Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow.

Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood-vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels.

Exploring Model Energy and Geometry Surfaces Using Sum of Squares Decompositions.

The difficulty in exploring potential energy surfaces, which are nonconvex, stems from the presence of many local minima, typically separated by high barriers and often disconnected in configurational space. We obtain the global minimum on model potential energy surfaces without sampling any minima a priori. Instead, a different problem is derived, which is convex and hence easy to solve, but which is guaranteed to either have the same solution or to be a lower bound to the true solution. A systematic way for improving the latter solutions is also given. Because many nonconvex problems are projections of higher dimensional convex problems, Parrilo has recently shown that by obtaining a sum of squares decomposition of the original problem, which can be subsequently transformed to a semidefinite program, a large class of nonconvex problems can be solved efficiently. The semidefinite duality formulation also provides a proof that the global minimum of the energy surface has either been found exactly or has been bounded from below. It additionally provides physical insight into the problem through a geometric interpretation. The sum of squares polynomial representation of the potential energy surface may further reveal information about the nature of the potential energy surface. We demonstrate the applicability of this approach to low-dimensional potential energy landscapes and discuss its merits and shortcomings. We further show how to apply it to geometric problems by obtaining the exact distance of closest approach of anisotropic particles. Efficient molecular dynamics simulations of mixtures of ellipsoids are illustrated.

Differential hydrophobicity drives self-assembly in Huntington's disease.

Identifying the driving forces and the mechanism of association of huntingtin-exon1, a close marker for the progress of Huntington's disease, is an important prerequisite to finding potential drug targets and, ultimately, a cure. We introduce here a modeling framework based on a key analogy of the physicochemical properties of the exon1 fragment to block copolymers. We use a systematic mesoscale methodology, based on dissipative particle dynamics, which is capable of overcoming kinetic barriers, thus capturing the dynamics of significantly larger systems over longer times than considered before. Our results reveal that the relative hydrophobicity of the poly(glutamine) block as compared with the rest of the (proline-based) exon1 fragment, ignored to date, constitutes a major factor in the initiation of the self-assembly process. We find that the assembly is governed by both the concentration of exon1 and the length of the poly(glutamine) stretch, with a low-length threshold for association, even at the lowest volume fractions we considered. Moreover, this self-association occurs irrespective of whether the glutamine stretch is in random-coil or hairpin configuration, leading to spherical or cylindrical assemblies, respectively. We discuss the implications of these results for reinterpretation of existing research within this context, including that the routes toward aggregation of exon1 may be distinct from those of the widely studied homopolymeric poly(glutamine) peptides.