-up. Twenty-six (42%) patients fulfilled criteria at diagnosis. After 53 months follow-up, 47 (78%) patients fulfilled criteria. In the 13 (22%) patients who remain McDonald criteria negative, a total of 20 red flags were identified, ranging from one to six per patient. Alternative diagnoses were considered and further investigations performed in 10 patients with no significantly abnormal results. CONCLUSION: Twenty-two percent of patients still do not fulfill McDonald criteria after 53 months. Dissemination in time was not proven in the majority of patients and the lack of follow-up neuroimaging was an important factor in this. Red flags may be useful in identifying alternative diagnoses, but the yield was low in our cohort.

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.

Vortex dynamics behind a self-oscillating inverted flag placed in a channel flow: Time-resolved particle image velocimetry measurements

Science.gov (United States)

Yu, Yuelong; Liu, Yingzheng; Chen, Yujia

2017-12-01

The unsteady flow behind an inverted flag placed in a water channel and then excited into a self-oscillating state is measured using time-resolved particle image velocimetry. The dynamically deformed profiles of the inverted flag are determined by a novel algorithm that combines morphological image processing and principle component analysis. Three modes are discovered with the successive decrease in the dimensionless bending stiffness: the biased mode, the flapping mode, and the deflected mode. The distinctly different flow behavior is discussed in terms of instantaneous velocity field, phase-averaged vorticity field, time-mean flow field, and turbulent kinetic energy. The results demonstrated that the biased mode generated abundant vortices at the oscillating side of the inverted flag. In the deflected mode, the inverted flag is highly deflected to one side of the channel and remains almost stationary, inducing two stable recirculation zones and a considerably inversed flow between them. In the flapping mode, the strongly oscillating flag periodically provides a strengthened influence on the fluid near the two sidewalls. The reverse von Kármán vortex street is well formed and energetic in the wake, and a series of high-speed impingement jets between the neighboring vortices are directed toward the sidewalls in a staggered fashion.

DICOM involving XML path-tag

Science.gov (United States)

Zeng, Qiang; Yao, Zhihong; Liu, Lei

2011-03-01

Digital Imaging and Communications in Medicine (DICOM) is a standard for handling, storing, printing, and transmitting information in medical imaging. XML (Extensible Markup Language) is a set of rules for encoding documents in machine-readable form which has become more and more popular. The combination of these two is very necessary and promising. Using XML tags instead of numeric labels in DICOM files will effectively increase the readability and enhance the clear hierarchical structure of DICOM files. However, due to the fact that the XML tags rely heavily on the orders of the tags, the strong data dependency has a lot of influence on the flexibility of inserting and exchanging data. In order to improve the extensibility and sharing of DICOM files, this paper introduces XML Path-Tag to DICOM. When a DICOM file is converted to XML format, adding simple Path-Tag into the DICOM file in place of complex tags will keep the flexibility of a DICOM file while inserting data elements and give full play to the advantages of the structure and readability of an XML file. Our method can solve the weak readability problem of DICOM files and the tedious work of inserting data into an XML file. In addition, we set up a conversion engine that can transform among traditional DICOM files, XML-DCM and XML-DCM files involving XML Path-Tag efficiently.

b-tagging in DELPHI at LEP

CERN Document Server

Abdallah, J; Adam, W; Adye, T; Adzic, P; Albrecht, T; Alderweireld, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W D; Arnoud, Y; Ask, S; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Ballestrero, A; Bambade, P; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Bates, M; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Berntzon, L; Bertrand, D; Besançon, M; Besson, N; Bibby, J; Biffi, P; Bloch, D; Blom, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Branchini, P; Brenner, R; Brodet, E; Brückman, P; Brunet, J M; Bugge, L; Buschmann, P; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Checchia, P; Chierici, R; Shlyapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Couchot, F; Crawley, B; Crennell, D J; Cuevas-Maestro, J; D'Almagne, B; D'Hondt, J; Dalmau, J; Da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; De Paula, L S; Di Ciaccio, Lucia; Dijkstra, H; Di Simone, A; Doroba, K; Drees, J; Dris, M; Eigen, G; Ekelöf, T J C; Ellert, M; Elsing, M; Espirito-Santo, M C; Fanourakis, G K; Fassouliotis, D; Feindt, M; Fernández, J; Ferrer, A; Ferro, F; Flagmeyer, U; Föth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J A; Gandelman, M; García, C; Gavillet, P; Gazis, E N; Geralis, T; Gokieli, R; Golob, B; Gómez-Cadenas, J J; Gómez-Ceballos, G; Gonçalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Hansen, J; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Hernando, J A; Herr, H; Heuser, J M; Holmgren, S O; Holt, P J; Houlden, M A; Hultqvist, K; Jackson, J N; Jalocha, P; Jarlskog, C; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Johansson, P D; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Karlsson, M; Katsanevas, S; Katsoufis, E C; Keränen, R; Kernel, G; Kersevan, Borut P; Kiiskinen, A P; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kuznetsov, O; Krumshtein, Z; Kucharczyk, M; Kucewicz, W; Kurowska, J; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; McNulty, R; Meroni, C; Meyer, W T; Migliore, E; Mitaroff, W A; Mjörnmark, U; Moa, T; Moch, M; Mönig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Müller, U; Münich, K; Mulders, M; Mundim, L; Murray, W; Muryn, B; Myatt, Gerald; Myklebust, T; Nassiakou, M; Navarria, Francesco Luigi; Nawrocki, K; Nicolaidou, R; Niezurawski, P; Nikolenko, M; Nomerotski, A; Norman, A; Nygren, A; Oblakowska-Mucha, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V F; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Pukhaeva, N; Pullia, Antonio; Rames, J; Ramler, L; Read, A; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P B; Richard, F; Rídky, J; Rivero, M; Rodríguez, D; Romero, A; Ronchese, P; Rosenberg, E I; Roudeau, Patrick; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovskii, A; Salmi, L; Salt, J; Savoy-Navarro, A; Schwickerath, U; Segar, A; Sekulin, R L; Siebel, M; Sissakian, A N; Smadja, G; Smirnova, O G; Sokolov, A; Sopczak, A; Sosnowski, R; Spassoff, Tz; Stanitzki, M; Stavitski, I; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Tabarelli de Fatis, T; Taffard, A C; Tegenfeldt, F; Timmermans, J; Tinti, N; Tkatchev, L G; Tobin, M; Todorovova, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Trischuk, W; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tyndel, M; Tzamarias, S; Uvarov, V; Valenti, G; van Dam, P; Van Eldik, J; Van Lysebetten, A; Van Remortel, N; Van Vulpen, I B; Vegni, G; Veloso, F; Venus, W A; Verbeure, F; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weilhammer, Peter; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O P; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zimin, N I; Zinchenko, A I; Zupan, M

2004-01-01

The standard method used for tagging b-hadrons in the DELPHI experiment at the CERN LEP Collider is discussed in detail. The main ingredient of b-tagging is the impact parameters of tracks, which relies mostly on the vertex detector. Additional information, such as the mass of particles associated to a secondary vertex, significantly improves the selection efficiency and the background suppression. The paper describes various discriminating variables used for the tagging and the procedure of their combination. In addition, applications of b-tagging to some physics analyses, which depend crucially on the performance and reliability of b-tagging, are described briefly.

Notes on SAW Tag Interrogation Techniques

Science.gov (United States)

Barton, Richard J.

2010-01-01

We consider the problem of interrogating a single SAW RFID tag with a known ID and known range in the presence of multiple interfering tags under the following assumptions: (1) The RF propagation environment is well approximated as a simple delay channel with geometric power-decay constant alpha >/= 2. (2) The interfering tag IDs are unknown but well approximated as independent, identically distributed random samples from a probability distribution of tag ID waveforms with known second-order properties, and the tag of interest is drawn independently from the same distribution. (3) The ranges of the interfering tags are unknown but well approximated as independent, identically distributed realizations of a random variable rho with a known probability distribution f(sub rho) , and the tag ranges are independent of the tag ID waveforms. In particular, we model the tag waveforms as random impulse responses from a wide-sense-stationary, uncorrelated-scattering (WSSUS) fading channel with known bandwidth and scattering function. A brief discussion of the properties of such channels and the notation used to describe them in this document is given in the Appendix. Under these assumptions, we derive the expression for the output signal-to-noise ratio (SNR) for an arbitrary combination of transmitted interrogation signal and linear receiver filter. Based on this expression, we derive the optimal interrogator configuration (i.e., transmitted signal/receiver filter combination) in the two extreme noise/interference regimes, i.e., noise-limited and interference-limited, under the additional assumption that the coherence bandwidth of the tags is much smaller than the total tag bandwidth. Finally, we evaluate the performance of both optimal interrogators over a broad range of operating scenarios using both numerical simulation based on the assumed model and Monte Carlo simulation based on a small sample of measured tag waveforms. The performance evaluation results not only

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...

On-line Flagging of Anomalies and Adaptive Sequential Hypothesis Testing for Fine-feature Characterization of Geosynchronous Satellites

Science.gov (United States)

Chaudhary, A.; Payne, T.; Kinateder, K.; Dao, P.; Beecher, E.; Boone, D.; Elliott, B.

The objective of on-line flagging in this paper is to perform interactive assessment of geosynchronous satellites anomalies such as cross-tagging of a satellites in a cluster, solar panel offset change, etc. This assessment will utilize a Bayesian belief propagation procedure and will include automated update of baseline signature data for the satellite, while accounting for the seasonal changes. Its purpose is to enable an ongoing, automated assessment of satellite behavior through its life cycle using the photometry data collected during the synoptic search performed by a ground or space-based sensor as a part of its metrics mission. The change in the satellite features will be reported along with the probabilities of Type I and Type II errors. The objective of adaptive sequential hypothesis testing in this paper is to define future sensor tasking for the purpose of characterization of fine features of the satellite. The tasking will be designed in order to maximize new information with the least number of photometry data points to be collected during the synoptic search by a ground or space-based sensor. Its calculation is based on the utilization of information entropy techniques. The tasking is defined by considering a sequence of hypotheses in regard to the fine features of the satellite. The optimal observation conditions are then ordered in order to maximize new information about a chosen fine feature. The combined objective of on-line flagging and adaptive sequential hypothesis testing is to progressively discover new information about the features of a geosynchronous satellites by leveraging the regular but sparse cadence of data collection during the synoptic search performed by a ground or space-based sensor. Automated Algorithm to Detect Changes in Geostationary Satellite's Configuration and Cross-Tagging Phan Dao, Air Force Research Laboratory/RVB By characterizing geostationary satellites based on photometry and color photometry, analysts can

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.

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.

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

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

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.

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

The blood-stained flags of liberty – The struggle for adequate signs of identity in New Caledonia

Directory of Open Access Journals (Sweden)

Lindenmann, Peter

2014-09-01

Full Text Available The Nouméa treaty of 1998 that created the framework for the transition of New Caledonia from a French overseas territory towards emancipation provided also for the creation of new identity markers. Lacking a shared understanding of history and a common vision for the future, the process of adopting a flag was blocked for more than ten years. As an intermediate solution the flag of the Kanak independence movement is hoisted side by side to the French tricolour since 2010. While some loyalist parties continue to campaign for a common flag, pro-independence parties are waiting to descend the tricolour, and others would favor the status quo. The unresolved question of the right symbol is also a reflection of the uncertain political future as the referendum on independence looms.

A Privacy Model for RFID Tag Ownership Transfer

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Xingchun Yang

2017-01-01

Full Text Available The ownership of RFID tag is often transferred from one owner to another in its life cycle. To address the privacy problem caused by tag ownership transfer, we propose a tag privacy model which captures the adversary’s abilities to get secret information inside readers, to corrupt tags, to authenticate tags, and to observe tag ownership transfer processes. This model gives formal definitions for tag forward privacy and backward privacy and can be used to measure the privacy property of tag ownership transfer scheme. We also present a tag ownership transfer scheme, which is privacy-preserving under the proposed model and satisfies the other common security requirements, in addition to achieving better performance.

The Explicit Construction of Einstein Finsler Metrics with Non-Constant Flag Curvature

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Enli Guo

2009-04-01

Full Text Available By using the Hawking Taub-NUT metric, this note gives an explicit construction of a 3-parameter family of Einstein Finsler metrics of non-constant flag curvature in terms of navigation representation.

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.

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

Purification and fluorescent labeling of the human serotonin transporter

DEFF Research Database (Denmark)

Rasmussen, Søren G F; Gether, Ulrik

2005-01-01

To establish a purification procedure for the human serotonin transporter (hSERT) we expressed in Sf9 insect cells an epitope-tagged version of the transporter containing a FLAG epitope at the N-terminus and a polyhistidine tail at the C-terminus (FLAG-hSERT-12H). For purification, the transporter...

Engineering the ATLAS TAG Browser

CERN Document Server

Zhang, Q; The ATLAS collaboration

2011-01-01

ELSSI is a web-based event metadata (TAG) browser and event-level selection service for ATLAS. TAGs from all ATLAS physics and Monte Carlo data sets are routinely loaded into Oracle databases as an integral part of event processing. As data volumes increase, more and more sites are joining the distributed TAG data hosting topology. Meanwhile, TAG content and database schemata continue to evolve as new user requirements and additional sources of metadata emerge. All of this has posed many challenges to the development of ELSSI, which must support vast amounts of TAG data while source, content, geographic locations, and user query patterns may change over time. In this paper, we describe some of the challenges encountered in the process of developing ELSSI, and the software engineering strategies adopted to address those challenges. Approaches to management of access to data, browsing, data rendering, query building, query validation, execution, connection management, and communication with auxiliary services a...

Engineering the ATLAS TAG Browser

CERN Document Server

Zhang, Q; The ATLAS collaboration

2011-01-01

ELSSI is a web-based event metadata (TAG) browser and event-level selection service for ATLAS. TAGs from all ATLAS physics and Monte Carlo data sets are routinely loaded into Oracle databases as an integral part of event processing. As data volumes increase, more and more sites are joining the distributed TAG data hosting topology[1]. Meanwhile, TAG content and database schemata continue to evolve as new user requirements and additional sources of metadata emerge. All of this has posed many challenges to the development of ELSSI, which must support vast amounts of TAG data while source, content, geographic locations, and user query patterns may change over time. In this paper, we describe some of the challenges encountered in the process of developing ELSSI, and the software engineering strategies adopted to address those challenges. Approaches to management of access to data, browsing, data rendering, query building, query validation, execution, connection management, and communication with auxiliary service...

Nuclear studies with tagged photons

International Nuclear Information System (INIS)

Axel, P.

1979-01-01

First, the photon tagging technique will be described schematically, and a brief history of photon tagging will be given, including the 20 year development of this technique at Illinois. In the second part some typical operating conditions will be indicated for our tagged photon facility. The final section of this paper will illustrate some types of experiments by showing data obtained recently. (KBE) 891 KBE/KBE 892 ARA

Human-Centered Implicit Tagging: Overview and Perspectives

NARCIS (Netherlands)

Soleymani, Mohammad; Pantic, Maja

2012-01-01

Tags are an effective form of metadata which help users to locate and browse multimedia content of interest. Tags can be generated by users (user-generated explicit tags), automatically from the content (content-based tags), or assigned automatically based on non-verbal behavioral reactions of users

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.

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.

The use of tags and tag clouds to discern credible content in online health message forums.

Science.gov (United States)

O'Grady, Laura; Wathen, C Nadine; Charnaw-Burger, Jill; Betel, Lisa; Shachak, Aviv; Luke, Robert; Hockema, Stephen; Jadad, Alejandro R

2012-01-01

Web sites with health-oriented content are potentially harmful if inaccurate or inappropriate medical information is used to make health-related decisions. Checklists, rating systems and guidelines have been developed to help people determine what is credible, but recent Internet technologies emphasize applications that are collaborative in nature, including tags and tag clouds, where site users 'tag' or label online content, each using their own labelling system. Concepts such as the date, reference, author, testimonial and quotations are considered predictors of credible content. An understanding of these descriptive tools, how they relate to the depiction of credibility and how this relates to overall efforts to label data in relation to the semantic web has yet to emerge. This study investigates how structured (pre-determined) and unstructured (user-generated) tags and tag clouds with a multiple word search feature are used by participants to assess credibility of messages posted in online message forums. The targeted respondents were those using web sites message forums for disease self-management. We also explored the relevancy of our findings to the labelling or indexing of data in the context of the semantic web. Diabetes was chosen as the content area in this study, since (a) this is a condition with increasing prevalence and (b) diabetics have been shown to actively use the Internet to manage their condition. From January to March 2010 participants were recruited using purposive sampling techniques. A screening instrument was used to determine eligibility. The study consisted of a demographic and computer usage survey, a series of usability tests and an interview. We tested participants (N=22) on two scenarios, each involving tasks that assessed their ability to tag content and search using a tag cloud that included six structured credibility terms (statistics, date, reference, author, testimonial and quotations). MORAE Usability software (version 3

Physiological and Biochemical Characteristics in Flag Leaves of the C Liangyou Series of Hybrid Rice Combinations at Late Growth Stages

Directory of Open Access Journals (Sweden)

Wen-bang TANG

2010-12-01

Full Text Available The contents of chlorophyll, soluble sugars, soluble proteins and thiobarbituric acid reaction substance (TBARS, chlorophyll fluorescence parameters, net photosynthetic rate as well as the activities of superoxide dismutase (SOD and peroxidase (POD of flag leaves at the late growth stages were studied by using C Liangyou series of hybrid rice combinitions as material and Shanyou 63 as control. The C Liangyou series of hybrid rice combinations used in the experiment included C Liangyou 396, C Liangyou 87, C Liangyou 755 and C Liangyou 34, which all used C815S as male sterile line. The contents of chlorophyll, soluble sugars and soluble proteins in flag leaves of the C Liangyou series combinations at the late growth stages were higher than those of the control, whereas the TBARS content was lower than that of the control. The activities of SOD and POD were significantly higher than those of the control on the 7th day after heading, and then decreased slowly. FPSII value and qP value of flag leaves decreased at the late growth stages, and these two parameters in flag leaves of the C Liangyou series combinations were higher than those of the control, while the qN value increased at the late growth stages and was lower than that of the control. The net photosynthetic rate of flag leaves at the late growth stage was higher compared with the control. These results suggest that slow senescence and strong photosynthetic capability in flag leaves at the late growth stages are the physiological basis of the C Liangyou series combinations.

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.

CNNs flag recognition preprocessing scheme based on gray scale stretching and local binary pattern

Science.gov (United States)

Gong, Qian; Qu, Zhiyi; Hao, Kun

2017-07-01

Flag is a rather special recognition target in image recognition because of its non-rigid features with the location, scale and rotation characteristics. The location change can be handled well by the depth learning algorithm Convolutional Neural Networks (CNNs), but the scale and rotation changes are quite a challenge for CNNs. Since it has good rotation and gray scale invariance, the local binary pattern (LBP) is combined with grayscale stretching and CNNs to make LBP and grayscale stretching as CNNs pretreatment, which can not only significantly improve the efficiency of flag recognition, but can also evaluate the recognition effect through ROC, accuracy, MSE and quality factor.

Scalable Faceted Ranking in Tagging Systems

Science.gov (United States)

Orlicki, José I.; Alvarez-Hamelin, J. Ignacio; Fierens, Pablo I.

Nowadays, web collaborative tagging systems which allow users to upload, comment on and recommend contents, are growing. Such systems can be represented as graphs where nodes correspond to users and tagged-links to recommendations. In this paper we analyze the problem of computing a ranking of users with respect to a facet described as a set of tags. A straightforward solution is to compute a PageRank-like algorithm on a facet-related graph, but it is not feasible for online computation. We propose an alternative: (i) a ranking for each tag is computed offline on the basis of tag-related subgraphs; (ii) a faceted order is generated online by merging rankings corresponding to all the tags in the facet. Based on the graph analysis of YouTube and Flickr, we show that step (i) is scalable. We also present efficient algorithms for step (ii), which are evaluated by comparing their results with two gold standards.

Exploring the Long Tail of Social Media Tags

NARCIS (Netherlands)

Kordumova, S.; van Gemert, J.; Snoek, C.G.M.; Tian, Q.; Sebe, N.; Qi, G.-J.; Huet, B.; Hong, R.; Liu, X.

2016-01-01

There are millions of users who tag multimedia content, generating a large vocabulary of tags. Some tags are frequent, while other tags are rarely used following a long tail distribution. For frequent tags, most of the multimedia methods that aim to automatically understand audio-visual content,

Flavour Tagging at LHCb

CERN Multimedia

Grabalosa Gandara, M

2009-01-01

To do precise CP violation measurements, the most possible accurate knowledge of the flavour at production of the reconstructed B meson is required. This poster summarizes the flavour tagging performances for the LHCb experiment. We use same side an opposite side algorithms to establish wheter the meson contained a b or a b\\bar quark. The final decision is obtained through a combination of several methods. The use of control channels, decays to a flavour specific final state, will allow to determine the wrong tag fraction \\omega (the probability of a tag to be wrong), which can be used as input for the determination of CKM unitary triangle angles.

Building Tag Clouds in Perl and PHP

CERN Document Server

Bumgardner, Jim

2006-01-01

Tag clouds are everywhere on the web these days. First popularized by the web sites Flickr, Technorati, and del.icio.us, these amorphous clumps of words now appear on a slew of web sites as visual evidence of their membership in the elite corps of "Web 2.0." This PDF analyzes what is and isn't a tag cloud, offers design tips for using them effectively, and then goes on to show how to collect tags and display them in the tag cloud format. Scripts are provided in Perl and PHP. Yes, some have said tag clouds are a fad. But as you will see, tag clouds, when used properly, have real merits. More

Methodologies for Improved Tag Cloud Generation with Clustering

DEFF Research Database (Denmark)

Leginus, Martin; Dolog, Peter; Lage, Ricardo Gomes

2012-01-01

Tag clouds are useful means for navigation in the social web systems. Usually the systems implement the tag cloud generation based on tag popularity which is not always the best method. In this paper we propose methodologies on how to combine clustering into the tag cloud generation to improve...... coverage and overlap. We study several clustering algorithms to generate tag clouds. We show that by extending cloud generation based on tag popularity with clustering we slightly improve coverage. We also show that if the cloud is generated by clustering independently of the tag popularity baseline we...

Process-independent radiative-correction formula for single-tag and double-tag measurements of γγ reactions

International Nuclear Information System (INIS)

Ong, S.; Kessler, P.

1988-01-01

A simple and process-independent formula is given for radiative corrections in single-tag and double-tag measurements of γγ reactions. Its conditions of validity are that (i) in the γγ process itself all particles produced are detected and (ii) final-state particles, including the tagged electron(s), are measured with a good resolution in energy and momentum

Discharge residence of TLD tagged fish

International Nuclear Information System (INIS)

Romberg, G.P.; Prepejchal, W.

1974-01-01

Although visual observations suggested that fish remained in the discharge for considerable periods, temperature-sensitive tags indicated the majority of fish spend less than 50 hr or 10 percent of the time at discharge temperatures. During 1974 a second fish tagging study was conducted, using temperature-sensitive tags to yield discharge residence times of Lake Michigan salmonids at Point Beach thermal discharge. Preliminary results revealed that many fish tag values were close to Unit I line indicating that calculated maximum discharge residence times for these fish will be nearly 100 percent of the elapsed time

Using Interference to Block RFID Tags

DEFF Research Database (Denmark)

Krigslund, Rasmus; Popovski, Petar; Pedersen, Gert Frølund

We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag.......We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag....

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.

Satellite Tags- Guam/CNMI EEZ

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Satellite tagging was implemented in 2013. Satellite tagging is conducted using a Dan Inject air rifle and deployment arrows designed by Wildlife Computers. Two...

MR molecular imaging of tumours using ferritin heavy chain reporter gene expression mediated by the hTERT promoter

Energy Technology Data Exchange (ETDEWEB)

Yang, Yan [Third Military Medical University, Department of Radiology, XinQiao Hospital, ChongQing (China); The First Affiliated Hospital of ChengDu Medical College, Department of Radiology, ChengDu (China); Gong, Ming-fu; Yang, Hua; Zhang, Song; Wang, Guang-xian; Su, Tong-sheng; Wen, Li; Zhang, Dong [Third Military Medical University, Department of Radiology, XinQiao Hospital, ChongQing (China)

2016-11-15

Using the human telomerase reverse transcriptase (hTERT) promoter and the modified ferritin heavy chain (Fth) reporter gene, reporter gene expression for MRI was examined in telomerase positive and negative tumour cells and xenografts. Activity of the reporter gene expression vector Lenti-hTERT-Fth1-3FLAG-Puro was compared to constitutive CMV-driven expression and to the untransfected parental control in five tumour cell lines: A549, SKOV3, 293T, U2OS and HPDLF. In vitro, transfected cells were evaluated for FLAG-tagged protein expression, iron accumulation and transverse relaxation. In vivo, tumours transduced by lentiviral vector injection were imaged using T2*WI. Changes in tumour signal intensity were validated by histology. Only telomerase positive tumour cells expressed FLAG-tagged Fth and displayed an increase in R2* above the parental control, with a corresponding change in T2*WI. In addition, only telomerase positive tumours, transduced by injection of the reporter gene expression construct, exhibited a change in signal intensity on T2*WI. Tumour histology verified the expression of FLAG-tagged Fth and iron accumulation in telomerase positive tissue. Reporter gene expression for MRI, using the Fth reporter and the hTERT promoter, may be a useful strategy for the non-invasive diagnosis of many types of cancer. (orig.)

Iodine Tagging Velocimetry and Mechanism in the Hypersonic Near Wake of a MultiPurpose Crew Vehicle

Science.gov (United States)

Balla, R. Jeffrey

2013-01-01

This study demonstrates a new molecular tagging velocimetry (MTV) method for velocity measurements of high speed flow. It demonstrates offbody Iodine Tagging Velocimetry (ITV) in the hypersonic near wake of a MultiPurpose Crew Vehicle (MPCV) model. Experiments are performed in the NASA-Langley 31-inch Mach 10 air wind tunnel. A 0.5% I2 / N2 mixture is seeded on the leeward backshell of the model using a pressure tap. I2 laser-induced fluorescence is excited along a 5.5 mm line using an ArF excimer laser near 193 nm. Results indicate I2 absorbs at least 2 photons to produce iodine ions and electrons. These recombine as the tagged region is displaced downstream to produce I (2P3/2) whose emission is monitored at 206 nm. Results at P0 = 2.41 MPa (350 psi), T0 = 990K, and 10 micro-sec transit times produce velocities from 630-820 m/sec across the I2 seeded jet at a distance of 38.2 mm (25.5 jet diameters) downstream from the jet orifice. Maximum wake jet velocities near the shear layer are 59% of freestream velocity.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

Method and apparatus for manufacturing gas tags

International Nuclear Information System (INIS)

Gross, K.C.; Laug, M.T.

1996-01-01

For use in the manufacture of gas tags employed in a gas tagging failure detection system for a nuclear reactor, a plurality of commercial feed gases each having a respective noble gas isotopic composition are blended under computer control to provide various tag gas mixtures having selected isotopic ratios which are optimized for specified defined conditions such as cost. Using a new approach employing a discrete variable structure rather than the known continuous-variable optimization problem, the computer controlled gas tag manufacturing process employs an analytical formalism from condensed matter physics known as stochastic relaxation, which is a special case of simulated annealing, for input feed gas selection. For a tag blending process involving M tag isotopes with N distinct feed gas mixtures commercially available from an enriched gas supplier, the manufacturing process calculates the cost difference between multiple combinations and specifies gas mixtures which approach the optimum defined conditions. The manufacturing process is then used to control tag blending apparatus incorporating tag gas canisters connected by stainless-steel tubing with computer controlled valves, with the canisters automatically filled with metered quantities of the required feed gases. 4 figs

Red flags to screen for malignancy and fracture in patients with low back pain: systematic review

DEFF Research Database (Denmark)

Downie, A.; Williams, C.M.; Henschke, N.

2013-01-01

Objective: To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. Design: Systematic review. Data sources: Medline, OldMedline, Embase, and CINAHL from......-test probability for detection of spinal malignancy was history of malignancy (33%, 22% to 46%). Conclusions: While several red flags are endorsed in guidelines to screen for fracture or malignancy, only a small subset of these have evidence that they are indeed informative. These findings suggest a need...

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.

Worker flag. Independent Electrical Policy

International Nuclear Information System (INIS)

Bahen, D.

2000-01-01

This work analyses the initiative of privatization of the Mexican Electric Industry and also it is showed the incoherence of this mistaken proposal. Along the same line is analysed tthe situation of the National Electric Sector and the working process for the distinct types of electric generation just as the syndical and labor situations. In consequence it is proposed an Independent Electrical Policy, which includes the integration of the Nationalized Electric Industry, the syndical union and the Unique Collective Contract. The purpose of this work is to contribute to the success of the electrical and nuclear struggle always maintaining in rising position the red flag of the proletariat. The author considers that the privatization means mercantilization of the human necessities. The privatization is not inevitable at condition of to exercise consequently the political actions necessary through alternatives includes: the worker control of production, research, and the National Electric strike. (Author)

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.

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

A suite of standard post-tagging evaluation metrics can help assess tag retention for field-based fish telemetry research

Science.gov (United States)

Gerber, Kayla M.; Mather, Martha E.; Smith, Joseph M.

2017-01-01

Telemetry can inform many scientific and research questions if a context exists for integrating individual studies into the larger body of literature. Creating cumulative distributions of post-tagging evaluation metrics would allow individual researchers to relate their telemetry data to other studies. Widespread reporting of standard metrics is a precursor to the calculation of benchmarks for these distributions (e.g., mean, SD, 95% CI). Here we illustrate five types of standard post-tagging evaluation metrics using acoustically tagged Blue Catfish (Ictalurus furcatus) released into a Kansas reservoir. These metrics included: (1) percent of tagged fish detected overall, (2) percent of tagged fish detected daily using abacus plot data, (3) average number of (and percent of available) receiver sites visited, (4) date of last movement between receiver sites (and percent of tagged fish moving during that time period), and (5) number (and percent) of fish that egressed through exit gates. These metrics were calculated for one to three time periods: early (of the study (5 months). Over three-quarters of our tagged fish were detected early (85%) and at the end (85%) of the study. Using abacus plot data, all tagged fish (100%) were detected at least one day and 96% were detected for > 5 days early in the study. On average, tagged Blue Catfish visited 9 (50%) and 13 (72%) of 18 within-reservoir receivers early and at the end of the study, respectively. At the end of the study, 73% of all tagged fish were detected moving between receivers. Creating statistical benchmarks for individual metrics can provide useful reference points. In addition, combining multiple metrics can inform ecology and research design. Consequently, individual researchers and the field of telemetry research can benefit from widespread, detailed, and standard reporting of post-tagging detection metrics.

Inclusive Flavour Tagging Algorithm

International Nuclear Information System (INIS)

Likhomanenko, Tatiana; Derkach, Denis; Rogozhnikov, Alex

2016-01-01

Identifying the flavour of neutral B mesons production is one of the most important components needed in the study of time-dependent CP violation. The harsh environment of the Large Hadron Collider makes it particularly hard to succeed in this task. We present an inclusive flavour-tagging algorithm as an upgrade of the algorithms currently used by the LHCb experiment. Specifically, a probabilistic model which efficiently combines information from reconstructed vertices and tracks using machine learning is proposed. The algorithm does not use information about underlying physics process. It reduces the dependence on the performance of lower level identification capacities and thus increases the overall performance. The proposed inclusive flavour-tagging algorithm is applicable to tag the flavour of B mesons in any proton-proton experiment. (paper)

Red flags in children with chronic abdominal pain and Crohn's disease-a single center experience.

Science.gov (United States)

El-Chammas, Khalil; Majeskie, Angela; Simpson, Pippa; Sood, Manu; Miranda, Adrian

2013-04-01

To compare history and symptoms at initial presentation of patients with chronic abdominal pain (CAP) and Crohn's disease (CD). Red flags are used to help determine which patients with CAP are likely to have an underlying disease such as CD. However, red flags have not been validated and pediatric studies are lacking. Patients seen in the outpatient Pediatric Gastroenterology Clinic at Children's Hospital of Wisconsin between 2005 and 2008 prospectively completed a demographic, history, and symptom questionnaire. Patients with abdominal pain for at least 1 month and no evidence of organic disease were compared with patients diagnosed with CD confirmed by mucosal biopsies. Data were collected on 606 patients (128 with CD and 478 with functional gastrointestinal disorders). Patients with functional gastrointestinal disorders had more stressors (P pain were no different between groups. Anemia, hematochezia, and weight loss were most predictive of CD (cumulative sensitivity of 94%). The presence of anemia, hematochezia, and weight loss help identify patients with CAP who require further work-up and referral to a pediatric gastroenterologist. Furthermore, waking from sleep or joint pain occurred similarly between groups and should not be considered as "red flags." Copyright © 2013. Published by Mosby, Inc.

Micro-battery Development for Juvenile Salmon Acoustic Telemetry System Applications

Science.gov (United States)

Chen, Honghao; Cartmell, Samuel; Wang, Qiang; Lozano, Terence; Deng, Z. Daniel; Li, Huidong; Chen, Xilin; Yuan, Yong; Gross, Mark E.; Carlson, Thomas J.; Xiao, Jie

2014-01-01

The Endangered Species Act requires actions that improve the passage and survival rates for migrating salmonoids and other fish species that sustain injury and mortality when passing through hydroelectric dams. To develop a low-cost revolutionary acoustic transmitter that may be injected instead of surgically implanted into the fish, one major challenge that needs to be addressed is the micro-battery power source. This work focuses on the design and fabrication of micro-batteries for injectable fish tags. High pulse current and required service life have both been achieved as well as doubling the gravimetric energy density of the battery. The newly designed micro-batteries have intrinsically low impedance, leading to significantly improved electrochemical performances at low temperatures as compared with commercial SR416 batteries. Successful field trial by using the micro-battery powered transmitters injected into fish has been demonstrated, providing an exemplary model of transferring fundamental research into practical devices with controlled qualities.

Surface Acoustic Wave Tag-Based Coherence Multiplexing

Science.gov (United States)

Youngquist, Robert C. (Inventor); Malocha, Donald (Inventor); Saldanha, Nancy (Inventor)

2016-01-01

A surface acoustic wave (SAW)-based coherence multiplexing system includes SAW tags each including a SAW transducer, a first SAW reflector positioned a first distance from the SAW transducer and a second SAW reflector positioned a second distance from the SAW transducer. A transceiver including a wireless transmitter has a signal source providing a source signal and circuitry for transmitting interrogation pulses including a first and a second interrogation pulse toward the SAW tags, and a wireless receiver for receiving and processing response signals from the SAW tags. The receiver receives scrambled signals including a convolution of the wideband interrogation pulses with response signals from the SAW tags and includes a computing device which implements an algorithm that correlates the interrogation pulses or the source signal before transmitting against the scrambled signals to generate tag responses for each of the SAW tags.

Micro-PIXE studies of char populations in northern Canada

International Nuclear Information System (INIS)

Campbell, J.L.; Babaluk, J.A.; Halden, N.M.; Kristofferson, A.H.; Maxwell, J.A.; Mejia, S.R.; Reist, J.D.; Teesdale, W.J.

1999-01-01

Micro-PIXE analysis of trace elements in otoliths has been used as the basis for several projects on char, a fish that is important for aboriginal subsistence fisheries in Arctic Canada. Life-history patterns were originally inferred from micro-PIXE line scans of Sr distribution. These were confirmed by superposition of Sr distribution patterns on optical images of otoliths of tag-recaptured fish. Char from various populations showed differentiation in otolith primordial Sr concentration; this enables us to differentiate biological stocks and, it is hoped, eventually to assign individuals from mixed-stock fisheries to their stock of origin. Zn oscillations also correlate with annular structure and provide additional temporally constrained information on fish habitat and behaviour

Group Discovery in a CollaborativeTagging System

OpenAIRE

Chen, Zijian

2007-01-01

Tagging refers to the process of adding metadata to describe things by usingone or several words. Collaborative Tagging systems, which allow different webusers to tag web content like weblogs, pictures, and bookmarks and so on, haverecently gained great popularity on internet. There are already a greatvariety of debates on internet of the advantages and disadvantages ofcollaborative tagging systems from the aspect of information organizing. Inthis paper, we primarily focus on a collaborative ...

Constructing and Validating the Foreign Language Attitudes and Goals Survey (FLAGS)

Science.gov (United States)

Cid, Eva; Granena, Gisela; Tragant, Elsa

2009-01-01

The present study describes the process that was followed in the construction and validation of the foreign language attitudes and goals survey (FLAGS), a new questionnaire based on qualitative data from Tragant and Munoz [Tragant, Munoz, C., 2000. "La motivacion y su relacion con la edad en un contexto escolar de aprendizaje de una lengua…

Analysis of tag-position bias in MPSS technology

Directory of Open Access Journals (Sweden)

Rattray Magnus

2006-04-01

Full Text Available Abstract Background Massively Parallel Signature Sequencing (MPSS technology was recently developed as a high-throughput technology for measuring the concentration of mRNA transcripts in a sample. It has previously been observed that the position of the signature tag in a transcript (distance from 3' end can affect the measurement, but this effect has not been studied in detail. Results We quantify the effect of tag-position bias in Classic and Signature MPSS technology using published data from Arabidopsis, rice and human. We investigate the relationship between measured concentration and tag-position using nonlinear regression methods. The observed relationship is shown to be broadly consistent across different data sets. We find that there exist different and significant biases in both Classic and Signature MPSS data. For Classic MPSS data, genes with tag-position in the middle-range have highest measured abundance on average while genes with tag-position in the high-range, far from the 3' end, show a significant decrease. For Signature MPSS data, high-range tag-position genes tend to have a flatter relationship between tag-position and measured abundance. Thus, our results confirm that the Signature MPSS method fixes a substantial problem with the Classic MPSS method. For both Classic and Signature MPSS data there is a positive correlation between measured abundance and tag-position for low-range tag-position genes. Compared with the effects of mRNA length and number of exons, tag-position bias seems to be more significant in Arabadopsis. The tag-position bias is reflected both in the measured abundance of genes with a significant tag count and in the proportion of unexpressed genes identified. Conclusion Tag-position bias should be taken into consideration when measuring mRNA transcript abundance using MPSS technology, both in Classic and Signature MPSS methods.

A CERN flag is set to wave up in the Himalayas

CERN Multimedia

Roberto Cantoni

2010-01-01

On 18 October, Hubert Reymond, from the Industrial Controls and Engineering group of the EN Department, will be leaving to Nepal with a CERN flag in his backpack. He will place it at the highest point of his trek across the Annapurna mountains in the Himalayas, Thorong La pass, at 5,416 m above sea level.   A view of the Annapurna mountains (source: www.flickr.com/minutesalone) “Is there any official CERN flag I can carry with me during my trek through Nepal?” Some days ago, the Press Office was confronted with this unusual (but see box) question from Hubert Reymond. From 18 October to 10 November, Reymond, who works as an industrial computing engineer in the EN Department, will be trekking across the 55 km-long Annapurna massif in the Himalayas, whose highest point lies at 8,091 m (making it the 10th-highest summit in the world). The area is well-known to trekkers from around the world, as it includes several world-class circuits, including the Annapurna circuit which Reym...

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.

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

Directory of Open Access Journals (Sweden)

Paul T Martin

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

Behavioral tagging of extinction learning.

Science.gov (United States)

de Carvalho Myskiw, Jociane; Benetti, Fernando; Izquierdo, Iván

2013-01-15

Extinction of contextual fear in rats is enhanced by exposure to a novel environment at 1-2 h before or 1 h after extinction training. This effect is antagonized by administration of protein synthesis inhibitors anisomycin and rapamycin into the hippocampus, but not into the amygdala, immediately after either novelty or extinction training, as well as by the gene expression blocker 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole administered after novelty training, but not after extinction training. Thus, this effect can be attributed to a mechanism similar to synaptic tagging, through which long-term potentiation can be enhanced by other long-term potentiations or by exposure to a novel environment in a protein synthesis-dependent fashion. Extinction learning produces a tag at the appropriate synapses, whereas novelty learning causes the synthesis of plasticity-related proteins that are captured by the tag, strengthening the synapses that generated this tag.

Annotating images by harnessing worldwide user-tagged photos

NARCIS (Netherlands)

Li, X.; Snoek, C.G.M.; Worring, M.

2009-01-01

Automatic image tagging is important yet challenging due to the semantic gap and the lack of learning examples to model a tag's visual diversity. Meanwhile, social user tagging is creating rich multimedia content on the Web. In this paper, we propose to combine the two tagging approaches in a

Evaluation of visible implant elastomer tags in zebrafish (Danio rerio

Directory of Open Access Journals (Sweden)

Claudia Hohn

2013-11-01

The use of the visible implant elastomer (VIE tagging system in zebrafish (Danio rerio was examined. Two tag orientations (horizontal and vertical at the dorsal fin base were tested for tag retention, tag fragmentation and whether VIE tags affected growth and survival of juvenile zebrafish (1–4 month post hatch. Six tag locations (abdomen, anal fin base, caudal peduncle, dorsal fin base, pectoral fin base, isthmus and 5 tag colors (yellow, red, pink, orange, blue were evaluated for ease of VIE tag application and tag visibility in adult zebrafish. Long-term retention (1 year and multiple tagging sites (right and left of dorsal fin and pectoral fin base were examined in adult zebrafish. Lastly, survival of recombination activation gene 1−/− (rag1−/− zebrafish was evaluated after VIE tagging. The best tag location was the dorsal fin base, and the most visible tag color was pink. Growth rate of juvenile zebrafish was not affected by VIE tagging. Horizontal tagging is recommended in early stages of fish growth (1–2 months post hatch. VIE tags were retained for 1 year and tagging did not interfere with long-term growth and survival. There was no mortality associated with VIE tagging in rag1−/− zebrafish. The VIE tagging system is highly suitable for small-sized zebrafish. When familiar with the procedure, 120 adult zebrafish can be tagged in one hour. It does not increase mortality in adult zebrafish or interfere with growth in juvenile or adult zebrafish.

Peptide-tagged proteins in aqueous two-phase systems

OpenAIRE

Nilsson, Anna

2002-01-01

This thesis deals with proteins containing peptide tags for improved partitioning in aqueous two-phase systems. Qualitatively the peptide-tagged protein partitioning could be predicted from peptide data, i.e. partitioning trends found for peptides were also found for the peptide-tagged proteins. However, full effect of the tag as expected from peptide partitioning was not found in the tagged protein. When alkyl-ethylene oxide surfactant was included in a two-polymer system, almost full effect...

Study of mast cell count in skin tags

Directory of Open Access Journals (Sweden)

Zaher Hesham

2007-01-01

Full Text Available Background: Skin tags or acrochordons are common tumors of middle-aged and elderly subjects. They consist of loose fibrous tissue and occur mainly on the neck and major flexures as small, soft, pedunculated protrusions. Objectives: The aim was to compare the mast cells count in skin tags to adjacent normal skin in diabetic and nondiabetic participants in an attempt to elucidate the possible role of mast cells in the pathogenesis of skin tags. Participants and Methods: Thirty participants with skin tags were divided into group I (15 nondiabetic participants and group II (15 diabetic participants. Three biopsies were obtained from each participant: a large skin tag, a small skin tag and adjacent normal skin. Mast cell count from all the obtained sections was carried out, and the mast cell density was expressed as the average mast cell count/high power field (HPF. Results: A statistically significant increase in mast cells count in skin tags in comparison to normal skin was detected in group I and group II. There was no statistically significant difference between mast cell counts in skin tags of both the groups. Conclusion: Both the mast cell mediators and hyperinsulinemia are capable of inducing fibroblast proliferation and epidermal hyperplasia that are the main pathologic abnormalities seen in all types of skin tags. However, the presence of mast cells in all examined skin tags regardless of diabetes and obesity may point to the possible crucial role of mast cells in the etiogenesis of skin tags through its interaction with fibroblasts and keratinocytes.

Tags in Domain-Specific Sites - New Information?

DEFF Research Database (Denmark)

Steinhauer, Jeremy; Delcambre, Lois M.L.; Maier, David

2011-01-01

If researchers use tags in retrieval applications they might assume, implicitly, that tags represent novel information, e.g., when they attribute performance improvement in their retrieval algorithm(s) to the use of tags. In this work, we investigate whether this assumption is true. We focus on t...

A suite of standard post-tagging evaluation metrics can help assess tag retention for field-based fish telemetry research

Science.gov (United States)

Gerber, Kayla M.; Mather, Martha E.; Smith, Joseph M.

2017-01-01

Telemetry can inform many scientific and research questions if a context exists for integrating individual studies into the larger body of literature. Creating cumulative distributions of post-tagging evaluation metrics would allow individual researchers to relate their telemetry data to other studies. Widespread reporting of standard metrics is a precursor to the calculation of benchmarks for these distributions (e.g., mean, SD, 95% CI). Here we illustrate five types of standard post-tagging evaluation metrics using acoustically tagged Blue Catfish (Ictalurus furcatus) released into a Kansas reservoir. These metrics included: (1) percent of tagged fish detected overall, (2) percent of tagged fish detected daily using abacus plot data, (3) average number of (and percent of available) receiver sites visited, (4) date of last movement between receiver sites (and percent of tagged fish moving during that time period), and (5) number (and percent) of fish that egressed through exit gates. These metrics were calculated for one to three time periods: early ( 5 days early in the study. On average, tagged Blue Catfish visited 9 (50%) and 13 (72%) of 18 within-reservoir receivers early and at the end of the study, respectively. At the end of the study, 73% of all tagged fish were detected moving between receivers. Creating statistical benchmarks for individual metrics can provide useful reference points. In addition, combining multiple metrics can inform ecology and research design. Consequently, individual researchers and the field of telemetry research can benefit from widespread, detailed, and standard reporting of post-tagging detection metrics.

Phloem Transport Of Arsenic Species From Flag Leaf To Grain During Grain Filling

Science.gov (United States)

Strategies to reduce arsenic (As) in rice grain, below concentrations that represent a serious human health concern, require that the mechanisms of As accumulation within grain be established. Therefore, retranslocation of As species from flag leaves into filling rice grain was ...

B-tagging in CMS at LHC

CERN Document Server

Cucciarelli, S

2003-01-01

This report provides a review of the main algorithms for offline inclusive b-tagging developed within the CMS community. Two b-tag algorithms, one based on the impact parameter measurement and the other based on the secondary vertices are discussed. The performance of these algorithms are presented for several jet transverse energies and pseudorapidity regions. An additional decay length based b-tag is also described and its preliminary performance is presented. (4 refs) .

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population

International Nuclear Information System (INIS)

Neri, Emanuele; Mantarro, Annalisa; Faggioni, Lorenzo; Scalise, Paola; Bemi, Pietro; Pancrazi, Francesca; D’Ippolito, Giuseppe; Bartolozzi, Carlo

2015-01-01

Highlights: • In the group receiving rectal tagging, mean per-polyp sensitivity, specificity were 96.1% and 95.3%; while in the group receiving oral tagging, mean per-polyp sensitivity, specificity were 89.4% and 95.8%. The difference between the two groups was not statistically significant (p = 0.549). • Rectal tagging can be an effective alternative to oral tagging. • Rectal tagging allowed greater patient acceptance and lower overall examination time. - Abstract: Purpose: To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. Materials and methods: Six-hundred asymptomatic subjects (male:female = 270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1 = poor, 2 = adequate, 3 = excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1 = poor, 2 = fair, 3 = average, 4 = good, 5 = excellent). Results: Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI 95% 85.4 ÷ 99.3%) vs 89.4% (CI 95% 65.4 ÷ 98.1%), 95.3% (CI 95% 90.7 ÷ 97.8%) vs 95.8% (CI 95% 87.6 ÷ 98.9%), 86.0% (CI 95% 73.6 ÷ 93.3) vs 85.0% (CI 95% 61.1 ÷ 96.0%), and 98.8% (CI 95% 95.3 ÷ 99.8%) vs 97.2% (CI 95% 89

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population

Energy Technology Data Exchange (ETDEWEB)

Neri, Emanuele, E-mail: emanuele.neri@med.unipi.it [Diagnostic and Interventional Radiology – Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa (Italy); Mantarro, Annalisa; Faggioni, Lorenzo; Scalise, Paola; Bemi, Pietro; Pancrazi, Francesca [Diagnostic and Interventional Radiology – Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa (Italy); D’Ippolito, Giuseppe [Federal University of São Paulo – Sena Madureira 1500 – Vila Mariana, UNIFESP, São Paulo, SP (Brazil); Bartolozzi, Carlo [Diagnostic and Interventional Radiology – Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa (Italy)

2015-09-15

Highlights: • In the group receiving rectal tagging, mean per-polyp sensitivity, specificity were 96.1% and 95.3%; while in the group receiving oral tagging, mean per-polyp sensitivity, specificity were 89.4% and 95.8%. The difference between the two groups was not statistically significant (p = 0.549). • Rectal tagging can be an effective alternative to oral tagging. • Rectal tagging allowed greater patient acceptance and lower overall examination time. - Abstract: Purpose: To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. Materials and methods: Six-hundred asymptomatic subjects (male:female = 270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1 = poor, 2 = adequate, 3 = excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1 = poor, 2 = fair, 3 = average, 4 = good, 5 = excellent). Results: Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI{sub 95%} 85.4 ÷ 99.3%) vs 89.4% (CI{sub 95%} 65.4 ÷ 98.1%), 95.3% (CI{sub 95%} 90.7 ÷ 97.8%) vs 95.8% (CI{sub 95%} 87.6 ÷ 98.9%), 86.0% (CI{sub 95%} 73.6 ÷ 93.3) vs 85.0% (CI{sub 95%} 61.1 ÷ 96.0%), and 98.8% (CI{sub 95

Validation of ultrasonography for non-invasive assessment of diaphragm function in muscular dystrophy.

Science.gov (United States)

Whitehead, Nicholas P; Bible, Kenneth L; Kim, Min Jeong; Odom, Guy L; Adams, Marvin E; Froehner, Stanley C

2016-12-15

strongly with ex vivo specific force. We then investigated the time course of diaphragm amplitude changes following administration of an adeno-associated viral vector expressing Flag-micro-dystrophin (AAV-μDys) to young adult mdx mice. Diaphragm amplitude peaked 4 weeks after AAV-μDys administration, and was 26% greater than control mdx mice at this time. This value decreased slightly to 21% above mdx controls after 12 weeks of treatment. Importantly, diaphragm amplitude again correlated strongly with ex vivo specific force. Also, diaphragm amplitude and specific force negatively correlated with fibrosis levels in the muscle. Together, our results validate diaphragm ultrasonography as a reliable technique for assessing time-dependent changes in dystrophic diaphragm function in vivo, and for evaluating potential therapies for DMD. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

First hoisting of the Portuguese flag at CERN

CERN Multimedia

Unknown, Unknown

1986-01-01

First hoisting of the Portuguese flag at CERN, following the country's membership. Photo taken on January 22 (or 23), 1986. From left to right: António Costa Lobo (Portugal's ambassador to the UN in Geneva), Gaspar Barreira, Karin Wall (José Mariano Gago's wife), José Mariano Gago (Portugal's JNICT president), Catarina Wall Gago (José Mariano Gago's daughter), João Varela, Herwig Schopper (CERN's Director-General), Eduardo Arantes e Oliveira (Portugal's Secretary of State for Science), , Margarida Nesbitt Rebelo, , Mário Pimenta, , Gustavo Castelo Branco, João Seixas, Sérgio Ramos, and Peter Sonderegger.

Diagnosis and management of transthyretin familial amyloid polyneuropathy in Japan: red-flag symptom clusters and treatment algorithm.

Science.gov (United States)

Sekijima, Yoshiki; Ueda, Mitsuharu; Koike, Haruki; Misawa, Sonoko; Ishii, Tomonori; Ando, Yukio

2018-01-17

Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare systemic disorder predominantly characterized by irreversible, progressive, and persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, which form amyloid fibrils that deposit in peripheral nerves and various organs, giving rise to peripheral and autonomic neuropathy and several non-disease specific symptoms.Phenotypic and genetic variability and non-disease-specific symptoms often delay diagnosis and lead to misdiagnosis. Red-flag symptom clusters simplify diagnosis globally. However, in Japan, types of TTR variants, age of onset, penetrance, and clinical symptoms of Val30Met are more varied than in other countries. Hence, development of a Japan-specific red-flag symptom cluster is warranted. Presence of progressive peripheral sensory-motor polyneuropathy and ≥1 red-flag sign/symptom (e.g. family history, autonomic dysfunction, cardiac involvement, carpal tunnel syndrome, gastrointestinal disturbances, unexplained weight loss, and immunotherapy resistance) suggests ATTR-FAP. Outside of Japan, pharmacotherapeutic options are first-line therapy. However, because of positive outcomes (better life expectancy and higher survival rates) with living donor transplant in Japan, liver transplantation remains first-line treatment, necessitating a Japan-specific treatment algorithm.Herein, we present a consolidated review of the ATTR-FAP Val30Met landscape in Japan and summarize findings from a medical advisory board meeting held in Tokyo on 18th August 2016, at which a Japan-specific ATTR-FAP red-flag symptom cluster and treatment algorithm was developed. Beside liver transplantation, a TTR-stabilizing agent (e.g. tafamidis) is a treatment option. Early

An Extended-Tag-Induced Matrix Factorization Technique for Recommender Systems

Directory of Open Access Journals (Sweden)

Huirui Han

2018-06-01

Full Text Available Social tag information has been used by recommender systems to handle the problem of data sparsity. Recently, the relationships between users/items and tags are considered by most tag-induced recommendation methods. However, sparse tag information is challenging to most existing methods. In this paper, we propose an Extended-Tag-Induced Matrix Factorization technique for recommender systems, which exploits correlations among tags derived by co-occurrence of tags to improve the performance of recommender systems, even in the case of sparse tag information. The proposed method integrates coupled similarity between tags, which is calculated by the co-occurrences of tags in the same items, to extend each item’s tags. Finally, item similarity based on extended tags is utilized as an item relationship regularization term to constrain the process of matrix factorization. MovieLens dataset and Book-Crossing dataset are adopted to evaluate the performance of the proposed algorithm. The results of experiments show that the proposed method can alleviate the impact of tag sparsity and improve the performance of recommender systems.

Optimization of mNeonGreen for Homo sapiens increases its fluorescent intensity in mammalian cells.

Science.gov (United States)

Tanida-Miyake, Emiko; Koike, Masato; Uchiyama, Yasuo; Tanida, Isei

2018-01-01

Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter. The resultant plasmid was introduced into HEK293 cells. The fluorescent intensity of humanized mNeonGreen was about 1.4-fold higher than that of the original mNeonGreen. The humanized mNeonGreen with a mitochondria-targeting signal showed mitochondrial distribution of mNeonGreen. We further generated an expression vector of humanized mNeonGreen with 3xFLAG tags at its carboxyl terminus as these tags are useful for immunological analyses. The 3xFLAG-tagged mNeonGreen was recognized well with an anti-FLAG-M2 antibody. These plasmids for the expression of humanized mNeonGreen and mNeonGreen-3xFLAG are useful tools for biological studies in mammalian cells using mNeonGreen.

Graph based techniques for tag cloud generation

DEFF Research Database (Denmark)

Leginus, Martin; Dolog, Peter; Lage, Ricardo Gomes

2013-01-01

Tag cloud is one of the navigation aids for exploring documents. Tag cloud also link documents through the user defined terms. We explore various graph based techniques to improve the tag cloud generation. Moreover, we introduce relevance measures based on underlying data such as ratings...... or citation counts for improved measurement of relevance of tag clouds. We show, that on the given data sets, our approach outperforms the state of the art baseline methods with respect to such relevance by 41 % on Movielens dataset and by 11 % on Bibsonomy data set....

Flavour Tagging developments within the LHCb experiment

CERN Document Server

Grabalosa, Marc

Flavour Tagging at the LHCb experiment is a fundamental tool for the measurement of B oscillations and the study of CP violation. This document explains the development of different tagging techniques and the different strategies used to combine them to determine the flavour of the B meson as precisely as possible. The response of the tagging algorithms also needs to be optimized and calibrated. Both procedures are described using the available LHCb datasets corresponding to various integrated luminosities. First results on the tagging performances are shown for different control channels and physics measurements.

A Personalized Tag-Based Recommendation in Social Web Systems

DEFF Research Database (Denmark)

Durao, Frederico; Dolog, Peter

2009-01-01

-based recommender system which suggests similar Web pages based on the similarity of their tags from a Web 2.0 tagging application. The proposed approach extends the basic similarity calculus with external factors such as tag popularity, tag representativeness and the affinity between user and tag. In order...... to study and evaluate the recommender system, we have conducted an experiment involving 38 people from 12 countries using data from Del.icio.us , a social bookmarking web system on which users can share their personal bookmarks......Tagging activity has been recently identified as a potential source of knowledge about personal interests, preferences, goals, and other attributes known from user models. Tags themselves can be therefore used for finding personalized recommendations of items. In this paper, we present a tag...

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

Directory of Open Access Journals (Sweden)

Emma Rybalka

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

Sentiment topic mining based on comment tags

Science.gov (United States)

Zhang, Daohai; Liu, Xue; Li, Juan; Fan, Mingyue

2018-03-01

With the development of e-commerce, various comments based on tags are generated, how to extract valuable information from these comment tags has become an important content of business management decisions. This study takes HUAWEI mobile phone tags as an example using the sentiment analysis and topic LDA mining method. The first step is data preprocessing and classification of comment tag topic mining. And then make the sentiment classification for comment tags. Finally, mine the comments again and analyze the emotional theme distribution under different sentiment classification. The results show that HUAWEI mobile phone has a good user experience in terms of fluency, cost performance, appearance, etc. Meanwhile, it should pay more attention to independent research and development, product design and development. In addition, battery and speed performance should be enhanced.

Soap films burst like flapping flags.

Science.gov (United States)

Lhuissier, Henri; Villermaux, Emmanuel

2009-07-31

When punctured, a flat soap film bursts by opening a hole driven by liquid surface tension. The hole rim does not, however, remain smooth but soon develops indentations at the tip of which ligaments form, ultimately breaking and leaving the initially connex film into a mist of disjointed drops. We report on original observations showing that these indentations result from a flaglike instability between the film and the surrounding atmosphere inducing an oscillatory motion out of its plane. Just like a flag edge flaps in the wind, the film is successively accelerated on both sides perpendicularly to its plane, inducing film thickness modulations and centrifuging liquid ligaments that finally pinch off to form the observed spray. This effect exemplifies how the dynamics of fragile objects such as thin liquid films is sensitive to their embedding medium.

