The Hemocompatibility of a Nitric Oxide Generating Polymer that Catalyzes S-nitrosothiol Decomposition in an Extracorporeal Circulation Model

Nitric oxide (NO) generating (NOGen) materials have been shown previously to create localized increases in NO concentration by the catalytic decomposition of blood S-nitrosothiols (RSNO) via copper (Cu)-containing polymer coatings and may improve extracorporeal circulation (ECC) hemocompatibility. In this work, a NOGen polymeric coating composed of a Cuo-nanoparticle (80 nm)-containing hydrophilic polyurethane (SP-60D-60) combined with the intravenous infusion of an RSNO, S- nitroso-N-acetylpenicillamine (SNAP), is evaluated in a 4 h rabbit thrombogenicity model and the anti-thrombotic mechanism is investigated. Polymer films containing 10 wt.% Cuo-nanoparticles coated on the inner walls of ECC circuits are employed concomitantly with systemic SNAP administration (0.1182 μmol/kg/min) to yield significantly reduced ECC thrombus formation compared to polymer control + systemic SNAP or 10 wt.% Cu NOGen + systemic saline after 4 h blood exposure (0.4 ± 0.2 NOGen/SNAP vs 4.9 ± 0.5 control/SNAP or 3.2 ± 0.2 pixels/cm2 NOGen/saline). Platelet count (3.9 ± 0.7 NOGen/SNAP vs 1.8 ± 0.1 control/SNAP or 3.0 ± 0.2 × 108/ml NOGen/saline) and plasma fibrinogen levels were preserved after 4 h blood exposure with the NOGen/SNAP combination vs either the control/SNAP or the NOGen/saline groups. Platelet function as measured by aggregometry (51 ± 9 NOGen/SNAP vs 49 ± 3% NOGen/saline) significantly decreased in both the NOGen/SNAP and NOGen/saline groups while platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was not decreased after 4 h on ECC to ex vivo collagen stimulation (26 ± 2 NOGen/SNAP vs 29 ± 1 MFI baseline). Western blotting showed that fibrinogen activation as assessed by Aγ dimer expression was reduced after 4 h on ECC with NOGen/SNAP (68 ± 7 vs 83 ± 3% control/SNAP). These results suggest that the NOGen polymer coating combined with SNAP infusion preserves platelets in blood exposure to ECCs by attenuating activated fibrinogen and preventing platelet aggregation. These NO-mediated platelet changes were shown to improve thromboresistance of the NOGen polymer-coated ECCs when adequate levels of RSNOs are present

Fabrication and In vivo Thrombogenecity Testing of Nitric Oxide Generating Artificial Lungs

Hollow fiber artificial lungs are increasingly being used for long-term applications. However, clot formation limits their use to 1–2 weeks. This study investigated the effect of nitric oxide generating (NOgen) hollow fibers on artificial lung thrombogenicity. Silicone hollow fibers were fabricated to incorporate 50 nm copper particles as a catalyst for NO generation from the blood. Fibers with and without (control) these particles were incorporated into artificial lungs with a 0.1 m2 surface area and inserted in circuits coated tip-to-tip with the NOgen material. Circuits (N = 5/each) were attached to rabbits in a pumpless, arterio-venous configuration and run for 4 h at an activated clotting time of 350–400 s. Three control circuits clotted completely, while none of the NOgen circuits failed. Accordingly, blood flows were significantly higher in the NOgen group (95.9 ± 11.7, p \u3c 0.01) compared to the controls (35.2 ± 19.7; mL/min), and resistance was significantly higher in the control group after 4 h (15.38 ± 9.65, p \u3c 0.001) than in NOgen (0.09 ± 0.03; mmHg/mL/min). On the other hand, platelet counts and plasma fibrinogen concentration expressed as percent of baseline in control group (63.7 ± 5.7%, 77.2 ± 5.6%; p \u3c 0.05) were greater than those in the NOgen group (60.4 ± 5.1%, 63.2 ± 3.7%). Plasma copper levels in the NOgen group were 2.8 times baseline at 4 h (132.8 ± 4.5 μg/dL) and unchanged in the controls. This study demonstrates that NO generating gas exchange fibers could be a potentially effective way to control coagulation inside artificial lungs

