82 resultados para GAlvin
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Multiple human skeletal and craniosynostosis disorders, including Crouzon, Pfeiffer, Jackson–Weiss, and Apert syndromes, result from numerous point mutations in the extracellular region of fibroblast growth factor receptor 2 (FGFR2). Many of these mutations create a free cysteine residue that potentially leads to abnormal disulfide bond formation and receptor activation; however, for noncysteine mutations, the mechanism of receptor activation remains unclear. We examined the effect of two of these mutations, W290G and T341P, on receptor dimerization and activation. These mutations resulted in cellular transformation when expressed as FGFR2/Neu chimeric receptors. Additionally, in full-length FGFR2, the mutations induced receptor dimerization and elevated levels of tyrosine kinase activity. Interestingly, transformation by the chimeric receptors, dimerization, and enhanced kinase activity were all abolished if either the W290G or the T341P mutation was expressed in conjunction with mutations that eliminate the disulfide bond in the third immunoglobulin-like domain (Ig-3). These results demonstrate a requirement for the Ig-3 cysteine residues in the activation of FGFR2 by noncysteine mutations. Molecular modeling also reveals that noncysteine mutations may activate FGFR2 by altering the conformation of the Ig-3 domain near the disulfide bond, preventing the formation of an intramolecular bond. This allows the unbonded cysteine residues to participate in intermolecular disulfide bonding, resulting in constitutive activation of the receptor.
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Pathogenic α-synuclein (αS) gene mutations occur in rare familial Parkinson’s disease (PD) kindreds, and wild-type αS is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer’s disease, but β-synuclein (βS) and γ-synuclein (γS) have not yet been implicated in neurological disorders. Here we show that in PD and DLB, but not normal brains, antibodies to αS and βS reveal novel presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 regions, whereas antibodies to γS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation of other synaptic proteins and synaptic vesicle-like structures in the αS- and βS-labeled hilar dystrophic neurites suggests that synaptic dysfunction may result from these lesions. Our findings broaden the concept of neurodegenerative “synucleinopathies” by implicating βS and γS, in addition to αS, in the onset/progression of PD and DLB.
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Crouzon syndrome is an autosomal dominant condition primarily characterized by craniosynostosis. This syndrome has been associated with a variety of amino acid point mutations in the extracellular domain of fibroblast growth factor receptor 2 (FGFR2). FGFR2/Neu chimeras were generated by substituting the extracellular domain of Neu with that of FGFR2 containing the following Crouzon mutations: Tyr-340-->His; Cys-342-->Tyr; Cys-342-->Arg; Cys-342-->Ser; Ser-354-->Cys: and delta17 (deletion of amino acids 345-361). Each of the mutant chimeric FGFR2/Neu constructs stimulated focus formation in NIH 3T3 cells, indicating that Crouzon mutations can stimulate signal transduction through a heterologous receptor tyrosine kinase. In vitro kinase assay results indicate that FGFR2 receptors containing Crouzon mutations have increased tyrosine kinase activity and, when analyzed under nonreducing conditions, exhibited disulfide-bonded dimers. Thus the human developmental abnormality Crouzon syndrome arises from constitutive activation of FGFR2 due to aberrant intermolecular disulfide-bonding. These results together with our earlier observation that achondroplasia results from constitutive activation of the related receptor FGFR3, leads to the prediction that other malformation syndromes attributed to FGFRs, such as Pfeiffer syndrome and Thanatophoric dysplasia, also arise from constitutive receptor activation.
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This report presents an overview of wave-current interacion, including comprehensive review of references to significant U.S. and foreign literature available through December 1981. Specific topics under review are the effects of horizontally and vertically varying currents on waves, wave refraction by currents, dissipation and turbulence, small- and medium-scale currents, caustics and focusing, and wave breaking. The results of the review are then examined for engineering applications. The most appropriate general-purpose computer program to include wave-current interaction is the Dutch Rijkswaterstaat program CREDIZ, which is based on a parabolic wave equation. Further applications include wave and current forces on structures and possibly sediment transport. The report concludes with a brief state-of-the-art review of wave-current interaction and a list of topics needing further research and development.
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This annotated bibliography discusses 60 key publications dealing with wave-current interaction. Each entry includes a bibliographic identification, keywords, a discussion of contents, and a statement of coastal engineering significance. An index of the entries by keywords is provided in an appendix. The recent growth of the wave-current interaction field is indicated by the fact that more than 30 percent of the selected publications were published in 1978 and 1979. (Author).
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"March 1977."
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"March 1964."
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"January 1965."
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"January 1977."
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"June 1980."
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As presently used, the immersed weight rate, I sub l, is the volume rate, Q, of longshore transport, multiplied by a constant. For use in engineering problems, I sub l must be converted back to the equivalent Q. The I sub l formulation may be important where the unit weight of sand differs significantly from the unit weight of sand at the open-coast sites contributing data to the design curve. Increase in void ratio may result in a 10- to 20-percent increase in actual (as compared to predicted) shoaling volumes where sand accumulates in protected water. Void ratio should be measured in field studies of longshore transport.
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Mode of access: Internet.
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Corrections mounted over text on p. 2, 7, 25-26, 82 and 129.
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Painted by Alvah Bradish (1806-1901), Professor of Fine Arts, UM, ca. 1860. Photographed by Scott Galvin (from a ladder, while original was still hanging at Palmer Commons, in frame) 12/07/09
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In this paper, we demonstrate the integration of a 3D hydrogel matrix within a hollow core photonic crystal fibre (HC-PCF). In addition, we also show the fluorescence of Cy5-labelled DNA molecules immobilized within the hydrogel formed in two different types of HC-PCF. The 3D hydrogel matrix is designed to bind with the amino groups of biomolecules using an appropriate cross-linker, providing higher sensitivity and selectivity than the standard 2D coverage, enabling a greater number of probe molecules to be available per unit area. The HC-PCFs, on the other hand, can be designed to maximize the capture of fluorescence to improve sensitivity and provide longer interaction lengths. This could enable the development of fibre-based point-of-care and remote systems, where the enhanced sensitivity would relax the constraints placed on sources and detectors. In this paper, we will discuss the formation of such polyethylene glycol diacrylate (PEGDA) hydrogels within a HC-PCF, including their optical properties such as light propagation and auto-fluorescence.