Operads for complex system design specification, analysis and synthesis.

As the complexity and heterogeneity of a system grows, the challenge of specifying, documenting and synthesizing correct, machine-readable designs increases dramatically. Separation of the system into manageable parts is needed to support analysis at various levels of granularity so that the system is maintainable and adaptable over its life cycle. In this paper, we argue that operads provide an effective knowledge representation to address these challenges.

Arterial pharmacokinetics of red wine polyphenols: implications for novel endovascular therapies targeting restenosis.

Drug-eluting stents (DESs) are endovascular devices that provide controlled release of compounds to interfere with restenosis, an adverse outcome of angioplasty characterized by thickening of the arterial wall. Accumulating evidence suggests that arterial pharmacokinetics determine the biological effect and potential toxicity of stent-based therapeutics. The aim of this study was to examine how drug polarity, drug load, and protein binding influence release from a polymer film and distribution within arterial tissue.

Novel nanocomposite stent coating releasing resveratrol and quercetin reduces neointimal hyperplasia and promotes re-endothelialization.

Late-term thrombosis associated with drug-eluting stents may be due to the non-selective actions of antimitogenic drugs on endothelial cells, leading to delayed vascular healing after stenting angioplasty. Currently, there is a need for stent-based therapies that can both attenuate neointimal hyperplasia and promote re-endothelialization. The aim of this study was to compare the effects of a resveratrol (R)- and quercetin (Q)-eluting stent with that of a bare metal stent (BMS) on neointimal hyperplasia and re-endothelialization in a rat model of arterial angioplasty and stenting.

A dietary approach to increase in-stent stenosis and face validity of a rat model for arterial angioplasty and stenting.

Objective: To expedite the investigation of new devices for inhibiting restenosis, we aimed to develop a modified model of arterial angioplasty and stenting in rats that showed greater face validity than the traditional rat model.

Methods: Carotid arteries from Sprague-Dawley rats fed a normal or an atherogenic diet containing a low dose of cholate underwent balloon pre-dilation followed by placement of a bare metal stent. Vessel patency was followed for 28d using ultrasound.

Synergistic effect of resveratrol and quercetin released from drug-eluting polymer coatings for endovascular devices.

This study describes the development and evaluation of novel polymer films that provide controlled release of two vascular-protective polyphenols for endovascular devices. Resveratrol (RESV) and quercetin (QUER) have antimigratory and antiproliferative actions on vascular smooth muscle cells (VSMCs), inhibit both platelet and inflammatory cell activation, and promote endothelial cell function. Our aim is to develop and characterize coatings that release these drugs within a therapeutic range.

Effect of the coating morphology on the drug release from engineered drug-polymer nanocomposites.

The ElectroNanospray process (Nanocopoeia, Inc) transforms drugs and polymers into many nanoscale material states including powders, liquids, encapsulated particles, and coatings. This enabling technology platform allows application of polymers and drugs to the surface of medical devices such as coronary stents in a single-stage process. Modification of ElectroNanospray process parameters resulted in surface coatings with rich morphologies ranging in appearance from smooth and heterogeneous to highly porous and rough (open matrix).

Multimodal dynamic imaging of therapeutic biomedical coatings in aqueous medium.

Drug release from therapeutic biomedical films such as drug-polymer composite coatings on drug eluting stents is a highly complex and poorly understood process. The dynamics of drug release and the evolution of surface morphology during release have direct impact on the performance of the device. This information is not easily accessible, and there have been few systematic studies to investigate drug release from biomedical coatings in real time.

Prevention of cold ischemia/rewarming-induced ERK 1/2, p38 kinase and HO-1 activation by trophic factor supplementation of UW solution.

We have previously shown that trophic factor supplementation (TFS) of University of Wisconsin (UW) solution reduced early apoptotic changes in vascular endothelial cells. Here, we examine the effect of TFS on cell signaling pathways related to cell growth, differentiation, and apoptosis after cold ischemic storage. In this study, the effect of TFS on the phosphorylation of signaling molecules ERK (extracellular regulated-signaling kinase) 1/2 and p38 MAPK (mitogen activated protein kinases) and of HO-1 (hemeoxygenase-1), relative to changes seen in unmodified UW solution, were determined by Western blot in cells stored under cold ischemic conditions.

The effect of trophic factor supplementation on cold ischemia-induced early apoptotic changes.

We have previously shown that trophic factor supplementation (TFS) of University of Wisconsin (UW) solution enhanced kidney viability after cold storage. Here, we use an in vitro model to study the effect of TFS on early apoptotic changes after cold ischemic storage. Mitochondrial membrane potential was determined by fluorescence intensity in primary canine kidney tubule cells, Madin-Darby canine kidney cells, and human umbilical vein endothelial cells.

Adolescent use and misuse of marijuana.

Substance use by adolescents and young adults continues to be a serious problem. Marijuana remains the most commonly used illicit substance with close to 50% of high school seniors admitting use at some time. Each year 2.

The effect of environmental factors on the response of human corneal epithelial cells to nanoscale substrate topography.

We have previously shown that human corneal epithelial cells sense and react to nanoscale substrate topographic stimuli [Teixeira AI, Abrams GA, Bertics PJ, Murphy CJ, Nealey PF. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J Cell Sci 2003;116(10):1881-92; Karuri NW, Liliensiek S, Teixeira AI, Abrams G, Campbell S, Nealey PF, et al.

Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor.

Understanding axonal formation and contact guidance are of critical importance for the design of materials that interface with neuronal tissue. Contact guidance of neurites by topographic features is well known, but the role that topography plays in the modulation of neuritogenesis has not been addressed. To test this, we cultured PC12 cells with a range of nerve growth factor (NGF) concentrations on surfaces with ridge widths ranging from 70 to 1900 nm.

Suppression of cold ischemic injury in stored kidneys by the antimicrobial peptide bactenecin.

Background: Cold ischemic injury plays an important role in short- and long-term function of kidneys after transplant. Antimicrobial peptides have not previously been studied for their impact on cold ischemia in transplanted kidneys.

Methods: Bactenecin (L- and D-forms) was added to University of Wisconsin (UW) preservation solution for 3-day cold storage of dog kidneys.

Temporal regulation of VEID-7-amino-4-trifluoromethylcoumarin cleavage activity and caspase-6 correlates with organelle loss during lens development.

Lens fiber cell differentiation involves extensive reconstruction of the cell's architecture, including the degradation and elimination of all membrane-bound organelles via a process that has been likened to apoptosis. Using caspase reporter assays under conditions in which nonspecific cleavage of the reporter peptides by the proteasome has been inhibited, we investigated whether any specific caspase activities are temporally correlated with this process of organelle loss. Extracts from neonatal mouse lenses contained strong VEID-7-amino-4-trifluoromethylcoumarin (AFC) and minor IETD-AFC and LEVD-AFC cleavage activities, but no DEVD-AFC cleavage activity.