Remarks on 2+1 Self-dual Chern-Simons Gravity

We study 2+1 Chern-Simons gravity at the classical action level. In particular we rederive the linear combinations of the ``standard'' and ``exotic'' Einstein actions, from the (anti) self-duality of the ``internal'' Lorentzian indices. The relation to a genuine four-dimensional (anti)self-dual topological theory greatly facilitates the analysis and its relation to hyperbolic three-dimensional geometry. Finally a non-abelian vector field ``dual'' action is also obtained.Comment: 16+1 pages, LaTeX file, no figures, clarifications and comments added, typos corrected and one reference adde

Effect of recent R_p and R_n measurements on extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors

The Gari-Krumpelmann (GK) models of nucleon electromagnetic form factors, in which the rho, omega, and phi vector meson pole contributions evolve at high momentum transfer to conform to the predictions of perturbative QCD (pQCD), was recently extended to include the width of the rho meson by substituting the result of dispersion relations for the pole and the addition of rho' (1450) isovector vector meson pole. This extended model was shown to produce a good overall fit to all the available nucleon electromagnetic form factor (emff) data. Since then new polarization data shows that the electric to magnetic ratios R_p and R_n obtained are not consistent with the older G_{Ep} and G_{En} data in their range of momentum transfer. The model is further extended to include the omega' (1419) isoscalar vector meson pole. It is found that while this GKex cannot simultaneously fit the new R_p and the old G_{En} data, it can fit the new R_p and R_n well simultaneously. An excellent fit to all the remaining data is obtained when the inconsistent G_{Ep} and G_{En} is omitted. The model predictions are shown up to momentum transfer squared, Q^2, of 8 GeV^2/c^2.Comment: 14 pages, 8 figures, using RevTeX4; email correspondence to [email protected] ; minor typos corrected, figures added, conclusions extende

On commensurable hyperbolic Coxeter groups

For Coxeter groups acting non-cocompactly but with finite covolume on real hyperbolic space Hn, new methods are presented to distinguish them up to (wide) commensurability. We exploit these ideas and determine the commensurability classes of all hyperbolic Coxeter groups whose fundamental polyhedra are pyramids over a product of two simplices of positive dimensions

Measurement of the Electric Form Factor of the Neutron at Q^2 = 0.3-0.8 (GeV/c)^2

The electric form factor of the neutron, G_En, has been measured at the Mainz Microtron by recoil polarimetry in the quasielastic D(e_pol,e'n_pol)p reaction. Three data points have been extracted at squared four-momentum transfers Q^2 = 0.3, 0.6 and 0.8 (GeV/c)^2. Corrections for nuclear binding effects have been applied.Comment: 9 pages, 7 figures, 2 tables. Accepted for publication in EPJ

Motion and position shifts induced by the double-drift stimulus are unaffected by attentional load.

The double-drift stimulus produces a strong shift in apparent motion direction that generates large errors of perceived position. In this study, we tested the effect of attentional load on the perceptual estimates of motion direction and position for double-drift stimuli. In each trial, four objects appeared, one in each quadrant of a large screen, and they moved upward or downward on an angled trajectory. The target object whose direction or position was to be judged was either cued with a small arrow prior to object motion (low attentional load condition) or cued after the objects stopped moving and disappeared (high attentional load condition). In Experiment 1, these objects appeared 10° from the central fixation, and participants reported the perceived direction of the target's trajectory after the stimulus disappeared by adjusting the direction of an arrow at the center of the response screen. In Experiment 2, the four double-drift objects could appear between 6 ° and 14° from the central fixation, and participants reported the location of the target object after its disappearance by moving the position of a small circle on the response screen. The errors in direction and position judgments showed little effect of the attentional manipulation-similar errors were seen in both experiments whether or not the participant knew which double-drift object would be tested. This suggests that orienting endogenous attention (i.e., by only attending to one object in the precued trials) does not interact with the strength of the motion or position shifts for the double-drift stimulus

A Measurement of the Electric Form Factor of the Neutron through d⃗(e⃗,e′n)p\vec{d}(\vec{e},e'n)p at Q2=0.5Q^2 = 0.5 (GeV/c)2^2

We report the first measurement of the neutron electric form factor $G_E^n$ via $\vec{d}(\vec{e},e'n)p$ using a solid polarized target. $G_E^n$ was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia, $^{15}$ND$_3$. The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility (TJNAF) in quasi free kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find $G_E^n = 0.04632\pm0.00616 (stat.) \pm0.00341 (syst.)$ at $Q^2 = 0.495$ (GeV/c)$^2$.Comment: Latex2e 5 pages, 3 figure

HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope

HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen