A membrane-based microfluidic device for controlling the flux of platelet agonists into flowing blood

The flux of platelet agonists into flowing blood is a critical event in thrombosis and hemostasis. However, few in vitro methods exist for examining and controlling the role of platelet agonists on clot formation and stability under hemodynamic conditions. In this paper, we describe a membrane-based method for introducing a solute into flowing blood at a defined flux. The device consisted of a track-etched polycarbonate membrane reversibly sealed between two microfluidic channels; one channel contained blood flowing at a physiologically relevant shear rate, and the other channel contained the agonist(s). An analytical model described the solute flux as a function of the membrane permeability and transmembrane pressure. The model was validated using luciferase as a model solute for transmembrane pressures of 50–400 Pa. As a proof-of-concept, the weak platelet agonist ADP was introduced into whole blood flowing at 250 s-1 at three fluxes (1.5, 2.4, and 4.4 × 10-18 mol µm-2 s-1). Platelet aggregation was monitored by fluorescence microscopy during the experiment and the morphology of aggregates was determined by post hoc confocal and electron microscopy. At the lowest flux (1.5 × 10-18 mol µm-2 s-1), we observed little to no aggregation. At the higher fluxes, we observed monolayer (2.4 × 10-18 mol µm-2 s-1) and multilayer (4.4 × 10-18 mol µm-2 s-1) aggregates of platelets and found that the platelet density within an aggregate increased with increasing ADP flux. We expect this device to be a useful tool in unraveling the role of platelet agonists on clot formation and stability

New Analysis Indicates No Thermal Inversion in the Atmosphere of HD 209458b

An important focus of exoplanet research is the determination of the atmospheric temperature structure of strongly irradiated gas giant planets, or hot Jupiters. HD 209458b is the prototypical exoplanet for atmospheric thermal inversions, but this assertion does not take into account recently obtained data or newer data reduction techniques. We re-examine this claim by investigating all publicly available Spitzer Space Telescope secondary-eclipse photometric data of HD 209458b and performing a self-consistent analysis. We employ data reduction techniques that minimize stellar centroid variations, apply sophisticated models to known Spitzer systematics, and account for time-correlated noise in the data. We derive new secondary-eclipse depths of 0.119 +/- 0.007%, 0.123 +/- 0.006%, 0.134 +/- 0.035%, and 0.215 +/- 0.008% in the 3.6, 4.5, 5.8, and 8.0 micron bandpasses, respectively. We feed these results into a Bayesian atmospheric retrieval analysis and determine that it is unnecessary to invoke a thermal inversion to explain our secondary-eclipse depths. The data are well-fitted by a temperature model that decreases monotonically between pressure levels of 1 and 0.01 bars. We conclude that there is no evidence for a thermal inversion in the atmosphere of HD 209458b.Comment: 8 pages, 5 figures; accepted for publication in Ap

Neutrophil String Formation: Hydrodynamic Thresholding and Cellular Deformation during Cell Collisions

Neutrophils unexpectedly display flow-enhanced adhesion (hydrodynamic thresholding) to L-selectin in rolling or aggregation assays. We report that the primary collision efficiency (ε) of flowing neutrophils with preadhered neutrophils on intercellular adhesion molecule-1 (ICAM-1) or fibrinogen also displayed a maximum of ε ~ 0.4–0.45 at a wall shear rate of 100 s-1, an example of thresholding. Primary collision lifetime with no detectable bonding decreased from 130 to 10 ms as wall shear rate increased from 30 to 300 s-1, whereas collision lifetimes with bonding decreased from 300 to 100 ms over this shear range using preadhered neutrophils on ICAM-1, with similar results for fibrinogen. Antibodies against L-selectin, but not against CD11a, CD11b, or CD18, reduced ε at 100 s-1 by \u3e85%. High resolution imaging detected large scale deformation of the flowing neutrophil during the collision at 100 s-1 with the apparent contact area increasing up to ~40 μm2. We observed the formation of long linear string assemblies of neutrophils downstream of neutrophils preadhered to ICAM-1, but not fibrinogen, with a maximum in string formation at 100 s-1. Secondary capture events to the ICAM-1 or fibrinogen coated surfaces after primary collisions were infrequent and short lived, typically lasting from 500 to 3500 ms. Between 5 and 20% of neutrophil interactions with ICAM-1 substrate converted to firm arrest (\u3e3500 ms) and greatly exceeded that observed for fibrinogen, thus defining the root cause of poor string formation on fibrinogen at all shear rates. Additionally, neutrophils mobilized calcium after incorporation into strings. Static adhesion also caused calcium mobilization, as did the subsequent onset of flow. To our knowledge, this is the first report of 1), hydrodynamic thresholding in neutrophil string formation; 2), string formation on ICAM-1 but not on fibrinogen; 3), large cellular deformation due to collisions at a venous shear rate; and 4), mechanosensing through neutrophil β2-integrin/adhesion. The increased contact area during deformation was likely responsible for the hydrodynamic threshold observed in the primary collision efficiency since no increase in primary collision lifetime was detected as shear forces were increased (for either surface coating)

