Binding of Pentagalloyl Glucose to Aortic Wall Proteins: Insights from Peptide Mapping and Simulated Docking Studies.

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples.

Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings.

Background: Innovations in drug eluting stent designs make it increasingly important to develop models for differentiating performance through spatial definition of drug, receptor binding and cell state.

Methods: Two designs of sirolimus analog eluting stents were implanted into porcine coronary arteries for 28, 60 or 90 days (n = 9/time point), durable coating (Xience) and deployable absorbable coating (MiStent). Explanted arteries were evaluated for drug content (n = 3/time point) by LC-MS/MS and for drug and target protein (mTOR) distributions by immunofluorescence (IF, n = 6/time point).

Evaluation of the MiStent sustained sirolimus eluting biodegradable polymer coated stent for the treatment of coronary artery disease: does uniform sustained abluminal drug release result in earlier strut coverage and better safety profile?

Treatment of coronary artery disease has made strides over the last decades. Development of drug eluting stents (DES), coated with a polymer layer and an anti-proliferative drug to reduce neointimal hyperplasia, has reduced the incidence of in-stent-restenosis relative to treatment with bare metal stents. Patients treated with first generation DES more likely suffer from (very) late events which can be cause by the permanent presence of a polymer.

Technical overview on the MiStent coronary stent.

Drug-eluting stents (DES) have dramatically improved the long-term efficacy of percutaneous coronary intervention (PCI). Over the last decade there have been numerous advances in DES platforms, however, all but one currently approved DES in the United States and many of the approved DES worldwide still have 3 common features: a metal stent platform, an anti-proliferative drug, and a permanent polymer. In this context, the polymer is critical to control drug release, but the polymer serves no purpose after the drug is eluted.

Operational models of infrastructure resilience.

We propose a definition of infrastructure resilience that is tied to the operation (or function) of an infrastructure as a system of interacting components and that can be objectively evaluated using quantitative models. Specifically, for any particular system, we use quantitative models of system operation to represent the decisions of an infrastructure operator who guides the behavior of the system as a whole, even in the presence of disruptions. Modeling infrastructure operation in this way makes it possible to systematically evaluate the consequences associated with the loss of infrastructure components, and leads to a precise notion of "operational resilience" that facilitates model verification, validation, and reproducible results.