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Sample records for 2-d flow cell

  1. 2D Kinetic Particle in Cell Simulations of a Shear-Flow Stabilized Z-Pinch

    NASA Astrophysics Data System (ADS)

    Tummel, Kurt; Higginson, Drew; Schmidt, Andrea; Link, Anthony; McLean, Harry; Shumlak, Uri; Nelson, Brian; Golingo, Raymond; Claveau, Elliot; Lawrence Livermore National Lab Team; University of Washington Team

    2016-10-01

    The Z-pinch is a relatively simple and attractive potential fusion reactor design, but attempts to develop such a reactor have consistently struggled to overcome Z-pinch instabilities. The ``sausage'' and ``kink'' modes are among the most robust and prevalent Z-pinch instabilities, but theory and simulations suggest that axial flow-shear, dvz / dr ≠ 0 , can suppress these modes. Experiments have confirmed that Z-pinch plasmas with embedded axial flow-shear display a significantly enhanced resilience to the sausage and kink modes at a demonstration current of 50kAmps. A new experiment is under way to test the concept at higher current, and efforts to model these plasmas are being expanded. The performance and stability of these devices will depend on features like the plasma viscosity, anomalous resistivity, and finite Larmor radius effects, which are most accurately characterized in kinetic models. To predict these features, kinetic simulations using the particle in cell code LSP are now in development, and initial benchmarking and 2D stability analyses of the sausage mode are presented here. These results represent the first kinetic modeling of the flow-shear stabilized Z-pinch. This work is funded by the USDOE/ARPAe Alpha Program. Prepared by LLNL under Contract DE-AC52-07NA27344.

  2. Relative dispersion in 2D stochastic flows

    NASA Astrophysics Data System (ADS)

    Piterbarg, L. I.

    We investigate the relative dispersion for two types of stochastic flows—Brownian flow (Kraichnan model) and a flow with memory (inertial particles). In the first case well-known asymptotics are rigorously derived for a self-similar spectrum of the velocity field by using a half-century-old Feller's theorem. Exact limits of the asymptotics and exact values for dimensionless constants are obtained. The second part of the paper addresses a relatively new object: the first-order Markov stochastic flow modelling inertial particle motion. Both local and non-local dynamics are investigated. In the first case an exact exponential asymptotic is obtained for the relative dispersion. In turn, two regimes are considered in the case of non-smooth forcing: weak and strong turbulence. For weak turbulence the obtained asymptotic of relative dispersion is similar to that of the Brownian flow. As for strong turbulence, an upper bound is obtained for the scaling of relative dispersion.

  3. Flow past 2-D Hemispherical Rigid Canopies

    NASA Astrophysics Data System (ADS)

    Carnasciali, Maria-Isabel

    2013-11-01

    The flow past a 2-dimensional rigid hemispherical shape is investigated using PIV. Flow field measurements and images were generated with the use of a Thermoflow® apparatus. Results of this study are compared to prior work (APS DFD 2012 Session E9.00003) which employed CFD to investigate the flow in the near wake of hemispherical parachutes. The various sized gaps/open areas were positioned at distinct locations. The work presented here is part of a larger research project to investigate flow fields in deceleration devices and parachutes. Understanding the pitch-stability of parachutes is essential for accurate design and implementation of these deceleration devices but they present a difficult system to analyze. The flexibility of the parachute fabric results in large variations in the parachute geometry leading to complex fluid-structure interactions. Such flow, combined with flow through gaps and open areas, has been postulated to shed alternating vortices causing pitching/oscillations of the canopy. The results presented provide some insight into which geometric features affect vortex shedding and may enable the redesign of the baseline parachute to minimize instabilities.

  4. Mean flow and anisotropic cascades in decaying 2D turbulence

    NASA Astrophysics Data System (ADS)

    Liu, Chien-Chia; Cerbus, Rory; Gioia, Gustavo; Chakraborty, Pinaki

    2015-11-01

    Many large-scale atmospheric and oceanic flows are decaying 2D turbulent flows embedded in a non-uniform mean flow. Despite its importance for large-scale weather systems, the affect of non-uniform mean flows on decaying 2D turbulence remains unknown. In the absence of mean flow it is well known that decaying 2D turbulent flows exhibit the enstrophy cascade. More generally, for any 2D turbulent flow, all computational, experimental and field data amassed to date indicate that the spectrum of longitudinal and transverse velocity fluctuations correspond to the same cascade, signifying isotropy of cascades. Here we report experiments on decaying 2D turbulence in soap films with a non-uniform mean flow. We find that the flow transitions from the usual isotropic enstrophy cascade to a series of unusual and, to our knowledge, never before observed or predicted, anisotropic cascades where the longitudinal and transverse spectra are mutually independent. We discuss implications of our results for decaying geophysical turbulence.

  5. SALE2D. General Transient Fluid Flow Algorithm

    SciTech Connect

    Amsden, A.A.; Ruppel, H.M.; Hirt, C.W.

    1981-06-01

    SALE2D calculates two-dimensional fluid flows at all speeds, from the incompressible limit to highly supersonic. An implicit treatment of the pressure calculation similar to that in the Implicit Continuous-fluid Eulerian (ICE) technique provides this flow speed flexibility. In addition, the computing mesh may move with the fluid in a typical Lagrangian fashion, be held fixed in an Eulerian manner, or move in some arbitrarily specified way to provide a continuous rezoning capability. This latitude results from use of an Arbitrary Lagrangian-Eulerian (ALE) treatment of the mesh. The partial differential equations solved are the Navier-Stokes equations and the mass and internal energy equations. The fluid pressure is determined from an equation of state and supplemented with an artificial viscous pressure for the computation of shock waves. The computing mesh consists of a two-dimensional network of quadrilateral cells for either cylindrical or Cartesian coordinates, and a variety of user-selectable boundary conditions are provided in the program.

  6. Flow transitions in a 2D directional solidification model

    NASA Technical Reports Server (NTRS)

    Larroude, Philippe; Ouazzani, Jalil; Alexander, J. Iwan D.

    1992-01-01

    Flow transitions in a Two Dimensional (2D) model of crystal growth were examined using the Bridgman-Stockbarger me thod. Using a pseudo-spectral Chebyshev collocation method, the governing equations yield solutions which exhibit a symmetry breaking flow tansition and oscillatory behavior indicative of a Hopf bifurcation at higher values of Ra. The results are discussed from fluid dynamic viewpoint, and broader implications for process models are also addressed.

  7. Transition to chaos in an open unforced 2D flow

    NASA Technical Reports Server (NTRS)

    Pulliam, Thomas H.; Vastano, John A.

    1993-01-01

    The present numerical study of unsteady, low Reynolds number flow past a 2D airfoil attempts to ascertain the bifurcation sequence leading from simple periodic to complex aperiodic flow with rising Reynolds number, as well as to characterize the degree of chaos present in the aperiodic flow and assess the role of numerics in the modification and control of the observed bifurcation scenario. The ARC2D Navier-Stokes code is used in an unsteady time-accurate mode for most of these computations. The system undergoes a period-doubling bifurcation to chaos as the Reynolds number is increased from 800 to 1600; its chaotic attractors are characterized by estimates of the fractal dimension and partial Liapunov exponent spectra.

  8. Advecting Procedural Textures for 2D Flow Animation

    NASA Technical Reports Server (NTRS)

    Kao, David; Pang, Alex; Moran, Pat (Technical Monitor)

    2001-01-01

    This paper proposes the use of specially generated 3D procedural textures for visualizing steady state 2D flow fields. We use the flow field to advect and animate the texture over time. However, using standard texture advection techniques and arbitrary textures will introduce some undesirable effects such as: (a) expanding texture from a critical source point, (b) streaking pattern from the boundary of the flowfield, (c) crowding of advected textures near an attracting spiral or sink, and (d) absent or lack of textures in some regions of the flow. This paper proposes a number of strategies to solve these problems. We demonstrate how the technique works using both synthetic data and computational fluid dynamics data.

  9. Capturing nonlocal effects in 2D granular flows

    NASA Astrophysics Data System (ADS)

    Kamrin, Ken; Koval, Georg

    2013-03-01

    There is an industrial need, and a scientific desire, to produce a continuum model that can predict the flow of dense granular matter in an arbitrary geometry. A viscoplastic continuum approach, developed over recent years, has shown some ability to approximate steady flow and stress profiles in multiple inhomogeneous flow environments. However, the model incorrectly represents phenomena observed in the slow, creeping flow regime. As normalized flow-rate decreases, granular stresses are observed to become largely rate-independent and a dominating length-scale emerges in the mechanics. This talk attempts to account for these effects, in the simplified case of 2D, using the notion of nonlocal fluidity, which has proven successful in treating nonlocal effects in emulsions. The idea is to augment the local granular fluidity law with a diffusive second-order term scaled by the particle size, which spreads flowing zones accordingly. Below the yield stress, the local contribution vanishes and the fluidity becomes rate-independent, as we require. We implement the modified law in multiple geometries and validate its flow and stress predictions in multiple geometries compared against discrete particle simulations. In so doing, we demonstrate that the nonlocal relation proposed is satisfied universally in a seemingly geometry-independent fashion.

  10. 2-D Model for Normal and Sickle Cell Blood Microcirculation

    NASA Astrophysics Data System (ADS)

    Tekleab, Yonatan; Harris, Wesley

    2011-11-01

    Sickle cell disease (SCD) is a genetic disorder that alters the red blood cell (RBC) structure and function such that hemoglobin (Hb) cannot effectively bind and release oxygen. Previous computational models have been designed to study the microcirculation for insight into blood disorders such as SCD. Our novel 2-D computational model represents a fast, time efficient method developed to analyze flow dynamics, O2 diffusion, and cell deformation in the microcirculation. The model uses a finite difference, Crank-Nicholson scheme to compute the flow and O2 concentration, and the level set computational method to advect the RBC membrane on a staggered grid. Several sets of initial and boundary conditions were tested. Simulation data indicate a few parameters to be significant in the perturbation of the blood flow and O2 concentration profiles. Specifically, the Hill coefficient, arterial O2 partial pressure, O2 partial pressure at 50% Hb saturation, and cell membrane stiffness are significant factors. Results were found to be consistent with those of Le Floch [2010] and Secomb [2006].

  11. CFD code comparison for 2D airfoil flows

    NASA Astrophysics Data System (ADS)

    Sørensen, Niels N.; Méndez, B.; Muñoz, A.; Sieros, G.; Jost, E.; Lutz, T.; Papadakis, G.; Voutsinas, S.; Barakos, G. N.; Colonia, S.; Baldacchino, D.; Baptista, C.; Ferreira, C.

    2016-09-01

    The current paper presents the effort, in the EU AVATAR project, to establish the necessary requirements to obtain consistent lift over drag ratios among seven CFD codes. The flow around a 2D airfoil case is studied, for both transitional and fully turbulent conditions at Reynolds numbers of 3 × 106 and 15 × 106. The necessary grid resolution, domain size, and iterative convergence criteria to have consistent results are discussed, and suggestions are given for best practice. For the fully turbulent results four out of seven codes provide consistent results. For the laminar-turbulent transitional results only three out of seven provided results, and the agreement is generally lower than for the fully turbulent case.

  12. NKG2D ligands mediate immunosurveillance of senescent cells

    PubMed Central

    Moshayev, Zhana; Vadai, Ezra; Wensveen, Felix; Ben-Dor, Shifra; Golani, Ofra; Polic, Bojan; Krizhanovsky, Valery

    2016-01-01

    Cellular senescence is a stress response mechanism that limits tumorigenesis and tissue damage. Induction of cellular senescence commonly coincides with an immunogenic phenotype that promotes self-elimination by components of the immune system, thereby facilitating tumor suppression and limiting excess fibrosis during wound repair. The mechanisms by which senescent cells regulate their immune surveillance are not completely understood. Here we show that ligands of an activating Natural Killer (NK) cell receptor (NKG2D), MICA and ULBP2 are consistently up-regulated following induction of replicative senescence, oncogene-induced senescence and DNA damage - induced senescence. MICA and ULBP2 proteins are necessary for efficient NK-mediated cytotoxicity towards senescent fibroblasts. The mechanisms regulating the initial expression of NKG2D ligands in senescent cells are dependent on a DNA damage response, whilst continuous expression of these ligands is regulated by the ERK signaling pathway. In liver fibrosis, the accumulation of senescent activated stellate cells is increased in mice lacking NKG2D receptor leading to increased fibrosis. Overall, our results provide new insights into the mechanisms regulating the expression of immune ligands in senescent cells and reveal the importance of NKG2D receptor-ligand interaction in protecting against liver fibrosis. PMID:26878797

  13. The 2005 Vazcun Valley Lahar: Evaluation of the TITAN2D Two-Phase Flow Model Using an Actual Event.

    NASA Astrophysics Data System (ADS)

    Williams, R.; Stinton, A. J.; Sheridan, M. F.

    2005-12-01

    TITAN2D is a depth-averaged, thin-layer computational fluid dynamics (CFD) code, suitable for simulating a variety of geophysical mass flows. TITAN2D output data include pile thickness and flow momentum at each time step for all cells traversed by the flow during the simulation. From this the flow limit, run-out path, pile velocity, deposit thickness, and travel time can be calculated. Results can be visualized in the open source GRASS GIS software or with the built-in TITAN2D viewer. A new two-phase TITAN2D version allows simulation of flows containing various mixtures of water and solids. The purpose of this study is to compare simulations by the two-phase flow version of TITAN2D with an actual event. The chosen natural flow is a small ash-rich lahar (volume approximately 60,000 m3) that occurred on 12 February 2005 in the Vazcún Valley, located on the north-east flank of Volcán Tungurahua, Ecuador. Lahars and pyroclastic flows along this valley could potentially threaten the 20,000 inhabitants living in and near the city of Baños. A variety of data sources exist for this lahar, including: pre- and post-event meter-scale topography, and photographic, video, seismic and acoustic flow monitoring (AFM) records from during the event. These data permit detailed comparisons between the dynamics of the actual lahar and those of the TITAN2D simulated flow. In particular, detailed comparisons are made between run-up heights, flow velocity, inundation area, and deposit area and thickness. Simulations utilize a variety of data derived from field observations such as lahar volume, solid to pore-fluid ratio and pre-event topography. TITAN2D is important in modeling lahars because it allows assessment of the impact of the flows on buildings and infrastructure lifelines located near drainages that descend from volcanoes.

  14. Improvement of a 2D numerical model of lava flows

    NASA Astrophysics Data System (ADS)

    Ishimine, Y.

    2013-12-01

    I propose an improved procedure that reduces an improper dependence of lava flow directions on the orientation of Digital Elevation Model (DEM) in two-dimensional simulations based on Ishihara et al. (in Lava Flows and Domes, Fink, JH eds., 1990). The numerical model for lava flow simulations proposed by Ishihara et al. (1990) is based on two-dimensional shallow water model combined with a constitutive equation for a Bingham fluid. It is simple but useful because it properly reproduces distributions of actual lava flows. Thus, it has been regarded as one of pioneer work of numerical simulations of lava flows and it is still now widely used in practical hazard prediction map for civil defense officials in Japan. However, the model include an improper dependence of lava flow directions on the orientation of DEM because the model separately assigns the condition for the lava flow to stop due to yield stress for each of two orthogonal axes of rectangular calculating grid based on DEM. This procedure brings a diamond-shaped distribution as shown in Fig. 1 when calculating a lava flow supplied from a point source on a virtual flat plane although the distribution should be circle-shaped. To improve the drawback, I proposed a modified procedure that uses the absolute value of yield stress derived from both components of two orthogonal directions of the slope steepness to assign the condition for lava flows to stop. This brings a better result as shown in Fig. 2. Fig. 1. (a) Contour plots calculated with the original model of Ishihara et al. (1990). (b) Contour plots calculated with a proposed model.

  15. Quasi-2D Unsteady Flow Procedure for Real Fluids

    DTIC Science & Technology

    2006-05-17

    flow in system lines, networks , and volumes. This new procedure has been implemented in both Matlab/Simulink® and Fortran95 . A variety of...as well as Fortran95 to allow for application on a wide variety of computer platforms. The computational efficiency of the various numerical... network are presented to demonstrate the capability of the current techniques and the unsteady flow physics that can occur in system lines. 15. SUBJECT

  16. 2D VARIABLY SATURATED FLOWS: PHYSICAL SCALING AND BAYESIAN ESTIMATION

    EPA Science Inventory

    A novel dimensionless formulation for water flow in two-dimensional variably saturated media is presented. It shows that scaling physical systems requires conservation of the ratio between capillary forces and gravity forces. A direct result of this finding is that for two phys...

  17. Lagrangian statistics and flow topology in forced 2-D turbulence

    SciTech Connect

    Kadoch, B.; Del-Castillo-Negrete, Diego B; Bos, W.J.T.; Schneider, Kai

    2011-01-01

    A study of the relationship between Lagrangian statistics and flow topology in fluid turbulence is presented. The topology is characterized using the Weiss criterion, which provides a conceptually simple tool to partition the flow into topologically different regions: elliptic (vortex dominated), hyperbolic (deformation dominated), and intermediate (turbulent background). The flow corresponds to forced two-dimensional Navier-Stokes turbulence in doubly periodic and circular bounded domains, the latter with no-slip boundary conditions. In the double periodic domain, the probability density function (pdf) of the Weiss field exhibits a negative skewness consistent with the fact that in periodic domains the flow is dominated by coherent vortex structures. On the other hand, in the circular domain, the elliptic and hyperbolic regions seem to be statistically similar. We follow a Lagrangian approach and obtain the statistics by tracking large ensembles of passively advected tracers. The pdfs of residence time in the topologically different regions are computed introducing the Lagrangian Weiss field, i.e., the Weiss field computed along the particles' trajectories. In elliptic and hyperbolic regions, the pdfs of the residence time have self-similar algebraic decaying tails. In contrast, in the intermediate regions the pdf has exponential decaying tails. The conditional pdfs (with respect to the flow topology) of the Lagrangian velocity exhibit Gaussian-like behavior in the periodic and in the bounded domains. In contrast to the freely decaying turbulence case, the conditional pdfs of the Lagrangian acceleration in forced turbulence show a comparable level of intermittency in both the periodic and the bounded domains. The conditional pdfs of the Lagrangian curvature are characterized, in all cases, by self-similar power-law behavior with a decay exponent of order - 2.

  18. Representativeness of 2D models to simulate 3D unstable variable density flow in porous media

    NASA Astrophysics Data System (ADS)

    Knorr, Bastian; Xie, Yueqing; Stumpp, Christine; Maloszewski, Piotr; Simmons, Craig T.

    2016-11-01

    Variable density flow in porous media has been studied primarily using numerical models because it is a semi-chaotic and transient process. Most of these studies have been 2D, owing to the computational restrictions on 3D simulations, and the ability to observe variable density flow in 2D experimentation. However, it is recognised that variable density flow is a three-dimensional process. A 3D system may cause weaker variable density flow than a 2D system due to stronger dispersion, but may also result in bigger fingers and hence stronger variable density flow because of more space for fingers to coalesce. This study aimed to determine the representativeness of 2D modelling to simulate 3D variable density flow. 3D homogeneous sand column experiments were conducted at three different water flow velocities with three different bromide tracer solutions mixed with methanol resulting in different density ratios. Both 2D axisymmetric and 3D numerical simulations were performed to reproduce experimental data. Experimental results showed that the magnitude of variable density flow increases with decreasing flow rates and decreasing density ratios. The shapes of the observed breakthrough curves differed significantly from those produced by 2D axisymmetric and 3D simulations. Compared to 2D simulations, the onset of instabilities was delayed but the growth was more pronounced in 3D simulations. Despite this difference, both 2D axisymmetric and 3D models successfully simulated mass recovery with high efficiency (between 77% and 99%). This study indicates that 2D simulations are sufficient to understand integrated features of variable density flow in homogeneous sand column experiments.

  19. Clogging and Intermittent Flow in a 2D Hopper

    NASA Astrophysics Data System (ADS)

    Nordstrom, Kerstin; Thackray, Emma

    2016-11-01

    We have constructed a quasi-two-dimensional system of bidisperse, millimeter-scale disks with photoelastic properties that make force networks within the material visible. The system is contained in an acrylic box with an adjustable bottom opening. We can approach the clogging transition by adjusting this opening and by adding external forcing to the top of the flowing pile. By placing the system between cross-polarizers, we can obtain high-speed video of this system during flow, and extract intensity signals that can be used to identify and quantify localized, otherwise indeterminate forces. We simultaneously track individual particle motions, which can be used to identify shear transformation zones in the system. We are therefore able to correlate local forces with rearrangements within the system, and characterize the evolution of this interplay on the approach to the clogging transition.

  20. A 2D flow visualization user study using explicit flow synthesis and implicit task design.

    PubMed

    Liu, Zhanping; Cai, Shangshu; Swan, J Edward; Moorhead, Robert J; Martin, Joel P; Jankun-Kelly, T J

    2012-05-01

    This paper presents a 2D flow visualization user study that we conducted using new methodologies to increase the objectiveness. We evaluated grid-based variable-size arrows, evenly spaced streamlines, and line integral convolution (LIC) variants (basic, oriented, and enhanced versions) coupled with a colorwheel and/or rainbow color map, which are representative of many geometry-based and texture-based techniques. To reduce data-related bias, template-based explicit flow synthesis was used to create a wide variety of symmetric flows with similar topological complexity. To suppress task-related bias, pattern-based implicit task design was employed, addressing critical point recognition, critical point classification, and symmetric pattern categorization. In addition, variable-duration and fixed-duration measurement schemes were utilized for lightweight precision-critical and heavyweight judgment intensive flow analysis tasks, respectively, to record visualization effectiveness. We eliminated outliers and used the Ryan REGWQ post-hoc homogeneous subset tests in statistical analysis to obtain reliable findings. Our study shows that a texture-based dense representation with accentuated flow streaks, such as enhanced LIC, enables intuitive perception of the flow, while a geometry-based integral representation with uniform density control, such as evenly spaced streamlines, may exploit visual interpolation to facilitate mental reconstruction of the flow. It is also shown that inappropriate color mapping (e.g., colorwheel) may add distractions to a flow representation.

  1. Quasi-2D Unsteady Flow Procedure for Real Fluids (PREPRINT)

    DTIC Science & Technology

    2006-05-17

    modeling paradigm, an existing user community across many disciplines, and commercially-funded code development and maintenance. A Fortran95 code...Matlab/Simulink® as well as Fortran95 to allow for application on a wide variety of computer platforms. The computational efficiency of the various...pipe network are presented to demonstrate the capability of the current techniques and the unsteady flow physics that can occur in system lines

  2. Divergences in KIR2D+ natural killer and KIR2D+CD8+ T-cell reconstitution following liver transplantation.

    PubMed

    López-Álvarez, M R; Campillo, J A; Legaz, I; Blanco-García, R M; Salgado-Cecilia, G; Bolarín, J M; Gimeno, L; Gil, J; García-Alonso, A M; Muro, M; Alvarez-López, M R; Miras, M; Minguela, A

    2011-03-01

    Natural killer (NK) and CD8(+) T cells may be active elements in the allograft response, but little is known about their role in liver transplantation. Some of these cells express killer immunoglobulin-like receptors (KIRs), which after binding specific ligands may transmit inhibitory/activating signals. In this study, circulating NK and CD8(+) T cells expressing CD158a/h (KIR2DL1/S1) or CD158b/j (KIR2DL2/3/S(2)) receptors were analyzed in 142 liver recipients by flow cytometry. They were underrepresented in patients before transplantation, but following transplantation, whereas the KIR2D(+) NK subsets experienced a late recuperation (day 365) mainly in C2-homozygous patients developing early acute rejection, recovery of the 2 CD8(+)KIR2D(+) T cells started earlier, showing significant differences on day 365 between patients without acute rejection and those suffering from it (p = 0.004 and p < 0.0001, respectively). These differences were also evident when the human leukocute antigen-C genotypes of the recipient were considered. In conclusion, whereas the late recovery of KIR2D(+) NK cells in C2/C2 patients appears to be linked to acute rejection, the increase in early CD8(+)KIR2D(+) T cells in overall liver recipients correlates with a most successful early graft outcome. Therefore, monitoring of KIR2D(+) cells appears to be a useful tool for liver transplant follow-up.

  3. Flow Solver for Incompressible 2-D Drive Cavity

    NASA Technical Reports Server (NTRS)

    Kalb, Virginia L.

    2008-01-01

    This software solves the Navier-Stokes equations for the incompressible driven cavity flow problem. The code uses second-order finite differencing on a staggered grid using the Chorin projection method. The resulting intermediate Poisson equation is efficiently solved using the fast Fourier transform. Time stepping is done using fourth-order Runge-Kutta for stability at high Reynolds numbers. Features include check-pointing, periodic field snapshots, ongoing reporting of kinetic energy and changes between time steps, time histories at selected points, and optional streakline generation.

  4. An Integrative Model of Excitation Driven Fluid Flow in a 2D Uterine Channel

    NASA Astrophysics Data System (ADS)

    Maggio, Charles; Fauci, Lisa; Chrispell, John

    2009-11-01

    We present a model of intra-uterine fluid flow in a sagittal cross-section of the uterus by inducing peristalsis in a 2D channel. This is an integrative multiscale computational model that takes as input fluid viscosity, passive tissue properties of the uterine channel and a prescribed wave of membrane depolarization. This voltage pulse is coupled to a model of calcium dynamics inside a uterine smooth muscle cell, which in turn drives a kinetic model of myosin phosphorylation governing contractile muscle forces. Using the immersed boundary method, these muscle forces are communicated to a fluid domain to simulate the contractions which occur in a human uterus. An analysis of the effects of model parameters on the flow properties and emergent geometry of the peristaltic channel will be presented.

  5. The 2D and 3D hypersonic flows with unstructured meshes

    NASA Technical Reports Server (NTRS)

    Thareja, Rajiv

    1993-01-01

    Viewgraphs on 2D and 3D hypersonic flows with unstructured meshes are presented. Topics covered include: mesh generation, mesh refinement, shock-shock interaction, velocity contours, mesh movement, vehicle bottom surface, and adapted meshes.

  6. Global regularity and uniqueness of weak solution for the 2-D liquid crystal flows

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Zhang, Zhifei

    We prove the global existence and regularity of weak solution for the 2-D liquid crystal flows with the large initial velocity. The uniqueness of weak solution is also proved by using the Littlewood-Paley analysis.

  7. Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells.

    PubMed

    Marchionatti, Ana M; Picotto, Gabriela; Narvaez, Carmen J; Welsh, Joellen; Tolosa de Talamoni, Nori G

    2009-02-01

    Calcitriol or 1,25(OH)(2)D(3) is a negative growth regulator of MCF-7 breast cancer cells. The growth arrest is due to apoptosis activation, which involves mitochondrial disruption. This effect is blunted in vitamin D resistant cells (MCF-7(DRes) cells). Menadione (MEN), a glutathione (GSH)-depleting compound, may potentiate antitumoral effects of anticancer drugs. The aim of this study was to investigate whether MEN enhances cellular responsiveness of MCF-7 cells to 1,25(OH)(2)D(3). Cells were cultured and treated with different concentrations of 1,25(OH)(2)D(3)+/-MEN or vehicle for 96 h. GSH levels and the activity of antioxidant enzymes were determined by spectrophotometry and ROS production by flow cytometry. Both drugs decreased growth and enhanced ROS in MCF-7 cells, obtaining the maximal effects when 1,25(OH)(2)D(3) was combined with MEN (P<0.01 vs. Control and vs. each compound alone). MCF-7(DRes) cells were not responsive to 1,25(OH)(2)D(3), but the cell proliferation was slightly inhibited by the combined treatment. Calcitriol and MEN separately enhanced antioxidant enzyme activities, but when they were used in combination, the effect was more pronounced (P<0.05 vs. Control and vs. each compound alone). MEN, calcitriol and the combined treatment decreased GSH levels (P<0.05 vs. Control). The data indicate that MEN potentiates the effect of 1,25(OH)(2)D(3) on growth arrest in MCF-7 cells by oxidative stress and increases the activities of antioxidant enzymes, probably as a compensatory mechanism.

  8. Numerical Simulation of Supersonic Compression Corners and Hypersonic Inlet Flows Using the RPLUS2D Code

    NASA Technical Reports Server (NTRS)

    Kapoor, Kamlesh; Anderson, Bernhard H.; Shaw, Robert J.

    1994-01-01

    A two-dimensional computational code, PRLUS2D, which was developed for the reactive propulsive flows of ramjets and scramjets, was validated for two-dimensional shock-wave/turbulent-boundary-layer interactions. The problem of compression corners at supersonic speeds was solved using the RPLUS2D code. To validate the RPLUS2D code for hypersonic speeds, it was applied to a realistic hypersonic inlet geometry. Both the Baldwin-Lomax and the Chien two-equation turbulence models were used. Computational results showed that the RPLUS2D code compared very well with experimentally obtained data for supersonic compression corner flows, except in the case of large separated flows resulting from the interactions between the shock wave and turbulent boundary layer. The computational results compared well with the experiment results in a hypersonic NASA P8 inlet case, with the Chien two-equation turbulence model performing better than the Baldwin-Lomax model.

  9. MAST solution of irrotational flow problems in 2D domains with strongly unstructured triangular meshes

    NASA Astrophysics Data System (ADS)

    Tucciarelli, T.

    2012-12-01

    A new methodology for the solution of irrotational 2D flow problems in domains with strongly unstructured meshes is presented. A fractional time step procedure is applied to the original governing equations, solving consecutively a convective prediction system and a diffusive corrective system. The non linear components of the problem are concentrated in the prediction step, while the correction step leads to the solution of a linear system, of the order of the number of computational cells. A MArching in Space and Time (MAST) approach is applied for the solution of the convective prediction step. The major advantages of the model, as well as its ability to maintain the solution monotonicity even in strongly irregular meshes, are briefly described. The algorithm is applied to the solution of diffusive shallow water equations in a simple domain.

  10. Fluctuating Pressure Data from 2-D Nozzle Cold Flow Tests (Dual Bell)

    NASA Technical Reports Server (NTRS)

    Nesman, Tomas E.

    2001-01-01

    Rocket engines nozzle performance changes as a vehicle climbs through the atmosphere. An altitude compensating nozzle, ACN, is intended to improve on a fixed geometry bell nozzle that performs at optimum at only one trajectory point. In addition to nozzle performance, nozzle transient loads are an important consideration. Any nozzle experiences large transient toads when shocks pass through the nozzle at start and shutdown. Additional transient toads will occur at transitional flow conditions. The objectives of cold flow nozzle testing at MSFC are CFD benchmark / calibration and Unsteady flow / sideloads. Initial testing performed with 2-D inserts to 14" transonic wind tunnel. Recent review of 2-D data in preparation for nozzle test facility 3-D testing. This presentation shows fluctuating pressure data and some observations from 2-D dual-bell nozzle cold flow tests.

  11. Effects of NKG2D haplotypes on the cell-surface expression of NKG2D protein on natural killer and CD8 T cells of peripheral blood among atomic-bomb survivors.

    PubMed

    Imai, Kazue; Hayashi, Tomonori; Yamaoka, Mika; Kajimura, Junko; Yoshida, Kengo; Kusunoki, Yoichiro; Nakachi, Kei

    2012-06-01

    NKG2D is a primary activating receptor that triggers cell-mediated cytotoxicity in NK cells against tumor and virus-infected cells. We previously identified the NKG2D haplotypes in the natural killer gene complex region on chromosome 12p. Two major haplotype alleles, LNK1 and HNK1, were closely related to low and high natural cytotoxic activity phenotypes, respectively. Furthermore, the haplotype of HNK1/HNK1 has revealed a decreased risk of cancer compared with LNK1/LNK1. In the present study, using flow cytometry, we evaluated the functional effects of NKG2D haplotypes and five htSNPs in terms of the cell-surface expression of NKG2D protein on NK and CD8 T cells of peripheral blood among 732 atomic-bomb survivors. NKG2D expression on NK cells showed significant increases, in the order of LNK1/LNK1, LNK1/HNK1 and HNK1/HNK1 haplotypes (p for trend=0.003), or with major homozygous, heterozygous, and minor homozygous genotypes for individual htSNPs (p for trend=0.02-0.003). The same trend was observed for NKG2D expression on CD8 T cells. Our findings indicate that the NKG2D haplotypes are associated with the expression levels of NKG2D protein on NK and CD8 T cells, resulting in inter-individual variations in human cytotoxic response.

  12. CD4+ NKG2D+ T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice

    PubMed Central

    Lin, Zhijie; Wang, Changrong; Xia, Haizui; Liu, Weiguang; Xiao, Weiming; Qian, Li; Jia, Xiaoqin; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

    2014-01-01

    The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4+ NKG2D+ T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset. PMID:24708417

  13. CD4(+) NKG2D(+) T cells induce NKG2D down-regulation in natural killer cells in CD86-RAE-1ε transgenic mice.

    PubMed

    Lin, Zhijie; Wang, Changrong; Xia, Haizui; Liu, Weiguang; Xiao, Weiming; Qian, Li; Jia, Xiaoqin; Ding, Yanbing; Ji, Mingchun; Gong, Weijuan

    2014-03-01

    The binding of NKG2D to its ligands strengthens the cross-talk between natural killer (NK) cells and dendritic cells, particularly at early stages, before the initiation of the adaptive immune response. We found that retinoic acid early transcript-1ε (RAE-1ε), one of the ligands of NKG2D, was persistently expressed on antigen-presenting cells in a transgenic mouse model (pCD86-RAE-1ε). By contrast, NKG2D expression on NK cells, NKG2D-dependent cytotoxicity and tumour rejection, and dextran sodium sulphate-induced colitis were all down-regulated in this mouse model. The down-regulation of NKG2D on NK cells was reversed by stimulation with poly (I:C). The ectopic expression of RAE-1ε on dendritic cells maintained NKG2D expression levels and stimulated the activity of NK cells ex vivo, but the higher frequency of CD4(+) NKG2D(+) T cells in transgenic mice led to the down-regulation of NKG2D on NK cells in vivo. Hence, high levels of RAE-1ε expression on antigen-presenting cells would be expected to induce the down-regulation of NK cell activation by a regulatory T-cell subset.

  14. 2D light scattering static cytometry for label-free single cell analysis with submicron resolution.

    PubMed

    Xie, Linyan; Yang, Yan; Sun, Xuming; Qiao, Xu; Liu, Qiao; Song, Kun; Kong, Beihua; Su, Xuantao

    2015-11-01

    Conventional optical cytometric techniques usually measure fluorescence or scattering signals at fixed angles from flowing cells in a liquid stream. Here we develop a novel cytometer that employs a scanning optical fiber to illuminate single static cells on a glass slide, which requires neither microfluidic fabrication nor flow control. This static cytometric technique measures two dimensional (2D) light scattering patterns via a small numerical aperture (0.25) microscope objective for label-free single cell analysis. Good agreement is obtained between the yeast cell experimental and Mie theory simulated patterns. It is demonstrated that the static cytometer with a microscope objective of a low resolution around 1.30 μm has the potential to perform high resolution analysis on yeast cells with distributed sizes. The capability of the static cytometer for size determination with submicron resolution is validated via measurements on standard microspheres with mean diameters of 3.87 and 4.19 μm. Our 2D light scattering static cytometric technique may provide an easy-to-use, label-free, and flow-free method for single cell diagnostics.

  15. Stability of two-dimensional (2D) natural convection flows in air-filled differentially heated cavities: 2D/3D disturbances

    NASA Astrophysics Data System (ADS)

    Xin, Shihe; Le Quéré, Patrick

    2012-06-01

    Following our previous two-dimensional (2D) studies of flows in differentially heated cavities filled with air, we studied the stability of 2D natural convection flows in these cavities with respect to 3D periodic perturbations. The basis of the numerical methods is a time-stepping code using the Chebyshev spectral collocation method and the direct Uzawa method for velocity-pressure coupling. Newton's iteration, Arnoldi's method and the continuation method have been used in order to, respectively, compute the 2D steady-state base solution, estimate the leading eigenmodes of the Jacobian and perform linear stability analysis. Differentially heated air-filled cavities of aspect ratios from 1 to 7 were investigated. Neutral curves (Rayleigh number versus wave number) have been obtained. It turned out that only for aspect ratio 7, 3D stationary instability occurs at slightly higher Rayleigh numbers than the onset of 2D time-dependent flow and that for other aspect ratios 3D instability always takes place before 2D time-dependent flows. 3D unstable modes are stationary and anti-centro-symmetric. 3D nonlinear simulations revealed that the corresponding pitchfork bifurcations are supercritical and that 3D instability leads only to weak flow in the third direction. Further 3D computations are also performed at higher Rayleigh number in order to understand the effects of the weak 3D fluid motion on the onset of time-dependent flow. 3D flow structures are responsible for the onset of time-dependent flow for aspect ratios 1, 2 and 3, while for larger aspect ratios they do not alter the transition scenario, which was observed in the 2D cases and that vertical boundary layers become unstable to traveling waves.

  16. Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications

    PubMed Central

    2012-01-01

    Background Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. Results We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. Conclusions Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells. PMID:22316211

  17. Use of finite volume radiation for predicting the Knudsen minimum in 2D channel flow

    SciTech Connect

    Malhotra, Chetan P.; Mahajan, Roop L.

    2014-12-09

    In an earlier paper we employed an analogy between surface-to-surface radiation and free-molecular flow to model Knudsen flow through tubes and onto planes. In the current paper we extend the analogy between thermal radiation and molecular flow to model the flow of a gas in a 2D channel across all regimes of rarefaction. To accomplish this, we break down the problem of gaseous flow into three sub-problems (self-diffusion, mass-motion and generation of pressure gradient) and use the finite volume method for modeling radiation through participating media to model the transport in each sub-problem as a radiation problem. We first model molecular self-diffusion in the stationary gas by modeling the transport of the molecular number density through the gas starting from the analytical asymptote for free-molecular flow to the kinetic theory limit of gaseous self-diffusion. We then model the transport of momentum through the gas at unit pressure gradient to predict Poiseuille flow and slip flow in the 2D gas. Lastly, we predict the generation of pressure gradient within the gas due to molecular collisions by modeling the transport of the forces generated due to collisions per unit volume of gas. We then proceed to combine the three radiation problems to predict flow of the gas over the entire Knudsen number regime from free-molecular to transition to continuum flow and successfully capture the Knudsen minimum at Kn ∼ 1.

  18. Parallelized CCHE2D flow model with CUDA Fortran on Graphics Process Units

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper presents the CCHE2D implicit flow model parallelized using CUDA Fortran programming technique on Graphics Processing Units (GPUs). A parallelized implicit Alternating Direction Implicit (ADI) solver using Parallel Cyclic Reduction (PCR) algorithm on GPU is developed and tested. This solve...

  19. Evaluation of 2D shallow-water model for spillway flow with a complex geometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although the two-dimensional (2D) shallow water model is formulated based on several assumptions such as hydrostatic pressure distribution and vertical velocity is negligible, as a simple alternative to the complex 3D model, it has been used to compute water flows in which these assumptions may be ...

  20. Non Lyapunov stability of a constant spatially developing 2-D gas flow

    NASA Astrophysics Data System (ADS)

    Balint, Agneta M.; Balint, Stefan; Tanasie, Loredana

    2017-01-01

    Different types of stabilities (global, local) and instabilities (global absolute, local convective) of the constant spatially developing 2-D gas flow are analyzed in a particular phase space of continuously differentiable functions, endowed with the usual algebraic operations and the topology generated by the uniform convergence on the plane. For this purpose the Euler equations linearized at the constant flow are used. The Lyapunov stability analysis was presented in [1] and this paper is a continuation of [1].

  1. Soap film as a 2D system: Diffusion and flow fields

    NASA Astrophysics Data System (ADS)

    Vivek, Skanda; Weeks, Eric

    2014-03-01

    We use microrheology to measure the 2D (interfacial) viscosity of soap films. Microrheology uses the diffusivity of tracer particles suspended in the soap film to infer viscosity. Our tracer particles are colloids of diameters d = 0.10 and 0.18 microns. We measure the interfacial viscosity of soap films ranging in thickness from 0.1 to 3 microns. The thickness of these films is measured using the infrared absorbance of the water based soap films. From film thickness, viscosity of the fluid used to make the film and particle diffusivity, we can infer the interfacial viscosity due to the surfactant layers at the film/air interfaces. We find positive constant interfacial viscosities for thin films (h/d < 5), within error. For thicker films, we find negative viscosities, indicating 3D effects begin to play a role, as air stresses become less important. The transition from 2D to 3D properties as a function of h/d is sharp at about h/d=6. Additionally, we measure larger length scale flow fields from correlated particle motions and find good agreement with what is expected from the theory of 2D fluids for all our films. In conclusion, single particle diffusion shows a sharp transition away from 2D like behavior as h/d increases, but the long-range flow fields still act as 2D.

  2. A depth-averaged 2-D model of flow and sediment transport in coastal waters

    NASA Astrophysics Data System (ADS)

    Sanchez, Alejandro; Wu, Weiming; Beck, Tanya M.

    2016-11-01

    A depth-averaged 2-D model has been developed to simulate unsteady flow and nonuniform sediment transport in coastal waters. The current motion is computed by solving the phase-averaged 2-D shallow water flow equations reformulated in terms of total-flux velocity, accounting for the effects of wave radiation stresses and general diffusion or mixing induced by current, waves, and wave breaking. The cross-shore boundary conditions are specified by assuming fully developed longshore current and wave setup that are determined using the reduced 1-D momentum equations. A 2-D wave spectral transformation model is used to calculate the wave height, period, direction, and radiation stresses, and a surface wave roller model is adopted to consider the effects of surface roller on the nearshore currents. The nonequilibrium transport of nonuniform total-load sediment is simulated, considering sediment entrainment by current and waves, the lag of sediment transport relative to the flow, and the hiding and exposure effect of nonuniform bed material. The flow and sediment transport equations are solved using an implicit finite volume method on a variety of meshes including nonuniform rectangular, telescoping (quadtree) rectangular, and hybrid triangular/quadrilateral meshes. The flow and wave models are integrated through a carefully designed steering process. The model has been tested in three field cases, showing generally good performance.

  3. Experimental and Computational Study of Multiphase Flow Hydrodynamics in 2D Trickle Bed Reactors

    NASA Astrophysics Data System (ADS)

    Nadeem, H.; Ben Salem, I.; Kurnia, J. C.; Rabbani, S.; Shamim, T.; Sassi, M.

    2014-12-01

    Trickle bed reactors are largely used in the refining processes. Co-current heavy oil and hydrogen gas flow downward on catalytic particle bed. Fine particles in the heavy oil and/or soot formed by the exothermic catalytic reactions deposit on the bed and clog the flow channels. This work is funded by the refining company of Abu Dhabi and aims at mitigating pressure buildup due to fine deposition in the TBR. In this work, we focus on meso-scale experimental and computational investigations of the interplay between flow regimes and the various parameters that affect them. A 2D experimental apparatus has been built to investigate the flow regimes with an average pore diameter close to the values encountered in trickle beds. A parametric study is done for the development of flow regimes and the transition between them when the geometry and arrangement of the particles within the porous medium are varied. Liquid and gas flow velocities have also been varied to capture the different flow regimes. Real time images of the multiphase flow are captured using a high speed camera, which were then used to characterize the transition between the different flow regimes. A diffused light source was used behind the 2D Trickle Bed Reactor to enhance visualizations. Experimental data shows very good agreement with the published literature. The computational study focuses on the hydrodynamics of multiphase flow and to identify the flow regime developed inside TBRs using the ANSYS Fluent Software package. Multiphase flow inside TBRs is investigated using the "discrete particle" approach together with Volume of Fluid (VoF) multiphase flow modeling. The effect of the bed particle diameter, spacing, and arrangement are presented that may be used to provide guidelines for designing trickle bed reactors.

  4. Numerical Instability in a 2D Gyrokinetic Code Caused by Divergent E × B Flow

    NASA Astrophysics Data System (ADS)

    Byers, J. A.; Dimits, A. M.; Matsuda, Y.; Langdon, A. B.

    1994-12-01

    In this paper, a numerical instability first observed in a 2D electrostatic gyrokinetic code is described. The instability should also be present in some form in many versons of particle-in-cell simulation codes that employ guiding center drifts. A perturbation analysis of the instability is given and its results agree quantitatively with the observations from the gyrokinetic code in all respects. The basic mechanism is a false divergence of the E × B flow caused by the interpolation between the grid and the particles as coupled with the specific numerical method for calculating E - ∇φ. Stability or instability depends in detail on the specific choice of particle interpolation method and field method. One common interpolation method, subtracted dipole, is stable. Other commonly used interpolation methods, linear and quadratic, are unstable when combined with a finite difference for the electric field. Linear and quadratic interpolation can be rendered stable if combined with another method for the electric field, the analytic differential of the interpolated potential.

  5. A comparative 2D modeling of debris-flow propagation and outcomes for end-users

    NASA Astrophysics Data System (ADS)

    Bettella, F.; Bertoldi, G.; Pozza, E.; McArdell, B. W.; D'Agostino, V.

    2012-04-01

    In Alpine regions gravity-driven natural hazards, in particular debris flows, endanger settlements and human life. Mitigation strategies based on hazard maps are necessary tools for land planning. These maps can be made more precise by using numerical models to forecasting the inundated areas after a careful setting of those 'key parameters' (K-P) which directly affect the flow motion and its interaction with the ground surface. Several physically based 2D models are available for practitioners and governmental agencies, but the selection criteria of model type and of the related K-P remain flexible and partly subjective. This remark has driven us to investigate how different models simulate different types of debris flows (from granular to muddy debris flows, going through intermediate types), in particular when the flow is influenced by the presence of deposition basins. Two commercial 2D physical models (RAMMS and FLO-2D) have been tested for five well-documented debris flows events from five Italian catchments were different geology and flow dynamics are observed: 1) a viscous debris flow occurred in 2009 in a catchment with a metamorphic geology (Gadria torrent, Bolzano Province); 2) the 2009 granular debris flow in an granitic geological setting (Rio Dosson, Trento Province); 3-4) two events occurred in the 'rio Val del Lago' and 'rio Molinara' (Trento Province) in 2010 where porphyritic lithology prevails (intermediate granular debris flow); 5) the Rotolon torrent (Vicenza Province) 2009 debris flow containing sedimentary rocks enclosed in an abundant clay-rich matrix (intermediate viscous case). Event volumes range from 5.000 to 50.000 cubic meters. The Gadria, Rotolon and Val del Lago events are also influenced by artificial retention basins. Case study simulations allowed delineation of some practical end-user suggestions and good practices in order to guide the model choice and the K-P setting, particularly related to different flow dynamics. The

  6. Simulation of a pulsatile non-Newtonian flow past a stenosed 2D artery with atherosclerosis.

    PubMed

    Tian, Fang-Bao; Zhu, Luoding; Fok, Pak-Wing; Lu, Xi-Yun

    2013-09-01

    Atherosclerotic plaque can cause severe stenosis in the artery lumen. Blood flow through a substantially narrowed artery may have different flow characteristics and produce different forces acting on the plaque surface and artery wall. The disturbed flow and force fields in the lumen may have serious implications on vascular endothelial cells, smooth muscle cells, and circulating blood cells. In this work a simplified model is used to simulate a pulsatile non-Newtonian blood flow past a stenosed artery caused by atherosclerotic plaques of different severity. The focus is on a systematic parameter study of the effects of plaque size/geometry, flow Reynolds number, shear-rate dependent viscosity and flow pulsatility on the fluid wall shear stress and its gradient, fluid wall normal stress, and flow shear rate. The computational results obtained from this idealized model may shed light on the flow and force characteristics of more realistic blood flow through an atherosclerotic vessel.

  7. Eulerian and Lagrangian methods for vortex tracking in 2D and 3D flows

    NASA Astrophysics Data System (ADS)

    Huang, Yangzi; Green, Melissa

    2014-11-01

    Coherent structures are a key component of unsteady flows in shear layers. Improvement of experimental techniques has led to larger amounts of data and requires of automated procedures for vortex tracking. Many vortex criteria are Eulerian, and identify the structures by an instantaneous local swirling motion in the field, which are indicated by closed or spiral streamlines or pathlines in a reference frame. Alternatively, a Lagrangian Coherent Structures (LCS) analysis is a Lagrangian method based on the quantities calculated along fluid particle trajectories. In the current work, vortex detection is demonstrated on data from the simulation of two cases: a 2D flow with a flat plate undergoing a 45 ° pitch-up maneuver and a 3D wall-bounded turbulence channel flow. Vortices are visualized and tracked by their centers and boundaries using Γ1, the Q criterion, and LCS saddle points. In the cases of 2D flow, saddle points trace showed a rapid acceleration of the structure which indicates the shedding from the plate. For channel flow, saddle points trace shows that average structure convection speed exhibits a similar trend as a function of wall-normal distance as the mean velocity profile, and leads to statistical quantities of vortex dynamics. Dr. Jeff Eldredge and his research group at UCLA are gratefully acknowledged for sharing the database of simulation for the current research. This work was supported by the Air Force Office of Scientific Research under AFOSR Award No. FA9550-14-1-0210.

  8. Thermal stability effects on the separated flow over a steep 2-D hill

    NASA Astrophysics Data System (ADS)

    Zhang, W.; Porte-Agel, F.

    2012-12-01

    Transport of momentum and scalars in turbulent boundary-layer flows over complex topography has been of great interest in the atmospheric sciences and wind engineering communities. Applications include but are not limited to weather forecasting, air pollution dispersion, aviation safety control, and wind energy project planning. Linear models have been well accepted to predict boundary-layer flows over topography with gentle slope. However, once the slope of the topography is sufficientlyo steep that flow separation occurs, linear models are not applicable. Modeling the turbulent transport of momentum and scalars in such flows has to be achieved through non-linear models, such as Reynolds-averaged Navier-Stokes solvers and large-eddy simulations (LES). Dynamics of the separated boundary-layer flows over steep topography is affected by the shape and size of the topography, surface characteristics (e.g., roughness and temperature) and atmospheric thermal stability. Most wind-tunnel experiments of boundary-layer flows over idealized topography (e.g. 2-D or 3-D hills, axisymmetric bumps) do not take thermal stability effects into account due to difficulty of physical simulation. We conducted comprehensive experimental investigation of stably- and unstably- stratified boundary layers over a steep 2-D hill in the thermally-controlled boundary-layer wind tunnel at the Saint Anthony Falls Laboratory. The 2-D model hill has a steepest slope of 0.73 and its shape follows a cosine square function: h=Hcos^2 (πx/L) for -L/2 ≤ x ≤ L/2 , where the maximum height H is 7 cm and the total width L is 15 cm. High-resolution Particle Image Velocimetry (PIV) provides dynamic information of the separated shear layer, the recirculation zone and flow reattachment. Turbulent momentum and scalar (heat) fluxes were characterized up to the top of the thermal boundary layer using a triple-wire (cross-wire and cold-wire) anemometer. Results indicate that promoted and suppressed turbulence

  9. NK cells enhance dendritic cell response against parasite antigens via NKG2D pathway.

    PubMed

    Guan, Hongbing; Moretto, Magali; Bzik, David J; Gigley, Jason; Khan, Imtiaz A

    2007-07-01

    Recent studies have shown that NK-dendritic cell (DC) interaction plays an important role in the induction of immune response against tumors and certain viruses. Although the effect of this interaction is bidirectional, the mechanism or molecules involved in this cross-talk have not been identified. In this study, we report that coculture with NK cells causes several fold increase in IL-12 production by Toxoplasma gondii lysate Ag-pulsed DC. This interaction also leads to stronger priming of Ag-specific CD8+ T cell response by these cells. In vitro blockade of NKG2D, a molecule present on human and murine NK cells, neutralizes the NK cell-induced up-regulation of DC response. Moreover, treatment of infected animals with Ab to NKG2D receptor compromises the development of Ag-specific CD8+ T cell immunity and reduces their ability to clear parasites. These studies emphasize the critical role played by NKG2D in the NK-DC interaction, which apparently is important for the generation of robust CD8+ T cell immunity against intracellular pathogens. To the best of our knowledge, this is the first work that describes in vivo importance of NKG2D during natural infection.

  10. TRENT2D WG: a smart web infrastructure for debris-flow modelling and hazard assessment

    NASA Astrophysics Data System (ADS)

    Zorzi, Nadia; Rosatti, Giorgio; Zugliani, Daniel; Rizzi, Alessandro; Piffer, Stefano

    2016-04-01

    Mountain regions are naturally exposed to geomorphic flows, which involve large amounts of sediments and induce significant morphological modifications. The physical complexity of this class of phenomena represents a challenging issue for modelling, leading to elaborate theoretical frameworks and sophisticated numerical techniques. In general, geomorphic-flows models proved to be valid tools in hazard assessment and management. However, model complexity seems to represent one of the main obstacles to the diffusion of advanced modelling tools between practitioners and stakeholders, although the UE Flood Directive (2007/60/EC) requires risk management and assessment to be based on "best practices and best available technologies". Furthermore, several cutting-edge models are not particularly user-friendly and multiple stand-alone software are needed to pre- and post-process modelling data. For all these reasons, users often resort to quicker and rougher approaches, leading possibly to unreliable results. Therefore, some effort seems to be necessary to overcome these drawbacks, with the purpose of supporting and encouraging a widespread diffusion of the most reliable, although sophisticated, modelling tools. With this aim, this work presents TRENT2D WG, a new smart modelling solution for the state-of-the-art model TRENT2D (Armanini et al., 2009, Rosatti and Begnudelli, 2013), which simulates debris flows and hyperconcentrated flows adopting a two-phase description over a mobile bed. TRENT2D WG is a web infrastructure joining advantages offered by the software-delivering model SaaS (Software as a Service) and by WebGIS technology and hosting a complete and user-friendly working environment for modelling. In order to develop TRENT2D WG, the model TRENT2D was converted into a service and exposed on a cloud server, transferring computational burdens from the user hardware to a high-performing server and reducing computational time. Then, the system was equipped with an

  11. Field Evaluation of a Novel 2D Preferential Flow Snowpack Hydrology Model

    NASA Astrophysics Data System (ADS)

    Leroux, N.; Pomeroy, J. W.; Kinar, N. J.

    2015-12-01

    Accurate estimation of snowmelt flux is of primary importance for runoff hydrograph prediction, which is used for water management and flood forecasting. Lateral flows and preferential flow pathways in porous media flow have proven critical for improving soil and groundwater flow models, but though many physically-based layered snowmelt models have been developed, only 1D matrix flow is accounted for in these models. Therefore, there is a need for snowmelt models that include these processes so as to examine the potential to improve snowmelt hydrological modelling. A 2D model is proposed that enables an improved understanding of energy and water flows within deep heterogeneous snowpacks, including those on slopes. A dual pathway theory is presented that simulates the formation of preferential flow paths, vertical and lateral water flows through the snow matrix and flow fingers, internal energy fluxes, melt, wet snow metamorphism, and internal refreezing. The dual pathway model utilizes an explicit finite volume method to solve for the energy and water flux equations over a non-orthogonal grid. It was run and evaluated using in-situ data collected from snowpit - accessed gravimetric, thermometric, photographic, and dielectric observations and novel non-invasive acoustic observations of layering, temperature, flowpath geometry, density and wetness at the Fortress Mountain Snow Laboratory, Alberta, Canada. The melt of a natural snowpack was artificially generated after detailed observation of snowpack initial conditions such as snow layer properties, temperature, and liquid water content. Snowpack ablation and liquid water content distribution over time were then measured and used for model parameterization and validation. Energy available at the snow surface and soil slope angle were set as mondel inputs. Model verification was based on snowpack property evolution. The heterogeneous flow model can be an important tool to help understand snowmelt flow processes, how

  12. A fast and accurate method to predict 2D and 3D aerodynamic boundary layer flows

    NASA Astrophysics Data System (ADS)

    Bijleveld, H. A.; Veldman, A. E. P.

    2014-12-01

    A quasi-simultaneous interaction method is applied to predict 2D and 3D aerodynamic flows. This method is suitable for offshore wind turbine design software as it is a very accurate and computationally reasonably cheap method. This study shows the results for a NACA 0012 airfoil. The two applied solvers converge to the experimental values when the grid is refined. We also show that in separation the eigenvalues remain positive thus avoiding the Goldstein singularity at separation. In 3D we show a flow over a dent in which separation occurs. A rotating flat plat is used to show the applicability of the method for rotating flows. The shown capabilities of the method indicate that the quasi-simultaneous interaction method is suitable for design methods for offshore wind turbine blades.

  13. Stabilizing effects on 2D channel flow due to longitudinal wall oscillation

    NASA Astrophysics Data System (ADS)

    Atobe, Takashi

    2017-01-01

    Stabilizing effect of longitudinal wall oscillation on two dimensional channel flow is analytically investigated. Model flow considered here is constituted of a superposition of the plane Poiseuille flow and the Stokes layer. The two walls are periodically oscillated in phase. Since the present system has a periodicity, the Floquet method is employed for the stability analysis. For this, a partial difference equation with a periodic function is derived from the time dependent version of the Orr-Sommerfeld equation using the Chebyshev spectral collocation method. The parameters governing the present system are the Reynolds number Re, the period Ω and amplitude Uw of the wall oscillation. Depending on the parameters, it is found that the 2D Tollmein-Shlichtin (TS) modes can be stabilized by the wall oscillation. Furthermore there are some case that 2D TS modes are more stabilized than the oblique TS mode. These results suggest that the oblique TS mode can appear earlier than the TS mode contrary to the Squire's Theorem.

  14. 2D application of a friction-limited model for debris flow propagation

    NASA Astrophysics Data System (ADS)

    Jaboyedoff, M.; Demierre, J.; Rudaz, B.

    2012-04-01

    Debris flows are each year responsible of severe infrastructure damages and human losses. Accurate simulation of this phenomenon allows for prevention of risks related to such events and can help for a sustainable territorial planning. A simple and intuitive 2-D debris flow model is developed using MatLab. It is based on the coupling of a mass point motion along the slope and the flattening of a volume linked to this mass point. Three main parameters have to be tuned in order to obtain a realistic prediction: the basal friction angle, the flattening coefficient and the debris flow maximum velocity. The model enables to simulate the location of the debris as a function of time and thus predict an important parameter of debris flow events, the runout distance. This tool allows for rapid calculations and has the advantage to use parameters that are easily assessable, such as the thickness of the debris flow deposit. The model is applied and compared to a debris flow event that occurred in Switzerland (Fully, VS) in October 2000. Following heavy rainfall and a hydroelectric pipe failure, a morainic deposit failed and propagated as a debris flow, reaching human-occupied areas (vineyards and roads). The event is well documented, with the initiation point, the flow velocity and runout distance known. A good agreement is found between the model prediction and the data from the debris flow event described above. This shows that the developed simple model can be an efficient tool to predict important debris flow characteristics, such as the runout distance. A further development would be to implement a 3-D model based on this approach

  15. Lyapunov stability of a spatially developing constant 2D gas flow

    NASA Astrophysics Data System (ADS)

    Balint, Agneta M.; Balint, Stefan; Szabo, Robert

    2017-01-01

    The well posedness of the perturbation propagation problem and the Lyapunov stability of a spatially developing constant 2D gas flow is analyzed in a particular infinite dimensional phase space. The elements of the phase space are continuously differentiable functions, the algebraic operations are usual and the topology is that generated by the uniform convergence. The well posedness of the propagation problem as well the Lyapunov stability with respect to the instantaneous and with respect to source produced permanent time harmonic perturbations is investigated. Some of the obtained results are completely different from those reported in the literature.

  16. Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine.

    PubMed

    Ross, Christina R; Temburnikar, Kartik W; Wilson, Gerald M; Seley-Radtke, Katherine L

    2015-04-15

    Halogenated thieno[3,2-d]pyrimidines exhibit antiproliferative activity against a variety of cancer cell models, such as the mouse lymphocytic leukemia cell line L1210 in which they induce apoptosis independent of cell cycle arrest. Here we assessed these activities on MDA-MB-231 cells, a well-established model of aggressive, metastatic breast cancer. While 2,4-dichloro[3,2-d]pyrimidine was less toxic to MDA-MB-231 cells than previously observed in the L1210 model, flow cytometry analysis showed that MDA-MB-231 cell death involved arrest at the G2/M stage of the cell cycle. Conversely, the introduction of bromine at C7 of the 2,4-dichloro[3,2-d]pyrimidine eliminated cell type-dependent differences in cytotoxicity or cell cycle status. Together, these data indicate that a substituent at C7 can profoundly modify the cytotoxic mechanism of halogenated thieno[3,2-d]pyrimidines in a cell type-specific manner.

  17. T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System

    PubMed Central

    Huang, Wei-Chen; Easom, Nicholas J.; Tang, Xin-Zi; Gill, Upkar S.; Singh, Harsimran; Robertson, Francis; Chang, Chiwen; Trowsdale, John; Davidson, Brian R.; Rosenberg, William M.; Fusai, Giuseppe; Toubert, Antoine; Kennedy, Patrick T.; Peppa, Dimitra

    2017-01-01

    NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)–specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0.001). NKG2D+NK cells were also increased and preferentially activated in the HBV-infected liver (p < 0.001), in direct proportion to the percentage of MICA/B-expressing CD4 T cells colocated within freshly isolated liver tissue (p < 0.001). This suggests that NKG2DL induced on T cells within a diseased organ can calibrate NKG2D-dependent activation of local NK cells; furthermore, NKG2D blockade could rescue HBV-specific and MICA/B-expressing T cells from HBV-infected livers. To our knowledge, this is the first ex vivo demonstration that non-virally infected human T cells can express NKG2DL, with implications for stress surveillance by the large number of NKG2D-expressing NK cells sequestered in the liver. PMID:28031333

  18. Chaotic advection and heat transfer in two similar 2-D periodic flows and in their corresponding 3-D periodic flows

    NASA Astrophysics Data System (ADS)

    Vinsard, G.; Dufour, S.; Saatdjian, E.; Mota, J. P. B.

    2016-03-01

    Chaotic advection can effectively enhance the heat transfer rate between a boundary and fluids with high Prandtl number. These fluids are usually highly viscous and thus turbulent agitation is not a viable solution since the energy required to mix the fluid would be prohibitive. Here, we analyze previously obtained results on chaotic advection and heat transfer in two similar 2-D periodic flows and on their corresponding 3-D periodic flows when an axial velocity component is superposed. The two flows studied are the flow between eccentric rotating cylinders and the flow between confocal ellipses. For both of these flows the analysis is simplified because the Stokes equations can be solved analytically to obtain a closed form solution. For both 2-D periodic flows, we show that chaotic heat transfer is enhanced by the displacement of the saddle point location during one period. Furthermore, the enhancement by chaotic advection in the elliptical geometry is approximately double that obtained in the cylindrical geometry because there are two saddle points instead of one. We also explain why, for high eccentricity ratios, there is no heat transfer enhancement in the cylindrical geometry. When an axial velocity component is added to both of these flows so that they become 3-D, previous work has shown that there is an optimum modulation frequency for which chaotic advection and heat transfer enhancement is a maximum. Here we show that the optimum modulation frequency can be derived from results without an axial flow. We also explain by physical arguments other previously unanswered questions in the published data.

  19. Reconfiguration of a flexible fiber immersed in a 2D dense granular flow close to the jamming transition

    NASA Astrophysics Data System (ADS)

    Kolb, Evelyne; Algarra, Nicolas; Vandembroucq, Damien; Lazarus, Arnaud

    2015-11-01

    We propose a new fluid/structure interaction in the unusual case of a dense granular medium flowing against an elastic fibre acting as a flexible intruder. We experimentally studied the deflection of a mylar flexible beam clamped at one side, the other free side facing a 2D granular flow in a horizontal cell moving at a constant velocity. We investigated the reconfiguration of the fibre as a function of the fibre's rigidity and of the granular packing fraction close but below the jamming in 2D. Imposing the fibre geometry like its length or thickness sets the critical buckling force the fibre is able to resist if it was not supported by lateral grains, while increasing the granular packing fraction might laterally consolidate the fibre and prevent it from buckling. But on the other side, the approach to jamming transition by increasing the granular packing fraction will be characterized by a dramatically increasing size of the cluster of connected grains forming a solid block acting against the fibre, which might promote the fibre's deflection. Thus, we investigated the granular flow fields, the fibre's deflexion as well as the forces experienced by the fibre and compared them with theoretical predictions from elastica for different loadings along the fibre. PMMH, CNRS UMR 7636, UPMC, ESPCI-ParisTech, 10 rue Vauquelin, 75231 Paris Cedex 05, France.

  20. Evolution of vortices in 2D boundary layer and in the Couette flow

    NASA Astrophysics Data System (ADS)

    Zametaev, Vladimir B.; Gorbushin, Anton R.

    2016-10-01

    A 2D incompressible laminar boundary layer and the Couette flow having the low velocity fluctuations are considered using asymptotic methods at high Reynolds number. Two classes of solutions for the first order inviscid perturbations have been derived. The integral-differential equation with initial data describing evolution of vortices in time have been solved numerically. It was found that the discontinuities are formed in a smooth solution for a vertical velocity component with the time increase. This first type solution explains instability mechanism in the Couette flow. The second class of solutions contains a singularity at the boundary layer bottom which reminds a source-sink with a variable intensity. The singularity can absorb the fluid from the main part of the boundary layer and eject it back with a possibly "new" vorticity.