Radical Initiated Polymerization In a Bifunctional Mixture Via Computer Simulation

Computer simulations are performed to study the polymerization behavior in a mixture of bifunctional groups such as olefins (A) and acrylates (B) in an effective solvent (a coarse description for vegetable oil derived macromonomers (VOMMs) in solution) on a cubic lattice. A set of interactions between these units and solvent (S) constituents and their relative concentrations (p(A), p(B), and p(S)) are considered. Samples are equilibrated with Metropolis algorithm to model the perceived behavior of VOMMs. The covalent bonding between monomeric units is then implemented via reaction pathways initiated by stochastic motion of free radicals (a very small fraction). The rate of reaction shows decay patterns with the time steps (t) with power laws (i.e., R(ab)alphat(-r), r congruent to 0.4-0.8), exponential decays (i.e., R(ab)alphae(-0.001t)), and their combination. Growth of A-B bonding is studied as a function of polymer concentration p=p(A)+p(B) for four different model systems appropriate for VOMMs. The data from the free radical initiated simulations are compared to the original simulations with homopolymerization. While most of the data are consistent with experimental observations, the variations are found to be model dependent. (C) 2004 American Institute of Physics

Cooperative Unmanned Aerial Surveillance Control System Architecture

Intelligence, surveillance and reconnaissance (ISR) is a high-demand Department of Defense mission performed by unmanned aircraft systems (UASs) at the tactical and theater levels. Coordinating UASs through cooperative control offers the advantages of persistence, distributed and adaptable sensor coverage, and reduced revisit time on points of interest. The purpose of this thesis is to apply systems engineering principles to the problem of developing a flexible, common control system for cooperative UAS surveillance at the tactical level. The AFIT team developed a concept of operations (CONOPS) encompassing various users and surveillance tasks. The team then used the scenarios in the CONOPS to build a conceptual architecture. Concurrently, the team constructed a developmental test system that closely resembled the architecture and successfully conducted flight tests of multiple aircraft. The team then used this architecture and the prototype system to identify significant technical risks and future research areas to be explored prior to the development of an operational system

Edge Shear Flows and Particle Transport near the Density Limit in the HL-2A Tokamak

Edge shear flow and its effect on regulating turbulent transport have long been suspected to play an important role in plasmas operating near the Greenwald density limit $n_G$. In this study, equilibrium profiles as well as the turbulent particle flux and Reynolds stress across the separatrix in the HL-2A tokamak are examined as $n_G$ is approached in ohmic L-mode discharges. As the normalized line-averaged density $\bar{n}_e/n_G$ is raised, the shearing rate of the mean poloidal flow $\omega_{\rm sh}$ drops, and the turbulent drive for the low-frequency zonal flow (the Reynolds power $\mathcal{P}_{Re}$) collapses. Correspondingly, the turbulent particle transport increases drastically with increasing collision rates. The geodesic acoustic modes (GAMs) gain more energy from the ambient turbulence at higher densities, but have smaller shearing rate than low-frequency zonal flows. The increased density also introduces decreased adiabaticity which not only enhances the particle transport but is also related to a reduction in the eddy-tilting and the Reynolds power. Both effects may lead to the cooling of edge plasmas and therefore the onset of MHD instabilities that limit the plasma density

Harry L. Goldsmith, Ph.D.

In honor of Dr. Harry L. Goldsmith\u27s 75th birthday, we present a collection of articles from his collaborators and colleagues to commemorate Harry\u27s outstanding contributions to the field of Biorheology. On any particular day, bioengineers around the world may find themselves fortunate enough to peer through a microscope to observe molecular or cellular level phenomena manifested before their eyes. Such observations of single molecule mechanics or blood flows or cellular deformation remind us of the power of clever experimental design and rigorous theoretical constructs as well as the complex beauty of dynamical systems in nature. In this spirit, the investigations reported in this issue of the Annals entitled Cellular Biorheology and Biomechanics have followed down many of the research paths pioneered by Dr. Harry Goldsmith

The opposites task: Using general rules to test cognitive flexibility in preschoolers

A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.

Circuit Theory

Contains research objectives and reports on two research projects.U.S. Air Force under Air Force Contract AF19(604)-5200Lincoln Laboratory, Purchase Order DDL-B22