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  • 1
    Electronic Resource
    Electronic Resource
    The Order of Exposure of Tau to Signal Transduction Kinases Alters the Generation of “AD-Like” Phosphoepitopes (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 223-233 
    Details
    ISSN: 1573-6830
    Keywords: tau ; kinases ; signal transduction ; Alzheimer's disease ; phosphorylation ; paired helical filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. The individual and sequential influence of protein kinase C (PKC), protein kinase A (PKA) and mitogen-activated protein kinase (MAP kinase) on human brain tau was examined. 2. A range of PKC concentrations generated certain phosphoepitopes common with paired helical filaments. These epitopes were masked by higher PKC concentrations, suggesting the presence of multiple tau phosphorylation sites for which PKC exhibited differing affinities and/or conformational alterations in tau induced by sequential PKC-mediated phosphorylation. 3. Prior phosphorylation by PKC enhanced the nature and extent of AD-like tau antigenicity generated by subsequent incubation with MAP kinase yet inhibited that generated by subsequent incubation with PKA. 4. Dephosphorylation of tau prior to incubation with kinases significantly altered the influence of individual and multiple kinase incubation on tau antigenicity in a site-specific manner, indicating that prior in situ phosphorylation events markedly influenced subsequent cell-free phosphorylation. 5. In addition to considerations of the potential impact of tau phosphorylation by individual kinases, these findings extend previous studies which indicate that tau antigenicity, and, presumably, its behavior in situ, is influenced by the sequential and convergent influences of multiple kinases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006977127422
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Hyperactivation of Mitogen-Activated Protein Kinase Increases Phospho-Tau Immunoreactivity Within Human Neuroblastoma: Additive and Synergistic Influence of Alteration of Additional Kinase Activities (1999)
    Springer
    Cellular and molecular neurobiology 19 (1999), S. 249-260 
    Details
    ISSN: 1573-6830
    Keywords: MAP kinase ; tau ; protein kinase C ; wortmannin ; PD98059 ; neuroblastoma ; Alzheimer's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mitogen-activated protein (MAP) kinase phosphorylates tau in cell-free analyses, but whether or not it does so within intact cells remains controversial. In the present study, microinjection of MAP kinase into SH-SY-5Y human neuroblastoma cells increased tau immunoreactivity toward the phosphodependent antibodies PHF-1 and AT-8. In contrast, treatment with a specific inhibitor of MAP kinase (PD98059) did not diminish “basal” levels of these immunoreactivities in otherwise untreated cells. These findings indicate that hyperactivation of MAP kinase increases phospho-tau levels within cells, despite that MAP kinase apparently does not substantially influence intracellular tau phosphorylation under normal conditions. These findings underscore that results obtained following inhibition of kinase activities do not necessarily provide an indication of the consequences accompanying hyperactivation of that same kinase. Several studies conducted in cell-free systems indicate that exposure of tau to multiple kinases can have synergistic effects on the nature and extent of tau phosphorylation. We therefore examined whether or not such effects could be demonstrated within these cells. Site-specific phospho-tau immunoreactivity was increased in additive and synergistic manners by treatment of injected cells with TPA (which activates PKC), calcium ionophore (which activates calcium-dependent kinases), and wortmannin (which inhibits PIP3 kinase). Alteration in total tau levels was insufficient to account for the full extent of the increase in phospho-tau immunoreactivity. These additional results indicate that multiple kinase activities modulate the influence of MAP kinase on tau within intact cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006981228331
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  • 3
    Electronic Resource
    Electronic Resource
    Phosphorylation of Tau Alters Its Association with the Plasma Membrane (2000)
    Springer
    Cellular and molecular neurobiology 20 (2000), S. 497-508 
    Details
    ISSN: 1573-6830
    Keywords: tau ; phosphorylation ; signal transduction ; protein kinase C ; Alzheimer's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. The potential functions of the microtubule-associated protein tau have been expanded by the recent demonstration of its interaction with the plasma membrane. Since the association of tau with microtubules is regulated by phosphorylation, herein we examine whether or not the association of tau with the plasma membrane is also regulated by phosphorylation. 2. A range of tau isoforms migrating from 46 to 64 kDa was associated with crude particulate fractions derived from SH-SY-5Y human neuroblastoma cells, and were retained during the initial stages of plasma membrane purification. During the extensive washing utilized in purification of the plasma membrane, portions of each of these isoforms were depleted from the resultant purified membrane. Immunoblot analysis with phospho-dependent and -independent antibodies revealed selective depletion of phospho isoforms during membrane washing. This effect was more pronounced for the slowest-migrating (64-kDa) tau isoform. 