  1. Integrated Coupling of Surface and Subsurface Flow with HYDRUS-2D

    NASA Astrophysics Data System (ADS)

    Hartmann, Anne; Šimůnek, Jirka; Wöhling, Thomas; Schütze, Niels

    2016-04-01

    Describing interactions between surface and subsurface flow processes is important to adequately define water flow in natural systems. Since overland flow generation is highly influenced by rainfall and infiltration, both highly spatially heterogeneous processes, overland flow is unsteady and varies spatially. The prediction of overland flow needs to include an appropriate description of the interactions between the surface and subsurface flow. Coupling surface and subsurface water flow is a challenging task. Different approaches have been developed during the last few years, each having its own advantages and disadvantages. A new approach by Weill et al. (2009) to couple overland flow and subsurface flow based on a generalized Richards equation was implemented into the well-known subsurface flow model HYDRUS-2D (Šimůnek et al., 2011). This approach utilizes the one-dimensional diffusion wave equation to model overland flow. The diffusion wave model is integrated in HYDRUS-2D by replacing the terms of the Richards equation in a pre-defined runoff layer by terms defining the diffusion wave equation. Using this approach, pressure and flux continuity along the interface between both flow domains is provided. This direct coupling approach provides a strong coupling of both systems based on the definition of a single global system matrix to numerically solve the coupled flow problem. The advantage of the direct coupling approach, compared to the loosely coupled approach, is supposed to be a higher robustness, when many convergence problems can be avoided (Takizawa et al., 2014). The HYDRUS-2D implementation was verified using a) different test cases, including a direct comparison with the results of Weill et al. (2009), b) an analytical solution of the kinematic wave equation, and c) the results of a benchmark test of Maxwell et al. (2014), that included several known coupled surface subsurface flow models. Additionally, a sensitivity analysis evaluating the effects

  2. Numerical and experimental study of gas flows in 2D and 3D microchannels

    NASA Astrophysics Data System (ADS)

    Guo, Xiaohui; Huang, Chihyung; Alexeenko, Alina; Sullivan, John

    2008-02-01

    In the experiments conducted at Purdue, the air flow in rectangular cross-section microchannels was investigated using pressure sensitive paint. The high resolution pressure measurements were obtained for inlet-to-outlet pressure ratios from 1.76 to 20 with the outlet Knudsen numbers in the range from 0.003 to 0.4 based on the hydraulic diameter of 151.7 µm and the length-to-height ratio of about 50. In the slip flow regime, the air flow was simulated by the 2D and 3D Navier-Stokes equations with no-slip and slip boundary conditions. For various pressure ratios, the entrance flow development, compressibility and rarefaction effects were observed in both experiments and numerical simulations. It was found that the accurate modeling of gas flows in finite-length channels requires the inlet and outlet reservoirs to be included in computations. Effects of entrance geometry on the friction factor were studied for 3D cases. In both experiments and numerical modeling, significant pressure drop was found starting at the inlet chamber. The numerical modeling also predicted an apparent temperature drop at the channel exit.

  3. Quasi-simultaneous interaction method for solving 2D boundary layer flows over plates and airfoils

    NASA Astrophysics Data System (ADS)

    Bijleveld, H. A.; Veldman, A. E. P.

    2012-11-01

    This paper studies unsteady 2D boundary layer flows over dented plates and a NACA 0012 airfoil. An inviscid flow is assumed to exist outside the boundary layer and is solved iteratively with the boundary layer flow together with the interaction method until a matching solution is achieved. Hereto a quasi-simultaneous interaction method is applied, in which the integral boundary layer equations are solved together with an interaction-law equation. The interaction-law equation is an approximation of the external flow and based on thin-airfoil theory. It is an algebraic relation between the velocity and displacement thickness. The interaction-law equation ensures that the eigenvalues of the system of equations do not have a sign change and that no singularities occur. Three numerical schemes are used to solve the boundary layer flow with the interaction method. These are: a standard scheme, a splitting method and a characteristics solver. All schemes use a finite difference discretization. The three schemes yield comparable results for the simulations carried out. The standard scheme is deviating most from the splitting and characteristics solvers. The results show that the eigenvalues remain positive, even in separation. As expected, the addition of the interaction-law equation prevents a sign change of the eigenvalues. The quasi-simultaneous interaction scheme is applicable to the three numerical schemes tested.

  4. Self-Organization in 2D Traffic Flow Model with Jam-Avoiding Drive

    NASA Astrophysics Data System (ADS)

    Nagatani, Takashi

    1995-04-01

    A stochastic cellular automaton (CA) model is presented to investigate the traffic jam by self-organization in the two-dimensional (2D) traffic flow. The CA model is the extended version of the 2D asymmetric exclusion model to take into account jam-avoiding drive. Each site contains either a car moving to the up, a car moving to the right, or is empty. A up car can shift right with probability p ja if it is blocked ahead by other cars. It is shown that the three phases (the low-density phase, the intermediate-density phase and the high-density phase) appear in the traffic flow. The intermediate-density phase is characterized by the right moving of up cars. The jamming transition to the high-density jamming phase occurs with higher density of cars than that without jam-avoiding drive. The jamming transition point p 2c increases with the shifting probability p ja. In the deterministic limit of p ja=1, it is found that a new jamming transition occurs from the low-density synchronized-shifting phase to the high-density moving phase with increasing density of cars. In the synchronized-shifting phase, all up cars do not move to the up but shift to the right by synchronizing with the move of right cars. We show that the jam-avoiding drive has an important effect on the dynamical jamming transition.

  5. Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells.

    PubMed

    Flynn, Maxfield P; Fiedler, Sarah E; Karlsson, Amelia B; Carr, Daniel W; Maizels, Evelyn T; Hunzicker-Dunn, Mary

    2016-08-01

    Preovulatory granulosa cells express the low-molecular-mass MAP2D variant of microtubule-associated protein 2 (MAP2). Activation of the luteinizing hormone choriogonadotropin receptor by human choriogonadotropin (hCG) promotes dephosphorylation of MAP2D on Thr256 and Thr259. We sought to evaluate the association of MAP2D with the cytoskeleton, and the effect of hCG on this association. MAP2D partially colocalized, as assessed by confocal immunofluorescence microscopy, with the vimentin intermediate filament and microtubule cytoskeletons in naive cells. In vitro binding studies showed that MAP2D bound directly to vimentin and β-tubulin. Phosphorylation of recombinant MAP2D on Thr256 and Thr259, which mimics the phosphorylation status of MAP2D in naive cells, reduces binding of MAP2D to vimentin and tubulin by two- and three-fold, respectively. PKA-dependent phosphorylation of vimentin (Ser32 and Ser38) promoted binding of vimentin to MAP2D and increased contraction of granulosa cells with reorganization of vimentin filaments and MAP2D from the periphery into a thickened layer surrounding the nucleus and into prominent cellular extensions. Chemical disruption of vimentin filament organization increased progesterone production. Taken together, these results suggest that hCG-stimulated dephosphorylation of MAP2D at Thr256 and Thr259, phosphorylation of vimentin at Ser38 and Ser72, and the resulting enhanced binding of MAP2D to vimentin might contribute to the progesterone synthetic response required for ovulation.

  6. NKG2D receptor regulates human effector T-cell cytokine production

    PubMed Central

    Barber, Amorette

    2011-01-01

    Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8+ T cells. Stimulation of CD8+ T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin–induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-α in a β-catenin– and PPARγ- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8+ T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex. PMID:21518928

  7. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection

    PubMed Central

    Deng, Weiwen; Gowen, Benjamin G.; Zhang, Li; Wang, Lin; Lau, Stephanie; Iannello, Alexandre; Xu, Jianfeng; Rovis, Tihana L.; Xiong, Na; Raulet, David H.

    2016-01-01

    Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D activating receptor on NK cells and/or T cells, and desensitize these cells. In contrast, we show that in mice, shedding of MULT1, a high affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are inhibitory, and suggest a new approach for cancer immunotherapy. PMID:25745066

  8. CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells

    PubMed Central

    Sauer, M; Schuldner, M; Hoffmann, N; Cetintas, A; Reiners, K S; Shatnyeva, O; Hallek, M; Hansen, H P; Gasser, S; von Strandmann, E P

    2017-01-01

    Tumor surveillance of natural killer (NK) cells is mediated by the cytotoxicity receptor natural-killer group 2 member D (NKG2D). Ligands for NKG2D are generally not expressed on healthy cells, but induced on the surface of malignant cells. To date, NKG2D ligand (NKG2D-L) induction was mainly described to depend on the activation of the DNA damage response, although the molecular mechanisms that regulate NKG2D-L expression remain largely unknown. Here, we show that the acetyltransferases CBP (CREB-binding protein) and p300 play a crucial role in the regulation of NKG2D-L on tumor cells. Loss of CBP/p300 decreased the basal cell surface expression of human ligands and reduced the upregulation of MICA/B and ULBP2 in response to histone deacetylase inhibitors or DNA damage. Furthermore, CBP/P300 deficiency abrogated the sensitivity of stressed cells to NK cell-mediated killing. CBP/p300 were also identified as major regulators of mouse NKG2D ligand RAE-1 in vitro and in vivo using the Eμ-Myc lymphoma model. Mechanistically, we observed an enhanced activation of the CBP/p300 binding transcription factor CREB (cAMP response element-binding protein) correlating to the NKG2D-L upregulation. Moreover, increased binding of CREB and CBP/p300 to NKG2D-L promoters and elevated histone acetylation were detectable. This study provides strong evidence for a major role of CBP and p300 in orchestrating NKG2D-L induction and consequently immunosurveillance of tumors in mice and humans. These findings might help to develop novel immunotherapeutic approaches against cancer. PMID:27477692

  9. Simulation of abrasive flow machining process for 2D and 3D mixture models

    NASA Astrophysics Data System (ADS)

    Dash, Rupalika; Maity, Kalipada

    2015-12-01

    Improvement of surface finish and material removal has been quite a challenge in a finishing operation such as abrasive flow machining (AFM). Factors that affect the surface finish and material removal are media viscosity, extrusion pressure, piston velocity, and particle size in abrasive flow machining process. Performing experiments for all the parameters and accurately obtaining an optimized parameter in a short time are difficult to accomplish because the operation requires a precise finish. Computational fluid dynamics (CFD) simulation was employed to accurately determine optimum parameters. In the current work, a 2D model was designed, and the flow analysis, force calculation, and material removal prediction were performed and compared with the available experimental data. Another 3D model for a swaging die finishing using AFM was simulated at different viscosities of the media to study the effects on the controlling parameters. A CFD simulation was performed by using commercially available ANSYS FLUENT. Two phases were considered for the flow analysis, and multiphase mixture model was taken into account. The fluid was considered to be a

  10. Crossing barriers: the new dimension of 2D cell migration assays.

    PubMed

    Van Horssen, Remco; ten Hagen, Timo L M

    2011-01-01

    In our body cells move in three dimensions, embedded in an extracellular matrix that varies in composition, density and stiffness, and this movement is fundamental to life. Next to 3D cell migration assays, representing these physiological circumstances, still we need 2D migrations assays to perform detailed studies on the contribution of matrix-components and (extra)cellular proteins to cell movements. Next to the debate on differences between 3D and 2D migration, there also are many new perspectives on the use and development of novel or modified 2D cell migration assays. Of special significance is the introduction of so-called barrier migration assays, methods that avoid cell and matrix damage, as complementation or replacement of scratch/wound healing assays. Here, we discuss the possibilities and limitations of different 2D barrier migration assays.

  11. 2D Biotope Mapping Using Combined LIDAR, Topographic Survey And Segmented 1D Flow Modelling

    NASA Astrophysics Data System (ADS)

    Entwistle, N. S.; Heritage, G. L.; Milan, D. J.

    2009-12-01

    Reach averaged habitat availability models such as PHABSIM are limited due principally to their failure to adequately map hydraulic habitat distribution at a representative scale. A lack of morphologic data, represented in the form of sparse geometric cross-sections fails to generate the necessary detail. Advances in data collection, improved spatial modelling algorithms and the advent of cross-section based segmentation routines in 1D hydraulic models provides the opportunity to revisit the issue of hydraulic habitat mapping and modelling. This paper presents a combined technique for habitat characterisation at the sub-bar scale is presented for the River Rede, Northumberland, UK. Terrestrial LIDAR data of floodplain, banks and exposed bar surfaces at an average 0.05 m spacing are combined with sparser total station survey data of submerged morphologic features. These data are interpolated to create a uniform DEM grid at 0.2 m spacing (adequate to detect the smallest variation in hydraulic habitat in this system). The data grid were then imported into the HECRAS 1D hydraulic model to generate a 2 m spaced series of cross-sections along a 220 m sinuous single thread reach exhibiting pool - riffle point-bar morphology. The hydraulic segmentation routine then generated estimates of depth averaged flow velocity, flow depth and sub unit discharge for 40 sub-divisions of the flow width for a series of flows from 0.5 m3s-1 up to bankfull flow of approximately 9 m3s-1. The resultant hydraulic data were exported in the project coordinate system and plotted to reveal the 2D pattern of hydraulic biotopes present across the range of flows modelled. The results reveal broadly realistic patterns consistent with previous empirical studies and compare well with LIDAR based biotope maps. Analysis of the temporal pattern of biotope change indicates that biotope diversity and complexity is at a maximum at lower flows and across shallower area (riffles) and that these dominate the

  12. Computation of nozzle flow fields using the PARC2D Navier-Stokes code

    NASA Technical Reports Server (NTRS)

    Collins, Frank G.

    1986-01-01

    Supersonic nozzles which operate at low Reynolds numbers and have large expansion ratios have very thick boundary layers at their exit. This leads to a very strong viscous/inviscid interaction upon the flow within the nozzle and the traditional nozzle design techniques which correct the inviscid core with a boundary layer displacement do not accurately predict the nozzle exit conditions. A full Navier-Stokes code (PARC2D) was used to compute the nozzle flow field. Grids were generated using the interactive grid generator code TBGG. All computations were made on the NASA MSFC CRAY X-MP computer. Comparison was made between the computations and in-house wall pressure measurements for CO2 flow through a conical nozzle having an area ratio of 40. Satisfactory agreement existed between the computations and measurements for a stagnation pressure of 29.4 psia and stagnation temperature of 1060 R. However, agreement did not exist at a stagnation pressure of 7.4 psia. Several reasons for the lack of agreement are possible. The computational code assumed a constant gas gamma whereas gamma for CO2 varied from 1.22 in the plenum chamber to 1.38 at the nozzle exit. Finally, it is possible that condensation occurred during the expansion at the lower stagnation pressure.

  13. Micro PIV measurements of turbulent flow over 2D structured roughness

    NASA Astrophysics Data System (ADS)

    Hartenberger, Joel; Perlin, Marc

    2015-11-01

    We investigate the turbulent boundary layer over surfaces with 2D spanwise square and triangular protrusions having nominal heights of 100 - 300 microns for Reynolds numbers ranging from Reτ ~ 1500 through Reτ ~ 4500 using a high speed, high magnification imaging system. Micro PIV analysis gives finely resolved velocity fields of the flow (on the order of 10 microns between vectors) enabling a detailed look at the inner region as well as the flow in the immediate vicinity of the roughness elements. Additionally, planar PIV with lower resolution is performed to capture the remainder of the boundary layer to the freestream flow. Varying the streamwise distance between individual roughness elements from one to ten times the nominal heights allows investigation of k-type and d-type roughness in both the transitionally rough and fully rough regimes. Preliminary results show a shift in the mean velocity profile similar to the results of previous studies. Turbulent statistics will be presented also. The authors would like to acknowledge the support of NAVSEA which funded this project through the Naval Engineering Education Center (NEEC).

  14. Direct numerical simulation of a 2D-stented aortic heart valve at physiological flow rates.

    PubMed

    Dimakopoulos, Y; Bogaerds, A C B; Anderson, P D; Hulsen, M A; Baaijens, F P T

    2012-01-01

    We study the nonlinear interaction of an aortic heart valve, composed of hyperelastic corrugated leaflets of finite density attached to a stented vessel under physiological flow conditions. In our numerical simulations, we use a 2D idealised representation of this arrangement. Blood flow is caused by a time-varying pressure gradient that mimics that of the aortic valve and corresponds to a peak Reynolds number equal to 4050. Here, we fully account for the shear-thinning behaviour of the blood and large deformations and contact between the leaflets by solving the momentum and mass balances for blood and leaflets. The mixed finite element/Galerkin method along with linear discontinuous Lagrange multipliers for coupling the fluid and elastic domains is adopted. Moreover, a series of challenging numerical issues such as the finite length of the computational domain and the conditions that should be imposed on its inflow/outflow boundaries, the accurate time integration of the parabolic and hyperbolic momentum equations, the contact between the leaflets and the non-conforming mesh refinement in part of the domain are successfully resolved. Calculations for the velocity and the shear stress fields of the blood reveal that boundary layers appear on both sides of a leaflet. The one along the ventricular side transfers blood with high momentum from the core region of the vessel to the annulus or the sinusoidal expansion, causing the continuous development of flow instabilities. At peak systole, vortices are convected in the flow direction along the annulus of the vessel, whereas during the closure stage of the valve, an extremely large vortex develops in each half of the flow domain.

  15. A friction to flow constitutive law and its application to a 2-D modeling of earthquakes

    NASA Astrophysics Data System (ADS)

    Shimamoto, Toshihiko; Noda, Hiroyuki

    2014-11-01

    Establishment of a constitutive law from friction to high-temperature plastic flow has long been a challenging task for solving problems such as modeling earthquakes and plate interactions. Here we propose an empirical constitutive law that describes this transitional behavior using only friction and flow parameters, with good agreements with experimental data on halite shear zones. The law predicts steady state and transient behaviors, including the dependence of the shear resistance of fault on slip rate, effective normal stress, and temperature. It also predicts a change in velocity weakening to velocity strengthening with increasing temperature, similar to the changes recognized for quartz and granite gouge under hydrothermal conditions. A slight deviation from the steady state friction law due to the involvement of plastic deformation can cause a large change in the velocity dependence. We solved seismic cycles of a fault across the lithosphere with the law using a 2-D spectral boundary integral equation method, revealing dynamic rupture extending into the aseismic zone and rich evolution of interseismic creep including slow slip prior to earthquakes. Seismic slip followed by creep is consistent with natural pseudotachylytes overprinted with mylonitic deformation. Overall fault behaviors during earthquake cycles are insensitive to transient flow parameters. The friction-to-flow law merges "Christmas tree" strength profiles of the lithosphere and rate dependency fault models used for earthquake modeling on a unified basis. Strength profiles were drawn assuming a strain rate for the flow regime, but we emphasize that stress distribution evolves reflecting the fault behavior. A fault zone model was updated based on the earthquake modeling.

  16. Thermochemical Nonequilibrium 2D Modeling of Nitrogen Inductively Coupled Plasma Flow

    NASA Astrophysics Data System (ADS)

    Yu, Minghao; Yusuke, Takahashi; Hisashi, Kihara; Ken-ichi, Abe; Kazuhiko, Yamada; Takashi, Abe; Satoshi, Miyatani

    2015-09-01

    Two-dimensional (2D) numerical simulations of thermochemical nonequilibrium inductively coupled plasma (ICP) flows inside a 10-kW inductively coupled plasma wind tunnel (ICPWT) were carried out with nitrogen as the working gas. Compressible axisymmetric Navier-Stokes (N-S) equations coupled with magnetic vector potential equations were solved. A four-temperature model including an improved electron-vibration relaxation time was used to model the internal energy exchange between electron and heavy particles. The third-order accuracy electron transport properties (3rd AETP) were applied to the simulations. A hybrid chemical kinetic model was adopted to model the chemical nonequilibrium process. The flow characteristics such as thermal nonequilibrium, inductive discharge, effects of Lorentz force were made clear through the present study. It was clarified that the thermal nonequilibrium model played an important role in properly predicting the temperature field. The prediction accuracy can be improved by applying the 3rd AETP to the simulation for this ICPWT. supported by Grant-in-Aid for Scientific Research (No. 23560954), sponsored by the Japan Society for the Promotion of Science

  17. Human NKG2D-ligands: cell biology strategies to ensure immune recognition

    PubMed Central

    Fernández-Messina, Lola; Reyburn, Hugh T.; Valés-Gómez, Mar

    2012-01-01

    Immune recognition mediated by the activating receptor NKG2D plays an important role for the elimination of stressed cells, including tumors and virus-infected cells. On the other hand, the ligands for NKG2D can also be shed into the sera of cancer patients where they weaken the immune response by downmodulating the receptor on effector cells, mainly NK and T cells. Although both families of NKG2D-ligands, major histocompatibility complex class I-related chain (MIC) A/B and UL16 binding proteins (ULBPs), are related to MHC molecules and their expression is increased after stress, many differences are observed in terms of their biochemical properties and cell trafficking. In this paper, we summarize the variety of NKG2D-ligands and propose that selection pressure has driven evolution of diversity in their trafficking and shedding, but not receptor binding affinity. However, it is also possible to identify functional properties common to individual ULBP molecules and MICA/B alleles, but not generally conserved within the MIC or ULBP families. These characteristics likely represent examples of convergent evolution for efficient immune recognition, but are also attractive targets for pathogen immune evasion strategies. Categorization of NKG2D-ligands according to their biological features, rather than their genetic family, may help to achieve a better understanding of NKG2D-ligand association with disease. PMID:23056001

  18. ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing

    PubMed Central

    Zocchi, Maria Raffaella; Camodeca, Caterina; Nuti, Elisa; Rossello, Armando; Venè, Roberta; Tosetti, Francesca; Dapino, Irene; Costa, Delfina; Musso, Alessandra; Poggi, Alessandro

    2016-01-01

    ABSTRACT Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the “A Disintegrin And Metalloproteases” (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X. PMID:27467923

  19. ADAM10 new selective inhibitors reduce NKG2D ligand release sensitizing Hodgkin lymphoma cells to NKG2D-mediated killing.

    PubMed

    Zocchi, Maria Raffaella; Camodeca, Caterina; Nuti, Elisa; Rossello, Armando; Venè, Roberta; Tosetti, Francesca; Dapino, Irene; Costa, Delfina; Musso, Alessandra; Poggi, Alessandro

    2016-05-01

    Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes of treatment. Members of the "A Disintegrin And Metalloproteases" (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors have been shown to exert antitumor effects. We have previously described an overexpression of ADAM10 in HL, together with increased release of NKG2D ligands (NKG2D-L) and reduced activation of effector T lymphocytes with anti-lymphoma capacity. Aim of the present work was to verify whether inhibition of ADAM10 in HL cells could restore the triggering of NKG2D-dependent anti-lymphoma T cell response. As no selective ADAM10 blockers have been reported so far, we synthesized the two hydroxamate compounds LT4 and MN8 with selectivity for ADAM10 over metalloproteases (MMPs), LT4 showing higher specificity for ADAM10 over ADAM17. We show that (i) HL lymph nodes (LN) and cultured HL cells express high levels of the mature active membrane form of ADAM10; (ii) ADAM10 is the major sheddase for the NKG2D-L in HL cells; (iii) the new LT4 and MN8 compounds strongly reduce the shedding of NKG2D-L by HL cell lines and enhance the binding of NKG2D receptor; (iv) of note, these new ADAM10 inhibitors increase the sensitivity of HL cell lines to NKG2D-dependent cell killing exerted by natural killer and γδ T cells. Overall, the biologic activity of LT4 and MN8 appears to be more potent than that of the commercial inhibitor GI254023X.

  20. Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

    PubMed

    Ingles, Sue Ann; Wu, Liang; Liu, Benjamin T; Chen, Yibu; Wang, Chun-Yeh; Templeman, Claire; Brueggmann, Doerthe

    2017-01-28

    Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)2D3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)2D3, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)2D3. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)2D3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.

  1. Turbulence modeling for subsonic separated flows over 2-D airfoils and 3-D wings

    NASA Astrophysics Data System (ADS)

    Rosen, Aaron M.

    Accurate predictions of turbulent boundary layers and flow separation through computational fluid dynamics (CFD) are becoming more and more essential for the prediction of loads in the design of aerodynamic flight components. Standard eddy viscosity models used in many commercial codes today do not capture the nonequilibrium effects seen in a separated flow and thus do not generally make accurate separation predictions. Part of the reason for this is that under nonequilibrium conditions such as a strong adverse pressure gradient, the history effects of the flow play an important role in the growth and decay of turbulence. More recent turbulence models such as Olsen and Coakley's Lag model and Lillard's lagRST model seek to simulate these effects by lagging the turbulent variables when nonequilibrium effects become important. The purpose of the current research is to assess how these nonequilibrium turbulence models capture the separated regions on various 2-D airfoils and 3-D wings. Nonequilibrium models including the Lag model and the lagRST model are evaluated in comparison with three baseline models (Spalart-Allmaras, Wilcox's k-omega, and Menter's SST) using a modified version of the OVERFLOW code. Tuning the model coefficients of the Lag and lagRST models is also explored. Results show that the various lagRST formulations display an improvement in velocity profile predictions over the standard RANS models, but have trouble capturing the edge of the boundary layer. Experimental separation location measurements were not available, but several trends are noted which may be useful to tuning the model coefficients in the future.

  2. Heat Flow Partitioning Between Continents and Oceans - from 2D to 3D

    NASA Astrophysics Data System (ADS)

    Moresi, L. N.; Cooper, C. M.; Lenardic, A.

    2010-12-01

    Scalings derived from thermal network theory explain how the presence of continents can influence the Earth’s overall heat loss. Intuitively, it may seem that increasing the proportion of a planet’s surface area covered by continents would decrease the efficiency of heat transfer given that continents do not participate in convective overturn. However, this ignores the potential feedback between the insulating effect of continents and the temperature-dependent viscosity of the mantle (Lenardic et al, 2005, Cooper et al, 2007). When this feedback is considered, a clear regime exists in which the partial stagnation and insulation of the surface by buoyant continental crust can lead to an increase in heat flow compared to the uninsulated case. The numerical results used to verify the scalings have mostly been conducted in two dimensions in order to cover a very wide range of Rayleigh number, fraction of continental coverage, and continental thickness. However as more recent results show that the configuration of the crust also plays a role in determining the heat flow partitioning and global heat flow (See Lenardic et al, “Continents, Super-Continents, Mantle Thermal Mixing, and Mantle Thermal Isolation” in this session), we have begun to repeat this exhaustive and exhausting 2D study in 3D. Cooper, C.M., A. Lenardic, and L.-N. Moresi "Effects of continental insulation and the partioning of heat producing elements on the Earth's heat loss." Geophys. Res. Lett., 33 ,10.1029, 2006. Lenardic, A., L.-N. Moresi, A.M. Jellinek, and M. Manga "Continental insulation, mantle cooling, and the surface area of oceans and continents." Earth Planet. Sci. Lett., 234 ,317-333, 2005.

  3. Full 2D observation of water surface elevation from SWOT under different flow conditions

    NASA Astrophysics Data System (ADS)

    Domeneghetti, Alessio; Schumann, Guy; Rui, Wei; Durand, Michael; Pavelsky, Tamlin

    2016-04-01

    The upcoming Surface Water and Ocean Topography (SWOT) satellite mission is a joint project of NASA, Centre National d'Etudes Spatiales (CNES, France), the Canadian Space Agency, and the Space Agency of the UK that will provide a first global, high-resolution observation of ocean and terrestrial water surface heights. Characterized by an observation swath of 120 km and an orbit repeat interval of about 21 days, SWOT will provide unprecedented bi-dimensional observations of rivers wider than 50-100 m. Despite many research activities that have investigated potential uses of remotely sensed data from SWOT, potentials and limitations of the spatial observations provided by the satellite mission for flood modeling still remain poorly understood and investigated. In this study we present a first analysis of the spatial observation of water surface elevation that is expected from SWOT for a 140 km reach of the middle-lower portion of the Po River, in Northern Italy. The river stretch is characterized by a main channel varying from 200-500 m in width and a floodplain that can be as wide as 5 km and that is delimited by a system of major embankments. The reconstruction of the hydraulic behavior of the Po River is performed by means of a quasi-2d model built with detailed topographic and bathymetric information (LiDAR, 2 m resolution), while the simulation of the spatial observation sensed by SWOT is performed with a SWOT simulator that mimics the satellite sensor characteristics. Referring to water surface elevations associated with different flow conditions (maximum, minimum and average flow reproduced by means of the quasi-2d numerical model) this work provides a first characterization of the spatial observations provided by SWOT and highlights the strengths and limitations of the expected products. By referring to a real river reach the analysis provides a credible example of the type of spatial observations that will be available after launch of SWOT and offers a first

  4. NKG2D+ IFN-γ+ CD8+ T Cells Are Responsible for Palladium Allergy

    PubMed Central

    Kawano, Mitsuko; Nakayama, Masafumi; Aoshima, Yusuke; Nakamura, Kyohei; Ono, Mizuho; Nishiya, Tadashi; Nakamura, Syou; Takeda, Yuri; Dobashi, Akira; Takahashi, Akiko; Endo, Misato; Ito, Akiyo; Ueda, Kyosuke; Sato, Naoki; Higuchi, Shigehito; Kondo, Takeru; Hashimoto, Suguru; Watanabe, Masamichi; Watanabe, Makoto; Takahashi, Tetsu; Sasaki, Keiichi; Nakamura, Masanori; Sasazuki, Takehiko; Narushima, Takayuki; Suzuki, Ryuji; Ogasawara, Kouetsu

    2014-01-01

    Nickel, cobalt, and chromium are well known to be causal agents of allergic contact dermatitis. Palladium (Pd) can also cause allergic disease and exposure results from wide use of this metal in dental restorations and jewelry. Metal allergy is categorized as a delayed-type hypersensitivity, and metal-responsive T cell clones have been isolated from allergic patients. However, compared to nickel, little is known about the pathology of allergic disease mediated by Pd, and pathogenic T cells are poorly understood. To identify the pathogenic T cells that are responsible for onset of Pd allergy, we enriched metal-responsive lymphocytes by sequential adoptive transfer of involved lymph node cells. Here we show that sequential adoptive transfer gradually increased the incidence and the intensity of Pd allergy, and CD8+ T cells are responsible for the disease as CD8+ T cell-depleted mice and β2-microglobulin-deficient mice did not develop Pd allergy. In addition, we found that draining lymph node cells skewed toward CD8+ T cells in response to Pd challenge in 8th adoptive transferred recipient mice. The CD8+ T cells expressed NKG2D, a costimulatory molecule involved in the production of IFN-γ. NKG2D ligand was also induced in Pd-injected tissues. Furthermore, both NKG2D ligand-transgenic mice, where NKG2D is downmodulated, and IFN-γ-deficient mice showed impaired Pd allergy. Taken together, these results indicate that IFN-γ-producing NKG2D+ CD8+ T cells are responsible for Pd allergy and suggest that NKG2D is a potential therapeutic target for treatment of metal allergy. PMID:24533050

  5. Naringenin enhances NK cell lysis activity by increasing the expression of NKG2D ligands on Burkitt's lymphoma cells.

    PubMed

    Kim, Jeong Hwa; Lee, Jae Kwon

    2015-11-01

    Natural killer (NK) cells are capable of identifying and killing tumor cells as well as virus infected cells without pre-sensitization. NK cells express activating and inhibitory receptors, and can distinguish between normal and tumor cells. The present study was designed to demonstrate the importance of the expression level of NKG2D ligands on the Burkitt's lymphoma cell line, Raji, in enhancing NK cell cytolytic activity. Various flavonoids were used as stimulants to enhance the expression of NKG2D ligands. NK cell lysis activity against Raji was not changed by pre-treatment of Raji with luteolin, kaempferol, taxifolin and hesperetin. However, treatment of Raji with naringenin showed increased sensitivity to NK cell lysis than untreated control cells. The activity of naringenin was due to enhanced NKG2D ligand expression. These results provide evidence that narigenin's antitumor activity may be due to targeting of NKG2D ligand expression and suggests a possible immunotherapeutic role for cancer treatment.

  6. Natural Killer Group 2, Member D/NKG2D Ligands in Hematopoietic Cell Transplantation

    PubMed Central

    Carapito, Raphael; Aouadi, Ismail; Ilias, Wassila; Bahram, Seiamak

    2017-01-01

    Natural killer group 2, member D (NKG2D) is an invariant activatory receptor present on subsets of natural killer and T lymphocytes. It stimulates the cytolytic effector response upon engagement of its various stress-induced ligands NKG2D ligands (NKG2DL). Malignant transformation and conditioning treatment prior to hematopoietic cell transplantation (HCT) are stress factors leading to the activation of the NKG2D/NKG2DL signaling in clinical settings. In the context of HCT, NKG2D-bearing cells can kill both tumor and healthy cells expressing NKG2DL. The NKG2D/NKG2DL engagement has therefore a key role in the regulation of one of the most salient issues in allogeneic HCT, i.e., maintaining a balance between graft-vs.-leukemia effect and graft-vs.-host disease. The present review summarizes the current state of our knowledge pertaining to the role of the NKG2D and NKG2DL in HCT.

  7. Titan2D Based Pyroclastic Flows Hazard Maps for Santa Ana Volcano, El Salvador

    NASA Astrophysics Data System (ADS)

    Bajo, J. V.; Martinez-Hackert, B.; Escobar, C. D.; Gutierrez, R. E.

    2009-05-01

    Santa Ana Volcano is located in the Apaneca Volcanic Field located to the west of El Salvador, Central America. It is one the six active volcanoes monitor by the Servicios Nacionales de Estudios Territoriales (SNET) in El Salvador, out of twenty that are considered active in this small country by Smithsonian definition. The Santa Ana Volcano is surrounded by rural communities in its proximal areas and in its close distal areas by the second largest city of the country. On October 1st 2005, after a few months of increased fumarolic and seismic activity, it erupted generating a 10 km high steam and ash plume, reportedly seen by some aircraft and estimated using photography by SNET members. Ash was deposited to the west, north-west part of the country, following typical wind pattern for the region, as well as small pyroclastic flows and major lahars in its eastern part. Coffee plantations were lost, as was some crop of coffee in the following season. However, to the west the ash fertilized the land and resulted in an enhanced harvest of coffee beans. Only 2 people were killed from the Blast, thanks to the auto evacuation of proximal communities. Whilst the last eruption had a relatively low human life toll, a stronger eruption spells havoc almost certainly for the region. At this moment no exhaustive study and understanding exists of the pyroclastic flows generated by the Santa Ana Volcano nor a map for this particular hazard. This study proposes the use of Titan2D for those two purposes, using a DEM generated by the SNET using topographic maps as well as DEMs generated using Advanced Spaceborne Thermal Emission and Reflection Radiometer Images (ASTER).

  8. The NKG2D ligand ULBP4 binds to TCRgamma9/delta2 and induces cytotoxicity to tumor cells through both TCRgammadelta and NKG2D.

    PubMed

    Kong, Yan; Cao, Wei; Xi, Xueyan; Ma, Chi; Cui, Lianxian; He, Wei

    2009-07-09

    UL16-binding proteins (ULBPs) belong to a family of ligands for NKG2D activating receptor of human natural killer (NK) cells. We previously reported that RAET1E2, a soluble isoform of the RAET1E (ULBP4), inhibits NKG2D-mediated NK cytotoxicity. In this study, we examined whether ULBP4 could be recognized by gammadeltaT cells via TCRgammadelta. Here we show that immobilized soluble ULBP4 (rULBP4) induces the proliferation of human ovarian epithelial carcinoma- or colonic carcinoma-derived Vdelta2(+) T cells in vitro. These Vdelta2(+) T cells secrete Th1 cytokines and display a strong cytolytic activity toward ULBP4-transfected targets. We also show that ULBP4 binds to a soluble chimeric protein containing TCRgamma9/delta2 and activates TCR(-) Jurkat T cells transfected with TCRgamma9/delta2. Moreover, both TCRgammadelta and NKG2D are involved in ULBP4-induced activation and cytotoxicity of gammadeltaT cells. We found that ULBP4 is expressed not only on human tumor cells, but also on Epstein-Barr virus (EBV)-infected peripheral blood cells. Taken together, our data suggest that ULBP4 functions as a ligand for both TCRgammadelta and NKG2D and may play a key role in immune surveillance of tumor development and clearance of viral infection.

  9. A 2D well-balanced shallow flow model for unstructured grids with novel slope source term treatment

    NASA Astrophysics Data System (ADS)

    Hou, Jingming; Liang, Qiuhua; Simons, Franz; Hinkelmann, Reinhard

    2013-02-01

    Within the framework of the Godunov-type cell-centered finite volume (CCFV) scheme, this paper proposes a 2D well-balanced shallow water model for unstructured grids. In this model, the face-based van Albada limiting scheme is employed in conjunction with a directional correction to reconstruct second order spatial values at the midpoint of the considered face. The Harten, Lax and van Leer approximate Riemann solver with the Contact wave restored (HLLC) is applied to compute the fluxes of mass and momentum, while the splitting implicit method is utilized to solve the friction source terms. The novel aspects of the model include the new limited directional correction with which the new local extrema caused by the unlimited correction are prevented efficiently, the simplified non-negative water depth reconstruction used to get rid of numerical instabilities and in turn to preserve mass conservation at wet-dry interfaces and the novel slope source term treatment which suits complex unstructured grids well by transforming the slope source of a cell into fluxes at its faces. This model is able to preserve the C-property and mass conservation, to achieve good convergence to steady state, to capture discontinuous flows and to handle complex flows involving wetting and drying over uneven beds on unstructured grids with poor connectivity in an accurate, efficient and robust way. These capabilities are verified against analytical solutions, numerical results of alternative models and experimental and field data.

  10. Enhanced photon absorption in spiral nanostructured solar cells using layered 2D materials.

    PubMed

    Tahersima, Mohammad H; Sorger, Volker J

    2015-08-28

    Recent investigations of semiconducting two-dimensional (2D) transition metal dichalcogenides have provided evidence for strong light absorption relative to its thickness attributed to high density of states. Stacking a combination of metallic, insulating, and semiconducting 2D materials enables functional devices with atomic thicknesses. While photovoltaic cells based on 2D materials have been demonstrated, the reported absorption is still just a few percent of the incident light due to their sub-wavelength thickness leading to low cell efficiencies. Here we show that taking advantage of the mechanical flexibility of 2D materials by rolling a molybdenum disulfide (MoS(2))/graphene (Gr)/hexagonal boron nitride stack to a spiral solar cell allows for optical absorption up to 90%. The optical absorption of a 1 μm long hetero-material spiral cell consisting of the aforementioned hetero stack is about 50% stronger compared to a planar MoS(2) cell of the same thickness; although the volumetric absorbing material ratio is only 6%. A core-shell structure exhibits enhanced absorption and pronounced absorption peaks with respect to a spiral structure without metallic contacts. We anticipate these results to provide guidance for photonic structures that take advantage of the unique properties of 2D materials in solar energy conversion applications.

  11. Cell Counting in Human Endobronchial Biopsies - Disagreement of 2D versus 3D Morphometry

    PubMed Central

    Bratu, Vlad A.; Erpenbeck, Veit J.; Fehrenbach, Antonia; Rausch, Tanja; Rittinghausen, Susanne; Krug, Norbert; Hohlfeld, Jens M.; Fehrenbach, Heinz

    2014-01-01

    Question Inflammatory cell numbers are important endpoints in clinical studies relying on endobronchial biopsies. Assumption-based bidimensional (2D) counting methods are widely used, although theoretically design-based stereologic three-dimensional (3D) methods alone offer an unbiased quantitative tool. We assessed the method agreement between 2D and 3D counting designs in practice when applied to identical samples in parallel. Materials and Methods Biopsies from segmental bronchi were collected from healthy non-smokers (n = 7) and smokers (n = 7), embedded and sectioned exhaustively. Systematic uniform random samples were immunohistochemically stained for macrophages (CD68) and T-lymphocytes (CD3), respectively. In identical fields of view, cell numbers per volume unit (NV) were assessed using the physical disector (3D), and profiles per area unit (NA) were counted (2D). For CD68+ cells, profiles with and without nucleus were separately recorded. In order to enable a direct comparison of the two methods, the zero-dimensional CD68+/CD3+-ratio was calculated for each approach. Method agreement was tested by Bland-Altmann analysis. Results In both groups, mean CD68+/CD3+ ratios for NV and NA were significantly different (non-smokers: 0.39 and 0.68, p<0.05; smokers: 0.49 and 1.68, p<0.05). When counting only nucleated CD68+ profiles, mean ratios obtained by 2D and 3D counting were similar, but the regression-based Bland-Altmann analysis indicated a bias of the 2D ratios proportional to their magnitude. This magnitude dependent deviation differed between the two groups. Conclusions 2D counts of cell and nuclear profiles introduce a variable size-dependent bias throughout the measurement range. Because the deviation between the 3D and 2D data was different in the two groups, it precludes establishing a ‘universal conversion formula’. PMID:24663339

  12. An Implicit 2-D Shallow Water Flow Model on Unstructured Quadtree Rectangular Mesh

    DTIC Science & Technology

    2011-01-01

    Hanson, H.; Wamsley, T., and Zundel, A. K., 2006. Two-dimensional depth-averaged circulation model CMS- M2D : Version 3.0, Report 2: Sediment...Militello, A.; Reed, C.W.; Zundel, A.K. and Kraus, N.C., 2004. Two-dimensional depth-averaged circulation model M2D : Version 2.0, Report 1, Technical

  13. Characterization of DNAPL Source Zone Architecture and Associated Plume Response in 2-D Aquifer Cell Experiments

    NASA Astrophysics Data System (ADS)

    Granbery, E. K.; Cápiro, N.; Christ, J.; Pennell, K.

    2008-12-01

    A series of two-dimensional (2-D) aquifer cell experiments was conducted to evaluate the effects of DNAPL source zone architecture on down-gradient plume and flux-averaged effluent concentrations. The aquifer cells (1.0 m length x 48 cm height x 1.4 cm internal thickness) were packed with different size fractions of quartz sands and low permeability lens configurations to achieve a range of source zone saturation distributions. A mixed DNAPL, consisting of 1:1 trichloroethene (TCE) and tetrachloroethene (PCE), was released into the source zone region of the aquifer cell at a flow rate of 2.0 ml/min and allowed to redistribute for a period of 48 hours. The DNAPL saturation distribution was quantified using a light transmission system and characterized by the ganglia-to-pool ratio (GTP, 0 to infinity) and ganglia fraction (GF, 0-100%), where saturations less than 0.13 represent discrete ganglia and saturations equal to or greater than 0.13 are considered to represent "pools". Effluent dissolved-phase TCE and PCE concentrations were monitored continuously, while down-gradient plume concentrations were collected periodically from 25 side-port samples. To accelerate mass removal, the aquifer cells were flushed with 1.5 pore volumes of 4% Tween 80, a nonionic, food-grade surfactant that has been shown to facilitate microbial reductive dechlorination. Experimental data are used to evaluate interrelationships between the initial source zone architecture, mass removal, reductions in mass flux, and plume evolution.

  14. Behaviour of a rimmed elliptical inclusion in 2D slow incompressible viscous flow

    NASA Astrophysics Data System (ADS)

    Mancktelow, N. S.

    2012-04-01

    The shape preferred orientation of natural populations of inclusions (or "porphyroclasts") is often inconsistent with predictions from established analytical theory for inclusions with coherent boundaries (e.g., Pennacchioni et al. 2001). A totally incoherent or slipping interface can explain observed stable back-rotated (or antithetic) orientations but not the observed cut-off axial ratio, below which inclusions still rotate. However, this behaviour is reproduced by a rimmed inclusion with a rim viscosity that is not infinitely weak but still weaker than the matrix (e.g., Schmid and Podladchikov 2005; Johnson et al. 2009). In this study, finite-element numerical modelling (FEM) is employed to investigate this system in 2D over a very wide parameter space, from a viscosity ratio (relative to the matrix) of the inclusion from 106 to 1, the rim from 10-6 to 1, the axial ratio from 1.00025 to 20, and the rim thickness from 5% to 20%. Theoretical consideration of a concentric elliptical inclusion and ellipse reduces the number of scalar values to be determined to fully characterize the system to two: one for the rate of stretch of the inclusion and one for the rate of rotation. From these two values, the rotation and stretching rate can be calculated for any orientation and 2D background flow field. For effectively rigid particles, the cut-off axial ratio between rotation and stabilization is determined by the remaining two parameters, namely the rim viscosity and the thickness, with low rim viscosity or thick rims promoting stabilization. The shape fabric of a population of particles in a high strain shear zone, presented as a typical Rf/φ plot, can be forward modelled using an initial value Ordinary Differential Equation (ODE) approach. Because the rim does not remain elliptical to high strain, this method cannot accurately model the behaviour of individual inclusions. However, a statistical approach, allowing variation in rim viscosity, which is also a proxy for

  15. Approaches to Modeling Coupled Flow and Reaction in a 2-D Cementation Experiment

    SciTech Connect

    Steefel, Carl; Cochepin, B.; Trotignon, L.; Bildstein, O.; Steefel, C.; Lagneau, V.; van der Lee, J.

    2008-04-01

    Porosity evolution at reactive interfaces is a key process that governs the evolution and performances of many engineered systems that have important applications in earth and environmental sciences. This is the case, for example, at the interface between cement structures and clays in deep geological nuclear waste disposals. Although in a different transport regime, similar questions arise for permeable reactive barriers used for biogeochemical remediation in surface environments. The COMEDIE project aims at investigating the coupling between transport, hydrodynamics and chemistry when significant variations of porosity occur. The present work focuses on a numerical benchmark used as a design exercise for the future COMEDIE-2D experiment. The use of reactive transport simulation tools like Hytec and Crunch provides predictions of the physico-chemical evolutions that are expected during the future experiments in laboratory. Focus is given in this paper on the evolution during the simulated experiment of precipitate, permeability and porosity fields. A first case is considered in which the porosity is constant. Results obtained with Crunch and Hytec are in relatively good agreement. Differences are attributable to the models of reactive surface area taken into account for dissolution/precipitation processes. Crunch and Hytec simulations taking into account porosity variations are then presented and compared. Results given by the two codes are in qualitative agreement, with differences attributable in part to the models of reactive surface area for dissolution/precipitation processes. As a consequence, the localization of secondary precipitates predicted by Crunch leads to lower local porosities than for predictions obtained by Hytec and thus to a stronger coupling between flow and chemistry. This benchmark highlights the importance of the surface area model employed to describe systems in which strong porosity variations occur as a result of dissolution

  16. Establishment and initial characterization of SOX2-overexpressing NT2/D1 cell clones.

    PubMed

    Drakulic, D; Krstic, A; Stevanovic, M

    2012-05-15

    SOX2, a universal marker of pluripotent stem cells, is a transcription factor that helps control embryonic development in vertebrates; its expression persists in neural stem/progenitor cells into adulthood. Considering the critical role of the SOX2 transcription factor in the regulation of genes required for self-renewal and pluripotency of stem cells, we developed and characterized SOX2-overexpressing NT2/D1 cell clones. Using Southern blot and semi-quantitative RT-PCR, we confirmed integration and expression of exogenous SOX2 in three NT2/D1 cell clones. Overexpression of the SOX2 gene was detected in two of these clones. SOX2 overexpression in NT2/D1 cell clones resulted in altered expression of key pluripotency genes OCT4 and NANOG. Furthermore, SOX2-overexpressing NT2/D1 cell clones entered into retinoic acid-dependent neural differentiation, even when there was elevated SOX2 expression. After 21 days of induction by retinoic acid, expression of neural markers (neuroD1 and synaptophysin) was higher in induced cell clones than in induced parental cells. The cell clone with SOX2 overexpression had an approximately 1.3-fold higher growth rate compared to parental cells. SOX2 overexpression did not increase the population of cells undergoing apoptosis. Taken together, we developed two SOX2-overexpressing cell clones, with constitutive SOX2 expression after three weeks of retinoic acid treatment. SOX2 overexpression resulted in altered expression of pluripotency-related genes, increased proliferation, and altered expression of neural markers after three weeks of retinoic acid treatment.

  17. Bridging the gap: from 2D cell culture to 3D microengineered extracellular matrices

    PubMed Central

    Li, Yanfen

    2016-01-01

    Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we will explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, we will review the maturation of micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues. PMID:26592366

  18. SIMULATIONS OF 2D AND 3D THERMOCAPILLARY FLOWS BY A LEAST-SQUARES FINITE ELEMENT METHOD. (R825200)

    EPA Science Inventory

    Numerical results for time-dependent 2D and 3D thermocapillary flows are presented in this work. The numerical algorithm is based on the Crank-Nicolson scheme for time integration, Newton's method for linearization, and a least-squares finite element method, together with a matri...

  19. Quantitative Proteomic and Phosphoproteomic Comparison of 2D and 3D Colon Cancer Cell Culture Models.

    PubMed

    Yue, Xiaoshan; Lukowski, Jessica K; Weaver, Eric M; Skube, Susan B; Hummon, Amanda B

    2016-12-02

    Cell cultures are widely used model systems. Some immortalized cell lines can be grown in either two-dimensional (2D) adherent monolayers or in three-dimensional (3D) multicellular aggregates, or spheroids. Here, the quantitative proteome and phosphoproteome of colon carcinoma HT29 cells cultures in 2D monolayers and 3D spheroids were compared with a stable isotope labeling of amino acids (SILAC) labeling strategy. Two biological replicates from each sample were examined, and notable differences in both the proteome and the phosphoproteome were determined by nanoliquid chromatography tandem mass spectrometry (LC-MS/MS) to assess how growth configuration affects molecular expression. A total of 5867 protein groups, including 2523 phosphoprotein groups and 8733 phosphopeptides were identified in the samples. The Gene Ontology analysis revealed enriched GO terms in the 3D samples for RNA binding, nucleic acid binding, enzyme binding, cytoskeletal protein binding, and histone binding for their molecular functions (MF) and in the process of cell cycle, cytoskeleton organization, and DNA metabolic process for the biological process (BP). The KEGG pathway analysis indicated that 3D cultures are enriched for oxidative phosphorylation pathways, metabolic pathways, peroxisome pathways, and biosynthesis of amino acids. In contrast, analysis of the phosphoproteomes indicated that 3D cultures have decreased phosphorylation correlating with slower growth rates and lower cell-to-extracellular matrix interactions. In sum, these results provide quantitative assessments of the effects on the proteome and phosphoproteome of culturing cells in 2D versus 3D cell culture configurations.

  20. Numerical Simulations of High-Frequency Respiratory Flows in 2D and 3D Lung Bifurcation Models

    NASA Astrophysics Data System (ADS)

    Chen, Zixi; Parameswaran, Shamini; Hu, Yingying; He, Zhaoming; Raj, Rishi; Parameswaran, Siva

    2014-07-01

    To better understand the human pulmonary system and optimize the high-frequency oscillatory ventilation (HFOV) design, numerical simulations were conducted under normal breathing frequency and HFOV condition using a CFD code Ansys Fluent and its user-defined C programs. 2D and 3D double bifurcating lung models were created, and the geometry corresponds to fifth to seventh generations of airways with the dimensions based on the Weibel's pulmonary model. Computations were carried out for different Reynolds numbers (Re = 400 and 1000) and Womersley numbers (α = 4 and 16) to study the air flow fields, gas transportation, and wall shear stresses in the lung airways. Flow structure was compared with experimental results. Both 2D and 3D numerical models successfully reproduced many results observed in the experiment. The oxygen concentration distribution in the lung model was investigated to analyze the influence of flow oscillation on gas transport inside the lung model.

  1. Defining an optimal surface chemistry for pluripotent stem cell culture in 2D and 3D

    NASA Astrophysics Data System (ADS)

    Zonca, Michael R., Jr.

    Surface chemistry is critical for growing pluripotent stem cells in an undifferentiated state. There is great potential to engineer the surface chemistry at the nanoscale level to regulate stem cell adhesion. However, the challenge is to identify the optimal surface chemistry of the substrata for ES cell attachment and maintenance. Using a high-throughput polymerization and screening platform, a chemically defined, synthetic polymer grafted coating that supports strong attachment and high expansion capacity of pluripotent stem cells has been discovered using mouse embryonic stem (ES) cells as a model system. This optimal substrate, N-[3-(Dimethylamino)propyl] methacrylamide (DMAPMA) that is grafted on 2D synthetic poly(ether sulfone) (PES) membrane, sustains the self-renewal of ES cells (up to 7 passages). DMAPMA supports cell attachment of ES cells through integrin beta1 in a RGD-independent manner and is similar to another recently reported polymer surface. Next, DMAPMA has been able to be transferred to 3D by grafting to synthetic, polymeric, PES fibrous matrices through both photo-induced and plasma-induced polymerization. These 3D modified fibers exhibited higher cell proliferation and greater expression of pluripotency markers of mouse ES cells than 2D PES membranes. Our results indicated that desirable surfaces in 2D can be scaled to 3D and that both surface chemistry and structural dimension strongly influence the growth and differentiation of pluripotent stem cells. Lastly, the feasibility of incorporating DMAPMA into a widely used natural polymer, alginate, has been tested. Novel adhesive alginate hydrogels have been successfully synthesized by either direct polymerization of DMAPMA and methacrylic acid blended with alginate, or photo-induced DMAPMA polymerization on alginate nanofibrous hydrogels. In particular, DMAPMA-coated alginate hydrogels support strong ES cell attachment, exhibiting a concentration dependency of DMAPMA. This research provides a

  2. Behaviour of gravisensitive cells on 2D and 3D clinostats

    NASA Astrophysics Data System (ADS)

    Strauch, Sebastian M.; Hemmersbach, Ruth; Seibt, Dieter; Schuber, Marianne; Hader, Donat-P.

    2005-08-01

    2D and 3D clinostats are widely applied to study the influence of simulated microgravity on different kinds of organisms and cell cultures [1]. To critically evaluate the results achieved (functional weightlessness, omnilateral gravistimulation or other side effects such as strong mechanical disturbances) a comparison between the applied simulation methods and real microgravity is necessary. In a first approach, the swimming behavior of Euglena gracilis, a "professional gravi-sensing" unicellular freshwater flagellate, was observed under 2D and 3D clinostat conditions as well as under real microgravity during a TEXUS sounding rocket flight.According to current theory Euglena perceives the gravity vector by stimulation of mechanosensitive channels: the cell mass, which is denser than the surrounding medium, exerts pressure onto the lower membrane and the resulting gated calcium influx modulates the beating pattern of the flagella [4].A changed influence of gravity of the cells can be directly visualized by changes in their orientation with respect to gravity (gravitaxis).

  3. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation

    PubMed Central

    Isernhagen, Antje; Malzahn, Dörthe; Viktorova, Elena; Elsner, Leslie; Monecke, Sebastian; von Bonin, Frederike; Kilisch, Markus; Wermuth, Janne Marieke; Walther, Neele; Balavarca, Yesilda; Stahl-Hennig, Christiane; Engelke, Michael; Walter, Lutz; Bickeböller, Heike; Kube, Dieter; Wulf, Gerald; Dressel, Ralf

    2015-01-01

    The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n = 452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR] = 0.77, P = 0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR] = 0.57, P = 0.0400) although homozygous carriers had an increased risk to experience this complication (OR = 1.92, P = 0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR = 0.54, P = 0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon-γ release, and faster co-stimulation of CD8+ T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8+ T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD. PMID:26483398

  4. Taxanes enhance trastuzumab-mediated ADCC on tumor cells through NKG2D-mediated NK cell recognition.

    PubMed

    Di Modica, Martina; Sfondrini, Lucia; Regondi, Viola; Varchetta, Stefania; Oliviero, Barbara; Mariani, Gabriella; Bianchi, Giulia Valeria; Generali, Daniele; Balsari, Andrea; Triulzi, Tiziana; Tagliabue, Elda

    2016-01-05

    Recent clinical data indicate a synergistic therapeutic effect between trastuzumab and taxanes in neoadjuvantly treated HER2-positive breast cancer (BC) patients. In HER2+ BC experimental models and patients, we investigated whether this synergy depends on the ability of drug-induced stress to improve NK cell effectiveness and thus trastuzumab-mediated ADCC. HER2+ BC cell lines BT474 and MDAMB361 treated with docetaxel showed up-modulation of NK activator ligands both in vitro and in vivo, accompanied by a 15-40% increase in in vitro trastuzumab-mediated ADCC; antibodies blocking the NKG2D receptor significantly reduced this enhancement. NKG2D receptor expression was increased by docetaxel treatment in circulating and splenic NK cells from mice xenografted with tumor cells, an increase related to expansion of the CD11b+Ly6G+ cell population. Accordingly, NK cells derived from HER2+ BC patients after treatment with taxane-containing therapy expressed higher levels of NKG2D receptor than before treatment. Moreover, plasma obtained from these patients recapitulated the modulation of NKG2D on healthy donors' NK cells, improving their trastuzumab-mediated activity in vitro. This enhancement occurred mainly using plasma from patients with low NKG2D basal expression. Our results indicate that taxanes increase tumor susceptibility to ADCC by acting on tumor and NK cells, and suggest that taxanes concomitantly administered with trastuzumab could maximize the antibody effect, especially in patients with low basal immune effector cytotoxic activity.

  5. Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells

    PubMed Central

    Jensen, Helle; Folkersen, Lasse; Skov, Søren

    2012-01-01

    NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression. PMID:22870231

  6. ZEUS-2D: A radiation magnetohydrodynamics code for astrophysical flows in two space dimensions. I - The hydrodynamic algorithms and tests.

    NASA Astrophysics Data System (ADS)

    Stone, James M.; Norman, Michael L.

    1992-06-01

    A detailed description of ZEUS-2D, a numerical code for the simulation of fluid dynamical flows including a self-consistent treatment of the effects of magnetic fields and radiation transfer is presented. Attention is given to the hydrodynamic (HD) algorithms which form the foundation for the more complex MHD and radiation HD algorithms. The effect of self-gravity on the flow dynamics is accounted for by an iterative solution of the sparse-banded matrix resulting from discretizing the Poisson equation in multidimensions. The results of an extensive series of HD test problems are presented. A detailed description of the MHD algorithms in ZEUS-2D is presented. A new method of computing the electromotive force is developed using the method of characteristics (MOC). It is demonstrated through the results of an extensive series of MHD test problems that the resulting hybrid MOC-constrained transport method provides for the accurate evolution of all modes of MHD wave families.

  7. Global 2D stability analysis of the cross lid-driven cavity flow with a streamfunction-vorticity approach

    NASA Astrophysics Data System (ADS)

    Gogoi, Bidyut B.

    2016-07-01

    We have recently analyzed the global two-dimensional (2D) stability of the staggered lid-driven cavity (LDC) flow with a higher order compact (HOC) approach. In the analysis, critical parameters are determined for both the parallel and anti-parallel motion of the lids and a detailed analysis has been carried out on either side of the critical values. In this article, we carry out an investigation of flow stabilities inside a two-sided cross lid-driven cavity with a pair of opposite lids moving in both parallel and anti-parallel directions. On discretization, the governing 2D Navier-Stokes (N-S) equations describing the steady flow and flow perturbations results in a generalized eigenvalue problem which is solved for determining the critical parameters on four different grids. Elaborate computation is performed for a wide range of Reynolds numbers (Re) on either side of the critical values in the range 200 ⩽ Re ⩽ 10000. For flows below the critical Reynolds number Rec, our numerical results are compared with established steady-state results and excellent agreement is obtained in all the cases. For Reynolds numbers above Rec, phase plane and spectral density analysis confirmed the existence of periodic, quasi-periodic, and stable flow patterns.

  8. Micro-PIV measurements of multiphase flow of water and supercritical CO2 in 2D heterogeneous porous micromodels

    NASA Astrophysics Data System (ADS)

    Li, Y.; Kazemifar, F.; Blois, G.; Christensen, K. T.

    2015-12-01

    Multiphase flow of water and supercritical carbon dioxide (CO2) in porous media is central to geological sequestration of CO2 into saline aquifers. However, our fundamental understanding of the coupled flow dynamics of CO2 and water in complex geologic media still remains limited, especially at the pore scale. Recently, studies have been carried out in 2D homogeneous models with the micro-PIV technique, yielding very interesting observations of pore-scale flow transport. The primary aim of this work is to leverage this experimental protocol to quantify the pore-scale flow of water and liquid/supercritical CO2 in 2D heterogeneous porous micromodels under reservoir-relevant conditions. The goal is to capture the dynamics of this multi-phase flow in a porous matrix that mimics the heterogeneity of natural rock. Fluorescent microscopy and the micro-PIV technique are employed to simultaneously measure the spatially-resolved instantaneous velocity field in the water and quantify the instantaneous spatial configuration of both phases. The results for heterogeneous micromodels will be presented and compared with those for homogeneous micromodels, yielding valuable insight into flow processes at the pore scale in natural rock.

  9. Adaptive clutter filter in 2-D color flow imaging based on in vivo I/Q signal.

    PubMed

    Zhou, Xiaoming; Zhang, Congyao; Liu, Dong C

    2014-01-01

    Color flow imaging has been well applied in clinical diagnosis. For the high quality color flow images, clutter filter is important to separate the Doppler signals from blood and tissue. Traditional clutter filters, such as finite impulse response, infinite impulse response and regression filters, were applied, which are based on the hypothesis that the clutter signal is stationary or tissue moves slowly. However, in realistic clinic color flow imaging, the signals are non-stationary signals because of accelerated moving tissue. For most related papers, simulated RF signals are widely used without in vivo I/Q signal. Hence, in this paper, adaptive polynomial regression filter, which is down mixing with instantaneous clutter frequency, was proposed based on in vivo carotid I/Q signal in realistic color flow imaging. To get the best performance, the optimal polynomial order of polynomial regression filter and the optimal polynomial order for estimation of instantaneous clutter frequency respectively were confirmed. Finally, compared with the mean blood velocity and quality of 2-D color flow image, the experiment results show that adaptive polynomial regression filter, which is down mixing with instantaneous clutter frequency, can significantly enhance the mean blood velocity and get high quality 2-D color flow image.

  10. Laser irradiated fluorescent perfluorocarbon microparticles in 2-D and 3-D breast cancer cell models

    NASA Astrophysics Data System (ADS)

    Niu, Chengcheng; Wang, Long; Wang, Zhigang; Xu, Yan; Hu, Yihe; Peng, Qinghai

    2017-03-01

    Perfluorocarbon (PFC) droplets were studied as new generation ultrasound contrast agents via acoustic or optical droplet vaporization (ADV or ODV). Little is known about the ODV irradiated vaporization mechanisms of PFC-microparticle complexs and the stability of the new bubbles produced. In this study, fluorescent perfluorohexane (PFH) poly(lactic-co-glycolic acid) (PLGA) particles were used as a model to study the process of particle vaporization and bubble stability following excitation in two-dimensional (2-D) and three-dimensional (3-D) cell models. We observed localization of the fluorescent agent on the microparticle coating material initially and after vaporization under fluorescence microscopy. Furthermore, the stability and growth dynamics of the newly created bubbles were observed for 11 min following vaporization. The particles were co-cultured with 2-D cells to form 3-D spheroids and could be vaporized even when encapsulated within the spheroids via laser irradiation, which provides an effective basis for further work.

  11. A 2-D oscillating flow analysis in Stirling engine heat exchangers

    NASA Technical Reports Server (NTRS)

    Ahn, Kyung H.; Ibrahim, Mounir B.

    1991-01-01

    A two dimensional oscillating flow analysis was conducted, simulating the gas flow inside Stirling heat exchangers. Both laminar and turbulent oscillating pipe flow were investigated numerically for Re(max) = 1920 (Va = 80), 10800 (Va = 272), 19300 (Va = 272), and 60800 (Va = 126). The results are compared with experimental results of previous investigators. Also, predictions of the flow regime on present oscillating flow conditions were checked by comparing velocity amplitudes and phase differences with those from laminar theory and quasi-steady profile. A high Reynolds number k-epsilon turbulence model was used for turbulent oscillating pipe flow. Finally, performance evaluation of the K-epsilon model was made to explore the applicability of quasi-steady turbulent models to unsteady oscillating flow analysis.

  12. Fas-ligand-mediated paracrine T cell regulation by the receptor NKG2D in tumor immunity.

    PubMed

    Groh, Veronika; Smythe, Kimberly; Dai, Zhenpeng; Spies, Thomas

    2006-07-01

    Tumor-associated ligands of the activating NKG2D receptor can effectively stimulate T cell responses at early but not late stages of tumor growth. In late-stage human tumor settings, we observed MIC-driven proliferation of NKG2D(+)CD4(+) T cells that produced the cytokine Fas ligand (FasL) as a result of NKG2D costimulation but were themselves protected from Fas-mediated growth arrest. In contrast, FasL suppressed proliferation of T cells in vitro that did not receive NKG2D costimulation. Similar observations with normal peripheral blood NKG2D(+)CD8(+) T cells demonstrated unrecognized NKG2D-mediated immune functions, whereby FasL release promotes tumor cell death and NKG2D costimulation prolongs T cell survival. These effects, beneficial in conditions of limited NKG2D ligand expression, may be counterweighed when massive expression and shedding of MIC occurs, such as in some late-stage tumors, that causes sustained NKG2D costimulation and population expansion of immunosuppressive T cells.

  13. Evaluating TITAN2D mass-flow model using the 1963 Little Tahoma Peak avalanches, Mount Rainier, Washington.

    NASA Astrophysics Data System (ADS)

    Sheridan, M. F.; Stinton, A. J.; Patra, A.; Pitman, B.; Bauer, A.; Nichita, C.

