Controlled Delivery of Sonic Hedgehog Morphogen and Its Potential for Cardiac Repair

The morphogen Sonic hedgehog (Shh) holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair. © 2013 Johnson, Wang

Gap-Leaping Vortical Currents

A one-parameter family of exact solutions describing the bifurcation of a steady two-dimensional current with uniform vorticity near a gap in a thin barrier is found. The unsteady evolution of source-driven flows toward these steady states is studied using a version of contour dynamics, appropriately modified to take into account the presence of a barrier with a single gap. It is shown that some of the steady solutions are realizable as large-time limits of the source-driven flows, although some are not owing to persistent eddy-shedding events in the vicinity of the gap. For the special case when there is zero net flux through the gap, numerical experiments show that the through-gap flux of vortical fluid increases with the width of the gap and that this flux approaches a steady limit with time

Surf-zone vortices over stepped topography

The problem of vortical motions in the surf zone is simplified by taking the bottom topography to be piecewise flat while allowing finite-height jumps in depth between flat regions. The motion of an arbitrary number of singular vortices is cast into Hamiltonian form and the rule for relating Hamiltonians in conformally equivalent domains derived. Examples are given of a singular vortex pair colliding head-on with a step, of a vortex propagating along a curved coast to cross a step, and of a vortex being swept past a circular island straddling a step. Surf-zone vortices are then modelled as finite-area vortex patches and their motion followed by contour dynamics. It is shown that the paths of singular vortices can yield highly accurate explicit predictions of the paths of the centroids of vortex patches. Possible applications to surf-zone rip currents are noted

Vortices near barriers with multiple gaps

Two models are presented for the motion of vortices near gaps in infinitely long barriers. The first model considers a line vortex for which the exact nonlinear trajectories satisfying the governing two-dimensional Euler equations are obtained analytically. The second model considers a finite-area patch of constant vorticity and is based on conformal mapping and the numerical method of contour surgery. The two models enable a comparison of the trajectories of line vortices and vortex patches. The case of a double gap formed by an island lying between two headlands is considered in detail. It is noted that Kelvin's theorem constrains the circulation around the island to be a constant and thus forces a time-dependent volume flux between the islands and the headlands. When the gap between the island and a headland is small this flux requires arbitrarily large flow speeds through the gap. In most examples the centroid of the patch is constrained to follow closely the trajectory of a line vortex of the same circulation. Exceptions occur when the through-gap flow forces the vortex patch close to an edge of the island where it splits into two with only part of the vortex passing through the gap. In general the part squeezing through a narrow gap returns to near-circular to have a diameter significantly larger than the gap width

Vortex scattering by step topography

The scattering at a rectilinear step change in depth of a shallow-water vortex pair consisting of two patches of equal but opposite-signed vorticity is studied. Using the constants of motion, an explicit relationship is derived relating the angle of incidence to the refracted angle after crossing. A pair colliding with a step from deep water crosses the escarpment and subsequently propagates in shallow water refracted towards the normal to the escarpment. A pair colliding with a step from shallow water either crosses and propagates in deep water refracted away from the normal or, does not cross the step and is instead totally internally reflected by the escarpment. For large depth changes, numerical computations show that the coherence of the vortex pair is lost on encountering the escarpment

Endogenous human cytomegalovirus gB is efficiently presented by MHC class II molecules to CD4+ CTL

Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB--expressed by adenovirus vectors or after HCMV infection--and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells

The longwave vorticity dynamics of rotating buoyant outflows

This paper discusses the evolution of coastal currents by considering, relative to a rotating frame, the flow development when buoyant fluid is injected into a quiescent fluid bounded by a solid wall. The initial rapid response is determined by the Coriolis force–pressure gradient balance with a Kelvin wave propagating rapidly, at the long-wave speed, with the bounding wall to its right (for positive rotation). However fluid columns can stretch or squash on ejection from coastal outflows so that the ejected fluid gains positive or negative relative vorticity. Depending on its sign, the image in the solid wall of this vorticity can reinforce or oppose the zero potential-vorticity-anomaly (PVa) current set up by the Kelvin wave (KW). This paper presents a simple, fully nonlinear, dispersive, quasi-geostrophic model to discuss the form of coastal outflows as the relative strength of vortex to KW driving is varied. The model retains sufficient physics to capture both effects at finite amplitude and thus the essential nonlinearity of the flow, but is sufficiently simple so as to allow highly accurate numerical integration of the full problem and also explicit, fully nonlinear solutions for the evolution of a uniform PVa outflow in the hydraulic limit. Outflow evolutions are shown to depend strongly on the sign of the PVa of the expelled fluid, which determines whether the vortex and KW driving are reinforcing or opposing, and on the ratio of the internal Rossby radius to the vortex-source scale, |V0/D 2Π0| 1/2 , of the flow (where D measures the outflow depth, Π0 the PVa of the outflow and V0 the volume flux of the outflow), which measures the relative strengths of the two drivers. Comparison of the explicit hydraulic solutions with the numerical integrations shows that the analytical solutions predict the flow development well with differences ascribable to dispersive Rossby waves on the current boundary and changes in the source region captured by the full equations but not present in the hydraulic solutions

Potential Vorticity Dynamics of Coastal Outflows

A simple quasigeostrophic model is used to examine the outflow from a river, estuary or strait into a coastal ocean. As shown by Johnson et al. (2016), these quasigeostrophic outflows are accurately described by analytical long wave solutions. This paper first uses these solutions and contour dynamics simulations to discuss the behaviour of coastal outflows. Second, it extends the model and the long wave theory to consider the effects of ambient currents, tides, winds or a variable source flux. Third, consideration of the momentum flux at the source is used to understand the turning of the current, showing that steady solutions conserve momentum, hence resolving the momentum imbalance paradox of Pichevin and Nof (1997). Finally, a new numerical scheme to compute steady outflow boundaries is developed. The model focuses on the key dynamics driven by the source velocity and the generation of vorticity as the buoyant fluid adjusts. The simplicity of the model, and insight given by the long wave solutions, enables a full understanding of the dynamics. The outflows display a range of behaviours including indefinitely growing near-source bulges, steady boundary profiles with varying offshore width, bidirectional currents and rarefying or eddy-like leading heads, all of which can be understood with the long wave theory. Despite the simplicity of the model, the results show good agreement in comparison with observations, experiments and numerical models

Beach vortices near circular topography

Finite-area monopolar vortices which propagate around topography without change in shape are computed for circular seamounts and wells including the limiting cases of each: islands and infinitely-deep wells. The time-dependent behaviour of vortex pairs propagating toward circular topography is also examined. Trajectories of pointvortex pairs exterior to the topography are found and compared to trajectories of vortex patches computed using contour dynamics

Finite Rossby radius effects on vortex motion near a gap

This work investigates the effect of the Rossby radius of deformation on the motion of a vortex near a gap in an infinitely long barrier. A key parameter determining the behaviour of the vortex is a, the ratio of the Rossby radius of deformation to the width of the gap. Assuming quasi-geostrophic dynamics for a single-layer, reduced-gravity fluid, an integral equation is derived whose solution gives the velocity at any point in the fluid. The integral equation is solved numerically and the velocity field is integrated to give the trajectories of point vortices. Combined with the method of contour dynamics, the method can be used to compute the evolution of finite area patches of constant vorticity. The trajectories of point vortices and vortex patches are compared. The patches are initially circular and the centroids of those vortex patches that remain close to circular follow the trajectory and speed of their equivalent point vortices when appropriately normalised. The critical point vortex trajectory (the separatrix) which divides vortices that leap across the gap and those that pass through, is computed for various a. Decreasing the Rossby radius of deformation increases the tendency of vortices to pass through the gap. The effect of various background flows on both point vortex and vortex patch motion is also described