The design and analysis of salmonid tagging studies in the Columbia Basin. Volume 2: Estimating salmonid survival with combined PIT-CWT tagging. Technical report

International Nuclear Information System (INIS)

Newman, K.

1997-06-01

Passive Integrated Transponder (PIT) tags and Coded Wire Tags (CWTs) in combination can provide information about salmonid survival that single tag releases may not. The release and recapture protocol affects which survival and recapture rates can be estimated and the precision of the estimates. For the particular case of Columbia river salmonids tagged with both PIT tags and CWTs, three different release and recapture protocols were evaluated. This report addresses the need to study the fate of salmon smolt in-river and their subsequent return as adults. Double-tagging procedures are investigated where PIT-tags would be used to provide in-river survival data during smolt outmigrations and coded-wire tags (CWT) used to provide adult return information. This report provides statistical models for the analysis of the joint data as well as recommendations on optimal tagging studies. Study costs and stress on smolt can be reduced by only PIT-tagging a subset of all the fish coded-wire-tagged, while retaining the information content and sampling precision

A hypergraph model of social tagging networks

International Nuclear Information System (INIS)

Zhang, Zi-Ke; Liu, Chuang

2010-01-01

The past few years have witnessed the great success of a new family of paradigms, so-called folksonomy, which allows users to freely associate tags with resources and efficiently manage them. In order to uncover the underlying structures and user behaviors in folksonomy, in this paper, we propose an evolutionary hypergraph model for explaining the emerging statistical properties. The present model introduces a novel mechanism that can not only assign tags to resources, but also retrieve resources via collaborative tags. We then compare the model with a real-world data set: Del.icio.us. Indeed, the present model shows considerable agreement with the empirical data in the following aspects: power-law hyperdegree distributions, negative correlation between clustering coefficients and hyperdegrees, and small average distances. Furthermore, the model indicates that most tagging behaviors are motivated by labeling tags on resources, and the tag plays a significant role in effectively retrieving interesting resources and making acquaintances with congenial friends. The proposed model may shed some light on the in-depth understanding of the structure and function of folksonomy

Associated Particle Tagging (APT) in Magnetic Spectrometers

Energy Technology Data Exchange (ETDEWEB)

Jordan, David V.; Baciak, James E.; Stave, Sean C.; Chichester, David; Dale, Daniel; Kim, Yujong; Harmon, Frank

2012-10-16

Summary In Brief The Associated Particle Tagging (APT) project, a collaboration of Pacific Northwest National Laboratory (PNNL), Idaho National Laboratory (INL) and the Idaho State University (ISU)/Idaho Accelerator Center (IAC), has completed an exploratory study to assess the role of magnetic spectrometers as the linchpin technology in next-generation tagged-neutron and tagged-photon active interrogation (AI). The computational study considered two principle concepts: (1) the application of a solenoidal alpha-particle spectrometer to a next-generation, large-emittance neutron generator for use in the associated particle imaging technique, and (2) the application of tagged photon beams to the detection of fissile material via active interrogation. In both cases, a magnetic spectrometer momentum-analyzes charged particles (in the neutron case, alpha particles accompanying neutron generation in the D-T reaction; in the tagged photon case, post-bremsstrahlung electrons) to define kinematic properties of the relevant neutral interrogation probe particle (i.e. neutron or photon). The main conclusions of the study can be briefly summarized as follows: Neutron generator: • For the solenoidal spectrometer concept, magnetic field strengths of order 1 Tesla or greater are required to keep the transverse size of the spectrometer smaller than 1 meter. The notional magnetic spectrometer design evaluated in this feasibility study uses a 5-T magnetic field and a borehole radius of 18 cm. • The design shows a potential for 4.5 Sr tagged neutron solid angle, a factor of 4.5 larger than achievable with current API neutron-generator designs. • The potential angular resolution for such a tagged neutron beam can be less than 0.5o for modest Si-detector position resolution (3 mm). Further improvement in angular resolution can be made by using Si-detectors with better position resolution. • The report documents several features of a notional generator design incorporating the

Comparison of Simultaneous PIV and Hydroxyl Tagging Velocimetry in Low Velocity Flows

Science.gov (United States)

Andre, Matthieu A.; Bardet, Philippe M.; Burns, Ross A.; Danehy, Paul M.

2016-01-01

Hydroxyl tagging velocimetry (HTV) is a molecular tagging velocimetry (MTV) technique that relies on the photo- dissociation of water vapor into OH radicals and their subsequent tracking using laser-induced fluorescence. At ambient temperature in air, the OH species lifetime is about 50 micro-s. The feasibility of using HTV for probing low- speed flows (a few m/s) is investigated by using an inert, heated gas as a means to increase the OH species lifetime. Unlike particle-based techniques, MTV does not suffer from tracer settling, which is particularly problematic at low speeds. Furthermore, the flow needs to be seeded with only a small mole fraction of water vapor, making it safer for both the user and facilities than other MTV techniques based on corrosive or toxic chemical tracers. HTV is demonstrated on a steam-seeded nitrogen jet at approximately 75 C in the laminar (Umean=3.31 m/s, Re=1,540), transitional (Umean=4.48 m/s, Re=2,039), and turbulent (Umean=6.91 m/s, Re=3,016) regimes at atmospheric pressure. The measured velocity profiles are compared with particle image velocimetry (PIV) measurements performed simultaneously with a second imager. Seeding for the PIV is achieved by introducing micron-sized water droplets into the flow with the steam; the same laser sheet is used for PIV and HTV to guarantee spatial and temporal overlap of the data. Optimizing each of these methods, however, requires conflicting operating conditions: higher temperatures benefit the HTV signals but reduce the available seed density for the PIV through evaporation. Nevertheless, data are found to agree within 10% for the instantaneous velocity profiles and within 5% for the mean profiles and demonstrate the feasibility of HTV for low-speed flows at moderate to high temperatures.

RFID Label Tag Design for Metallic Surface Environments

Directory of Open Access Journals (Sweden)

Ki Hwan Eom

2011-01-01

Full Text Available This paper describes a metal mount RFID tag that works reliably on metallic surfaces. The method proposes the use of commercial label type RFID tags with 2.5 mm thick Styrofoam103.7 with a relative permittivity of 1.03 attached on the back of the tag. In order to verify the performance of the proposed method, we performed experiments on an electric transformer supply chain system. The experimental results showed that the proposed tags can communicate with readers from a distance of 2 m. The recognition rates are comparable to those of commercial metallic mountable tags.

Pop-up Archival Transmitting (PAT) fish tag data

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The cooperative tagging center (CTC) began deploying electronic tags in 2002. To date over 300 tags have been deployed. The following species have been monitored:...

The Micro-Vertex-Detector for the P-bar ANDA experiment

International Nuclear Information System (INIS)

Zotti, Laura

2013-01-01

P-bar ANDA is a fixed target experiment that will be carried out at the future FAIR facility. P-bar ANDA will provide an excellent tool to address fundamental question in the field of hadronic physics, with a physic program that extends from the investigation of QCD (providing insight in the mechanisms of mass generation and confinement) to the test of fundamental symmetries. The Micro-Vertex-Detector located in the innermost part of the central tracking system will be composed by hybrid pixel and double-sided micro-strip silicon detectors. The Micro-Vertex-Detector will play an important role for the P-bar ANDA physics goals. The possibility to reconstruct the secondary vertices and the applicability of a precise D meson tagging is essential for the spectroscopy in the open charm sector and the charmonium mass region. To this aim the Micro-Vertex-Detector features a spatial resolution better than 100μm, a time resolution better than 20ns, a limited material budget, and a high data rate capability in a triggerless environment. An overview of the Micro-Vertex-Detector related to the physics goals will be presented.

W/Top/Higgs-tagging in ATLAS

CERN Document Server

Norjoharuddeen, Nurfikri; The ATLAS collaboration

2017-01-01

We present updates of W, Top and Higgs tagging studies with the ATLAS detector. The performance of 2 variable taggers, HEPTopTagger and shower deconstruction are compared in Monte Carlo simulations. To asses the modelling of the taggers’ performance, the tagging efficiencies are measured, with the full 2015+2016 dataset, in semi-leptonic top quark pair events and the background rejections are measured in dijet and photon+jet topologies. Recent developments in subjet reconstruction techniques for high transverse momentum Higgs->bb tagging are also presented.

Development of techniques for tagging precursor and essential chemicals

Energy Technology Data Exchange (ETDEWEB)

Swansiger, W.A.; Shepodd, T.J. [Sandia National Labs., Livermore, CA (United States); Phillips, M.L.F. [Sandia National Labs., Albuquerque, NM (United States)

1994-01-01

The ability to identify the manufacturers and distributors of chemicals seized in raids of illicit drug labs would be of great value in controlling the diversion of these chemicals. We developed a tagging scheme based on the addition of sub-ppM concentrations of various combinations of rare-earth elements to the target chemicals and evaluated a number of techniques for detecting the tags. We developed soluble tags for tagging liquids and selected Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) as the preferred detection technique. We developed insoluble tags for tagging solids and developed methods to analyze them and mix them into solid precursors. We have successfully demonstrated the tagging of several solvents and two of the precursor chemicals used in one of the most popular clandestine methamphetamine syntheses (ephedrine reacting with hydriodic acid/red phosphorus). The tagging scheme is capable of yielding tens of thousands of signatures (using holmium as an internal standard and up to 9 rare-earths at up to 3 concentrations yields 3{sup 9} {minus} 1 = 19,682 signatures) and is applicable to most of the chemicals on the precursor and essential chemicals list. In the concentrations employed, the tags are safe enough to be added to pharmaceuticals and cheap enough to tag tanker loads of chemicals.

HMSRP Hawaiian Monk Seal Tag Data

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains records for all tags applied to Hawaiian monk seals since 1981. These tags were applied by PSD personnel and cooperating scientists as part of...

Measuring and Predicting Tag Importance for Image Retrieval.

Science.gov (United States)

Li, Shangwen; Purushotham, Sanjay; Chen, Chen; Ren, Yuzhuo; Kuo, C-C Jay

2017-12-01

Textual data such as tags, sentence descriptions are combined with visual cues to reduce the semantic gap for image retrieval applications in today's Multimodal Image Retrieval (MIR) systems. However, all tags are treated as equally important in these systems, which may result in misalignment between visual and textual modalities during MIR training. This will further lead to degenerated retrieval performance at query time. To address this issue, we investigate the problem of tag importance prediction, where the goal is to automatically predict the tag importance and use it in image retrieval. To achieve this, we first propose a method to measure the relative importance of object and scene tags from image sentence descriptions. Using this as the ground truth, we present a tag importance prediction model to jointly exploit visual, semantic and context cues. The Structural Support Vector Machine (SSVM) formulation is adopted to ensure efficient training of the prediction model. Then, the Canonical Correlation Analysis (CCA) is employed to learn the relation between the image visual feature and tag importance to obtain robust retrieval performance. Experimental results on three real-world datasets show a significant performance improvement of the proposed MIR with Tag Importance Prediction (MIR/TIP) system over other MIR systems.

Strategies Used In Capture The Flag Events Contributing To Team Performance

Science.gov (United States)

2016-03-01

words) Capture-the-flag (CTF) exercises are useful pedagogical tools and have been employed, both formally and informally, by academic institutions...Much like their physical counterparts, cyber CTF exercises hold pedagogical value and are gaining wide popularity. Existing studies on CTF exercises...examined either how they benefit learning, or are best conducted. To our knowledge, no formal study has yet looked at the relationship between the

APPECT: An Approximate Backbone-Based Clustering Algorithm for Tags

DEFF Research Database (Denmark)

Zong, Yu; Xu, Guandong; Jin, Pin

2011-01-01

algorithm for Tags (APPECT). The main steps of APPECT are: (1) we execute the K-means algorithm on a tag similarity matrix for M times and collect a set of tag clustering results Z={C1,C2,…,Cm}; (2) we form the approximate backbone of Z by executing a greedy search; (3) we fix the approximate backbone...... as the initial tag clustering result and then assign the rest tags into the corresponding clusters based on the similarity. Experimental results on three real world datasets namely MedWorm, MovieLens and Dmoz demonstrate the effectiveness and the superiority of the proposed method against the traditional...... Agglomerative Clustering on tagging data, which possess the inherent drawbacks, such as the sensitivity of initialization. In this paper, we instead make use of the approximate backbone of tag clustering results to find out better tag clusters. In particular, we propose an APProximate backbonE-based Clustering...

Magnetic vector field tag and seal

Science.gov (United States)

Johnston, Roger G.; Garcia, Anthony R.

2004-08-31

One or more magnets are placed in a container (preferably on objects inside the container) and the magnetic field strength and vector direction are measured with a magnetometer from at least one location near the container to provide the container with a magnetic vector field tag and seal. The location(s) of the magnetometer relative to the container are also noted. If the position of any magnet inside the container changes, then the measured vector fields at the these locations also change, indicating that the tag has been removed, the seal has broken, and therefore that the container and objects inside may have been tampered with. A hollow wheel with magnets inside may also provide a similar magnetic vector field tag and seal. As the wheel turns, the magnets tumble randomly inside, removing the tag and breaking the seal.

Clone tag detection in distributed RFID systems

Science.gov (United States)

Kamaludin, Hazalila; Mahdin, Hairulnizam

2018-01-01

Although Radio Frequency Identification (RFID) is poised to displace barcodes, security vulnerabilities pose serious challenges for global adoption of the RFID technology. Specifically, RFID tags are prone to basic cloning and counterfeiting security attacks. A successful cloning of the RFID tags in many commercial applications can lead to many serious problems such as financial losses, brand damage, safety and health of the public. With many industries such as pharmaceutical and businesses deploying RFID technology with a variety of products, it is important to tackle RFID tag cloning problem and improve the resistance of the RFID systems. To this end, we propose an approach for detecting cloned RFID tags in RFID systems with high detection accuracy and minimal overhead thus overcoming practical challenges in existing approaches. The proposed approach is based on consistency of dual hash collisions and modified count-min sketch vector. We evaluated the proposed approach through extensive experiments and compared it with existing baseline approaches in terms of execution time and detection accuracy under varying RFID tag cloning ratio. The results of the experiments show that the proposed approach outperforms the baseline approaches in cloned RFID tag detection accuracy. PMID:29565982

Vector boson tagged jets and jet substructure

Directory of Open Access Journals (Sweden)

Vitev Ivan

2018-01-01

Full Text Available In these proceedings, we report on recent results related to vector boson-tagged jet production in heavy ion collisions and the related modification of jet substructure, such as jet shapes and jet momentum sharing distributions. Z0-tagging and γ-tagging of jets provides new opportunities to study parton shower formation and propagation in the quark-gluon plasma and has been argued to provide tight constrains on the energy loss of reconstructed jets. We present theoretical predictions for isolated photon-tagged and electroweak boson-tagged jet production in Pb+Pb collisions at √sNN = 5.02 TeV at the LHC, addressing the modification of their transverse momentum and transverse momentum imbalance distributions. Comparison to recent ATLAS and CMS experimental measurements is performed that can shed light on the medium-induced radiative corrections and energy dissipation due to collisional processes of predominantly quark-initiated jets. The modification of parton splitting functions in the QGP further implies that the substructure of jets in heavy ion collisions may differ significantly from the corresponding substructure in proton-proton collisions. Two such observables and the implication of tagging on their evaluation is also discussed.

Clone tag detection in distributed RFID systems.

Science.gov (United States)

Kamaludin, Hazalila; Mahdin, Hairulnizam; Abawajy, Jemal H

2018-01-01

Although Radio Frequency Identification (RFID) is poised to displace barcodes, security vulnerabilities pose serious challenges for global adoption of the RFID technology. Specifically, RFID tags are prone to basic cloning and counterfeiting security attacks. A successful cloning of the RFID tags in many commercial applications can lead to many serious problems such as financial losses, brand damage, safety and health of the public. With many industries such as pharmaceutical and businesses deploying RFID technology with a variety of products, it is important to tackle RFID tag cloning problem and improve the resistance of the RFID systems. To this end, we propose an approach for detecting cloned RFID tags in RFID systems with high detection accuracy and minimal overhead thus overcoming practical challenges in existing approaches. The proposed approach is based on consistency of dual hash collisions and modified count-min sketch vector. We evaluated the proposed approach through extensive experiments and compared it with existing baseline approaches in terms of execution time and detection accuracy under varying RFID tag cloning ratio. The results of the experiments show that the proposed approach outperforms the baseline approaches in cloned RFID tag detection accuracy.

A comparative evaluation of three methods used to tag South African ...

African Journals Online (AJOL)

Tagging effects and loss rates of 60 Roman Chrysoblephus laticeps tagged with dart tags with barbs (D-tags), T-bar filaments (T-tags) and visible implant fluorescent elastomer (VIFE) tags were investigated. The fish were tagged and monitored in a controlled tank experiment over a period of 198 days. Application technique ...

Extending a Hybrid Tag-Based Recommender System with Personalization

DEFF Research Database (Denmark)

Durao, Frederico; Dolog, Peter

2010-01-01

extension for a hybrid tag-based recommender system, which suggests similar Web pages based on the similarity of their tags. The semantic extension aims at discovering tag relations which are not considered in basic syntax similarity. With the goal of generating more semantically grounded recommendations......, the proposal extends a hybrid tag-based recommender system with a semantic factor, which looks for tag relations in different semantic sources. In order to evaluate the benefits acquired with the semantic extension, we have compared the new findings with results from a previous experiment involving 38 people......Tagging activity has been recently identified as a potential source of knowledge about personal interests, preferences, goals, and other attributes known from user models. Tags themselves can be therefore used for finding personalized recommendations of items. This paper proposes a semantic...

Heterologous expression of plant cell wall glycosyltransferases in Pichia, pea and tobacco

DEFF Research Database (Denmark)

Petersen, Bent Larsen; Damager, Iben; Faber, Kirsten

Cell). In the present study, Flag-tagged (MDYKDDDD) RGXT2 was expressed in Pichia pastoris as secreted soluble protein, in pea (using the Pea early browning virus as expression vector) as soluble intra-cellular protein and in tobacco as full length membrane bound protein. The amount of expressed...... to participate in plant CW biosynthesis, has been achieved in only a few cases. We have previously reported the characterisation of two highly homologous plant-specific membrane-bound GTs, which when expressed as secreted tagged soluble proteins in the baculo virus system, catalysed the transfer of xylose from...... protein was estimated using anti Flag Ab and corresponding activity monitored. Pros and cons of using the various expression systems are discussed....

Tag and Neighbor based Recommender systems for Medical events

DEFF Research Database (Denmark)

Bayyapu, Karunakar Reddy; Dolog, Peter

2010-01-01

This paper presents an extension of a multifactor recommendation approach based on user tagging with term neighbours. Neighbours of words in tag vectors and documents provide for hitting larger set of documents and not only those matching with direct tag vectors or content of the documents. Tag...... in the situations where the quality of tags is lower. We discuss the approach on the examples from the existing Medworm system to indicate the usefulness of the approach....

POS-Tagging for informal language (study in Indonesian tweets)

Science.gov (United States)

Suryawati, Endang; Munandar, Devi; Riswantini, Dianadewi; Fatchuttamam Abka, Achmad; Arisal, Andria

2018-03-01

This paper evaluates Part-of-Speech Tagging for the formal Indonesian language can be used for the tagging process of Indonesian tweets. In this study, we add five additional tags which reflect to social media attributes to the existing original tagset. Automatic POS tagging process is done by stratified training process with 1000, 1600, and 1800 of annotated tweets. It shows that the process can achieve up to 66.36% accuracy. The experiment with original tagset gives slightly better accuracy (67.39%) than the experiment with five additional tags, but will lose important informations which given by the five additional tagset.POS-Tagging for Informal Language (Study in Indonesian Tweets).

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

Developing an early alert system for metastatic spinal cord compression (MSCC): Red Flag credit cards.

Science.gov (United States)

Turnpenney, Jackie; Greenhalgh, Sue; Richards, Lena; Crabtree, Annamaria; Selfe, James

2015-01-01

To produce a user-friendly list of metastatic spinal cord compression (MSCC) Red Flags for non-specialist 'generalist' front-line clinicians working in primary-care settings. The issue of identifying MSCC early to prevent serious long-term disability was a key theme identified by the Task and Finish Group at Greater Manchester and Cheshire Cancer Network (GMCCN) in 2009. It was this group who initially brokered and then coordinated the current development as part of their strategic approach to improving care for MSCC patients. A consensus-building approach that considered the essential minimum data requirements to raise the index of suspicion suggestive of MSCC was adopted. This followed a model of cross-boundary working to facilitate the mutual sharing of expertise across a variety of relevant clinical specialisms. A guideline aimed at helping clinicians to identify the early signs and symptoms of MSCC was produced in the form of a credit card. This credit card includes key statements about MSCC, signposting to key sources of additional information and a user-friendly list of Red Flags which has been developed into an eight-item Red Flag mnemonic. To date, an excess of 120,000 cards have been printed by a variety of organisations and the distribution of the cards is ongoing across the United Kingdom and the Republic of Ireland.

Superstring field theories on super-flag manifolds: superdiff S1/S1 and superdiff S1/super S1

International Nuclear Information System (INIS)

Zhao Zhiyong; Wu, Ke; Saito, Takesi

1987-01-01

We generalize the geometric approach of Bowick and Rajeev [BR] to superstring field theories. The anomaly is identified with nonvanishing of the Ricci curvature of the super-flag manifold. We explicitly calculate the curvatures of superdiff S 1 /S 1 and superdiff S 1 /superS 1 using super-Toeplitz operator techniques. No regularization is needed in this formalism. The critical dimension D=10 is rediscovered as a result of vanishing curvature of the product bundle over the super-flag manifold. (orig.)

Tagging in Volunteered Geographic Information: An Analysis of Tagging Practices for Cities and Urban Regions in OpenStreetMap

Directory of Open Access Journals (Sweden)

Nikola Davidovic

2016-12-01

Full Text Available In Volunteered Geographic Information (VGI projects, the tagging or annotation of objects is usually performed in a flexible and non-constrained manner. Contributors to a VGI project are normally free to choose whatever tags they feel are appropriate to annotate or describe a particular geographic object or place. In OpenStreetMap (OSM, the Map Features part of the OSM Wiki serves as the de-facto rulebook or ontology for the annotation of features in OSM. Within Map Features, suggestions and guidance on what combinations of tags to use for certain geographic objects are outlined. In this paper, we consider these suggestions and recommendations and analyse the OSM database for 40 cities around the world to ascertain if contributors to OSM in these urban areas are using this guidance in their tagging practices. Overall, we find that compliance with the suggestions and guidance in Map Features is generally average or poor. This leads us to conclude that contributors in these areas do not always tag features with the same level of annotation. Our paper also confirms anecdotal evidence that OSM Map Features is less influential in how OSM contributors tag objects.

Preliminary evaluation of the effectiveness of visible implant elastomer and coded wire tags for tagging young-of-the-year Atlantic sturgeon, Acipenser oxyrinchus

Directory of Open Access Journals (Sweden)

Kapusta Andrzej

2015-12-01

Full Text Available The aim of the study was to determine the retention rates of visible implant elastomer (VIE and coded wire tags (CWT and the impact tagging had on the growth of Atlantic sturgeon, Acipenser oxyrinchus Mitchill, during an eight-week rearing period under laboratory conditions. Two size groups of young-of-the-year (YOY sturgeon were used in the study. The tagging was not found to have a significant impact on the final total length or body weight or the condition coefficient of the sturgeon from either size group. Sturgeon survival in the different groups ranged from 90.6 to 100%. Mortality was not noted until two (CWT and four (VIE weeks following tagging and was probably not linked to tagging. The retention rate for VIE tags implanted in the rostrum in both size groups was 100%, while for tags implanted at the base of the pectoral fin was 93.5%. The retention of CWT in the smaller fish was 90%, and in the larger sturgeon it was 100%. Tagging small sturgeon with CWT and VIE is minimally invasive, and it did not impact the growth or condition of the tagged fish.

38 CFR 1.9 - Description, use, and display of VA seal and flag.

Science.gov (United States)

2010-07-01

... stars represent the five branches of military service. The crossed flags represent our nation's history... employees. (D) Official VA signs. (E) Official publications or graphics issued by and attributed to VA, or...) Souvenir or novelty items. (iii) Toys or commercial gifts or premiums. (iv) Letterhead design, except on...

CD109 is a component of exosome secreted from cultured cells

International Nuclear Information System (INIS)

Sakakura, Hiroki; Mii, Shinji; Hagiwara, Sumitaka; Kato, Takuya; Yamamoto, Noriyuki; Hibi, Hideharu; Takahashi, Masahide; Murakumo, Yoshiki

2016-01-01

Exosomes are 50–100-nm-diameter membrane vesicles released from various types of cells. Exosomes retain proteins, mRNAs and miRNAs, which can be transported to surrounding cells. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, and is released from the cell surface to the culture medium in vitro. Recently, it was reported that secreted CD109 from the cell surface downregulates transforming growth factor-β signaling in human keratinocytes. In this study, we revealed that CD109 is a component of the exosome in conditioned medium. FLAG-tagged human CD109 (FLAG-CD109) in conditioned medium secreted from HEK293 cells expressing FLAG-CD109 (293/FLAG-CD109) was immunoprecipitated with anti-FLAG affinity gel, and the co-precipitated proteins were analyzed by mass spectrometry and western blotting. Exosomal proteins were associated with CD109. We revealed the presence of CD109 in exosome fractions from conditioned medium of 293/FLAG-CD109. Moreover, the localization of CD109 in the exosome was demonstrated using immuno-electron microscopy. When we used HEK293 cells expressing FLAG-tagged truncated CD109, which does not contain the C-terminal region, the association of truncated CD109 with exosomes was not detected in conditioned medium. These findings indicate that CD109 is an exosomal protein and that the C-terminal region of CD109 is required for its presence in the exosome. - Highlights: • CD109 is an exosomal protein. • The C-terminal region of CD109 is required for its presence in the exosome. • Part of the secreted CD109 is present in the exosome-free fraction in the conditioned medium.

CD109 is a component of exosome secreted from cultured cells

Energy Technology Data Exchange (ETDEWEB)

Sakakura, Hiroki [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan); Mii, Shinji [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Hagiwara, Sumitaka [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya (Japan); Kato, Takuya [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Yamamoto, Noriyuki; Hibi, Hideharu [Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya (Japan); Takahashi, Masahide, E-mail: mtakaha@med.nagoya-u.ac.jp [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Murakumo, Yoshiki, E-mail: murakumo@med.kitasato-u.ac.jp [Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa (Japan)

2016-01-22

Exosomes are 50–100-nm-diameter membrane vesicles released from various types of cells. Exosomes retain proteins, mRNAs and miRNAs, which can be transported to surrounding cells. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, and is released from the cell surface to the culture medium in vitro. Recently, it was reported that secreted CD109 from the cell surface downregulates transforming growth factor-β signaling in human keratinocytes. In this study, we revealed that CD109 is a component of the exosome in conditioned medium. FLAG-tagged human CD109 (FLAG-CD109) in conditioned medium secreted from HEK293 cells expressing FLAG-CD109 (293/FLAG-CD109) was immunoprecipitated with anti-FLAG affinity gel, and the co-precipitated proteins were analyzed by mass spectrometry and western blotting. Exosomal proteins were associated with CD109. We revealed the presence of CD109 in exosome fractions from conditioned medium of 293/FLAG-CD109. Moreover, the localization of CD109 in the exosome was demonstrated using immuno-electron microscopy. When we used HEK293 cells expressing FLAG-tagged truncated CD109, which does not contain the C-terminal region, the association of truncated CD109 with exosomes was not detected in conditioned medium. These findings indicate that CD109 is an exosomal protein and that the C-terminal region of CD109 is required for its presence in the exosome. - Highlights: • CD109 is an exosomal protein. • The C-terminal region of CD109 is required for its presence in the exosome. • Part of the secreted CD109 is present in the exosome-free fraction in the conditioned medium.

Evaluation of PIT-tagging in cyprinids

DEFF Research Database (Denmark)

Skov, Christian; Brodersen, J.; Brönmark, C.

2005-01-01

Laboratory and field experiments were used to investigate how different marking procedures, with 23 mm PIT (passive integrated transponders) - tags. affected mortality, body condition and tag expulsion in small roach Rutilus rutilus and rudd Scardinus erythrophthalmus (117 to 163 mm total length...

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.

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.

Tagging: An Organization Scheme for the Internet

Directory of Open Access Journals (Sweden)

Marijke A. Visser

2010-03-01

Full Text Available How should the information on the Internet be organized? This question and the possible solutions spark debates among people concerned with how we identify, classify, and retrieve Internet content. This paper discusses the benefits and the controversies of using a tagging system to organize Internet resources. Tagging refers to a classification system where individual Internet users apply labels, or tags, to digital resources. Tagging increased in popularity with the advent of Web 2.0 applications that encourage interaction among users. As more information is available digitally, the challenge to find an organizational system scalable to the Internet will continue to require forward thinking. Trained to ensure access to a range of informational resources, librarians need to be concerned with access to Internet content. Librarians can play a pivotal role by advocating for a system that supports the user at the moment of need. Tagging may just be the necessary system.

Social and Behavioral Aspects of a Tag-Based Recommender System

DEFF Research Database (Denmark)

Durao, Frederico; Dolog, Peter

2009-01-01

Collaborative tagging has emerged as a useful means to organize and share resources on the Web. Recommender systems have been utilized tags for identifying similar resources and generate personalized recommendations. In this paper, we analyze social and behavioral aspects of a tag-based recommender...... system which suggests similar Web pages based on the similarity of their tags. Tagging behavior and language anomalies in tagging activities are some aspects examined from an experiment involving 38 people from 12 countries....

Key mediators modulating TAG synthesis and accumulation in ...

African Journals Online (AJOL)

the key mediators on TAG synthesis and accumulation, among which diacylglycerol acyltransferases (DGATs) is discussed for its clear role in TAG amount and composition. Furthermore TAG-accosiated proteins called oleosins are also discussed in depth due to their determination on the amount and size of oil bodies.

Bus and Tag Terminators for IBM system/360

CERN Multimedia

Control units were connected to the channels with "Bus and Tag" cable pairs. The bus cables carried the address and data information and the tag cables identified what data was on the bus. There were three general types of bus-and-tag cables produced by IBM.

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

TagPad

DEFF Research Database (Denmark)

Bornoe, Nis; Barkhuus, Louise

2013-01-01

The area of cyberinfrastructures has looked extensively at research within the natural sciences, however, the social sciences have been largely overlooked in terms of novel data collection and analysis systems. We developed a probe tool, TagPad, to look at the process for social science data...

Incorporating user motivations to design for video tagging

NARCIS (Netherlands)

van Velsen, Lex Stefan; Melenhorst, M.S.

2009-01-01

User video tagging can enhance the indexing of large collections of videos, or can provide the basis for personalizing output. However, before the benefits of tagging can be reaped, users must be motivated to provide videos with tags. This article describes a two-stage study that aimed at collecting

Application to the conservation of RF tags in the radiation environment

International Nuclear Information System (INIS)

Teraura, Nobuyuki; Ito, Kunio; Takahashi, Naoki; Sakurai, Kouichi

2011-01-01

RF tags that are implemented RFID technology as tag has been used in various fields. Tags have been developed, such as resistance to chemicals and high temperature resistant RF tags are also used in specialized fields. The RF tag apply to the existing nuclear field, had been concerned about the effects of radiation to the RF tags. Now, since the RF tag with a goal to develop radiation-proof, we have examined, such as applying for maintenance of nuclear facilities under radiation environment. We report the results and RF tags to be radiation resistant. (author)

Serotype determination of Salmonella by xTAG assay.

Science.gov (United States)

Zheng, Zhibei; Zheng, Wei; Wang, Haoqiu; Pan, Jincao; Pu, Xiaoying

2017-10-01

Currently, no protocols or commercial kits are available to determine the serotypes of Salmonella by using Luminex MAGPIX®. In this study, an xTAG assay for serotype determination of Salmonella suitable for Luminex MAGPIX® is described and 228 Salmonella isolates were serotype determined by this xTAG assay. The xTAG assay consists of two steps: 1) Multiplex PCR to amplify simultaneously O, H and Vi antigen genes of Salmonella, and 2) Magplex-TAG™ microsphere hybridization to identify accurately the specific PCR products of different antigens. Compared with the serotyping results of traditional serum agglutination test, the sensitivity and specificity of the xTAG assay were 95.1% and 100%, respectively. The agreement rate of these two assays was 95.2%. Compared with Luminex xMAP® Salmonella Serotyping Assay (SSA) kit, the advantages of this xTAG assay are: First, the magnetic beads make it applicable to both the Luminex®100/200™ and MAGPIX® systems. Second, only primers rather than both primers and probes are needed in the xTAG assay, and the process of coupling antigen-specific oligonucleotide probes to beads is circumvented, which make the xTAG assay convenient to be utilized by other laboratories. The xTAG assay may serve as a rapid alternative or complementary method for traditional Salmonella serotyping tests, especially for laboratories that utilize the MAGPIX® systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of coded-wire-tagging on stream-dwelling Sea Lamprey larvae

Science.gov (United States)

Johnson, Nicholas; Swink, William D.; Dawson, Heather A.; Jones, Michael L.

2016-01-01

The effects of coded wire tagging Sea Lamprey Petromyzon marinus larvae from a known-aged stream-dwelling population were assessed. Tagged larvae were significantly shorter on average than untagged larvae from 3 to 18 months after tagging. However, 30 months after tagging, the length distribution of tagged and untagged larvae did not differ and tagged Sea Lampreys were in better condition (i.e., higher condition factor) and more likely to have undergone metamorphosis than the untagged population. The reason why tagged larvae were more likely to metamorphose is not clear, but the increased likelihood of metamorphosis could have been a compensatory response to the period of slower growth after tagging. Slower growth after tagging was consistent across larval size-classes, so handling and displacement from quality habitat during the early part of the growing season was likely the cause rather than the tag burden. The tag effects observed in this study, if caused by displacement and handling, may be minimized in future studies if tagging is conducted during autumn after growth has concluded for the year.

Fundamental statistical features and self-similar properties of tagged networks

International Nuclear Information System (INIS)

Palla, Gergely; Farkas, Illes J; Pollner, Peter; Vicsek, Tamas; Derenyi, Imre

2008-01-01

We investigate the fundamental statistical features of tagged (or annotated) networks having a rich variety of attributes associated with their nodes. Tags (attributes, annotations, properties, features, etc) provide essential information about the entity represented by a given node, thus, taking them into account represents a significant step towards a more complete description of the structure of large complex systems. Our main goal here is to uncover the relations between the statistical properties of the node tags and those of the graph topology. In order to better characterize the networks with tagged nodes, we introduce a number of new notions, including tag-assortativity (relating link probability to node similarity), and new quantities, such as node uniqueness (measuring how rarely the tags of a node occur in the network) and tag-assortativity exponent. We apply our approach to three large networks representing very different domains of complex systems. A number of the tag related quantities display analogous behaviour (e.g. the networks we studied are tag-assortative, indicating possible universal aspects of tags versus topology), while some other features, such as the distribution of the node uniqueness, show variability from network to network allowing for pin-pointing large scale specific features of real-world complex networks. We also find that for each network the topology and the tag distribution are scale invariant, and this self-similar property of the networks can be well characterized by the tag-assortativity exponent, which is specific to each system.

The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission.

Science.gov (United States)

Baillie, Charles A; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C William; Behta, Maryam; Umscheid, Craig A

2013-12-01

Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Retrospective and prospective cohort. Healthcare system consisting of 3 hospitals. All adult patients admitted from August 2009 to September 2012. An automated readmission risk flag integrated into the EHR. Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Using retrospective data, a single risk factor, ≥ 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. © 2013 Society of Hospital Medicine.

The Effects of Target Audience on Social Tagging

Science.gov (United States)

Alsarhan, Hesham

2013-01-01

Online social bookmarking systems allow users to assign tags (i.e., keywords) to represent the content of resources. Research on the effects of target audience on social tagging suggests that taggers select different tags for themselves, their community (e.g., family, friends, colleagues), and the general public (Panke & Gaiser, 2009; Pu &…

Analysis of tag-based Recommendation Performance for a Semantic Wiki

DEFF Research Database (Denmark)

Durao, Frederico; Dolog, Peter

2009-01-01

Recommendations play a very important role for revealing related topics addressed in the wikis beyond the currently viewed page. In this paper, we extend KiWi, a semantic wiki with three different recommendation approaches. The first approach is implemented as a traditional tag-based retrieval......, the second takes into account external factors such as tag popularity, tag representativeness and the affinity between user and tag and the third approach recommends pages in grouped by tag. The experiment evaluates the wiki performance in different scenarios regarding the amount of pages, tags and users...

UTag: Long-range Ultra-wideband Passive Radio Frequency Tags

Energy Technology Data Exchange (ETDEWEB)

Dowla, F

2007-03-14

Long-range, ultra-wideband (UWB), passive radio frequency (RF) tags are key components in Radio Frequency IDentification (RFID) system that will revolutionize inventory control and tracking applications. Unlike conventional, battery-operated (active) RFID tags, LLNL's small UWB tags, called 'UTag', operate at long range (up to 20 meters) in harsh, cluttered environments. Because they are battery-less (that is, passive), they have practically infinite lifetimes without human intervention, and they are lower in cost to manufacture and maintain than active RFID tags. These robust, energy-efficient passive tags are remotely powered by UWB radio signals, which are much more difficult to detect, intercept, and jam than conventional narrowband frequencies. The features of long range, battery-less, and low cost give UTag significant advantage over other existing RFID tags.

Tagging, Encoding, and Jones Optimality

DEFF Research Database (Denmark)

Danvy, Olivier; Lopez, Pablo E. Martinez

2003-01-01

A partial evaluator is said to be Jones-optimal if the result of specializing a self-interpreter with respect to a source program is textually identical to the source program, modulo renaming. Jones optimality has already been obtained if the self-interpreter is untyped. If the selfinterpreter...... is typed, however, residual programs are cluttered with type tags. To obtain the original source program, these tags must be removed. A number of sophisticated solutions have already been proposed. We observe, however, that with a simple representation shift, ordinary partial evaluation is already Jones......-optimal, modulo an encoding. The representation shift amounts to reading the type tags as constructors for higherorder abstract syntax. We substantiate our observation by considering a typed self-interpreter whose input syntax is higher-order. Specializing this interpreter with respect to a source program yields...