    2003-04-01

    The TITAN2D geophysical mass-flow model that is currently under development is evaluated by comparing simulation results with those obtained from another flow model, FLOW3D, and the published data on the 1963 Little Tahoma Peak avalanches on Mount Rainier, Washington. The avalanches, totaling approximately 10 x 106 m3 of brecciated lava flows and other debris, traveled 6.8 km horizontally and fell 1.8 km vertically (H/L = 0.246). Velocities calculated from run up range from 24-42 m/sec and may have been as high as 130 m/sec as the avalanches moved over Emmons Glacier. The avalanches formed a deposit up to 30 m thick. The FLOW3D model uses a sliding block principle to simulate flow movement over a TIN. Results from this model show similarities in terms of velocity history, location of run up areas, run out length and aerial distribution of deposit, although post-avalanche topography in the TIN affects the latter. The TITAN2D model is appropriate for fluid flow in open channels. It is a 2-D, depth-averaged model that uses a raster grid instead of a TIN for the topography. The model flow initiates as a pile defined as an ellipsoid by a height (z) and a radius in the x and y planes. Flow parameters are the internal friction and bed friction angles. Results from this model are promising. Good comparisons can be drawn early during the simulations when the model results fit closely with the mapped extent of the avalanches. However, as the simulated flows move downstream they deviate more from the mapped extent. An area that needs to be addressed is the incorporation of variable bed friction in the model. Simulations done using a low bed friction angle appropriate for movement on the glacier traveled far beyond the limits of the actual deposits, while a high angle suitable for flow over a gravely surface caused the avalanches to stop well short of the mapped limits, never leaving Emmons Glacier. Incorporation of variable bed friction angles into the model using GIS will

  14. Tumour-experienced T cells promote NK cell activity through trogocytosis of NKG2D and NKp46 ligands

    PubMed Central

    Domaica, Carolina I; Fuertes, Mercedes B; Rossi, Lucas E; Girart, María V; Ávila, Damián E; Rabinovich, Gabriel A; Zwirner, Norberto W

    2009-01-01

    Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)-γ secretion on engagement of the natural-killer group (NKG)2D receptor or members of the natural cytotoxicity receptor (NCR) family, such as NKp46, by ligands expressed on tumour cells. However, it remains unknown whether T cells can regulate NK cell-mediated anti-tumour responses. Here, we investigated the early events occurring during T cell–tumour cell interactions, and their impact on NK cell functions. We observed that on co-culture with some melanomas, activated CD4+ T cells promoted degranulation, and NKG2D- and NKp46-dependent IFN-γ secretion by NK cells, probably owing to the capture of NKG2D and NKp46 ligands from the tumour-cell surface (trogocytosis). This effect was observed in CD4+, CD8+ and resting T cells, which showed substantial amounts of cell surface major histocompatibility complex class I chain-related protein A on co-culture with tumour cells. Our findings identify a new, so far, unrecognized mechanism by which effector T cells support NK cell function through the capture of specific tumour ligands with profound implications at the crossroad of innate and adaptive immunity. PMID:19498463

  15. Role of 2-D periodic symmetrical nanostructures in improving efficiency of thin film solar cells

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Jiang, Liyong; Li, Xiangyin

    2016-01-01

    We systematically investigated several different nanostructures in crystalline silicon (c-Si) thin film solar cells and then proposed a brand-new structure with two dimensional (2-D) periodic dielectric cylinders on the top and annular metal columns on bottom surface to enhance the optical harvesting. The periodic symmetrical nanostructures affect the solar cell efficiency due to the grating diffraction effect of dielectric columns and surface plasmon polaritons (SPPs) effect induced by metal nanostructures at the dielectric-metal interface. About 52.1% more optical absorption and 33.3% more power conversion efficiency are obtained, and the maximum short current reaches to 33.24 mA/cm2.

  16. 2D-CELL: image processing software for extraction and analysis of 2-dimensional cellular structures

    NASA Astrophysics Data System (ADS)

    Righetti, F.; Telley, H.; Leibling, Th. M.; Mocellin, A.

    1992-01-01

    2D-CELL is a software package for the processing and analyzing of photographic images of cellular structures in a largely interactive way. Starting from a binary digitized image, the programs extract the line network (skeleton) of the structure and determine the graph representation that best models it. Provision is made for manually correcting defects such as incorrect node positions or dangling bonds. Then a suitable algorithm retrieves polygonal contours which define individual cells — local boundary curvatures are neglected for simplicity. Using elementary analytical geometry relations, a range of metric and topological parameters describing the population are then computed, organized into statistical distributions and graphically displayed.

  17. A viscous-inviscid interaction method for 2-D unsteady, compressible flows

    NASA Technical Reports Server (NTRS)

    Tuncer, Ismail H.; Ekaterinaris, John A.; Platzer, Max F.

    1993-01-01

    A Navier-Stokes/potentia/flow interactive solution method suitable for the solution of steady-state and unsteady flowfields around airfoils has been developed. The Navier-Stokes equations are solved in the close proximity of an airfoil and in its wake. The inviscid flowfield surrounding the viscous flow regions is assumed to be irrotational and isentropic. In the inviscid flow region, the potential flow equations, which are based on distributed sources and vortices, are solved. The two solutions are strongly coupled through the application of their boundary conditions. The strongly coupled Navier-Stokes/potential flow interactive solution method confines computations to a small domain in the proximity of an airfoil. For steady flow solutions, the computational domain may be confined to a region which extends less than one-fifth of a chord length distance away from the airfoil surface. Computed solutions have the same accuracy as the full domain NavierStokes solutions. Yet, as a result of the significantly reduced computational domain and increased convergence rates, the Navier-Stokes/potential flow interactive solution method is about 40 percent more efficient computationally.

  18. Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural killer cells.

    PubMed

    Boerman, Gerharda H; van Ostaijen-ten Dam, Monique M; Kraal, Kathelijne C J M; Santos, Susy J; Ball, Lynne M; Lankester, Arjan C; Schilham, Marco W; Egeler, R Maarten; van Tol, Maarten J D

    2015-05-01

    Children with advanced stages (relapsed/refractory and stage IV) of rhabdomyosarcoma (RMS) have a poor prognosis despite intensive chemotherapy and autologous stem cell rescue, with 5-year survival rates ranging from 5 to 35 %. Development of new, additional treatment modalities is necessary to improve the survival rate. In this preclinical study, we investigated the potential of resting and cytokine-activated natural killer (NK) cells to lyse RMS cell lines, as well as the pathways involved, to explore the eventual clinical application of (activated) NK cell immunotherapy. RMS cell lines (n = 3 derived from embryonal RMS and n = 2 derived from alveolar RMS) were susceptible to cytolysis mediated by resting NK cells, and this susceptibility was significantly increased using IL-15-activated NK cells. Flow cytometry and cytolytic assays were used to define the activating and inhibitory pathways of NK cells involved in recognizing and lysing RMS cells. NKG2D and DNAM-1 receptor-ligand interactions were essential in cytolysis by resting NK cells, as simultaneous blocking of both pathways resulted in almost complete abrogation of the cytotoxicity. In contrast, combined blocking of DNAM-1 and NKG2D only led to partial reduction of the lytic activity of IL-15-activated NK cells. In this respect, residual lysis was, at least partly, mediated by pathways involving the natural cytotoxicity receptors NKp30 and NKp46. These findings support further exploration of NK cell-based immunotherapy as adjuvant modality in current treatment strategies of RMS.

  19. A numerical method for computing unsteady 2-D boundary layer flows

    NASA Technical Reports Server (NTRS)

    Krainer, Andreas

    1988-01-01

    A numerical method for computing unsteady two-dimensional boundary layers in incompressible laminar and turbulent flows is described and applied to a single airfoil changing its incidence angle in time. The solution procedure adopts a first order panel method with a simple wake model to solve for the inviscid part of the flow, and an implicit finite difference method for the viscous part of the flow. Both procedures integrate in time in a step-by-step fashion, in the course of which each step involves the solution of the elliptic Laplace equation and the solution of the parabolic boundary layer equations. The Reynolds shear stress term of the boundary layer equations is modeled by an algebraic eddy viscosity closure. The location of transition is predicted by an empirical data correlation originating from Michel. Since transition and turbulence modeling are key factors in the prediction of viscous flows, their accuracy will be of dominant influence to the overall results.

  20. Levels of regulatory T cells CD69(+)NKG2D(+)IL-10(+) are increased in patients with autoimmune thyroid disorders.

    PubMed

    Rodríguez-Muñoz, Ana; Vitales-Noyola, Marlen; Ramos-Levi, Ana; Serrano-Somavilla, Ana; González-Amaro, Roberto; Marazuela, Mónica

    2016-03-01

    Regulatory T (Treg) cells play an important role in the pathogenesis of autoimmune thyroid disorders (AITD). New subsets of CD4(+)CD69(+) and CD4(+)NKG2D(+) T lymphocytes that behave as regulatory cells have been recently reported. The role of these immunoregulatory lymphocytes has not been previously explored in AITD. We analyzed by multi-parametric flow cytometry different Treg cell subsets in peripheral blood from 32 patients with AITD and 19 controls, and in thyroid tissue from seven patients. The suppressive activity was measured by an assay of inhibition of lymphocyte activation. We found a significant increased percentage of CD4(+)CD69(+)IL-10(+), CD4(+)CD69(+)NKG2D(+), and CD4(+)CD69(+)IL-10(+)NKG2D(+) cells, in peripheral blood from GD patients compared to controls. The increase in CD4(+)CD69(+)IL-10(+) and CD4(+)CD69(+)IL-10(+)NKG2D(+) T cells was especially remarkable in patients with active Graves' ophthalmopathy (GO), and a significant positive correlation between GO activity and CD4(+)CD69(+)IL-10(+) or CD4(+)CD69(+)IL-10(+)NKG2D(+) cells was also found. In addition, these cells were increased in patients with a more severe and/or prolonged disease. Thyroid from AITD patients showed an increased proportion of CD69(+) regulatory T cells subpopulations compared to autologous peripheral blood. The presence of CD69(+), NKG2D(+), and IL-10(+) cells was confirmed by immunofluorescence microscopy. In vitro functional assays showed that CD69(+) Treg cells exerted an important suppressive effect on the activation of T effector cells in controls, but not in AITD patients. Our findings suggest that the levels of CD69(+) regulatory lymphocytes are increased in AITD patients, but they are apparently unable to down-modulate the autoimmune response and tissue damage.

  1. Evaluating Titan2D mass-flow model using the 1963 Little Tahoma Peak avalanches, Mount Rainier, Washington

    NASA Astrophysics Data System (ADS)

    Sheridan, M. F.; Stinton, A. J.; Patra, A.; Pitman, E. B.; Bauer, A.; Nichita, C. C.

    2005-01-01

    The Titan2D geophysical mass-flow model is evaluated by comparing its simulation results and those obtained from another flow model, FLOW3D, with published data on the 1963 Little Tahoma Peak avalanches on Mount Rainier, Washington. The avalanches, totaling approximately 10×10 6 m 3 of broken lava blocks and other debris, traveled 6.8 km horizontally and fell 1.8 km vertically ( H/ L=0.246). Velocities calculated from runup range from 24 to 42 m/s and may have been as high as 130 m/s while the avalanches passed over Emmons Glacier. Titan2D is a code for an incompressible Coulomb continuum; it is a depth-averaged, 'shallow-water', granular-flow model. The conservation equations for mass and momentum are solved with a Coulomb-type friction term at the basal interface. The governing equations are solved on multiple processors using a parallel, adaptive mesh, Godunov scheme. Adaptive gridding dynamically concentrates computing power in regions of special interest; mesh refinement and coarsening key on the perimeter of the moving avalanche. The model flow initiates as a pile defined as an ellipsoid by a height ( z) and an elliptical base defined by radii in the x and y planes. Flow parameters are the internal friction angle and bed friction angle. Results from the model are similar in terms of velocity history, lateral spreading, location of runup areas, and final distribution of the Little Tahoma Peak deposit. The avalanches passed over the Emmons Glacier along their upper flow paths, but lower in the valley they traversed stream gravels and glacial outwash deposits. This presents difficulty in assigning an appropriate bed friction angle for the entire deposit. Incorporation of variable bed friction angles into the model using GIS will help to resolve this issue.

  2. Characterization of Unsteady Flow Structures Near Landing-Edge Slat. Part 2; 2D Computations

    NASA Technical Reports Server (NTRS)

    Khorrami, Mehdi; Choudhari, Meelan M.; Jenkins, Luther N.

    2004-01-01

    In our previous computational studies of a generic high-lift configuration, quasi-laminar (as opposed to fully turbulent) treatment of the slat cove region proved to be an effective approach for capturing the unsteady dynamics of the cove flow field. Combined with acoustic propagation via Ffowes Williams and Hawkings formulation, the quasi-laminar simulations captured some important features of the slat cove noise measured with microphone array techniques. However. a direct assessment of the computed cove flow field was not feasible due to the unavailability of off-surface flow measurements. To remedy this shortcoming, we have undertaken a combined experiment and computational study aimed at characterizing the flow structures and fluid mechanical processes within the slat cove region. Part I of this paper outlines the experimental aspects of this investigation focused on the 30P30N high-lift configuration; the present paper describes the accompanying computational results including a comparison between computation and experiment at various angles of attack. Even through predictions of the time-averaged flow field agree well with the measured data, the study indicates the need for further refinement of the zonal turbulence approach in order to capture the full dynamics of the cove's fluctuating flow field.

  3. Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy

    PubMed Central

    Ghasemi, Reza; Lazear, Eric; Wang, Xiaoli; Arefanian, Saeed; Zheleznyak, Alexander; Carreno, Beatriz M.; Higashikubo, Ryuji; Gelman, Andrew E.; Kreisel, Daniel; Fremont, Daved H.; Krupnick, Alexander Sasha

    2016-01-01

    Despite over 20 years of clinical use, IL-2 has not fulfilled expectations as a safe and effective form of tumour immunotherapy. Expression of the high affinity IL-2Rα chain on regulatory T cells mitigates the anti-tumour immune response and its expression on vascular endothelium is responsible for life threatening complications such as diffuse capillary leak and pulmonary oedema. Here we describe the development of a recombinant fusion protein comprised of a cowpox virus encoded NKG2D binding protein (OMCP) and a mutated form of IL-2 with poor affinity for IL-2Rα. This fusion protein (OMCP-mutIL-2) potently and selectively activates IL-2 signalling only on NKG2D-bearing cells, such as natural killer (NK) cells, without broadly activating IL-2Rα-bearing cells. OMCP-mutIL-2 provides superior tumour control in several mouse models of malignancy and is not limited by mouse strain-specific variability of NK function. In addition, OMCP-mutIL-2 lacks the toxicity and vascular complications associated with parental wild-type IL-2. PMID:27650575

  4. Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy.

    PubMed

    Ghasemi, Reza; Lazear, Eric; Wang, Xiaoli; Arefanian, Saeed; Zheleznyak, Alexander; Carreno, Beatriz M; Higashikubo, Ryuji; Gelman, Andrew E; Kreisel, Daniel; Fremont, Daved H; Krupnick, Alexander Sasha

    2016-09-21

    Despite over 20 years of clinical use, IL-2 has not fulfilled expectations as a safe and effective form of tumour immunotherapy. Expression of the high affinity IL-2Rα chain on regulatory T cells mitigates the anti-tumour immune response and its expression on vascular endothelium is responsible for life threatening complications such as diffuse capillary leak and pulmonary oedema. Here we describe the development of a recombinant fusion protein comprised of a cowpox virus encoded NKG2D binding protein (OMCP) and a mutated form of IL-2 with poor affinity for IL-2Rα. This fusion protein (OMCP-mutIL-2) potently and selectively activates IL-2 signalling only on NKG2D-bearing cells, such as natural killer (NK) cells, without broadly activating IL-2Rα-bearing cells. OMCP-mutIL-2 provides superior tumour control in several mouse models of malignancy and is not limited by mouse strain-specific variability of NK function. In addition, OMCP-mutIL-2 lacks the toxicity and vascular complications associated with parental wild-type IL-2.

  5. Decreased percentage of NKG2D+NK cells in patients with incident onset of Type 1 Diabetes.

    PubMed

    Zhang, Yupan; Wang, Haifeng; Lou, Xiaoqian; Qu, Xiaozhang; Gao, Lichao; Liu, Xiaolei; Li, Man; Guo, Hui; Jiang, Yanfang

    2017-02-01

    Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency owing to autoimmune destruction of the pancreatic β cells. A significant decrease in natural killer (NK) cells in peripheral blood has been observed in patients with untreated T1DM. In the present study, we aimed to explore the role of NK cells and their subsets in young T1DM patients. A total of 30 children and adolescents with untreated T1DM and 27 healthy controls (HC) were recruited in this study. Flow cytometry analysis indicated that the percentage of peripheral blood CD3-CD56+ NK cells and NK cells subsets (CD56bright, CD56dim and CD56neg), were significantly decreased in the T1DM patients compared to healthy controls. In addition, the percentage of inducible CD107a+ and IFN-γ-secreting NK cells was significantly decreased compared to HC. Interestingly, the percentage of NKG2D+ NK cells negatively correlated with the level of serum TCHOL and TG in T1DM patients. Our data indicate that decreased number and impaired function of NK cells may have a role in the pathogenesis of T1DM.

  6. An experimental study of flow separation over a flat plate with 2D transverse grooves

    NASA Astrophysics Data System (ADS)

    Jones, Emily Michelle

    Nature has long been an inspiration for research in engineering. In particular, the biological surfaces of aquatic swimmers have been studied for their potential as drag reducing surfaces. The hydrodynamic benefit of riblets, or grooves embedded parallel to the flow, which appear on many aquatic biological surfaces, have been well documented and implemented in practical engineering applications. However the skin of dolphins is embedded with grooves that run perpendicular to the flow of water over their bodies. It is theorized that the transverse grooves present on dolphin skin trap vortices between them, creating a partial slip condition over the surface and inducing turbulence augmentation in the boundary layer, thus controlling boundary layer separation over the dolphin's skin. Similarly, sharks are covered with scales that are flexible at the base and capable of bristling, forming grooves running transverse to the flow. It is theorized that the scales bristle when encountering a reversing flow, thereby trapping vortices between the scales and, similarly, delaying boundary layer separation. In an attempt to test this hypothesis and study these affects, a spinning cylinder was used in a water tunnel to induce separation over a flat plate with 2 mm, rectangular transverse grooves and sinusoidal grooves of similar scaling. The results were compared to tripped, turbulent boundary layer separation occurring over a flat plate without grooves using time-resolved particle image velocimetry. The strength of the adverse pressure gradient was varied, and the observed delay in flow separation and other affects upon the boundary layer are discussed.

  7. Application of a 2D air flow model to soil vapor extraction and bioventing case studies

    SciTech Connect

    Mohr, D.H.; Merz, P.H.

    1995-05-01

    Soil vapor extraction (SVE) is frequently the technology of choice to clean up hydrocarbon contamination in unsaturated soil. A two-dimensional air flow model provides a practical tool to evaluate pilot test data and estimate remediation rates for soil vapor extraction systems. The model predictions of soil vacuum versus distance are statistically compared to pilot test data for 65 SVE wells at 44 sites. For 17 of 21 sites where there was asphalt paving, the best agreement was obtained for boundary conditions with no barrier to air flow at the surface. The model predictions of air flow rates and stream lines around the well allow an estimate of the gasoline removal rates by both evaporation and bioremediation. The model can be used to quickly estimate the effective radius of influence, defined here as the maximum distance from the well where there is enough air flow to remove the contaminant present within the allowable time. The effective radius of influence is smaller than a radius of influence defined by soil vacuum only. For a case study, in situ bioremediation rates were estimated using the air flow model and compared to independent estimates based on changes in soil temperature. These estimate bioremediation rates for heavy fuel oil ranged from 2.5 to 11 mg oil degraded per kg soil per day, in agreement with values in the literature.

  8. Active control of microbubbles stream in multi-bifurcated flow by using 2D phased array ultrasound transducer.

    PubMed

    Koda, Ren; Koido, Jun; Hosaka, Naoto; Ito, Takumi; Onogi, Shinya; Mochizuki, Takashi; Masuda, Kohji; Ikeda, Seiichi; Arai, Fumihito

    2013-01-01

    We have previously reported our attempt to propel microbbles in flow by a primary Bjerknes force, which is a physical phenomenon where an acoustic wave pushes an obstacle along its direction of propagation. However, when ultrasound was emitted from surface of the body, controlling bubbles in against flow was needed. It is unpractical to use multiple transducers to produce the same number of focal points because single element transducer cannot produce more than two focal points. In this study, we introduced a complex artificial blood vessel according to a capillary model and a 2D array transducer to produce multiple focal points for active control of microbubbles in against flow. Furthermore, we investigated bubble control in viscous fluid. As the results, we confirmed clearly path selection of MBs in viscous fluid as well as in water.

  9. 2D Homologous Perovskites as Light-Absorbing Materials for Solar Cell Applications.

    PubMed

    Cao, Duyen H; Stoumpos, Constantinos C; Farha, Omar K; Hupp, Joseph T; Kanatzidis, Mercouri G

    2015-06-24

    We report on the fabrication and properties of the semiconducting 2D (CH3(CH2)3NH3)2(CH3NH3)(n-1)Pb(n)I(3n+1) (n = 1, 2, 3, and 4) perovskite thin films. The band gaps of the series decrease with increasing n values, from 2.24 eV (CH3(CH2)3NH3)2PbI4 (n = 1) to 1.52 eV CH3NH3PbI3 (n = ∞). The compounds exhibit strong light absorption in the visible region, accompanied by strong photoluminescence at room temperature, rendering them promising light absorbers for photovoltaic applications. Moreover, we find that thin films of the semi-2D perovskites display an ultrahigh surface coverage as a result of the unusual film self-assembly that orients the [Pb(n)I(3n+1)](-) layers perpendicular to the substrates. We have successfully implemented this 2D perovskite family in solid-state solar cells, and obtained an initial power conversion efficiency of 4.02%, featuring an open-circuit voltage (V(oc)) of 929 mV and a short-circuit current density (J(sc)) of 9.42 mA/cm(2) from the n = 3 compound. This result is even more encouraging considering that the device retains its performance after long exposure to a high-humidity environment. Overall, the homologous 2D halide perovskites define a promising class of stable and efficient light-absorbing materials for solid-state photovoltaics and other applications.

  10. Grid-refinement study of hypersonic laminar flow over a 2-D ramp

    NASA Technical Reports Server (NTRS)

    Thomas, James L.; Rudy, David H.; Kumar, Ajay; Van Leer, Bram

    1991-01-01

    Computations were made for those test cases of Problem 3 which were designated as laminar flows, viz., test cases 3.1, 3.2, 3.4, and 3.5. These test cases corresponded to flows over a flat plate and a compression ramp at high Mach number and at high Reynolds number. The computations over the compression ramps indicate a substantial streamwise extent of separation. Based on previous experience with separated laminar flows at high Mach numbers which indicated a substantial effect with spatial grid refinement, a series of computations with different grid sizes were performed. Also, for the flat plate, comparisons of the results for two different algorithms were made.

  11. Magnetic field applied to thermochemical non-equilibrium reentry flows in 2D - five species

    NASA Astrophysics Data System (ADS)

    Sávio de Góes Maciel, Edisson

    2015-07-01

    In this work, a study involving magnetic field actuation over reentry flows in thermochemical non-equilibrium is performed. The Euler and Navier-Stokes equations are studied. The proposed numerical algorithm is centred and second-order accurate. The hypersonic flow around a blunt body is simulated. Three time integration methods are tested. The reactive simulations involve Earth atmosphere of five species. The work of Gaitonde is the reference to couple the fluid dynamics and Maxwell equations of electromagnetism. The results have indicated that the Maciel scheme, using the Mavriplis dissipation model, yields the best prediction of the stagnation pressure.

  12. Arabidopsis metacaspase 2d is a positive mediator of cell death induced during biotic and abiotic stresses.

    PubMed

    Watanabe, Naohide; Lam, Eric

    2011-06-01

    Cysteine proteases such as caspases play important roles in programmed cell death (PCD) of metazoans. Plant metacaspases (MCPs), a family of cysteine proteases structurally related to caspases, have been hypothesized to be ancestors of metazoan caspases, despite their different substrate specificity. Arabidopsis thaliana contains six type II MCP genes (AtMCP2a-f). Whether and how these individual members are involved in controlling PCD in plants remains largely unknown. Here we investigated the function and regulation of AtMCP2d, the predominant and constitutively expressed member of type II MCPs, in stress-inducible PCD. Two AtMCP2d mutants (mcp2d-1 and mcp2d-3) exhibited reduced sensitivity to PCD-inducing mycotoxin fumonisin B1 as well as oxidative stress inducers, whereas AtMCP2d over-expressors were more sensitive to these agents, and exhibited accelerated cell-death progression. We found that AtMCP2d exclusively localizes to the cytosol, and its accumulation and self-processing patterns were age-dependent in leaves. Importantly, active proteolytic processing of AtMCP2d proteins dependent on its catalytic activity was observed in mature leaves during mycotoxin-induced cell death. We also found that mcp2d-1 leaves exhibited reduced cell death in response to Pseudomonas syringae carrying avirulent gene avrRpt2, and that self-processing of AtMCP2d was also detected in wild-type leaves in response to this pathogen. Furthermore, increases in processed AtMCP2d proteins were found to correlate with conditional cell-death induction in two lesion-mimic mutants (cpr22 and ssi4) that exhibit spontaneous cell-death phenotypes. Taken together, our data strongly suggest that AtMCP2d plays a positive regulatory role in biotic and abiotic stress-induced PCD.

  13. MEAN FLOW AND TURBULENCE MEASUREMENTS AROUND A 2-D ARRAY OF BUILDINGS IN A WIND TUNNEL

    EPA Science Inventory

    In order to predict the dispersion of harmful materials released in or near an urban environment, it is important to first understand the complex flow patterns which result from the interaction of the wind with buildings and, more commonly, clusters of buildings. Recent advanc...

  14. Turbulence Measurements on a 2D NACA 0036 with Synthetic Jet Flow Control

    NASA Technical Reports Server (NTRS)

    Wilson, J. S.

    2006-01-01

    An active flow control experiment was conducted on a 2-ft chord NACA 0036 airfoil in a 3-ft by 4-ft Wind Tunnel at Re = 1 x 10(exp 6). The model was equipped with synthetic jet actuators at x/c = 0.30 and 0.65 that provided 120 Hz periodic excitation at a C(sub mu) 0.86% through 0.06-in wide slots. Three different slot con gurations were tested, including a baseline with no slots. Surface pressure data was collected to compare to previous tests and to combine with turbulence data to aid future CFD modeling efforts. Turbulence data, measured by hot-wire, was compared with and without flow control. Pressure data corroborates previous test data and provides more points for CFD validation. Hot-wire results showed ow control reduced the separated wake size and brought the high Reynolds stress shear layer closer to the airfoil surface. The position of this layer to the surface was altered more significantly than the magnitude of the peak stresses. Flow control was shown to increase turbulent energy in the attached boundary layer downstream of the slot but to have little effect upstream. These results provide further justification to continue assessing the potential of active flow control to reduce drag of helicopter airframe components.

  15. Steady film flow over 2D topography with air inclusion formed inside the trench

    NASA Astrophysics Data System (ADS)

    Tsamopoulos, John; Varchanis, Stylianos; Dimakopoulos, Yannis

    2016-11-01

    Liquid film flow along an inclined, solid substrate featuring periodic rectangular trenches may either completely wet the trench floor (Wenzel state) or pin on the entrance and exit corners of the trench (Cassie state) or assume any other configuration in between these two extremes. In the intermediate cases a second gas-liquid interface inside the trench is formed, which adheres to the walls of the trench forming two three-phase contact lines, and encloses a different amount of air under different physical conditions. The Galerkin finite element method is used to solve the Navier-Stokes equations in a physical domain, which is adaptively re-meshed. Multiple steady solutions, connected by turning points and transcritical bifurcations as well as isolated solution branches, are revealed by pseudo arc-length continuation. Two possible cases of a single air inclusion inside the trench are examined. The penetration of the liquid inside the trench is enhanced primarily by increasing either the wettability of the substrate or the capillarity or by decreasing the flow rate. Flow hysteresis may occur when the liquid does not penetrate deep enough inside the trench leading to different flow patterns. The interplay of inertia, viscous, gravity and capillary forces along with substrate wettability determines the volume of the air encapsulated in the trench and the extent of free surface deformation. GSRT of Greece via the program "Excellence" and the LIMMAT foundation.

  16. Computational results for flows over 2-D ramp and 3-D obstacle with an upwind Navier-Stokes solver

    NASA Technical Reports Server (NTRS)

    Venkatapathy, Ethiraj

    1990-01-01

    An implicit, finite-difference, upwind, full Navier-Stokes solver was applied to supersonic/hypersonic flows over two-dimensional ramps and three-dimensional obstacle. Some of the computed results are presented. The numerical scheme used in the study is an implicit, spacially second order accurate, upwind, LU-ADI scheme based on Roe's approximate Reimann solver with MUSCL differencing of Van Leer. An algebraic grid generation scheme based on generalized interpolation scheme was used in generating the grids for the various 2-D and 3-D problems.

  17. Computational results for 2-D and 3-D ramp flows with an upwind Navier-Stokes solver

    NASA Technical Reports Server (NTRS)

    Venkatapathy, Ethiraj

    1991-01-01

    An implicit, finite-difference, upwind, full Navier-Stokes solver was applied to supersonic/hypersonic flows over two-dimensional ramps and three-dimensional obstacle. Some of the computed results are presented. The numerical scheme used in the study is an implicit, spatially second order accurate, upwind, LU-ADI scheme based on Roe's approximate Reimann solver with MUSCL differencing of Van Leer. An algebraic grid generation scheme based on generalized interpolation scheme was used in generating the grids for the various 2-D and 3-D problems.

  18. 2D models of gas flow and ice grain acceleration in Enceladus' vents using DSMC methods

    NASA Astrophysics Data System (ADS)

    Tucker, Orenthal J.; Combi, Michael R.; Tenishev, Valeriy M.

    2015-09-01

    The gas distribution of the Enceladus water vapor plume and the terminal speeds of ejected ice grains are physically linked to its subsurface fissures and vents. It is estimated that the gas exits the fissures with speeds of ∼300-1000 m/s, while the micron-sized grains are ejected with speeds comparable to the escape speed (Schmidt, J. et al. [2008]. Nature 451, 685-688). We investigated the effects of isolated axisymmetric vent geometries on subsurface gas distributions, and in turn, the effects of gas drag on grain acceleration. Subsurface gas flows were modeled using a collision-limiter Direct Simulation Monte Carlo (DSMC) technique in order to consider a broad range of flow regimes (Bird, G. [1994]. Molecular Gas Dynamics and the Direct Simulation of Gas Flows. Oxford University Press, Oxford; Titov, E.V. et al. [2008]. J. Propul. Power 24(2), 311-321). The resulting DSMC gas distributions were used to determine the drag force for the integration of ice grain trajectories in a test particle model. Simulations were performed for diffuse flows in wide channels (Reynolds number ∼10-250) and dense flows in narrow tubular channels (Reynolds number ∼106). We compared gas properties like bulk speed and temperature, and the terminal grain speeds obtained at the vent exit with inferred values for the plume from Cassini data. In the simulations of wide fissures with dimensions similar to that of the Tiger Stripes the resulting subsurface gas densities of ∼1014-1020 m-3 were not sufficient to accelerate even micron-sized ice grains to the Enceladus escape speed. In the simulations of narrow tubular vents with radii of ∼10 m, the much denser flows with number densities of 1021-1023 m-3 accelerated micron-sized grains to bulk gas speed of ∼600 m/s. Further investigations are required to understand the complex relationship between the vent geometry, gas source rate and the sizes and speeds of ejected grains.

  19. A High Order Discontinuous Galerkin Method for 2D Incompressible Flows

    NASA Technical Reports Server (NTRS)

    Liu, Jia-Guo; Shu, Chi-Wang

    1999-01-01

    In this paper we introduce a high order discontinuous Galerkin method for two dimensional incompressible flow in vorticity streamfunction formulation. The momentum equation is treated explicitly, utilizing the efficiency of the discontinuous Galerkin method The streamfunction is obtained by a standard Poisson solver using continuous finite elements. There is a natural matching between these two finite element spaces, since the normal component of the velocity field is continuous across element boundaries. This allows for a correct upwinding gluing in the discontinuous Galerkin framework, while still maintaining total energy conservation with no numerical dissipation and total enstrophy stability The method is suitable for inviscid or high Reynolds number flows. Optimal error estimates are proven and verified by numerical experiments.

  20. Flow transition with 2-D roughness elements in a 3-D channel

    NASA Technical Reports Server (NTRS)

    Liu, Zhining; Liu, Chaoquin; Mccormick, Stephen F.

    1993-01-01

    We develop a new numerical approach to study the spatially evolving instability of the streamwise dominant flow in the presence of roughness elements. The difficulty in handling the flow over the boundary surface with general geometry is removed by using a new conservative form of the governing equations and an analytical mapping. The numerical scheme uses second-order backward Euler in time, fourth-order central differences in all three spatial directions, and boundary-fitted staggered grids. A three-dimensional channel with multiple two-dimensional-type roughness elements is employed as the test case. Fourier analysis is used to decompose different Fourier modes of the disturbance. The results show that surface roughness leads to transition at lower Reynolds number than for smooth channels.

  1. A high-order discontinuous Galerkin method for 2D incompressible flows

    SciTech Connect

    Liu, J.G.; Shu, C.W.

    2000-05-20

    In this paper the authors introduce a high-order discontinuous Galerkin method for two-dimensional incompressible flow in the vorticity stream-function formulation. The momentum equation is treated explicitly, utilizing the efficiency of the discontinuous Galerkin method. The stream function is obtained by a standard Poisson solver using continuous finite elements. There is a natural matching between these two finite element spaces, since the normal component of the velocity field is continuous across element boundaries. This allows for a correct upwinding gluing in the discontinuous Galerkin framework, while still maintaining total energy conservation with no numerical dissipation and total entropy stability. The method is efficient for inviscid or high Reynolds number flows. Optimal error estimates are proved and verified by numerical experiments.

  2. Film flows and self-organized patterns of 2D-localized structures

    SciTech Connect

    Frenkel, A.L.

    1996-12-31

    Films flowing down an inclined plane are considered. An unconventional perturbation approach is discussed. It yields the most general evolution equation for film thickness and the least restrictive conditions for its validity. Results of numerical simulations of the dissipative-dispersive evolution equation indicate that novel, more complex type of spatiotemporal patterns can exist for strange attractors of nonequilibrium systems. It is suggested that real-life experiments satisfying the validity conditions of this theory are possible.

  3. A 2D multiring model of blood flow in elastic arteries

    NASA Astrophysics Data System (ADS)

    Ghigo, Arthur; Lagrée, Pierre-Yves; Fullana, Jose-Maria

    2016-11-01

    Three-dimensional simulations of blood flow in elastic arteries are difficult and costly due to the complex fluid-structure interactions between the motion of the fluid and the displacement of the wall. We propose a two-dimensional multiring model to overcome those difficulties and obtain at a reasonable computational cost an asymptotically valid description of blood flow in large elastic arteries. The multiring equations are derived by integrating over concentric rings of fluid a simplified system of equations based on a long wave approximation of the axisymmetric Navier-Stokes equations and a thin-cylinder description of the arterial wall. Contrary to classical one-dimensional models, obtained by integrating the same system over a single ring, the multiring model computes the velocity profile as well as the wall shear stress and requires no a priori estimation of model coefficients. We show that by numerically solving the multiring system of equations, we are able to compute a large range of classical blood flow solutions, ranging from the elastic Womersley solution to the rigid tube Poiseuille solution.

  4. Numerical solution of 2D wet steam flow with non-equilibrium condensation and real thermodynamics

    SciTech Connect

    Hric, V.; Halama, J.

    2015-03-10

    An approach to modeling of wet steam flow with non-equilibrium condensation phenomenon is presented. The first part of our flow model is homogeneous Euler system of transport equations for mass, momentum and total energy of wet steam (mixture). The additional second part describes liquid phase via non-homogeneous system of transport equations for moments of droplets number distribution function and relies on corrected classical nucleation theory. Moment equations are closed by linearization of droplet growth rate model. All necessary relations for thermodynamic properties of steam are provided by IAPWS set of equations. However, properties of condensate are simply modeled by liquid saturation data. Two real equations of state are implemented. Recently developed CFD formulation for entropy (does not require iteration process) and so-called IAPWS special gas equation for Helmholtz energy (one iteration loop is necessary). Flow model is validated on converging-diverging supersonic nozzle with Barschdorff geometry. Simulations were performed by in-house CFD code based on finite volume method and stiff character of equations was solved by symmetrical time operator splitting. Achieved results satisfactorily agreed with experimental data.

  5. Symplectically invariant flow equations for N = 2, D = 4 gauged supergravity with hypermultiplets

    NASA Astrophysics Data System (ADS)

    Klemm, Dietmar; Petri, Nicolò; Rabbiosi, Marco

    2016-04-01

    We consider N = 2 supergravity in four dimensions, coupled to an arbitrary number of vector- and hypermultiplets, where abelian isometries of the quaternionic hyperscalar target manifold are gauged. Using a static and spherically or hyperbolically symmetric ansatz for the fields, a one-dimensional effective action is derived whose variation yields all the equations of motion. By imposing a sort of Dirac charge quantization condition, one can express the complete scalar potential in terms of a superpotential and write the action as a sum of squares. This leads to first-order flow equations, that imply the second-order equations of motion. The first-order flow turns out to be driven by Hamilton's characteristic function in the Hamilton-Jacobi formalism, and contains among other contributions the superpotential of the scalars. We then include also magnetic gaugings and generalize the flow equations to a symplectically covariant form. Moreover, by rotating the charges in an appropriate way, an alternative set of non-BPS first-order equations is obtained that corresponds to a different squaring of the action. Finally, we use our results to derive the attractor equations for near-horizon geometries of extremal black holes.

  6. Enhanced Kalman Filtering for a 2D CFD NS Wind Farm Flow Model

    NASA Astrophysics Data System (ADS)

    Doekemeijer, B. M.; van Wingerden, J. W.; Boersma, S.; Pao, L. Y.

    2016-09-01

    Wind turbines are often grouped together for financial reasons, but due to wake development this usually results in decreased turbine lifetimes and power capture, and thereby an increased levelized cost of energy (LCOE). Wind farm control aims to minimize this cost by operating turbines at their optimal control settings. Most state-of-the-art control algorithms are open-loop and rely on low fidelity, static flow models. Closed-loop control relying on a dynamic model and state observer has real potential to further decrease wind's LCOE, but is often too computationally expensive for practical use. In this paper two time-efficient Kalman filter (KF) variants are outlined incorporating the medium fidelity, dynamic flow model “WindFarmSimulator” (WFSim). This model relies on a discretized set of Navier-Stokes equations in two dimensions to predict the flow in wind farms at low computational cost. The filters implemented are an Ensemble KF and an Approximate KF. Simulations in which a high fidelity simulation model represents the true wind farm show that these filters are 101 —102 times faster than a regular KF with comparable or better performance, correcting for wake dynamics that are not modeled in WFSim (noticeably, wake meandering and turbine hub effects). This is a first big step towards real-time closed-loop control for wind farms.

  7. SOX2 overexpression affects neural differentiation of human pluripotent NT2/D1 cells.

    PubMed

    Klajn, A; Drakulic, D; Tosic, M; Pavkovic, Z; Schwirtlich, M; Stevanovic, M

    2014-11-01

    SOX2 is one of the key transcription factors involved in maintenance of neural progenitor identity. However, its function during the process of neural differentiation, including phases of lineage-specification and terminal differentiation, is still poorly understood. Considering growing evidence indicating that SOX2 expression level must be tightly controlled for proper neural development, the aim of this research was to analyze the effects of constitutive SOX2 overexpression on outcome of retinoic acid-induced neural differentiation of pluripotent NT2/D1 cells. We demonstrated that in spite of constitutive SOX2 overexpression, NT2/D1 cells were able to reach final phases of neural differentiation yielding both neuronal and glial cells. However, SOX2 overexpression reduced the number of mature MAP2-positive neurons while no difference in the number of GFAP-positive astrocytes was detected. In-depth analysis at single-cell level showed that SOX2 downregulation was in correlation with both neuronal and glial phenotype acquisitions. Interestingly, while in mature neurons SOX2 was completely downregulated, astrocytes with low level of SOX2 expression were detected. Nevertheless, cells with high level of SOX2 expression were incapable of entering in either of two differentiation pathways, neurogenesis or gliogenesis. Accordingly, our results indicate that fine balance between undifferentiated state and neural differentiation depends on SOX2 expression level. Unlike neurons, astrocytes could maintain low level of SOX2 expression after they acquired glial fate. Further studies are needed to determine whether differences in the level of SOX2 expression in GFAP-positive astrocytes are in correlation with their self-renewal capacity, differentiation status, and/or their phenotypic characteristics.

  8. Enhanced durability of polymer electrolyte membrane fuel cells by functionalized 2D boron nitride nanoflakes.

    PubMed

    Oh, Keun-Hwan; Lee, Dongju; Choo, Min-Ju; Park, Kwang Hyun; Jeon, Seokwoo; Hong, Soon Hyung; Park, Jung-Ki; Choi, Jang Wook

    2014-05-28

    We report boron nitride nanoflakes (BNNFs), for the first time, as a nanofiller for polymer electrolyte membranes in fuel cells. Utilizing the intrinsic mechanical strength of two-dimensional (2D) BN, addition of BNNFs even at a marginal content (0.3 wt %) significantly improves mechanical stability of the most representative hydrocarbon-type (HC-type) polymer electrolyte membrane, namely sulfonated poly(ether ether ketone) (sPEEK), during substantial water uptake through repeated wet/dry cycles. For facile processing with BNNFs that frequently suffer from poor dispersion in most organic solvents, we non-covalently functionalized BNNFs with 1-pyrenesulfonic acid (PSA). Besides good dispersion, PSA supports efficient proton transport through its sulfonic functional groups. Compared to bare sPEEK, the composite membrane containing BNNF nanofiller exhibited far improved long-term durability originating from enhanced dimensional stability and diminished chronic edge failure. This study suggests that introduction of properly functionalized 2D BNNFs is an effective strategy in making various HC-type membranes sustainable without sacrificing their original adventurous properties in polymer electrolyte membrane fuel cells.

  9. Laser irradiated fluorescent perfluorocarbon microparticles in 2-D and 3-D breast cancer cell models

    PubMed Central

    Niu, Chengcheng; Wang, Long; Wang, Zhigang; Xu, Yan; Hu, Yihe; Peng, Qinghai

    2017-01-01

    Perfluorocarbon (PFC) droplets were studied as new generation ultrasound contrast agents via acoustic or optical droplet vaporization (ADV or ODV). Little is known about the ODV irradiated vaporization mechanisms of PFC-microparticle complexs and the stability of the new bubbles produced. In this study, fluorescent perfluorohexane (PFH) poly(lactic-co-glycolic acid) (PLGA) particles were used as a model to study the process of particle vaporization and bubble stability following excitation in two-dimensional (2-D) and three-dimensional (3-D) cell models. We observed localization of the fluorescent agent on the microparticle coating material initially and after vaporization under fluorescence microscopy. Furthermore, the stability and growth dynamics of the newly created bubbles were observed for 11 min following vaporization. The particles were co-cultured with 2-D cells to form 3-D spheroids and could be vaporized even when encapsulated within the spheroids via laser irradiation, which provides an effective basis for further work. PMID:28262671

  10. Effects on Tumor Development and Metastatic Dissemination by the NKG2D Lymphocyte Receptor Expressed on Cancer Cells

    PubMed Central

    El-Gazzar, Ahmed; Cai, Xin; Reeves, Rebecca S.; Dai, Zhenpeng; Caballero-Benitez, Andrea; McDonald, David L.; Vazquez, Julio; Gooley, Ted A.; Sale, George E.; Spies, Thomas; Groh, Veronika

    2014-01-01

    The stimulatory NKG2D lymphocyte receptor together with its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. However, with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune evasion and suppression. Recent findings have added yet another functional dimension wherein cancer cells themselves coopt NKG2D for their own benefit to complement the presence of its ligands for self stimulation of parameters of tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing by employing orthotopic xenotransplant breast cancer models in mice. Using human cancer lines with ectopic NKG2D expression and RNAi-mediated protein depletion among other controls, we show that NKG2D self-stimulation has tumor promoting capacity. NKG2D signals had no notable effects on cancer cell proliferation and survival but acted at the level of angiogenesis, thus promoting tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects on tumor initiation may represent another factor in the observed overall enhancement of tumor development. Altogether, these results may impact immunotherapy approaches, which currently do not account for such NKG2D effects in cancer patients and thus could be misdirected as underlying assumptions are incomplete. PMID:24141776

  11. Effects on tumor development and metastatic dissemination by the NKG2D lymphocyte receptor expressed on cancer cells.

    PubMed

    El-Gazzar, A; Cai, X; Reeves, R S; Dai, Z; Caballero-Benitez, A; McDonald, D L; Vazquez, J; Gooley, T A; Sale, G E; Spies, T; Groh, V

    2014-10-09

    The stimulatory NKG2D lymphocyte receptor together with its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. However, with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune evasion and suppression. Recent findings have added yet another functional dimension, wherein cancer cells themselves co-opt NKG2D for their own benefit to complement the presence of its ligands for self-stimulation of parameters of tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing by employing orthotopic xenotransplant breast cancer models in mice. Using human cancer lines with ectopic NKG2D expression and RNA interference (RNAi)-mediated protein depletion among other controls, we show that NKG2D self-stimulation has tumor-promoting capacity. NKG2D signals had no notable effects on cancer cell proliferation and survival but acted at the level of angiogenesis, thus promoting tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects on tumor initiation may represent another factor in the observed overall enhancement of tumor development. Altogether, these results may have an impact on immunotherapy approaches, which currently do not account for such NKG2D effects in cancer patients and thus could be misdirected as underlying assumptions are incomplete.

  12. Analysis of High-Speed Rotating Flow in 2D Polar (r - θ)Coordinate

    NASA Astrophysics Data System (ADS)

    Pradhan, S.

    2016-03-01

    The generalized analytical model for the radial boundary layer in a high-speed rotating cylinder is formulated for studying the gas flow field due to insertion of mass, momentum and energy into the rotating cylinder in the polar (r - θ) plane. The analytical solution includes the sixth order differential equation for the radial boundary layer at the cylindrical curved surface in terms of master potential (χ) , which is derived from the equations of motion in a polar (r - θ) plane. The linearization approximation (Wood & Morton, J. Fluid Mech-1980; Pradhan & Kumaran, J. Fluid Mech-2011; Kumaran & Pradhan, J. Fluid Mech-2014) is used, where the equations of motion are truncated at linear order in the velocity and pressure disturbances to the base flow, which is a solid-body rotation. Additional assumptions in the analytical model include constant temperature in the base state (isothermal condition), and high Reynolds number, but there is no limitation on the stratification parameter. In this limit, the gas flow is restricted to a boundary layer of thickness (Re (1 / 3) R) at the wall of the cylinder. Here, the stratification parameter A = √ ((mΩ 2R2) / (2kB T)) . This parameter Ais the ratio of the peripheral speed, ΩR , to the most probable molecular speed, √(2 k_B T/m), the Reynolds number Re = (ρ _w ΩR2 / μ) , where m is the molecular mass, Ω and R are the rotational speed and radius of the cylinder, k_B is the Boltzmann constant, T is the gas temperature, ρ_w is the gas density at wall, and μ is the gas viscosity. The analytical solutions are then compared with direct simulation Monte Carlo (DSMC) simulations.

  13. Computational modelling on 2D magnetohydrodynamic flow of Sisko fluid over a time dependent stretching surface

    NASA Astrophysics Data System (ADS)

    Mahmood, T.; Shahzad, A.; Iqbal, Z.; Ahmed, J.; Khan, M.

    A study is presented for the flow and heat transfer of Sisko fluid model over an unsteady stretching sheet in the presence of uniform magnetic field. While taking newly developed similarity transformations, the governing time dependent partial differential equations are reduced to nonlinear ordinary differential equations. Numerical solutions of the reduced nonlinear differential equations are found by employing Shooting method. The influence of physical parameters of interest on the velocity and temperature profiles are highlighted graphically and examined in detail. Moreover, the skin friction coefficient and Nusselt number are tabulated against influential parameters. Skin friction coefficient increases with unsteadiness parameter, magnetic field and suction parameter.

  14. SWAT and River-2D Modelling of Pinder River for Analysing Snow Trout Habitat under Different Flow Abstraction Scenarios

    NASA Astrophysics Data System (ADS)

    Nale, J. P.; Gosain, A. K.; Khosa, R.

    2015-12-01

    Pinder River, one of major headstreams of River Ganga, originates in Pindari Glaciers of Kumaon Himalayas and after passing through rugged gorges meets Alaknanda at Karanprayag forming one of the five celestial confluences of Upper Ganga region. While other sub-basins of Upper Ganga are facing severe ecological losses, Pinder basin is still in its virginal state and is well known for its beautiful valleys besides being host to unique and rare biodiversity. A proposed 252 MW run-of-river hydroelectric project at Devsari on this river has been a major concern on account of its perceived potential for egregious environmental and social impacts. In this context, the study presented tries to analyse the expected changes in aquatic habitat conditions after this project is operational (with different operation policies). SWAT hydrological modelling platform has been used to derive stream flow simulations under various scenarios ranging from the present to the likely future conditions. To analyse the habitat conditions, a two dimensional hydraulic-habitat model 'River-2D', a module of iRIC software, is used. Snow trout has been identified as the target keystone species and its habitat preferences, in the form of flow depths, flow velocity and substrate condition, are obtained from diverse sources of related literature and are provided as Habitat Suitability Indices to River-2D. Bed morphology constitutes an important River-2D input and has been obtained, for the designated 1 km long study reach of Pinder upto Karanprayag, from a combination of actual field observations and supplemented by SRTM 1 Arc-Second Global digital elevation data. Monthly Weighted Usable Area for three different life stages (Spawning, Juvenile and Adult) of Snow Trout are obtained corresponding to seven different flow discharges ranging from 10 cumec to 1000 cumec. Comparing the present and proposed future river flow conditions obtained from SWAT modelling, losses in Weighted Usable Area, for the

  15. Black string first order flow in N = 2, d = 5 abelian gauged supergravity

    NASA Astrophysics Data System (ADS)

    Klemm, Dietmar; Petri, Nicolò; Rabbiosi, Marco

    2017-01-01

    We derive both BPS and non-BPS first-order flow equations for magnetically charged black strings in five-dimensional N = 2 abelian gauged supergravity, using the Hamilton-Jacobi formalism. This is first done for the coupling to vector multiplets only and U(1) Fayet-Iliopoulos (FI) gauging, and then generalized to the case where also hyper-multiplets are present, and abelian symmetries of the quaternionic hyperscalar target space are gauged. We then use these results to derive the attractor equations for near-horizon geometries of extremal black strings, and solve them explicitely for the case where the constants appearing in the Chern-Simons term of the supergravity action satisfy an adjoint identity. This allows to compute in generality the central charge of the two-dimensional conformal field theory that describes the black strings in the infrared, in terms of the magnetic charges, the CY intersection numbers and the FI constants. Finally, we extend the r-map to gauged supergravity and use it to relate our flow equations to those in four dimensions.

  16. Manifest: A computer program for 2-D flow modeling in Stirling machines

    NASA Technical Reports Server (NTRS)

    Gedeon, David

    1989-01-01

    A computer program named Manifest is discussed. Manifest is a program one might want to use to model the fluid dynamics in the manifolds commonly found between the heat exchangers and regenerators of Stirling machines; but not just in the manifolds - in the regenerators as well. And in all sorts of other places too, such as: in heaters or coolers, or perhaps even in cylinder spaces. There are probably nonStirling uses for Manifest also. In broad strokes, Manifest will: (1) model oscillating internal compressible laminar fluid flow in a wide range of two-dimensional regions, either filled with porous materials or empty; (2) present a graphics-based user-friendly interface, allowing easy selection and modification of region shape and boundary condition specification; (3) run on a personal computer, or optionally (in the case of its number-crunching module) on a supercomputer; and (4) allow interactive examination of the solution output so the user can view vector plots of flow velocity, contour plots of pressure and temperature at various locations and tabulate energy-related integrals of interest.

  17. A 2-D Implicit, Energy and Charge Conserving Particle In Cell Method

    SciTech Connect

    McPherson, Allen L.; Knoll, Dana A.; Cieren, Emmanuel B.; Feltman, Nicolas; Leibs, Christopher A.; McCarthy, Colleen; Murthy, Karthik S.; Wang, Yijie

    2012-09-10

    Recently, a fully implicit electrostatic 1D charge- and energy-conserving particle-in-cell algorithm was proposed and implemented by Chen et al ([2],[3]). Central to the algorithm is an advanced particle pusher. Particles are moved using an energy conserving scheme and are forced to stop at cell faces to conserve charge. Moreover, a time estimator is used to control errors in momentum. Here we implement and extend this advanced particle pusher to include 2D and electromagnetic fields. Derivations of all modifications made are presented in full. Special consideration is taken to ensure easy coupling into the implicit moment based method proposed by Taitano et al [19]. Focus is then given to optimizing the presented particle pusher on emerging architectures. Two multicore implementations, and one GPU (Graphics Processing Unit) implementation are discussed and analyzed.

  18. A 2D Simulation of the Flow Separation Control over a NACA0015 Airfoil Using a Synthetic Jet Actuator

    NASA Astrophysics Data System (ADS)

    Boukenkoul, M. A.; Li, F. C.; Aounallah, M.

    2017-03-01

    The present study aims to investigate numerically the flow control possibility using a synthetic jet actuation over a bi-dimensional NACA0015 airfoil manoeuvring at a highly turbulent flow (8.9e105 Reynolds to chord number). The 2-D flow behaviour was computed using the ANSYS Fluent commercial code. The so-called Reynolds Averaged Navier-Stocks (RANS) approach has been tested for one (Spalat-Allmaras S-A) and two (K-ε) transport equations for the turbulence modelling. Both present a weakness to predict the stall angle effectively. The S-A lift coefficient slope seems to be the closest to the experimental data. The synthetic jet control exhibits an extraordinary lift coefficient enhancement at high Angles Of Attack (AOA) but seems to be less obvious at low AOA, where the flow is still attached. A synthetic jet of a Strouhal (St = 2) and momentum (Cμ of 0.56%), delays the stall onset from 15 to 19deg with enhancing the lift coefficient by 40%. The actual work has been enriched by studying the effect of the jet’s frequency and momentum on the lift temporal signal. Also, the interaction between the mean flow and the synthetic jet structures topology was undertaken.

  19. Heat transfer of laminar flow over a 2-D backward facing step with isotropic porous floor segments

    SciTech Connect

    Abu-Hijleh, B.A.K

    1997-07-01

    Forced convection due to fluid flow over a backward facing step has been studied extensively. Flow through porous media occurs in a wide range of engineering applications such as the flow through insulation material, grain storage, and water movement through a geothermal reservoir. Control of the heat transfer characteristics is desirable, and the control mechanism can be either active or passive. Here, the incompressible laminar (Re{sub H} = 100) reattaching flow over a 2-D backward facing step with different length porous floor segments was solved numerically using the finite element method. The focus of this study is the change in the forced convection heat transfer characteristics of the flow field due to the addition of porous floor segments. Several isotropic porous floor segment configurations with different lengths and depths were studied. The porosity of the segments was varied over a wide range by changing the value of the pressure loss coefficient (KP = 10{sup {minus}2}--10{sup 6}). The changes in the local and overall Nusselt number are reported and discussed. Depending on the configuration, axial variation of the local Nusselt number could be altered. For all configurations, the overall Nusselt number decreased by as much as 16% while the maximum local Nusselt number increased by as much as 170%, both relative to their respective values for the reference case of solid floor.

  20. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells

    PubMed Central

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N.; Glenn, Sean T.; Liu, Song; Trump, Donald L.; Johnson, Candace S.

    2014-01-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. MiRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253 J and 253J-BV cells express endogenous vitamin D receptor (VDR) which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253 J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. PMID:25263658

  1. Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

    PubMed

    Weinger, Jason G; Plaisted, Warren C; Maciejewski, Sonia M; Lanier, Lewis L; Walsh, Craig M; Lane, Thomas E

    2014-10-01

    Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway.

  2. Video lensfree microscopy of 2D and 3D culture of cells

    NASA Astrophysics Data System (ADS)

    Allier, C. P.; Vinjimore Kesavan, S.; Coutard, J.-G.; Cioni, O.; Momey, F.; Navarro, F.; Menneteau, M.; Chalmond, B.; Obeid, P.; Haguet, V.; David-Watine, B.; Dubrulle, N.; Shorte, S.; van der Sanden, B.; Di Natale, C.; Hamard, L.; Wion, D.; Dolega, M. E.; Picollet-D'hahan, N.; Gidrol, X.; Dinten, J.-M.

    2014-03-01

    Innovative imaging methods are continuously developed to investigate the function of biological systems at the microscopic scale. As an alternative to advanced cell microscopy techniques, we are developing lensfree video microscopy that opens new ranges of capabilities, in particular at the mesoscopic level. Lensfree video microscopy allows the observation of a cell culture in an incubator over a very large field of view (24 mm2) for extended periods of time. As a result, a large set of comprehensive data can be gathered with strong statistics, both in space and time. Video lensfree microscopy can capture images of cells cultured in various physical environments. We emphasize on two different case studies: the quantitative analysis of the spontaneous network formation of HUVEC endothelial cells, and by coupling lensfree microscopy with 3D cell culture in the study of epithelial tissue morphogenesis. In summary, we demonstrate that lensfree video microscopy is a powerful tool to conduct cell assays in 2D and 3D culture experiments. The applications are in the realms of fundamental biology, tissue regeneration, drug development and toxicology studies.

  3. Rifaximin-mediated changes to the epithelial cell proteome: 2-D gel analysis.

    PubMed

    Schrodt, Caroline; McHugh, Erin E; Gawinowicz, Mary Ann; Dupont, Herbert L; Brown, Eric L

    2013-01-01

    Rifaximin is a semi-synthetic rifamycin derivative that is used to treat different conditions including bacterial diarrhea and hepatic encephalopathy. Rifaximin is of particular interest because it is poorly adsorbed in the intestines and has minimal effect on colonic microflora. We previously demonstrated that rifaximin affected epithelial cell physiology by altering infectivity by enteric pathogens and baseline inflammation suggesting that rifaximin conferred cytoprotection against colonization and infection. Effects of rifaximin on epithelial cells were further examined by comparing the protein expression profile of cells pretreated with rifaximin, rifampin (control antibiotic), or media (untreated). Two-dimensional (2-D) gel electrophoresis identified 36 protein spots that were up- or down-regulated by over 1.7-fold in rifaximin treated cells compared to controls. 15 of these spots were down-regulated, including annexin A5, intestinal-type alkaline phosphatase, histone H4, and histone-binding protein RbbP4. 21 spots were up-regulated, including heat shock protein (HSP) 90α and fascin. Many of the identified proteins are associated with cell structure and cytoskeleton, transcription and translation, and cellular metabolism. These data suggested that in addition to its antimicrobial properties, rifaximin may alter host cell physiology that provides cytoprotective effects against bacterial pathogens.

  4. 2D transient granular flows over obstacles: experimental and numerical work

    NASA Astrophysics Data System (ADS)

    Juez, Carmelo; Caviedes-Voullième, Daniel; Murillo, Javier; García-Navarro, Pilar

    2016-04-01

    Landslides are an ubiquitous natural hazard, and therefore human infrastructure and settlements are often at risk in mountainous regions. In order to better understand and predict landslides, systematic studies of the phenomena need to be undertaken. In particular, computational tools which allow for analysis of field problems require to be thoroughly tested, calibrated and validated under controlled conditions. And to do so, it is necessary for such controlled experiments to be fully characterized in the same terms as the numerical model requires. This work presents an experimental study of dry granular flow over a rough bed with topography which resembles a mountain valley. It has an upper region with a very high slope. The geometry of the bed describes a fourth order polynomial curve, with a low point with zero slope, and afterwards a short region with adverse slope. Obstacles are present in the lower regions which are used as model geometries of human structures. The experiments consisted of a sudden release a mass of sand on the upper region, and allowing it to flow downslope. Furthermore, it has been frequent in previous studies to measure final states of the granular mass at rest, but seldom has transient data being provided, and never for the entire field. In this work we present transient measurements of the moving granular surfaces, obtained with a consumer-grade RGB-D sensor. The sensor, developed for the videogame industry, allows to measure the moving surface of the sand, thus obtaining elevation fields. The experimental results are very consistent and repeatable. The measured surfaces clearly show the distinctive features of the granular flow around the obstacles and allow to qualitatively describe the different flow patterns. More importantly, the quantitative description of the granular surface allows for benchmarking and calibration of predictive numerical models, key in scaling the small-scale experimental knowledge into the field. In addition, as

  5. A Beam-Fourier Technique for the Numerical Investigation of 2D Nonlinear Convective Flows

    NASA Astrophysics Data System (ADS)

    Papanicolaou, N. C.

    2011-11-01

    In the current work, we develop a numerical method suitable for treating the problem of nonlinear two-dimensional flows in rectangular domains. For the spatial approximation we employ the Fourier-Galerkin approach. More specifically, our basis functions are products of trigonometric and Beam functions. This choice means that the solutions automatically satisfy the boundary and periodic conditions in the x and y directions respectively. The accuracy of the method is assessed by applying it to model problems which admit exact analytical solutions. The numerical and analytic solutions are found to be in good agreement. The convergence rate of the spectral coefficients is found to be fifth-order algebraic in the x-direction and y-direction, confirming the efficiency and speed of our technique.

  6. NKG2D functions as an activating receptor on natural killer cells in the common marmoset (Callithrix jacchus).

    PubMed

    Watanabe, Masamichi; Kudo, Yohei; Kawano, Mitsuko; Nakayama, Masafumi; Nakamura, Kyohei; Kameda, Mai; Ebara, Masamune; Sato, Takeki; Nakamura, Marina; Omine, Kaito; Kametani, Yoshie; Suzuki, Ryuji; Ogasawara, Kouetsu

    2014-11-01

    The natural killer group 2 membrane D (NKG2D) receptor is an NK-activating receptor that plays an important role in host defense against tumors and viral infections. Although the marmoset is an important and reliable animal model, especially for the study of human-specific viral infections, functional characterization of NKG2D on marmoset NK cells has not previously been conducted. In the present study, we investigated a subpopulation of marmoset NK cells that express NKG2D and exhibit cytolytic potential. On the basis of their CD16 and CD56 expression patterns, marmoset NK cells can be classified into three subpopulations: CD16(+) CD56(-), CD16(-) CD56(+) and CD16(-) CD56(-) cells. NKG2D expression on marmoset CD16(+) CD56(-) and CD16(-) CD56(+) splenocytes was confirmed using an NKG2D ligand composed of an MHC class I chain-related molecule A (MICA)-Fc fusion protein. When marmoset splenocytes were cultured with IL-2 for 4 days, NKG2D expression was retained on CD16(+) CD56(-) and CD16(-) CD56(+). In addition, CD16(+) CD56(+) cells within the marmoset NK population appeared which expressed NKG2D after IL-2 stimulation. IL-2-activated marmoset NK cells showed strong cytolytic activity against K562 target cells and target cells stably expressing MICA. Further, the cytolytic activity of marmoset splenocytes was significantly reduced after addition of MICA-Fc fusion protein. Thus, NKG2D functions as an activating receptor on marmoset NK cells that possesses cytotoxic potential, and phenotypic profiles of marmoset NK cell subpopulations are similar to those seen in humans.

  7. Development of 2D dynamic model for hydrogen-fed and methane-fed solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Luo, X. J.; Fong, K. F.

    2016-10-01

    A new two-dimensional (2D) dynamic model is developed in Fortran to study the mass and energy transport, the velocity field and the electrochemical phenomena of high-temperature solid oxide fuel cell (SOFC). The key feature of this model is that gas properties, reaction heat, open circuit voltage, ohmic voltage and exchange current density are temperature-dependent. Based on this, the change of gas temperature and related characteristics can be evaluated in this study. The transient performances of SOFC, like heat-up and start-up processes, are therefore assessed accordingly. In this 2D dynamic SOFC model, chemical and electrochemical reaction, flow field, mass and energy transfer models are coupled in order to determine the current density, the mass fraction and the temperature of gas species. Mass, momentum and energy balance equations are discretized by finite difference method. Performance evaluation in current density, electrical efficiency and overall efficiency is conducted for the effects of different operating parameters in SOFC. The present model can serve as a valuable tool for in-depth performance evaluation of other design and operating parameters of SOFC unit, as well as further dynamic simulation and optimization of SOFC as a prime mover in cogeneration or trigeneration system.

  8. Myocyte enhancer factor 2D regulates ectoderm specification and adhesion properties of animal cap cells in the early Xenopus embryo.

    PubMed

    Katz Imberman, Sandra; Kolpakova, Alina; Keren, Aviad; Bengal, Eyal

    2015-08-01

    In Xenopus, animal cap (AC) cells give rise to ectoderm and its derivatives: epidermis and the central nervous system. Ectoderm has long been considered a default pathway of embryonic development, with cells that are not under the influence of vegetal Nodal signaling adopting an ectodermal program of gene expression. In the present study, we describe the involvement of the animally-localized maternal transcription factor myocyte enhancer factor (Mef) 2D in regulating the identity of AC cells. We find that Mef2D is required for the formation of both ectodermal lineages: neural and epidermis. Gain and loss of function experiments indicate that Mef2D regulates early gastrula expression of key ectodermal/epidermal genes in the animal region. Mef2D controls the activity of zygotic bone morphogenetic protein (BMP) signaling known to dictate the epidermal differentiation program. Exogenous expression of Mef2D in vegetal blastomeres was sufficient to induce ectopic expression of ectoderm/epidermal genes in the vegetal half of the embryo, when Nodal signaling was inhibited. Depletion of Mef2D caused a loss of AC cell adhesion that was rescued by the expression of E-cadherin or bone morphogenetic protein 4. In addition, expression of Mef2D in the prospective endoderm caused unusual aggregation of vegetal cells with animal cells in vitro and inappropriate segregation to other germ layers in vivo. Mef2D cooperates with another animally-expressed transcription factor, FoxI1e. Together, they regulate the expression of genes encoding signaling proteins and the transcription factors that control the regional identity of animal cells. Therefore, we describe a new role for the animally-localized Mef2D protein in early ectoderm specification, which is similar to that of the vegetally-localized VegT in endoderm and mesoderm formation.

