554 research outputs found

    Ehlers-Danlos Syndrome Type IV: A Genetic Disorder in Many Guises

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    An Exact Line Search method for solving generalized continuous-time algebraic Riccati equations

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    ©1998 IEEE. Personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution to servers or lists, or to reuse any copyrighted component of this work in other works must be obtained from the IEEE.We present a Newton-like method for solving algebraic Riccati equations that uses Exact Line Search to improve the sometimes erratic convergence behavior of Newton's method. It avoids the problem of a disastrously large first step and accelerates convergence when Newton steps are too small or too long, The additional work to perform the Line search is small relative to the work needed to calculate the Newton step

    An Arithmetic for Matrix Pencils: Theory and New Algorithms

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    This paper introduces arithmetic-like operations on matrix pencils. The pencil-arithmetic operations extend elementary formulas for sums and products of rational numbers and include the algebra of linear transformations as a special case. These operations give an unusual perspective on a variety of pencil related computations. We derive generalizations of monodromy matrices and the matrix exponential. A new algorithm for computing a pencil arithmetic generalization of the matrix sign function does not use matrix inverses and gives an empirically forward numerically stable algorithm for extracting deflating subspaces

    Development and mapping of SNP assays in allotetraploid cotton

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    A narrow germplasm base and a complex allotetraploid genome have made the discovery of single nucleotide polymorphism (SNP) markers difficult in cotton (Gossypiumhirsutum). To generate sequence for SNP discovery, we conducted a genome reduction experiment (EcoRI, BafI double digest, followed by adapter ligation, biotin–streptavidin purification, and agarose gel separation) on two accessions of G. hirsutum and two accessions of G. barbadense. From the genome reduction experiment, a total of 2.04 million genomic sequence reads were assembled into contigs with an N50 of 508 bp and analyzed for SNPs. A previously generated assembly of expressed sequence tags (ESTs) provided an additional source for SNP discovery. Using highly conservative parameters (minimum coverage of 8× at each SNP and 20% minor allele frequency), a total of 11,834 and 1,679 non-genic SNPs were identified between accessions of G. hirsutum and G. barbadense in genome reduction assemblies, respectively. An additional 4,327 genic SNPs were also identified between accessions of G. hirsutum in the EST assembly. KBioscience KASPar assays were designed for a portion of the intra-specific G. hirsutum SNPs. From 704 non-genic and 348 genic markers developed, a total of 367 (267 non-genic, 100 genic) mapped in a segregating F2 population (Acala Maxxa × TX2094) using the Fluidigm EP1 system. A G. hirsutum genetic linkage map of 1,688 cM was constructed based entirely on these new SNP markers. Of the genic-based SNPs, we were able to identify within which genome (‘A’ or ‘D’) each SNP resided using diploid species sequence data. Genetic maps generated by these newly identified markers are being used to locate quantitative, economically important regions within the cotton genome

    Numerical computation of deflating subspaces of skew-Hamiltonian/Hamiltonian pencils

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    Working title was “Numerical Computation of Deflating Subspaces of Embedded Hamiltonian and Symplectic Pencils"We discuss the numerical solution of structured generalized eigenvalue problems that arise from linear- quadratic optimal control problems, H infinity optimization, multibody systems, and many other areas of applied mathematics, physics, and chemistry. The classical approach for these problems requires computing invariant and deflating subspaces of matrices and matrix pencils with Hamiltonian and/ or skew- Hamiltonian structure. We extend the recently developed methods for Hamiltonian matrices to the general case of skew- Hamiltonian/ Hamiltonian pencils. The algorithms circumvent problems with skew- Hamiltonian/ Hamiltonian matrix pencils that lack structured Schur forms by embedding them into matrix pencils that always admit a structured Schur form. The rounding error analysis of the resulting algorithms is favorable. For the embedded matrix pencils, the algorithms use structure- preserving unitary matrix computations and are strongly backwards stable, i. e., they compute the exact structured Schur form of a nearby matrix pencil with the same structure.All authors were partially supported by Deutsche Forschungsgemeinschaft, Research Grant Me 790/7-2 and Sonderforschungsbereich 393, “Numerische Simulation auf massiv parallelen Rechnern”

    Osteogenesis Imperfecta: The Molecular Basis of Clinical Heterogeneity a

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73685/1/j.1749-6632.1988.tb55324.x.pd

    Lentiviral-mediated gene correction of mucopolysaccharidosis type IIIA

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    BACKGROUND: Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of the mucopolysaccharidoses. The disease is caused by a deficiency of the lysosomal enzyme sulphamidase and results in the storage of the glycosaminoglycan (GAG), heparan sulphate. MPS IIIA is characterised by widespread storage and urinary excretion of heparan sulphate, and a progressive and eventually profound neurological course. Gene therapy is one of the few avenues of treatment that hold promise of a sustainable treatment for this disorder. METHODS: The murine sulphamidase gene cDNA was cloned into a lentiviral vector and high-titre virus produced. Human MPS IIIA fibroblast cultures were transduced with the sulphamidase vector and analysed using molecular, enzymatic and metabolic assays. High-titre virus was intravenously injected into six 5-week old MPS IIIA mice. Three of these mice were pre-treated with hyperosmotic mannitol. The weight of animals was monitored and GAG content in urine samples was analysed by polyacrylamide gel electrophoresis. RESULTS: Transduction of cultured MPS IIIA fibroblasts with the sulphamidase gene corrected both the enzymatic and metabolic defects. Sulphamidase secreted by gene-corrected cells was able to cross correct untransduced MPS IIIA cells. Urinary GAG was found to be greatly reduced in samples from mice receiving the vector compared to untreated MPS IIIA controls. In addition, the weight of treated mice became progressively normalised over the 6-months post-treatment. CONCLUSION: Lentiviral vectors appear promising vehicles for the development of gene therapy for MPS IIIA
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