Electronic tagging and integrated product intelligence

Science.gov (United States)

Swerdlow, Martin; Weeks, Brian

1996-03-01

The advent of 'intelligent,' electronic data bearing tags is set to revolutionize the way industrial and retail products are identified and tracked throughout their life cycles. The dominant system for unique identification today is the bar code, which is based on printed symbology and regulated by the International Article Numbering Association. Bar codes provide users with significant operational advantages and generate considerable added value to packaging companies, product manufacturers, distributors and retailers, across supply chains in many different sectors, from retailing, to baggage handling and industrial components, e.g., for vehicles or aircraft. Electronic tags offer the potential to: (1) record and store more complex data about the product or any modifications which occur during its life cycle; (2) access (and up-date) stored data in real time in a way which does not involve contact with the product or article; (3) overcome the limitations imposed by systems which rely on line-of-sight access to stored data. Companies are now beginning to consider how electronic data tags can be used, not only to improve the efficiency of their supply chain processes, but also to revolutionize the way they do business. This paper reviews the applications and business opportunities for electronic tags and outlines CEST's strategy for achieving an 'open' standard which will ensure that tags from different vendors can co-exist on an international basis.

Overview of the recombinant proteins purification by affinity tags and ...

African Journals Online (AJOL)

From protein within isolation process which the same matter increases labor costs further and prevents application of these tags in industrial scale. Therefore proper replacement is emphasized for enzymatic removal of purification tags. Keywords: protein purification; recombinant proteins; self-cleavable tags; Intein tags; ...

Experiment list: SRX319557 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available se embryonic stem cells || genotype/variation=expressing Flag-bio tagged Nanog || chip beads=Dynabeads MyOne... Streptavidin T1 || chip beads vendor=Invitrogen http://dbarchive.biosciencedbc.j

Passive UHF RFID Tag with Multiple Sensing Capabilities

Directory of Open Access Journals (Sweden)

José Fernández-Salmerón

2015-10-01

Full Text Available This work presents the design, fabrication, and characterization of a printed radio frequency identification tag in the ultra-high frequency band with multiple sensing capabilities. This passive tag is directly screen printed on a cardboard box with the aim of monitoring the packaging conditions during the different stages of the supply chain. This tag includes a commercial force sensor and a printed opening detector. Hence, the force applied to the package can be measured as well as the opening of the box can be detected. The architecture presented is a passive single-chip RFID tag. An electronic switch has been implemented to be able to measure both sensor magnitudes in the same access without including a microcontroller or battery. Moreover, the chip used here integrates a temperature sensor and, therefore, this tag provides three different parameters in every reading.

Perception without self-matching in conditional tag based cooperation.

Science.gov (United States)

McAvity, David M; Bristow, Tristen; Bunker, Eric; Dreyer, Alex

2013-09-21

We consider a model for the evolution of cooperation in a population where individuals may have one of a number of different heritable and distinguishable markers or tags. Individuals interact with each of their neighbors on a square lattice by either cooperating by donating some benefit at a cost to themselves or defecting by doing nothing. The decision to cooperate or defect is contingent on each individual's perception of its interacting partner's tag. Unlike in other tag-based models individuals do not compare their own tag to that of their interaction partner. That is, there is no self-matching. When perception is perfect the cooperation rate is substantially higher than in the usual spatial prisoner's dilemma game when the cost of cooperation is high. The enhancement in cooperation is positively correlated with the number of different tags. The more diverse a population is the more cooperative it becomes. When individuals start with an inability to perceive tags the population evolves to a state where individuals gain at least partial perception. With some reproduction mechanisms perfect perception evolves, but with others the ability to perceive tags is imperfect. We find that perception of tags evolves to lower levels when the cost of cooperation is higher. Copyright © 2013 Elsevier Ltd. All rights reserved.

77 FR 51761 - Proposed Information Collection; Comment Request; Groundfish Tagging Program

Science.gov (United States)

2012-08-27

... required by the Paperwork Reduction Act of 1995. DATES: Written comments must be submitted on or before... are two general categories of tags. Simple plastic tags (spaghetti tags) are external tags... fish. Archival tags are microchips with sensors encased in plastic cylinders that record the depth...

Coenzyme- and His-tag-induced crystallization of octopine dehydrogenase

International Nuclear Information System (INIS)

Smits, Sander H. J.; Mueller, Andre; Grieshaber, Manfred K.; Schmitt, Lutz

2008-01-01

The crystal structure of octopine dehydrogenase revealed a specific role of the His 5 tag in inducing the crystal contacts required for successful crystallization. Over the last decade, protein purification has become more efficient and standardized through the introduction of affinity tags. The choice and position of the tag, however, can directly influence the process of protein crystallization. Octopine dehydrogenase (OcDH) without a His tag and tagged protein constructs such as OcDH-His 5 and OcDH-LEHis 6 have been investigated for their crystallizability. Only OcDH-His 5 yielded crystals; however, they were multiple. To improve crystal quality, the cofactor NADH was added, resulting in single crystals that were suitable for structure determination. As shown by the structure, the His 5 tag protrudes into the cleft between the NADH and l-arginine-binding domains and is mainly fixed in place by water molecules. The protein is thereby stabilized to such an extent that the formation of crystal contacts can proceed. Together with NADH, the His 5 tag obviously locks the enzyme into a specific conformation which induces crystal growth

Gpn3 is polyubiquitinated on lysine 216 and degraded by the proteasome in the cell nucleus in a Gpn1-inhibitable manner.

Science.gov (United States)

Méndez-Hernández, Lucía E; Robledo-Rivera, Angelica Y; Macías-Silva, Marina; Calera, Mónica R; Sánchez-Olea, Roberto

2017-11-01

Gpn1 associates with Gpn3, and both are required for RNA polymerase II nuclear targeting. Global studies have identified by mass spectrometry that human Gpn3 is ubiquitinated on lysines 189 and 216. Our goals here were to determine the type, physiological importance, and regulation of Gpn3 ubiquitination. After inhibiting the proteasome with MG132, Gpn3-Flag was polyubiquitinated on K216, but not K189, in HEK293T cells. Gpn3-Flag exhibited nucleo-cytoplasmic shuttling, but polyubiquitination and proteasomal degradation of Gpn3-Flag occurred only in the cell nucleus. Polyubiquitination-deficient Gpn3-Flag K216R displayed a longer half-life than Gpn3-Flag in two cell lines. Interestingly, Gpn1-EYFP inhibited Gpn3-Flag polyubiquitination in a dose-dependent manner. In conclusion, Gpn1-inhibitable, nuclear polyubiquitination on lysine 216 regulates the half-life of Gpn3 by tagging it for proteasomal degradation. © 2017 Federation of European Biochemical Societies.

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.

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.

Evaluation of normalization methods in mammalian microRNA-Seq data

Science.gov (United States)

Garmire, Lana Xia; Subramaniam, Shankar

2012-01-01

Simple total tag count normalization is inadequate for microRNA sequencing data generated from the next generation sequencing technology. However, so far systematic evaluation of normalization methods on microRNA sequencing data is lacking. We comprehensively evaluate seven commonly used normalization methods including global normalization, Lowess normalization, Trimmed Mean Method (TMM), quantile normalization, scaling normalization, variance stabilization, and invariant method. We assess these methods on two individual experimental data sets with the empirical statistical metrics of mean square error (MSE) and Kolmogorov-Smirnov (K-S) statistic. Additionally, we evaluate the methods with results from quantitative PCR validation. Our results consistently show that Lowess normalization and quantile normalization perform the best, whereas TMM, a method applied to the RNA-Sequencing normalization, performs the worst. The poor performance of TMM normalization is further evidenced by abnormal results from the test of differential expression (DE) of microRNA-Seq data. Comparing with the models used for DE, the choice of normalization method is the primary factor that affects the results of DE. In summary, Lowess normalization and quantile normalization are recommended for normalizing microRNA-Seq data, whereas the TMM method should be used with caution. PMID:22532701

Algorithms on Flag Manifolds for Knowledge Discovery in N-way Arrays

Science.gov (United States)

2015-11-20

subspace representations. For instance, the d- dimensional subspace in the flag corresponds to the extrinsic manifold mean. When the set of subspaces is...one-dimensional subspace of V and let θ(L, Vi) denote the principal angle between L and Vi. Motivated by a problem in data analysis, we seek an L that...appear less frequently in the literature may be more appropriate for certain tasks. The extrinsic manifold mean, the L 2-median, and the ag mean are

Experiment list: SRX319556 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ype=mouse embryonic stem cells || genotype/variation=expressing Flag-bio tagged Dax1 || chip beads=Dynabeads... MyOne Streptavidin T1 || chip beads vendor=Invitrogen http://dbarchive.bioscienc

Experiment list: SRX319553 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available se embryonic stem cells || genotype/variation=expressing Flag-bio tagged Tip60 || chip beads=Dynabeads MyOne... Streptavidin T1 || chip beads vendor=Invitrogen http://dbarchive.biosciencedbc.j

Experiment list: SRX319555 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ype=mouse embryonic stem cells || genotype/variation=expressing Flag-bio tagged Dax1 || chip beads=Dynabeads... MyOne Streptavidin T1 || chip beads vendor=Invitrogen http://dbarchive.bioscienc

Experiment list: SRX319551 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available use embryonic stem cells || genotype/variation=expressing Flag-bio tagged Dmap1 || chip beads=Dynabeads MyOn...e Streptavidin T1 || chip beads vendor=Invitrogen http://dbarchive.biosciencedbc.

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...

Sequence tagging reveals unexpected modifications in toxicoproteomics

Science.gov (United States)

Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

2010-01-01

Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

User Interface Program for secure electronic tags

International Nuclear Information System (INIS)

Cai, Y.; Koehl, E.R.; Carlson, R.D.; Raptis, A.C.

1995-05-01

This report summarizes and documents the efforts of Argonne National Laboratory (ANL) in developing a secure tag communication user interface program comprising a tag monitor and a communication tool. This program can perform the same functions as the software that was developed at the Lawrence Livermore National Laboratory (LLNL), but it is enhanced with a user-friendly screen. It represents the first step in updating the TRANSCOM Tracking System (TRANSCOM) by incorporating a tag communication screen menu into the main menu of the TRANSCOM user program. A working version of TRANSCOM, enhanced with ANL secure-tag graphics, will strongly support the Department of Energy Warhead Dismantlement/Special Nuclear Materials Control initiatives. It will allow commercial satellite tracking of the movements and operational activities of treaty-limited items and transportation vehicles throughout Europe and the former USSR, as well as the continental US

Device-free object tracking using passive tags

CERN Document Server

Han, Jinsong; Zhao, Kun; Jiang, Zhiping

2014-01-01

This SpringerBrief examines the use of cheap commercial passive RFID tags to achieve accurate device-free object-tracking. It presents a sensitive detector, named Twins, which uses a pair of adjacent passive tags to detect uncooperative targets (such as intruders). Twins leverages a newly observed phenomenon called critical state that is caused by interference among passive tags.The author expands on the previous object tracking methods, which are mostly device-based, and reveals a new interference model and their extensive experiments for validation. A prototype implementation of the Twins-ba

An unusual case of seed dispersal in an invasive aquatic; yellow flag iris (Iris pseudacorus)

Science.gov (United States)

Understanding reproductive mode of invasive plants can help managers plan more efficacious control. Invasive aquatics typically reproduce primarily through vegetative means. Yellow flag iris is an invasive plant species often growing as an emergent aquatic. There have been contradictory reports of i...

Social tagging in support of cancer patients’ information interaction

DEFF Research Database (Denmark)

Ådland, Marit Kristine; Lykke, Marianne

2012-01-01

Purpose: The purpose of this paper is to explore whether and how social tagging can be useful in an information website for cancer patients and their relatives. Methodology/approach: Three studies have been carried out in order to investigate the research questions. Firstly, we reviewed and analy......Purpose: The purpose of this paper is to explore whether and how social tagging can be useful in an information website for cancer patients and their relatives. Methodology/approach: Three studies have been carried out in order to investigate the research questions. Firstly, we reviewed...... and analyzed literature about cancer patients’ information needs and seeking behavior, and about social tagging and patient terminology. Secondly, we analyzed tags applied to blog postings at Blogomkraeft.dk, a blog site at the Danish information web site Cancer.dk. The tags were compared with the formal...... browsing structure of Cancer.dk. Results from the two studies were used to develop a prototype for social tagging at Cancer.dk. Thus thirdly, we evaluated the prototype in a usability study. Findings: We found that tags have the potential to describe and provide access to web site content from the users...

A Hybrid Probabilistic Model for Unified Collaborative and Content-Based Image Tagging.

Science.gov (United States)

Zhou, Ning; Cheung, William K; Qiu, Guoping; Xue, Xiangyang

2011-07-01

The increasing availability of large quantities of user contributed images with labels has provided opportunities to develop automatic tools to tag images to facilitate image search and retrieval. In this paper, we present a novel hybrid probabilistic model (HPM) which integrates low-level image features and high-level user provided tags to automatically tag images. For images without any tags, HPM predicts new tags based solely on the low-level image features. For images with user provided tags, HPM jointly exploits both the image features and the tags in a unified probabilistic framework to recommend additional tags to label the images. The HPM framework makes use of the tag-image association matrix (TIAM). However, since the number of images is usually very large and user-provided tags are diverse, TIAM is very sparse, thus making it difficult to reliably estimate tag-to-tag co-occurrence probabilities. We developed a collaborative filtering method based on nonnegative matrix factorization (NMF) for tackling this data sparsity issue. Also, an L1 norm kernel method is used to estimate the correlations between image features and semantic concepts. The effectiveness of the proposed approach has been evaluated using three databases containing 5,000 images with 371 tags, 31,695 images with 5,587 tags, and 269,648 images with 5,018 tags, respectively.

Tri-Clustered Tensor Completion for Social-Aware Image Tag Refinement.

Science.gov (United States)

Tang, Jinhui; Shu, Xiangbo; Qi, Guo-Jun; Li, Zechao; Wang, Meng; Yan, Shuicheng; Jain, Ramesh

2017-08-01

Social image tag refinement, which aims to improve tag quality by automatically completing the missing tags and rectifying the noise-corrupted ones, is an essential component for social image search. Conventional approaches mainly focus on exploring the visual and tag information, without considering the user information, which often reveals important hints on the (in)correct tags of social images. Towards this end, we propose a novel tri-clustered tensor completion framework to collaboratively explore these three kinds of information to improve the performance of social image tag refinement. Specifically, the inter-relations among users, images and tags are modeled by a tensor, and the intra-relations between users, images and tags are explored by three regularizations respectively. To address the challenges of the super-sparse and large-scale tensor factorization that demands expensive computing and memory cost, we propose a novel tri-clustering method to divide the tensor into a certain number of sub-tensors by simultaneously clustering users, images and tags into a bunch of tri-clusters. And then we investigate two strategies to complete these sub-tensors by considering (in)dependence between the sub-tensors. Experimental results on a real-world social image database demonstrate the superiority of the proposed method compared with the state-of-the-art methods.

Exploiting phase measurements of EPC Gen2 RFID tags

NARCIS (Netherlands)

Huiting, J.; Flisijn, Hubert; Kokkeler, Andre B.J.; Smit, Gerardus Johannes Maria

2013-01-01

This paper presents a 2d localization system for UHF RFID tags. By measuring the phase between the transmitted continuous wave and received backscatter from the tag at different frequencies, it is possible to estimate the distance between the reader and tag. By determining distance estimates to

Experiment list: SRX319550 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available e embryonic stem cells || genotype/variation=expressing Flag-bio tagged Myc || chip beads=Dynabeads MyOne Streptavidin T1 || chip bea...ds vendor=Invitrogen http://dbarchive.biosciencedbc.jp/k

OSIRIS-REx Touch-And-Go (TAG) Navigation Performance

Science.gov (United States)

Berry, Kevin; Antreasian, Peter; Moreau, Michael C.; May, Alex; Sutter, Brian

2015-01-01

The Origins Spectral Interpretation Resource identification Security Regolith Explorer (OSIRIS-REx) mission is a NASA New Frontiers mission launching in 2016 to rendezvous with the near-Earth asteroid (101955) Bennu in late 2018. Following an extensive campaign of proximity operations activities to characterize the properties of Bennu and select a suitable sample site, OSIRIES-REx will fly a Touch-And-Go (TAG) trajectory to the asteroid's surface to obtain a regolith sample. The paper summarizes the mission design of the TAG sequence, the propulsive required to achieve the trajectory, and the sequence of events leading up to the TAG event. The paper will summarize the Monte-Carlo simulation of the TAG sequence and present analysis results that demonstrate the ability to conduct the TAG within 25 meters of the selected sample site and +-2 cms of the targeted contact velocity. The paper will describe some of the challenges associated with conducting precision navigation operations and ultimately contacting a very small asteroid.

OSIRI-REx Touch and Go (TAG) Navigation Performance

Science.gov (United States)

Berry, Kevin; Antreasian, Peter; Moreau, Michael C.; May, Alex; Sutter, Brian

2015-01-01

The Origins Spectral Interpretation Resource Identification Security Regolith Explorer (OSIRIS-REx) mission is a NASA New Frontiers mission launching in 2016 to rendezvous with the near-Earth asteroid (101955) Bennu in late 2018. Following an extensive campaign of proximity operations activities to characterize the properties of Bennu and select a suitable sample site, OSIRIS-REx will fly a Touch-And-Go (TAG) trajectory to the asteroid's surface to obtain a regolith sample. The paper summarizes the mission design of the TAG sequence, the propulsive maneuvers required to achieve the trajectory, and the sequence of events leading up to the TAG event. The paper also summarizes the Monte-Carlo simulation of the TAG sequence and presents analysis results that demonstrate the ability to conduct the TAG within 25 meters of the selected sample site and 2 cm/s of the targeted contact velocity. The paper describes some of the challenges associated with conducting precision navigation operations and ultimately contacting a very small asteroid.

Tagging like Humans: Diverse and Distinct Image Annotation

KAUST Repository

Wu, Baoyuan

2018-03-31

In this work we propose a new automatic image annotation model, dubbed {\\\\bf diverse and distinct image annotation} (D2IA). The generative model D2IA is inspired by the ensemble of human annotations, which create semantically relevant, yet distinct and diverse tags. In D2IA, we generate a relevant and distinct tag subset, in which the tags are relevant to the image contents and semantically distinct to each other, using sequential sampling from a determinantal point process (DPP) model. Multiple such tag subsets that cover diverse semantic aspects or diverse semantic levels of the image contents are generated by randomly perturbing the DPP sampling process. We leverage a generative adversarial network (GAN) model to train D2IA. Extensive experiments including quantitative and qualitative comparisons, as well as human subject studies, on two benchmark datasets demonstrate that the proposed model can produce more diverse and distinct tags than the state-of-the-arts.

High-p{sub T} B-tagging and top-tagging with variable-R jets in ATLAS

Energy Technology Data Exchange (ETDEWEB)

Behr, Katharina [Sub-department of Particle Physics, University of Oxford, Denys-Wilkinson Building, Keble Road, Oxford OX1 3RH (United Kingdom)

2015-07-01

Variable-R jets, whose effective size is inversely proportional to their transverse momentum, are a versatile tool for object reconstruction across the large transverse momentum regime accessible during Run 2 of the LHC. I discuss the performance of Variable-R jets in two different contexts: (1) Boosted top-tagging. The separation between the decay products of highly energetic top quarks decreases with p{sub T}{sup top} causing them to overlap and merge into a single jet. Taggers relying on large fixed-R jets overestimate the real size of the top jet in the highly boosted regime and are more susceptible to the effects of pile-up. Variable-R jets are studied as the basis for more natural taggers which may not even require grooming. (2) B-tagging. The b-tagging performance in boosted topologies suffers in the presence of close-by jets. This limits the sensitivity of many searches such as those in boosted hh → 4b final states. New b-taggers relying on track jets with smaller sizes than the traditional R=0.4 to better isolate the b-hadron decay show significant improvements in highly boosted scenarios but perform worse at low transverse momenta where they fail to capture the full b-jet. Variable-R track jets provide a unified approach to b-tagging in both p{sub T} regimes.