  9. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development

    PubMed Central

    Ortega-Molina, Ana; Boss, Isaac W.; Canela, Andres; Pan, Heng; Jiang, Yanwen; Zhao, Chunying; Jiang, Man; Hu, Deqing; Agirre, Xabier; Niesvizky, Itamar; Lee, Ji-Eun; Chen, Hua-Tang; Ennishi, Daisuke; Scott, David W.; Mottok, Anja; Hother, Christoffer; Liu, Shichong; Cao, Xing-Jun; Tam, Wayne; Shaknovich, Rita; Garcia, Benjamin A.; Gascoyne, Randy D.; Ge, Kai; Shilatifard, Ali; Elemento, Olivier; Nussenzweig, Andre; Melnick, Ari M.; Wendel, Hans-Guido

    2015-01-01

    The lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL). However, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a bona fide tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice. KMT2D deficiency also delays germinal center (GC) involution, impedes B cell differentiation and class switch recombination (CSR). Integrative genomic analyses indicate that KMT2D affects H3K4 methylation and expression of a specific set of genes including those in the CD40, JAK-STAT, Toll-like receptor, and B cell receptor pathways. Notably, other KMT2D target genes include frequently mutated tumor suppressor genes such as TNFAIP3, SOCS3, and TNFRSF14. Therefore, KMT2D mutations may promote malignant outgrowth by perturbing the expression of tumor suppressor genes that control B cell activating pathways. PMID:26366710

  10. Temporal evolution of magma flow and degassing conditions during dome growth, insights from 2D numerical modeling

    NASA Astrophysics Data System (ADS)

    Chevalier, Laure; Collombet, Marielle; Pinel, Virginie

    2017-03-01

    Understanding magma degassing evolution during an eruption is essential to improving forecasting of effusive/explosive regime transitions at andesitic volcanoes. Lava domes frequently form during effusive phases, inducing a pressure increase both within the conduit and within the surrounding rocks. To quantify the influence of dome height on magma flow and degassing, we couple magma and gas flow in a 2D numerical model. The deformation induced by magma flow evolution is also quantified. From realistic initial magma flow conditions in effusive regime (Collombet, 2009), we apply increasing pressure at the conduit top as the dome grows. Since volatile solubility increases with pressure, dome growth is then associated with an increase in magma dissolved water content at a given depth, which corresponds with a decrease in magma porosity and permeability. Magma flow evolution is associated with ground deflation of a few μrad in the near field. However this signal is not detectable as it is hidden by dome subsidence (a few mrad). A Darcy flow model is used to study the impact of pressure and permeability conditions on gas flow in the conduit and surrounding rock. We show that dome permeability has almost no influence on magma degassing. However, increasing pressure in the surrounding rock, due to dome loading, as well as decreasing magma permeability in the conduit limit permeable gas loss at the conduit walls, thus causing gas pressurization in the upper conduit by a few tens of MPa. Decreasing magma permeability and increasing gas pressure increase the likelihood of magma explosivity and hazard in the case of a rapid decompression due to dome collapse.

  11. Time-Dependent 2D Modeling of Magnetron Plasma Torch in Turbulent Flow

    NASA Astrophysics Data System (ADS)

    Li, Lincun; Xia, Weidong

    2008-06-01

    A theoretical model is presented to describe the electromagnetic, heat transfer and fluid flow phenomena within a magnetron plasma torch and in the resultant plume, by using a commercial computational fluid dynamics (CFD) code FLUENT. Specific calculations are presented for a pure argon system (i.e., an argon plasma discharging into an argon environment), operated in a turbulent mode. An important finding of this work is that the external axial magnetic field (AMF) may have a significant effect on the behavior of arc plasma and thus affects the resulting plume. The AMF impels the plasma to retract axially and expand radially. As a result, the plasma intensity distribution on the cross section of torch seems to be more uniform. Numerical results also show that with AMF, the highest plasma temperature decreases and the anode arc root moves upstream significantly, while the current density distribution at the anode is more concentrated with a higher peak value. In addition, the use of AMF then induces a strong backflow at the torch spout and its magnitude increases with the AMF strength but decreases with the inlet gas velocity.

  12. A new anemometer for 2D atmospheric flow measurements in rough environments

    NASA Astrophysics Data System (ADS)

    Heisselmann, Hendrik; Hoelling, Michael; Peinke, Joachim

    2010-11-01

    One major downside of cup anemometry is the different response time for increasing and decreasing wind speeds, causing a systematic over-estimation of the mean wind speed under turbulent conditions. Especially under harsh environmental conditions like in offshore operation, the measuring principle leads to a wear of bearings causing a de-calibration over time and the requirement of regular maintenance. Therefore, we propose the newly developed sphere anemometer as a simple and robust alternative without any moving parts. The sphere anemometer consists of a flexible tube with a sphere mounted on top of it. The drag force acting on the sphere and its support causes a deflection, which is measured by means of a light pointer. Via calibration, this allows for simultaneous determination of wind speed and direction using only one sensor. In our contribution, we introduce the anemometer's setup and it's optimization towards offshore application. Additionally, experimental results obtained from wind tunnel measurements of turbulent flows are presented. Measurements under real wind conditions are compared to those of state-of-the-art wind speed sensors, such as cup and ultrasonic anemometers.

  13. Modeling water flow and nitrate dynamics in a plastic mulch vegetable cultivation system using HYDRUS-2D

    NASA Astrophysics Data System (ADS)

    Filipović, Vilim; Romić, Davor; Romić, Marija; Matijević, Lana; Mallmann, Fábio J. K.; Robinson, David A.

    2016-04-01

    Growing vegetables commercially requires intensive management and involves high irrigation demands and input of agrochemicals. Plastic mulch application in combination with drip irrigation is a common agricultural management technique practiced due to variety of benefits to the crop, mostly vegetable biomass production. However, the use of these techniques can result in various impacts on water and nutrient distribution in underlying soil and consequently affect nutrient leaching towards groundwater resources. The aim of this work is to estimate the effect of plastic mulch cover in combination with drip irrigation on water and nitrate dynamics in soil using HYDRUS-2D model. The field site was located in Croatian costal karst area on a Gleysol (WRB). The experiment was designed according to the split-plot design in three repetitions and was divided into plots with plastic mulch cover (MULCH) and control plots with bare soil (CONT). Each of these plots received applications of three levels of nitrogen fertilizer: 70, 140, and 210 kg per ha. All plots were equipped with drip irrigation and cropped with bell pepper (Capsicum annuum L. cv. Bianca F1). Lysimeters were installed at 90 cm depth in all plots and were used for monitoring the water and nitrate outflow. HYDRUS-2D was used for modeling the water and nitrogen outflow in the MULCH and CONT plots, implementing the proper boundary conditions. HYDRUS-2D simulated results showed good fitting to the field site observed data in both cumulative water and nitrate outflow, with high level of agreement. Water flow simulations produced model efficiency of 0.84 for CONT and 0.56 for MULCH plots, while nitrate simulations showed model efficiency ranging from 0.67 to 0.83 and from 0.70 to 0.93, respectively. Additional simulations were performed with the absence of the lysimeter, revealing faster transport of nitrates below drip line in the CONT plots, mostly because of the increased surface area subjected to precipitation

  14. Functional Dichotomy between NKG2D and CD28-Mediated Co-Stimulation in Human CD8+ T Cells

    PubMed Central

    Rajasekaran, Kamalakannan; Xiong, Va; Fong, Lee; Gorski, Jack; Malarkannan, Subramaniam

    2010-01-01

    Both CD28 and NKG2D can function as co-stimulatory receptors in human CD8+ T cells. However, their independent functional contributions in distinct CD8+ T cell subsets are not well understood. In this study, CD8+ T cells in human peripheral blood- and lung-derived lymphocytes were analyzed for CD28 and NKG2D expression and function. We found a higher level of CD28 expression in PBMC-derived naïve (CD45RA+CD27+) and memory (CD45RA−CD27+) CD8+ T cells (CD28Hi), while its expression was significantly lower in effector (CD45RA+CD27−) CD8+ T cells (CD28Lo). Irrespective of the differences in the CD28 levels, NKG2D expression was comparable in all three CD8+ T cell subsets. CD28 and NKG2D expressions followed similar patterns in human lung-resident GILGFVFTL/HLA-A2-pentamer positive CD8+ T cells. Co-stimulation of CD28Lo effector T cells via NKG2D significantly increased IFN-γ and TNF-α levels. On the contrary, irrespective of its comparable levels, NKG2D-mediated co-stimulation failed to augment IFN-γ and TNF-α production in CD28Hi naïve/memory T cells. Additionally, CD28-mediated co-stimulation was obligatory for IL-2 generation and thereby its production was limited only to the CD28Hi naïve/memory subsets. MICA, a ligand for NKG2D was abundantly expressed in the tracheal epithelial cells, validating the use of NKG2D as the major co-stimulatory receptor by tissue-resident CD8+ effector T cells. Based on these findings, we conclude that NKG2D may provide an expanded level of co-stimulation to tissue-residing effector CD8+ T cells. Thus, incorporation of co-stimulation via NKG2D in addition to CD28 is essential to activate tumor or tissue-infiltrating effector CD8+ T cells. However, boosting a recall immune response via memory CD8+ T cells or vaccination to stimulate naïve CD8+ T cells would require CD28-mediated co-stimulation. PMID:20844584

  15. Stratification of size-bidisperse granular mixtures in a quasi-2D bounded heap with periodic flow modulation

    NASA Astrophysics Data System (ADS)

    Xiao, Hongyi; Deng, Zhekai; Umbanhowar, Paul; Ottino, Julio; Lueptow, Richard

    2016-11-01

    Segregation of disperse granular materials in unsteady flows is ubiquitous in nature and industry, yet remains largely unexplored. In this study, unsteady flows are generated by feeding size-bidisperse granular mixtures onto a quasi-2D bounded heap using alternating feed rates, which results in stratified layers of large and small particles. The mechanism of stratification is investigated in detail using Discrete Element Method (DEM) simulations of the flow. During the transition from the slow to the fast feed rate, a segregating wedge propagates downstream and forms a large particle layer extending upstream. During the opposite transition, upstream segregated small particles relax downstream and form a small particle layer extending downstream. The transient kinematics from DEM simulations are quantified and used to inform a time-dependent continuum model that captures the interplay of advection, diffusion, and segregation in the flowing layer. The continuum model reproduces the principle characteristics of the stratification patterns observed in experiments and simulations. Funded by NSF Grant CBET-1511450.

  16. Natural killer cell NKG2D and granzyme B are critical for allergic pulmonary inflammation⋆

    PubMed Central

    Farhadi, Nazanin; Lambert, Laura; Triulzi, Chiara; Openshaw, Peter J.M.; Guerra, Nadia; Culley, Fiona J.

    2014-01-01

    Background The diverse roles of innate immune cells in the pathogenesis of asthma remain to be fully defined. Natural killer (NK) cells are innate lymphocytes that can regulate adaptive immune responses. NK cells are activated in asthma; however, their role in allergic airway inflammation is not fully understood. Objective We investigated the importance of NK cells in house dust mite (HDM)-triggered allergic pulmonary inflammation. Specifically, we aimed to determine the role of the major NK-cell activating receptor NKG2D and NK-cell effector functions mediated by granzyme B. Methods Allergic airway inflammation was induced in the airways of mice by repeated intranasal HDM extract administration and responses in wild-type and NKG2D-deficient mice were compared. Adoptive transfer studies were used to identify the cells and mechanisms involved. Results Mice that lacked NKG2D were resistant to the induction of allergic inflammation and showed little pulmonary eosinophilia, few airway TH2 cells, and no rise in serum IgE after multiple HDM-allergen exposures. However, NKG2D was not required for pulmonary inflammation after a single inoculation of allergen. NKG2D-deficient mice showed no alteration in responses to respiratory virus infection. Transfer of wild-type NK cells (but not CD3+ cells) into NKG2D-deficient mice restored allergic inflammatory responses only if the NK cells expressed granzyme B. Conclusions These studies established a pivotal role for NK-cell NKG2D and granzyme B in the pathogenesis of HDM-induced allergic lung disease, and identified novel therapeutic targets for the prevention and treatment of asthma. PMID:24290277

  17. 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] controls growth plate development by inhibiting apoptosis in the reserve zone and stimulating response to 1alpha,25(OH)2D3 in hypertrophic cells.

    PubMed

    Boyan, B D; Hurst-Kennedy, J; Denison, T A; Schwartz, Z

    2010-07-01

    Previously we showed that costochondral growth plate resting zone (RC) chondrocytes response primarily to 24R,25(OH)2D3 whereas prehypertrophic and hypertrophic (GC) cells respond to 1alpha,25(OH)2D3. 24R,25(OH)2D3 increases RC cell proliferation and inhibits activity of matrix processing enzymes, suggesting it stabilizes cells in the reserve zone, possibly by inhibiting the matrix degradation characteristic of apoptotic hypertrophic GC cells. To test this, apoptosis was induced in rat RC cells by treatment with exogenous inorganic phosphate (Pi). 24R,25(OH)2D3 blocked apoptotic effects in a dose-dependent manner. Similarly, apoptosis was induced in ATDC5 cell cultures and 24R,25(OH)2D3 blocked this effect. Further studies indicated that 24R,25(OH)2D3 acts via at least two independent pathways. 24R,25(OH)2D3 increases LPA receptor-1 (LPA R1) expression and production of lysophosphatidic acid (LPA), and subsequent LPA R1/3-dependent signaling, thereby decreasing p53 abundance. LPA also increases the Bcl-2/Bax ratio. In addition, 24R,25(OH)2D3 acts by increasing PKC activity. 24R,25(OH)2D3 stimulates 1-hydroxylase activity, resulting in increased levels of 1,25(OH)2D3, and it increases levels of phospholipase A2 activating protein, which is required for rapid 1alpha,25(OH)2D3-dependent activation of PKC in GC cells. These results suggest that 24R,25(OH)2D3 modulates growth plate development by controlling the rate and extent of RC chondrocyte transition to a GC chondrocyte phenotype.

  18. Validation of TITAN2D flow model code for pyroclastic flows and debris avalanches at Soufrière Hills Volcano, Montserrat, BWI

    NASA Astrophysics Data System (ADS)

    Widiwijayanti, C.; Voight, B.; Hidayat, D.; Patra, A.; Pitman, E.

    2004-12-01

    Soufrière Hills Volcano (SHV), Montserrat, has experienced numerous episodes of dome collapses since 1996. They range from relatively small rockfalls to major dome collapses, several >10x106 m3, and one >100x106 m3 (Calder, Luckett, Sparks and Voight 2002; Voight et al. 2002). The hazard implications for such events are significant at both local and regional scales, and include pyroclastic surges, explosions, and tsunami. Problems arise in forecasting and hazards mitigation, particularly in zoning for populated areas. Determining the likely extent of flow deposits is important for hazard zonation. For this, detailed mapping (topography of source areas and paths, material properties, structure, track roughness and erosion) has an important role, giving clues on locations of future collapse and runout paths. Here we present an application of a numerical computation model of geophysical mass flow using the TITAN2D code (Patra et al. 2004; Pitman et al. 2004), to simulate dome collapses at SHV. The majority of collapse-type pyroclastic flows at SHV are consistent with an initiation by gravitational collapse of oversteepened flanks of the dome. If the gravity controls the energy for such processes, then the flow tracks can be predicted on the basis of topography, and friction influences runout. TITAN2D is written to simulate this type of volcanic flow, and the SHV database is used to validate the code and provide calibrated data on friction properties. The topographic DEM was successively updated by adding flow deposit thicknesses for previous collapses. Simulation results were compared to observed flow parameters, including flow path, deposit volume, duration, velocity, and runout distance of individual flows, providing calibration data on internal and bed friction, and demonstrating the validity and limitations of such modeling for practical volcanic hazard assessment.

  19. Optical and electrical study of organic solar cells with a 2D grating anode.

    PubMed

    Sha, Wei E I; Choy, Wallace C H; Wu, Yumao; Chew, Weng Cho

    2012-01-30

    We investigate both optical and electrical properties of organic solar cells (OSCs) incorporating 2D periodic metallic back grating as an anode. Using a unified finite-difference approach, the multiphysics modeling framework for plasmonic OSCs is established to seamlessly connect the photon absorption with carrier transport and collection by solving the Maxwell's equations and semiconductor equations (Poisson, continuity, and drift-diffusion equations). Due to the excited surface plasmon resonance, the significantly nonuniform and extremely high exciton generation rate near the metallic grating are strongly confirmed by our theoretical model. Remarkably, the nonuniform exciton generation indeed does not induce more recombination loss or smaller open-circuit voltage compared to 1D multilayer standard OSC device. The increased open-circuit voltage and reduced recombination loss by the plasmonic OSC are attributed to direct hole collections at the metallic grating anode with a short transport path. The work provides an important multiphysics understanding for plasmonic organic photovoltaics.

  20. CD155 on HIV-Infected Cells Is Not Modulated by HIV-1 Vpu and Nef but Synergizes with NKG2D Ligands to Trigger NK Cell Lysis of Autologous Primary HIV-Infected Cells.

    PubMed

    Davis, Zachary B; Sowrirajan, Bharatwaj; Cogswell, Andrew; Ward, Jeffery P; Planelles, Vicente; Barker, Edward

    2017-02-01

    Activation of primary CD4(+) T cells induces the CD155, but not the CD112 ligands for the natural killer (NK) cell activation receptor (aNKR) CD226 [DNAX accessory molecule-1 (DNAM-1)]. We hypothesize that HIV productively infects activated CD4(+) T cells and makes itself vulnerable to NK cell-mediated lysis when CD155 on infected T cells engages DNAM-1. The primary objective of this study is to determine whether CD155 alone or together with NKG2D ligands triggers autologous NK cell lysis of HIV-infected T cells and whether HIV modulates CD155. To determine whether HIV modulates this activation ligand, we infected "activated" CD4(+) T cells with HIV in the absence or presence of Nef and/or Vpu and determined by flow cytometry whether they modulated CD155. To determine if CD155 alone, or together with NKG2D ligands, triggered NK cell lysis of autologous HIV-infected T cells, we treated purified NK cells with DNAM-1 and/or NKG2D blocking antibodies before the addition of purified autologous HIV-infected cells in cytolytic assays. Finally, we determined whether DNAM-1 works together with NKG2D as an NK cell coactivation receptor (caNKR) or whether they work independently as aNKRs to induce an NK cell lytic response. We demonstrate that HIV and specifically Nef and/or Vpu do not modulate CD155 on infected primary T cells; and both CD155 and NKG2D ligands synergize as aNKRs to trigger NK cell lysis of the infected cell.

  1. Sensitivity analysis of 2D steady-state shallow water flow. Application to free surface flow model calibration

    NASA Astrophysics Data System (ADS)

    Guinot, Vincent; Cappelaere, Bernard

    2009-04-01

    This paper presents the analytical properties of the solutions of the sensitivity equations for steady-state, two-dimensional shallow water flow. These analytical properties are used to provide guidelines for model calibration and validation. The sensitivity of the water depth/level and that of the longitudinal unit discharge are shown to contain redundant information. Under subcritical conditions, the sensitivities of the flow variables are shown to obey an anisotropic elliptic equation. The main directions of the contour lines for water depth and the longitudinal unit discharge sensitivity are parallel and perpendicular to the flow, while they are diagonal to the flow for the transverse unit discharge sensitivity. Moreover, the sensitivity for all three variables extends farther in the transverse direction than in the longitudinal direction, the anisotropy ratio being a function of the sole Froude number. For supercritical flow, the sensitivity obeys an anisotropic hyperbolic equation. These findings are confirmed by application examples on idealized and real-world simulations. The sensitivities to the geometry, friction coefficient or model boundary conditions are shown to behave in different ways, thus providing different types of information for model calibration and validation.

  2. ZEUS-2D: A Radiation Magnetohydrodynamics Code for Astrophysical Flows in Two Space Dimensions. II. The Magnetohydrodynamic Algorithms and Tests

    NASA Astrophysics Data System (ADS)

    Stone, James M.; Norman, Michael L.

    1992-06-01

    In this, the second of a series of three papers, we continue a detailed description of ZEUS-2D, a numerical code for the simulation of fluid dynamical flows in astrophysics including a self-consistent treatment of the effects of magnetic fields and radiation transfer. In this paper, we give a detailed description of the magnetohydrodynamical (MHD) algorithms in ZEUS-2D. The recently developed constrained transport (CT) algorithm is implemented for the numerical evolution of the components of the magnetic field for MHD simulations. This formalism guarantees the numerically evolved field components will satisfy the divergence-free constraint at all times. We find, however, that the method used to compute the electromotive forces must be chosen carefully to propagate accurately all modes of MHD wave families (in particular shear Alfvén waves). A new method of computing the electromotive force is developed using the method of characteristics (MOC). It is demonstrated through the results of an extensive series of MHD test problems that the resulting hybrid MOC-CT method provides for the accurate evolution of all modes of MHD wave families.

  3. Autonomous Stimulation of Cancer Cell Plasticity by the Human NKG2D Lymphocyte Receptor Coexpressed with Its Ligands on Cancer Cells

    PubMed Central

    Cai, Xin; Dai, Zhenpeng; Reeves, Rebecca S.; Caballero-Benitez, Andrea; Duran, Kate L.; Delrow, Jeffrey J.; Porter, Peggy L.

    2014-01-01

    The stimulatory NKG2D receptor on lymphocytes promotes tumor immune surveillance by targeting ligands selectively induced on cancer cells. Progressing tumors counteract by employing tactics to disable lymphocyte NKG2D. This negative dynamic is escalated as some human cancer cells co-opt expression of NKG2D, thereby complementing the presence of its ligands for autonomous stimulation of oncogenic signaling. Clinical association data imply relationships between cancer cell NKG2D and metastatic disease. Here we show that NKG2D promotes cancer cell plasticity by induction of phenotypic, molecular, and functional signatures diagnostic of the epithelial–mesenchymal transition, and of stem-like traits via induction of Sox9, a key transcriptional regulator of breast stem cell maintenance. These findings obtained with model breast tumor lines and xenotransplants were recapitulated by ex vivo cancer cells from primary invasive breast carcinomas. Thus, NKG2D may have the capacity to drive high malignancy traits underlying metastatic disease. PMID:25291178

  4. 2D fluid model analysis for the effect of 3D gas flow on a capacitively coupled plasma deposition reactor

    NASA Astrophysics Data System (ADS)

    Kim, Ho Jun; Lee, Hae June

    2016-06-01

    The wide applicability of capacitively coupled plasma (CCP) deposition has increased the interest in developing comprehensive numerical models, but CCP imposes a tremendous computational cost when conducting a transient analysis in a three-dimensional (3D) model which reflects the real geometry of reactors. In particular, the detailed flow features of reactive gases induced by 3D geometric effects need to be considered for the precise calculation of radical distribution of reactive species. Thus, an alternative inclusive method for the numerical simulation of CCP deposition is proposed to simulate a two-dimensional (2D) CCP model based on the 3D gas flow results by simulating flow, temperature, and species fields in a 3D space at first without calculating the plasma chemistry. A numerical study of a cylindrical showerhead-electrode CCP reactor was conducted for particular cases of SiH4/NH3/N2/He gas mixture to deposit a hydrogenated silicon nitride (SiN x H y ) film. The proposed methodology produces numerical results for a 300 mm wafer deposition reactor which agree very well with the deposition rate profile measured experimentally along the wafer radius.

  5. Ataxia-telangiectasia mutated kinase-mediated upregulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility.

    PubMed

    Luis Espinoza, J; Takami, Akiyoshi; Trung, Ly Q; Nakao, Shinji

    2013-06-01

    The powerful activating receptor NKG2D is expressed by natural killer (NK) cells and promotes cytotoxic lysis of cancer cells expressing NKG2D ligands (NKG2D-Ls). We report the effective induction of NKG2D-Ls, achieved with the naturally occurring polyphenol resveratrol, in a broad range of leukemia cells. In this study, resveratrol upregulated the NKG2D-Ls MHC class I chain-related proteins MICA and MICB, and UL16-binding proteins ULBP1, ULBP2, and ULBP3 in most of the leukemia cells analyzed. Ligand upregulation induced by resveratrol was impaired by pharmacological and genetic disruption of ataxia-telangiectasia mutated kinase, the main regulator of NKG2D-L expression. Leukemia cells treated with resveratrol were more susceptible to killing by NK cells than untreated cells, and the enhanced cytotoxicity of NK cells was blocked by treatment of NK cells with anti-NKG2D mAbs. Interestingly, resveratrol consistently upregulated the NKG2D receptor expression and enhanced NKG2D-mediated functions in resting NK cells obtained from healthy individuals. Therefore, resveratrol has attractive immunotherapeutic potential.

  6. Large eddy simulations for quasi-2D turbulence in shallow flows: A comparison between different subgrid scale models

    NASA Astrophysics Data System (ADS)

    Awad, Esam; Toorman, Erik; Lacor, Chris

    2009-06-01

    In this study, the performance of the horizontal large eddy simulation module, developed at the University of Leuven (HLES-KULeuven module) is assessed. A comparison between different subgrid scale models has been carried out. The study is concerned with the non-rotating and unstratified flows. The results of the simulation for an oscillatory backward facing (BFS) flow are presented in case of an expanding flume based on a one-length scale approach and a two-length scale approach. Three subgrid scale (SGS) models have been tested: Smagorinsky SGS model (Smagorinsky, J., (1963). General circulation experiments with the primitive equations, I. the basic experiments. Monthly Weather Review, 91(3), 99-164), Uittenbogaard SGS model (Uittenbogaard, R.E., and van Vossen, B., (2004). Subgrid-scale model for quasi-2D turbulence in shallow water. Shallow Flows. Jirka and Uijttewaal (Eds.), Taylor & Francis Group, London, ISBN 90 5809 700 5) and a proposed two-length scale approach. The first two models are considered to be a one-length scale models. A simulation without a subgrid scale model for the horizontal mixing has also been conducted. In all simulations, a quadratic friction model parameterizes the dissipation produced by the 3D-subdepth scale turbulence. The two-length scale concept uses a newly mixing length formulation for the quasi-2D turbulence and doesn't depend on the filter width in contrast to the one-length scale approach, in which the mixing length is function of the filter width. The outputs of the HLES-KULeuven module have been compared with the experimental data taken from Stelling, G.S., and Wang, L.X., (1984). Experiments and computations on separating flow in an expanding flume. Dept. Civil Engineering, Delft University of Technology, Report 2-84.). The two-length scale approach has been validated with experimental data from SERC Flood Channel Facility at HR Wallingford. In general, there is a qualitative agreement with the experimental data. It has

  7. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells.

    PubMed

    Carbone, Ennio; Neri, Paola; Mesuraca, Maria; Fulciniti, Mariateresa T; Otsuki, Takemi; Pende, Daniela; Groh, Veronika; Spies, Thomas; Pollio, Giuditta; Cosman, David; Catalano, Lucio; Tassone, Pierfrancesco; Rotoli, Bruno; Venuta, Salvatore

    2005-01-01

    The role of natural killer (NK) cells in multiple myeloma is not fully understood. Here, NK susceptibility of myeloma cells derived from distinct disease stages was evaluated in relation to major histocompatibility complex (MHC) class I, MHC class I chain-related protein A (MICA), MHC class I chain-related protein B (MICB), and UL16 binding protein (ULBP) expression. MHC class I molecules were hardly detectable on bone marrow cells of early-stage myeloma, while late-stage pleural effusion-derived cell lines showed a strong MHC class I expression. Conversely, a high MICA level was found on bone marrow myeloma cells, while it was low or not measurable on pleural effusion myeloma cells. The reciprocal surface expression of these molecules on bone marrow- and pleural effusion-derived cell was confirmed at mRNA levels. While bone marrow-derived myeloma cells were readily recognized by NK cells, pleural effusion-derived lines were resistant. NK protection of pleural effusion cells was MHC class I dependent. Receptor blocking experiments demonstrated that natural cytotoxicity receptor (NCR) and NK receptor member D of the lectin-like receptor family (NKG2D) were the key NK activating receptors for bone marrow-derived myeloma cell recognition. In ex vivo experiments patient's autologous fresh NK cells recognized bone marrow-derived myeloma cells. Our data support the hypothesis that NK cell cytotoxicity could sculpture myeloma and represents an important immune effector mechanism in controlling its intramedullary stages.

  8. Debris Flow Simulation using FLO-2D on the 2004 Landslide Area of Real, General Nakar, and Infanta, Philippines

    NASA Astrophysics Data System (ADS)

    Llanes, F.; dela Resma, M.; Ferrer, P.; Realino, V.; Aquino, D. T.; Eco, R. C.; Lagmay, A.

    2013-12-01

    From November 14 to December 3, 2004, Luzon Island was ravaged by 4 successive typhoons: Typhoon Mufia, Tropical Storm Merbok, Tropical Depression Winnie, and Super Typhoon Nanmadol. Tropical Depression Winnie was the most destructive of the four when it triggered landslides on November 29 that devastated the municipalities of Infanta, General Nakar, and Real in Quezon Province, southeast Luzon. Winnie formed east of Central Luzon on November 27 before it moved west-northwestward over southeastern Luzon on November 29. A total of 1,068 lives were lost and more than USD 170 million worth of damages to crops and infrastructure were incurred from the landslides triggered by Typhoon Winnie on November 29 and the flooding caused by the 4 typhoons. FLO-2D, a flood routing software for generating flood and debris flow hazard maps, was utilized to simulate the debris flows that could potentially affect the study area. Based from the rainfall intensity-duration-frequency analysis, the cumulative rainfall from typhoon Winnie on November 29 which was approximately 342 mm over a 9-hour period was classified within a 100-year return period. The Infanta station of the Philippine Atmospheric Geophysical and Astronomical Services Administration (PAGASA) was no longer able to measure the amount of rainfall after this period because the rain gauge in that station was washed away by floods. Rainfall data with a 100-year return period was simulated over the watersheds delineated from a SAR-derived digital elevation model. The resulting debris flow hazard map was compared with results from field investigation and previous studies made on the landslide event. The simulation identified 22 barangays (villages) with a total of 45,155 people at risk of turbulent flow and flooding.

  9. TITAN2D simulations of pyroclastic flows at Cerro Machín Volcano, Colombia: Hazard implications

    NASA Astrophysics Data System (ADS)

    Murcia, H. F.; Sheridan, M. F.; Macías, J. L.; Cortés, G. P.

    2010-03-01

    Cerro Machín is a dacitic tuff ring located in the central part of the Colombian Andes. It lies at the southern end of the Cerro Bravo-Cerro Machín volcanic belt. This volcano has experienced at least six major explosive eruptions during the last 5000 years. These eruptions have generated pyroclastic flows associated with Plinian activity that have traveled up to 8 km from the crater, and pyroclastic flows associated with Vulcanian activity with shorter runouts of 5 km from the source. Today, some 21,000 people live within a 8 km radius of Cerro Machín. The volcano is active with fumaroles and has shown increasing seismic activity since 2004, and therefore represents a potentially increasing threat to the local population. To evaluate the possible effects of future eruptions that may generate pyroclastic density currents controlled by granular flow dynamics we performed flow simulations with the TITAN2D code. These simulations were run in all directions around the volcano, using the input parameters of the largest eruption reported. The results show that an eruption of 0.3 km 3 of pyroclastic flows from a collapsing Plinian column would travel up to 9 km from the vent, emplacing a deposit thicker than 60 m within the Toche River valley. Deposits >45 m thick can be expected in the valleys of San Juan, Santa Marta, and Azufral creeks, while 30 m thick deposits could accumulate within the drainages of the Tochecito, Bermellón, and Coello Rivers. A minimum area of 56 km 2 could be affected directly by this kind of eruption. In comparison, Vulcanian column-collapse pyroclastic flows of 0.1 km 3 would travel up to 6 km from the vent depositing >45 m thick debris inside the Toche River valley and more than 30 m inside the valleys of San Juan, Santa Marta, and Azufral creeks. The minimum area that could be affected directly by this kind of eruption is 33 km 2. The distribution and thickness of the deposits obtained by these simulations are consistent with the hazard

  10. Development of drug loaded nanoparticles for tumor targeting. Part 1: synthesis, characterization, and biological evaluation in 2D cell cultures

    NASA Astrophysics Data System (ADS)

    El-Dakdouki, Mohammad H.; Puré, Ellen; Huang, Xuefei

    2013-04-01

    significantly enhanced through receptor mediated endocytosis. In addition, if the receptor is recycled to the cell surface, the NP cargo can be transported out of the cells, which is then taken up by neighboring cells thus enhancing solid tumor penetration. To validate our hypothesis, in the first of two articles, we report the synthesis of doxorubicin (DOX)-loaded, hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44, a receptor expressed on the cancer cell surface. HA was conjugated onto amine-functionalized SNPs prepared through an oil-water microemulsion method. The immobilization of the cytotoxic drug DOX was achieved through an acid sensitive hydrazone linkage. The NPs were fully characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements, thermogravimetric analysis (TGA), UV-vis absorbance, and nuclear magnetic resonance (NMR). Initial biological evaluation experiments demonstrated that compared to ligand-free SNPs, the uptake of HA-SNPs by the CD44-expressing SKOV-3 ovarian cancer cells was significantly enhanced when evaluated in the 2D monolayer cell culture. Mechanistic studies suggested that cellular uptake of HA-SNPs was mainly through CD44 mediated endocytosis. HA-SNPs with immobilized DOX were endocytosed efficiently by the SKOV-3 cells as well. The enhanced tumor penetration and drug delivery properties of HA-SNPs will be evaluated in 3D tumor models in the subsequent paper. Electronic supplementary information (ESI) available: Detailed experimental procedures for the synthesis and characterization of nanoparticles, confocal studies, flow cytometry, and supporting figures and tables. See DOI: 10.1039/c3nr33777d

  11. The FlatModel: a 2D numerical code to evaluate debris flow dynamics. Eastern Pyrenees basins application.

    NASA Astrophysics Data System (ADS)

    Bateman, A.; Medina, V.; Hürlimann, M.

    2009-04-01

    Debris flows are present in every country where a combination of high mountains and flash floods exists. In the northern part of the Iberian Peninsula, at the Pyrenees, sporadic debris events occur. We selected two different events. The first one was triggered at La Guingueta by the big exceptional flood event that produced many debris flows in 1982 which were spread all over the Catalonian Pyrenees. The second, more local event occurred in 2000 at the mountain Montserrat at the Pre-litoral mountain chain. We present here some results of the FLATModel, entirely developed at the Research Group in Sediment Transport of the Hydraulic, Marine and Environmental Engineering Department (GITS-UPC). The 2D FLATModel is a Finite Volume method that uses the Godunov scheme. Some numerical arranges have been made to analyze the entrainment process during the events, the Stop & Go phenomena and the final deposit of the material. The material rheology implemented is the Voellmy approach, because it acts very well evaluating the frictional and turbulent behavior. The FLATModel uses a GIS environment that facilitates the data analysis as the comparison between field and numerical data. The two events present two different characteristics, one is practically a one dimensional problem of 1400 m in length and the other has a more two dimensional behavior that forms a big fan.

  12. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  13. FDTD analysis of 2D triangular-lattice photonic crystals with arbitrary-shape inclusions based on unit cell transformation

    NASA Astrophysics Data System (ADS)

    Ma, Zetao; Ogusu, Kazuhiko

    2009-04-01

    A finite-difference time-domain method based on Yee's orthogonal cell is utilized to calculate the band structures of 2D triangular-lattice-based photonic crystals through a simple modification to properly shifting the boundaries of the original unit cell. A strategy is proposed for transforming the triangular unit cell into an orthogonal one, which can be used to calculate the band structures of 2D PhCs with various shapes of inclusions, such as triangular, quadrangular, and hexagonal shapes, to overcome the shortage of plane-wave expansion method for circular one. The band structures of 2D triangular-lattice-based PhCs with hexagonal air-holes are calculated and discussed for different values of its radius and rotation angle. The obtained results provide an insight to manipulate the band structures of PhCs.

  14. Separation of basic proteins from Leishmania using a combination of Free flow electrophoresis (FFE) and 2D electrophoresis (2-DE) under basic conditions.

    PubMed

    Brotherton, Marie-Christine; Racine, Gina; Ouellette, Marc

    2015-01-01

    Basic proteins, an important class of proteins in intracellular organisms such as Leishmania, are usually underrepresented on 2D gels. This chapter describes a method combining basic proteins fractionation using Free flow electrophoresis in isoelectric focusing mode (IEF-FFE) followed by protein separation using two-dimensional gel electrophoresis (2-DE) in basic conditions. The combination of these two techniques represents a great improvement for the visualization of Leishmania proteins with basic pI using 2D gels.

  15. Observation and simulation of heterogeneous 2D water and solute flow processes in ditch beds for subsequent catchment modelling

    NASA Astrophysics Data System (ADS)

    Dages, Cecile; Samouelian, Anatja; Lanoix, Marthe; Dollinger, Jeanne; Chakkour, Sara; Chovelon, Gabrielle; Trabelsi, Khouloud; Voltz, Marc

    2015-04-01

    Ditches are involved in the transfer of pesticide to surface and groundwaters (e.g. Louchart et al., 2001). Soil horizons underlying ditch beds may present specific soil characteristics compared to neighbouring field soils due to erosion/deposition processes, to the specific biological activities (rooting dynamic and animal habitat) in the ditches (e.g. Vaughan et al., 2008) and to management practices (burning, dredging, mowing,...). Moreover, in contrast to percolation processes in field soils that can be assumed to be mainly 1D vertical, those occurring in the ditch beds are by essence 2D or even 3D. Nevertheless, due to a lake of knowledge, these specific aspects of transfer within ditch beds are generally omitted for hydrological simulation at the catchment scale (Mottes et al., 2014). Accordingly, the aims of this study were i) to characterize subsurface solute transfer through ditch beds and ii) to determine equivalent hydraulic parameters of the ditch beds for use in catchment scale hydrological simulations. A complementary aim was to evaluate the error in predictions performed when percolation in ditches is assumed to be similar to that in the neighbouring field soil. First, bromide transfer experiments were performed on undisturbed soil column (15 cm long with a 15 cm inner-diameter), horizontally and vertically sampled within each soil horizon underlying a ditch bed and within the neighboring field. Columns were sampled at the Roujan catchment (Hérault, France), which belongs to the long term Mediterranean hydrological observatory OMERE (Voltz and Albergel, 2002). Second, for each column, a set of parameters was determined by inverse optimization with mobile-immobile or dual permeability models, with CXTFIT (Toride et al., 1999) or with HYDRUS (Simunek et al., 1998). Third, infiltration and percolation in the ditch was simulated by a 2D flow domain approach considering the 2D variation in hydraulic properties of the cross section of a ditch bed. Last

  16. Cytomegalovirus-Associated CD4(+) CD28(null) Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction.

    PubMed

    Shabir, S; Smith, H; Kaul, B; Pachnio, A; Jham, S; Kuravi, S; Ball, S; Chand, S; Moss, P; Harper, L; Borrows, R

    2016-04-01

    Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4(+) T cells lacking costimulatory CD28 (CD4(+) CD28(null) cells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4(+) CD28(null) cells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4(+) CD27(-) CD28(null) cells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4(+) CD28(null) cell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4(+) CD28(null) cell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes.

  17. 2D design rule and layout analysis using novel large-area first-principles-based simulation flow incorporating lithographic and stress effects

    NASA Astrophysics Data System (ADS)

    Prins, Steven L.; Blatchford, James; Olubuyide, Oluwamuyiwa; Riley, Deborah; Chang, Simon; Hong, Qi-Zhong; Kim, T. S.; Borges, Ricardo; Lin, Li

    2009-03-01

    As design rules and corresponding logic standard cell layouts continue to shrink node-on-node in accordance with Moore's law, complex 2D interactions, both intra-cell and between cells, become much more prominent. For example, in lithography, lack of scaling of λ/NA implies aggressive use of resolution enhancement techniques to meet logic scaling requirements-resulting in adverse effects such as 'forbidden pitches'-and also implies an increasing range of optical influence relative to cell size. These adverse effects are therefore expected to extend well beyond the cell boundary, leading to lithographic marginalities that occur only when a given cell is placed "in context" with other neighboring cells in a variable design environment [1]. This context dependence is greatly exacerbated by increased use of strain engineering techniques such as SiGe and dual-stress liners (DSL) to enhance transistor performance, both of which also have interaction lengths on the order of microns. The use of these techniques also breaks the formerly straightforward connection between lithographic 'shapes' and end-of-line electrical performance, thus making the formulation of design rules that are robust to process variations and complex 2D interactions more difficult. To address these issues, we have developed a first-principles-based simulation flow to study contextdependent electrical effects in layout, arising not only from lithography, but also from stress and interconnect parasitic effects. This flow is novel in that it can be applied to relatively large layout clips- required for context-dependent analysis-without relying on semi-empirical or 'black-box' models for the fundamental electrical effects. The first-principles-based approach is ideal for understanding contextdependent effects early in the design phase, so that they can be mitigated through restrictive design rules. The lithographic simulations have been discussed elsewhere [1] and will not be presented in detail. The

  18. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer

    SciTech Connect

    Chitcholtan, Kenny; Asselin, Eric; Parent, Sophie; Sykes, Peter H.; Evans, John J.

    2013-01-01

    Three-dimensional (3D) in vitro models have an invaluable role in understanding the behaviour of tumour cells in a well defined microenvironment. This is because some aspects of tumour characteristics cannot be fully recapitulated in a cell monolayer (2D). In the present study, we compared growth patterns, expression of signalling molecules, and metabolism-associated proteins of endometrial cancer cell lines in 3D and 2D cell cultures. Cancer cells formed spherical structures in 3D reconstituted basement membrane (3D rBM), and the morphological appearance was cell line dependent. Cell differentiation was observed after 8 days in the 3D rBM. There was reduced proliferation, detected by less expression of PCNA in 3D rBM than in 2D cell monolayers. The addition of exogenous epidermal growth factor (EGF) to cancer cells induced phosphorylation of EGFR and Akt in both cell culture conditions. The uptake of glucose was selectively altered in the 3D rBM, but there was a lack of association with Glut-1 expression. The secretion of vascular endothelial growth factor (VEGF) and prostaglandin E{sub 2} (PGE{sub 2}) was selectively altered in 3D rBM, and it was cell line dependent. Our data demonstrated that 3D rBM as an in vitro model can influence proliferation and metabolism of endometrial cancer cell behaviour compared to 2D cell monolayer. Changes are specific to individual cell types. The use of 3D rBM is, therefore, important in the in vitro study of targeted anticancer therapies.

  19. 1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

    NASA Astrophysics Data System (ADS)

    Corall, Silke; Haraszti, Tamas; Bartoschik, Tanja; Spatz, Joachim Pius; Ludwig, Thomas; Cavalcanti-Adam, Elisabetta Ada

    2014-03-01

    Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cell-binding site mutation, we determined that -integrin is the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of - and -integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane.

  20. Numerical model of water flow and solute accumulation in vertisols using HYDRUS 2D/3D code

    NASA Astrophysics Data System (ADS)

    Weiss, Tomáš; Dahan, Ofer; Turkeltub, Tuvia

    2015-04-01

    Keywords: dessication-crack-induced-salinization, preferential flow, conceptual model, numerical model, vadose zone, vertisols, soil water retention function, HYDRUS 2D/3D Vertisols cover a hydrologically very significant area of semi-arid regions often through which water infiltrates to groundwater aquifers. Understanding of water flow and solute accumulation is thus very relevant to agricultural activity and water resources management. Previous works suggest a conceptual model of dessication-crack-induced-salinization where salinization of sediment in the deep section of the vadose zone (up to 4 m) is induced by subsurface evaporation due to convective air flow in the dessication cracks. It suggests that the salinization is induced by the hydraulic gradient between the dry sediment in the vicinity of cracks (low potential) and the relatively wet sediment further from the main cracks (high potential). This paper presents a modified previously suggested conceptual model and a numerical model. The model uses a simple uniform flow approach but unconventionally prescribes the boundary conditions and the hydraulic parameters of soil. The numerical model is bound to one location close to a dairy farm waste lagoon, but the application of the suggested conceptual model could be possibly extended to all semi-arid regions with vertisols. Simulations were conducted using several modeling approaches with an ultimate goal of fitting the simulation results to the controlling variables measured in the field: temporal variation in water content across thick layer of unsaturated clay sediment (>10 m), sediment salinity and salinity the water draining down the vadose zone to the water table. The development of the model was engineered in several steps; all computed as forward solutions by try-and-error approach. The model suggests very deep instant infiltration of fresh water up to 12 m, which is also supported by the field data. The paper suggests prescribing a special atmospheric

  1. Electrocapturing flow cell

    DOEpatents

    Morozov, Victor

    2011-04-05

    A flow cell for electrophoretically-assisted capturing analytes from a flow. The flow cell includes a specimen chamber, a first membrane, a second membrane, a first electrode chamber, and a second electrode chamber. The specimen chamber may have a sample inlet and a sample outlet. A first portion of the first membrane may be coupled to a first portion of the specimen chamber. A first portion of the second membrane may be coupled to a second portion of the specimen chamber. The first electrode chamber may be configured to accept a charge. A portion of the first electrode chamber may be coupled to a second portion of the first membrane. A second electrode chamber may be configured to accept an opposite charge. A portion of the second electrode chamber may be coupled to a second portion of the second membrane.

  2. Crosstalk between SOXB1 proteins and WNT/β-catenin signaling in NT2/D1 cells.

    PubMed

    Mojsin, Marija; Topalovic, Vladanka; Vicentic, Jelena Marjanovic; Schwirtlich, Marija; Stanisavljevic, Danijela; Drakulic, Danijela; Stevanovic, Milena

    2015-11-01

    During early vertebrate embryogenesis, the expression of SOXB1 proteins is precisely regulated by a number of different mechanisms, including Wnt/β-catenin signaling. This is essential for controlling the balance between stemness and differentiation in embryonic stem cells. In the present study, we analyzed the molecular mechanism of LiCl action in NT2/D1 cells and examined the crosstalk between SOXB1 proteins and Wnt signaling in this model system. We have shown that LiCl increases β-catenin level, induces its translocation to the nucleus and consequently up-regulates β-catenin/Tcf-dependent transcription in NT2/D1 cells. Our results also suggest that LiCl treatment leads to increased expression of SOX2 and SOX3 proteins in NT2/D1 cells through activation of canonical Wnt signaling. Finally, we have detected a negative feedback loop between β-catenin and SOX2 expression in NT2/D1 cells. Since β-catenin and SOX2 have been linked to processes of self-renewal and pluripotency, our results have implications for future research on the maintenance of stemness and lineage commitment of embryonic stem cells.

  3. Regulation of podocalyxin trafficking by Rab small GTPases in 2D and 3D epithelial cell cultures

    PubMed Central

    Mrozowska, Paulina S.

    2016-01-01

    MDCK II cells, a widely used model of polarized epithelia, develop into different structures depending on culture conditions: two-dimensional (2D) monolayers when grown on synthetic supports or three-dimensional (3D) cysts when surrounded by an extracellular matrix. The establishment of epithelial polarity is accompanied by transcytosis of the apical marker podocalyxin from the outer plasma membrane to the newly formed apical domain, but its exact route and regulation remain poorly understood. Here, through comprehensive colocalization and knockdown screenings, we identified the Rab GTPases mediating podocalyxin transcytosis and showed that different sets of Rabs coordinate its transport during cell polarization in 2D and 3D structures. Moreover, we demonstrated that different Rab35 effectors regulate podocalyxin trafficking in 2D and 3D environments; trafficking is mediated by OCRL in 2D monolayers and ACAP2 in 3D cysts. Our results give substantial insight into regulation of the transcytosis of this apical marker and highlight differences between trafficking mechanisms in 2D and 3D cell cultures. PMID:27138252

  4. Comparison of 2D and 3D Numerical Models with Experiments of Tsunami Flow through a Built Environment

    NASA Astrophysics Data System (ADS)

    LeVeque, R. J.; Motley, M. R.

    2015-12-01

    A series of tsunami wave basin experiments of flow through a scale model of Seaside, Oregon have been used as validation data for a 2015 benchmarking workshop hosted by the National Tsunami Mitigation Program, which focused on better understanding the ability of tsunami models to predict flow velocities and inundation depths following a coastal inundation event. As researchers begin to assess the safety of coastal infrastructures, proper assessment of tsunami-induced forces on coastal structures is critical. Hydrodynamic forces on these structures are fundamentally proportional to the local momentum flux of the fluid, and experimental data included momentum flux measurements at many instrumented gauge locations. The GeoClaw tsunami model, which solves the two-dimensional shallow water equations, was compared against other codes during the benchmarking workshop, and more recently a three-dimensional computational fluid dynamics model using the open-source OpenFOAM software has been developed and results from this model are being compared with both the experimental data and the 2D GeoClaw results. In addition, the 3D model allows for computation of fluid forces on the faces of structures, permitting an investigation of the common use of momentum flux as a proxy for these forces. This work aims to assess the potential to apply these momentum flux predictions locally within the model to determine tsunami-induced forces on critical structures. Difficulties in working with these data sets and cross-model comparisons will be discussed. Ultimately, application of the more computationally efficient GeoClaw model, informed by the 3D OpenFOAM models, to predict forces on structures at the community scale can be expected to improve the safety and resilience of coastal communities.

  5. Trehalose effectiveness as a cryoprotectant in 2D and 3D cell cultures of human embryonic kidney cells.

    PubMed

    Hara, Jared; Tottori, Jordan; Anders, Megan; Dadhwal, Smritee; Asuri, Prashanth; Mobed-Miremadi, Maryam

    2017-05-01

    Post cryopreservation viability of human embryonic kidney (HEK) cells under two-dimensional (2D) and three-dimensional (3D) culture conditions was studied using trehalose as the sole cryoprotective agent. An L9 (3(4)) Taguchi design was used to optimize the cryoprotection cocktail seeding process prior to slow-freezing with the specific aim of maximizing cell viability measured 7 days post thaw, using the combinatorial cell viability and in-vitro cytotoxicity WST assay. At low (200 mM) and medium (800 mM) levels of trehalose concentration, encapsulation in alginate offered a greater protection to cryopreservation. However, at the highest trehalose concentration (1200 mM) and in the absence of the pre-incubation step, there was no statistical difference at the 95% CI (p = 0.0212) between the viability of the HEK cells under 2D and 3D culture conditions estimated to be 17.9 ± 4.6% and 14.0 ± 3.6%, respectively. A parallel comparison between cryoprotective agents conducted at the optimal levels of the L9 study, using trehalose, dimethylsulfoxide and glycerol in alginate microcapsules yielded a viability of 36.0 ± 7.4% for trehalose, in average 75% higher than the results associated with the other two cell membrane-permeating compounds. In summary, the effectiveness of trehalose has been demonstrated by the fact that 3D cell cultures can readily be equilibrated with trehalose before cryopreservation, thus mitigating the cytotoxic effects of glycerol and dimethylsulfoxide.

  6. The overexpression of SOX2 affects the migration of human teratocarcinoma cell line NT2/D1.

    PubMed

    Drakulic, Danijela; Vicentic, Jelena Marjanovic; Schwirtlich, Marija; Tosic, Jelena; Krstic, Aleksandar; Klajn, Andrijana; Stevanovic, Milena

    2015-03-01

    The altered expression of the SOX2 transcription factor is associated with oncogenic or tumor suppressor functions in human cancers. This factor regulates the migration and invasion of different cancer cells. In this study we investigated the effect of constitutive SOX2 overexpression on the migration and adhesion capacity of embryonal teratocarcinoma NT2/D1 cells derived from a metastasis of a human testicular germ cell tumor. We detected that increased SOX2 expression changed the speed, mode and path of cell migration, but not the adhesion ability of NT2/D1 cells. Additionally, we demonstrated that SOX2 overexpression increased the expression of the tumor suppressor protein p53 and the HDM2 oncogene. Our results contribute to the better understanding of the effect of SOX2 on the behavior of tumor cells originating from a human testicular germ cell tumor. Considering that NT2/D1 cells resemble cancer stem cells in many features, our results could contribute to the elucidation of the role of SOX2 in cancer stem cells behavior and the process of metastasis.

  7. Theoretical studies of effects of 2D plasmonic grating on electrical properties of organic solar cells

    NASA Astrophysics Data System (ADS)

    Sha, Wei E. I.; Choy, Wallace C. H.; Chew, Weng Cho

    2012-09-01

    Although various optical designs and physical mechanisms have been studied both experimentally and theoretically to improve the optical absorption of organic solar cells (OSCs) by incorporating metallic nanostructures, the effects of plasmonic nanostructures on the electrical properties of OSCs is still not fully understood. Hence, it is highly desirable to study the changes of electrical properties induced by plasmonic structures and the corresponding physics for OSCs. In this work, we develop a multiphysics model for plasmonic OSCs by solving the Maxwell's equations and semiconductor equations (Poisson, continuity, and drift-diffusion equations) with unified finite-difference method. Both the optical and electrical properties of OSCs incorporating a 2D metallic grating anode are investigated. For typical active polymer materials, low hole mobility, which is about one magnitude smaller than electron mobility, dominates the electrical property of OSCs. Since surface plasmon resonances excited by the metallic grating will produce concentrated near-field penetrated into the active polymer layer and decayed exponentially away from the metal-polymer interface, a significantly nonuniform and extremely high exciton generation rate is obtained near the grating. Interestingly, the reduced recombination loss and the increased open-circuit voltage can be achieved in plasmonic OSCs. The physical origin of the phenomena lies at direct hole collections to the metallic grating anode with a short transport path. In comparison with the plasmonic OSC, the hole transport in a multilayer planar OSC experiences a long transport path and time because the standard planar OSC has a high exciton generation rate at the transparent front cathode. The unveiled multiphysics is particularly helpful for designing high-performance plasmonic OSCs.

  8. An Implicit 2-D Depth-Averaged Finite-Volume Model of Flow and Sediment Transport in Coastal Waters

    DTIC Science & Technology

    2010-01-01

    Two-dimensional depth-averaged circulation model CMS- M2D : Version 3.0, Report 2: Sediment transport and morphology change, Technical Report ERDC/CHL TR...dimensional depth-averaged circulation model M2D : Version 2.0, Report 1, Technical documentation and user’s guide. ERDC/CHL TR-04-2, Coastal and Hydraulics

  9. Study on the Multi-phase Flow and Fluid Saturation in 2D Fractured Media by Light Transmission Technique

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Ye, S.; Wu, J.

    2013-12-01

    Immiscible two-phase flows in fractured media are encountered in many engineering processes such as recovery of oil and gas, exploitation of geothermal energy, and groundwater contamination by immiscible chemicals. A two-dimensional rough wall parallel plate fracture model was set up and light transmission method (LTM) was applied to study two-phase flow system in fractured media. The fracture model stood with up and bottom flow and no flow on other two sides. A charge-coupled device (CCD) camera was used to monitor the migration of DNAPL and gas bubbles in the fracture model. To simulate two-phase system in fracture media, air was injected into the water saturated cell (C1) through the middle of the bottom and NAPL was injected into another water saturated cell (C2) through the middle of the top of the cell. The results show LTM was an effective way in monitoring the migration of DNAPL and gas bubbles in the fracture models. Gas moved upwards quickly to the top of C1 in the way of air bubbles generated at the injection position and formed a continuous distribution. The migration of TCE was controlled by its own weight and fracture aperture. TCE migrated to large aperture firstly when moving downwards, and intruded into smaller one with accumulation of TCE. Light Intensity-Saturation Models (LISMs) were developed to estimate the gas or NAPL saturation in two-phase system. The volume amount of infiltration of gas bubbles or NAPL could be estimated from light intensities by LISMs. There were strong correlations between the added and calculated amounts of gas or TCE. It is feasible to use the light transmission method to characterize the movement and spatial distribution of gas or NAPL in fractured media.

  10. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.

    PubMed

    Chang, Chih-Jung; Chen, Yi-Yuan M; Lu, Chia-Chen; Lin, Chuan-Sheng; Martel, Jan; Tsai, Sheng-Hui; Ko, Yun-Fei; Huang, Tsung-Teng; Ojcius, David M; Young, John D; Lai, Hsin-Chih

    2014-04-01

    Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

  11. Documentation of computer program VS2D to solve the equations of fluid flow in variably saturated porous media

    USGS Publications Warehouse

    Lappala, E.G.; Healy, R.W.; Weeks, E.P.

    1987-01-01

    This report documents FORTRAN computer code for solving problems involving variably saturated single-phase flow in porous media. The flow equation is written with total hydraulic potential as the dependent variable, which allows straightforward treatment of both saturated and unsaturated conditions. The spatial derivatives in the flow equation are approximated by central differences, and time derivatives are approximated either by a fully implicit backward or by a centered-difference scheme. Nonlinear conductance and storage terms may be linearized using either an explicit method or an implicit Newton-Raphson method. Relative hydraulic conductivity is evaluated at cell boundaries by using either full upstream weighting, the arithmetic mean, or the geometric mean of values from adjacent cells. Nonlinear boundary conditions treated by the code include infiltration, evaporation, and seepage faces. Extraction by plant roots that is caused by atmospheric demand is included as a nonlinear sink term. These nonlinear boundary and sink terms are linearized implicitly. The code has been verified for several one-dimensional linear problems for which analytical solutions exist and against two nonlinear problems that have been simulated with other numerical models. A complete listing of data-entry requirements and data entry and results for three example problems are provided. (USGS)

  12. NKG2D stimulation of CD8+ T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice.

    PubMed

    Kavazović, Inga; Lenartić, Maja; Jelenčić, Vedrana; Jurković, Slaven; Lemmermann, Niels A W; Jonjić, Stipan; Polić, Bojan; Wensveen, Felix M

    2017-04-04

    NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8(+) T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8(+) T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8(+) T-cell formation. NKG2D-deficiency that is restricted to murine CD8(+) T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8(+) T cells via the Dap10 signaling pathway. T-cell development, homing and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T-cell receptor stimuli were used. Transfer of antigen-specific CD8(+) T cells demonstrated that NKG2D-deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D-deficient cells to produce cytokines could be overcome with injection of IL-15 super-agonist during priming. In summary, our data shows that NKG2D has a non-redundant role in priming of CD8(+) T cells to produce antiviral cytokines. Upon viral infection, classical Dendritic cells induce expression of the NKG2D ligand H60. NKG2D stimulation during priming enhances the ability of CD8 T cells to produce cytokines but not increases cytotoxic potential upon T cell receptor engagement in the periphery. This article is protected by copyright. All rights reserved.

  13. A Two-Dimensional Difference Gel Electrophoresis (2D-DIGE) Protocol for Studies of Neural Precursor Cells.

    PubMed

    Guest, Paul C

    2017-01-01

    This chapter describes the basics of two-dimensional difference gel electrophoresis (2D-DIGE) for multiplex analysis of up to distinct proteomes. The example given describes the analysis of undifferentiated and differentiated neural precursor cells labelled with fluorescent Cy3 and Cy5 dyes in comparison to a pooled standard labelled with Cy2. After labelling, the proteomes are mixed together and electrophoresed on the same 2D gels. Scanning the gels at wavelengths specific for each dye allows direct overlay of the two different proteomes and the differences in abundance of specific protein spots can be determined through comparison to the pooled standard.

  14. Signal Factors Secreted by 2D and Spheroid Mesenchymal Stem Cells and by Cocultures of Mesenchymal Stem Cells Derived Microvesicles and Retinal Photoreceptor Neurons

    PubMed Central

    Mao, Mao; Zhou, Liang

    2017-01-01

    We aim to identify levels of signal factors secreted by MSCs cultured in 2D monolayers (2D-MSCs), spheroids (spheroids MSCs), and cocultures of microvesicles (MVs) derived from 2D-MSCs or spheroid MSCs and retinal photoreceptor neurons. We seeded 2D-MSCs, spheroid MSCs, and cells derived from spheroids MSCs at equal numbers. MVs isolated from all 3 culture conditions were incubated with 661W cells. Levels of 51 signal factors in conditioned medium from those cultured conditions were quantified with bead-based assay. We found that IL-8, IL-6, and GROα were the top three most abundant signal factors. Moreover, compared to 2D-MSCs, levels of 11 cytokines and IL-2Rα were significantly increased in conditioned medium from spheroid MSCs. Finally, to test if enhanced expression of these factors reflects altered immunomodulating activities, we assessed the effect of 2D-MSC-MVs and 3D-MSC-MVs on CD14+ cell chemoattraction. Compared to 2D-MSC-MVs, 3D-MSC-MVs significantly decreased the chemotactic index of CD14+ cells. Our results suggest that spheroid culture conditions improve the ability of MSCs to selectively secrete signal factors. Moreover, 3D-MSC-MVs also possessed an enhanced capability to promote signal factors secretion compared to 2D-MSC-MVs and may possess enhanced immunomodulating activities and might be a better regenerative therapy for retinal degenerative diseases. PMID:28194184

  15. 2D/3D perovskite hybrids as moisture-tolerant and efficient light absorbers for solar cells.

    PubMed

    Ma, Chaoyan; Leng, Chongqian; Ji, Yixiong; Wei, Xingzhan; Sun, Kuan; Tang, Linlong; Yang, Jun; Luo, Wei; Li, Chaolong; Deng, Yunsheng; Feng, Shuanglong; Shen, Jun; Lu, Shirong; Du, Chunlei; Shi, Haofei

    2016-11-03

    The lifetime and power conversion efficiency are the key issues for the commercialization of perovskite solar cells (PSCs). In this paper, the development of 2D/3D perovskite hybrids (CA2PbI4/MAPbIxCl3-x) was firstly demonstrated to be a reliable method to combine their advantages, and provided a new concept for achieving both stable and efficient PSCs through the hybridization of perovskites. 2D/3D perovskite hybrids afforded significantly-improved moisture stability of films and devices without encapsulation in a high humidity of 63 ± 5%, as compared with the 3D perovskite (MAPbIxCl3-x). The 2D/3D perovskite-hybrid film did not undergo any degradation after 40 days, while the 3D perovskite decomposed completely under the same conditions after 8 days. The 2D/3D perovskite-hybrid device maintained 54% of the original efficiency after 220 hours, whereas the 3D perovskite device lost all the efficiency within only 50 hours. Moreover, the 2D/3D perovskite hybrid achieved comparable device performances (PCE: 13.86%) to the 3D perovskite (PCE: 13.12%) after the optimization of device fabrication conditions.

  16. Flow field design development using the segmented cell approach

    SciTech Connect

    Bender, G.; Ramsey, J. C.

    2002-01-01

    We report on fuel cell flow-field development employing two-dimensional computational fluid dynamics (2-D CFD). Simulation of the flow distribution of a parallel channel flow-field, with a simple one-channel manifold, predicted inhomogeneous performance distribution within the cell. Further modeling, focusing on modification of the inlet and outlet flow fields, was used to predict a more homogeneous flow distribution in the flow-field. Attempts were made to verify the theoretical predictions experimentally by application of the segmented cell system. Measurements of the current distribution and CO transient response supported the 2-D CFD predictions. However, the margin of error between predicted and experimental results was considered insufficient to be of practical use. Future work will involve the evaluation of 3-D CFD to achieve the appropriate level of accuracy.

  17. An MEK-cofilin signalling module controls migration of human T cells in 3D but not 2D environments.

    PubMed

    Klemke, Martin; Kramer, Elisabeth; Konstandin, Mathias H; Wabnitz, Guido H; Samstag, Yvonne

    2010-09-01

    T cells infiltrate peripheral tissues to execute immunosurveillance and effector functions. For this purpose, T cells first migrate on the two-dimensional (2D) surface of endothelial cells to undergo transendothelial migration. Then they change their mode of movement to undergo migration within the three-dimensional (3D)-extracellular matrix of the infiltrated tissue. As yet, no molecular mechanisms are known, which control migration exclusively in either 2D or 3D environments. Here, we describe a signalling module that controls T-cell chemotaxis specifically in 3D environments. In chemotaxing T cells, Ras activity is spatially restricted to the lamellipodium. There, Ras initiates activation of MEK, which in turn inhibits LIM-kinase 1 activity, thereby allowing dephosphorylation of the F-actin-remodelling protein cofilin. Interference with this MEK-cofilin module by either inhibition of MEK or by knockdown of cofilin reduces speed and directionality of chemotactic migration in 3D-extracellular matrices, but not on 2D substrates. This MEK-cofilin module may have an important function in the tissue positioning of T cells during an immune response.

  18. P02.04MICRORNA-MEDIATED DOWN-REGULATION OF NKG2D LIGAND EXPRESSION REDUCES GLIOMA CELL IMMUNOGENICITY

    PubMed Central

    Codo, P.; Weller, M.; Meister, G.; Szabo, E.; Steinle, A.; Wolter, M.; Reifenberger, G.; Roth, P.

    2014-01-01

    Glioblastoma is a primary brain tumor with a dismal prognosis despite comprehensive therapeutic regimens. It is characterized by diffuse infiltration of the surrounding healthy brain tissue, well-adapted to hypoxic conditions and regarded as paradigmatic for tumor-associated immunosuppression. One of the major activating receptors of natural killer (NK) cells is NKG2D. It binds to at least 8 ligands (NKG2DL) which are induced after malignant transformation and cellular stress. Regulation of NKG2DL expression may be affected by endogenous RNA molecules known as microRNA (miRNA). Here, we aimed at characterizing the role of miRNA in the control of NKG2DL expression in glioma cells. We selected 6 miRNA that were described or predicted to target NKG2DL. Three of the miRNA candidates, miR-20a, miR-93 and miR-106b, were expressed in glioma cell lines and were also detected in glioblastoma tissue specimens. Silencing of these miRNA with locked nucleic acid (LNA) molecules resulted in an up-regulation of NKG2DL cell surface levels which translated into increased sensitivity to immune cell killing. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced immune cell lysis upon miRNA silencing was mediated through the NKG2D system. We conclude that the expression of several miRNA may contribute to the immune escape of glioma cells at the level of the NKG2D system. Therapeutic targeting of miRNA that regulate NKG2DL levels may therefore represent a promising approach to allow for more potent immune responses against glioblastoma.

  19. Influence of basement membrane proteins and endothelial cell-derived factors on the morphology of human fetal-derived astrocytes in 2D.

    PubMed

    Levy, Amanda F; Zayats, Maya; Guerrero-Cazares, Hugo; Quiñones-Hinojosa, Alfredo; Searson, Peter C

    2014-01-01

    Astrocytes are the most prevalent type of glial cell in the brain, participating in a variety of diverse functions from regulating cerebral blood flow to controlling synapse formation. Astrocytes and astrocyte-conditioned media are widely used in models of the blood-brain barrier (BBB), however, very little is known about astrocyte culture in 2D. To test the hypothesis that surface coating and soluble factors influence astrocyte morphology in 2D, we quantitatively analyzed the morphology of human fetal derived astrocytes on glass, matrigel, fibronectin, collagen IV, and collagen I, and after the addition soluble factors including platelet-derived growth factor (PDGF), laminin, basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF). Matrigel surface coatings, as well as addition of leukemia inhibitory factor (LIF) to the media, were found to have the strongest effects on 2D astrocyte morphology, and may be important in improving existing BBB models. In addition, the novel set of quantitative parameters proposed in this paper provide a test for determining the influence of compounds on astrocyte morphology, both to screen for new endothelial cell-secreted factors that influence astrocytes, and to determine in a high-throughput way which factors are important for translation to more complex, 3D BBB models.