3. This putative influence of phosphorylation on the association of tau with the plasma membrane was further probed by transfection of SH-SY-5Y human neuroblastoma cells with a tau construct that could associate with the plasma membrane but not with microtubules. Treatment with phorbol ester or calcium ionophore, both of which increased phospho-tau levels within the cytosol and plasma membrane, was accompanied by the dissociation of this tau construct from the membrane. 4. These data indicate that phosphorylation regulates the association with the plasma membrane. Dissociation from the membrane by phosphorylation may place tau at risk for hyperphosphorylation and ultimate PHF formation in a manner previously considered for tau dissociated from microtubules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007075115574
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  • 4
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    Effect of turbulence models on criticality conditions in swirling flows (1995)
    In:  CASI
    Details
    Publication Date: 2013-08-31
    Description: The critical state of vortex cores downstream of vortex breakdown has been studied. Base vortical flows were computed using the Reynolds-averaged, axisymmetric Navier-Stokes equations. Standard K - epsilon, RNG and second-order Reynolds stress models were employed. Results indicate that the return to supercriticality is highly dependent on the turbulence model. The K - epsilon model predicted a rapid return of the vortex to supercritical conditions, the location of which showed little sensitivity to changes in the swirl ratio. The Reynolds stress model predicted that the vortex remains subcritical to the end of the domain for each of the swirl ratios employed, and provided results in qualitative agreement with experimental work. The RNG model produced intermediate results, with a downstream movement in the critical location with increasing swirl. Calculations for which area reductions were introduced at the exit in a subcritical flow were also performed using the Reynolds stress model. The structure of the resulting recirculation zone was altered significantly. However, when area reductions were employed within supercritical flows as predicted using the two-equation models, no significant influence on the recirculation zone was noted.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: NASA. Lewis Research Center, The Sixth Annual Thermal and Fluids Analysis Workshop; p 163-173
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  • 5
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    Numerical experiments on boundary-layer receptivity (1987)
    In:  Other Sources
    Details
    Publication Date: 2011-08-19
    Description: The incompressible laminar flow over an infinitely thin flat plate is obtained using a Navier-Stokes code in vorticity-velocity variables. The flow at and near the leading edge of the plate is an integral part of the solution algorithm which requires no special treatment; thus allowing for the flow field in this region to be studied in detail. An incident plane sound wave is imposed in the free-stream flow and the receptivity of the boundary layer is studied with particular emphasis to the flow near and at the leading edge.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
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  • 6
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    The present state and future direction of second order closure models for compressible flows (1992)
    In:  CASI
    Details
    Publication Date: 2013-08-29
    Description: The topics are presented in viewgraph form and include: (1) Reynolds stress closure models; (2) Favre averages and governing equations; (3) the model for the deviatoric part of the pressure-strain rate correlation; (4) the SSG pressure-strain correlation model; (5) a compressible turbulent dissipation rate model; (6) variable viscosity effects; (7) near-wall stiffness problems; (8) models of the Reynolds mass and heat flux; and (9) a numerical solution of the compressible turbulent transport equation.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: NASA. Lewis Research Center, Workshop on Engineering Turbulence Modeling; p 249-275
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  • 7
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    Studies in turbulence (1992)
    In:  Other Sources
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    Publication Date: 2019-01-25
    Description: Various papers on turbulence are presented. Individual topics addressed include: modeling the dissipation rate in rotating turbulent flows, mapping closures for turbulent mixing and reaction, understanding turbulence in vortex dynamics, models for the structure and dynamics of near-wall turbulence, complexity of turbulence near a wall, proper orthogonal decomposition, propagating structures in wall-bounded turbulence flows. Also discussed are: constitutive relation in compressible turbulence, compressible turbulence and shock waves, direct simulation of compressible turbulence in a shear flow, structural genesis in wall-bounded turbulence flows, vortex lattice structure of turbulent shear slows, etiology of shear layer vortices, trilinear coordinates in fluid mechanics.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: ; 615 p.
