Laminar natural convection over a slender vertical frustrum of a cone with constant wall heat flux

The problem of laminar natural convection flow over a slender frustrum of a cone with constant wall heat flux is treated in this paper. The governing differential equations are solved by a combination of quasilinearization and finite-difference methods. Numerical solutions are obtained for Prandtl numbers from 0.1 to 100 for a range of values of transverse curvature parameter. It is found that the effect of transverse curvature is of great significance in such flows. In dieser Arbeit wird das Problem der laminaren, natürlichen Konvektionsströmung öber einem dünnen Kegelstumpf mit konstantem Wandwärmestrom behandelt. Die maßgeblichen Differentialgleichungen werden mit Hilfe einer Kombination von Quasilinearisierung und Differenzenverfahren gelöst. Numerische Lösungen werden für die Prandtl ' sehen Zahlen zwischen 0. l und 100 innerhalb eines Bereiches von Querkrüm mungswerten erhalten. Es wird gezeigt, daß der Einfluß der Querkrümmung in solchen Strömungen von großer Bedeutung ist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46650/1/231_2005_Article_BF00997635.pd

Laminar natural convection over a slender vertical frustum of a cone

The problem of laminar, natural convection flow over a slender frustum of a cone is treated in this paper. The governing differential equations are solved by a combination of quasi-linearization and finite-difference methods. Numerical solutions are obtained for Pr=0.7 and for a range of values of the transverse curvature parameter. It is shown that the effect of transverse curvature is of great significance in such flows. In diesem Bericht ist das Problem der laminaren natürlichen Konvektionsströmung an einem dünnen Kegelstumpf behandelt. Die maßgebliche Differentialgleichung ist durch eine Verbindung von Quasilinearisation und Differenzenverfahren gelöst. Eine numerische Lösung für Pr=0.7 wird für verschiedene Werte eines Krümmungsparameters angegeben. Es ist gezeigt, daß in solchen Strömungen dieser Krümmungsparameter eine große Bedeutung besitzt.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46649/1/231_2005_Article_BF01002323.pd

Increased intestinal permeability and tight junction disruption by altered expression and localization of occludin in a murine graft versus host disease model

<p>Abstract</p> <p>Background</p> <p>Hematopoietic stem cell transplantation is increasingly performed for hematologic diseases. As a major side effect, acute graft versus host disease (GvHD) with serious gastrointestinal symptoms including diarrhea, gastrointestinal bleeding and high mortality can be observed. Because surveillance and biopsies of human gastrointestinal GvHD are difficult to perform, rare information of the alterations of the gastrointestinal barrier exists resulting in a need for systematic animal models.</p> <p>Methods</p> <p>To investigate the effects of GvHD on the intestinal barrier of the small intestine we utilized an established acute semi allogenic GvHD in C57BL/6 and B6D2F1 mice.</p> <p>Results</p> <p>By assessing the differential uptake of lactulose and mannitol in the jejunum, we observed an increased paracellular permeability as a likely mechanism for disturbed intestinal barrier function. Electron microscopy, immunohistochemistry and PCR analysis indicated profound changes of the tight-junction complex, characterized by downregulation of the tight junction protein occludin without any changes in ZO-1. Furthermore TNF-α expression was significantly upregulated.</p> <p>Conclusions</p> <p>This analysis in a murine model of GvHD of the small intestine demonstrates serious impairment of intestinal barrier function in the jejunum, with an increased permeability and morphological changes through downregulation and localization shift of the tight junction protein occludin.</p

Super-Resolution Dynamic Imaging of Dendritic Spines Using a Low-Affinity Photoconvertible Actin Probe

The actin cytoskeleton of dendritic spines plays a key role in morphological aspects of synaptic plasticity. The detailed analysis of the spine structure and dynamics in live neurons, however, has been hampered by the diffraction-limited resolution of conventional fluorescence microscopy. The advent of nanoscopic imaging techniques thus holds great promise for the study of these processes. We implemented a strategy for the visualization of morphological changes of dendritic spines over tens of minutes at a lateral resolution of 25 to 65 nm. We have generated a low-affinity photoconvertible probe, capable of reversibly binding to actin and thus allowing long-term photoactivated localization microscopy of the spine cytoskeleton. Using this approach, we resolve structural parameters of spines and record their long-term dynamics at a temporal resolution below one minute. Furthermore, we have determined changes in the spine morphology in response to pharmacologically induced synaptic activity and quantified the actin redistribution underlying these changes. By combining PALM imaging with quantum dot tracking, we could also simultaneously visualize the cytoskeleton and the spine membrane, allowing us to record complementary information on the morphological changes of the spines at super-resolution

Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Network electro-thermal simulation of non-isothermal magnetohydrodynamic heat transfer from a transpiring cone with buoyancy and pressure work

The steady, axisymmetric laminar natural convection boundary layer flow from a non-isothermal vertical circular porous cone under a transverse magnetic field, with the cone vertex located at the base, is considered. The pressure work effect is included in the analysis. The governing boundary layer equations are formulated in an (x,y) coordinate system (parallel and normal to the cone slant surface), and the magnetic field effects are simulated with a hydromagnetic body force term in the momentum equation. A dimensionless transformation is performed rendering the momentum and also heat conservation equations. The thermal convection flow is shown to be controlled by six thermophysical parameters- local Hartmann number, local Grashof number, pressure work parameter, temperature power law exponent, Prandtl number and the transpiration parameter. The transformed parabolic partial differential equations are solved numerically using the Network Simulation Method (NSM) based on the electrical-thermodynamic analogy. Excellent correlation of the zero Hartmann number case is achieved with earlier electrically non-conducting solutions. Local shear stress function (skin friction) is found to be strongly decreased with an increase in Prandtl number (Pr), with negative values (corresponding to flow reversal) identified for highest Pr with further distance along the streamwise direction. A rise in local Hartmann number, is observed to depress skin friction. Increasing temperature power law index, corresponding to steeper temperature gradient at the wall, strongly reduces skin friction at the cone surface. A positive rise in pressure work parameter decreases skin friction whereas a negative increase elevates the skin friction for some distance along the cone surface from the apex. Local heat transfer gradient is markedly boosted with a rise in Prandtl number but decreased principally at the cone surface with increasing local Hartmann number. Increasing temperature power law index conversely increases the local heat transfer gradient, at the cone surface. A positive rise in pressure work parameter increases local heat transfer gradient while negative causes it to decrease. A rise in local Grashof number boosts local skin friction and velocity into the boundary layer; local heat transfer gradient is also increased with a rise in local Grashof number whereas the temperature in the boundary layer is noticeably reduced. Applications of the work arise in spacecraft magnetogas dynamics, chemical cooling systems and industrial magnetic materials processing

Loss of Caveolin-1 Accelerates Neurodegeneration and Aging

The aged brain exhibits a loss in gray matter and a decrease in spines and synaptic densities that may represent a sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched in cholesterol, glycosphingolipids, and sphingomyelin, are essential for the development and stabilization of synapses. Caveolin-1 (Cav-1), a cholesterol binding protein organizes synaptic signaling components within MLR. It is unknown whether loss of synapses is dependent on an age-related loss of Cav-1 expression and whether this has implications for neurodegenerative diseases such as Alzheimer's disease.We analyzed brains from young (Yg, 3-6 months), middle age (Md, 12 months), aged (Ag, >18 months), and young Cav-1 KO mice and show that localization of PSD-95, NR2A, NR2B, TrkBR, AMPAR, and Cav-1 to MLR is decreased in aged hippocampi. Young Cav-1 KO mice showed signs of premature neuronal aging and degeneration. Hippocampi synaptosomes from Cav-1 KO mice showed reduced PSD-95, NR2A, NR2B, and Cav-1, an inability to be protected against cerebral ischemia-reperfusion injury compared to young WT mice, increased Aβ, P-Tau, and astrogliosis, decreased cerebrovascular volume compared to young WT mice. As with aged hippocampi, Cav-1 KO brains showed significantly reduced synapses. Neuron-targeted re-expression of Cav-1 in Cav-1 KO neurons in vitro decreased Aβ expression.Therefore, Cav-1 represents a novel control point for healthy neuronal aging and loss of Cav-1 represents a non-mutational model for Alzheimer's disease

A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle

Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP) of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C) coupling of uterine smooth muscle cells (USMC). Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: currents (L- and T-type), current, an hyperpolarization-activated current, three voltage-gated currents, two -activated current, -activated current, non-specific cation current, - exchanger, - pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area∶volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular computed from known fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing . This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes), the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, and phasic force. In summary, our advanced mathematical model provides a powerful tool to investigate the physiological ionic mechanisms underlying the genesis of uterine electrical E-C coupling of labor and parturition. This will furnish the evolution of descriptive and predictive quantitative models of myometrial electrogenesis at the whole cell and tissue levels