  20. Electric field-controlled directed migration of neural progenitor cells in 2D and 3D environments.

    PubMed

    Meng, Xiaoting; Li, Wenfei; Young, Fraser; Gao, Runchi; Chalmers, Laura; Zhao, Min; Song, Bing

    2012-02-16

    Endogenous electric fields (EFs) occur naturally in vivo and play a critical role during tissue/organ development and regeneration, including that of the central nervous system(1,2). These endogenous EFs are generated by cellular regulation of ionic transport combined with the electrical resistance of cells and tissues. It has been reported that applied EF treatment can promote functional repair of spinal cord injuries in animals and humans(3,4). In particular, EF-directed cell migration has been demonstrated in a wide variety of cell types(5,6), including neural progenitor cells (NPCs)(7,8). Application of direct current (DC) EFs is not a commonly available technique in most laboratories. We have described detailed protocols for the application of DC EFs to cell and tissue cultures previously(5,11). Here we present a video demonstration of standard methods based on a calculated field strength to set up 2D and 3D environments for NPCs, and to investigate cellular responses to EF stimulation in both single cell growth conditions in 2D, and the organotypic spinal cord slice in 3D. The spinal cordslice is an ideal recipient tissue for studying NPC ex vivo behaviours, post-transplantation, because the cytoarchitectonic tissue organization is well preserved within these cultures(9,10). Additionally, this ex vivo model also allows procedures that are not technically feasible to track cells in vivo using time-lapse recording at the single cell level. It is critically essential to evaluate cell behaviours in not only a 2D environment, but also in a 3D organotypic condition which mimicks the in vivo environment. This system will allow high-resolution imaging using cover glass-based dishes in tissue or organ culture with 3D tracking of single cell migration in vitro and ex vivo and can be an intermediate step before moving onto in vivo paradigms.

  1. STAT3 contributes to NK cell recognition by modulating expression of NKG2D ligands in adriamycin-resistant K562/AO2 cells.

    PubMed

    Cai, Xiaohui; Lu, Xuzhang; Jia, Zhuxia; Zhang, Xiuwen; Han, Wenmin; Rong, Xiao; Ma, Lingdi; Zhou, Min; Chen, Baoan

    2015-11-01

    Leukemic cells can survive after chemotherapy by acquisition of multidrug resistance genes, but other phenotypes related to escape from immune recognition remain elusive. Adriamycin-resistant K562/AO2 cells are less susceptible to elimination by NK cells compared with wild type K562 cells due to lower expression of NKG2D ligands. Treatment of K562/AO2 cells with STAT3 inhibitor VII resulted in reduced expression of multidrug resistance gene P-glycoprotein, and up-regulation of NKG2D ligands on K562/AO2 cells. Meanwhile, K562/AO2 cells treated with STAT3 inhibitor proliferated less and were more susceptible to killing by NK cells than untreated K562/AO2 cells. The enhanced cytotoxicity of NK cells against K562/AO2 cells was partly blocked by treatment of NK cells with anti-NKG2D antibodies. These data suggest that STAT3 contributes to NK cell recognition by modulating NKG2D ligands in K562/AO2 cells, which may a mechanism by which cells survive and cause relapse of leukemia.

  2. The 2D method for determining the temperatures field of the gas flow at the outlet of a multi-channel heat exchanger

    NASA Astrophysics Data System (ADS)

    Slesareva, E. Yu; Elistratov, S. L.; Ovchinnikov, V. V.

    2016-10-01

    The method for experimental determination of energy efficiency in the multichannel heat exchanger was tested. The visualization of a temperatures field has been performed to determine the thermal structure of gas flows with the use of fast-response fine- meshed wire. Thermograms of the temperature fields of the multi-channels assembly at the outlet were registered by thermal imaging camera. Results show that the 2D method provides a sufficient time resolution for the temperature field for the steady-state gas flow regime, heat generation, and nonsteady regime. The 2D method allows us to determine the gas stream parameters at the channel outlet in real time, which are necessary for determining the efficiency of the heat exchanger. Qualitative and quantitative characters of temperature changes in the thermograms are consistent with modern physical understanding of the gas flow in channels.

  3. NKG2D- and T-cell receptor-dependent lysis of malignant glioma cell lines by human γδ T cells: Modulation by temozolomide and A disintegrin and metalloproteases 10 and 17 inhibitors

    PubMed Central

    Chitadze, Guranda; Lettau, Marcus; Luecke, Stefanie; Wang, Ting; Janssen, Ottmar; Fürst, Daniel; Mytilineos, Joannis; Wesch, Daniela; Oberg, Hans-Heinrich; Held-Feindt, Janka; Kabelitz, Dieter

    2016-01-01

    ABSTRACT The interaction of the MHC class I-related chain molecules A and B (MICA and MICB) and UL-16 binding protein (ULBP) family members expressed on tumor cells with the corresponding NKG2D receptor triggers cytotoxic effector functions in NK cells and γδ T cells. However, as a mechanism of tumor immune escape, NKG2D ligands (NKG2DLs) can be released from the cell surface. In this study, we investigated the NKG2DL system in different human glioblastoma (GBM) cell lines, the most lethal brain tumor in adults. Flow cytometric analysis and ELISA revealed that despite the expression of various NKG2DLs only ULBP2 is released as a soluble protein via the proteolytic activity of “a disintegrin and metalloproteases” (ADAM) 10 and 17. Moreover, we report that temozolomide (TMZ), a chemotherapeutic agent in clinical use for the treatment of GBM, increases the cell surface expression of NKG2DLs and sensitizes GBM cells to γδ T cell-mediated lysis. Both NKG2D and the T-cell receptor (TCR) are involved. The cytotoxic activity of γδ T cells toward GBM cells is strongly enhanced in a TCR-dependent manner by stimulation with pyrophosphate antigens. These data clearly demonstrate the complexity of mechanisms regulating NKG2DL expression in GBM cells and further show that treatment with TMZ can increase the immunogenicity of GBM. Thus, TMZ might enhance the potential of the adoptive transfer of ex vivo expanded γδ T cells for the treatment of malignant glioblastoma. PMID:27141377

  4. Vinculin Regulates Directionality and Cell Polarity in 2D, 3D Matrix and 3D Microtrack Migration.

    PubMed

    Rahman, Aniqua; Carey, Shawn P; Kraning-Rush, Casey M; Goldblatt, Zachary E; Bordeleau, Francois; Lampi, Marsha C; Lin, Deanna Y; García, Andrés J; Reinhart-King, Cynthia A

    2016-03-09

    During metastasis, cells can use proteolytic activity to form tube-like "microtracks" within the extracellular matrix (ECM). Using these microtracks, cells can migrate unimpeded through the stroma. To investigate the molecular mechanisms of microtrack migration, we developed an in vitro 3D micromolded collagen platform. When in microtracks, cells tend to migrate unidirectionally. Since focal adhesions are the primary mechanism by which cells interact with the ECM, we examined the roles of several focal adhesion molecules in driving unidirectional motion. Vinculin knockdown results in the repeated reversal of migration direction compared with control cells. Tracking the position of the Golgi centroid relative to the position of the nucleus centroid reveals that vinculin knockdown disrupts cell polarity in microtracks. Vinculin also directs migration on 2D substrates and in 3D uniform collagen matrices, indicated by reduced speed, shorter net displacement and decreased directionality in vinculin-deficient cells. In addition, vinculin is necessary for Focal Adhesion Kinase (FAK) activation in 3D as vinculin knockdown results in reduced FAK activation in both 3D uniform collagen matrices and microtracks, but not on 2D substrates, and accordingly, FAK inhibition halts cell migration in 3D microtracks. Together, these data indicate that vinculin plays a key role in polarization during migration.

  5. Collagen esterification enhances the function and survival of pancreatic β cells in 2D and 3D culture systems

    SciTech Connect

    Ko, Jae Hyung; Kim, Yang Hee; Jeong, Seong Hee; Lee, Song; Park, Si-Nae; Shim, In Kyong; Kim, Song Cheol

    2015-08-07

    Collagen, one of the most important components of the extracellular matrix (ECM), may play a role in the survival of pancreatic islet cells. In addition, chemical modifications that change the collagen charge profile to a net positive charge by esterification have been shown to increase the adhesion and proliferation of various cell types. The purpose of this study was to characterize and compare the effects of native collagen (NC) and esterified collagen (EC) on β cell function and survival. After isolation by the collagenase digestion technique, rat islets were cultured with NC and EC in 2 dimensional (2D) and 3 dimensional (3D) environments for a long-term duration in vitro. The cells were assessed for islet adhesion, morphology, viability, glucose-induced insulin secretion, and mRNA expression of glucose metabolism-related genes, and visualized by scanning electron microscopy (SEM). Islet cells attached tightly in the NC group, but islet cell viability was similar in both the NC and EC groups. Glucose-stimulated insulin secretion was higher in the EC group than in the NC group in both 2D and 3D culture. Furthermore, the mRNA expression levels of glucokinase in the EC group were higher than those in the NC group and were associated with glucose metabolism and insulin secretion. Finally, SEM observation confirmed that islets had more intact component cells on EC sponges than on NC sponges. These results indicate that modification of collagen may offer opportunities to improve function and viability of islet cells. - Highlights: • We changed the collagen charge profile to a net positive charge by esterification. • Islets cultured on esterified collagen improved survival in both 2D and 3D culture. • Islets cultured on esterified collagen enhanced glucose-stimulated insulin release. • High levels of glucokinase mRNA may be associated with increased insulin release.

  6. Enhanced photovoltaic properties of dye-sensitized solar cell based on ultrathin 2D TiO2 nanostructures

    NASA Astrophysics Data System (ADS)

    Zhang, Putao; Hu, Zhiqiang; Wang, Yan; Qin, Yiying; Sun, Xiao Wei; Li, Wenqin; Wang, Jinmin

    2016-04-01

    Ultrathin two-dimensional (2D) TiO2 nanostructures with a thickness of ∼5 nm and a specific surface area of 257.3 m2 g-1 were synthesized by a hydrothermal process. The 2D TiO2 nanostructures and P25 nanoparticles were introduced as scattering layer and underlayer to construct a bi-layer photoanode in a dye-sensitized solar cell (DSSC). The as-prepared DSSC exhibits an enhanced power conversion efficiency (5.14%), which is 23.9% higher than that of pure P25 DSSC (4.15%). Electrochemical impedance spectroscopy (EIS) indicates that DSSC based on P25-2D TiO2 nanostructures shows a longer life time and a larger recombination resistance. The enhanced photovoltaic properties are attributed to the excellent light scattering capability and high capacity for dye adsorption of 2D TiO2 nanostructures, which makes them a promising candidate as an efficient scattering layer in high-performance DSSCs.

  7. 2D protrusion but not motility predicts growth factor-induced cancer cell migration in 3D collagen.

    PubMed

    Meyer, Aaron S; Hughes-Alford, Shannon K; Kay, Jennifer E; Castillo, Amalchi; Wells, Alan; Gertler, Frank B; Lauffenburger, Douglas A

    2012-06-11

    Growth factor-induced migration is a critical step in the dissemination and metastasis of solid tumors. Although differences in properties characterizing cell migration on two-dimensional (2D) substrata versus within three-dimensional (3D) matrices have been noted for particular growth factor stimuli, the 2D approach remains in more common use as an efficient surrogate, especially for high-throughput experiments. We therefore were motivated to investigate which migration properties measured in various 2D assays might be reflective of 3D migratory behavioral responses. We used human triple-negative breast cancer lines stimulated by a panel of receptor tyrosine kinase ligands relevant to mammary carcinoma progression. Whereas 2D migration properties did not correlate well with 3D behavior across multiple growth factors, we found that increased membrane protrusion elicited by growth factor stimulation did relate robustly to enhanced 3D migration properties of the MDA-MB-231 and MDA-MB-157 lines. Interestingly, we observed this to be a more reliable relationship than cognate receptor expression or activation levels across these and two additional mammary tumor lines.

  8. Delayed Feedback Control of 2D Roll-Cell by Pulsed Jets

    NASA Astrophysics Data System (ADS)

    Ogawara, Kakuji

    1998-11-01

    Experimental study and numerical experiments were conducted to examine applicability of Pyragas' delayed feedback(DFB) control theory for active control of fluid flow. Although many attempts of turbulence active control have been made, most of those experimental studies experience "out of control" state in the case of using larger feedback gain. In the present study, we assume this "out of control" state as Chaos, and apply chaos control theory to prevent the flow field from falling into "out of control" state. Experiments were carried out for low Reynolds number oil flow in a rectangle thin container, whose aspect ratio is 6:1:0.5. Two pulsed jets were used as actuator in order to keep the circulation of the flow in container constant. Fluid flow was observed using Particle Image Velocimetry (PIV) technology and the flow state was estimated by moving least square (MLS) method. As a result, we found that Pyragas control was effective to prevent chaos for active control fo fluid flow. Numerical simulations were also carried out by using the coupled map lattice(CML). CML is known as a simple model with the essential feature of spatio-temporal chaos. DFB control was applied for CML to examine possibility of active control of turbulence. Simulating results show that the present method can stabilize the whole system of CML.

  9. The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3

    PubMed Central

    Ni, Lulu; Wang, Lixin; Yao, Chao; Ni, Zhongya; Liu, Fei; Gong, Chenyuan; Zhu, Xiaowen; Yan, Xuewei; Watowich, Stephanie S.; Lee, Dean A.; Zhu, Shiguo

    2017-01-01

    NKG2D is a major activating receptor of NK cells and plays a critical role in tumor immunosurveillance. NKG2D expression in NK cells is inhibited by the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and enhanced by the narrow-spectrum HDAC inhibitor entinostat. We previously demonstrated that entinostat enhanced NKG2D transcription by increasing acetylation of Histones H3 and H4. However, the mechanism by which VPA reduces NKG2D expression in NK cells is not known. We have also shown that NKG2D transcription is regulated by STAT3 phosphorylation. In this study, we investigated regulation of NKG2D expression in NK cells by VPA and entinostat by assessing protein expression, phosphorylation, and interaction of HDACs and STAT3. We find that VPA selectively inhibits STAT3 tyrosine705 phosphorylation, but entinostat does not. STAT3 complexes with HDAC3, and HDAC3 inhibition represses STAT3 phosphorylation and therefore NKG2D expression. NK cells from STAT3 wild-type mice downregulate NKG2D in response to VPA, but not NK cells from STAT3 knockout mice. These results show that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. PMID:28338101

  10. Engagement of TLR3, TLR7, and NKG2D regulate IFN-gamma secretion but not NKG2D-mediated cytotoxicity by human NK cells stimulated with suboptimal doses of IL-12.

    PubMed

    Girart, María V; Fuertes, Mercedes B; Domaica, Carolina I; Rossi, Lucas E; Zwirner, Norberto W

    2007-09-15

    NK cells express different TLRs, such as TLR3, TLR7, and TLR9, but little is known about their role in NK cell stimulation. In this study, we used specific agonists (poly(I:C), loxoribine, and synthetic oligonucleotides containing unmethylated CpG sequences to stimulate human NK cells without or with suboptimal doses of IL-12, IL-15, or IFN-alpha, and investigated the secretion of IFN-gamma, cytotoxicity, and expression of the activating receptor NKG2D. Poly(I:C) and loxoribine, in conjunction with IL-12, but not IL-15, triggered secretion of IFN-gamma. Inhibition of IFN-gamma secretion by chloroquine suggested that internalization of the TLR agonists was necessary. Also, secretion of IFN-gamma was dependent on MEK1/ERK, p38 MAPK, p70(S6) kinase, and NF-kappaB, but not on calcineurin. IFN-alpha induced a similar effect, but promoted lesser IFN-gamma secretion. However, cytotoxicity (51Cr release assays) against MHC class I-chain related A (MICA)- and MICA+ tumor targets remained unchanged, as well as the expression of the NKG2D receptor. Excitingly, IFN-gamma secretion was significantly increased when NK cells were stimulated with poly(I:C) or loxoribine and IL-12, and NKG2D engagement was induced by coculture with MICA+ tumor cells in a PI3K-dependent manner. We conclude that resting NK cells secrete high levels of IFN-gamma in response to agonists of TLR3 or TLR7 and IL-12, and this effect can be further enhanced by costimulation through NKG2D. Hence, integration of the signaling cascades that involve TLR3, TLR7, IL-12, and NKG2D emerges as a critical step to promote IFN-gamma-dependent NK cell-mediated effector functions, which could be a strategy to promote Th1-biased immune responses in pathological situations such as cancer.

  11. TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells.

    PubMed

    Eisele, Günter; Wischhusen, Jörg; Mittelbronn, Michel; Meyermann, Richard; Waldhauer, Inja; Steinle, Alexander; Weller, Michael; Friese, Manuel A

    2006-09-01

    NKG2D ligands (NKG2DL) are expressed by infected and transformed cells. They transmit danger signals to NKG2D-expressing immune cells, leading to lysis of NKG2DL-expressing cells. We here report that the NKG2DL MHC class I-chain-related molecules A and B (MICA/B) and UL16-binding proteins (ULBP) 1-3 are expressed in human brain tumours in vivo, while expression levels are low or undetectable in normal brain. MICA and ULBP2 expression decrease with increasing WHO grade of malignancy, while MICB and ULBP1 are expressed independently of tumour grade. We further delineate two independent mechanisms that can explain these expression patterns: (i) transforming growth factor-beta (TGF-beta) is upregulated during malignant progression and selectively downregulates MICA, ULBP2 and ULBP4 expression, while MICB, ULBP1 and ULBP3 are unaffected. (ii) Cleavage of MICA and ULBP2 is reduced by inhibition of metalloproteinases (MP), whereas no changes in the expression levels of other NKG2DL were detected. Consequently, NKG2DL-dependent NK cell-mediated lysis is enhanced by depletion of TGF-beta or inhibition of MP. Thus, escape from NKG2D-mediated immune surveillance of malignant gliomas in vivo may be promoted by the inhibition of MICA and ULBP2 expression via an autocrine TGF-beta loop and by MP-dependent shedding from the cell surface. Loss of MICA and ULBP2, in contrast to other NKG2DL, may be particularly important in glioma immune escape, and differential regulation of human NKG2DL expression is part of the immunosuppressive properties of human malignant glioma cells.

  12. A microfluidic device for 2D to 3D and 3D to 3D cell navigation

    NASA Astrophysics Data System (ADS)

    Shamloo, Amir; Amirifar, Leyla

    2016-01-01

    Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be obtained by diffusion. The device was designed by a numerical simulation so that the uniformity of the concentration gradients throughout the cell culture chamber was obtained. Adult neural cells were cultured within this device and they showed different branching and axonal navigation phenotypes within varying nerve growth factor (NGF) concentration profiles. Neural stem cells were also cultured within varying collagen matrix densities while exposed to NGF concentrations and they experienced 3D to 3D collective migration. By generating vascular endothelial growth factor concentration gradients, adult human dermal microvascular endothelial cells also migrated in a 2D to 3D manner and formed a stable lumen within a specific collagen matrix density. It was observed that a minimum absolute concentration and concentration gradient were required to stimulate migration of all types of the cells. This device has the advantage of changing multiple parameters simultaneously and is expected to have wide applicability in cell studies.

  13. Nonrigid Registration of 2-D and 3-D Dynamic Cell Nuclei Images for Improved Classification of Subcellular Particle Motion

    PubMed Central

    Kim, Il-Han; Chen, Yi-Chun M.; Spector, David L.; Eils, Roland; Rohr, Karl

    2012-01-01

    The observed motion of subcellular particles in fluorescence microscopy image sequences of live cells is generally a superposition of the motion and deformation of the cell and the motion of the particles. Decoupling the two types of movements to enable accurate classification of the particle motion requires the application of registration algorithms. We have developed an intensity-based approach for nonrigid registration of multi-channel microscopy image sequences of cell nuclei. First, based on 3-D synthetic images we demonstrate that cell nucleus deformations change the observed motion types of particles and that our approach allows to recover the original motion. Second, we have successfully applied our approach to register 2-D and 3-D real microscopy image sequences. A quantitative experimental comparison with previous approaches for nonrigid registration of cell microscopy has also been performed. PMID:20840894

  14. Limbal melanocytes support limbal epithelial stem cells in 2D and 3D microenvironments.

    PubMed

    Dziasko, Marc A; Tuft, Stephen J; Daniels, Julie T

    2015-09-01

    Human limbal epithelial stem cells (LESCs) are essential for the maintenance of the corneal epithelium of the ocular surface. LESCs are located within limbal crypts between the palisades of Vogt in the limbus; the interface between the peripheral cornea and conjunctiva. The limbal crypts have been proposed as a LESC niche owing to their support of epithelial cells, which can form holoclone colonies in vitro. Closely associated with the limbal crypts is a concentrated population of melanocytes. The anatomical location and close proximity to putative LESC suggests that melanocytes might play a role in maintenance of these stem cells in the niche. The aim of this study was to assess the ability of human limbal melanocytes (hLM) to support the expansion of human limbal epithelial cells (LECs) in vitro as an indicator of functional cell-cell interaction. After observing that hLM co-localize with clusters of compact epithelial cells in the native limbal crypts, hLM were isolated from crypt-rich cadaveric limbal biopsies and used as feeders for the culture of LECs. Interestingly, LECs grown on mitotically active hLM were able to generate large epithelial colonies that contained small and compact cells with morphological stem cell characteristics. Immunocytochemistry revealed that LECs expanded on hLM were positive for the expression of the putative stem cell markers CK15, Bmi-1 and p63α and negative for the marker of terminal cell differentiation CK3. LECs and hLM were finally co-cultured on RAFT (real architecture for 3D tissue) collagen tissue equivalents. In 3D co-cultures, hLM promoted multi-layering of the epithelial sheet in which basal cells were maintained in an undifferentiated state. Taken together, these observations suggest melanocytes could play an important role in the maintenance of LESCs in the native human limbal stem cell niche.

  15. DNA demethylation and histone H3K9 acetylation determine the active transcription of the NKG2D gene in human CD8+ T and NK cells

    PubMed Central

    Fernández-Sánchez, Alba; Baragaño Raneros, Aroa; Carvajal Palao, Reyes; Sanz, Ana B.; Ortiz, Alberto; Ortega, Francisco; Suárez-Álvarez, Beatriz; López-Larrea, Carlos

    2013-01-01

    The human activating receptor NKG2D is mainly expressed by NK, NKT, γδ T and CD8+ T cells and, under certain conditions, by CD4+ T cells. This receptor recognizes a diverse family of ligands (MICA, MICB and ULBPs 1–6) leading to the activation of effector cells and triggering the lysis of target cells. The NKG2D receptor-ligand system plays an important role in the immune response to infections, tumors, transplanted graft and autoantigens. Elucidation of the regulatory mechanisms of NKG2D is therefore essential for therapeutic purposes. In this study, we speculate whether epigenetic mechanisms, such as DNA methylation and histone acetylation, participate in NKG2D gene regulation in T lymphocytes and NK cells. DNA methylation in the NKG2D gene was observed in CD4+ T lymphocytes and T cell lines (Jurkat and HUT78), while this gene was unmethylated in NKG2D-positive cells (CD8+ T lymphocytes, NK cells and NKL cell line) and associated with high levels of histone H3 lysine 9 acetylation (H3K9Ac). Treatment with the histone acetyltransferase (HAT) inhibitor curcumin reduces H3K9Ac levels in the NKG2D gene, downregulates NKG2D transcription and leads to a marked reduction in the lytic capacity of NKG2D-mediated NKL cells. These findings suggest that differential NKG2D expression in the different cell subsets is regulated by epigenetic mechanisms and that its modulation by epigenetic treatments might provide a new strategy for treating several pathologies. PMID:23235109

  16. The human NKG2D ligand ULBP2 can be expressed at the cell surface with or without a GPI anchor and both forms can activate NK cells

    PubMed Central

    Fernández-Messina, Lola; Ashiru, Omodele; Agüera-González, Sonia; Reyburn, Hugh T.; Valés-Gómez, Mar

    2011-01-01

    The activating immune receptor NKG2D binds to several stress-induced ligands that are structurally different. MHC-class-I-related chain (MIC) A/B molecules have a transmembrane domain, whereas most UL16 binding proteins (ULBPs) are glycosylphosphatidylinositol (GPI)-linked molecules. The significance of this variability in membrane anchors is unclear. Here, we demonstrate that ULBP2, but not ULBP1 or ULBP3, can reach the cell surface without the GPI modification. Several proteins are expressed at the cell surface as both transmembrane and GPI-linked molecules, either via alternative splicing or by the expression of linked genes. However, to our knowledge, ULBP2 is the first single mammalian cDNA that can be expressed as either a transmembrane or a GPI-anchored protein. The rate of maturation and the levels of cell surface expression of the non-GPI-linked form were lower than those of the GPI-linked ULBP2. Nonetheless, non-GPI ULBP2 was recognised by NKG2D and triggered NK cell cytotoxicity. These data show that differences in membrane attachment by NKG2D ligands are more important for regulation of their surface expression than for cytotoxic recognition by NKG2D and emphasise that detailed characterisation of the cell biology of individual NKG2D ligands will be necessary to allow targeted modulation of this system. PMID:21224393

  17. Characterization of the turbulent bistable flow regime of a 2 D bluff body wake disturbed by a small control cylinder

    NASA Astrophysics Data System (ADS)

    Parezanović, Vladimir; Monchaux, Romain; Cadot, Olivier

    2015-01-01

    A small control cylinder placed in a turbulent wake of a much larger 2 D bluff body can cause a significant increase in drag fluctuations. These fluctuations occur on timescales longer than the timescales of the vortex shedding. The critical positions of the control cylinder are highly localized. Ensemble averages of PIV acquisitions and pressure measurements at the base of the bluff body reveal a bistable wake regime. Long duration hot-wire measurements are used to characterize the states and the transition process. The results show that a stochastic process is responsible for the transitions between the two stable states.

  18. Identification of the wave speed and the second viscosity of cavitation flows with 2D RANS computations - Part I

    NASA Astrophysics Data System (ADS)

    Decaix, J.; Alligné, S.; Nicolet, C.; Avellan, F.; Münch, C.

    2015-12-01

    1D hydro-electric models are useful to predict dynamic behaviour of hydro-power plants. Regarding vortex rope and cavitation surge in Francis turbines, the 1D models require some inputs that can be provided by numerical simulations. In this paper, a 2D cavitating Venturi is considered. URANS computations are performed to investigate the dynamic behaviour of the cavitation sheet depending on the frequency variation of the outlet pressure. The results are used to calibrate and to assess the reliability of the 1D models.

  19. Surface Acoustic Waves (SAW)-Based Biosensing for Quantification of Cell Growth in 2D and 3D Cultures

    PubMed Central

    Wang, Tao; Green, Ryan; Nair, Rajesh Ramakrishnan; Howell, Mark; Mohapatra, Subhra; Guldiken, Rasim; Mohapatra, Shyam Sundar

    2015-01-01

    Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and therefore requires a parallel set-up of several replicates for time-lapse or dose–response studies. Thus, developing a non-invasive and touch-free detection of cell growth in longitudinal studies of 3D tumor spheroid cultures or of stem cell regeneration remains a major unmet need. Since surface acoustic waves (SAWs) permit mass loading-based biosensing and have been touted due to their many advantages including low cost, small size and ease of assembly, we examined the potential of SAW-biosensing to detect and quantify cell growth. Herein, we demonstrate that a shear horizontal-surface acoustic waves (SH-SAW) device comprising two pairs of resonators consisting of interdigital transducers and reflecting fingers can be used to quantify mass loading by the cells in suspension as well as within a 3D cell culture platform. A 3D COMSOL model was built to simulate the mass loading response of increasing concentrations of cells in suspension in the polydimethylsiloxane (PDMS) well in order to predict the characteristics and optimize the design of the SH-SAW biosensor. The simulated relative frequency shift from the two oscillatory circuit systems (one of which functions as control) were found to be concordant to experimental data generated with RAW264.7 macrophage and A549 cancer cells. In addition, results showed that SAW measurements per se did not affect viability of cells. Further, SH-SAW biosensing was applied to A549 cells cultured on a 3D electrospun nanofiber scaffold that generate tumor spheroids (tumoroids) and the results showed the device's ability to detect changes in tumor spheroid growth over the course of eight days. Taken together, these results demonstrate the use of SH-SAW device for detection and quantification of cell growth changes over time in 2D suspension cultures and in 3D cell

  20. Surface Acoustic Waves (SAW)-Based Biosensing for Quantification of Cell Growth in 2D and 3D Cultures.

    PubMed

    Wang, Tao; Green, Ryan; Nair, Rajesh Ramakrishnan; Howell, Mark; Mohapatra, Subhra; Guldiken, Rasim; Mohapatra, Shyam Sundar

    2015-12-19

    Detection and quantification of cell viability and growth in two-dimensional (2D) and three-dimensional (3D) cell cultures commonly involve harvesting of cells and therefore requires a parallel set-up of several replicates for time-lapse or dose-response studies. Thus, developing a non-invasive and touch-free detection of cell growth in longitudinal studies of 3D tumor spheroid cultures or of stem cell regeneration remains a major unmet need. Since surface acoustic waves (SAWs) permit mass loading-based biosensing and have been touted due to their many advantages including low cost, small size and ease of assembly, we examined the potential of SAW-biosensing to detect and quantify cell growth. Herein, we demonstrate that a shear horizontal-surface acoustic waves (SH-SAW) device comprising two pairs of resonators consisting of interdigital transducers and reflecting fingers can be used to quantify mass loading by the cells in suspension as well as within a 3D cell culture platform. A 3D COMSOL model was built to simulate the mass loading response of increasing concentrations of cells in suspension in the polydimethylsiloxane (PDMS) well in order to predict the characteristics and optimize the design of the SH-SAW biosensor. The simulated relative frequency shift from the two oscillatory circuit systems (one of which functions as control) were found to be concordant to experimental data generated with RAW264.7 macrophage and A549 cancer cells. In addition, results showed that SAW measurements per se did not affect viability of cells. Further, SH-SAW biosensing was applied to A549 cells cultured on a 3D electrospun nanofiber scaffold that generate tumor spheroids (tumoroids) and the results showed the device's ability to detect changes in tumor spheroid growth over the course of eight days. Taken together, these results demonstrate the use of SH-SAW device for detection and quantification of cell growth changes over time in 2D suspension cultures and in 3D cell

  1. [Detection of hybrid DQ molecules by the use of T cell clone and 2D-gel analyses].

    PubMed

    Hawkin, S

    1986-11-01

    The HLA-D region incorporates three subregions, DR, DQ and DP, encoding for three sets of Ia molecules. Whereas DR antigens consist of a constant alpha chain and an extremely polymorphic beta chain, both of alpha and beta chain of DQ antigens show moderate polymorphism. This indicated us the existence of hybrid HLA-DQ molecules in HLA-D heterozygous cells, resulting from the association of an alpha chain and a beta chain encoded by genes located on the two separate haplotypes. In this report, hybrid DQ antigens were demonstrated by using cytotoxic T cell-clone. A cytotoxic T cell clone, which was generated by mixed lymphocyte reaction against a lymphoblastoid B cell line, EBV-Fuk (HLA-DR1/4, DQw1/Wa), recognized only heterogenous lymphoblastoid B cell lines (HLA-DR1/4, DQw1/Wa). Cytotoxic T cell clone, however, didn't react with B cell lines which are homozygous for HLA-DR1, DQw1 or DR4/DQWa. This suggests the T cell clone recognized the hybrid DQ molecules expressed only on heterozygous cell lines. Further confirmation was obtained by inhibition test using monoclonal antibody and biochemically by 2-D gel analyses. Biological significance of hybrid DQ antigens were discussed.

  2. 2D Computational Fluid Dynamic Modeling of Human Ventricle System Based on Fluid-Solid Interaction and Pulsatile Flow.

    PubMed

    Masoumi, Nafiseh; Framanzad, F; Zamanian, Behnam; Seddighi, A S; Moosavi, M H; Najarian, S; Bastani, Dariush

    2013-01-01

    Many diseases are related to cerebrospinal fluid (CSF) hydrodynamics. Therefore, understanding the hydrodynamics of CSF flow and intracranial pressure is helpful for obtaining deeper knowledge of pathological processes and providing better treatments. Furthermore, engineering a reliable computational method is promising approach for fabricating in vitro models which is essential for inventing generic medicines. A Fluid-Solid Interaction (FSI)model was constructed to simulate CSF flow. An important problem in modeling the CSF flow is the diastolic back flow. In this article, using both rigid and flexible conditions for ventricular system allowed us to evaluate the effect of surrounding brain tissue. Our model assumed an elastic wall for the ventricles and a pulsatile CSF input as its boundary conditions. A comparison of the results and the experimental data was done. The flexible model gave better results because it could reproduce the diastolic back flow mentioned in clinical research studies. The previous rigid models have ignored the brain parenchyma interaction with CSF and so had not reported the back flow during the diastolic time. In this computational fluid dynamic (CFD) analysis, the CSF pressure and flow velocity in different areas were concordant with the experimental data.

  3. 2D Computational Fluid Dynamic Modeling of Human Ventricle System Based on Fluid-Solid Interaction and Pulsatile Flow

    PubMed Central

    Masoumi, Nafiseh; Framanzad, F.; Zamanian, Behnam; Seddighi, A.S.; Moosavi, M.H.; Najarian, S.; Bastani, Dariush

    2013-01-01

    Many diseases are related to cerebrospinal fluid (CSF) hydrodynamics. Therefore, understanding the hydrodynamics of CSF flow and intracranial pressure is helpful for obtaining deeper knowledge of pathological processes and providing better treatments. Furthermore, engineering a reliable computational method is promising approach for fabricating in vitro models which is essential for inventing generic medicines. A Fluid-Solid Interaction (FSI)model was constructed to simulate CSF flow. An important problem in modeling the CSF flow is the diastolic back flow. In this article, using both rigid and flexible conditions for ventricular system allowed us to evaluate the effect of surrounding brain tissue. Our model assumed an elastic wall for the ventricles and a pulsatile CSF input as its boundary conditions. A comparison of the results and the experimental data was done. The flexible model gave better results because it could reproduce the diastolic back flow mentioned in clinical research studies. The previous rigid models have ignored the brain parenchyma interaction with CSF and so had not reported the back flow during the diastolic time. In this computational fluid dynamic (CFD) analysis, the CSF pressure and flow velocity in different areas were concordant with the experimental data. PMID:25337330

  4. Fc-optimized NKG2D-Fc constructs induce NK cell antibody-dependent cellular cytotoxicity against breast cancer cells independently of HER2/neu expression status.

    PubMed

    Raab, Stefanie; Steinbacher, Julia; Schmiedel, Benjamin J; Kousis, Philaretos C; Steinle, Alexander; Jung, Gundram; Grosse-Hovest, Ludger; Salih, Helmut R

    2014-10-15

    The ability of NK cells to mediate Ab-dependent cellular cytotoxicity (ADCC) largely contributes to the clinical success of antitumor Abs, including trastuzumab, which is approved for the treatment of breast cancer with HER2/neu overexpression. Notably, only ∼25% of breast cancer patients overexpress HER2/neu. Moreover, HER2/neu is expressed on healthy cells, and trastuzumab application is associated with side effects. In contrast, the ligands of the activating immunoreceptor NKG2D (NKG2DL) are selectively expressed on malignant cells. In this study, we took advantage of the tumor-associated expression of NKG2DL by using them as target Ags for NKG2D-IgG1 fusion proteins optimized by amino acid exchange S239D/I332E in their Fc part. Compared to constructs with wild-type Fc parts, fusion proteins carrying the S239D/I332E modification (NKG2D-Fc-ADCC) mediated highly enhanced degranulation, ADCC, and IFN-γ production of NK cells in response to breast cancer cells. NKG2D-Fc-ADCC substantially enhanced NK reactivity also against HER2/neu-low targets that were unaffected by trastuzumab, as both compounds mediated their immunostimulatory effects in strict dependence of target Ag expression levels. Thus, in line with the hierarchically organized potential of the various activating receptors governing NK reactivity and due to its highly increased affinity to CD16, NKG2D-Fc-ADCC potently enhances NK cell reactivity despite the inevitable reduction of activating signals upon binding to NKG2DL. Due to the tumor-restricted expression of NKG2DL, NKG2D-Fc-ADCC may constitute an attractive means for immunotherapy especially of HER2/neu-low or -negative breast cancer.

  5. 2D modeling of silicon based thin film dual and triple junction solar cells

    NASA Astrophysics Data System (ADS)

    Xiao, Y. G.; Uehara, K.; Lestrade, M.; Li, Z. Q.; Li, Z. M. S.

    2009-08-01

    Based on Crosslight APSYS, thin film amorphous Si (a-Si:H)/microcrystalline (μc-Si) dual-junction (DJ) and a- Si:H/amorphous SiGe:H (a-SiGe:H)/μc-Si triple-junction (TJ) solar cells are modeled. Basic physical quantities like band diagrams, optical absorption and generation are obtained. Quantum efficiency and I-V curves for individual junctions are presented for current matching analyses. The whole DJ and TJ cell I-V curves are also presented and the results are discussed with respect to the top surface ZnO:Al TCO layer affinity. The interface texture effect is modeled with FDTD (finite difference time domain) module and results for top junction are presented. The modeling results give possible clues to achieve high efficiency for DJ and TJ thin film solar cells.

  6. VFLOW2D - A Vorte-Based Code for Computing Flow Over Elastically Supported Tubes and Tube Arrays

    SciTech Connect

    WOLFE,WALTER P.; STRICKLAND,JAMES H.; HOMICZ,GREGORY F.; GOSSLER,ALBERT A.

    2000-10-11

    A numerical flow model is developed to simulate two-dimensional fluid flow past immersed, elastically supported tube arrays. This work is motivated by the objective of predicting forces and motion associated with both deep-water drilling and production risers in the oil industry. This work has other engineering applications including simulation of flow past tubular heat exchangers or submarine-towed sensor arrays and the flow about parachute ribbons. In the present work, a vortex method is used for solving the unsteady flow field. This method demonstrates inherent advantages over more conventional grid-based computational fluid dynamics. The vortex method is non-iterative, does not require artificial viscosity for stability, displays minimal numerical diffusion, can easily treat moving boundaries, and allows a greatly reduced computational domain since vorticity occupies only a small fraction of the fluid volume. A gridless approach is used in the flow sufficiently distant from surfaces. A Lagrangian remap scheme is used near surfaces to calculate diffusion and convection of vorticity. A fast multipole technique is utilized for efficient calculation of velocity from the vorticity field. The ability of the method to correctly predict lift and drag forces on simple stationary geometries over a broad range of Reynolds numbers is presented.

  7. The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance

    PubMed Central

    Breslin, Susan; O'Driscoll, Lorraine

    2016-01-01

    Solid tumours naturally grow in 3D wherein the spatial arrangement of cells affects how they interact with each other. This suggests that 3D cell culture may mimic the natural in vivo setting better than traditional monolayer (2D) cell culture, where cells are grown attached to plastic. Here, using HER2-positive breast cancer cell lines as models (BT474, HCC1954, EFM192A), the effects of culturing cells in 3D using the poly-HEMA method compared to 2D cultures were assessed in terms of cellular viability, response/resistance to anti-cancer drugs, protein expression and enzyme activity. Scanning electron microscopy showed the morphology of cells in 3D to be substantially different to those cultured in 2D. Cell viability in 3D cells was substantially lower than that of cells in 2D cultures, while 3D cultures were more resistant to the effects of HER-targeted (neratinib) and classical chemotherapy (docetaxel) drugs. Expression of proteins involved in cell survival, transporters associated with drug resistance and drug targets were increased in 3D cultures. Finally, activity of drug metabolising enzyme CYP3A4 was substantially increased in 3D compared to 2D cultures. Together this data indicates that the biological information represented by 3D and 2D cell cultures is substantially different i.e. 3D cell cultures demonstrate higher innate resistance to anti-cancer drugs compared to 2D cultures, which may be facilitated by the altered receptor proteins, drug transporters and metabolising enzyme activity. This highlights the importance of considering 3D in addition to 2D culture methods in pre-clinical studies of both newer targeted and more traditional anti-cancer drugs. PMID:27304190

  8. The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance.

    PubMed

    Breslin, Susan; O'Driscoll, Lorraine

    2016-07-19

    Solid tumours naturally grow in 3D wherein the spatial arrangement of cells affects how they interact with each other. This suggests that 3D cell culture may mimic the natural in vivo setting better than traditional monolayer (2D) cell culture, where cells are grown attached to plastic. Here, using HER2-positive breast cancer cell lines as models (BT474, HCC1954, EFM192A), the effects of culturing cells in 3D using the poly-HEMA method compared to 2D cultures were assessed in terms of cellular viability, response/resistance to anti-cancer drugs, protein expression and enzyme activity. Scanning electron microscopy showed the morphology of cells in 3D to be substantially different to those cultured in 2D. Cell viability in 3D cells was substantially lower than that of cells in 2D cultures, while 3D cultures were more resistant to the effects of HER-targeted (neratinib) and classical chemotherapy (docetaxel) drugs. Expression of proteins involved in cell survival, transporters associated with drug resistance and drug targets were increased in 3D cultures. Finally, activity of drug metabolising enzyme CYP3A4 was substantially increased in 3D compared to 2D cultures. Together this data indicates that the biological information represented by 3D and 2D cell cultures is substantially different i.e. 3D cell cultures demonstrate higher innate resistance to anti-cancer drugs compared to 2D cultures, which may be facilitated by the altered receptor proteins, drug transporters and metabolising enzyme activity. This highlights the importance of considering 3D in addition to 2D culture methods in pre-clinical studies of both newer targeted and more traditional anti-cancer drugs.

  9. Synthesizing 2D MoS2 Nanofins on carbon nanospheres as catalyst support for Proton Exchange Membrane Fuel Cells

    NASA Astrophysics Data System (ADS)

    Hu, Yan; Chua, Daniel H. C.

    2016-06-01

    Highly dense 2D MoS2 fin-like nanostructures on carbon nanospheres were fabricated and formed the main catalyst support structure in the oxygen reduction reaction (ORR) for polymer electrolyte membrane (PEM) fuel cells. These nanofins were observed growing perpendicular to the carbon nanosphere surface in random orientations and high resolution transmission electron microscope confirmed 2D layers. The PEM fuel cell test showed enhanced electrochemical activity with good stability, generating over 8.5 W.mgPt‑1 as compared to standard carbon black of 7.4 W.mgPt‑1 under normal operating conditions. Electrochemical Impedance Spectroscopy confirmed that the performance improvement is highly due to the excellent water management of the MoS2 lamellar network, which facilitates water retention at low current density and flood prevention at high current density. Reliability test further demonstrated that these nanofins are highly stable in the electrochemical reaction and is an excellent ORR catalyst support.

  10. Synthesizing 2D MoS2 Nanofins on carbon nanospheres as catalyst support for Proton Exchange Membrane Fuel Cells

    PubMed Central

    Hu, Yan; Chua, Daniel H. C.

    2016-01-01

    Highly dense 2D MoS2 fin-like nanostructures on carbon nanospheres were fabricated and formed the main catalyst support structure in the oxygen reduction reaction (ORR) for polymer electrolyte membrane (PEM) fuel cells. These nanofins were observed growing perpendicular to the carbon nanosphere surface in random orientations and high resolution transmission electron microscope confirmed 2D layers. The PEM fuel cell test showed enhanced electrochemical activity with good stability, generating over 8.5 W.mgPt−1 as compared to standard carbon black of 7.4 W.mgPt−1 under normal operating conditions. Electrochemical Impedance Spectroscopy confirmed that the performance improvement is highly due to the excellent water management of the MoS2 lamellar network, which facilitates water retention at low current density and flood prevention at high current density. Reliability test further demonstrated that these nanofins are highly stable in the electrochemical reaction and is an excellent ORR catalyst support. PMID:27302135

  11. A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers

    PubMed Central

    Espinoza, J. Luis; Nguyen, Viet H.; Ichimura, Hiroshi; Pham, Trang T. T.; Nguyen, Cuong H.; Pham, Thuc V.; Elbadry, Mahmoud I.; Yoshioka, Katsuji; Tanaka, Junji; Trung, Ly Q.; Takami, Akiyoshi; Nakao, Shinji

    2016-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174. In a group of 123 patients with HPV+ anogenital cancers, the low cytotoxicity allele LNK was significantly associated with increased cancer susceptibility (p = 0.016). Similar results were also observed in a group of 153 women with cervical cancer (p = 0.05). In functional studies, NK cells from individuals with LNK genotype showed a lower NKG2D expression and displayed less efficient NKG2D-mediated functions than NK cells with HNK genotype. Notably, the rs1049174 variant occurs within a targeting site for miR-1245, a negative regulator of NKG2D expression. Compared with the higher cytotoxicity allele HNK, the LNK allele was more efficiently targeted by miR-1245 and thus determined lower NKG2D expression in NK cells with the LNK genotype. The NKG2D variants may influence cancer immunosurveillance and thus determine susceptibility to various malignancies, including HPV-induced cancers. PMID:27995954

  12. A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers.

    PubMed

    Espinoza, J Luis; Nguyen, Viet H; Ichimura, Hiroshi; Pham, Trang T T; Nguyen, Cuong H; Pham, Thuc V; Elbadry, Mahmoud I; Yoshioka, Katsuji; Tanaka, Junji; Trung, Ly Q; Takami, Akiyoshi; Nakao, Shinji

    2016-12-20

    Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174. In a group of 123 patients with HPV+ anogenital cancers, the low cytotoxicity allele LNK was significantly associated with increased cancer susceptibility (p = 0.016). Similar results were also observed in a group of 153 women with cervical cancer (p = 0.05). In functional studies, NK cells from individuals with LNK genotype showed a lower NKG2D expression and displayed less efficient NKG2D-mediated functions than NK cells with HNK genotype. Notably, the rs1049174 variant occurs within a targeting site for miR-1245, a negative regulator of NKG2D expression. Compared with the higher cytotoxicity allele HNK, the LNK allele was more efficiently targeted by miR-1245 and thus determined lower NKG2D expression in NK cells with the LNK genotype. The NKG2D variants may influence cancer immunosurveillance and thus determine susceptibility to various malignancies, including HPV-induced cancers.

  13. Chimeric NKG2D CAR-expressing T cell-mediated attack of human ovarian cancer is enhanced by histone deacetylase inhibition.

    PubMed

    Song, De-Gang; Ye, Qunrui; Santoro, Stephen; Fang, Chongyun; Best, Andrew; Powell, Daniel J

    2013-03-01

    NKG2D ligands (NKG2DLs) are widely expressed on ovarian cancers to various degrees, making them attractive targets for immunotherapy. Here, we applied a chimeric antigen receptor (CAR) approach for the targeting of NKG2DLs expressed on human ovarian cancer cells and evaluated the impact of pharmacological upregulation of NKG2DLs on immune recognition. Various NKG2DLs, including MICA/B and ULBP-1, -2, -3, and -4, were expressed at various levels on the surface of all established ovarian cancer cell lines and primary ovarian cancer samples tested. To redirect human T cells against NKG2DLs, an NKG2DL-specific CAR was generated by fusing the extracellular domain of the NKG2D receptor to the 4-1BB costimulatory and CD3-ζ chain signaling domains. In vitro expansion of chimeric NKG2D CAR T cells was delayed compared with untransduced T cells and control CAR T cells; the likely result of fratricide among activated T cells expressing NKG2DLs. However, NKG2D CAR T cells did expand and were selectively enriched during prolonged culture. In coculture, CD4(+) and CD8(+) NKG2D CAR T cells specifically recognized and killed NKG2DL-expressing ovarian cancer cell lines but not NKG2DL-negative cells. Notably, pretreatment of ovarian cancer cells expressing moderate to low levels of NKG2DLs with the histone deacetylase inhibitor sodium valproate (VPA) upregulated NKG2DL cell surface expression and consequently enhanced their immune recognition by chimeric NKG2D CAR T cells. Our results demonstrate that VPA-induced upregulation of NKG2DL expression enhances the immune recognition of ovarian cancer cells by engineered NKG2D CAR T cells, and rationalizes the use of VPA in combination with NKG2DL-targeted immunotherapy in ovarian cancer.

  14. Chimeric NKG2D CAR-Expressing T Cell-Mediated Attack of Human Ovarian Cancer Is Enhanced by Histone Deacetylase Inhibition

    PubMed Central

    Song, De-Gang; Ye, Qunrui; Santoro, Stephen; Fang, Chongyun; Best, Andrew

    2013-01-01

    Abstract NKG2D ligands (NKG2DLs) are widely expressed on ovarian cancers to various degrees, making them attractive targets for immunotherapy. Here, we applied a chimeric antigen receptor (CAR) approach for the targeting of NKG2DLs expressed on human ovarian cancer cells and evaluated the impact of pharmacological upregulation of NKG2DLs on immune recognition. Various NKG2DLs, including MICA/B and ULBP-1, -2, -3, and -4, were expressed at various levels on the surface of all established ovarian cancer cell lines and primary ovarian cancer samples tested. To redirect human T cells against NKG2DLs, an NKG2DL-specific CAR was generated by fusing the extracellular domain of the NKG2D receptor to the 4-1BB costimulatory and CD3-ζ chain signaling domains. In vitro expansion of chimeric NKG2D CAR T cells was delayed compared with untransduced T cells and control CAR T cells; the likely result of fratricide among activated T cells expressing NKG2DLs. However, NKG2D CAR T cells did expand and were selectively enriched during prolonged culture. In coculture, CD4+ and CD8+ NKG2D CAR T cells specifically recognized and killed NKG2DL-expressing ovarian cancer cell lines but not NKG2DL-negative cells. Notably, pretreatment of ovarian cancer cells expressing moderate to low levels of NKG2DLs with the histone deacetylase inhibitor sodium valproate (VPA) upregulated NKG2DL cell surface expression and consequently enhanced their immune recognition by chimeric NKG2D CAR T cells. Our results demonstrate that VPA-induced upregulation of NKG2DL expression enhances the immune recognition of ovarian cancer cells by engineered NKG2D CAR T cells, and rationalizes the use of VPA in combination with NKG2DL-targeted immunotherapy in ovarian cancer. PMID:23297870

  15. Influence of Tricuspid Bioprosthetic Mitral Valve Orientation Regarding the Flow Field Inside the Left Ventricle: In Vitro Hydrodynamic Characterization Based on 2D PIV Measurements.

    PubMed

    Bazan, Ovandir; Ortiz, Jayme P; Fukumasu, Newton K; Pacifico, Antonio L; Yanagihara, Jurandir I

    2016-02-01

    The flow patterns of a prosthetic heart valve in the aortic or mitral position can change according to its type and orientation. This work describes the use of 2D particle image velocimetry (PIV) applied to the in vitro flow fields characterization inside the upper part of a left ventricular model at various heart rates and as a function of two orientations of stented tricuspid mitral bioprostheses. In the ventricular model, each mitral bioprosthesis (27 and 31 mm diameter) was installed in two orientations, rotated by 180°, while the aortic bileaflet mechanical valve (27 mm diameter) remained in a fixed orientation. The results (N = 50) showed changes in the intraventricular flow fields according to the mitral bioprostheses positioning. Also, changes in the aortic upstream velocity profiles were noticed as a function of mitral orientations.

  16. Resistance to Cytarabine Induces the Up-regulation of NKG2D Ligands and Enhances Natural Killer Cell Lysis of Leukemic Cells1

    PubMed Central

    Ogbomo, Henry; Michaelis, Martin; Klassert, Denise; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2008-01-01

    Prolonged treatment of leukemic cells with chemotherapeutic agents frequently results in development of drug resistance. Moreover, selection of drug-resistant cell populations may be associated with changes in malignant properties such as proliferation rate, invasiveness, and immunogenicity. In the present study, the sensitivity of cytarabine (1-β-d-arabinofuranosylcytosine, araC)-resistant and parental human leukemic cell lines (T-lymphoid H9 and acute T-lymphoblastic leukemia Molt-4) to natural killer (NK) cell-mediated killing was investigated. The results obtained demonstrate that araC-resistant H9 and Molt-4 (H9rARAC100 and Molt-4rARAC100) cell lines are more sensitive to NK cell-mediated lysis than their respective parental cell lines. This increased sensitivity was associated with a higher surface expression of ligands for the NK cell-activating receptor NKG2D, notably UL16 binding protein-2 (ULBP-2) and ULBP-3 in H9rARAC100 and Molt-4rARAC100 cell lines. Blocking ULBP-2 and ULBP-3 or NKG2D with monoclonal antibody completely abrogated NK cell lysis. Constitutive phosphorylated extracellular signal-regulated kinase (ERK) but not pAKT was higher in araC-resistant cells than in parental cell lines. Inhibition of ERK using ERK inhibitor PD98059 decreased both ULBP-2/ULBP-3 expression and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in H9 parental cells resulted in increased ULBP-2/ULBP-3 expression and enhanced NK cell lysis. These results demonstrate that increased sensitivity of araC-resistant leukemic cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway. PMID:19048119

  17. A 2D Particle in Cell model for ion extraction and focusing in electrostatic accelerators.

    PubMed

    Veltri, P; Cavenago, M; Serianni, G

    2014-02-01

    Negative ions are fundamental to produce intense and high energy neutral beams used to heat the plasma in fusion devices. The processes regulating the ion extraction involve the formation of a sheath on a scale comparable to the Debye length of the plasma. On the other hand, the ion acceleration as a beam is obtained on distances greater than λD. The paper presents a model for both the phases of ion extraction and acceleration of the ions and its implementation in a numerical code. The space charge of particles is deposited following usual Particle in Cell codes technique, while the field is solved with finite element methods. Some hypotheses on the beam plasma transition are described, allowing to model both regions at the same time. The code was tested with the geometry of the NIO1 negative ions source, and the results are compared with existing ray tracing codes and discussed.

  18. Characterization of Phenotypic and Transcriptional Differences in Human Pluripotent Stem Cells under 2D and 3D Culture Conditions.

    PubMed

    Kamei, Ken-Ichiro; Koyama, Yoshie; Tokunaga, Yumie; Mashimo, Yasumasa; Yoshioka, Momoko; Fockenberg, Christopher; Mosbergen, Rowland; Korn, Othmar; Wells, Christine; Chen, Yong

    2016-11-01

    Human pluripotent stem cells hold great promise for applications in drug discovery and regenerative medicine. Microfluidic technology is a promising approach for creating artificial microenvironments; however, although a proper 3D microenvironment is required to achieve robust control of cellular phenotypes, most current microfluidic devices provide only 2D cell culture and do not allow tuning of physical and chemical environmental cues simultaneously. Here, the authors report a 3D cellular microenvironment plate (3D-CEP), which consists of a microfluidic device filled with thermoresponsive poly(N-isopropylacrylamide)-β-poly(ethylene glycol) hydrogel (HG), which enables systematic tuning of both chemical and physical environmental cues as well as in situ cell monitoring. The authors show that H9 human embryonic stem cells (hESCs) and 253G1 human induced pluripotent stem cells in the HG/3D-CEP system maintain their pluripotent marker expression under HG/3D-CEP self-renewing conditions. Additionally, global gene expression analyses are used to elucidate small variations among different test environments. Interestingly, the authors find that treatment of H9 hESCs under HG/3D-CEP self-renewing conditions results in initiation of entry into the neural differentiation process by induction of PAX3 and OTX1 expression. The authors believe that this HG/3D-CEP system will serve as a versatile platform for developing targeted functional cell lines and facilitate advances in drug screening and regenerative medicine.

  19. Section 1. Simulation of surface-water integrated flow and transport in two-dimensions: SWIFT2D user's manual

    USGS Publications Warehouse

    Schaffranek, Raymond W.

    2004-01-01

    A numerical model for simulation of surface-water integrated flow and transport in two (horizontal-space) dimensions is documented. The model solves vertically integrated forms of the equations of mass and momentum conservation and solute transport equations for heat, salt, and constituent fluxes. An equation of state for salt balance directly couples solution of the hydrodynamic and transport equations to account for the horizontal density gradient effects of salt concentrations on flow. The model can be used to simulate the hydrodynamics, transport, and water quality of well-mixed bodies of water, such as estuaries, coastal seas, harbors, lakes, rivers, and inland waterways. The finite-difference model can be applied to geographical areas bounded by any combination of closed land or open water boundaries. The simulation program accounts for sources of internal discharges (such as tributary rivers or hydraulic outfalls), tidal flats, islands, dams, and movable flow barriers or sluices. Water-quality computations can treat reactive and (or) conservative constituents simultaneously. Input requirements include bathymetric and topographic data defining land-surface elevations, time-varying water level or flow conditions at open boundaries, and hydraulic coefficients. Optional input includes the geometry of hydraulic barriers and constituent concentrations at open boundaries. Time-dependent water level, flow, and constituent-concentration data are required for model calibration and verification. Model output consists of printed reports and digital files of numerical results in forms suitable for postprocessing by graphical software programs and (or) scientific visualization packages. The model is compatible with most mainframe, workstation, mini- and micro-computer operating systems and FORTRAN compilers. This report defines the mathematical formulation and computational features of the model, explains the solution technique and related model constraints, describes the

  20. Controls on the Flow Regime and Thermal Structure of the Subduction Zone Mantle Wedge: A Systematic 2-D and 3-D Investigation

    NASA Astrophysics Data System (ADS)

    Le Voci, Giuseppe; Davies, Rhodri; Goes, Saskia; Kramer, Stephan; Wilson, Cian

    2014-05-01

    Arc volcanism at subduction zones is likely regulated by the mantle wedge's flow regime and thermal structure and, hence, numerous studies have attempted to quantify the principal controls on mantle wedge conditions. Here, we build on these previous studies by undertaking the first systematic 2-D and 3-D numerical investigation, across a wide parameter-space, into how hydration and thermal buoyancy influence the wedge's flow regime and associated thermal structure, above a kinematically driven subducting plate. We find that small-scale convection (SSC), resulting from Rayleigh-Taylor instabilities, or drips, off the base of the overriding lithosphere, is a typical occurrence, if: (i) viscosities are < 5×1018 Pa s; and (ii) hydrous weakening of wedge rheology extends at least 100-150 km from the trench. In 2-D models, instabilities generally take the form of 'drips'. Although along-strike averages of wedge velocities and temperature in 3-D structure are consistent with those in 2-D, fluctuations are larger in 3-D. Furthermore, in 3-D, two separate, but interacting, longitudinal Richter roll systems form (with their axes aligned perpendicular to the trench), the first below the arc region and the second below the back-arc region. These instabilities result in transient and spatial temperature fluctuations of 100-150K, which are sufficient to influence melting, the stability of hydrous minerals and the dehydration of crustal material. Furthermore, they are efficient at eroding the overriding lithosphere, particularly in 3-D and, thus, provide a means to explain observations of high heat flow and thin back-arc lithosphere at many subduction zones, if back-arc mantle is hydrated.

  1. Laser characterization of the unsteady 2-D ion flow field in a Hall thruster with breathing mode oscillations

    NASA Astrophysics Data System (ADS)

    Lucca Fabris, Andrea; Young, Christopher; MacDonald-Tenenbaum, Natalia; Hargus, William, Jr.; Cappelli, Mark

    2016-10-01

    Hall thrusters are a mature form of electric propulsion for spacecraft. One commonly observed low frequency (10-50 kHz) discharge current oscillation in these E × B devices is the breathing mode, linked to a propagating ionization front traversing the channel. The complex time histories of ion production and acceleration in the discharge channel and near-field plume lead to interesting dynamics and interactions in the central plasma jet and downstream plume regions. A time-resolved laser-induced fluorescence (LIF) diagnostic non-intrusively measures 2-D ion velocity and relative ion density throughout the plume of a commercial BHT-600 Hall thruster manufactured by Busek Co. Low velocity classes of ions observed in addition to the main accelerated population are linked to propellant ionization outside of the device. Effects of breathing mode dynamics are shown to persist far downstream where modulations in ion velocity and LIF intensity are correlated with discharge current oscillations. This work is sponsored by the U.S. Air Force Office of Scientific Research with Dr. M. Birkan as program manager. C.Y. acknowledges support from the DOE NSSA Stewardship Science Graduate Fellowship under contract DE-FC52-08NA28752.

  2. A Parallel 2D Numerical Simulation of Tumor Cells Necrosis by Local Hyperthermia

    NASA Astrophysics Data System (ADS)

    Reis, R. F.; Loureiro, F. S.; Lobosco, M.

    2014-03-01

    Hyperthermia has been widely used in cancer treatment to destroy tumors. The main idea of the hyperthermia is to heat a specific region like a tumor so that above a threshold temperature the tumor cells are destroyed. This can be accomplished by many heat supply techniques and the use of magnetic nanoparticles that generate heat when an alternating magnetic field is applied has emerged as a promise technique. In the present paper, the Pennes bioheat transfer equation is adopted to model the thermal tumor ablation in the context of magnetic nanoparticles. Numerical simulations are carried out considering different injection sites for the nanoparticles in an attempt to achieve better hyperthermia conditions. Explicit finite difference method is employed to solve the equations. However, a large amount of computation is required for this purpose. Therefore, this work also presents an initial attempt to improve performance using OpenMP, a parallel programming API. Experimental results were quite encouraging: speedups around 35 were obtained on a 64-core machine.

  3. Seeing through the trick of cancer cells via 2D gels.

    PubMed

    Mao, Lei

    2013-12-01

    The advancement of modern therapy concepts has dramatically extended the postsurvival rates of patients with malignant gastric cancer. However, a remaining setback is the drug resistance of recurrent cancer, which casts a dark shadow over disease prognosis. The original work of Klein et al. [Proteomics Clin. Appl. 2013, 7, 813-824] has outlined a rational experimental approach to decipher the mechanistic pathway of cancer drug resistance by proteomic approach. They used gel-based comparative proteomics to analyze the nuclear proteome of a human gastric cancer cell line (AGS) with and without inactivation of hypoxia-inducible factor 1 (HIF-1), a transcription factor and master regulator of hypoxia adaptation. Using the classical 2DE-MS approach, these researchers observed 163 HIF-1 responsive proteins, among which over half of them could be confidently identified by MS. From this large dataset, the authors proposed an enhanced nuclear translocation of some proteasomal proteins upon inactivation of HIF-1. Overall, this work appropriately used proteomics as a hypothesis-free, top-down approach to dissect imperative clinical problems.

  4. 2D ratiometric fluorescent pH sensor for tracking of cells proliferation and metabolism.

    PubMed

    Ma, Jun; Ding, Changqin; Zhou, Jie; Tian, Yang

    2015-08-15

    Extracellular pH plays a vital role no matter in physiological or pathological studies. In this work, a hydrogel, CD@Nile-FITC@Gel (Gel sensor), entrapping the ratiometric fluorescent probe CD@Nile-FITC was developed. The Gel sensor was successfully used for real-time extracellular pH monitoring. In the case of CD@Nile-FITC, pH-sensitive fluorescent dye fluorescein isothiocyanate (FITC) was chosen as the response signal for H(+) and Nile blue chloride (Nile) as the reference signal. The developed fluorescent probe exhibited high selectivity for pH over other metal ions and amino acids. Meanwhile, the carbon-dots-based inorganic-organic probe demonstrated excellent photostability against long-term light illumination. In order to study the extracellular pH change in processes of cell proliferation and metabolism, CD@Nile-FITC probe was entrapped in sodium alginate gel and consequently formed CD@Nile-FITC@Gel. The MTT assay showed low cytotoxicity of the Gel and the pH titration indicated that it could monitor the pH fluctuations linearly and rapidly within the pH range of 6.0-9.0, which is valuable for physiological pH determination. As expected, the real-time bioimaging of the probe was successfully achieved.

  5. 3D computations of flow field in a guide vane blading designed by means of 2D model for a low head hydraulic turbine

    NASA Astrophysics Data System (ADS)

    Krzemianowski, Z.; Puzyrewski, R.

    2014-08-01

    The paper presents the main parameters of the flow field behind the guide vane cascade designed by means of 2D inverse problem and following check by means of 3D commercial program ANSYS/Fluent applied for a direct problem. This approach of using different models reflects the contemporary design procedure for non-standardized turbomachinery stage. Depending on the model, the set of conservation equation to be solved differs, although the physical background remains the same. The example of computations for guide vane cascade for a low head hydraulic turbine is presented.

  6. Coupling between shallow water and solute flow equations: analysis and management of source terms in 2D

    NASA Astrophysics Data System (ADS)

    Murillo, J.; Burguete, J.; Brufau, P.; García-Navarro, P.

    2005-09-01

    A two-dimensional model for the simulation of solute transport by convection and diffusion into shallow water flow over variable bottom is presented. It is based on a finite volume method over triangular unstructured grids. A first order upwind technique is applied to solve the flux terms in both the flow and solute equations and the bed slope source terms and a centred discretization is applied to the diffusion and friction terms. The convenience of considering the fully coupled system of equations is indicated and the methodology is well explained. Three options are suggested and compared in order to deal with the diffusion terms. Some comparisons are carried out in order to show the performance in terms of accuracy and computational effort of the different options.

  7. Physical enviroment of 2-D animal cell aggregates formed in a short pathlength ultrasound standing wave trap.

    PubMed

    Bazou, Despina; Kuznetsova, Larisa A; Coakley, W Terence

    2005-03-01

    2-D mammalian cell aggregates can be formed and levitated in a 1.5 MHz single half wavelength ultrasound standing wave trap. The physical environment of cells in such a trap has been examined. Attention was paid to parameters such as temperature, acoustic streaming, cavitation and intercellular forces. The extent to which these factors might be intrusive to a neural cell aggregate levitated in the trap was evaluated. Neural cells were exposed to ultrasound at a pressure amplitude of 0.54 MPa for 30 s; a small aggregate had been formed at the center of the trap. The pressure amplitude was then decreased to 0.27 MPa for 2 min, at which level the aggregation process continued at a slower rate. The pressure amplitude was then decreased to 0.06 MPa for 1 h. Temperature measurements that were conducted in situ with a 200 microm thermocouple over a 30 min period showed that the maximum temperature rise was less than 0.5 K. Acoustic streaming was measured by the particle image velocimetry method (PIV). It was shown that the hydrodynamic stress imposed on cells by acoustic streaming is less than that imposed by gentle preparative centrifugation procedures. Acoustic spectrum analysis showed that cavitation activity does not occur in the cell suspensions sonicated at the above pressures. White noise was detected only at a pressure amplitude of 1.96 MPa. Finally, it was shown that the attractive acoustic force between ultrasonically agglomerated cells is small compared with the normal attractive van der Waals force that operates at close cell surface separations. It is concluded that the standing wave trap operates only to concentrate cells locally, as in tissue, and does not modify the in vitro expression of surface receptor interactions.