    Format: text
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  • 8
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    Modeling the dissipation rate in rotating turbulent flows (1990)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: A variety of modifications to the modeled dissipation rate transport equation that have been proposed during the past two decades to account for rotational strains are examined. The models are subjected to two crucial test cases: the decay of isotropic turbulence in a rotating frame and homogeneous shear flow in a rotating frame. It is demonstrated that these modifications do not yield substantially improved predictions for these two test cases and in many instances give rise to unphysical behavior. An alternative proposal, based on the use of the tensor dissipation rate, is made for the development of improved models.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: NASA-CR-187485 , ICASE-90-88 , NAS 1.26:187485 , AD-A232079
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  • 9
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    An analysis of RNG based turbulence models for homogeneous shear flow (1991)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: In a recent paper, the authors compared the performance of a variety of turbulence models including the k-epsilon model and the second-order closure model based on Renormalization Group (RNG) Methods. The performance of these RNG models in homogeneous turbulent shear flow was found to be quite poor, apparently due to the value of the constant C(sub epsilon1) in the modeled dissipation rate equation which was substantially lower than its traditional value. However, recently a correction has been made in the RNG based calculation of C(sub epsilon1). It is shown that with the new value of C(sub epsilon1), the performance of the RNG k-epsilon model is substantially improved. On the other hand, while the predictions of the revised RNG second-order closure model are better, some lingering problems still remain which can be easily remedied by the addition of higher order terms.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: NASA-CR-187552 , NAS 1.26:187552 , ICASE-91-37 , AD-A236667
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  • 10
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    Modeling the pressure-strain correlation of turbulence: An invariant dynamical systems approach (1990)
    In:  CASI
    Details
    Publication Date: 2019-06-28
    Description: The modeling of the pressure-strain correlation of turbulence is examined from a basic theoretical standpoint with a view toward developing improved second-order closure models. Invariance considerations along with elementary dynamical systems theory are used in the analysis of the standard hierarchy of closure models. In these commonly used models, the pressure-strain correlation is assumed to be a linear function of the mean velocity gradients with coefficients that depend algebraically on the anisotropy tensor. It is proven that for plane homogeneous turbulent flows the equilibrium structure of this hierarchy of models is encapsulated by a relatively simple model which is only quadratically nonlinear in the anisotropy tensor. This new quadratic model - the SSG model - is shown to outperform the Launder, Reece, and Rodi model (as well as more recent models that have a considerably more complex nonlinear structure) in a variety of homogeneous turbulent flows. Some deficiencies still remain for the description of rotating turbulent shear flows that are intrinsic to this general hierarchy of models and, hence, cannot be overcome by the mere introduction of more complex nonlinearities. It is thus argued that the recent trend of adding substantially more complex nonlinear terms containing the anisotropy tensor may be of questionable value in the modeling of the pressure-strain correlation. Possible alternative approaches are discussed briefly.
    Keywords: FLUID MECHANICS AND HEAT TRANSFER
    Type: NASA-CR-181979 , NAS 1.26:181979 , ICASE-90-5 , AD-A227187
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