Tagging behaviour with support from controlled vocabulary

DEFF Research Database (Denmark)

Lykke, Marianne; Høj, Anne Lyhne; Madsen, Line Nørgaard

2011-01-01

) and an enhanced tagging system (experimental system) that additionally offers suggestions from the Dewey Decimal Classification system (DDC). In the experimental study twenty-eight political students completed four tagging tasks, each comprising fifteen documents. The focus was to examine how suggestions from...

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

Expression and stability of foreign epitopes introduced into 3A nonstructural protein of foot-and-mouth disease virus.

Directory of Open Access Journals (Sweden)

Pinghua Li

Full Text Available Foot-and-mouth disease virus (FMDV is an aphthovirus that belongs to the Picornaviridae family and causes one of the most important animal diseases worldwide. The capacity of other picornaviruses to express foreign antigens has been extensively reported, however, little is known about FMDV. To explore the potential of FMDV as a viral vector, an 11-amino-acid (aa HSV epitope and an 8 aa FLAG epitope were introduced into the C-terminal different regions of 3A protein of FMDV full-length infectious cDNA clone. Recombinant viruses expressing the HSV or FLAG epitope were successfully rescued after transfection of both modified constructs. Immunofluorescence assay, Western blot and sequence analysis showed that the recombinant viruses stably maintained the foreign epitopes even after 11 serial passages in BHK-21 cells. The 3A-tagged viruses shared similar plaque phenotypes and replication kinetics to those of the parental virus. In addition, mice experimentally infected with the epitope-tagged viruses could induce tag-specific antibodies. Our results demonstrate that FMDV can be used effectively as a viral vector for the delivery of foreign tags.

Expression and Stability of Foreign Epitopes Introduced into 3A Nonstructural Protein of Foot-and-Mouth Disease Virus

Science.gov (United States)

Li, Pinghua; Bai, Xingwen; Cao, Yimei; Han, Chenghao; Lu, Zengjun; Sun, Pu; Yin, Hong; Liu, Zaixin

2012-01-01

Foot-and-mouth disease virus (FMDV) is an aphthovirus that belongs to the Picornaviridae family and causes one of the most important animal diseases worldwide. The capacity of other picornaviruses to express foreign antigens has been extensively reported, however, little is known about FMDV. To explore the potential of FMDV as a viral vector, an 11-amino-acid (aa) HSV epitope and an 8 aa FLAG epitope were introduced into the C-terminal different regions of 3A protein of FMDV full-length infectious cDNA clone. Recombinant viruses expressing the HSV or FLAG epitope were successfully rescued after transfection of both modified constructs. Immunofluorescence assay, Western blot and sequence analysis showed that the recombinant viruses stably maintained the foreign epitopes even after 11 serial passages in BHK-21 cells. The 3A-tagged viruses shared similar plaque phenotypes and replication kinetics to those of the parental virus. In addition, mice experimentally infected with the epitope-tagged viruses could induce tag-specific antibodies. Our results demonstrate that FMDV can be used effectively as a viral vector for the delivery of foreign tags. PMID:22848509

Tag cloud generation for results of multiple keywords queries

DEFF Research Database (Denmark)

Leginus, Martin; Dolog, Peter; Lage, Ricardo Gomes

2013-01-01

In this paper we study tag cloud generation for retrieved results of multiple keyword queries. It is motivated by many real world scenarios such as personalization tasks, surveillance systems and information retrieval tasks defined with multiple keywords. We adjust the state-of-the-art tag cloud...... generation techniques for multiple keywords query results. Consequently, we conduct the extensive evaluation on top of three distinct collaborative tagging systems. The graph-based methods perform significantly better for the Movielens and Bibsonomy datasets. Tag cloud generation based on maximal coverage...

Tag-KEM from Set Partial Domain One-Way Permutations

Science.gov (United States)

Abe, Masayuki; Cui, Yang; Imai, Hideki; Kurosawa, Kaoru

Recently a framework called Tag-KEM/DEM was introduced to construct efficient hybrid encryption schemes. Although it is known that generic encode-then-encrypt construction of chosen ciphertext secure public-key encryption also applies to secure Tag-KEM construction and some known encoding method like OAEP can be used for this purpose, it is worth pursuing more efficient encoding method dedicated for Tag-KEM construction. This paper proposes an encoding method that yields efficient Tag-KEM schemes when combined with set partial one-way permutations such as RSA and Rabin's encryption scheme. To our knowledge, this leads to the most practical hybrid encryption scheme of this type. We also present an efficient Tag-KEM which is CCA-secure under general factoring assumption rather than Blum factoring assumption.

200-MeV bremsstrahlung tagged photon beams at Sendai

International Nuclear Information System (INIS)

Hirose, K.; Chiba, M.; Inoue, M.; Kanda, H.; Kimura, R.; Kino, K.; Kobayashi, Y.; Konno, O.; Maeda, K.; Miyase, H.; Miyamoto, A.; Ohtsuki, T.; Saito, A.; Suda, T.; Takahashi, K.; Tamae, T.; Terasaki, Y.; Terasawa, T.; Tsubota, H.; Tsuruta, T.; Utoyama, M.; Yuuki, H.; Yamaguchi, Y.; Yamazaki, H.

2006-01-01

A new beam line for photonuclear reaction experiments using tagged photons has been constructed to take advantage of the completion of the 1.2-GeV STretcher Booster (STB) ring at the Laboratory of Nuclear Science (LNS), Tohoku University. A photon tagging system was installed at the end of the new beam line. It provides bremsstrahlung tagged photon beams in an energy range from 0.2E 0 to 0.8E 0 MeV at the incident electron energy E 0 with an energy resolution of ΔE/E∼10 -2 . The tagged photon intensity I= 6 photons/s is available for typical photonuclear reaction experiments. We introduce the basic parameters of the tagged photons by showing the commissioning data

Some Fundamental Limits on SAW RFID Tag Information Capacity and Collision Resolution

Science.gov (United States)

Barton, Richard J.

2013-01-01

In this paper, we apply results from multi-user information theory to study the limits of information capacity and collision resolution for SAW RFID tags. In particular, we derive bounds on the achievable data rate per tag as a function of fundamental parameters such as tag time-bandwidth product, tag signal-to-noise ratio (SNR), and number of tags in the environment. We also discuss the implications of these bounds for tag waveform design and tag interrogation efficiency

THE FLAG: A Web Resource of Innovative Assessment Tools for Faculty in College Science, Mathematics, Engineering, and Technology

Science.gov (United States)

Zeilik, M.; Mathieu, R. D.; National InstituteScience Education; College Level-One Team

2000-12-01

Even the most dedicated college faculty often discover that their students fail to learn what was taught in their courses and that much of what students do learn is quickly forgotten after the final exam. To help college faculty improve student learning in college Science, Mathematics, Engineering and Technology (SMET), the College Level - One Team of the National Institute for Science Education has created the "FLAG" a Field-tested Learning Assessment Guide for SMET faculty. Developed with funding from the National Science Foundation, the FLAG presents in guidebook format a diverse and robust collection of field-tested classroom assessment techniques (CATs), with supporting information on how to apply them in the classroom. Faculty can download the tools and techniques from the website, which also provides a goals clarifier, an assessment primer, a searchable database, and links to additional resources. The CATs and tools have been reviewed by an expert editorial board and the NISE team. These assessment strategies can help faculty improve the learning environments in their SMET courses especially the crucial introductory courses that most strongly shape students' college learning experiences. In addition, the FLAG includes the web-based Student Assessment of Learning Gains. The SALG offers a convenient way to evaluate the impact of your courses on students. It is based on findings that students' estimates of what they gained are more reliable and informative than their observations of what they liked about the course or teacher. It offers accurate feedback on how well the different aspects of teaching helped the students to learn. Students complete the SALG online after a generic template has been modified to fit the learning objectives and activities of your course. The results are presented to the teacher as summary statistics automatically. The FLAG can be found at the NISE "Innovations in SMET Education" website at www.wcer.wisc.edu/nise/cl1

Cross-Lingual Morphological Tagging for Low-Resource Languages

OpenAIRE

Buys, Jan; Botha, Jan A.

2016-01-01

Morphologically rich languages often lack the annotated linguistic resources required to develop accurate natural language processing tools. We propose models suitable for training morphological taggers with rich tagsets for low-resource languages without using direct supervision. Our approach extends existing approaches of projecting part-of-speech tags across languages, using bitext to infer constraints on the possible tags for a given word type or token. We propose a tagging model using Ws...

Plastic-casting intrinsic-surface unique identifier (tag)

International Nuclear Information System (INIS)

Palm, R.G.; De Volpi, A.

1995-04-01

This report describes the development of an authenticated intrinsic-surf ace tagging method for unique- identification of controlled items. Although developed for control of items limited by an arms control treaty, this method has other potential applications to keep track of critical or high-value items. Each tag (unique-identifier) consists of the intrinsic, microscopic surface topography of a small designated area on a controlled item. It is implemented by making a baseline plastic casting of the designated tag area and usually placing a cover (for example, a bar-code label) over this area to protect the surface from environmental alteration. The plastic casting is returned to a laboratory and prepared for high-resolution scanning electron microscope imaging. Several images are digitized and stored for use as a standard for authentication of castings taken during future inspections. Authentication is determined by numerically comparing digital images. Commercially available hardware and software are used for this tag. Tag parameters are optimized, so unique casting images are obtained from original surfaces, and images obtained from attempted duplicate surfaces are detected. This optimization uses the modulation transfer function, a first principle of image analysis, to determine the parameters. Surface duplication experiments confirmed the optimization

Combination of same-side with opposite-side flavour tagging

CERN Document Server

Calvo, M; Musy, M

2010-01-01

A considerable number of CP violation measurements require the most possible accurate knowledge of the flavour at production of the reconstructed $B$ meson. The performance of different flavour tagging methods will be measured from control channels. One of the possible tagging methods that can be used is the one known as $Same Side kaon$. In this note we present how to calibrate the response of the tagging algorithms using the data and combine the result with the so called $Opposite Side tagging$. Also trigger and selection effects are briefly discussed.

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.

A Novel Image Tag Completion Method Based on Convolutional Neural Transformation

KAUST Repository

Geng, Yanyan; Zhang, Guohui; Li, Weizhi; Gu, Yi; Liang, Ru-Ze; Liang, Gaoyuan; Wang, Jingbin; Wu, Yanbin; Patil, Nitin; Wang, Jing-Yan

2017-01-01

In the problems of image retrieval and annotation, complete textual tag lists of images play critical roles. However, in real-world applications, the image tags are usually incomplete, thus it is important to learn the complete tags for images. In this paper, we study the problem of image tag complete and proposed a novel method for this problem based on a popular image representation method, convolutional neural network (CNN). The method estimates the complete tags from the convolutional filtering outputs of images based on a linear predictor. The CNN parameters, linear predictor, and the complete tags are learned jointly by our method. We build a minimization problem to encourage the consistency between the complete tags and the available incomplete tags, reduce the estimation error, and reduce the model complexity. An iterative algorithm is developed to solve the minimization problem. Experiments over benchmark image data sets show its effectiveness.

A Novel Image Tag Completion Method Based on Convolutional Neural Transformation

KAUST Repository

Geng, Yanyan

2017-10-24

In the problems of image retrieval and annotation, complete textual tag lists of images play critical roles. However, in real-world applications, the image tags are usually incomplete, thus it is important to learn the complete tags for images. In this paper, we study the problem of image tag complete and proposed a novel method for this problem based on a popular image representation method, convolutional neural network (CNN). The method estimates the complete tags from the convolutional filtering outputs of images based on a linear predictor. The CNN parameters, linear predictor, and the complete tags are learned jointly by our method. We build a minimization problem to encourage the consistency between the complete tags and the available incomplete tags, reduce the estimation error, and reduce the model complexity. An iterative algorithm is developed to solve the minimization problem. Experiments over benchmark image data sets show its effectiveness.

Improving tag/seal technologies: the vulnerability assessment component

International Nuclear Information System (INIS)

Jones, J.L.

1996-01-01

The Department of Energy (DOE), specifically the Office of Nonproliferation and National Security, has sponsored the development of numerous tag and seal technologies for high-security/high-valued applications. One important component in this technology development effort has been the continuous integration of vulnerability assessments. The Idaho National Engineering Laboratory (INEL) has been the lead laboratory for vulnerability assessments of fiber-optic-based tag/seal technologies. This paper presents a brief historical overview and the current status of the DOE high-security tag/seal development program and discusses INEL's adversarial role and assessment philosophy. Verification testing criteria used to define ''successful'' tampering attempts/attacks are discussed. Finally, the advantages of integrating a vulnerability assessment into the development of commercial security tag/seals are presented

Tissue-specific tagging of endogenous loci in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Kate Koles

2016-01-01

Full Text Available Fluorescent protein tags have revolutionized cell and developmental biology, and in combination with binary expression systems they enable diverse tissue-specific studies of protein function. However these binary expression systems often do not recapitulate endogenous protein expression levels, localization, binding partners and/or developmental windows of gene expression. To address these limitations, we have developed a method called T-STEP (tissue-specific tagging of endogenous proteins that allows endogenous loci to be tagged in a tissue specific manner. T-STEP uses a combination of efficient CRISPR/Cas9-enhanced gene targeting and tissue-specific recombinase-mediated tag swapping to temporally and spatially label endogenous proteins. We have employed this method to GFP tag OCRL (a phosphoinositide-5-phosphatase in the endocytic pathway and Vps35 (a Parkinson's disease-implicated component of the endosomal retromer complex in diverse Drosophila tissues including neurons, glia, muscles and hemocytes. Selective tagging of endogenous proteins allows, for the first time, cell type-specific live imaging and proteomics in complex tissues.

Improved determination of left ventricular volume with myocardial tagging

International Nuclear Information System (INIS)

Peshock, R.M.; Takai, H.; Baker, K.V.; Clarke, G.D.; McDonald, G.G.; Parkey, R.W.

1991-01-01

Cine MR imaging can be used to determine ventricular volume and ejection fraction. However, definition of the endocardial surface can be difficult, leading some investigators to suggest that black-blood studies are preferable. Grid tagging with use of spatial modulation of magnetization has been used to improve assessments of wall motion. The purpose of this paper, is to determine if grid tagging would also facilitate definition of the endocardial border for volume and ejection fraction calculations. Grid tagging based on spatial modulation of magnetization was implemented on a Toshiba 0.5-T MR imaging device. Standard RAO images were obtained in 10 normal volunteers with use of standard cine MR imaging sequences (33/22) with and without grid tagging. Images were analyzed to determine ventricular volume, cardiac output and wall motion. Images obtained without tagging generally showed good contrast at end diastole, but definition of the endocardial border was frequently more difficult in middle to late systole. Images with tagging provided significantly better definition of endocardial borders, particularly during systole

Tagging, Encoding, and Jones Optimality

DEFF Research Database (Denmark)

Danvy, Olivier; López, Pablo Ernesto Martínes

2003-01-01

A partial evaluator is said to be Jones-optimal if the result of specializing a self-interpreter with respect to a source program is textually identical to the source program, modulo renaming. Jones optimality has already been obtained if the self-interpreter is untyped. If the selfinterpreter...... is typed, however, residual programs are cluttered with type tags. To obtain the original source program, these tags must be removed. A number of sophisticated solutions have already been proposed. We observe, however, that with a simple representation shift, ordinary partial evaluation is already Jones...

Experiment list: SRX319552 [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available embryonic stem cells || genotype/variation=expressing Flag-bio tagged E2F4 || chip beads=Dynabeads MyOne Streptavidin T1 || chip bea...ds vendor=Invitrogen http://dbarchive.biosciencedbc.jp/k

U.S. BICENTENNIAL EXPOSITION & PAINTING OF AMERICAN FLAG ON VAB

Science.gov (United States)

1976-01-01

Transformation of the U. S. Bicentennial on Science and Technology from an artist's concept to reality is well underway at KSC. At lower right are stages of the Saturn V rocket which will form part of the Exposition. Four of the 15 domes erected to house exhibits by 16 federal agencies and numerous industrial firms are visible in the foreground. At left center, workmen on a scaffold can be seen completing the blue field on the American flag being painted on the Vehicle Assembly Building. The Exposition will be open to the public from May 30 through September 7.

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.

76 FR 1665 - Stakeholder Meetings Regarding the U.S.-Flag Great Lakes Fleet Revitalization Study; Correction

Science.gov (United States)

2011-01-11

... DEPARTMENT OF TRANSPORTATION Maritime Administration [Docket No. MARAD-2010-0111] Stakeholder Meetings Regarding the U.S.-Flag Great Lakes Fleet Revitalization Study; Correction AGENCY: Maritime Administration, Department of Transportation. ACTION: Correction Notice. SUMMARY: On December 29, 2010, at 75 FR...

b-flavour tagging in pp collisions

CERN Multimedia

Birnkraut, Alex

2015-01-01

An essential ingredient of all time-dependent CP violation studies of B mesons is the ability to tag the initial flavour of the B meson. The harsh environment of 7 and 8 TeV pp collisions makes this a particularly difficult enterprise. We report progresses in the flavour tagging of B0 and Bs mesons, including developments of novel techniques like the use of an opposite side charm tagger.

Effect of anesthetic, tag size, and surgeon experience on postsurgical recovering after implantation of electronic tags in a neotropical fish: Prochilodus lineatus (Valenciennes, 1837 (Characiformes: Prochilodontidae

Directory of Open Access Journals (Sweden)

João M. Lopes

Full Text Available ABSTRACT Implantation of telemetry transmitters in fish can be affected by different parameters. This study aimed to evaluate the effect of type of anesthetic, tag size, and surgeon experience on surgical and postsurgical wound healing in the neotropical fish Prochilodus lineatus . In total, eighty fish were surgically implanted with telemetry transmitters and forty fish were kept as controls. Forty fish were implanted with a small tag and other forty were implanted with a large tag. Similarly, forty fish were anesthetized with eugenol and forty fish were anesthetized by electroanesthesia, and forty surgeries were performed by an expert surgeon and forty surgeries were performed by novice surgeons. At the end of the experimental period seventeen (21.3% tagged fish had postsurgical complications, including death (1.3%, tag expulsion (2.5%, antenna migration (2.5%, and infection (15%. Tag size was the key determinant for postsurgical complications. Surgical details and postsurgical wound healing were not affected by type of anesthetic. Incision size, duration of surgery, and wound area were significantly affected by tag size and surgeon experience, and the number of sutures was significantly affected by tag size only. The results indicate that successful implantation of telemetry transmitters is dependent upon surgeon experience and tag size.

CT colonography with rectal iodine tagging: Feasibility and comparison with oral tagging in a colorectal cancer screening population.