  8. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice

    PubMed Central

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, YongKeun

    2016-01-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated. PMID:27605489

  9. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice

    NASA Astrophysics Data System (ADS)

    Kim, Kyoohyun; Choe, Kibaek; Park, Inwon; Kim, Pilhan; Park, Yongkeun

    2016-09-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mice were also investigated.

  10. ICEG2D (v2.0) - An Integrated Software Package for Automated Prediction of Flow Fields for Single-Element Airfoils With Ice Accretion

    NASA Technical Reports Server (NTRS)

    Thompson David S.; Soni, Bharat K.

    2001-01-01

    An integrated geometry/grid/simulation software package, ICEG2D, is being developed to automate computational fluid dynamics (CFD) simulations for single- and multi-element airfoils with ice accretions. The current version, ICEG213 (v2.0), was designed to automatically perform four primary functions: (1) generate a grid-ready surface definition based on the geometrical characteristics of the iced airfoil surface, (2) generate high-quality structured and generalized grids starting from a defined surface definition, (3) generate the input and restart files needed to run the structured grid CFD solver NPARC or the generalized grid CFD solver HYBFL2D, and (4) using the flow solutions, generate solution-adaptive grids. ICEG2D (v2.0) can be operated in either a batch mode using a script file or in an interactive mode by entering directives from a command line within a Unix shell. This report summarizes activities completed in the first two years of a three-year research and development program to address automation issues related to CFD simulations for airfoils with ice accretions. As well as describing the technology employed in the software, this document serves as a users manual providing installation and operating instructions. An evaluation of the software is also presented.

  11. Multi-GPU unsteady 2D flow simulation coupled with a state-to-state chemical kinetics

    NASA Astrophysics Data System (ADS)

    Tuttafesta, Michele; Pascazio, Giuseppe; Colonna, Gianpiero

    2016-10-01

    In this work we are presenting a GPU version of a CFD code for high enthalpy reacting flow, using the state-to-state approach. In supersonic and hypersonic flows, thermal and chemical non-equilibrium is one of the fundamental aspects that must be taken into account for the accurate characterization of the plasma and state-to-state kinetics is the most accurate approach used for this kind of problems. This model consists in writing a continuity equation for the population of each vibrational level of the molecules in the mixture, determining at the same time the species densities and the distribution of the population in internal levels. An explicit scheme is employed here to integrate the governing equations, so as to exploit the GPU structure and obtain an efficient algorithm. The best performances are obtained for reacting flows in state-to-state approach, reaching speedups of the order of 100, thanks to the use of an operator splitting scheme for the kinetics equations.

  12. Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo.

    PubMed

    Ogawa, Tatsuya; Tsuji-Kawahara, Sachiyo; Yuasa, Takae; Kinoshita, Saori; Chikaishi, Tomomi; Takamura, Shiki; Matsumura, Haruo; Seya, Tsukasa; Saga, Toshihiko; Miyazawa, Masaaki

    2011-06-01

    Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptor in vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D-RAE-1 interactions in vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.

  13. The Effects of Far-Field Boundary Conditions on 2D Numerical Solutions for Continental Rifting: Tests and Recipes for Improved Treatment of Asthenosphere Flow and Melting

    NASA Astrophysics Data System (ADS)

    Morgan, J. P.; de Monserrat, A.; Hall, R.; Taramon, J. M.; Perez-Gussinye, M.

    2015-12-01

    This work focuses on improving current 2D numerical approaches to modeling the boundary conditions associated with computing accurate deformation and melting associated with continental rifting. Recent models primarily use far-field boundary conditions that have been used for decades with little assessment of their effects on asthenospheric flow beneath the rifting region. All are clearly extremely oversimplified — Huismans and Buiter assume there is no vertical flow into the rifting region, with the asthenosphere flowing uniformly into the rifting region from the sides beneath lithosphere moving in the opposing direction, Armitage et al. and van Wijk use divergent velocities on the upper boundary to impose break-up within a Cartesian box, while other studies generally assume there is uniform horizontal flow away from the center of rifting, with uniform vertical flow replenishing the material pulled out of the sides of the computational region. All are likely to significantly shape the pattern of asthenospheric flow beneath the stretching lithosphere that is associated with pressure-release melting and rift volcanism. Thus while ALL may lead to similar predictions of the effects of crustal stretching and thinning, NONE may lead to accurate determination of the the asthenospheric flow and melting associated with lithospheric stretching and breakup. Here we discuss a suite of numerical experiments that compare these choices to likely more realistic boundary condition choices like the analytical solution for flow associated with two diverging plates stretching over a finite-width region, and a high-resolution 2-D region embedded within a cylindrical annulus 'whole mantle cross-section' at 5% extra numerical problem size. Our initial results imply that the choice of far-field boundary conditions does indeed significantly influence predicted melting distributions and melt volumes associated with continental breakup. For calculations including asthenospheric melting

  14. Instantaneous 2D Velocity and Temperature Measurements in High Speed Flows Based on Spectrally Resolved Molecular Rayleigh Scattering

    NASA Technical Reports Server (NTRS)

    Seasholtz, Richard G.

    1995-01-01

    A Rayleigh scattering diagnostic for high speed flows is described for the simultaneous, instantaneous measurement of gas temperature and velocity at a number (up to about one hundred) of locations in a plane illuminated by an injection-seeded, frequency doubled Nd:YAG laser. Molecular Rayleigh scattered light is collected and passed through a planar mirror Fabry-Perot interferometer. The resulting image is analyzed to determine the gas temperature and bulk velocity at each of the regions. The Cramer Rao lower bound for measurement uncertainty is calculated. Experimental data is presented for a free jet and for preliminary measurements in the Lewis 4 inch by 10 inch supersonic wind tunnel.

  15. Fringe-controlled biodegradation under dynamic conditions: quasi 2-D flow-through experiments and reactive-transport modeling.

    PubMed

    Eckert, Dominik; Kürzinger, Petra; Bauer, Robert; Griebler, Christian; Cirpka, Olaf A

    2015-01-01

    Biodegradation in contaminated aquifers has been shown to be most pronounced at the fringe of contaminant plumes, where mixing of contaminated water and ambient groundwater, containing dissolved electron acceptors, stimulates microbial activity. While physical mixing of contaminant and electron acceptor by transverse dispersion has been shown to be the major bottleneck for biodegradation in steady-state plumes, so far little is known on the effect of flow and transport dynamics (caused, e.g., by a seasonally fluctuating groundwater table) on biodegradation in these systems. Towards this end we performed experiments in quasi-two-dimensional flow-through microcosms on aerobic toluene degradation by Pseudomonas putida F1. Plume dynamics were simulated by vertical alteration of the toluene plume position and experimental results were analyzed by reactive-transport modeling. We found that, even after disappearance of the toluene plume for two weeks, the majority of microorganisms stayed attached to the sediment and regained their full biodegradation potential within two days after reappearance of the toluene plume. Our results underline that besides microbial growth, also maintenance and dormancy are important processes that affect biodegradation performance under transient environmental conditions and therefore deserve increased consideration in future reactive-transport modeling.

  16. 1D Modeling of the Initial Stage of Wire Explosions and 2D Modeling of the m=0 Sausage Instability With Sheared Axial Flow

    NASA Astrophysics Data System (ADS)

    Makhin, Volodymyr; Sotnikov, Vladimir; Bauer, Bruno; Lindemuth, Irvin; Sheehey, Peter

    2001-10-01

    1D modeling of the initial state of wire explosions (“cold start” with updated SESAME tables) was examined using 1D version of the Eulerian Magnetohydrodynamic Radiative Code (MHRDR). Simulations were carried out for two regimes: with (black body radiative model) and without radiative losses. Results of the simulations revealed strong dependence of the time of explosion and expansion speed of the wire on the implemented radiative model. This shows that it is necessary to accurately include radiative losses to model “cold start” wire explosions. 2D modeling of the m=0 sausage instability with sheared axial flow. The MHRDR simulations were used to obtain the growth rate of the m=0 sausage instability in plasma column with initial Bennett equilibrium profile with and without shear flow. These growth rates appeared to be in good agreement with growth rates calculated from the linearized MHD equations.

  17. Ex vivo 2D and 3D HSV-2 infection model using human normal vaginal epithelial cells.

    PubMed

    Zhu, Yaqi; Yang, Yan; Guo, Juanjuan; Dai, Ying; Ye, Lina; Qiu, Jianbin; Zeng, Zhihong; Wu, Xiaoting; Xing, Yanmei; Long, Xiang; Wu, Xufeng; Ye, Lin; Wang, Shubin; Li, Hui

    2017-01-27

    Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

  18. Inhibition of UBE2D3 Expression Attenuates Radiosensitivity of MCF-7 Human Breast Cancer Cells by Increasing hTERT Expression and Activity

    PubMed Central

    Hu, Liu; Li, Fen; Ren, Li; Yu, Haijun; Liu, Yu; Xia, Ling; Lei, Han; Liao, Zhengkai; Zhou, Fuxiang; Xie, Conghua; Zhou, Yunfeng

    2013-01-01

    The known functions of telomerase in tumor cells include replenishing telomeric DNA and maintaining cell immortality. We have previously shown the existence of a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Here we set out to elucidate the molecular mechanisms underlying regulation by telomerase of radiosensitivity in MCF-7 cells. Toward this aim, yeast two-hybrid (Y2H) screening of a human laryngeal squamous cell carcinoma radioresistant (Hep2R) cDNA library was first performed to search for potential hTERT interacting proteins. We identified ubiquitin-conjugating enzyme E2D3 (UBE2D3) as a principle hTERT-interacting protein and validated this association biochemically. ShRNA-mediated inhibition of UBE2D3 expression attenuated MCF-7 radiosensitivity, and induced the accumulation of hTERT and cyclin D1 in these cells. Moreover, down-regulation of UBE2D3 increased hTERT activity and cell proliferation, accelerating G1 to S phase transition in MCF-7 cells. Collectively these findings suggest that UBE2D3 participates in the process of hTERT-mediated radiosensitivity in human breast cancer MCF-7 cells by regulating hTERT and cyclin D1. PMID:23741361

  19. Optimal Boundary Control of a Simplified Ericksen-Leslie System for Nematic Liquid Crystal Flows in 2D

    NASA Astrophysics Data System (ADS)

    Cavaterra, Cecilia; Rocca, Elisabetta; Wu, Hao

    2017-02-01

    In this paper, we investigate an optimal boundary control problem for a two dimensional simplified Ericksen-Leslie system modelling the incompressible nematic liquid crystal flows. The hydrodynamic system consists of the Navier-Stokes equations for the fluid velocity coupled with a convective Ginzburg-Landau type equation for the averaged molecular orientation. The fluid velocity is assumed to satisfy a no-slip boundary condition, while the molecular orientation is subject to a time-dependent Dirichlet boundary condition that corresponds to the strong anchoring condition for liquid crystals. We first establish the existence of optimal boundary controls. Then we show that the control-to-state operator is Fréchet differentiable between appropriate Banach spaces and derive first-order necessary optimality conditions in terms of a variational inequality involving the adjoint state variables.

  20. RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

    PubMed Central

    Jung, Heiyoun; Hsiung, Benjamin; Pestal, Kathleen; Procyk, Emily

    2012-01-01

    The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes. PMID:23166357

  1. Use of Caval Subtraction 2D Phase-Contrast MR Imaging to Measure Total Liver and Hepatic Arterial Blood Flow: Preclinical Validation and Initial Clinical Translation.

    PubMed

    Chouhan, Manil D; Mookerjee, Rajeshwar P; Bainbridge, Alan; Walker-Samuel, Simon; Davies, Nathan; Halligan, Steve; Lythgoe, Mark F; Taylor, Stuart A

    2016-09-01

    Purpose To validate caval subtraction two-dimensional (2D) phase-contrast magnetic resonance (MR) imaging measurements of total liver blood flow (TLBF) and hepatic arterial fraction in an animal model and evaluate consistency and reproducibility in humans. Materials and Methods Approval from the institutional ethical committee for animal care and research ethics was obtained. Fifteen Sprague-Dawley rats underwent 2D phase-contrast MR imaging of the portal vein (PV) and infrahepatic and suprahepatic inferior vena cava (IVC). TLBF and hepatic arterial flow were estimated by subtracting infrahepatic from suprahepatic IVC flow and PV flow from estimated TLBF, respectively. Direct PV transit-time ultrasonography (US) and fluorescent microsphere measurements of hepatic arterial fraction were the standards of reference. Thereafter, consistency of caval subtraction phase-contrast MR imaging-derived TLBF and hepatic arterial flow was assessed in 13 volunteers (mean age, 28.3 years ± 1.4) against directly measured phase-contrast MR imaging PV and proper hepatic arterial inflow; reproducibility was measured after 7 days. Bland-Altman analysis of agreement and coefficient of variation comparisons were undertaken. Results There was good agreement between PV flow measured with phase-contrast MR imaging and that measured with transit-time US (mean difference, -3.5 mL/min/100 g; 95% limits of agreement [LOA], ±61.3 mL/min/100 g). Hepatic arterial fraction obtained with caval subtraction agreed well with those with fluorescent microspheres (mean difference, 4.2%; 95% LOA, ±20.5%). Good consistency was demonstrated between TLBF in humans measured with caval subtraction and direct inflow phase-contrast MR imaging (mean difference, -1.3 mL/min/100 g; 95% LOA, ±23.1 mL/min/100 g). TLBF reproducibility at 7 days was similar between the two methods (95% LOA, ±31.6 mL/min/100 g vs ±29.6 mL/min/100 g). Conclusion Caval subtraction phase-contrast MR imaging is a simple and clinically

  2. Rising of a single Taylor drop in a stagnant liquid—2D laminar flow and axisymmetry limits

    NASA Astrophysics Data System (ADS)

    Direito, F. J. N.; Campos, J. B. L. M.; Miranda, J. M.

    2016-05-01

    A numerical (computational fluid dynamics (CFD)) study concerning the rise of individual liquid Taylor drops through vertical columns of stagnant heavier liquids is presented in this paper. CFD simulations were performed in Ansys Fluent, using its implementation of volume of fluid method, assuming the flow to be axisymmetric and laminar. Different physical conditions were tested, corresponding to different combinations of relevant dimensionless parameters and the numerical method was validated through experimental data available in the literature. The viscosity ratio between the lighter and the heavier liquid was within the range 0.01-40 and Eötvös number was between 8 and 30. Morton number was within the interval of 2.32 × 10-6-100. Froude number results were compared to data from a literature correlation. The accordance is acceptable for the ranges studied. Velocity profiles in significant regions are reported (drop nose, drop bottom and continuous phase liquid film). The influence of changing one dimensionless parameter alone was assessed. For small and large viscosity ratios, axisymmetric behavior is not a valid assumption.

  3. Substantial increase in the frequency of circulating CD4+NKG2D+ T cells in patients with cervical intraepithelial neoplasia grade 1

    PubMed Central

    2013-01-01

    Background The NKG2D receptor confers important activating signals to NK cells via ligands expressed during cellular stress and viral infection. This receptor has generated great interest because not only is it expressed on NK cells, but it is also seen in virtually all CD8+ cytotoxic T cells and is classically considered absent in CD4+ T cells. However, recent studies have identified a distinctive population of CD4+ T cells that do express NKG2D, which could represent a particular cytotoxic effector population involved in viral infections and chronic diseases. On the other hand, increased incidence of human papillomavirus-associated lesions in CD4+ T cell-immunocompromised individuals suggests that CD4+ T cells play a key role in controlling the viral infection. Therefore, this study was focused on identifying the frequency of NKG2D-expressing CD4+ T cells in patients with cervical intraepithelial neoplasia (CIN) 1. Additionally, factors influencing CD4+NKG2D+ T cell expansion were also measured. Results Close to 50% of patients with CIN 1 contained at least one of the 37 HPV types detected by our genotyping system. A tendency for increased CD4+ T cells and CD8+ T cells and decreased NK cells was found in CIN 1 patients. The percentage of circulating CD4+ T cells co-expressing the NKG2D receptor significantly increased in women with CIN 1 versus control group. Interestingly, the increase of CD4+NKG2D+ T cells was seen in patients with CIN 1, despite the overall levels of CD4+ T cells did not significantly increase. We also found a significant increase of soluble MICB in CIN 1 patients; however, no correlation with the presence of CD4+NKG2D+ T cells was seen. While TGF-beta was significantly decreased in the group of CIN 1 patients, both TNF-alpha and IL-15 showed a tendency to increase in this group. Conclusions Taken together, our results suggest that the significant increase within the CD4+NKG2D+ T cell population in CIN 1 patients might be the result of a

  4. Recruitment of activating NK-cell receptors 2B4 and NKG2D to membrane microdomains in mammalian cells is dependent on their transmembrane regions.

    PubMed

    Gütgemann, Stephan A; Sandusky, Mina M; Wingert, Sabine; Claus, Maren; Watzl, Carsten

    2015-04-01

    Membrane microdomains play an important role in the regulation of natural killer (NK) cell activities. These cholesterol-rich membrane domains are enriched at the activating immunological synapse and several activating NK-cell receptors are known to localize to membrane microdomains upon receptor engagement. In contrast, inhibitory receptors do not localize in these specialized membrane domains. In addition, the functional competence of educated NK cells correlates with a confinement of activating receptors in membrane microdomains. However, the molecular basis for this confinement is unknown. Here, we investigate the structural requirements for the recruitment of the human-activating NK-cell receptors NKG2D and 2B4 to detergent-resistant membrane fractions in the murine BA/F3 cell line and in the human NK-cell line NKL. This stimulation-dependent recruitment occurred independently of the intracellular domains of the receptors. However, either interfering with the association between NKG2D and DAP10, or mutating the transmembrane region of 2B4 impacted the recruitment of the receptors to detergent-resistant membrane fractions and modulated the function of 2B4 in NK cells. Our data suggest a potential interaction between the transmembrane region of NK-cell receptors and membrane lipids as a molecular mechanism involved in determining the membrane confinement of activating NK-cell receptors.

  5. Micro-PIV measurements of multiphase flow of water and liquid CO2 in 2D homogeneous and heterogeneous porous micromodels

    NASA Astrophysics Data System (ADS)

    Li, Yaofa; Kazemifar, Farzan; Blois, Gianluca; Christensen, Kenneth

    2015-11-01

    Geological sequestration of carbon dioxide (CO2) has been of great interest primarily for the reason of CO2 emission reduction and enhanced oil recovery. Yet, our fundamental understanding of the coupled flow dynamics of CO2 and water in geologic media still remains limited, especially at the pore scale. Therefore, in this work the pore-scale flow of water and liquid/supercritical CO2 are quantified in 2D homogeneous and heterogeneous porous micro-models under reservoir-relevant conditions. Fluorescent microscopy and the micro-PIV technique are employed to simultaneously visualize both phases and obtain the velocity field in the aqueous phase. The velocity measurements in the homogeneous micro-model illustrate active and passive flow pathways and circulation regions near the fluid-fluid interfaces induced by shear. Moreover, the results for heterogeneous micro-models are presented and compared with those for homogeneous micro-models, which give valuable insight into flow processes at the pore scale in natural rock.

  6. Wind-tunnel experiments of turbulent flow over a surface-mounted 2-D block in a thermally-stratified boundary layer

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Markfort, Corey; Porté-Agel, Fernando

    2014-11-01

    Turbulent flows over complex surface topography have been of great interest in the atmospheric science and wind engineering communities. The geometry of the topography, surface roughness and temperature characteristics as well as the atmospheric thermal stability play important roles in determining momentum and scalar flux distribution. Studies of turbulent flow over simplified topography models, under neutrally stratified boundary-layer conditions, have provided insights into fluid dynamics. However, atmospheric thermal stability has rarely been considered in laboratory experiments, e.g., wind-tunnel experiments. Series of wind-tunnel experiments of thermally-stratified boundary-layer flow over a surface-mounted 2-D block, in a well-controlled boundary-layer wind tunnel, will be presented. Measurements using high-resolution PIV, x-wire/cold-wire anemometry and surface heat flux sensors were conducted to quantify the turbulent flow properties, including the size of the recirculation zone, coherent vortex structures and the subsequent boundary layer recovery. Results will be shown to address thermal stability effects on momentum and scalar flux distribution in the wake, as well as dominant mechanism of turbulent kinetic energy generation and consumption. The authors gratefully acknowledge funding from the Swiss National Foundation (Grant 200021-132122), the National Science Foundation (Grant ATM-0854766) and NASA (Grant NNG06GE256).

  7. Loss of CD28 within CD4(+) T cell subsets from cervical cancer patients is accompanied by the acquisition of intracellular perforin, and is further enhanced by NKG2D expression.

    PubMed

    Escarra-Senmarti, Marta; Bueno-Topete, Miriam Ruth; Jave-Suarez, Luis Felipe; Gomez-Bañuelos, Eduardo; Gutierrez-Franco, Jorge; Vega-Magaña, Natali; Aguilar-Lemarroy, Adriana; Pereira-Suarez, Ana Laura; Haramati, Jesse; Del Toro-Arreola, Susana

    2017-02-01

    CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties. We have recently reported the existence of two separate CD4(+)NKG2D(+) T cell populations, which were defined by the presence or absence of the co-stimulatory molecule CD28, with the CD4(+)CD28(null)NKG2D(+) population more frequently observed in women with cervical cancer. This has led to the present effort to further characterize this population and to determine if the loss of CD28 influences the acquisition of cytotoxic or regulatory markers. In the present work, a multicolor flow cytometry protocol was used to analyze the expression of cytotoxic and immunoregulatory markers on circulating CD4(+) T cells characterized by the presence or absence of CD28 and NKG2D in patients with invasive cervical carcinoma and age/gender-matched healthy controls. A noticeable expansion of CD4(+)CD28(null) cells, many of them NKG2D(+), were observed in selected cervical cancer samples. This CD4(+)CD28(null) T cell population was characterized by a lack of immunoregulatory markers, as well as very low basal levels of intracellular IFN-γ, TNF-α, TGF-β, and IL-10. Intracellular perforin, however, was found to be significantly increased in this CD4(+)CD28(null) population, and increases in the mean fluorescence intensity of perforin were found to be enhanced by the presence of NKG2D. In conclusion, our data provide the first evidence of a strict link between the absence of CD28 and the expression of perforin, which is likewise enhanced by the expression of NKG2D

  8. Silencing NKG2D ligand-targeting miRNAs enhances natural killer cell-mediated cytotoxicity in breast cancer.

    PubMed

    Shen, Jiaying; Pan, Jie; Du, Chengyong; Si, Wengong; Yao, Minya; Xu, Liang; Zheng, Huilin; Xu, Mingjie; Chen, Danni; Wang, Shu; Fu, Peifen; Fan, Weimin

    2017-04-06

    NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DLs). NKG2DLs are expressed on malignant cells and sensitize them to early elimination by cytotoxic lymphocytes. We investigated the clinical importance of NKG2DLs and the mechanism of NKG2DL regulation in breast cancer (BC). Among the NKG2DLs MICA/B and ULBP1/2/3, the expression levels of MICA/B in BC tissues were inversely associated with the Tumor Node Metastasis stage. We first found that the high expression of MICB, but not MICA, was an independent prognostic factor for overall survival in patients with BC. Investigation into the mechanism revealed that a group of microRNAs (miRNAs) belonging to the miR-17-92 cluster, especially miR-20a, decreased the expression of ULBP2 and MICA/B. These miRNAs downregulated the expression of MICA/B by targeting the MICA/B 3'-untranslated region and downregulated ULBP2 by inhibiting the MAPK/ERK signaling pathway. Functional analysis showed that the silencing of NKG2DL-targeting miRNAs in BC cells increased NK cell-mediated cytotoxicity in vitro and inhibited immune escape in vivo. In addition, histone deacetylase inhibitors (HDACis) increased NKG2DL expression in BC cells by inhibiting members of the miR-17-92 cluster. Thus, targeting miRNAs with antisense inhibitors or HDACis may represent a novel approach for increasing the immunogenicity of BC.

  9. 1α,25(OH)2D3-dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells.

    PubMed

    Buitrago, Claudia G; Arango, Nadia S; Boland, Ricardo L

    2012-04-01

    We previously reported that 1α,25-dihydroxy-vitamin D(3) [1α,25(OH)(2)D(3)] induces non-transcriptional rapid responses through activation of Src and MAPKs in the skeletal muscle cell line C2C12. In the present study we investigated the modulation of Akt by the secosteroid hormone in C2C12 cells at proliferative stage (myoblasts) and at early differentiation stage. In proliferating cells, 1α,25(OH)(2)D(3) activates Akt by phosphorylation in Ser473 in a time-dependent manner (5-60 min). When these cells were pretreated with methyl-beta-cyclodextrin to disrupt caveolae microdomains, hormone-induced activation of Akt was suppressed. Similar results were obtained by siRNA silencing of caveolin-1 expression, further indicating that hormone effects on cell membrane caveolae are required for downstream signaling. PI3K and p38 MAPK, but not ERK1/2, participate in 1α,25(OH)(2)D(3) activation of Akt in myoblasts. The involvement of p38 MAPK in Akt phosphorylation by the hormone probably occurs through MAPK-activated protein kinase 2 (MK2), which is activated by the steroid. In addition, the participation of Src in Akt phosphorylation by 1α,25(OH)(2)D(3) was demonstrated using the inhibitor PP2 and antisense oligodeoxynucleotides that suppress Src expression. We also observed that PI3K participates in hormone-induced proliferation. During the early phase of C2C12 cell differentiation 1α,25(OH)(2)D(3) also increases Akt phosphorylation and activates Src. Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1α,25(OH)(2)D(3). Altogether, these data suggest that 1α,25(OH)(2)D(3) upregulates Akt through Src, PI(3)K, and p38 MAPK to stimulate myogenesis in C2C12 cells.

  10. 1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial–Mesenchymal Transition

    PubMed Central

    Hou, Yong-Feng; Gao, Si-Hai; Wang, Ping; Zhang, He-Mei; Liu, Li-Zhi; Ye, Meng-Xuan; Zhou, Guang-Ming; Zhang, Zeng-Li; Li, Bing-Yan

    2016-01-01

    Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)2D3] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)2D3 could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-β1(TGF-β1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)2D3 not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-β1. We discovered that 1α,25(OH)2D3 increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)2D3 reduced the expression level of transcription factors of EMT, such as slug, snail, and β-catenin. These results indicate that 1α,25(OH)2D3 suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)2D3 might be a potential therapeutic agent for the treatment of ovarian cancer. PMID:27548154

  11. 11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor

    PubMed Central

    Bin, Haijun; Gao, Liang; Zhang, Zhi-Guo; Yang, Yankang; Zhang, Yindong; Zhang, Chunfeng; Chen, Shanshan; Xue, Lingwei; Yang, Changduk; Xiao, Min; Li, Yongfang

    2016-01-01

    Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si–C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm−2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials. PMID:27905397

  12. 11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor

    NASA Astrophysics Data System (ADS)

    Bin, Haijun; Gao, Liang; Zhang, Zhi-Guo; Yang, Yankang; Zhang, Yindong; Zhang, Chunfeng; Chen, Shanshan; Xue, Lingwei; Yang, Changduk; Xiao, Min; Li, Yongfang

    2016-12-01

    Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si-C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm-2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials.

  13. 11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor.

    PubMed

    Bin, Haijun; Gao, Liang; Zhang, Zhi-Guo; Yang, Yankang; Zhang, Yindong; Zhang, Chunfeng; Chen, Shanshan; Xue, Lingwei; Yang, Changduk; Xiao, Min; Li, Yongfang

    2016-12-01

    Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si-C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm(-2) benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials.

  14. Modelling river bank erosion using a 2D depth-averaged numerical model of flow and non-cohesive, non-uniform sediment transport

    NASA Astrophysics Data System (ADS)

    El Kadi Abderrezzak, Kamal; Die Moran, Andrés; Tassi, Pablo; Ata, Riadh; Hervouet, Jean-Michel

    2016-07-01

    Bank erosion can be an important form of morphological adjustment in rivers. With the advances made in computational techniques, two-dimensional (2D) depth-averaged numerical models have become valuable tools for resolving many engineering problems dealing with sediment transport. The objective of this research work is to present a simple, new, bank-erosion operator that is integrated into a 2D Saint-Venant-Exner morphodynamic model. The numerical code is based on an unstructured grid of triangular elements and finite-element algorithms. The slope of each element in the grid is compared to the angle of repose of the bank material. Elements for which the slope is too steep are tilted to bring them to the angle of repose along a horizontal axis defined such that the volume loss above the axis is equal to the volume gain below, thus ensuring mass balance. The model performance is assessed using data from laboratory flume experiments and a scale model of the Old Rhine. For the flume experiment case with uniform bank material, relevant results are obtained for bank geometry changes. For the more challenging case (i.e. scale model of the Old Rhine with non-uniform bank material), the numerical model is capable of reproducing the main features of the bank failure, induced by the newly designed groynes, as well as the transport of the mobilized sediment material downstream. Some deviations between the computed results and measured data are, however, observed. They are ascribed to the effects of three-dimensional (3D) flow structures, pore pressure and cohesion, which are not considered in the present 2D model.

  15. Biomechanics of cell rolling: shear flow, cell-surface adhesion, and cell deformability.

    PubMed

    Dong, C; Lei, X X

    2000-01-01

    The mechanics of leukocyte (white blood cell; WBC) deformation and adhesion to endothelial cells (EC) has been investigated using a novel in vitro side-view flow assay. HL-60 cell rolling adhesion to surface-immobilized P-selectin was used to model the WBC-EC adhesion process. Changes in flow shear stress, cell deformability, or substrate ligand strength resulted in significant changes in the characteristic adhesion binding time, cell-surface contact and cell rolling velocity. A 2-D model indicated that cell-substrate contact area under a high wall shear stress (20 dyn/cm2) could be nearly twice of that under a low stress (0.5 dyn/cm2) due to shear flow-induced cell deformation. An increase in contact area resulted in more energy dissipation to both adhesion bonds and viscous cytoplasm, whereas the fluid energy that inputs to a cell decreased due to a flattened cell shape. The model also predicted a plateau of WBC rolling velocity as flow shear stresses further increased. Both experimental and computational studies have described how WBC deformation influences the WBC-EC adhesion process in shear flow.

  16. RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity.

    PubMed

    Cao, Wei; Xi, Xueyan; Hao, Zhiyong; Li, Wenjing; Kong, Yan; Cui, Lianxian; Ma, Chi; Ba, Denian; He, Wei

    2007-06-29

    UL16-binding proteins (ULBPs, also termed as retinoic acid early transcripts, encoded by RAET1 genes), a family of ligands for NKG2D in humans, are frequently expressed by tumor cells and mediate cytotoxicities of natural killer (NK) cells and CD8(+) alphabeta T cells to tumor cells. ULBP1, ULBP2, ULBP3, and RAET1L link to membrane through glycosylphosphatidylinositol, whereas RAET1E and RAET1G contain transmembrane and cytoplasmic domains. Proteolytic cleavage of ULBP2 produces truncated and soluble forms that may counteract NKG2D-mediated tumor immune surveillance. In this study, we report that RAET1E can produce a soluble, 35-kDa protein (termed as RAET1E2) lacking the transmembrane region by selective splicing in tumor cells. The expressions of both RAET1E2 transcripts and protein can be found in different tumor cells and tissues. Preincubation of NK-92 cells, a human NK cell line, with culture supernatants from tumor cell lines expressing RAET1E2 or RAET1E2 gene-transfected COS-7 cells resulted in decreased expression of NKG2D on NK-92 cells. Furthermore, incubation of NK-92 cells with recombinant RAET1E2 protein also decreased the surface expression of NKG2D and resulted in marked reduction in cytotoxicities to MGC-803, HepG2, or K562 tumor cells. Taken together, our data provide strong evidence for an immune escape mechanism of tumors via alternative splicing of ULBP RNA to generate a free soluble ULBP protein, RAET1E2, that may impair NKG2D-mediated NK cell cytotoxicity to tumors.

  17. Geophysical Fluid Flow Cell Simulation

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Computer simulation of atmospheric flow corresponds well to imges taken during the second Geophysical Fluid Flow Cell (BFFC) mission. The top shows a view from the pole, while the bottom shows a view from the equator. Red corresponds to hot fluid rising while blue shows cold fluid falling. This simulation was developed by Anil Deane of the University of Maryland, College Park and Paul Fischer of Argorne National Laboratory. Credit: NASA/Goddard Space Flight Center

  18. Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

    PubMed Central

    Sakha, Sujata; Muramatsu, Tomoki; Ueda, Koji; Inazawa, Johji

    2016-01-01

    Metastasis is associated with poor prognosis in cancers. Exosomes, which are packed with RNA and proteins and are released in all biological fluids, are emerging as an important mediator of intercellular communication. However, the function of exosomes remains poorly understood in cancer metastasis. Here, we demonstrate that exosomes isolated by size-exclusion chromatography from a highly metastatic human oral cancer cell line, HOC313-LM, induced cell growth through the activation of ERK and AKT as well as promoted cell motility of the poorly metastatic cancer cell line HOC313-P. MicroRNA (miRNA) array analysis identified two oncogenic miRNAs, miR-342–3p and miR-1246, that were highly expressed in exosomes. These miRNAs were transferred to poorly metastatic cells by exosomes, which resulted in increased cell motility and invasive ability. Moreover, miR-1246 increased cell motility by directly targeting DENN/MADD Domain Containing 2D (DENND2D). Taken together, our findings support the metastatic role of exosomes and exosomal miRNAs, which highlights their potential for applications in miRNA-based therapeutics. PMID:27929118

  19. Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction.

    PubMed

    Mathew, Stephen O; Chaudhary, Pankaj; Powers, Sheila B; Vishwanatha, Jamboor K; Mathew, Porunelloor A

    2016-10-18

    Prostate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors. Previously, we identified Lectin-like transcript-1 (LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A inhibits NK cell activation. In this study, we have found that LLT1 was overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in primary prostate cancer tissues both at the mRNA and protein level. We further showed that LLT1 is retained intracellularly in normal prostate cells with minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of prostate cancer cells. The results indicate that prostate cancer cells may evade immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and therefore may be a new therapeutic option for treatment of prostate cancer.

  20. Experimental quantification of pore-scale flow of water and liquid CO2 in 2D heterogeneous porous micromodels at reservoir conditions

    NASA Astrophysics Data System (ADS)

    Li, Yaofa; Kazemifar, Farzan; Blois, Gianluca; Christensen, Kenneth

    2016-11-01

    Pore-scale flow interactions between water and supercritical CO2 is relevant to large-scale geologic sequestration of CO2. Recent studies have provided evidence of strong instabilities at the meniscus resulting in burst events and onset of inertial effects. This supports the notion that pore-scale physics cannot be captured by Darcian models and unsteady events play a defining role in CO2 transport/trapping processes and such burst events may generate pressure fluctuations that can be linked to micro-seismic events in the pore structure. To this end, the pore-scale flow of water and liquid/supercritical CO2 is investigated under reservoir-relevant conditions in 2D heterogeneous porous micro-models that reflect the complexity of a real sandstone. Fluorescent microscopy and micro-PIV are complemented by a fast differential pressure transmitter, allowing for simultaneous quantification of the flow field within and the instantaneous pressure drop across the micromodels. A number of CO2 invasion patterns and corresponding pressure drop variations are observed over a range of wettability conditions, yielding a more comprehensive picture of the CO2 drainage processes. This work was primarily supported as part of the Center for Geologic Storage of CO2 , an EFRC funded by the U.S. Department of Energy, Office of Science and partially supported by WPI-I2CNER based at Kyushu University, Japan.

  1. A methodology for linking 2D overland flow models with the sewer network model SWMM 5.1 based on dynamic link libraries.

    PubMed

    Leandro, Jorge; Martins, Ricardo

    2016-01-01

    Pluvial flooding in urban areas is characterized by a gradually varying inundation process caused by surcharge of the sewer manholes. Therefore urban flood models need to simulate the interaction between the sewer network and the overland flow in order to accurately predict the flood inundation extents. In this work we present a methodology for linking 2D overland flow models with the storm sewer model SWMM 5. SWMM 5 is a well-known free open-source code originally developed in 1971. The latest major release saw its structure re-written in C ++ allowing it to be compiled as a command line executable or through a series of calls made to function inside a dynamic link library (DLL). The methodology developed herein is written inside the same DLL in C + +, and is able to simulate the bi-directional interaction between both models during simulation. Validation is done in a real case study with an existing urban flood coupled model. The novelty herein is that the new methodology can be added to SWMM without the need for editing SWMM's original code. Furthermore, it is directly applicable to other coupled overland flow models aiming to use SWMM 5 as the sewer network model.

  2. IDO metabolite produced by EBV-transformed B cells inhibits surface expression of NKG2D in NK cells via the c-Jun N-terminal kinase (JNK) pathway.

    PubMed

    Song, Hyunkeun; Park, Hyunjin; Kim, Jiyoung; Park, Gabin; Kim, Yeong-Seok; Kim, Sung Mok; Kim, Daejin; Seo, Su Kil; Lee, Hyun-Kyung; Cho, DaeHo; Hur, Daeyoung

    2011-05-01

    Natural Killer cells are known to play a major role in the innate immune response against viral infections and tumor cells. Several viruses, such as CMV, EBV and HIV-1, have acquired strategies to escape elimination by NK cells. In this study, we observed that EBV infection increased expression of IDO on B cells. To evaluate the function of IDO associated with EBV infection, we investigated whether EBV-induced IDO could modulate expression of NK cell-activation receptor, NKG2D. When NK cells were co-incubated with EBV transformed B cells, surface expression of NKG2D was significantly reduced in NK cells. Incubation with L-kynurenine, an IDO metabolite, down-modulated NKG2D expression in NK cells in a dose- and time-dependent manner. Incubation with the JNK inhibitor SP600125 also inhibited NKG2D expression in NK cells. In addition, we observed that the effect of L-kynurenine was blocked by JNK agonist, anisomycin, suggesting the involvement of the JNK pathway in the signal transduction of L-kynurenine-reduced NKG2D expression. Furthermore, IL-18 significantly reduced L-kynurenine-induced down-regulation of NKG2D expression in NK cells. Taken together, these data indicate that down-regulation of NKG2D by EBV-induced IDO metabolite provides a potential mechanism by which EBV escapes NKG2D-mediated attack by immune cells.

  3. GEL-STATE NMR OF BALL-MILLED WHOLE CELL WALLS IN DMSO-d6 USING 2D SOLUTION-STATE NMR SPECTROSCOPY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant cell walls were used for obtaining 2D solution-state NMR spectra without actual solubilization or structural modification. Ball-milled whole cell walls were swelled directly in the NMR tube with DMSO-d6 where they formed a gel. There are relatively few gel-state NMR studies. Most have involved...

  4. Electromagnetic 2D/3D Particle-in-Cell simulations of the solar wind interaction with lunar crustal anomalies.

    NASA Astrophysics Data System (ADS)

    Deca, Jan; Lapenta, Giovanni; Lembège, Bertrand; Divin, Andrey; Markidis, Stefano; Amaya, Jorge

    2013-04-01

    We present the first 2D/3D fully kinetic Particle-in-Cell simulations of the solar wind interaction with lunar crustal magnetic anomalies. The simulations are performed using the implicit electromagnetic Particle-in-Cell code iPIC3D [Markidis, Lapenta & Rizwan-uddin, 2010]. Multiscale physics is resolved for all plasma components (heavy ions, protons and electrons) in the code, recently updated with a set of open boundary conditions designed for solar wind-body interactions. We use a dipole to model the crustal anomaly. The dipole center is located outside the computational domain and the boundary representing the lunar surface is modeled as a particle-absorbing plane. Photo-emission from the lunar surface is at this point not included, but will be in future work. We study the behaviour of the dipole model with variable surface magnetic field strength under changing solar wind conditions and confirm that lunar crustal magnetic fields may indeed be strong enough to stand off the solar wind and form a mini-magnetosphere, as suggested by MHD simulations [Harnett & Winglee, 2000, 2002, 2003] and spacecraft observations [Kurata et al., 2005; Halekas et al., 2008; Wieser et al., 2010]. 3D-PIC simulations reveal to be very helpful to analyze the diversion/braking of the particle flux and the characteristics of the resulting particles accumulation. The particle flux to the surface is significantly reduced at the magnetic anomaly, surrounded by a region of enhanced density due to the magnetic mirror effect. Finally we will present preliminary results on the interaction of the solar wind with weaker magnetic anomalies in which highly non-adiabatic interactions are expected.

  5. Flow through, immunomagnetic cell separation.

    PubMed

    Chalmers, J J; Zborowski, M; Sun, L; Moore, L

    1998-01-01

    A brief, process-oriented overview of immunologically based cell separation technology is presented. In addition, the design and preliminary experimental data of two unique flow-through immunomagnetic cell separation devices are presented. The first design is based on a dipole magnetic field, while the second design is basis on a quadrupole magnetic field. The dipole design can "fractionate" an inlet, magnetically labeled, cell stream into different outlet streams on the basis of the degree to which the cell is immunomagnetically labeled. The quadrupole separator splits an inlet, immunomagnetically labeled, cell stream into two outlet streams in which the purity, recovery, and potentially the degree to which the cells are immunomagnetically labeled is controlled by the flow rates in the inlet and outlet flows. A 99% purity and 86% recovery have been achieved with this system. Some distinct advantages of these two systems are the potential of high purity, recovery, and throughput at a cost which is potentially significantly lower than current, comparable technologies.

  6. The Effect of 1α,25(OH)2D3 on Osteogenic Differentiation of Stem Cells from Dental Pulp of Exfoliated Deciduous Teeth

    PubMed Central

    Mojarad, Farzad; Amiri, Iraj; Rafatjou, Rezvan; Janeshin, Atousa; Farhadian, Maryam

    2016-01-01

    Statement of the Problem: Stem cells from human exfoliated deciduous teeth (SHEDs) are a population of highly proliferative cells, being capable of differentiating into osteogenic, odontogenic, adipocytes, and neural cells. Vitamin D3 metabolites such as 1α, 25-dihydroxyvitamin D3 are key factors in the regulation of bone metabolism. Purpose: The aim of this study was to investigate the effect of 1α, 25-dihydroxyvitamin D3 on osteogenic differentiation (alkaline phosphatase activity and alizarin red staining) of stem cells of exfoliated deciduous teeth. Materials and Method: Dental pulp was removed from freshly extracted primary teeth and immersed in a digestive solution. Then, the dental pulp cells were immersed in α-MEM (minimum essential medium) to which 10% fetal bovine serum was added. After the third passage, the cells were isolated from the culture plate and were used for osteogenic differentiation. As a control group, the cells were cultured in osteogenic cell culture medium. As the case group, the cells were cultured in osteogenic culture medium supplemented with 100 nM 1α,25 (OH)2D3. The alkaline phosphatase (ALP) activity and alizarin red staining were analyzed to evaluate the osteogenic differentiation at day 21. The results were analyzed by using t-test. Results: Compared with the control group, significant increase was observed in ALP activity of SHEDs after being treated with 1α,25(OH)2D3 (p= 0.002). Alizarin red staining demonstrated that the cells exposed to 1α,25(OH)2D3 induced higher mineralized nodules (p< 0.001). Conclusion: Osteoblast differentiation in SHEDs was stimulated by 1α,25(OH) 2D3. It can be concluded that 1α,25(OH)2D3 can improve osteoblastic differentiation. PMID:27942551

  7. An all-regime Lagrange-Projection like scheme for 2D homogeneous models for two-phase flows on unstructured meshes

    NASA Astrophysics Data System (ADS)

    Chalons, Christophe; Girardin, Mathieu; Kokh, Samuel

    2017-04-01

    We propose an all regime Lagrange-Projection like numerical scheme for 2D homogeneous models for two-phase flows. By all regime, we mean that the numerical scheme is able to compute accurate approximate solutions with an under-resolved discretization, i.e. a mesh size and time step much bigger than the Mach number M of the mixture. The key idea is to decouple acoustic, transport and phase transition phenomenon using a Lagrange-Projection decomposition in order to treat implicitly (fast) acoustic and phase transition phenomenon and explicitly the (slow) transport phenomena. Then, extending a strategy developed in the case of the usual gas dynamics equations, we alter the numerical flux in the acoustic approximation to obtain a uniform truncation error in terms of M. This modified scheme is conservative and endowed with good stability properties with respect to the positivity of the density and preserving the mass fraction within the interval (0 , 1). Numerical evidences are proposed and show the ability of the scheme to deal with cases where the flow regime may vary from low to high Mach values.

  8. Spatiotemporal changes in Cx30 and Cx43 expression during neuronal differentiation of P19 EC and NT2/D1 cells.

    PubMed

    Wan, Carthur K; O'Carroll, Simon J; Kim, Sue-Ling; Green, Colin R; Nicholson, Louise F B

    2013-12-01

    While connexins (Cxs) are thought to be involved in differentiation, their expression and role has yet to be fully elucidated. We investigated the temporal expression of Cx30, Cx36 and Cx43 in two in vitro models of neuronal differentiation: human NT2/D1 and murine P19 cells, and the spatial localisation of Cx30 and Cx43 in these models. A temporal Cx43 downregulation was confirmed in both cell lines during RA-induced neuronal differentiation using RT-PCR (P < 0.05) preceding an increase in neuronal doublecortin protein. RT-PCR showed Cx36 was upregulated twofold in NT2/D1 cells (P < 0.05) and sixfold in P19 cells (P < 0.001) during neuronal differentiation. Cx30 exhibited a transient peak in expression midway through the timecourse of differentiation increasing threefold in NT2/D1 cells (P < 0.001) and eightfold in P19 cells (P < 0.01). Qualitative immunocytochemistry was used to examine spatiotemporal patterns of Cx protein distribution alongside neuronal differentiation markers. The temporal immunolabelling pattern was similar to that seen using RT-PCR. Cx43 was observed intracellularly and on cell surfaces, while Cx30 was seen as puncta. Spatially Cx43 was seen on doublecortin-negative cells, which may indicate Cx43 downregulation is requisite for differentiation in these models. Conversely, Cx30 puncta were observed on doublecortin-positive and -negative cells in NT2/D1 cells and examination of the Cx30 peak showed puncta also localized to nestin-positive cells, with few puncta on MAP2-positive cells. In P19 cells Cx30 was localized on clusters of cells surrounded by MAP2- and doublecortin-positive processes. The expression pattern of Cx30 indicates a role in neuronal differentiation; the nature of that role warrants future investigation.

  9. BET_VH probabilistic assessment of pyroclastic flows hazard at El Misti volcano, South Peru, based on geological record and numerical simulations with TITAN2D

    NASA Astrophysics Data System (ADS)

    Constantinescu, R.; Thouret, J. C.; Sandri, L.; Irimus, I. A.; Stefanescu, R.

    2012-04-01

    Pyroclastic density currents, which include pyroclastic surges and pyroclastic flows (PFs), are among the most dangerous volcanic phenomena. We present a probabilistic hazard assessment of the PFs generated from eruptive column collapse at El Misti volcano (5822 m) in South Peru. The high relief of the cone, the location of the city of Arequipa (~1,000,000 people) on two large volcanoclastic fans and the H (3.5 km)/L (17 km) ratio (0.2) between the summit and the city center, make PFs a direct threat. We consider three eruption scenario sizes: small Vulcanian/Phreatomagmatic (VEI 2), medium Sub-Plinian (VEI 3-4), and large Plinian (VEI 4+). We use the Event-Tree approach in a Bayesian scheme with BET_VH (Bayesian Event Tree for Volcanic Hazard) software. Quantitative data that stem from numerical simulations from TITAN2D (termed prior models) and from stratigraphic record (termed past data) are input to BET_VH, which enables us to compute the probabilities (in a 1-year time window) of (i) having an eruption (ii) in a selected location/vent (iii) of a specific size, (iv) and that this eruption will produce PFs (v) that will reach a location of interest around El Misti. TITAN2D simulation runs, expressed as color-coded thicknesses of PDC deposits, fit well the extent of past PFs deposits, including thick confined deposits (0.5-7 m) in the Rio Chili canyon and its tributary ravines (Quebradas San Lazaro, Huarangal and Agua Salada).The unconfined, thinner (≤10cm) deposits, as displayed by simulation runs on the interfluves, is attributed to ash-cloud surges. Such thin, fine ash deposits have not been emphasized in geological maps either because they have been removed away or remain yet unrecognized. The simulated Vulcanian flows, restricted to the upper part of the cone, become confined (0.1-1m thick) in the ravines which converge towards each of the three Quebradas. The simulated Subplinian PF deposits reach 0.1 to 1 m thick in the Quebradas and 1-4 m WNW of El

  10. Loqs depends on R2D2 to localize in D2 body-like granules and functions in RNAi pathways in silkworm cells.

    PubMed

    Zhu, Li; Tatsuke, Tsuneyuki; Xu, Jian; Li, Zhiqing; Mon, Hiroaki; Lee, Jae Man; Kusakabe, Takahiro

    2015-09-01

    The phenomenon of RNA interference (RNAi) has been found in various organisms. However, the proteins implicated in RNAi pathway in different species show distinct roles. Knowledge on the underlying mechanism of lepidopteron RNAi is quite lacking such as the roles of Loquacious (Loqs) and R2D2, the dsRNA-binding proteins in silkworm RNAi pathway. Here, we report that Loqs and R2D2 protein depletion affected efficiency of dsRNA-mediated RNAi pathway. Besides, Loqs was found to co-localize with Dicer2 to some specific cytoplasmic foci, which were looked like D2-bodies marked by R2D2 and Dicer2 in Fly cells, thereby calling the foci as D2 body-like granules. Using RNAi methods, Loqs was found to be the key protein in these granules, although R2D2 determined the localization of Loqs in D2 body-like granules. Interestingly, in the R2D2-depeted silkworm cells, the formation of processing bodies, another cytoplasmic foci, was affected. These data indicated R2D2 regulated these two kinds of cytoplasmic foci. Domain deletion analysis demonstrated that dsRBD 1 and 2 were required for Loqs in D2 body-like granules and dsRBD 2 and 3 were required for Loqs to interact with R2D2 and Ago1, respectively. Altogether, our observations provide important information for further study on D2 body-like granules, the newly found cytoplasmic foci in silkworm cells.

  11. 3D rotating wall vessel and 2D cell culture of four veterinary virus pathogens: A comparison of virus yields, portions of infectious particles and virus growth curves.

    PubMed

    Malenovská, Hana

    2016-02-01

    Only very few comparative studies have been performed that evaluate general trends of virus growth under 3D in comparison with 2D cell culture conditions. The aim of this study was to investigate differences when four animal viruses are cultured in 2D and 3D. Suid herpesvirus 1 (SuHV-1), Vesicular stomatitis virus (VSIV), Bovine adenovirus (BAdV) and Bovine parainfluenza 3 virus (BPIV-3) were cultivated in 3D rotating wall vessels (RWVs) and conventional 2D cultures. The production of virus particles, the portion of infectious particles, and the infectious growth curves were compared. For all viruses, the production of virus particles (related to cell density), including the non-infectious ones, was lower in 3D than in 2D culture. The production of only infectious particles was significantly lower in BAdV and BPIV-3 in 3D cultures in relation to cell density. The two cultivation approaches resulted in significantly different virus particle-to-TCID50 ratios in three of the four viruses: lower in SuHV-1 and BPIV-3 and higher in BAdV in 3D culture. The infectious virus growth rates were not significantly different in all viruses. Although 3D RWV culture resulted in lower production of virus particles compared to 2D systems, the portion of infectious particles was higher for some viruses.

  12. Whole cell quenched flow analysis.

    PubMed

    Chiang, Ya-Yu; Haeri, Sina; Gizewski, Carsten; Stewart, Joanna D; Ehrhard, Peter; Shrimpton, John; Janasek, Dirk; West, Jonathan

    2013-12-03

    This paper describes a microfluidic quenched flow platform for the investigation of ligand-mediated cell surface processes with unprecedented temporal resolution. A roll-slip behavior caused by cell-wall-fluid coupling was documented and acts to minimize the compression and shear stresses experienced by the cell. This feature enables high-velocity (100-400 mm/s) operation without impacting the integrity of the cell membrane. In addition, rotation generates localized convection paths. This cell-driven micromixing effect causes the cell to become rapidly enveloped with ligands to saturate the surface receptors. High-speed imaging of the transport of a Janus particle and fictitious domain numerical simulations were used to predict millisecond-scale biochemical switching times. Dispersion in the incubation channel was characterized by microparticle image velocimetry and minimized by using a horizontal Hele-Shaw velocity profile in combination with vertical hydrodynamic focusing to achieve highly reproducible incubation times (CV = 3.6%). Microfluidic quenched flow was used to investigate the pY1131 autophosphorylation transition in the type I insulin-like growth factor receptor (IGF-1R). This predimerized receptor undergoes autophosphorylation within 100 ms of stimulation. Beyond this demonstration, the extreme temporal resolution can be used to gain new insights into the mechanisms underpinning a tremendous variety of important cell surface events.

  13. Selective upregulation of the expression of plasma membrane calcium ATPase isoforms upon differentiation and 1,25(OH)2D3-vitamin treatment of colon cancer cells.

    PubMed

    Ribiczey, Polett; Papp, Béla; Homolya, László; Enyedi, Ágnes; Kovács, Tünde

    2015-08-14

    We have previously presented co-expression of the plasma membrane calcium ATPase isoforms 4b (PMCA4b) and 1b (PMCA1b) in colon carcinoma cells, and selective upregulation of PMCA4b during differentiation initiated by short chain fatty acids or post-confluent growth. Here we show that the induction of PMCA4b expression is a characteristic feature of the post-confluency-induced differentiation of both enterocyte-type and goblet cell-type colon cancer cells. Vitamin D3 (1,25(OH)2D3) is a well-known regulator of intestinal Ca(2+) absorption and of basic cell functions such as growth and differentiation in various cell types. As PMCA proteins are involved both in intestinal Ca(2+) absorption and adenocarcinoma cell differentiation, we investigated the effect of 1,25(OH)2D3 on PMCA expression in enterocyte-like colon carcinoma cells, and monitored its effect on the expression of various differentiation markers. 1,25(OH)2D3 stimulated PMCA1b, but not PMCA4b expression without modulating the expression of the majority of the differentiation markers examined. Caco-2 cells differentiated in post-confluent cultures present normal enterocyte-like intestinal epithelial phenotype. To better understand the role of PMCA proteins in vectorial Ca(2+) transport by enterocytes, we also studied their subcellular localization in mature polarized Caco-2 cells. Both PMCA isoforms were located to the basolateral membrane, and the PMCA-specific immunofluorescent signal was significantly higher in vitamin D3-treated cells, underlining the 1,25(OH)2D3-induced upregulation of PMCA (presumably 1b isoform) expression in differentiated Caco-2 cells. We suggest that while PMCA1b has a housekeeping function in colon cancer cells, PMCA4b participates in the reorganization of the Ca(2+) signalling machinery during cell differentiation. The subcellular localization of PMCA1b and its selective 1,25(OH)2D3-dependent upregulation indicate that this isoform may have a specific role in 1,25(OH)2D3

  14. Cytotoxic responses of carnosic acid and doxorubicin on breast cancer cells in butterfly-shaped microchips in comparison to 2D and 3D culture.

    PubMed

    Yildiz-Ozturk, Ece; Gulce-Iz, Sultan; Anil, Muge; Yesil-Celiktas, Ozlem

    2017-04-01

    Two dimensional (2D) cell culture systems lack the ability to mimic in vivo conditions resulting in limitations for preclinical cell-based drug and toxicity screening assays and modelling tumor biology. Alternatively, 3D cell culture systems mimic the specificity of native tissue with better physiological integrity. In this regard, microfluidic chips have gained wide applicability for in vitro 3D cancer cell studies. The aim of this research was to develop a 3D biomimetic model comprising culture of breast cancer cells in butterfly-shaped microchip to determine the cytotoxicity of carnosic acid and doxorubicin on both estrogen dependent (MCF-7) and independent (MDA-MB231) breast cancer cells along with healthy mammary epithelial cells (MCF-10A) in 2D, 3D Matrigel™ and butterfly-shaped microchip environment. According to the developed mimetic model, carnosic acid exhibited a higher cytotoxicity towards MDA-MB 231, while doxorubicin was more effective against MCF-7. Although the cell viabilities were higher in comparison to 2D and 3D cell culture systems, the responses of the investigated molecules were different in the microchips based on the molecular weight and structural complexity indicating the importance of biomimicry in a physiologically relevant matrix.

  15. The inhibitory effects of synthetic short peptides, mimicking MICA and targeting at NKG2D receptors, on function of NK cells.

    PubMed

    Zhang, Bin; Wei, Haiming; Zheng, Xiaodong; Zhang, Jian; Sun, Rui; Tian, Zhigang

    2005-03-01

    NKG2D is an activating receptor expressed on most of human NK cells, one of whose ligands is MICA. Based on the crystal structure of NKG2D-MICA complex, we synthesized three short peptides (P1, P2 and P3), mimicking functional alpha1 and alpha2 domain of MICA. The inhibitory effects of three peptides on NK-92 cells, a human NK cell line against Hela cells were observed and the inhibitory percentage was 38% at maximum for P1+P2+P3 in concentration of 1nM. The same peptides had no effect on NK-92 cell against target cells lacking MICA (K562 cells line). The unrelated peptides as controls had no effect on the system. Two peptides (P2 and P3) were prolonged at one or both ends, and the longer forms of peptides exerted stronger inhibitory effects than their shorter forms. Each combination of two peptides exerted a stronger function than single peptide (P1, P2, P3), indicating that shedding of longer amino acid sequence of alpha1 domain or more domain sites of MICA are better than shorter sequence and fewer sites. P1+P2+P3 revealed the almost same inhibitory rate as the soluble MICA (sMICA). P1+P2+P3 were also able to alleviate the concanavalin A-induced murine autoimmune hepatitis in vivo, conforming the similarity of NKG2D between human and mice. The results demonstrate that MICA-mimicking peptides will be useful to search the specific functional sites for NKG2D-MICA interaction, but also promising in explaining NKG2D-related autoimmunity.

  16. Modulation of NKG2D-mediated cytotoxic functions of natural killer cells by viral protein R from HIV-1 primary isolates.

    PubMed

    Pham, Tram N Q; Richard, Jonathan; Gerard, Francine C A; Power, Christopher; Cohen, Éric A

    2011-12-01

    HIV-1 viral protein R (Vpr) from laboratory-adapted virus strains activates the DNA damage/stress sensor ATR kinase and induces cell cycle arrest at the G(2)/M phase through a process that requires Vpr to engage the DDB1-CUL4A (VprBP/DCAF-1) E3 ligase complex. Activation of this DNA damage/stress checkpoint in G(2) by Vpr was shown to modulate NKG2D-dependent NK cell effector functions via enhancing expression of NKG2D ligands, notably ULBP2. However, it is unknown whether Vpr from HIV-1 primary isolates (groups M, N, O, and P) could modulate NKG2D-mediated cytotoxic functions of NK cells. Here, we report that Vpr from most HIV-1 primary isolates can upregulate ULBP2 expression and induce NKG2D-dependent NK cell killing. Importantly, these activities were always accompanied by an active G(2) cell cycle arrest function. Interestingly, Vpr variants from group P and a clade D isolate of group M were defective at enhancing NKG2D-mediated NK cell lysis owing to their inability to augment ULBP2 expression. However, distinct mechanisms were responsible for their failure to do so. While Vpr from group P was deficient in its ability to engage the DDB1-CUL4A (VprBP/DCAF-1) E3 ligase complex, the Vpr variant from group D was unable to properly localize to the nucleus, underlining the importance of these biological properties in Vpr function. In conclusion, the ability of Vpr from HIV-1 primary isolates to regulate NK cell effector function underscores the importance of this HIV-1 accessory protein in the modulation of the host's innate immune responses.

  17. SUTRA: A model for 2D or 3D saturated-unsaturated, variable-density ground-water flow with solute or energy transport

    USGS Publications Warehouse

    Voss, Clifford I.; Provost, A.M.

    2002-01-01

    SUTRA (Saturated-Unsaturated Transport) is a computer program that simulates fluid movement and the transport of either energy or dissolved substances in a subsurface environment. This upgraded version of SUTRA adds the capability for three-dimensional simulation to the former code (Voss, 1984), which allowed only two-dimensional simulation. The code employs a two- or three-dimensional finite-element and finite-difference method to approximate the governing equations that describe the two interdependent processes that are simulated: 1) fluid density-dependent saturated or unsaturated ground-water flow; and 2) either (a) transport of a solute in the ground water, in which the solute may be subject to: equilibrium adsorption on the porous matrix, and both first-order and zero-order production or decay; or (b) transport of thermal energy in the ground water and solid matrix of the aquifer. SUTRA may also be used to simulate simpler subsets of the above processes. A flow-direction-dependent dispersion process for anisotropic media is also provided by the code and is introduced in this report. As the primary calculated result, SUTRA provides fluid pressures and either solute concentrations or temperatures, as they vary with time, everywhere in the simulated subsurface system. SUTRA flow simulation may be employed for two-dimensional (2D) areal, cross sectional and three-dimensional (3D) modeling of saturated ground-water flow systems, and for cross sectional and 3D modeling of unsaturated zone flow. Solute-transport simulation using SUTRA may be employed to model natural or man-induced chemical-species transport including processes of solute sorption, production, and decay. For example, it may be applied to analyze ground-water contaminant transport problems and aquifer restoration designs. In addition, solute-transport simulation with SUTRA may be used for modeling of variable-density leachate movement, and for cross sectional modeling of saltwater intrusion in

  18. Cell cycle arrest and apoptosis induced by 1α,25(OH)2D3 and TX 527 in Kaposi sarcoma is VDR dependent.

    PubMed

    González-Pardo, Verónica; Suares, Alejandra; Verstuyf, Annemieke; De Clercq, Pierre; Boland, Ricardo; de Boland, Ana Russo

    2014-10-01

    We have previously shown that 1α,25(OH)2-Vitamin D3 [1α,25(OH)2D3] and its less calcemic analog TX 527 inhibit the proliferation of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR) and this could be partially explained by the inhibition of the NF-κB pathway. In this work, we further explored the mechanism of action of both vitamin D compounds in Kaposi sarcoma. We investigated whether the cell cycle arrest and subsequent apoptosis of endothelial cells (SVEC) and SVEC transformed by vGPCR (SVEC-vGPCR) elicited by 1α,25(OH)2D3 and TX 527 were mediated by the vitamin D receptor (VDR). Cell cycle analysis of SVEC and SVEC-vGPCR treated with 1α,25(OH)2D3 (10nM, 48h) revealed that 1α,25(OH)2D3 increased the percentage of cells in the G0/G1 phase and diminished the percentage of cells in the S phase of the cell cycle. Moreover, the number of cells in the S phase was higher in SVEC-vGPCR than in SVEC due to vGPCR expression. TX 527 exerted similar effects on growth arrest in SVEC-vGPCR cells. The cell cycle changes were suppressed when the expression of the VDR was blocked by a stable transfection of shRNA against VDR. Annexin V-PI staining demonstrated apoptosis in both SVEC and SVEC-vGPCR after 1α,25(OH)2D3 and TX 527 treatment (10nM, 24h). Cleavage of caspase-3 detected by Western blot analysis was increased to a greater extent in SVEC than in SVEC-vGPCR cells, and this effect was also blocked in VDR knockdown cells. Altogether, these results suggest that 1α,25(OH)2D3 and TX 527 inhibit the proliferation of SVEC and SVEC-vGPCR and induce apoptosis by a mechanism that involves the VDR.

  19. NKG2D - RAE-1 receptor-ligand variation does not account for the Natural Killer cell defect in nonobese diabetic mice1

    PubMed Central

    Maier, Lisa M.; Howlett, Sarah; Rainbow, Kara; Clark, Jan; Howson, Joanna M.M.; Todd, John A.; Wicker, Linda S.

    2008-01-01

    Natural Killer (NK) cells from nonobese diabetic (NOD) mice induced with poly I:C in vivo exhibit low cytotoxicity against a range of target cells, but the genetic mechanisms controlling this defect are yet to be elucidated. Defects in the expression of NKG2D and its ligands, the RAE-1 molecules, have been hypothesized to contribute to the reduced NK function present in NOD mice. Here we show that segregation of the NK-mediated killing phenotype did not correlate with the NOD Raet1 haplotype, and that the large alterations in NKG2D expression previously reported on NK cells expanded in vitro were not observed in primary, poly I:C-elicited NK cells in vivo. Additional studies indicate a complex genetic control of defective NOD NK cells, including genes linked to the MHC and possibly those that are associated with an altered cytokine response to the TLR3-agonist, poly I:C. PMID:18981127

  20. A rapid and efficient 2D/3D nuclear segmentation method for analysis of early mouse embryo and stem cell image data.

    PubMed

    Lou, Xinghua; Kang, Minjung; Xenopoulos, Panagiotis; Muñoz-Descalzo, Silvia; Hadjantonakis, Anna-Katerina

    2014-03-11

    Segmentation is a fundamental problem that dominates the success of microscopic image analysis. In almost 25 years of cell detection software development, there is still no single piece of commercial software that works well in practice when applied to early mouse embryo or stem cell image data. To address this need, we developed MINS (modular interactive nuclear segmentation) as a MATLAB/C++-based segmentation tool tailored for counting cells and fluorescent intensity measurements of 2D and 3D image data. Our aim was to develop a tool that is accurate and efficient yet straightforward and user friendly. The MINS pipeline comprises three major cascaded modules: detection, segmentation, and cell position classification. An extensive evaluation of MINS on both 2D and 3D images, and comparison to related tools, reveals improvements in segmentation accuracy and usability. Thus, its accuracy and ease of use will allow MINS to be implemented for routine single-cell-level image analyses.

  1. Comparison of several radiation effects in human MCF10A mammary epithelial cells cultured as 2D monolayers or 3D acinar stuctures in matrigel.

    PubMed

    Lin, Yu-Fen; Nagasawa, Hatsumi; Peng, Yuanlin; Chuang, Eric Y; Bedford, Joel S

    2009-06-01

    It has been argued that the cell-cell and cell-matrix interaction networks in normal tissues are disrupted by radiation and that this largely controls many of the most important cellular radiation responses. This has led to the broader assertion that individual cells in normal tissue or a 3D normal-tissue-like culture will respond to radiation very differently than the same cells in a 2D monolayer culture. While many studies have shown that, in some cases, cell-cell contact in spheroids of transformed or tumor cell lines can alter radiation responses relative to those for the same cells in monolayer cultures, a question remains regarding the possible effect of the above-mentioned disruption of signaling networks that operate more specifically for cells in normal tissues or in a 3D tissue-like context. To test the generality of this notion, we used human MCF-10A cells, an immortalized mammary epithelial cell line that produces acinar structures in culture with many properties of human mammary ducts. We compared the dose responses for these cells in the 2D monolayer and in 3D ductal or acinar structures. The responses examined were reproductive cell death, induction of chromosomal aberrations, and the levels of gamma-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 h of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose responses of these cells in 2D or 3D growth conditions. While this does not mean that such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur.

  2. Computer-aided 2D and 3D quantification of human stem cell fate from in vitro samples using Volocity high performance image analysis software.

    PubMed

    Piltti, Katja M; Haus, Daniel L; Do, Eileen; Perez, Harvey; Anderson, A J; Cummings, B J

    2011-11-01

    Accurate automated cell fate analysis of immunostained human stem cells from 2- and 3-dimensional (2D-3D) images would improve efficiency in the field of stem cell research. Development of an accurate and precise tool that reduces variability and the time needed for human stem cell fate analysis will improve productivity and interpretability of the data across research groups. In this study, we have created protocols for high performance image analysis software Volocity® to classify and quantify cytoplasmic and nuclear cell fate markers from 2D-3D images of human neural stem cells after in vitro differentiation. To enhance 3D image capture efficiency, we optimized the image acquisition settings of an Olympus FV10i® confocal laser scanning microscope to match our quantification protocols and improve cell fate classification. The methods developed in this study will allow for a more time efficient and accurate software based, operator validated, stem cell fate classification and quantification from 2D and 3D images, and yield the highest ≥94.4% correspondence with human recognized objects.

  3. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3

    PubMed Central

    Chiang, Kun-Chun; Yeh, Chun-Nan; Huang, Cheng-Cheng; Yeh, Ta-Sen; S. Pang, Jong-Hwei; Hsu, Jun-Te; Chen, Li-Wei; Kuo, Sheng-Fong; Kittaka, Atsushi; Chen, Tai C.; Juang, Horng-Heng

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA. PMID:27529229

  4. Differential effects of MAPK pathway inhibitors on migration and invasiveness of BRAF(V600E) mutant thyroid cancer cells in 2D and 3D culture.

    PubMed

    Ingeson-Carlsson, Camilla; Martinez-Monleon, Angela; Nilsson, Mikael

    2015-11-01

    Tumor microenvironment influences targeted drug therapy. In this study we compared drug responses to RAF and MEK inhibitors on tumor cell migration in 2D and 3D culture of BRAF(V600E) mutant cell lines derived from human papillary (BCPAP) and anaplastic (SW1736) thyroid carcinomas. Scratch wounding was compared to a double-layered collagen gel model developed for analysis of directed tumor cell invasion during prolonged culture. In BCPAP both PLX4720 and U0126 inhibited growth and migration in 2D and decreased tumor cell survival in 3D. In SW1736 drugs had no effect on migration in 2D but decreased invasion in 3D, however this related to reduced growth. Dual inhibition of BRAF(V600E) and MEK reduced but did not prevent SW1736 invasion although rebound phosphorylation of ERK in response to PLX4720 was blocked by U0126. These findings indicate that anti-tumor drug effects in vitro differ depending on culture conditions (2D vs. 3D) and that the invasive features of anaplastic thyroid cancer depend on non-MEK mechanism(s).

  5. Valproic Acid Upregulates NKG2D Ligand Expression through an ERK-dependent Mechanism and Potentially Enhances NK Cell-mediated Lysis of Myeloma1

    PubMed Central

    Wu, Xiaosong; Tao, Yi; Hou, Jun; Meng, Xiuqin; Shi, Jumei

    2012-01-01

    Modulation of the antitumor immune response through the engagement of NKG2D receptors with their ligands (L) on targets represents a promising therapeutic approach against cancer. In this study, we tested the effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on the expression of NKG2D ligands in myeloma cells. We demonstrated that VPA was able to upregulate both protein and mRNA expression of major histocompatibility complex class I-related chain (MIC) A/B and UL16-binding protein (ULBP) 2 without any significant effect on the expression of ULBP1, ULBP3, and ULBP4 or induction of other natural killer (NK) cell ligands, such as NKp30-L, NKp44-L, and NKp46-L in myeloma cells. A 51Cr release assay and degranulation assay indicated that the induction of MICA/B and ULBP2 augmented NK cell-mediated lysis of myeloma cells, which was abolished by the addition of a blocking NKG2D antibody. Activation of constitutively phosphorylated extracellular signal-regulated kinase (ERK) by VPA is essential for the up-regulation of MICA/B and ULBP2 expressions. Inhibition of ERK using ERK inhibitor PD98059 decreased both MICA/B and ULBP2 expressions and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in ARK resulted in increased MICA/B and ULBP2 expressions and enhanced NK cell lysis. These data indicate that increased sensitivity of VPA-treated myeloma cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway. Our results provide evidence that targeting ERK signaling pathway may be an additional mechanism supporting the antimyeloma activity of HDAC inhibitors and suggest its possible immunotherapeutic value for myeloma treatment. PMID:23308050

  6. Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth.

    PubMed

    Hervieu, Alice; Rébé, Cédric; Végran, Frédérique; Chalmin, Fanny; Bruchard, Mélanie; Vabres, Pierre; Apetoh, Lionel; Ghiringhelli, François; Mignot, Grégoire

    2013-02-01

    Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex class I molecules on tumor cells, rendering them sensitive to cytotoxic CD8(+) T cells. Accordingly, DTIC markedly enhanced cytotoxic T lymphocyte antigen 4 inhibition efficacy in vivo in an NK-dependent manner. These results underscore the immunogenic properties of DTIC and provide a rationale to combine DTIC with immunotherapeutic agents that relieve immunosuppression in vivo.

  7. Effect of 1,25-(OH)2D3 and lipopolysaccharide on mononuclear cell inflammation in type 2 diabetes mellitus and diabetic nephropathy uremia.

    PubMed

    Wu, E L; Cui, H X

    2016-08-29

    The prevention and treatment of type-2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), which are disorders with high incidence rates, is of primary importance. In this study, we analyzed the effect of 1,25-(OH)2D3 and lipopolysaccharide (LPS) in combination with interleukin (IL)-15 on the inflammatory immune response and expression of vitamin D receptor (VDR) in mononuclear cells of T2DM and DN uremia (DNU) patients. The human acute monocytic leukemia cell line THP-1 was treated with peripheral blood serum isolated from 30 healthy controls and T2DM and DNU patients each, cultured in the presence or absence of 1,25-(OH)2D3, and subsequently treated with LPS and IL-15. The VDR mRNA and protein expression in THP-1 cells was detected by real-time polymerase chain reaction and western blot (and immunofluorescence assay), respectively, and IL-6 and IL-10 concentrations in the culture supernatant were detected by enzyme-linked immunosorbent assay. LPS treatment induced a significant decrease in VDR mRNA expression in T2DM and DNU serum-treated THP-1 cells compared to the control cells (P < 0.05). The VDR protein expression in DNU serum-treated THP-1 cells was also significantly down-regulated (P < 0.05). LPS treatment induced IL-6 secretion in serum-treated THP-1 cells (P < 0.05), while 1,25-(OH)2D3 treatment inhibited IL-6 secretion to some extent. These findings suggested that LPS down-regulates the expression of VDR in mononuclear cells of T2DM and DNU patients and induces an imbalance in the pro-inflammatory and anti-inflammatory cytokine response, while 1,25-(OH)2D3 partially reversed the effect of LPS and protected patients with T2DM and DNU.

  8. Contrasting Effects of the Cytotoxic Anticancer Drug Gemcitabine and the EGFR Tyrosine Kinase Inhibitor Gefitinib on NK Cell-Mediated Cytotoxicity via Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells

    PubMed Central

    Okita, Riki; Wolf, Diana; Yasuda, Koichiro; Maeda, Ai; Yukawa, Takuro; Saisho, Shinsuke; Shimizu, Katsuhiko; Yamaguchi, Yoshiyuki; Oka, Mikio; Nakayama, Eiichi; Lundqvist, Andreas; Kiessling, Rolf; Seliger, Barbara; Nakata, Masao

    2015-01-01

    Introduction Several cytotoxic anticancer drugs inhibit DNA replication and/or mitosis, while EGFR tyrosine kinase inhibitors inactivate EGFR signalling in cancer cell. Both types of anticancer drugs improve the overall survival of the patients with non-small-cell lung cancer (NSCLC), although tumors often become refractory to this treatment. Despite several mechanisms by which the tumors become resistant having been described the effect of these compounds on anti-tumor immunity remains largely unknown. Methods This study examines the effect of the cytotoxic drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on the expression of NK group 2 member D (NKG2D) ligands as well as the sensitivity of NSCLC cells to the NK-mediated lysis. Results We demonstrate that Gemcitabine treatment leads to an enhanced expression, while Gefitinib downregulated the expression of molecules that act as key ligands for the activating receptor NKG2D and promote NK cell-mediated recognition and cytolysis. Gemcitabine activated ATM and ATM- and Rad-3-related protein kinase (ATR) pathways. The Gemcitabine-induced phosphorylation of ATM as well as the upregulation of the NKG2D ligand expression could be blocked by an ATM-ATR inhibitor. In contrast, Gefitinib attenuated NKG2D ligand expression. Silencing EGFR using siRNA or addition of the PI3K inhibitor resulted in downregulation of NKG2D ligands. The observations suggest that the EGFR/PI3K pathway also regulates the expression of NKG2D ligands. Additionally, we showed that both ATM-ATR and EGFR regulate MICA/B via miR20a. Conclusion In keeping with the effect on NKG2D expression, Gemcitabine enhanced NK cell-mediated cytotoxicity while Gefitinib attenuated NK cell killing in NSCLC cells. PMID:26439264

  9. Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems.

    PubMed

    Brajša, Karmen; Vujasinović, Ines; Jelić, Dubravko; Trzun, Marija; Zlatar, Ivo; Karminski-Zamola, Grace; Hranjec, Marijana

    2016-12-01

    Due to a poor clinical predictive power of 2D cell cultures, standard tool for in vitro assays in drug discovery process, there is increasing interest in developing 3D in vitro cell cultures, biologically relevant assay feasible for the development of robust preclinical anti-cancer drug screening platforms. Herein, we tested amidino-substituted benzimidazoles and benzimidazo[1,2-a]quinolines as a small platform for comparison of antitumor activity in 2D and 3D cell culture systems and correlation with structure-activity relationship. 3D cell culture method was applied on a human cancer breast (SK-BR-3, MDA-MB-231, T-47D) and pancreatic cancer cells (MIA PaCa-2, PANC-1). Results obtained in 2D and 3D models were highly comparable, but in some cases we have observed significant disagreement indicating that some prominent compounds can be discarded in early phase of researching because of compounds with false positive result. To confirm which of cell culture systems is more accurate, in vivo profiling is needed.

  10. Increased sMICA and TGFβ1 levels in HNSCC patients impair NKG2D-dependent functionality of activated NK cells

    PubMed Central

    Klöß, Stephan; Chambron, Nicole; Gardlowski, Tanja; Arseniev, Lubomir; Koch, Joachim; Esser, Ruth; Glienke, Wolfgang; Seitz, Oliver; Köhl, Ulrike

    2015-01-01

    Disseminated head-and-neck squamous cell carcinoma (HNSCC) escapes immune surveillance and thus frequently manifests as fatal disease. Here, we report on the distribution of distinct immune cell subpopulations, natural killer (NK) cell cytotoxicity and tumor immune escape mechanisms (TIEMs) in 55 HNSCC patients, either at initial diagnosis or present with tumor relapse. Compared to healthy controls, the regulatory NK cells and the ratio of pro/anti-inflammatory cytokines were decreased in HNSCC patients, while soluble major histocompatibility complex Class I chain-related peptide A (sMICA) and transforming growth factor β1 (TGFβ1) plasma levels were markedly elevated. Increased sMICA and TGFβ1 concentrations correlated with tumor progression and staging characteristics in 7 follow-up HNSCC patients, with significantly elevated levels of both soluble factors from the time of initial diagnosis to that of relapse. Patient plasma containing elevated sMICA and TGFβ1 markedly impaired NKG2D-dependent cytotoxicity against HNSCC cells upon incubation with patient-derived and IL-2 activated NK cells vs. those derived from healthy donors. Decreased antitumor recognition was accompanied by reduced NKG2D expression on the NK cell surface and an enhanced caspase-3 activity. In-vitro blocking and neutralization experiments demonstrated a synergistic negative impact of sMICA and TGFβ1 on NK cell functionality. Although we previously showed the feasibility and safety of transfer of allogeneic donor NK cells in a prior clinical study encompassing various leukemia and tumor patients, our present results suggest the need for caution regarding the sole use of adoptive NK cell transfer. The presence of soluble NKG2D ligands in the plasma of HNSCC patients and the decreased NK cell cytotoxicity due to several factors, especially TGFβ1, indicates timely depletion of these immunosuppressing molecules may promote NK cell-based immunotherapy. PMID:26451327

  11. Regulation of adipose-tissue-derived stromal cell orientation and motility in 2D- and 3D-cultures by direct-current electrical field.

    PubMed

    Yang, Gang; Long, Haiyan; Ren, Xiaomei; Ma, Kunlong; Xiao, Zhenghua; Wang, Ying; Guo, Yingqiang

    2017-02-01

    Cell alignment and motility play a critical role in a variety of cell behaviors, including cytoskeleton reorganization, membrane-protein relocation, nuclear gene expression, and extracellular matrix remodeling. Direct current electric field (EF) in vitro can direct many types of cells to align vertically to EF vector. In this work, we investigated the effects of EF stimulation on rat adipose-tissue-derived stromal cells (ADSCs) in 2D-culture on plastic culture dishes and in 3D-culture on various scaffold materials, including collagen hydrogels, chitosan hydrogels and poly(L-lactic acid)/gelatin electrospinning fibers. Rat ADSCs were exposed to various physiological-strength EFs in a homemade EF-bioreactor. Changes of morphology and movements of cells affected by applied EFs were evaluated by time-lapse microphotography, and cell survival rates and intracellular calcium oscillations were also detected. Results showed that EF facilitated ADSC morphological changes, under 6 V/cm EF strength, and that ADSCs in 2D-culture aligned vertically to EF vector and kept a good cell survival rate. In 3D-culture, cell galvanotaxis responses were subject to the synergistic effect of applied EF and scaffold materials. Fast cell movement and intracellular calcium activities were observed in the cells of 3D-culture. We believe our research will provide some experimental references for the future study in cell galvanotaxis behaviors.

  12. Augmented anti-tumor activity of NK-92 cells expressing chimeric receptors of TGF-βR II and NKG2D.

    PubMed

    Wang, Zhongjuan; Guo, Linghua; Song, Yuan; Zhang, Yinsheng; Lin, Dandan; Hu, Bo; Mei, Yu; Sandikin, Dedy; Liu, Haiyan

    2017-04-01

    The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor). NK-92 cells expressing TN receptors were resistant to TGF-β-induced suppressive signaling and did not down-regulate NKG2D. These modified NK-92 cells had higher killing capacity and interferon γ (IFN-γ) production against tumor cells compared with the control cells and their cytotoxicity could be further enhanced by TGF-β. More interestingly, the NK-92 cells expressing TN receptors were better chemo-attracted to the tumor cells expressing TGF-β. The presence of these modified NK-92 cells significantly inhibited the differentiation of human naïve CD4(+) T cells to regulatory T cells. NK-92-TN cells could also inhibit tumor growth in vivo in a hepatocellular carcinoma xenograft tumor model. Therefore, TN chimeric receptors can be a novel strategy to augment anti-tumor efficacy in NK cell adoptive therapy.

  13. NEDD9 stabilizes focal adhesions, increases binding to the extra-cellular matrix and differentially effects 2D versus 3D cell migration.

    PubMed

    Zhong, Jessie; Baquiran, Jaime B; Bonakdar, Navid; Lees, Justin; Ching, Yu Wooi; Pugacheva, Elena; Fabry, Ben; O'Neill, Geraldine M

    2012-01-01

    The speed of cell migration on 2-dimensional (2D) surfaces is determined by the rate of assembly and disassembly of clustered integrin receptors known as focal adhesions. Different modes of cell migration that have been described in 3D environments are distinguished by their dependence on integrin-mediated interactions with the extra-cellular matrix. In particular, the mesenchymal invasion mode is the most dependent on focal adhesion dynamics. The focal adhesion protein NEDD9 is a key signalling intermediary in mesenchymal cell migration, however whether NEDD9 plays a role in regulating focal adhesion dynamics has not previously been reported. As NEDD9 effects on 2D migration speed appear to depend on the cell type examined, in the present study we have used mouse embryo fibroblasts (MEFs) from mice in which the NEDD9 gene has been depleted (NEDD9 -/- MEFs). This allows comparison with effects of other focal adhesion proteins that have previously been demonstrated using MEFs. We show that focal adhesion disassembly rates are increased in the absence of NEDD9 expression and this is correlated with increased paxillin phosphorylation at focal adhesions. NEDD9-/- MEFs have increased rates of migration on 2D surfaces, but conversely, migration of these cells is significantly reduced in 3D collagen gels. Importantly we show that myosin light chain kinase is activated in 3D in the absence of NEDD9 and is conversely inhibited in 2D cultures. Measurement of adhesion strength reveals that NEDD9-/- MEFs have decreased adhesion to fibronectin, despite upregulated α5β1 fibronectin receptor expression. We find that β1 integrin activation is significantly suppressed in the NEDD9-/-, suggesting that in the absence of NEDD9 there is decreased integrin receptor activation. Collectively our data suggest that NEDD9 may promote 3D cell migration by slowing focal adhesion disassembly, promoting integrin receptor activation and increasing adhesion force to the ECM.

  14. Microarray analyses to quantify advantages of 2D and 3D hydrogel culture systems in maintaining the native valvular interstitial cell phenotype.

    PubMed

    Mabry, Kelly M; Payne, Samuel Z; Anseth, Kristi S

    2016-01-01

    Valvular interstitial cells (VICs) actively maintain and repair heart valve tissue; however, persistent activation of VICs to a myofibroblast phenotype can lead to aortic stenosis. To better understand and quantify how microenvironmental cues influence VIC phenotype and myofibroblast activation, we compared expression profiles of VICs cultured on poly(ethylene glycol) (PEG) gels to those cultured on tissue culture polystyrene (TCPS), as well as fresh isolates. In general, VICs cultured in hydrogel matrices had lower levels of activation (<10%), similar to levels seen in healthy valve tissue, while VICs cultured on TCPS were ∼75% activated myofibroblasts. VICs cultured on TCPS also exhibited a higher magnitude of perturbations in gene expression than soft hydrogel cultures when compared to the native phenotype. Using peptide-modified PEG gels, VICs were seeded on (2D), as well as encapsulated in (3D), matrices of the same composition and modulus. Despite similar levels of activation, VICs cultured in 2D had distinct variations in transcriptional profiles compared to those in 3D hydrogels. Genes related to cell structure and motility were particularly affected by the dimensionality of the culture platform, with higher expression levels in 2D than in 3D. These results indicate that dimensionality may play a significant role in dictating cell phenotype (e.g., through differences in polarity, diffusion of soluble signals), and emphasize the importance of using multiple metrics when characterizing cell phenotype.

  15. Fractal dimension as a measure of altered actin cytoskeleton in MC3T3-E1 cells under simulated microgravity using 3-D/2-D clinostats.

    PubMed

    Qian, A R; Li, D; Han, J; Gao, X; Di, S M; Zhang, W; Hu, L F; Shang, Peng

    2012-05-01

    Osteoblasts, the bone-forming cells, respond to various mechanical forces, such as stretch and fluid shear force in essentially similar ways. The cytoskeleton, as the load-bearing architecture of the cell, is sensitive to altered inertial forces. Disruption of the cytoskeleton will result in alteration of cellular structure and function. However, it is difficult to quantitatively illustrate cytoskeletal rearrangement because of the complexity of cytoskeletal structure. Usually, the morphological changes in actin organization caused by external stimulus are basically descriptive. In this study, fractal dimensions (D) analysis was used to quantify the morphological changes in the actin cytoskeleton of osteoblast-like cells (MC3T3-E1) under simulated microgravity using 3-D/2-D clinostats. The ImageJ software was used to count the fractal dimension of actin cytoskeleton by box-counting methods. Real-time PCR and immunofluroscent assays were used to further confirm the results obtained by fractal dimension analysis. The results showed significant decreases in D value of actin cytoskeleton, β-actin mRNA expression, and the mean fluorescence intensity of F-actin in osteoblast-like cells after 24 or 48 h of incubation under 3-D/2-D clinorotation condition compared with control. The findings indicate that 3-D/2-D clinorotation affects both actin cytoskeleton architecture and mRNA expression, and fractal may be a promising approach for quantitative analysis of the changes in cytoskeleton in different environments.

  16. Search for limiting factors in the RNAi pathway in silkmoth tissues and the Bm5 cell line: the RNA-binding proteins R2D2 and Translin.

    PubMed

    Swevers, Luc; Liu, Jisheng; Huvenne, Hanneke; Smagghe, Guy

    2011-01-01

    RNA interference (RNAi), an RNA-dependent gene silencing process that is initiated by double-stranded RNA (dsRNA) molecules, has been applied with variable success in lepidopteran insects, in contrast to the high efficiency achieved in the coleopteran Tribolium castaneum. To gain insight into the factors that determine the efficiency of RNAi, a survey was carried out to check the expression of factors that constitute the machinery of the small interfering RNA (siRNA) and microRNA (miRNA) pathways in different tissues and stages of the silkmoth, Bombyx mori. It was found that the dsRNA-binding protein R2D2, an essential component in the siRNA pathway in Drosophila, was expressed at minimal levels in silkmoth tissues. The silkmoth-derived Bm5 cell line was also deficient in expression of mRNA encoding full-length BmTranslin, an RNA-binding factor that has been shown to stimulate the efficiency of RNAi. However, despite the lack of expression of the RNA-binding proteins, silencing of a luciferase reporter gene was observed by co-transfection of luc dsRNA using a lipophilic reagent. In contrast, gene silencing was not detected when the cells were soaked in culture medium supplemented with dsRNA. The introduction of an expression construct for Tribolium R2D2 (TcR2D2) did not influence the potency of luc dsRNA to silence the luciferase reporter. Immunostaining experiments further showed that both TcR2D2 and BmTranslin accumulated at defined locations within the cytoplasm of transfected cells. Our results offer a first evaluation of the expression of the RNAi machinery in silkmoth tissues and Bm5 cells and provide evidence for a functional RNAi response to intracellular dsRNA in the absence of R2D2 and Translin. The failure of TcR2D2 to stimulate the intracellular RNAi pathway in Bombyx cells is discussed.

  17. Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

    NASA Technical Reports Server (NTRS)

    Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

    2011-01-01

    Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

  18. Mean cell size and collagen orientation from 2D Fourier analysis on confocal laser scanning microscopy and two-photon fluorescence microscopy on human skin in vivo

    NASA Astrophysics Data System (ADS)

    Lucassen, Gerald W.; Bakker, Bernard L.; Neerken, Sieglinde; Hendriks, Rob F. M.

    2003-07-01

    We present results from 2D Fourier analysis on 3D stacks of images obtained by confocal laser scanning reflectance microscopy (CLSM) and two-photon fluorescence microscopy (2PM) on human skin in vivo. CLSM images were obtained with a modified commercial system (Vivascope1000, Lucid Inc, excitation wavelength 830 nm) equipped with a piezo-focusing element (350 μm range) for depth positioning of the objective lens. 2PM was performed with a specially designed set-up with excitation wavelength 730 nm. Mean cell size in the epidermal layer and structural orientation in the dermal layer have been determined as a function of depth by 2D Fourier analysis. Fourier analysis on microscopic images enables automatic non-invasive quantitative structural analysis (mean cell size and orientation) of living human skin.

  19. Effect of 1,25(OH)2D3 on transdifferentiation of rat renal tubular epithelial cells induced by high glucose

    PubMed Central

    Hu, Hongtao; Xu, Shen; Hu, Shuang; Gao, Yue; Shui, Hua

    2016-01-01

    Deficiency in vitamin D and its active metabolite is a characteristic of chronic kidney diseases (CKDs). Previous studies have reported that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, can attenuate renal interstitial fibrosis. The present study aimed to explore the effect of 1,25(OH)2D3 on the transdifferentiation of NRK-52E rat renal tubular epithelial cells (RTECs) induced by high glucose, as well as the expression of vitamin D receptor (VDR) and production of angiotensin (Ang) II. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses were performed to detect the protein and mRNA expression of α-smooth muscle actin (α-SMA), E-cadherin and VDR. Furthermore, the production of Ang II was analyzed by enzyme-linked immunosorbent assay (ELISA). Treatment with high glucose decreased E-cadherin and VDR, while increasing α-SMA and Ang II, and of note, these changes were attenuated by 1,25(OH)2D3 in a dose-dependent manner. In conclusion, the present study revealed that 1,25(OH)2D3 inhibits high glucose-induced transdifferentiation of rat RTECs in a dose-dependent manner, which may be associated with the downregulation of Ang II and upregulation of VDR. PMID:28101343

  20. Fine tuning a well-oiled machine: Influence of NK1.1 and NKG2D on NKT cell development and function

    PubMed Central

    Joshi, Sunil K.; Lang, Mark L.

    2013-01-01

    Natural Killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but nonetheless expressed by NKT cells. These include several activating and inhibitory receptors that may fine-tune NKT development and survival, as well as activation via antigen receptors. Herein, we review the possible roles of the NK1.1 and NKG2D receptors in regulating development and function of NKT cells in health and disease. We suggest that pharmacological alteration of NKT activity should consider the potential complexities commensurate with NK1.1 and NKG2D expression. PMID:23800654

  1. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells

    PubMed Central

    Nemere, I.; Farach-Carson, M. C.; Rohe, B.; Sterling, T. M.; Norman, A. W.; Boyan, B. D.; Safford, S. E.

    2004-01-01

    We used a ribozyme loss-of-function approach to demonstrate that the protein product of a cDNA encoding a multifunctional membrane-associated protein binds the seco-steroid 1,25(OH)2D3 and transduces its stimulatory effects on phosphate uptake. These results are paralleled by studies in which the ability of the hormone to stimulate phosphate uptake in isolated chick intestinal epithelial cells is abolished by preincubation with Ab099 directed against the amino terminus of the protein. We now report the complete sequence of the cloned chicken cDNA for the 1,25D3-MARRS (membrane-associated, rapid-response steroid-binding) protein and reveal it to be identical to the multifunctional protein ERp57. Functional studies showed that active ribozyme, but not a scrambled control, decreased specific membrane-associated 1,25(OH)2D3 binding, but did not affect binding to the nuclear receptor for 1,25(OH)2D3. Seco-steroid-dependent stimulation of protein kinase C activity was diminished as 1,25D3-MARRS protein levels were reduced in the presence of the ribozyme, as judged by Western blot analyses. Phosphate uptake in isolated cells is an index of intestinal phosphate transport that occurs during growth and maturation. Whereas cells and perfused duodena robustly responded to 1,25(OH)2D3 in preparations from young birds, older animals no longer responded with stimulated phosphate uptake or transport. The age-related decline was accompanied by a decrease in 1,25D3-MARRS mRNA that was apparent up to 1 year of age. Together, these studies functionally link phosphate transport in the chick duodenum with the 1,25D3-MARRS protein and point to a previously uncharacterized role for this multifunctional protein class. PMID:15123837

  2. Data of the recombination loss mechanisms analysis on Al2O3 PERC cell using PC1D and PC2D simulations.

    PubMed

    Huang, Haibing; Lv, Jun; Bao, Yameng; Xuan, Rongwei; Sun, Shenghua; Sneck, Sami; Li, Shuo; Modanese, Chiara; Savin, Hele; Wang, Aihua; Zhao, Jianhua

    2017-04-01

    This data article is related to our recently published article ('20.8% industrial PERC solar cell: ALD Al2O3 rear surface passivation, efficiency loss mechanisms analysis and roadmap to 24%', Huang et al., 2017 [1]) where we have presented a systematic evaluation of the overall cell processing and a cost-efficient industrial roadmap for PERC cells. Aside from the information already presented in Huang et al., 2017 [1], here we provide data related to Sectin 3 in Huang et al., 2017 [1] concerning the analysis of the recombination losses׳ mechanisms by PC1D V5.9 and PC2D simulations (Clugston and Basore, 1997, Basore and Cabanas-Holmen, 2011, Cabanas-Holmen and Basore, 2012 and Cabanas-Holmen and Basore, 2012.) [2], [3], [4], [5] on our current industrial Al2O3 PERC cell. The data include: i) PC2D simulations on J02, ii) the calculation of series resistance and back surface recombination velocity (BSRV) on the rear side metallization of PERC cell for the case of a point contact, and iii) the PC1D simulation on the cumulative photo-generation and recombination along the distance from the front surface. Finally, the roadmap of the solar cell efficiency for an industrial PERC technology up to 24% is presented, with the aim of providing a potential guideline for industrial researchers.

  3. Mirrored serpentine flow channels for fuel cell

    DOEpatents

    Rock, Jeffrey Allan

    2000-08-08

    A PEM fuel cell having serpentine flow field channels wherein the input/inlet legs of each channel border the input/inlet legs of the next adjacent channels in the same flow field, and the output/exit legs of each channel border the output/exit legs of the next adjacent channels in the same flow field. The serpentine fuel flow channels may be longer, and may contain more medial legs, than the serpentine oxidant flow channels.

  4. 2-D numerical simulations of groundwater flow, heat transfer and 4He transport — implications for the He terrestrial budget and the mantle helium heat imbalance

    NASA Astrophysics Data System (ADS)

    Castro, Maria Clara; Patriarche, Delphine; Goblet, Patrick

    2005-09-01

    Because helium and heat production results from a common source, a continental 4He crustal flux of 4.65 * 10 - 14 mol m - 2 s - 1 has been estimated based on heat flow considerations. In addition, because the observed mantle He / heat flux ratio at the proximity of mid-ocean ridges (6.6 * 10 - 14 mol J - 1 ) is significantly lower than the radiogenic production ratio (1.5 * 10 - 12 mol J - 1 ), the presence of a terrestrial helium-heat imbalance was suggested. The latter could be explained by the presence of a layered mantle in which removal of He is impeded from the lower mantle [R.K. O'Nions, E.R. Oxburgh, Heat and helium in the Earth, Nature 306 (1983) 429-431; E.R. Oxburgh, R.K. O'Nions, Helium loss, tectonics, and the terrestrial heat budget, Science 237 (1987) 1583-1588]. van Keken et al. [P.E. van Keken, C.J. Ballentine, D. Porcelli, A dynamical investigation of the heat and helium imbalance, Earth Planet, Sci. Lett. 188 (2001) 421-434] have recently claimed that the helium-heat imbalance remains a robust observation. Such conclusions, however, were reached under the assumption that a steady-state regime was in place for both tracers and that their transport properties are similar at least in the upper portion of the crust. Here, through 2-D simulations of groundwater flow, heat transfer and 4He transport carried out simultaneously in the Carrizo aquifer and surrounding formations in southwest Texas, we assess the legitimacy of earlier assumptions. Specifically, we show that the driving transport mechanisms for He and heat are of a fundamentally different nature for a high range of permeabilities ( k ≤ 10 - 16 m 2) found in metamorphic and volcanic rocks at all depths in the crust. The assumption that transport properties for these two tracers are similar in the crust is thus unsound. We also show that total 4He / heat flux ratios lower than radiogenic production ratios do not reflect a He deficit in the crust or mantle original reservoir. Instead, they

  5. A robust cell counting approach based on a normalized 2D cross-correlation scheme for in-line holographic images.

    PubMed

    Ra, Ho-Kyeong; Kim, Hyungseok; Yoon, Hee Jung; Son, Sang Hyuk; Park, Taejoon; Moon, Sangjun

    2013-09-07

    To achieve the important aims of identifying and marking disease progression, cell counting is crucial for various biological and medical procedures, especially in a Point-Of-Care (POC) setting. In contrast to the conventional manual method of counting cells, a software-based approach provides improved reliability, faster speeds, and greater ease of use. We present a novel software-based approach to count in-line holographic cell images using the calculation of a normalized 2D cross-correlation. This enables fast, computationally-efficient pattern matching between a set of cell library images and the test image. Our evaluation results show that the proposed system is capable of quickly counting cells whilst reliably and accurately following human counting capability. Our novel approach is 5760 times faster than manual counting and provides at least 68% improved accuracy compared to other image processing algorithms.

  6. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

    PubMed

    Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

    2016-04-07

    Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.

  7. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size

    PubMed Central

    Otani, Tomoki; Marchetto, Maria C.; Gage, Fred H.; Simons, Benjamin D.; Livesey, Frederick J.

    2016-01-01

    Summary Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. PMID:27049876

  8. Marked change in microRNA expression during neuronal differentiation of human teratocarcinoma NTera2D1 and mouse embryonal carcinoma P19 cells

    SciTech Connect

    Hohjoh, Hirohiko Fukushima, Tatsunobu

    2007-10-19

    MicroRNAs (miRNAs) are small noncoding RNAs, with a length of 19-23 nucleotides, which appear to be involved in the regulation of gene expression by inhibiting the translation of messenger RNAs carrying partially or nearly complementary sequences to the miRNAs in their 3' untranslated regions. Expression analysis of miRNAs is necessary to understand their complex role in the regulation of gene expression during the development, differentiation and proliferation of cells. Here we report on the expression profile analysis of miRNAs in human teratocarcinoma NTere2D1, mouse embryonic carcinoma P19, mouse neuroblastoma Neuro2a and rat pheochromocytoma PC12D cells, which can be induced into differentiated cells with long neuritic processes, i.e., after cell differentiation, such that the resultant cells look similar to neuronal cells. The data presented here indicate marked changes in the expression of miRNAs, as well as genes related to neuronal development, occurred in the differentiation of NTera2D1 and P19 cells. Significant changes in miRNA expression were not observed in Neuro2a and PC12D cells, although they showed apparent morphologic change between undifferentiated and differentiated cells. Of the miRNAs investigated, the expression of miRNAs belonging to the miR-302 cluster, which is known to be specifically expressed in embryonic stem cells, and of miR-124a specific to the brain, appeared to be markedly changed. The miR-302 cluster was potently expressed in undifferentiated NTera2D1 and P19 cells, but hardly in differentiated cells, such that miR-124a showed an opposite expression pattern to the miR-302 cluster. Based on these observations, it is suggested that the miR-302 cluster and miR-124a may be useful molecular indicators in the assessment of degree of undifferentiation and/or differentiation in the course of neuronal differentiation.

  9. NKG2D ligands as therapeutic targets

    PubMed Central

    Spear, Paul; Wu, Ming-Ru; Sentman, Marie-Louise; Sentman, Charles L.

    2013-01-01

    The Natural Killer Group 2D (NKG2D) receptor plays an important role in protecting the host from infections and cancer. By recognizing ligands induced on infected or tumor cells, NKG2D modulates lymphocyte activation and promotes immunity to eliminate ligand-expressing cells. Because these ligands are not widely expressed on healthy adult tissue, NKG2D ligands may present a useful target for immunotherapeutic approaches in cancer. Novel therapies targeting NKG2D ligands for the treatment of cancer have shown preclinical success and are poised to enter into clinical trials. In this review, the NKG2D receptor and its ligands are discussed in the context of cancer, infection, and autoimmunity. In addition, therapies targeting NKG2D ligands in cancer are also reviewed. PMID:23833565

  10. Fuel cell with internal flow control

    DOEpatents

    Haltiner, Jr., Karl J.; Venkiteswaran, Arun [Karnataka, IN

    2012-06-12

    A fuel cell stack is provided with a plurality of fuel cell cassettes where each fuel cell cassette has a fuel cell with an anode and cathode. The fuel cell stack includes an anode supply chimney for supplying fuel to the anode of each fuel cell cassette, an anode return chimney for removing anode exhaust from the anode of each fuel cell cassette, a cathode supply chimney for supplying oxidant to the cathode of each fuel cell cassette, and a cathode return chimney for removing cathode exhaust from the cathode of each fuel cell cassette. A first fuel cell cassette includes a flow control member disposed between the anode supply chimney and the anode return chimney or between the cathode supply chimney and the cathode return chimney such that the flow control member provides a flow restriction different from at least one other fuel cell cassettes.

  11. Optoelectronics with 2D semiconductors

    NASA Astrophysics Data System (ADS)

    Mueller, Thomas

    2015-03-01

    Two-dimensional (2D) atomic crystals, such as graphene and layered transition-metal dichalcogenides, are currently receiving a lot of attention for applications in electronics and optoelectronics. In this talk, I will review our research activities on electrically driven light emission, photovoltaic energy conversion and photodetection in 2D semiconductors. In particular, WSe2 monolayer p-n junctions formed by electrostatic doping using a pair of split gate electrodes, type-II heterojunctions based on MoS2/WSe2 and MoS2/phosphorene van der Waals stacks, 2D multi-junction solar cells, and 3D/2D semiconductor interfaces will be presented. Upon optical illumination, conversion of light into electrical energy occurs in these devices. If an electrical current is driven, efficient electroluminescence is obtained. I will present measurements of the electrical characteristics, the optical properties, and the gate voltage dependence of the device response. In the second part of my talk, I will discuss photoconductivity studies of MoS2 field-effect transistors. We identify photovoltaic and photoconductive effects, which both show strong photoconductive gain. A model will be presented that reproduces our experimental findings, such as the dependence on optical power and gate voltage. We envision that the efficient photon conversion and light emission, combined with the advantages of 2D semiconductors, such as flexibility, high mechanical stability and low costs of production, could lead to new optoelectronic technologies.

  12. Verification and benchmarking of MAGNUM-2D: a finite element computer code for flow and heat transfer in fractured porous media

    SciTech Connect

    Eyler, L.L.; Budden, M.J.

    1985-03-01

    The objective of this work is to assess prediction capabilities and features of the MAGNUM-2D computer code in relation to its intended use in the Basalt Waste Isolation Project (BWIP). This objective is accomplished through a code verification and benchmarking task. Results are documented which support correctness of prediction capabilities in areas of intended model application. 10 references, 43 figures, 11 tables.

  13. VERA2D-84: a computer program for two-dimensional analysis of flow, heat, and mass transfer in evaporative cooling towers. Volume 2. User's manual. Final report

    SciTech Connect

    Majumdar, A.K.; Agrawal, N.K.; Keeton, L.W.; Singhal, A.K.

    1985-07-01

    Cooling towers that do not meet design performance standards can add millions of dollars to the long-term operating costs of generating plants. The VERA2D-84 code offers a reliable method for predicting the performance of natural-draft and mechanical-draft towers on the basis of physical design information.

  14. Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase.

    PubMed

    Jiang, Jian-kang; Boxer, Matthew B; Vander Heiden, Matthew G; Shen, Min; Skoumbourdis, Amanda P; Southall, Noel; Veith, Henrike; Leister, William; Austin, Christopher P; Park, Hee Won; Inglese, James; Cantley, Lewis C; Auld, Douglas S; Thomas, Craig J

    2010-06-01

    Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2.

  15. Effects of 1,25(OH)2D3 on Cancer Cells and Potential Applications in Combination with Established and Putative Anti-Cancer Agents

    PubMed Central

    Abu el Maaty, Mohamed A.; Wölfl, Stefan

    2017-01-01

    The diverse effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the bio-active form of vitamin D, on cancer cell metabolism and proliferation has made it an interesting candidate as a supporting therapeutic option in cancer treatment. An important strategy in cancer therapy is the use of combination chemotherapy to overcome drug resistance associated with numerous anti-cancer agents and to provide better means of avoiding undesirable side effects. This complex strategy is widely adopted by oncologists and several established “cocktails” of chemotherapeutics are routinely administered to cancer patients. Among the principles followed in designing such treatment regimens is the use of drugs with different mechanisms of action to overcome the issue of tumor heterogeneity and to evade resistance. In light of the profound and diverse effects of 1,25(OH)2D3 reported by in vitro and in vivo studies, we discuss how these effects could support the use of this molecule in combination with “classical” cytotoxic drugs, such as platins and anti-metabolites, for the treatment of solid and hematological tumors. We also examine recent evidence supporting synergistic activities with other promising anti-cancer drug candidates, and postulate mechanisms through which 1,25(OH)2D3 may help evade chemoresistance. PMID:28124999

  16. Focused fluid-flow processes through high-quality bathymetric, 2D seismic and Chirp data from the southern parts of the Bay of Biscay, France

    NASA Astrophysics Data System (ADS)

    Baudon, Catherine; Gillet, Hervé; Cremer, Michel

    2013-04-01

    High-quality bathymetric, 2D seismic and Chirp data located in the southern parts of the Bay of Biscay, France, collected by the University of Bordeaux 1 (Cruises ITSAS 2, 2001; PROSECAN 3, 2006 and SARGASS, 2010) have recently been compiled. The survey area widely covers the Capbreton Canyon, which lies on the boundary between two major structural zones: the Aquitanian passive margin to the North, and the Basque-Cantabrian margin to the South which corresponds to the offshore Pyrenean front. The dataset revealed a large number of key seafloor features potentially associated with focused fluid-flow processes and subsurface sediment-remobilization. Focused fluid migration through sub-seabed sediments is a common phenomenon on continental margins worldwide and has widespread implications from both industrial and fundamental perspectives, from seafloor marine environmental issues to petroleum exploration and hazard assessments. Our study analyses the relationships between seafloor features, deeper structures and fluid migration through the Plio-Quaternary sedimentary pile. The geometrical characteristics, mechanisms of formation and kinematics of four main groups of seabed features have been investigated. (i) A 150km2 field of pockmarks can be observed on the Basque margin. These features are cone-shaped circular or elliptical depressions that are either randomly distributed as small pockmarks (diameter < 20m) or aligned in trains of large pockmarks (ranging from 200 to 600m in diameter) along shallow troughs leading downstream to the Capbreton Canyon. Seismic data show that most pockmarks reach the seabed through vertically staked V-shaped features but some are buried and show evidence of lateral migration through time. (ii) A second field of widely-spaced groups of pockmarks pierce the upper slope of the Aquitanian margin. These depressions are typically a few hundred meters in diameter and seem to be preferentially located in the troughs or on the stoss sides of

  17. RGD-conjugated rod-like viral nanoparticles on 2D scaffold improved bone differentiation of mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Wang, Qian; Pongkwan, Sitasuwan; Lee, L.; Li, Kai; Nguyen, Huong

    2014-05-01

    Viral nanoparticles have uniform and well-defined nano-structures and can be produced in large quantities. Several plant viral nanoparticles have been tested in biomedical applications due to the lack of mammalian cell infectivity. We are particularly interested in using Tobacco mosaic virus (TMV), which has been demonstrated to enhance bone tissue regeneration, as a tuneable nanoscale building block for biomaterials development. Unmodified TMV particles have been shown to accelerate osteogenic differentiation of adult stem cells by synergistically upregulating BMP2 and IBSP expression with dexamethasone. However, the lack of affinity to mammalian cell surface resulted in low initial cell adhesion. In this study, to increase cell binding capacity of TMV based material the chemical functionalization of TMV with arginine-glycine-aspartic acid (RGD) peptide was explored. An azide-derivatized RGD peptide was “clicked” to tyrosine residues on TMV outer surface via an efficient copper(I) catalysed azide-alkyne cycloaddition reaction. The ligand spacing is calculated to be 2-4 nm, which could offer a polyvalent ligand clustering effect for enhanced cell receptor signalling, further promoting the proliferation and osteogenic differentiation of bone marrow derived mesenchymal stem cells.

  18. Opportunities for Live Cell FT-Infrared Imaging: Macromolecule Identification with 2D and 3D Localization

    PubMed Central

    Mattson, Eric C.; Aboualizadeh, Ebrahim; Barabas, Marie E.; Stucky, Cheryl L.; Hirschmugl, Carol J.

    2013-01-01

    Infrared (IR) spectromicroscopy, or chemical imaging, is an evolving technique that is poised to make significant contributions in the fields of biology and medicine. Recent developments in sources, detectors, measurement techniques and speciman holders have now made diffraction-limited Fourier transform infrared (FTIR) imaging of cellular chemistry in living cells a reality. The availability of bright, broadband IR sources and large area, pixelated detectors facilitate live cell imaging, which requires rapid measurements using non-destructive probes. In this work, we review advances in the field of FTIR spectromicroscopy that have contributed to live-cell two and three-dimensional IR imaging, and discuss several key examples that highlight the utility of this technique for studying the structure and chemistry of living cells. PMID:24256815

  19. Opportunities for live cell FT-infrared imaging: macromolecule identification with 2D and 3D localization.

    PubMed

    Mattson, Eric C; Aboualizadeh, Ebrahim; Barabas, Marie E; Stucky, Cheryl L; Hirschmugl, Carol J

    2013-11-19

    Infrared (IR) spectromicroscopy, or chemical imaging, is an evolving technique that is poised to make significant contributions in the fields of biology and medicine. Recent developments in sources, detectors, measurement techniques and speciman holders have now made diffraction-limited Fourier transform infrared (FTIR) imaging of cellular chemistry in living cells a reality. The availability of bright, broadband IR sources and large area, pixelated detectors facilitate live cell imaging, which requires rapid measurements using non-destructive probes. In this work, we review advances in the field of FTIR spectromicroscopy that have contributed to live-cell two and three-dimensional IR imaging, and discuss several key examples that highlight the utility of this technique for studying the structure and chemistry of living cells.

  20. 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy

    PubMed Central

    Gao, Ling; Cui, Weina; Zhang, Pengyuan; Jang, Albert; Zhu, Wuqiang; Zhang, Jianyi

    2016-01-01

    Utilizing a fast 31P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux PCr→ATP), and k constant of CK forward flux rate (kPCr→ATP) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling. PMID:27606901

  1. Organic Solar Cells Based on a 2D Benzo[1,2-b:4,5-b']difuran-Conjugated Polymer with High-Power Conversion Efficiency.

    PubMed

    Huo, Lijun; Liu, Tao; Fan, Bingbing; Zhao, Zhiyuan; Sun, Xiaobo; Wei, Donghui; Yu, Mingming; Liu, Yunqi; Sun, Yanming

    2015-11-18

    A novel 2D benzodifuran (BDF)-based copolymer (PBDF-T1) is synthesized. Polymer solar cells fabricated with PBDF-T1 show high power conversion efficiency of 9.43% and fill factor of 77.4%, which is higher than the performance of its benzothiophene (BDT) counterpart (PBDT-T1). These results provide important progress for BDF-based copolymers and demonstrate that BDF-based copolymers can be competitive with the well-studied BDT counterparts via molecular structure design and device optimization.

  2. Blood Cell Interactions and Segregation in Flow

    PubMed Central

    Munn, Lance L.; Dupin, Michael M.

    2009-01-01

    For more than a century, pioneering researchers have been using novel experimental and computational approaches to probe the mysteries of blood flow. Thanks to their efforts, we know that blood cells generally prefer to migrate to the axis of flow, that red and white cells segregate in flow, and that cell deformability and their tendency to reversibly aggregate contribute to the non-Newtonian nature of this unique fluid. All of these properties have beneficial physiological consequences, allowing blood to perform a variety of critical functions. Our current understanding of these unusual flow properties of blood have been made possible by the ingenuity and diligence of a number of researchers, including Harry Goldsmith, who developed novel technologies to visualize and quantify the flow of blood at the level of individual cells. Here we summarize efforts in our lab to continue this tradition and to further our understanding of how blood cells interact with each other and with the blood vessel wall. PMID:18188702

  3. Optimization of Metal Coverage on the Emitter in n-Type Interdigitated Back Contact Solar Cells Using a PC2D Simulation

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Chen, Chen; Jia, Rui; Janssen, G. J. M.; Zhang, Dai-Sheng; Xing, Zhao; Bronsveld, P. C. P.; Weeber, A. W.; Jin, Zhi; Liu, Xin-Yu

    2013-07-01

    In interdigitated back contact (IBC) solar cells, the metal-electrode coverage on a p-type emitter is optimized by a PC2D simulation. The result shows that the variation of the metal coverage ratio (MCR) will affect both the surface passivation and the electrode-contact properties for the p-type emitter in IBC solar cells. We find that when Rc ranges from 0.08 to 0.16Ω·cm2, the MCR is optimized with a value of 25% and 33%, resulting in a highest energy-conversion efficiency. The dependences of both Voc and fill factor on MCR are simulated in order to explore the mechanism of the IBC solar cells.

  4. RAPID 2D NMR METHOD FOR DETERMINING P-COUMARATE AND FERULATE LEVELS IN CORN (AND OTHER GRASS) CELL WALLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grass cell wall components are acylated by the hydroxycinnamates p-coumarate and ferulate. p-Coumarates largely acylate lignin sidechains, exclusively at the gamma-position, whereas ferulates primarily acylate the arabinosyl C5-position of arabinoxylans. Such components can be quantified as the corr...

  5. NK cells are primed by ANRS MVA(HIV)-infected DCs, via a mechanism involving NKG2D and membrane-bound IL-15, to control HIV-1 infection in CD4+ T cells.

    PubMed

    Moreno-Nieves, Uriel Y; Didier, Céline; Lévy, Yves; Barré-Sinoussi, Françoise; Scott-Algara, Daniel

    2014-08-01

    Natural killer (NK) cells are the major antiviral effector cell population of the innate immune system. It has been demonstrated that NK-cell activity can be modulated by the interaction with dendritic cells (DCs). The HIV-1 vaccine candidate Modified Vaccinia Ankara encoding an HIV polypeptide (MVA(HIV)), developed by the French National Agency for Research on AIDS (ANRS), has the ability to prime NK cells to control HIV-1 infection in DCs. However, whether or not MVA(HIV)-primed NK cells are able to better control HIV-1 infection in CD4(+) T cells, and the mechanism underlying the specific priming, remain undetermined. In this study, we show that MVA(HIV)-primed NK cells display a greater capacity to control HIV-1 infection in autologous CD4(+) T cells. We also highlight the importance of NKG2D engagement on NK cells and DC-produced IL-15 to achieve the anti-HIV-1 specific priming, as blockade of either NKG2D or IL-15 during MVA(HIV)-priming lead to a subsequent decreased control of HIV-1 infection in autologous CD4(+) T cells. Furthermore, we show that the decreased control of HIV-1 infection in CD4(+) T cells might be due, at least in part, to the decreased expression of membrane-bound IL-15 (mbIL-15) on DCs when NKG2D is blocked during MVA(HIV)-priming of NK cells.

  6. Interactions of 1D- and 2D-layered inorganic nanoparticles with fibroblasts and human mesenchymal stem cells

    SciTech Connect

    Rashkow, Jason Thomas; Talukdar, Yahfi; Lalwani, Gaurav; Sitharaman, Balaji

    2015-06-01

    Here, this study investigates the effects of tungsten disulfide nanotubes (WSNTs) and molybdenum disulfide nanoplatelets (MSNPs) on fibroblasts (NIH-3T3) and mesenchymal stem cells (MSCs) to determine safe dosages for potential biomedical applications. Cytotoxicity of MSNPs and WSNTs (5–300 μg/ml) on NIH-3T3 and MSCs was assessed at 6, 12 or 24 h. MSC differentiation to adipocytes and osteoblasts was assessed following treatment for 24 h. Only NIH-3T3 cells treated with MSNPs showed dose or time dependent increase in cytotoxicity. Differentiation markers of MSCs in treated groups were unaffected compared with untreated controls. In conclusion, MSNPs and WSNTs at concentrations less than 50 μg/ml are potentially safe for treatment of fibroblasts or MSCs for up to 24 h.

  7. Interactions of 1D- and 2D-layered inorganic nanoparticles with fibroblasts and human mesenchymal stem cells

    DOE PAGES

    Rashkow, Jason Thomas; Talukdar, Yahfi; Lalwani, Gaurav; ...

    2015-06-01

    Here, this study investigates the effects of tungsten disulfide nanotubes (WSNTs) and molybdenum disulfide nanoplatelets (MSNPs) on fibroblasts (NIH-3T3) and mesenchymal stem cells (MSCs) to determine safe dosages for potential biomedical applications. Cytotoxicity of MSNPs and WSNTs (5–300 μg/ml) on NIH-3T3 and MSCs was assessed at 6, 12 or 24 h. MSC differentiation to adipocytes and osteoblasts was assessed following treatment for 24 h. Only NIH-3T3 cells treated with MSNPs showed dose or time dependent increase in cytotoxicity. Differentiation markers of MSCs in treated groups were unaffected compared with untreated controls. In conclusion, MSNPs and WSNTs at concentrations less thanmore » 50 μg/ml are potentially safe for treatment of fibroblasts or MSCs for up to 24 h.« less

  8. 1D-2D carbon heterostructure with low Pt loading as a superior cathode electrode for dye-sensitized solar cell

    NASA Astrophysics Data System (ADS)

    Nechiyil, Divya; Ramaprabhu, S.

    2017-02-01

    Cost-effective counter electrode (CE) with high electrocatalytic performance is very much essential for the wide application of dye-sensitized solar cells (DSSC). The 1D-2D carbon heterostructure (Pt/GR@CNT) with low platinum (Pt) loading has been synthesized by a facile in situ microwave-assisted polyol-reduction method. The excellent electrocatalytic activity as well as photovoltaic performance was achieved due to the combination of 2D graphene nanoribbons (GR) and 1D multi-walled carbon nanotubes (CNT) with high catalytically active Pt nanoparticles. Microwave-assisted longitudinal unzipping of few outer layers of CNTs along with co-reduction of Pt nanoparticles is an effective method to create electrochemically active defective edge sites, which have a crucial role in enhancing electrochemical performance. Synergistic effect of ultra-fine Pt nanoparticles, partially unzipped graphene nanoribbons and inner core tubes of CNTs modulates the power conversion efficiency of solar cell to 5.57% ± 0.03 as compared with 4.73% ± 0.13 of CNTs. Pt/GR@CNT CE even with low Pt loading of 14 μg cm-2 showcases equivalent performance with that of pure Pt counter electrode.

  9. Graphene Paper Decorated with a 2D Array of Dendritic Platinum Nanoparticles for Ultrasensitive Electrochemical Detection of Dopamine Secreted by Live Cells

    PubMed Central

    Zan, Xiaoli; Wang, Chenxu

    2016-01-01

    Abstract To circumvent the bottlenecks of non‐flexibility, low sensitivity, and narrow workable detection range of conventional biosensors for biological molecule detection (e.g., dopamine (DA) secreted by living cells), a new hybrid flexible electrochemical biosensor has been created by decorating closely packed dendritic Pt nanoparticles (NPs) on freestanding graphene paper. This innovative structural integration of ultrathin graphene paper and uniform 2D arrays of dendritic NPs by tailored wet chemical synthesis has been achieved by a modular strategy through a facile and delicately controlled oil–water interfacial assembly method, whereby the uniform distribution of catalytic dendritic NPs on the graphene paper is maximized. In this way, the performance is improved by several orders of magnitude. The developed hybrid electrode shows a high sensitivity of 2 μA cm−2 μm −1, up to about 33 times higher than those of conventional sensors, a low detection limit of 5 nm, and a wide linear range of 87 nm to 100 μm. These combined features enable the ultrasensitive detection of DA released from pheochromocytoma (PC 12) cells. The unique features of this flexible sensor can be attributed to the well‐tailored uniform 2D array of dendritic Pt NPs and the modular electrode assembly at the oil–water interface. Its excellent performance holds much promise for the future development of optimized flexible electrochemical sensors for a diverse range of electroactive molecules to better serve society. PMID:26918612

  10. Plasmonic spectrum on 1D and 2D periodic arrays of rod-shape metal nanoparticle pairs with different core patterns for biosensor and solar cell applications

    NASA Astrophysics Data System (ADS)

    Kumara, N. T. R. N.; Chou Chau, Yuan-Fong; Huang, Jin-Wei; Huang, Hung Ji; Lin, Chun-Ting; Chiang, Hai-Pang

    2016-11-01

    Simulations of surface plasmon resonance (SPR) on the near field intensity and absorption spectra of one-dimensional (1D) and two-dimensional (2D) periodic arrays of rod-shape metal nanoparticle (MNP) pairs using the finite element method (FEM) and taking into account the different core patterns for biosensor and solar cell applications are investigated. A tunable optical spectrum corresponding to the transverse SPR modes is observed. The peak resonance wavelength (λ res) can be shifted to red as the core patterns in rod-shape MNPs have been changed. We find that the 2D periodic array of core-shell MNP pairs (case 2) exhibit a red shifted SPR that can be tuned the gap enhancement and absorption efficiency simultaneously over an extended wavelength range. The tunable optical performances give us a qualitative idea of the geometrical properties of the periodic array of rod-shape MNP pairs on SPRs that can be as a promising candidate for plasmonic biosensor and solar cell applications.

  11. CD3(+) CD8(+) NKG2D(+) T Lymphocytes Induce Apoptosis and Necroptosis in HLA-negative Cells via FasL-Fas Interaction.

    PubMed

    Ivanova, O K; Sharapova, T N; Romanova, E A; Sashchenko, L P; Yashin, D V

    2017-03-15

    An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4(+) CD25(+) lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8+ lymphocytes. We show that after a tumor antigen contact the IL-2 activated CD8+ lymphocytes acquire ability to lyse tumor cells bearing this antigen. However, activation of the CD8+ lymphocytes in the absence of antigen causes appearance of a cytotoxic population of CD8 + NKG2D+ lymphocytes, which are able to lyse HLA-negative cancer cells that have lost the classic mechanism of antigen presentation. These cells recognize the noncanonical MicA antigen on the surface of HLA-negative K562 cells but kill them via the FasL-Fas interaction, as do cytotoxic T lymphocytes. FasL presented on the lymphocyte surface can trigger both apoptosis and necroptosis. Unlike in the case of TNFR1, another cell death receptor, no switching to alternative processes has been observed upon induction of Fas-dependent cell death. It may well be that the apoptotic and necroptotic signals are transduced separately in the latter case, with the ability of FasL(+) lymphocytes to induce necroptosis allowing them to kill tumor cells that escape apoptosis. This article is protected by copyright. All rights reserved.

  12. Performance Mapping Studies in Redox Flow Cells

    NASA Technical Reports Server (NTRS)

    Hoberecht, M. A.; Thaller, L. H.

    1981-01-01

    Pumping power requirements in any flow battery system constitute a direct parasitic energy loss. It is therefore useful to determine the practical lower limit for reactant flow rates. Through the use of a theoretical framework based on electrochemical first principles, two different experimental flow mapping techniques were developed to evaluate and compare electrodes as a function of flow rate. For the carbon felt electrodes presently used in NASA-Lewis Redox cells, a flow rate 1.5 times greater than the stoichiometric rate seems to be the required minimum.

  13. The chemical composition of animal cells reconstructed from 2D and 3D ToF-SIMS analysis

    NASA Astrophysics Data System (ADS)

    Breitenstein, D.; Rommel, C. E.; Stolwijk, J.; Wegener, J.; Hagenhoff, B.

    2008-12-01

    This paper gives an overview on the progress achieved in our lab within the last two years in the analysis of single cells and tissue-like cell layers by time-of-flight secondary ion mass spectrometry (ToF-SIMS). Basically two types of investigations were performed: on the one hand a two-dimensional imaging and on the other hand a three-dimensional microarea analysis. In both cases chemical fixation in combination with slow air-drying were used as easy sample preparation method. It was the goal of both approaches to identify the distribution of natural components as well as the localisation of xenobiotic fluorophors. In our experimental set-ups the distribution of phophatidylcholine and amino-acid signals were in line with the expectation. In contrast, the distribution of the fluorophor ethidiumhomodimer could only be detected within the two-dimensional imaging, whereas it was not detected in the three-dimensional analysis. Also four other fluorophors failed in the latter approach. Thus, in our hands the three-dimensional detection is to date limited to certain molecules with a comparably low mass and/or an intrinsical charge.

  14. 1,25(OH)2D3 attenuates TGF-β1/β2-induced increased migration and invasion via inhibiting epithelial-mesenchymal transition in colon cancer cells.

    PubMed

    Chen, Shanwen; Zhu, Jing; Zuo, Shuai; Ma, Ju; Zhang, Junling; Chen, Guowei; Wang, Xin; Pan, Yisheng; Liu, Yucun; Wang, Pengyuan

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial-mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actin induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells.

  15. Solution-processed 2D niobium diselenide nanosheets as efficient hole-transport layers in organic solar cells.

    PubMed

    Gu, Xing; Cui, Wei; Song, Tao; Liu, Changhai; Shi, Xiaoze; Wang, Suidong; Sun, Baoquan

    2014-02-01

    Thin-layer, two-dimensional NbSe2 nanosheets with lower trap density have been obtained and act as an alternative hole-transporting layer to replace MoO3 in organic solar cells. If poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}):[6,6]-phenyl-C71-butyric acid methyl ester acts as an active layer, a power conversion efficiency of 8.10 % has been achieved without any further thermal treatment. The properties of this hole-transporting layer were investigated and the improvements in the devices are discussed.

  16. Application of rank-ordered multifractal analysis (ROMA) to intermittent fluctuations in 3D turbulent flows, 2D MHD simulation and solar wind data

    NASA Astrophysics Data System (ADS)

    Wu, C.; Chang, T.

    2010-12-01

    A new method in describing the multifractal characteristics of intermittent events was introduced by Cheng and Wu [Chang T. and Wu C.C., Physical Rev, E77, 045401(R), 2008]. The procedure provides a natural connection between the rank-ordered spectrum and the idea of one-parameter scaling for monofractals. This technique has been demonstrated using results obtained from a 2D MHD simulation. It has also been successfully applied to in-situ solar wind observations [Chang T., Wu, C.C. and Podesta, J., AIP Conf Proc. 1039, 75, 2008], and the broadband electric field oscillations from the auroral zone [Tam, S.W.Y. et al., Physical Rev, E81, 036414, 2010]. We take the next step in this procedure. By using the ROMA spectra and the scaled probability distribution functions (PDFs), raw PDFs can be calculated, which can be compared directly with PDFs from observations or simulation results. In addition to 2D MHD simulation results and in-situ solar wind observation, we show clearly using the ROMA analysis the multifractal character of the 3D fluid simulation data obtained from the JHU turbulence database cluster at http://turbulence.pha.jhu.edu. In particular, we show the scaling of the non-symmetrical PDF for the parallel-velocity fluctuations of this 3D fluid data.

  17. Histochemical examination of adipose derived stem cells combined with β-TCP for bone defects restoration under systemic administration of 1α,25(OH)2D3.

    PubMed

    Feng, Wei; Lv, Shengyu; Cui, Jian; Han, Xiuchun; Du, Juan; Sun, Jing; Wang, Kefeng; Wang, Zhenming; Lu, Xiong; Guo, Jie; Oda, Kimimitsu; Amizuka, Norio; Xu, Xin; Li, Minqi

    2015-09-01

    The purpose of this study was to evaluate the effects of osteogenic differentiated adipose-derived stem cell (ADSC) loaded beta-tricalcium phosphate (β-TCP) in the restoration of bone defects under intraperitoneal administration of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3). ADSCs were isolated from the fat tissue of 8 week old Wister rats and co-cultured with β-TCP for 21 days under osteogenic induction. Then the ADSC-β-TCP complexes were implanted into bone defects in the femora of rats. 1α,25(OH)2D3 (VD) or normal saline (NS) was administrated intraperitoneally every other day after the surgery. Femora were harvested at day 7, day 14 and day 28 post-surgery. There were 4 groups for all specimens: β-TCP-NS group; β-TCP-ADSC-NS group; β-TCP-VD group and β-TCP-ADSC-VD group. Alkaline phosphatase (ALP) was up-regulated obviously in ADSC groups compared with non-ADSC groups at day 7, day 14 and day 28, although high expression of runt-related transcription factor 2 (RUNX2) was only seen at day 7. Furthermore, the number of TRAP-positive osteoclasts and the expression of cathepsin K (CK) were significantly decreased in VD groups compared with non-VD groups at day 7 and day 14. As a most significant finding, the β-TCP-ADSC-VD group showed the highest BV/TV ratio compared with the other three groups at day 28. Taken together, ADSC-loaded β-TCP under the administration of 1α,25(OH)2D3 made a promising therapy for bone defects restoration.

  18. Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes.

    PubMed

    Ahmad, Shiekh Tanveer; Arjumand, Wani; Seth, Amlesh; Nafees, Sana; Rashid, Summya; Ali, Nemat; Hamiza, Oday O; Sultana, Sarwat

    2013-10-01

    The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) "variant" genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233-3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p(trend) = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) "variant" genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233-3.342; P = 0.005]. There was a significant association (p(trend) = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians.

  19. A New Cell-Centered Implicit Numerical Scheme for Ions in the 2-D Axisymmetric Code Hall2de

    NASA Technical Reports Server (NTRS)

    Lopez Ortega, Alejandro; Mikellides, Ioannis G.

    2014-01-01

    We present a new algorithm in the Hall2De code to simulate the ion hydrodynamics in the acceleration channel and near plume regions of Hall-effect thrusters. This implementation constitutes an upgrade of the capabilities built in the Hall2De code. The equations of mass conservation and momentum for unmagnetized ions are solved using a conservative, finite-volume, cell-centered scheme on a magnetic-field-aligned grid. Major computational savings are achieved by making use of an implicit predictor/multi-corrector algorithm for time evolution. Inaccuracies in the prediction of the motion of low-energy ions in the near plume in hydrodynamics approaches are addressed by implementing a multi-fluid algorithm that tracks ions of different energies separately. A wide range of comparisons with measurements are performed to validate the new ion algorithms. Several numerical experiments with the location and value of the anomalous collision frequency are also presented. Differences in the plasma properties in the near-plume between the single fluid and multi-fluid approaches are discussed. We complete our validation by comparing predicted erosion rates at the channel walls of the thruster with measurements. Erosion rates predicted by the plasma properties obtained from simulations replicate accurately measured rates of erosion within the uncertainty range of the sputtering models employed.