Science.gov (United States)

Neri, Emanuele; Mantarro, Annalisa; Faggioni, Lorenzo; Scalise, Paola; Bemi, Pietro; Pancrazi, Francesca; D'Ippolito, Giuseppe; Bartolozzi, Carlo

2015-09-01

To evaluate feasibility, diagnostic performance, patient acceptance, and overall examination time of CT colonography (CTC) performed through rectal administration of iodinated contrast material. Six-hundred asymptomatic subjects (male:female=270:330; mean 63 years) undergoing CTC for colorectal cancer screening on an individual basis were consecutively enrolled in the study. Out of them, 503 patients (group 1) underwent CTC with rectal tagging, of which 55 had a total of 77 colonic lesions. The remaining 97 patients (group 2) were randomly selected to receive CTC with oral tagging of which 15 had a total of 20 colonic lesions. CTC findings were compared with optical colonoscopy, and per-segment image quality was visually assessed using a semi-quantitative score (1=poor, 2=adequate, 3=excellent). In 70/600 patients (11.7%), CTC was performed twice with both types of tagging over a 5-year follow-up cancer screening program. In this subgroup, patient acceptance was rated via phone interview two weeks after CTC using a semi-quantitative scale (1=poor, 2=fair, 3=average, 4=good, 5=excellent). Mean per-polyp sensitivity, specificity, positive and negative predictive values of CTC with rectal vs oral tagging were 96.1% (CI95% 85.4÷99.3%) vs 89.4% (CI95% 65.4÷98.1%), 95.3% (CI95% 90.7÷97.8%) vs 95.8% (CI95% 87.6÷98.9%), 86.0% (CI95% 73.6÷93.3) vs 85.0% (CI95% 61.1÷96.0%), and 98.8% (CI95% 95.3÷99.8%) vs 97.2% (CI95% 89.4÷99.5%), respectively (p>0.05). Polyp detection rates were not statistically different between groups 1 and 2 (p>0.05). Overall examination time was significantly shorter with rectal than with oral tagging (18.3±3.5 vs 215.6±10.3 minutes, respectively; pRectal iodine tagging can be an effective alternative to oral tagging for CTC with the advantages of greater patient acceptance and lower overall examination time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

77 FR 76367 - Availability of E-Tag Information to Commission Staff

Science.gov (United States)

2012-12-28

...-Tag Access to MMUs, RTOs and ISOs........ 43 1. E-Tag NOPR 43 2. Comments 44 3. Commission... requires that Regional Transmission Organizations (RTOs), Independent System Operators (ISOs) and their... MMUs for RTOs and ISOs to have access to complete e-Tag information, including access to e-Tags for...

A tool for conditions tag management in ATLAS

International Nuclear Information System (INIS)

Sharmazanashvili, A; Batiashvili, G; Gvaberidze, G; Shekriladze, L; Formica, A

2014-01-01

ATLAS Conditions data include about 2 TB in a relational database and 400 GB of files referenced from the database. Conditions data is entered and retrieved using COOL, the API for accessing data in the LCG Conditions Database infrastructure. It is managed using an ATLAS-customized python based tool set. Conditions data are required for every reconstruction and simulation job, so access to them is crucial for all aspects of ATLAS data taking and analysis, as well as by preceding tasks to derive optimal corrections to reconstruction. Optimized sets of conditions for processing are accomplished using strict version control on those conditions: a process which assigns COOL Tags to sets of conditions, and then unifies those conditions over data-taking intervals into a COOL Global Tag. This Global Tag identifies the set of conditions used to process data so that the underlying conditions can be uniquely identified with 100% reproducibility should the processing be executed again. Understanding shifts in the underlying conditions from one tag to another and ensuring interval completeness for all detectors for a set of runs to be processed is a complex task, requiring tools beyond the above mentioned python utilities. Therefore, a JavaScript /PHP based utility called the Conditions Tag Browser (CTB) has been developed. CTB gives detector and conditions experts the possibility to navigate through the different databases and COOL folders; explore the content of given tags and the differences between them, as well as their extent in time; visualize the content of channels associated with leaf tags. This report describes the structure and PHP/ JavaScript classes of functions of the CTB.

Implementing traceability using particle randomness-based textile printed tags

Science.gov (United States)

Agrawal, T. K.; Koehl, L.; Campagne, C.

2017-10-01

This article introduces a random particle-based traceability tag for textiles. The proposed tag not only act as a unique signature for the corresponding textile product but also possess the features such as easy to manufacture and hard to copy. It seeks applications in brand authentication and traceability in textile and clothing (T&C) supply chain. A prototype has been developed by screen printing process, in which micron-scale particles were mixed with the printing paste and printed on cotton fabrics to attain required randomness. To encode the randomness, the image of the developed tag was taken and analyzed using image processing. The randomness of the particles acts as a product key or unique signature which is required to decode the tag. Finally, washing and abrasion resistance tests were conducted to check the durability of the printed tag.

Directly Printable Frequency Signature Chipless RFID Tag for IoT Applications

Directory of Open Access Journals (Sweden)

H. Anam

2017-04-01

Full Text Available This Paper proposes a low-cost, compact, flexible passive chipless RFID tag that has been designed and analyzed. The tag is a bowtie-shaped resonator based structure with 36 slots; where each patch is loaded with 18 slots. The tag is set in a way that each slot in a patch corresponds to a metal gap in the other patch. Hence there is no mutual interference, and high data capacity of 36 bits is achieved in such compact size. Each slot corresponds to a resonance frequency in the RCS curve, and each resonance corresponds to a bit. The tag has been realized for Taconic TLX-0, PET, and Kapton®HN (DuPontTM substrates with copper, aluminum, and silver nanoparticle-based ink (Cabot CCI-300 as conducting materials. The tag exhibits flexibility and well optimized while remaining in a compact size. The proposed tag yields 36 bits in a tag dimension of 24.5 x 25.5 mm^2. These 36 bits can tag 2^36 number of objects/items. The ultimate high capacity, compact size, flexible passive chipless RFID tag can be arrayed in various industrial and IoT-based applications.

Flavour Tagging Algorithms and Performances in LHCb

CERN Document Server

Calvi, M; Musy, M

2007-01-01

In this note we describe the general characteristics of the LHCb flavour tagging algorithms and summarize the tagging performances on the Monte Carlo samples generated for the Data Challenge 2004 in different decay channels. We also discuss some systematics effects and possible methods to extract the mistag fraction in real data.

A measurement of Rb using mutually exclusive tags

Science.gov (United States)

Barate, R.; Buskulic, D.; Decamp, D.; Ghez, P.; Goy, C.; Lees, J.-P.; Lucotte, A.; Minard, M.-N.; Nief, J.-Y.; Pietrzyk, B.; Casado, M. P.; Chmeissani, M.; Comas, P.; Crespo, J. M.; Delfino, M.; Fernandez, E.; Fernandez-Bosman, M.; Garrido, Ll.; Juste, A.; Martinez, M.; Miquel, R.; Mir, Ll. M.; Orteu, S.; Padilla, C.; Park, I. C.; Pascual, A.; Perlas, J. A.; Riu, I.; Sanchez, F.; Teubert, F.; Colaleo, A.; Creanza, D.; de Palma, M.; Gelao, G.; Iaselli, G.; Maggi, G.; Maggi, M.; Marinelli, N.; Nuzzo, S.; Ranieri, A.; Raso, G.; Ruggieri, F.; Selvaggi, G.; Silvestris, L.; Tempesta, P.; Tricomi, A.; Zito, G.; Huang, X.; Lin, J.; Ouyang, Q.; Wang, T.; Xie, Y.; Xu, R.; Xue, S.; Zhang, J.; Zhang, L.; Zhao, W.; Abbaneo, D.; Alemany, R.; Becker, U.; Bazarko, A. O.; Bright-Thomas, P.; Cattaneo, M.; Cerutti, F.; Drevermann, H.; Forty, R. W.; Frank, M.; Hagelberg, R.; Harvey, J.; Janot, P.; Jost, B.; Kneringer, E.; Knobloch, J.; Lehraus, I.; Lutters, G.; Mato, P.; Minten, A.; Moneta, L.; Pacheco, A.; Pusztaszeri, J.-F.; Ranjard, F.; Rensing, P.; Rizzo, G.; Rolandi, L.; Schlatter, D.; Schmitt, M.; Schneider, O.; Tejessy, W.; Tomalin, I. R.; Wachsmuth, H.; Wagner, A.; Ajaltouni, Z.; Barrès, A.; Boyer, C.; Falvard, A.; Ferdi, C.; Gay, P.; Guicheney, C.; Henrard, P.; Jousset, J.; Michel, B.; Monteil, S.; Montret, J.-C.; Pallin, D.; Perret, P.; Podlyski, F.; Proriol, J.; Rosnet, P.; Rossignol, J.-M.; Fearnley, T.; Hansen, J. B.; Hansen, J. D.; Hansen, J. R.; Hansen, P. H.; Nilsson, B. S.; Rensch, B.; Wäänänen, A.; Daskalakis, G.; Kyriakis, A.; Markou, C.; Simopoulou, E.; Siotis, I.; Vayaki, A.; Blondel, A.; Bonneaud, G.; Brient, J. C.; Bourdon, P.; Rougé, A.; Rumpf, M.; Valassi, A.; Verderi, M.; Videau, H.; Candlin, D. J.; Parsons, M. I.; Focardi, E.; Parrini, G.; Zachariadou, K.; Corden, M.; Georgiopoulos, C.; Jaffe, D. E.; Antonelli, A.; Bencivenni, G.; Bologna, G.; Bossi, F.; Campana, P.; Capon, G.; Casper, D.; Chiarella, V.; Felici, G.; Laurelli, P.; Mannocchi, G.; Murtas, F.; Murtas, G. P.; Passalacqua, L.; Pepe-Altarelli, M.; Curtis, L.; Dorris, S. J.; Halley, A. W.; Knowles, I. G.; Lynch, J. G.; O'Shea, V.; Raine, C.; Scarr, J. M.; Smith, K.; Teixeira-Dias, P.; Thompson, A. S.; Thomson, E.; Thomson, F.; Turnbull, R. M.; Geweniger, C.; Graefe, G.; Hanke, P.; Hansper, G.; Hepp, V.; Kluge, E. E.; Putzer, A.; Schmidt, M.; Sommer, J.; Tittel, K.; Werner, S.; Wunsch, M.; Beuselinck, R.; Binnie, D. M.; Cameron, W.; Dornan, P. J.; Girone, M.; Goodsir, S.; Martin, E. B.; Moutoussi, A.; Nash, J.; Sedgbeer, J. K.; Stacey, A. M.; Williams, M. D.; Dissertori, G.; Ghete, V. M.; Girtler, P.; Kuhn, D.; Rudolph, G.; Betteridge, A. P.; Bowdery, C. K.; Colrain, P.; Crawford, G.; Finch, A. J.; Foster, F.; Hughes, G.; Sloan, T.; Williams, M. I.; Galla, A.; Giehl, I.; Greene, A. M.; Hoffmann, C.; Jakobs, K.; Kleinknecht, K.; Quast, G.; Renk, B.; Rohne, E.; Sander, H.-G.; van Gemmeren, P.; Zeitnitz, C.; Aubert, J. J.; Benchouk, C.; Bonissent, A.; Bujosa, G.; Calvet, D.; Carr, J.; Coyle, P.; Diaconu, C.; Etienne, F.; Konstantinidis, N.; Leroy, O.; Motsch, F.; Payre, P.; Rousseau, D.; Talby, M.; Sadouki, A.; Thulasidas, M.; Trabelsi, K.; Aleppo, M.; Ragusa, F.; Berlich, R.; Blum, W.; Brown, D.; Büscher, V.; Dietl, H.; Dydak, F.; Ganis, G.; Gotzhein, C.; Kroha, H.; Lütjens, G.; Lutz, G.; Männer, W.; Moser, H.-G.; Richter, R.; Rosado-Schlosser, A.; Schael, S.; Settles, R.; Seywerd, H.; St. Denis, R.; Stenzel, H.; Wiedenmann, W.; Wolf, G.; Boucrot, J.; Callot, O.; Chen, S.; Choi, Y.; Cordier, A.; Davier, M.; Duflot, L.; Grivaz, J.-F.; Heusse, Ph.; Höcker, A.; Jacholkowska, A.; Jacquet, M.; Kim, D. W.; Le Diberder, F.; Lefrançois, J.; Lutz, A.-M.; Nilolic, I.; Schune, M.-H.; Simion, S.; Tournefier, E.; Veillet, J.-J.; Videau, I.; Zerwas, D.; Azzurri, P.; Bagliesi, G.; Batignani, G.; Bettarini, S.; Bozzi, C.; Calderini, G.; Carpinelli, M.; Ciocci, M. A.; Ciulli, V.; dell'Orso, R.; Fantechi, R.; Ferrante, I.; Foà, L.; Forti, F.; Giassi, A.; Giorgi, M. A.; Gregorio, A.; Ligabue, F.; Lusiani, A.; Marrocchesi, P. S.; Messineo, A.; Palla, F.; Sanguinetti, G.; Sciabà, A.; Spagnolo, P.; Steinberger, J.; Tenchini, R.; Tonelli, G.; Vannini, C.; Venturi, A.; Verdini, P. G.; Blair, G. A.; Bryant, L. M.; Chambers, J. T.; Gao, Y.; Green, M. G.; Medcalf, T.; Perrodo, P.; Strong, J. A.; von Wimmersperg-Toeller, J. H.; Botterill, D. R.; Clifft, R. W.; Edgecock, T. R.; Haywood, S.; Maley, P.; Norton, P. R.; Thompson, J. C.; Wright, A. E.; Bloch-Devaux, B.; Colas, P.; Emery, S.; Kozanecki, W.; Lançon, E.; Lemaire, M. C.; Locci, E.; Perez, P.; Rander, J.; Renardy, J.-F.; Roussarie, A.; Schuller, J.-P.; Schwindling, J.; Trabelsi, A.; Vallage, B.; Black, S. N.; Dann, J. H.; Johnson, R. P.; Kim, H. Y.; Litke, A. M.; McNeil, M. A.; Taylor, G.; Booth, C. N.; Boswell, R.; Brew, C. A. J.; Cartwright, S.; Combley, F.; Kelly, M. S.; Lehto, M.; Newton, W. M.; Reeve, J.; Thompson, L. F.; Böhrer, A.; Brandt, S.; Cowan, G.; Grupen, C.; Saraiva, P.; Smolik, L.; Stephan, F.; Apollonio, M.; Bosisio, L.; Della Marina, R.; Giannini, G.; Gobbo, B.; Musolino, G.; Rothberg, J.; Wasserbaech, S.; Armstrong, S. R.; Charles, E.; Elmer, P.; Ferguson, D. P. S.; Gao, Y. S.; González, S.; Greening, T. C.; Hayes, O. J.; Hu, H.; Jin, S.; McNamara, P. A.; Nachtman, J. M.; Nielsen, J.; Orejudos, W.; Pan, Y. B.; Saadi, Y.; Scott, I. J.; Walsh, J.; Sau, Lan Wu; Wu, X.; Yamartino, J. M.; Zobernig, G.

1997-02-01

A measurement of Rb using five mutually exclusive hemisphere tags has been performed by ALEPH using the full LEP1 statistics. Three tags are designed to select the decay of the Z0 to b quarks, while the remaining two selectZ0 decays to c and light quarks, and are used to measure the tagging efficiencies. The result, Rb = 0.2159 +/- 0.0009 (stat) +/- 0.0011 (syst), is in agreement with the electroweak theory prediction of 0.2158 +/- 0.0003.

Flagging optically shallow pixels for improved analysis of ocean color data

Science.gov (United States)

McKinna, L. I. W.; Werdell, J.; Knowles, D., Jr.

2016-02-01

Ocean color remote-sensing is routinely used to derive marine geophysical parameters from sensor-observed water-leaving radiances. However, in clear geometrically shallow regions, traditional ocean color algorithms can be confounded by light reflected from the seafloor. Such regions are typically referred to as "optically shallow". When performing spatiotemporal analyses of ocean color datasets, optically shallow features such as coral reefs can lead to unexpected regional biases. Benthic contamination of the water-leaving radiance is dependent on bathymetry, water clarity and seafloor albedo. Thus, a prototype ocean color processing flag called OPTSHAL has been developed that takes all three variables into account. In the method described here, the optical depth of the water column at 547 nm, ζ(547), is predicted from known bathymetry and estimated inherent optical properties. If ζ(547) is less then the pre-defined threshold, a pixel is flagged as optically shallow. Radiative transfer modeling was used to identify the appropriate threshold value of ζ(547) for a generic benthic sand albedo. OPTSHAL has been evaluated within the NASA Ocean Biology Processing Group's L2GEN code. Using MODIS Aqua imagery, OPTSHAL was tested in two regions: (i) the Pedro Bank south-west of Jamaica, and (ii) the Great Barrier Reef, Australia. It is anticipated that OPTSHAL will benefit end-users when quality controlling derived ocean color products. Further, OPTSHAL may prove useful as a mechanism for switching between optically deep and shallow algorithms during ocean color processing.

Comparison of three nonlinear models to describe long-term tag shedding by lake trout

Science.gov (United States)

Fabrizio, Mary C.; Swanson, Bruce L.; Schram, Stephen T.; Hoff, Michael H.

1996-01-01

We estimated long-term tag-shedding rates for lake trout Salvelinus namaycush using two existing models and a model we developed to account for the observed permanence of some tags. Because tag design changed over the course of the study, we examined tag-shedding rates for three types of numbered anchor tags (Floy tags FD-67, FD-67C, and FD-68BC) and an unprinted anchor tag (FD-67F). Lake trout from the Gull Island Shoal region, Lake Superior, were double-tagged, and subsequent recaptures were monitored in annual surveys conducted from 1974 to 1992. We modeled tag-shedding rates, using time at liberty and probabilities of tag shedding estimated from fish released in 1974 and 1978–1983 and later recaptured. Long-term shedding of numbered anchor tags in lake trout was best described by a nonlinear model with two parameters: an instantaneous tag-shedding rate and a constant representing the proportion of tags that were never shed. Although our estimates of annual shedding rates varied with tag type (0.300 for FD-67, 0.441 for FD-67C, and 0.656 for FD-68BC), differences were not significant. About 36% of tags remained permanently affixed to the fish. Of the numbered tags that were shed (about 64%), two mechanisms contributed to tag loss: disintegration and dislodgment. Tags from about 11% of recaptured fish had disintegrated, but most tags were dislodged. Unprinted tags were shed at a significant but low rate immediately after release, but the long-term, annual shedding rate of these tags was only 0.013. Compared with unprinted tags, numbered tags dislodged at higher annual rates; we hypothesized that this was due to the greater frictional drag associated with the larger cross-sectional area of numbered tags.

A wireless sensor tag platform for container security and integrity

Science.gov (United States)

Amaya, Ivan A.; Cree, Johnathan V.; Mauss, Fredrick J.

2011-04-01

Cargo containers onboard ships are widely used in the global supply chain. The need for container security is evidenced by the Container Security Initiative launched by the U.S. Bureau of Customs and Border Protection (CBP). One method of monitoring cargo containers is using low power wireless sensor tags. The wireless sensor tags are used to set up a network that is comprised of tags internal to the container and a central device. The sensor network reports alarms and other anomalies to a central device, which then relays the message to an outside network upon arrival at the destination port. This allows the port authorities to have knowledge of potential security or integrity issues before physically examining the container. Challenges of using wireless sensor tag networks for container security include battery life, size, environmental conditions, information security, and cost among others. PNNL developed an active wireless sensor tag platform capable of reporting data wirelessly to a central node as well as logging data to nonvolatile memory. The tags, operate at 2.4 GHz over an IEEE 802.15.4 protocol, and were designed to be distributed throughout the inside of a shipping container in the upper support frame. The tags are mounted in a housing that allows for simple and efficient installation or removal prior to, during, or after shipment. The distributed tags monitor the entire container volume. The sensor tag platform utilizes low power electronics and provides an extensible sensor interface for incorporating a wide range of sensors including chemical, biological, and environmental sensors.

Tag gas burnup based on three-dimensional FTR analysis

International Nuclear Information System (INIS)

Kidman, R.B.

1976-01-01

Flux spectra from a three-dimensional diffusion theory analysis of the Fast Test Reactor (FTR) are used to predict gas tag ratio changes, as a function of exposure, for each FTR fuel and absorber subassembly plenum. These flux spectra are also used to predict Xe-125 equilibrium activities in absorber plena in order to assess the feasibility of using Xe-125 gamma rays to detect and distinguish control rod failures from fuel rod failures. Worst case tag burnup changes are used in conjunction with burnup and mass spectrometer uncertainties to establish the minimum spacing of tags which allows the tags to be unambiguously identified