  20. Rapid 2D incoherent mirror fabrication by laser interference lithography and wet etching for III-V MQW solar cells

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Freundlich, Alex

    2016-03-01

    Optimization of non-planar antireflective coating and back- (or front-) surface texturing are widely studied as advanced light management approach to further reduce the reflection losses and increase the sunlight absorption path in solar cells. Rear reflectors have been developed from coherent mirrors to incoherent mirrors in order to further increase light path, which can significantly improve the efficiency and allow for much thinner devices. A Lambertian surface, which has the most random texture, can theoretically raise the light path to 4n2 times that of a smooth surface. It's a challenge however to fabricate ideal Lambertian texture, especially in a fast and low cost way. In this work, a method is developed to overcome this challenge that combines the use of laser interference lithography (LIL) and selective wet etching. This approach allows for a rapid (10 min) wafer scale (3 inch wafer) texture processing with sub-wavelength (nano)-scale control of the pattern and the pitch. The technique appears as being particularly attractive for the development of ultrathin III-V devices, or in overcoming the weak sub-bandgap absorption in devices incorporating quantum dots or quantum wells. The structure of the device is demonstrated, without affecting active layers.

  1. Differential response to 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3) in non-small cell lung cancer cells with distinct oncogene mutations1

    PubMed Central

    Zhang, Qiuhong; Kanterewicz, Beatriz; Shoemaker, Suzanne; Hu, Qiang; Liu, Song; Atwood, Kristopher; Hershberger, Pamela

    2012-01-01

    We previously demonstrated that non-small cell lung cancer (NSCLC) cells and primary human lung tumors aberrantly express the vitamin D3-catabolizing enzyme, CYP24, and that CYP24 restricts transcriptional regulation and growth control by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) in NSCLC cells. To ascertain the basis for CYP24 dysregulation, we assembled a panel of cell lines that represent distinct molecular classes of lung cancer: Cell lines were selected which harbored mutually exclusive mutations in either the K-ras or the Epidermal Growth Factor Receptor (EGFR) genes. We observed that K-ras mutant lines displayed a basal vitamin D receptor (VDR)lowCYP24high phenotype, whereas EGFR mutant lines had a VDRhighCYP24low phenotype. A mutation-associated difference in CYP24 expression was also observed in clinical specimens. Specifically, K-ras mutation was associated with a median 4.2-fold increase in CYP24 mRNA expression (p = 4.8 × 10−7) compared to EGFR mutation in a series of 147 primary lung adenocarcinoma cases. Because of their differential basal expression of VDR and CYP24, we hypothesized that NSCLC cells with an EGFR mutation would be more responsive to 1,25(OH)2D3 treatment than those with a K-ras mutation. To test this, we measured the ability of 1,25(OH)2D3 to increase reporter gene activity, induce transcription of endogenous target genes, and suppress colony formation. In each assay, the extent of 1,25(OH)2D3 response was greater in EGFR mutation-positive HCC827 and H1975 cells than in K-ras mutation-positive A549 and 128.88T cells. We subsequently examined the effect of combining 1,25(OH)2D3 with erlotinib, which is used clinically in the treatment of EGFR mutation-positive NSCLC. 1,25(OH)2D3/erlotinib combination resulted in significantly greater growth inhibition than either single agent in both the erlotinib-sensitive HCC827 cell line and the erlotinib-resistant H1975 cell line. These data are the first to suggest that EGFR mutations may

  2. Overhead Projection Cell for Streamline Flow

    ERIC Educational Resources Information Center

    Waage, Harold M.

    1969-01-01

    Describes the construction and operation of an overhead projection apparatus designed to demonstrate streamline flow of a liquid. The apparatus consists of a Plexiglass tank containing water in which plates forming the cell are submerged, a constant level reservoir, an overflow device and a system for marking the flow lines with a dye. (LC)

  3. 2D Particle-In-Cell simulations of the electron-cyclotron instability and associated anomalous transport in Hall-Effect Thrusters

    NASA Astrophysics Data System (ADS)

    Croes, Vivien; Lafleur, Trevor; Bonaventura, Zdenek; Péchereau, François; Bourdon, Anne; Chabert, Pascal

    2016-09-01

    This work studies the electron-cyclotron instability in Hall-Effect Thrusters (HETs) using a 2D Particle-In-Cell (PIC) simulation. The simulation is configured with a Cartesian coordinate system where a magnetic field, B0, is aligned along the X-axis (radial direction, including absorbing walls), a constant electric field, E0, along the Z-axis (axial direction, perpendicular to simulation plane), and the E0xB0 direction along the Y-axis (O direction, with periodic boundaries). Although for low plasma densities classical electron-neutral collisions theory describes well electron transport, at sufficiently high densities (as measured in HETs) a strong instability can be observed that enhances the electron mobility, even in the absence of collisions. The instability generates high frequency ( MHz) and short wavelength ( mm) fluctuations in both the electric field and charged particle densities. We investigate the correlation between these fluctuations and their role with anomalous electron transport; complementing previous 1D simulations. Plasma is self-consistently heated by the instability, but since the latter does not reach saturation in an infinitely long 2D system, saturation is achieved through implementation of a finite axial length that models convection in E0 direction. With support of Safran Aircraft Engines.

  4. Vertical 2D Heterostructures

    NASA Astrophysics Data System (ADS)

    Lotsch, Bettina V.

    2015-07-01

    Graphene's legacy has become an integral part of today's condensed matter science and has equipped a whole generation of scientists with an armory of concepts and techniques that open up new perspectives for the postgraphene area. In particular, the judicious combination of 2D building blocks into vertical heterostructures has recently been identified as a promising route to rationally engineer complex multilayer systems and artificial solids with intriguing properties. The present review highlights recent developments in the rapidly emerging field of 2D nanoarchitectonics from a materials chemistry perspective, with a focus on the types of heterostructures available, their assembly strategies, and their emerging properties. This overview is intended to bridge the gap between two major—yet largely disjunct—developments in 2D heterostructures, which are firmly rooted in solid-state chemistry or physics. Although the underlying types of heterostructures differ with respect to their dimensions, layer alignment, and interfacial quality, there is common ground, and future synergies between the various assembly strategies are to be expected.

  5. 2D DIGE analysis of the bursa of Fabricius reveals characteristic proteome profiles for different stages of chicken B-cell development.

    PubMed

    Korte, Julia; Fröhlich, Thomas; Kohn, Marina; Kaspers, Bernd; Arnold, Georg J; Härtle, Sonja

    2013-01-01

    Antibody producing B-cells are an essential component of the immune system. In contrast to human and mice where B-cells develop in the bone marrow, chicken B-cells develop in defined stages in the bursa of Fabricius, a gut associated lymphoid tissue. In order to gain a better understanding of critical biological processes like immigration of B-cell precursors into the bursa anlage, their differentiation and final emigration from the bursa we analyzed the proteome dynamics of this organ during embryonic and posthatch development. Samples were taken from four representative developmental stages (embryonic day (ED) 10, ED18, day 2, and day 28) and compared in an extensive 2D DIGE approach comprising six biological replicates per time point. Cluster analysis and PCA demonstrated high reliability and reproducibility of the obtained data set and revealed distinctive proteome profiles for the selected time points, which precisely reflect the differentiation processes. One hundred fifty three protein spots with significantly different intensities were identified by MS. We detected alterations in the abundance of several proteins assigned to retinoic acid metabolism (e.g. retinal-binding protein 5) and the actin-cytoskeleton (e.g. vinculin and gelsolin). By immunohistochemistry, desmin was identified as stromal cell protein associated with the maturation of B-cell follicles. Strongest protein expression difference (10.8-fold) was observed for chloride intracellular channel 2. This protein was thus far not associated with B-cell biology but our data suggest an important function in bursa B-cell development.

  6. 2D modeling and simulation of the flow dynamics, electric field and reactions in a low-temperature, atmospheric-pressure nitrogen plasma sharp-end plate-to-plane configuration and CVD reactor

    NASA Astrophysics Data System (ADS)

    De Wilde, Juray; Lorant, Christophe; Descamps, Pierre

    2017-04-01

    In atmospheric-pressure plasma reactors, the flow dynamics can be complex, determine the reactor performance and complicate scale-up. Coupling computational fluid dynamics to the calculation of the electric field and plasma chemistry is challenging because of the numerical stiffness introduced by the difference in time scale of the different phenomena involved. Focusing on low-temperature, atmospheric-pressure pure nitrogen plasma, a model and model reduction based solution strategy to deal with the numerical stiffness are presented and evaluated. The influence of the electric field on the flow dynamics and species concentration fields is first qualitatively studied by means of 2D simulations of a sharp-end plate-to-plane configuration. Next, a specific reactor prototype for low-temperature, atmospheric-pressure plasma-enhanced chemical vapor deposition for in-line surface treatments is simulated to illustrate the importance of accounting for the detailed flow dynamics.

  7. Photonic light-trapping versus Lambertian limits in thin film silicon solar cells with 1D and 2D periodic patterns.

    PubMed

    Bozzola, Angelo; Liscidini, Marco; Andreani, Lucio Claudio

    2012-03-12

    We theoretically investigate the light-trapping properties of one- and two-dimensional periodic patterns etched on the front surface of c-Si and a-Si thin film solar cells with a silver back reflector and an anti-reflection coating. For each active material and configuration, absorbance A and short-circuit current density Jsc are calculated by means of rigorous coupled wave analysis (RCWA), for different active materials thicknesses in the range of interest of thin film solar cells and in a wide range of geometrical parameters. The results are then compared with Lambertian limits to light-trapping for the case of zero absorption and for the general case of finite absorption in the active material. With a proper optimization, patterns can give substantial absorption enhancement, especially for 2D patterns and for thinner cells. The effects of the photonic patterns on light harvesting are investigated from the optical spectra of the optimized configurations. We focus on the main physical effects of patterning, namely a reduction of reflection losses (better impedance matching conditions), diffraction of light in air or inside the cell, and coupling of incident radiation into quasi-guided optical modes of the structure, which is characteristic of photonic light-trapping.

  8. Quantifying the flow dynamics of supercritical CO2-water displacement in a 2D porous micromodel using fluorescent microscopy and microscopic PIV

    NASA Astrophysics Data System (ADS)

    Kazemifar, Farzan; Blois, Gianluca; Kyritsis, Dimitrios C.; Christensen, Kenneth T.

    2016-09-01

    The multi-phase flow of liquid/supercritical CO2 and water (non-wetting and wetting phases, respectively) in a two-dimensional silicon micromodel was investigated at reservoir conditions (80 bar, 24 °C and 40 °C). The fluorescent microscopy and microscopic particle image velocimetry (micro-PIV) techniques were combined to quantify the flow dynamics associated with displacement of water by CO2 (drainage) in the porous matrix. To this end, water was seeded with fluorescent tracer particles, CO2 was tagged with a fluorescent dye and each phase was imaged independently using spectral separation in conjunction with microscopic imaging. This approach allowed simultaneous measurement of the spatially-resolved instantaneous velocity field in the water and quantification of the spatial configuration of the two fluid phases. The results, acquired with sufficient time resolution to follow the dynamic progression of both phases, provide a comprehensive picture of the flow physics during the migration of the CO2 front, the temporal evolution of individual menisci, and the growth of fingers within the porous microstructure. During that growth process, velocity jumps 20-25 times larger in magnitude than the bulk velocity were measured in the water phase and these bursts of water flow occurred both in-line with and against the bulk flow direction. These unsteady velocity events support the notion of pressure bursts and Haines jumps during pore drainage events as previously reported in the literature [1-3]. After passage of the CO2 front, shear-induced flow was detected in the trapped water ganglia in the form of circulation zones near the CO2-water interfaces as well as in the thin water films wetting the surfaces of the silicon micromodel. To our knowledge, the results presented herein represent the first quantitative spatially and temporally resolved velocity-field measurements at high pressure for water displacement by liquid/supercritical CO2 injection in a porous micromodel.

  9. Anti-cancer effect of Betulin on a human lung cancer cell line: a pharmacoproteomic approach using 2 D SDS PAGE coupled with nano-HPLC tandem Mass Spectrometry.

    PubMed

    Pyo, Jae Sung; Roh, Si Hun; Kim, Dae Ki; Lee, Jin Gyun; Lee, Yong Yook; Hong, Soon Sun; Kwon, Sung Won; Park, Jeong Hill

    2009-02-01

    Betulin is a representative compound of Betula platyphylla, a tree species belonging to the Betulaceae family. In this investigation, we revealed that betulin showed anticancer activity on human lung cancer A549 cells by inducing apoptosis and changes in protein expression profiles were observed. Upon flow cytometry analysis, the surface of betulin-treated cells was found to be annexin-V positive and propidium iodide (PI) negative, which indicated that the cells were apoptotic. In order to identify the molecular players involved in betulin-induced apoptosis, cellular proteins were applied to two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (2 D SDS PAGE) for differential proteomic analysis. As a result, four downregulated proteins and three upregulated proteins were identified by nano-HPLC MS/MS. The four downregulated proteins were poly(rC)-binding protein 1, isoform 1 of 3-hydroxyacyl-CoA dehydrogenase type 2, heat shock protein 90-alpha 2, and enoyl-CoA hydratase; the three upregulated proteins were aconitate hydratase, malate dehydrogenase, and splicing factor arginine/serine-rich 1. These differentially expressed proteins explained the cytotoxicity of betulin against human lung cancer A549 cells, and the proteomic approach was thus shown to be a potential tool for understanding the pharmacological activities of pharmacophores.

  10. 2D dry granular free-surface transient flow over complex topography with obstacles. Part II: Numerical predictions of fluid structures and benchmarking

    NASA Astrophysics Data System (ADS)

    Juez, C.; Caviedes-Voullième, D.; Murillo, J.; García-Navarro, P.

    2014-12-01

    Dense granular flows are present in geophysics and in several industrial processes, which has lead to an increasing interest for the knowledge and understanding of the physics which govern their propagation. For this reason, a wide range of laboratory experiments on gravity-driven flows have been carried out during the last two decades. The present work is focused on geomorphological processes and, following previous work, a series of laboratory studies which constitute a further step in mimicking natural phenomena are described and simulated. Three situations are considered with some common properties: a two-dimensional configuration, variable slope of the topography and the presence of obstacles. The setup and measurement technique employed during the development of these experiments are deeply explained in the companion work. The first experiment is based on a single obstacle, the second one is performed against multiple obstacles and the third one studies the influence of a dike on which overtopping occurs. Due to the impact of the flow against the obstacles, fast moving shocks appear, and a variety of secondary waves emerge. In order to delve into the physics of these types of phenomena, a shock-capturing numerical scheme is used to simulate the cases. The suitability of the mathematical models employed in this work has been previously validated. Comparisons between computed and experimental data are presented for the three cases. The computed results show that the numerical tool is able to predict faithfully the overall behavior of this type of complex dense granular flow.

  11. Assessment of Left Ventricular 2D Flow Pathlines during Early Diastole Using Spatial Modulation of Magnetization with Polarity Alternating Velocity Encoding (SPAMM-PAV): a study in normal volunteers and canine animals with myocardial infarction

    PubMed Central

    Zhang, Ziheng; Friedman, Daniel; Dione, Donald P.; Lin, Ben A.; Duncan, James S.; Sinusas, Albert J.; Sampath, Smita

    2013-01-01

    A high temporal resolution 2D flow pathline analysis method that describes the spatio-temporal distribution of blood entering the left ventricle during early diastolic filling is presented. Filling patterns in normal volunteers (n=8) and canine animals (baseline (n=1) and infarcted (n=6)) are studied using this approach. Data is acquired using our recently reported MR technique, SPAMM-PAV, which permits simultaneous quantification of blood velocities and myocardial strain at high temporal resolution of 14 ms. Virtual emitter particles, released from the mitral valve plane every time frame during rapid filling, are tracked to depict the propagation of 2D pathlines on the imaged plane. The pathline regional distribution patterns are compared with regional myocardial longitudinal strains and regional chamber longitudinal pressure gradients. Our results demonstrate strong spatial inter-dependence between left ventricular (LV) filling patterns and LV mechanical function. Significant differences in pathline-described filling patterns are observed in the infarcted animals. Quantitative analysis of net kinetic energy for each set of pathlines is performed. Peak net kinetic energy of 0.06±0.01 mJ in normal volunteers, 0.043 mJ in baseline dog, 0.143±0.03 mJ in three infarcted dogs with nominal flow dysfunction, and 0.016±0.007 mJ in three infarcted dogs with severe flow dysfunction is observed. PMID:23044637

  12. 2D semiconductor optoelectronics

    NASA Astrophysics Data System (ADS)

    Novoselov, Kostya

    The advent of graphene and related 2D materials has recently led to a new technology: heterostructures based on these atomically thin crystals. The paradigm proved itself extremely versatile and led to rapid demonstration of tunnelling diodes with negative differential resistance, tunnelling transistors, photovoltaic devices, etc. By taking the complexity and functionality of such van der Waals heterostructures to the next level we introduce quantum wells engineered with one atomic plane precision. Light emission from such quantum wells, quantum dots and polaritonic effects will be discussed.

  13. PIV, 2D-LIF and 1D-Raman measurements of flow field, composition and temperature in premixed gas turbine flames

    SciTech Connect

    Stopper, U.; Aigner, M.; Ax, H.; Meier, W.; Sadanandan, R.; Stoehr, M.; Bonaldo, A.

    2010-04-15

    Several laser diagnostic measurement techniques have been applied to study the lean premixed natural gas/air flames of an industrial swirl burner. This was made possible by equipping the burner with an optical combustion chamber that was installed in the high-pressure test rig facility at the DLR Institute of Combustion Technology in Stuttgart. The burner was operated with preheated air at various operating conditions with pressures up to p = 6 bar and a maximum thermal power of P = 1 MW. The instantaneous planar flow field inside the combustor was studied with particle image velocimetry (PIV). Planar laser induced fluorescence (PLIF) of OH radicals on a single-shot basis was used to determine the shape and the location of the flame front as well as the spatial distribution of reaction products. 1D laser Raman spectroscopy was successfully applied for the measurement of the temperature and the concentration of major species under realistic gas turbine conditions. Results of the flow field analysis show the shape and the size of the main flow regimes: the inflow region, the inner and the outer recirculation zone. The highly turbulent flow field of the inner shear layer is found to be dominated by small and medium sized vortices. High RMS fluctuations of the flow velocity in the exhaust gas indicate the existence of a rotating exhaust gas swirl. From the PLIF images it is seen that the primary reactions happened in the shear layers between inflow and the recirculation zones and that the appearance of the reaction zones changed with flame parameters. The results of the multiscalar Raman measurements show a strong variation of the local mixture fraction allowing conclusions to be drawn about the premix quality. Furthermore, mixing effects of unburnt fuel and air with fully reacted combustion products are studied giving insights into the processes of the turbulence-chemistry interaction. (author)

  14. Association between genetic taste sensitivity, 2D:4D ratio, dental caries prevalence, and salivary flow rate in 6-14-year-old children: a cross-sectional study

    PubMed Central

    Lakshmi, Chintamaneni Raja; Radhika, Doppalapudi; Prabhat, Mpv; Bhavana, Sujana mulk; Sai Madhavi, Nallamilli

    2016-01-01

    Background. The aim of this study was to assess the relationship between genetic taste sensitivity, dietary preferences and salivary flow rate in 6‒14-year-old children for identification of individuals at higher risk of developing dental caries. Methods. A total of 500 children 6‒14 years of age, of both genders, who reported to the Department of Oral Medicine and Radiology, were included. Propylthiouracil (PROP) sensitivity test was carried out and the subjects whose perception was bitter were grouped as tasters, whereas those who were unable to perceive any taste were grouped as non-tasters. The 2D:4D ratio was obtained by measuring the length ratio of index finger to ring finger with the help of a digital Vernier caliper. Evaluation of dietary preferences was carried out using a 24-hour dietary recall and accordingly they were categorized as sweet likers and dislikers. The salivary flow rate was estimated by collecting unstimulated saliva by spitting method. Data were analyzed with Student’s t-test and chi-squared test. Results. The results suggested a positive relation between low digit ratio (2D:4D), non-tasters, sweet likers and high caries index among the participants with a highly significant statistical difference (P ≤ 0.000). Tasters had high mean of USSR (0.48) than non-tasters (0.29), which was statistically significant. Conclusion. The present research revealed a positive correlation between all the parameters evaluated. Therefore an individual considered as non-taster by PROP was a sweet liker with low 2D:4D ratio, reduced salivary flow rate and high caries index. PMID:27651879

  15. Association between genetic taste sensitivity, 2D:4D ratio, dental caries prevalence, and salivary flow rate in 6-14-year-old children: a cross-sectional study.

    PubMed

    Lakshmi, Chintamaneni Raja; Radhika, Doppalapudi; Prabhat, Mpv; Bhavana, Sujana Mulk; Sai Madhavi, Nallamilli

    2016-01-01

    Background. The aim of this study was to assess the relationship between genetic taste sensitivity, dietary preferences and salivary flow rate in 6‒14-year-old children for identification of individuals at higher risk of developing dental caries. Methods. A total of 500 children 6‒14 years of age, of both genders, who reported to the Department of Oral Medicine and Radiology, were included. Propylthiouracil (PROP) sensitivity test was carried out and the subjects whose perception was bitter were grouped as tasters, whereas those who were unable to perceive any taste were grouped as non-tasters. The 2D:4D ratio was obtained by measuring the length ratio of index finger to ring finger with the help of a digital Vernier caliper. Evaluation of dietary preferences was carried out using a 24-hour dietary recall and accordingly they were categorized as sweet likers and dislikers. The salivary flow rate was estimated by collecting unstimulated saliva by spitting method. Data were analyzed with Student's t-test and chi-squared test. Results. The results suggested a positive relation between low digit ratio (2D:4D), non-tasters, sweet likers and high caries index among the participants with a highly significant statistical difference (P ≤ 0.000). Tasters had high mean of USSR (0.48) than non-tasters (0.29), which was statistically significant. Conclusion. The present research revealed a positive correlation between all the parameters evaluated. Therefore an individual considered as non-taster by PROP was a sweet liker with low 2D:4D ratio, reduced salivary flow rate and high caries index.

  16. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089

    NASA Technical Reports Server (NTRS)

    Narayanan, R.; Smith, C. L.; Weigel, N. L.

    2002-01-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect. Copyright 2002 Elsevier Science Inc.

  17. Vector-averaged gravity-induced changes in cell signaling and vitamin D receptor activity in MG-63 cells are reversed by a 1,25-(OH)2D3 analog, EB1089.

    PubMed

    Narayanan, R; Smith, C L; Weigel, N L

    2002-09-01

    Skeletal unloading in an animal hindlimb suspension model and microgravity experienced by astronauts or as a result of prolonged bed rest causes site-specific losses in bone mineral density of 1%-2% per month. This is accompanied by reductions in circulating levels of 1,25-(OH)(2)D(3), the active metabolite of vitamin D. 1,25-(OH)(2)D(3), the ligand for the vitamin D receptor (VDR), is important for calcium absorption and plays a role in differentiation of osteoblasts and osteoclasts. To examine the responses of cells to activators of the VDR in a simulated microgravity environment, we used slow-turning lateral vessels (STLVs) in a rotating cell culture system. We found that, similar to cells grown in microgravity, MG-63 cells grown in the STLVs produce less osteocalcin, alkaline phosphatase, and collagen Ialpha1 mRNA and are less responsive to 1,25-(OH)(2)D(3). In addition, expression of VDR was reduced. Moreover, growth in the STLV caused activation of the stress-activated protein kinase pathway (SAPK), a kinase that inhibits VDR activity. In contrast, the 1,25-(OH)(2)D(3) analog, EB1089, was able to compensate for some of the STLV-associated responses by reducing SAPK activity, elevating VDR levels, and increasing expression of osteocalcin and alkaline phosphatase. These studies suggest that, not only does simulated microgravity reduce differentiation of MG-63 cells, but the activity of the VDR, an important regulator of bone metabolism, is reduced. Use of potent, less calcemic analogs of 1,25-(OH)(2)D(3) may aid in overcoming this defect.

  18. Comparative 2D-DIGE proteomic analysis of ovarian carcinoma cells: toward a reorientation of biosynthesis pathways associated with acquired platinum resistance.

    PubMed

    Lincet, Hubert; Guével, Blandine; Pineau, Charles; Allouche, Stéphane; Lemoisson, Edwige; Poulain, Laurent; Gauduchon, Pascal

    2012-02-02

    Ovarian cancer is the fifth most frequent cause of cancer death in women. Emergence of chemoresistance in the course of treatments with platinum drugs is in part responsible for therapeutic failures. In order to improve the understanding of the complex mechanisms involved in acquired platinum chemoresistance, we decided to compare the basal protein expression profile of the platinum-sensitive cell line OAW42 and that of its resistant counterpart OAW42-R by a proteomic approach. Reversed-phase HPLC pre-fractionated extracts from both cell lines were subjected to 2D-DIGE coupled to mass spectrometry (MS). Forty eight differentially expressed proteins were identified, 39 being up-regulated and 19 down-regulated in OAW42-R versus OAW42 cells. From the current knowledge on biological activities of most differentially expressed proteins, it can be inferred that the acquisition of resistance was associated with a global reorganization of biochemical pathways favoring the production of precursors for biosynthesis, and with the mobilization of macromolecule quality control mechanisms, preserving RNA and protein integrity under damage-inducing conditions.

  19. High flow-resolution for mobility estimation in 2D-ENMR of proteins using maximum entropy method (MEM-ENMR).

    PubMed

    Thakur, Sunitha B; He, Qiuhong

    2006-11-01

    Multidimensional electrophoretic NMR (nD-ENMR) is a potentially powerful tool for structural characterization of co-existing proteins and protein conformations. By applying a DC electric field pulse, the electrophoretic migration rates of different proteins were detected experimentally in a new dimension of electrophoretic flow. The electrophoretic mobilities were employed to differentiate protein signals. In U-shaped ENMR sample chambers, individual protein components in a solution mixture followed a cosinusoidal electrophoretic interferogram as a function of its unique electrophoretic migration rate. After Fourier transformation in the electrophoretic flow dimension, the protein signals were resolved at different resonant frequencies proportional to their electrophoretic mobilities. Currently, the mobility resolution of the proteins in the electrophoretic flow dimension is limited by severe truncations of the electrophoretic interferograms due to the finite electric field strength available before the onset of heat-induced convection. In this article, we present a successful signal processing method, the Burg's maximum entropy method (MEM), to analyze the truncated ENMR signals (MEM-ENMR). Significant enhancement in flow resolution was demonstrated using two-dimensional ENMR of two protein samples: a lysozyme solution and a solution mixture of bovine serum albumin (BSA) and ubiquitin. The electrophoretic mobilities of lysozyme, BSA and ubiquitin were measured from the MEM analysis as 7.5x10(-5), 1.9x10(-4) and 8.7x10(-5) cm2 V-1 s-1, respectively. Results from computer simulations confirmed a complete removal of truncation artifacts in the MEM-ENMR spectra with 3- to 6-fold resolution enhancement.

  20. Simulation of Mean Flow and Turbulence over a 2D Building Array Using High-Resolution CFD and a Distributed Drag Force Approach

    DTIC Science & Technology

    2016-06-16

    Journal of Wind Engineering ELSEVIER and Industrial Aerodynamics 92 (2004) 117-158 www.elsevier.com/locate/jweia Simulation of mean flow and...detailed and comprehensive wind tunnel data set. Vertical profiles of the mean streamwise velocity and the turbulence kinetic energy are presented and...compared to those measured in the wind tunnel simulation. It is found that the performance of all the turbulence models investigated is generally

  1. Pitot survey of exhaust flow field of a 2-D scramjet nozzle at Mach 6 with air or freon and argon used for exhaust simulation

    NASA Technical Reports Server (NTRS)

    Monta, William J.

    1992-01-01

    A pitot-rake survey of the simulated exhaust of a half-span scramjet nozzle model was conducted in the Langley 20-Inch Mach 6 Tunnel to provide an additional data set for computational fluid dynamics (CFD) code comparisons. A wind-tunnel model was tested with a 26-tube pitot rake that could be manually positioned along the mid-semispan plane of the model. The model configuration had an external expansion surface of 20 degrees and an internal cowl expansion of 12 degrees; tests were also performed with a flow fence. Tests were conducted at a free-stream Reynolds number of approximately 6.5 x 10(exp 6) per foot and a model angle of attack of -0.75 degrees. The two exhaust gas mediums that were tested were air and a Freon 12-argon mixture. Each medium was tested at two jet total pressures at approximately 28 and 14 psia. This document presents the flow-field survey results in graphical as well as tabular form, and several observations concerning the results are discussed. The surveys reveal the major expected flow-field characteristics for each test configuration. For a 50-percent freon 12 and 50-percent argon mixture by volume (Fr-Ar), the exhaust jet pressures were slightly higher than those for air. The addition of a flow fence slightly raised the pitot pressure for the Fr-Ar mixture, but it produced little change for air. For the Fr-Ar exhaust, the plume was larger and the region between the shock wave and plume was smaller.

  2. Dielectric Barrier Discharge Plasma Actuators with Novel Geometries for Flow Modification: Experimental Measurements and Validation with a 2-D Fluid Model

    DTIC Science & Technology

    2013-12-30

    Dielectric barrier discharge ( DBD ) U U U UU 16 Noah Hershkowitz 608-831-5862 SF-298 Abstract / Contract No. FA9550-10-1-0565 Optical characteristics of...surface dielectric barrier discharge ( DBD ) plasma actuators with wire/planar electrodes were studied using an intensified charge-coupled device camera and...grounded planar electrode were observed for the first time. Time resolved velocity measurements of the air flow fields induced by planar DBD actuators

  3. A numerical study of steady 2D flow around NACA 0015 and NACA 0012 hydrofoil with free surface using VOF method

    NASA Astrophysics Data System (ADS)

    Adjali, Saadia; Belkadi, Mustapha; Aounallah, Mohammed; Imine, Omar

    2015-05-01

    Accurate simulation of turbulent free surface flows around surface ships has a central role in the optimal design of such naval vessels. The flow problem to be simulated is rich in complexity and poses many modeling challenges because of the existence of breaking waves around the ship hull, and because of the interaction of the two-phase flow with the turbulent boundary layer. In this paper, our goal is to estimate the lift and drag coefficients for NACA 0012 of hydrofoil advancing in calm water under steady conditions with free surface and emerged NACA 0015. The commercial CFD software FLUENT version 14 is used for the computations in the present study. The calculated grid is established using the code computer GAMBIT 2.3.26.The shear stress k-ωSST model is used for turbulence modeling and the volume of fluid technique is employed to simulate the free-surface motion. In this computation, the second order upwind scheme is used for discretizing the convection terms in the momentum transport equations, the Modified HRIC scheme for VOF discretisation. The results obtained compare well with the experimental data.

  4. Protection of rat intestinal epithelial cells from ischemia/reperfusion injury by (D-Ala2, D-Leu5)-enkephalin through inhibition of the MKK7-JNK signaling pathway

    PubMed Central

    WANG, ZHENRAN; TANG, BO; TANG, FANG; LI, YANG; ZHANG, GUANGYU; ZHONG, LI; DONG, CHENCHENG; HE, SONGQING

    2015-01-01

    Previous studies have demonstrated that (D-Ala2, D-Leu5)-enkephalin (DADLE) protects rats from hepatic ischemia/reperfusion (I/R) injury. In the present study, DADLE was also observed to alleviate IR-induced intestinal epithelial cell injury in rats by inhibiting mitogen-activated protein kinase kinase 7 (MKK7)-c-Jun N-terminal kinase (JNK) pathway signaling. To investigate the protective effect of DADLE on hypoxia/reoxygenation injury in rat intestinal epithelial cells, rat intestinal epithelial cells were treated with different concentrations of DADLE, following which the cell survival rate was determined using a tetrazolium (MTT) colorimetric assay, and apoptosis was determined using flow cytometry. To confirm whether the protective effect of DADLE was due to its effect on MKK7-JNK signaling, the phosphorylation levels of MKK7 and JNK were analyzed using western blot analysis following treatment with different concentrations of DADLE. The results demonstrated that, following treatment with DADLE, the survival rate of the rat intestinal cells subjected to I/R-induced injury increased significantly and the apoptotic rate decreased in a concentration-dependent manner. In addition, the levels of phosphorylated MKK7 and JNK decreased in a concentration-dependent manner following treatment with DADLE. Silencing the gene expression of MKK7 using small interfering RNA prior to DADLE treatment resulted in a reduction in the protective effects of DADLE on the rat intestinal epithelial cells subjected to I/R injury. Collectively, the results of the present study demonstrated that the protective effects of DADLE in I/R injury in rat intestinal cells occurred through inhibition of the MKK7-JNK pathway. PMID:26126577

  5. Non-Fullerene Polymer Solar Cells Based on Alkylthio and Fluorine Substituted 2D-Conjugated Polymers Reach 9.5% Efficiency.

    PubMed

    Bin, Haijun; Zhang, Zhi-Guo; Gao, Liang; Chen, Shanshan; Zhong, Lian; Xue, Lingwei; Yang, Changduk; Li, Yongfang

    2016-04-06

    Non-fullerene polymer solar cells (PSCs) with solution-processable n-type organic semiconductor (n-OS) as acceptor have seen rapid progress recently owing to the synthesis of new low bandgap n-OS, such as ITIC. To further increase power conversion efficiency (PCE) of the devices, it is of a great challenge to develop suitable polymer donor material that matches well with the low bandgap n-OS acceptors thus providing complementary absorption and nanoscaled blend morphology, as well as suppressed recombination and minimized energy loss. To address this challenge, we synthesized three medium bandgap 2D-conjugated bithienyl-benzodithiophene-alt-fluorobenzotriazole copolymers J52, J60, and J61 for the application as donor in the PSCs with low bandgap n-OS ITIC as acceptor. The three polymers were designed with branched alkyl (J52), branched alkylthio (J60), and linear alkylthio (J61) substituent on the thiophene conjugated side chain of the benzodithiophene (BDT) units for studying effect of the substituents on the photovoltaic performance of the polymers. The alkylthio side chain, red-shifted absorption down-shifted the highest occupied molecular orbital (HOMO) level and improved crystallinity of the 2D conjugated polymers. With linear alkylthio side chain, the tailored polymer J61 exhibits an enhanced JSC of 17.43 mA/cm(2), a high VOC of 0.89 V, and a PCE of 9.53% in the best non-fullerene PSCs with the polymer as donor and ITIC as acceptor. To the best of our knowledge, the PCE of 9.53% is one of the highest values reported in literature to date for the non-fullerene PSCs. The results indicate that J61 is a promising medium bandgap polymer donor in non-fullerene PSCs.

  6. Cellulose Structural Polymorphism in Plant Primary Cell Walls Investigated by High-Field 2D Solid-State NMR Spectroscopy and Density Functional Theory Calculations.

    PubMed

    Wang, Tuo; Yang, Hui; Kubicki, James D; Hong, Mei

    2016-06-13

    The native cellulose of bacterial, algal, and animal origins has been well studied structurally using X-ray and neutron diffraction and solid-state NMR spectroscopy, and is known to consist of varying proportions of two allomorphs, Iα and Iβ, which differ in hydrogen bonding, chain packing, and local conformation. In comparison, cellulose structure in plant primary cell walls is much less understood because plant cellulose has lower crystallinity and extensive interactions with matrix polysaccharides. Here we have combined two-dimensional magic-angle-spinning (MAS) solid-state nuclear magnetic resonance (solid-state NMR) spectroscopy at high magnetic fields with density functional theory (DFT) calculations to obtain detailed information about the structural polymorphism and spatial distributions of plant primary-wall cellulose. 2D (13)C-(13)C correlation spectra of uniformly (13)C-labeled cell walls of several model plants resolved seven sets of cellulose chemical shifts. Among these, five sets (denoted a-e) belong to cellulose in the interior of the microfibril while two sets (f and g) can be assigned to surface cellulose. Importantly, most of the interior cellulose (13)C chemical shifts differ significantly from the (13)C chemical shifts of the Iα and Iβ allomorphs, indicating that plant primary-wall cellulose has different conformations, packing, and hydrogen bonding from celluloses of other organisms. 2D (13)C-(13)C correlation experiments with long mixing times and with water polarization transfer revealed the spatial distributions and matrix-polysaccharide interactions of these cellulose structures. Celluloses f and g are well mixed chains on the microfibril surface, celluloses a and b are interior chains that are in molecular contact with the surface chains, while cellulose c resides in the core of the microfibril, outside spin diffusion contact with the surface. Interestingly, cellulose d, whose chemical shifts differ most significantly from those of

  7. Cellulose Structural Polymorphism in Plant Primary Cell Walls Investigated by High-Field 2D Solid-State NMR Spectroscopy and Density Functional Theory Calculations

    PubMed Central

    Wang, Tuo; Yang, Hui; Kubicki, James D.; Hong, Mei

    2017-01-01

    The native cellulose of bacterial, algal, and animal origins has been well studied structurally using X-ray and neutron diffraction and solid-state NMR spectroscopy, and is known to consist of varying proportions of two allomorphs, Iα and Iβ, which differ in hydrogen bonding, chain packing, and local conformation. In comparison, cellulose structure in plant primary cell walls is much less understood because plant cellulose has lower crystallinity and extensive interactions with matrix polysaccharides. Here we have combined two-dimensional magic-angle-spinning (MAS) solid-state nuclear magnetic resonance (solid-state NMR) spectroscopy at high magnetic fields with density functional theory (DFT) calculations to obtain detailed information about the structural polymorphism and spatial distributions of plant primary-wall cellulose. 2D 13C-13C correlation spectra of uniformly 13C-labeled cell walls of several model plants resolved seven sets of cellulose chemical shifts. Among these, five sets (denoted a-e) belong to cellulose in the interior of the microfibril while two sets (f and g) can be assigned to surface cellulose. Importantly, most of the interior cellulose 13C chemical shifts differ significantly from the 13C chemical shifts of the Iα and Iβ allomorphs, indicating that plant primary-wall cellulose has different conformations, packing and hydrogen bonding from celluloses of other organisms. 2D 13C-13C correlation experiments with long mixing times and with water polarization transfer revealed the spatial distributions and matrix-polysaccharide interactions of these cellulose structures. Cellulose f and g are well mixed chains on the microfibril surface, cellulose a and b are interior chains that are in molecular contact with the surface chains, while cellulose c resides in the core of the microfibril, outside spin diffusion contact with the surface. Interestingly, cellulose d, whose chemical shifts differ most significantly from those of bacterial, algal

  8. Expression of transcription factors after short-term exposure of Arabidopsis thaliana cell cultures to hypergravity and simulated microgravity (2-D/3-D clinorotation, magnetic levitation)

    NASA Astrophysics Data System (ADS)

    Babbick, M.; Dijkstra, C.; Larkin, O. J.; Anthony, P.; Davey, M. R.; Power, J. B.; Lowe, K. C.; Cogoli-Greuter, M.; Hampp, R.

    Gravity is an important environmental factor that controls plant growth and development. Studies have shown that the perception of gravity is not only a property of specialized cells, but can also be performed by undifferentiated cultured cells. In this investigation, callus of Arabidopsis thaliana cv. Columbia was used to investigate the initial steps of gravity-related signalling cascades, through altered expression of transcription factors (TFs). TFs are families of small proteins that regulate gene expression by binding to specific promoter sequences. Based on microarray studies, members of the gene families WRKY, MADS-box, MYB, and AP2/EREBP were selected for investigation, as well as members of signalling chains, namely IAA 19 and phosphoinositol-4-kinase. Using qRT-PCR, transcripts were quantified within a period of 30 min in response to hypergravity (8 g), clinorotation [2-D clinostat and 3-D random positioning machine (RPM)] and magnetic levitation (ML). The data indicated that (1) changes in gravity induced stress-related signalling, and (2) exposure in the RPM induced changes in gene expression which resemble those of magnetic levitation. Two dimensional clinorotation resulted in responses similar to those caused by hypergravity. It is suggested that RPM and ML are preferable to simulate microgravity than clinorotation.

  9. Structure and Metabolic-Flow Analysis of Molecular Complexity in a (13) C-Labeled Tree by 2D and 3D NMR.

    PubMed

    Komatsu, Takanori; Ohishi, Risa; Shino, Amiu; Kikuchi, Jun

    2016-05-10

    Improved signal identification for biological small molecules (BSMs) in a mixture was demonstrated by using multidimensional NMR on samples from (13) C-enriched Rhododendron japonicum (59.5 atom%) cultivated in air containing (13) C-labeled carbon dioxide for 14 weeks. The resonance assignment of 386 carbon atoms and 380 hydrogen atoms in the mixture was achieved. 42 BSMs, including eight that were unlisted in the spectral databases, were identified. Comparisons between the experimental values and the (13) C chemical shift values calculated by density functional theory supported the identifications of unlisted BSMs. Tracing the (13) C/(12) C ratio by multidimensional NMR spectra revealed faster and slower turnover ratios of BSMs involved in central metabolism and those categorized as secondary metabolites, respectively. The identification of BSMs and subsequent flow analysis provided insight into the metabolic systems of the plant.

  10. Comparison of 2D and 3D Computational Multiphase Fluid Flow Models of Oxygen Lancing of Pyrometallurgical Furnace Tap-Holes

    NASA Astrophysics Data System (ADS)

    Erwee, M. W.; Reynolds, Q. G.; Zietsman, J. H.

    2016-06-01

    Furnace tap-holes vary in design depending on the type of furnace and process involved, but they share one common trait: The tap-hole must be opened and closed periodically. In general, tap-holes are plugged with refractory clay after tapping, thereby stopping the flow of molten material. Once a furnace is ready to be tapped, drilling and/or lancing with oxygen are typically used to remove tap-hole clay from the tap-hole. Lancing with oxygen is an energy-intensive, mostly manual process, which affects the performance and longevity of the tap-hole refractory material as well as the processes inside the furnace. Computational modeling offers an opportunity to gain insight into the possible effects of oxygen lancing on various aspects of furnace operation.

  11. Transition to turbulence: 2D directed percolation

    NASA Astrophysics Data System (ADS)

    Chantry, Matthew; Tuckerman, Laurette; Barkley, Dwight

    2016-11-01

    The transition to turbulence in simple shear flows has been studied for well over a century, yet in the last few years has seen major leaps forward. In pipe flow, this transition shows the hallmarks of (1 + 1) D directed percolation, a universality class of continuous phase transitions. In spanwisely confined Taylor-Couette flow the same class is found, suggesting the phenomenon is generic to shear flows. However in plane Couette flow the largest simulations and experiments to-date find evidence for a discrete transition. Here we study a planar shear flow, called Waleffe flow, devoid of walls yet showing the fundamentals of planar transition to turbulence. Working with a quasi-2D yet Navier-Stokes derived model of this flow we are able to attack the (2 + 1) D transition problem. Going beyond the system sizes previously possible we find all of the required scalings of directed percolation and thus establish planar shears flow in this class.

  12. Microconfined flow behavior of red blood cells.

    PubMed

    Tomaiuolo, Giovanna; Lanotte, Luca; D'Apolito, Rosa; Cassinese, Antonio; Guido, Stefano

    2016-01-01

    Red blood cells (RBCs) perform essential functions in human body, such as gas exchange between blood and tissues, thanks to their ability to deform and flow in the microvascular network. The high RBC deformability is mainly due to the viscoelastic properties of the cell membrane. Since an impaired RBC deformability could be found in some diseases, such as malaria, sickle cell anemia, diabetes and hereditary disorders, there is the need to provide further insight into measurement of RBC deformability in a physiologically relevant flow field. Here, RBCs deformability has been studied in terms of the minimum apparent plasma-layer thickness by using high-speed video microscopy of RBCs flowing in cylindrical glass capillaries. An in vitro systematic microfluidic investigation of RBCs in micro-confined conditions has been performed, resulting in the determination of the RBCs time recovery constant, RBC volume and surface area and RBC membrane shear elastic modulus and surface viscosity. It has been noticed that the deformability of RBCs induces cells aggregation during flow in microcapillaries, allowing the formation of clusters of cells. Overall, our results provide a novel technique to estimate RBC deformability and also RBCs collective behavior, which can be used for the analysis of pathological RBCs, for which reliable quantitative methods are still lacking.

  13. Transfer of the human NKG2D ligands UL16 binding proteins (ULBP) 1-3 is related to lytic granule release and leads to ligand retransfer and killing of ULBP-recipient natural killer cells.

    PubMed

    López-Cobo, Sheila; Romera-Cárdenas, Gema; García-Cuesta, Eva M; Reyburn, Hugh T; Valés-Gómez, Mar

    2015-09-01

    After immune interactions, membrane fragments can be transferred between cells. This fast transfer of molecules is transient and shows selectivity for certain proteins; however, the constraints underlying acquisition of a protein are unknown. To characterize the mechanism and functional consequences of this process in natural killer (NK) cells, we have compared the transfer of different NKG2D ligands. We show that human NKG2D ligands can be acquired by NK cells with different efficiencies. The main findings are that NKG2D ligand transfer is related to immune activation and receptor-ligand interaction and that NK cells acquire these proteins during interactions with target cells that lead to degranulation. Our results further demonstrate that NK cells that have acquired NKG2D ligands can stimulate activation of autologous NK cells. Surprisingly, NK cells can also re-transfer the acquired molecule to autologous effector cells during this immune recognition that leads to their death. These data demonstrate that transfer of molecules occurs as a consequence of immune recognition and imply that this process might play a role in homeostatic tuning-down of the immune response or be used as marker of interaction.

  14. Post-translational modification of the NKG2D ligand RAET1G leads to cell surface expression of a glycosylphosphatidylinositol-linked isoform.

    PubMed

    Ohashi, Maki; Eagle, Robert A; Trowsdale, John

    2010-05-28

    NKG2D is an important activating receptor on lymphocytes. In human, it interacts with two groups of ligands: the major histocompatibility complex class I chain-related A/B (MICA/B) family and the UL-16 binding protein (ULBP) family, also known as retinoic acid early transcript (RAET1). MIC proteins are membrane-anchored, but all of the ULBP/RAET1 proteins, except for RAET1E and RAET1G, are glycosylphosphatidylinositol (GPI)-anchored. To address the reason for these differences we studied the association of RAET1G with the membrane. Using epitope-tagged RAET1G protein in conjunction with antibodies to different parts of the molecule and in pulse-chase experiments, we showed that the C terminus of the protein was cleaved soon after protein synthesis. Endoglycosidase H and peptide N-glycosidase treatment and cell surface immunoprecipitation indicated that most of the protein stayed in the endoplasmic reticulum, but some of the cleaved form was modified in the Golgi and transported to the cell surface. We examined the possibility of GPI anchoring of the protein in three ways: (i) Phosphatidylinositol (PI)-specific phospholipase C released the PI-linked form of the protein. (ii) The surface expression pattern of RAET1G decreased in cells defective in GPI anchoring through mutant GPI-amidase. (iii) Site-directed mutagenesis, to disrupt residues predicted to facilitate GPI-anchoring, resulted in diminished surface expression of RAET1G. Thus, a form of RAET1G is GPI-anchored, in line with most other ULBP/RAET1 family proteins. The cytoplasmic tail and transmembrane domains appear to result from gene duplication and frameshift mutation. Together with our previous results, our data suggest that RAET1G is regulated post-translationally to produce a GPI-anchored isoform.

  15. Post-translational Modification of the NKG2D Ligand RAET1G Leads to Cell Surface Expression of a Glycosylphosphatidylinositol-linked Isoform*

    PubMed Central

    Ohashi, Maki; Eagle, Robert A.; Trowsdale, John

    2010-01-01

    NKG2D is an important activating receptor on lymphocytes. In human, it interacts with two groups of ligands: the major histocompatibility complex class I chain-related A/B (MICA/B) family and the UL-16 binding protein (ULBP) family, also known as retinoic acid early transcript (RAET1). MIC proteins are membrane-anchored, but all of the ULBP/RAET1 proteins, except for RAET1E and RAET1G, are glycosylphosphatidylinositol (GPI)-anchored. To address the reason for these differences we studied the association of RAET1G with the membrane. Using epitope-tagged RAET1G protein in conjunction with antibodies to different parts of the molecule and in pulse-chase experiments, we showed that the C terminus of the protein was cleaved soon after protein synthesis. Endoglycosidase H and peptide N-glycosidase treatment and cell surface immunoprecipitation indicated that most of the protein stayed in the endoplasmic reticulum, but some of the cleaved form was modified in the Golgi and transported to the cell surface. We examined the possibility of GPI anchoring of the protein in three ways: (i) Phosphatidylinositol (PI)-specific phospholipase C released the PI-linked form of the protein. (ii) The surface expression pattern of RAET1G decreased in cells defective in GPI anchoring through mutant GPI-amidase. (iii) Site-directed mutagenesis, to disrupt residues predicted to facilitate GPI-anchoring, resulted in diminished surface expression of RAET1G. Thus, a form of RAET1G is GPI-anchored, in line with most other ULBP/RAET1 family proteins. The cytoplasmic tail and transmembrane domains appear to result from gene duplication and frameshift mutation. Together with our previous results, our data suggest that RAET1G is regulated post-translationally to produce a GPI-anchored isoform. PMID:20304922

  16. Free flow cell electrophoresis using zwitterionic buffer

    NASA Technical Reports Server (NTRS)

    Rodkey, R. Scott

    1990-01-01

    Studies of a zwitterionic buffer formulated for cell electrophoresis were done using the McDonnell-Douglas Continuous Flow Electrophoresis System. Standard buffers were analyzed for their stability in the electrical field and the results showed that both buffers tested were inherently unstable. Further, titration studies showed that the standards buffers buffered poorly at the pH employed for electrophoresis. The zwitterionic buffer buffered well at its nominal pH and was shown to be stable in the electrical field. Comparative studies of the buffer with standard cell separation buffers using formalin fixed rabbit and goose red blood cells showed that the zwitterionic buffer gave better resolution of the fixed cells. Studies with viable hybridoma cells showed that buffer Q supported cell viability equal to Hank's Balanced Salt Solution and that hybridoma cells in different stages of the growth cycle demonstrated reproducible differences in electrophoretic mobility.

  17. A high-throughput 2D-analytical technique to obtain single protein parameters from complex cell lysates for in silico process development of ion exchange chromatography.

    PubMed

    Kröner, Frieder; Elsäßer, Dennis; Hubbuch, Jürgen

    2013-11-29

    The accelerating growth of the market for biopharmaceutical proteins, the market entry of biosimilars and the growing interest in new, more complex molecules constantly pose new challenges for bioseparation process development. In the presented work we demonstrate the application of a multidimensional, analytical separation approach to obtain the relevant physicochemical parameters of single proteins in a complex mixture for in silico chromatographic process development. A complete cell lysate containing a low titre target protein was first fractionated by multiple linear salt gradient anion exchange chromatography (AEC) with varying gradient length. The collected fractions were subsequently analysed by high-throughput capillary gel electrophoresis (HT-CGE) after being desalted and concentrated. From the obtained data of the 2D-separation the retention-volumes and the concentration of the single proteins were determined. The retention-volumes of the single proteins were used to calculate the related steric-mass action model parameters. In a final evaluation experiment the received parameters were successfully applied to predict the retention behaviour of the single proteins in salt gradient AEC.

  18. 2D particle-in-cell simulations of the electron drift instability and associated anomalous electron transport in Hall-effect thrusters

    NASA Astrophysics Data System (ADS)

    Croes, Vivien; Lafleur, Trevor; Bonaventura, Zdeněk; Bourdon, Anne; Chabert, Pascal

    2017-03-01

    In this work we study the electron drift instability in Hall-effect thrusters (HETs) using a 2D electrostatic particle-in-cell (PIC) simulation. The simulation is configured with a Cartesian coordinate system modeling the radial-azimuthal (r{--}θ ) plane for large radius thrusters. A magnetic field, {{B}}0, is aligned along the Oy axis (r direction), a constant applied electric field, {{E}}0, along the Oz axis (perpendicular to the simulation plane), and the {{E}}0× {{B}}0 direction is along the Ox axis (θ direction). Although electron transport can be well described by electron–neutral collisions for low plasma densities, at high densities (similar to those in typical HETs), a strong instability is observed that enhances the electron cross-field mobility; even in the absence of electron–neutral collisions. The instability generates high frequency (of the order of MHz) and short wavelength (of the order of mm) fluctuations in both the azimuthal electric field and charged particle densities, and propagates in the {{E}}0× {{B}}0 direction with a velocity close to the ion sound speed. The correlation between the electric field and density fluctuations (which leads to an enhanced electron–ion friction force) is investigated and shown to be directly responsible for the increased electron transport. Results are compared with a recent kinetic theory, showing good agreement with the instability properties and electron transport.

  19. Comparative 2D-DIGE proteomic analysis of bovine mammary epithelial cells during lactation reveals protein signatures for lactation persistency and milk yield.

    PubMed

    Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K; Grover, Sunita; Dang, Ajay K; Mukesh, Manishi; Prakash, B S; Mohanty, Ashok K

    2014-01-01

    Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.

  20. Towards optical cell transfection inside a micro flow cell

    NASA Astrophysics Data System (ADS)

    Breunig, H. G.; Uchugonova, A.; König, K.

    2014-03-01

    For optical transfection, cells are shortly subjected to intense, focused laser radiation which leads to a temporary opening in the cell membrane. Although the method is very efficient and ensures high cell viability, the targeting of single cells with laser pulses is a tedious and slow approach. We present first measurements aiming at an experimental setup which is suitable for high throughput and automated optical cell transfection. In our setup, cells flow through a micro flow cell where they are spatially confined. The laser radiation is focused into the cell in a way that an elongated focal region is realized. This makes the time consuming aiming of the laser beam at individual cells unnecessary and opens the possibility to develop a completely automated system. The elongated laser focal region is realized by a quasi-Bessel beam which is generated by an axicon lens setup and continuously scanned from side to side of the cell. We present test measurements of the newly employed setup and discuss its suitability to be fully integrated into a flow cell sequencing system.

  1. Time-lapse microscopy and classification of 2D human mesenchymal stem cells based on cell shape picks up myogenic from osteogenic and adipogenic differentiation.

    PubMed

    Seiler, Christof; Gazdhar, Amiq; Reyes, Mauricio; Benneker, Lorin M; Geiser, Thomas; Siebenrock, Klaus A; Gantenbein-Ritter, Benjamin

    2014-09-01

    Current methods to characterize mesenchymal stem cells (MSCs) are limited to CD marker expression, plastic adherence and their ability to differentiate into adipogenic, osteogenic and chondrogenic precursors. It seems evident that stem cells undergoing differentiation should differ in many aspects, such as morphology and possibly also behaviour; however, such a correlation has not yet been exploited for fate prediction of MSCs. Primary human MSCs from bone marrow were expanded and pelleted to form high-density cultures and were then randomly divided into four groups to differentiate into adipogenic, osteogenic chondrogenic and myogenic progenitor cells. The cells were expanded as heterogeneous and tracked with time-lapse microscopy to record cell shape, using phase-contrast microscopy. The cells were segmented using a custom-made image-processing pipeline. Seven morphological features were extracted for each of the segmented cells. Statistical analysis was performed on the seven-dimensional feature vectors, using a tree-like classification method. Differentiation of cells was monitored with key marker genes and histology. Cells in differentiation media were expressing the key genes for each of the three pathways after 21 days, i.e. adipogenic, osteogenic and chondrogenic, which was also confirmed by histological staining. Time-lapse microscopy data were obtained and contained new evidence that two cell shape features, eccentricity and filopodia (= 'fingers') are highly informative to classify myogenic differentiation from all others. However, no robust classifiers could be identified for the other cell differentiation paths. The results suggest that non-invasive automated time-lapse microscopy could potentially be used to predict the stem cell fate of hMSCs for clinical application, based on morphology for earlier time-points. The classification is challenged by cell density, proliferation and possible unknown donor-specific factors, which affect the performance of

  2. Tracking Epithelial Cell Junctions in C. elegans Embryogenesis With Active Contours Guided by SIFT Flow

    PubMed Central

    Lee, Chen-Yu; Gonçalves, Monira; Chisholm, Andrew D.; Cosman, Pamela C.

    2015-01-01

    Quantitative analysis of cell shape in live samples is an important goal in developmental biology. Automated or semiautomated segmentation and tracking of cell nuclei has been successfully implemented in several biological systems. Segmentation and tracking of cell surfaces has been more challenging. Here, we present a new approach to tracking cell junctions in the developing epidermis of C. elegans embryos. Epithelial junctions as visualized with DLG-1::GFP form lines at the subapical circumference of differentiated epidermal cells and delineate changes in epidermal cell shape and position. We develop and compare two approaches for junction segmentation. For the first method (projection approach), 3-D cell boundaries are projected into 2D for segmentation using active contours with a nonintersecting force, and subsequently tracked using scale-invariant feature transform (SIFT) flow. The resulting 2-D tracked boundaries are then back-projected into 3-D space. The second method (volumetric approach) uses a 3-D extended version of active contours guided by SIFT flow in 3-D space. In both methods, cell junctions are manually located at the first time point and tracked in a fully automated way for the remainder of the video. Using these methods, we have generated the first quantitative description of ventral epidermal cell movements and shape changes during epidermal enclosure. PMID:24771564

  3. Biofilm responses to smooth flow fields and chemical gradients in novel microfluidic flow cells

    PubMed Central

    Song, Jisun L.; Au, Kelly H.; Huynh, Kimberly T.

    2013-01-01

    We present two novel microfluidic flow cells developed to provide reliable control of flow distributions and chemical gradients in biofilm studies. We developed a single-inlet microfluidic flow cell to support biofilm growth under a uniform velocity field, and a double-inlet flow cell to provide a very smooth transverse concentration gradient. Both flow cells consist of a layer of polydimethylsiloxane (PDMS) bonded to glass cover slips and were fabricated using the replica molding technique. We demonstrate the capabilities of the flow cells by quantifying flow patterns before and after growth of Pseudomonas aeruginosa biofilms through particle imaging velocimetry, and by evaluating concentration gradients within the double-inlet microfluidic flow cell. Biofilm growth substantially increased flow complexity by diverting flow around biomass, creating high- and low-velocity regions and surface friction. Under a glucose gradient in the double-inlet flow cell, P. aeruginosa biofilms grew in proportion to the local glucose concentration, producing distinct spatial patterns in biofilm biomass relative to the imposed glucose gradient. When biofilms were subjected to a ciprofloxacin gradient, spatial patterns of fractions of dead cells were also in proportion to the local antibiotic concentration. These results demonstrate that the microfluidic flow cells are suitable for quantifying flow complexities resulting from flow-biofilm interactions and investigating spatial patterns of biofilm growth under chemical gradients. These novel microfluidic flow cells will facilitate biofilm research that requires flow control and in situ imaging, particularly investigations of biofilm-environment interactions. PMID:24038055

  4. Artificial Hair Cells for Sensing Flows

    NASA Technical Reports Server (NTRS)

    Chen, Jack

    2007-01-01

    The purpose of this article is to present additional information about the flow-velocity sensors described briefly in the immediately preceding article. As noted therein, these sensors can be characterized as artificial hair cells that implement an approximation of the sensory principle of flow-sensing cilia of fish: A cilium is bent by an amount proportional to the flow to which it is exposed. A nerve cell at the base of the cilium senses the flow by sensing the bending of the cilium. In an artificial hair cell, the artificial cilium is a microscopic cantilever beam, and the bending of an artificial cilium is measured by means of a strain gauge at its base (see Figure 1). Figure 2 presents cross sections of a representative sensor of this type at two different stages of its fabrication process. The process consists of relatively- low-temperature metallization, polymer-deposition, microfabrication, and surface-micromachining subprocesses, including plastic-deformation magnetic assembly (PDMA), which is described below. These subprocesses are suitable for a variety of substrate materials, including silicon, some glasses, and some polymers. Moreover, because it incorporates a polymeric supporting structure, this sensor is more robust, relative to its silicon-based counterparts.

  5. 2D quasiperiodic plasmonic crystals

    PubMed Central

    Bauer, Christina; Kobiela, Georg; Giessen, Harald

    2012-01-01

    Nanophotonic structures with irregular symmetry, such as quasiperiodic plasmonic crystals, have gained an increasing amount of attention, in particular as potential candidates to enhance the absorption of solar cells in an angular insensitive fashion. To examine the photonic bandstructure of such systems that determines their optical properties, it is necessary to measure and model normal and oblique light interaction with plasmonic crystals. We determine the different propagation vectors and consider the interaction of all possible waveguide modes and particle plasmons in a 2D metallic photonic quasicrystal, in conjunction with the dispersion relations of a slab waveguide. Using a Fano model, we calculate the optical properties for normal and inclined light incidence. Comparing measurements of a quasiperiodic lattice to the modelled spectra for angle of incidence variation in both azimuthal and polar direction of the sample gives excellent agreement and confirms the predictive power of our model. PMID:23209871

  6. 2D immunoblots show differential response of mouse IgG and IgM antibodies to antigens of mammary carcinoma 4 T1 cells

    PubMed Central

    2014-01-01

    Background Immunosuppression in breast cancer has been reported in women and in the highly metastatic mouse mammary tumor model 4 T1. The immunosuppressive environment complicates the use of the humoral response against the tumor as an immunodiagnostic tool. IgM has not been used in immunodiagnostic in part because its antitumor responses, both innate and adaptive, have not been studied in function of time in breast cancer. We show a new approach to analyzing the mouse humoral immune response, and compare the evolution with time of IgG and IgM responses against the antigens of 4 T1 cells. Methods The study is based on 2-dimensional immunoblotting detection of antigens from 4 T1 cells by the IgG and IgM antibodies in the serum of female mice injected with 4 T1 cells. Results There was a high variability in the intra-and inter-mouse response. Variability in the IgM response was manifested as a pattern of spots that could become a multibinomial variable of 0 and 1, which could represent a signature of the immune response. Different numbers of spots was found in the IgG and IgM responses from week 1 to 5. On average, the IgM had more but the IgG response decrease with the time. The natural IgM at t = 0 responds stronger than w1; the adaptive response of both IgM and IgG were elicited where, with the former being stronger better than the latter. Antigens that are recognized by some female mice in the first week are also recognized by other female mice at time 0. Contamination of the natural IgM makes difficult use the adaptive IgM as a tool for immunodiagnostic. Conclusions IgM and IgG response varied with the time and individuals. Spot variation in 2D pattern for the natural IgM could be expressed as a binomial signature, which opens up the way to correlate a particular pattern with resistance or susceptibility. This uncovers a battery of IgMs for each individual to confront cancer or infections. The possibility to differentiate between adaptive IgM antibodies

  7. High speed flow cytometric separation of viable cells

    DOEpatents

    Sasaki, Dennis T.; Van den Engh, Gerrit J.; Buckie, Anne-Marie

    1995-01-01

    Hematopoietic cell populations are separated to provide cell sets and subsets as viable cells with high purity and high yields, based on the number of original cells present in the mixture. High-speed flow cytometry is employed using light characteristics of the cells to separate the cells, where high flow speeds are used to reduce the sorting time.

  8. High speed flow cytometric separation of viable cells

    DOEpatents

    Sasaki, D.T.; Van den Engh, G.J.; Buckie, A.M.

    1995-11-14

    Hematopoietic cell populations are separated to provide cell sets and subsets as viable cells with high purity and high yields, based on the number of original cells present in the mixture. High-speed flow cytometry is employed using light characteristics of the cells to separate the cells, where high flow speeds are used to reduce the sorting time.

  9. Development of wide-angle 2D light scattering static cytometry

    NASA Astrophysics Data System (ADS)

    Xie, Linyan; Liu, Qiao; Shao, Changshun; Su, Xuantao

    2016-10-01

    We have recently developed a 2D light scattering static cytometer for cellular analysis in a label-free manner, which measures side scatter (SSC) light in the polar angular range from 79 to 101 degrees. Compared with conventional flow cytometry, our cytometric technique requires no fluorescent labeling of the cells, and static cytometry measurements can be performed without flow control. In this paper we present an improved label-free static cytometer that can obtain 2D light scattering patterns in a wider angular range. By illuminating the static microspheres on chip with a scanning optical fiber, wide-angle 2D light scattering patterns of single standard microspheres with a mean diameter of 3.87 μm are obtained. The 2D patterns of 3.87 μm microspheres contain both large-angle forward scatter (FSC) and SSC light in the polar angular range from 40 to 100 degrees, approximately. Experimental 2D patterns of 3.87 μm microspheres are in good agreement with Mie theory simulated ones. The wide-angle light scattering measurements may provide a better resolution for particle analysis as compared with the SSC measurements. Two dimensional light scattering patterns of HL-60 human acute leukemia cells are obtained by using our static cytometer. Compared with SSC 2D light scattering patterns, wide-angle 2D patterns contain richer information of the HL-60 cells. The obtaining of 2D light scattering patterns in a wide angular range could help to enhance the capabilities of our label-free static cytometry for cell analysis.

  10. Deterministic Aperiodic Sickle Cell Blood Flows

    NASA Astrophysics Data System (ADS)

    Atsaves, Louis; Harris, Wesley

    2013-11-01

    In this paper sickle cell blood flow in the capillaries is modeled as a hydrodynamical system. The hydrodynamical system consists of the axisymmetric unsteady, incompressible Navier-Stokes equations and a set of constitutive equations for oxygen transport. Blood cell deformation is not considered in this paper. The hydrodynamical system is reduced to a system of non-linear partial differential equations that are then transformed into a system of three autonomous non-linear ordinary differential equations and a set of algebraic equations. We examine the hydrodynamical system to discern stable/unstable, periodic/nonperiodic, reversible/irreversible properties of the system. The properties of the solutions are driven in large part by the coefficients of the governing system of equations. These coefficients depend on the physiological properties of the sickle cell blood. The chaotic nature of the onset of crisis in sickle cell<