Platelet-Derived PCSK9 Is Associated with LDL Metabolism and Modulates Atherothrombotic Mechanisms in Coronary Artery Disease

Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in the regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors of this article sought to characterize platelets as a major source of PCSK9 and PCSK9’s role in atherothrombosis. In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity, and platelet-derived PCSK9 release were analyzed. The role of platelet PCSK9 on platelet and monocyte function was investigated in vitro. Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration, and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation. The authors identified platelets as a source of PCSK9 in CAD, which may have an impact on LDL metabolism. Furthermore, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation, which may contribute to the reported beneficial clinical effects.     

Nano-engineered microcapsules of tannic acid and chitosan for protein encapsulation

Tannic acid (TA), a high molecular weight polyphenol of natural origin, was assembled in alternation with chitosan (CH) using a layer-by-layer technique. The deposition of tannic acid and chitosan layers on flat supports was monitored by quartz crystal microbalance, UV-vis spectroscopy, and electrophoretic mobility measurements on microparticles. Hollow (TA/CH)4 capsules were built and their permeability as a function of pH and molecular weight of a penetrating compound was investigated. The pH-permeability threshold for TA/CH capsules is shifted to lower pH for 2 pH units, as compared with commonly used polyallylamine/polystyrene sulfonate capsules. A more pronounced dependence of the TA/CH capsules' permeability on molecular weight of encapsulated substances allows better control over their release properties. Bovine serum albumin was loaded into (TA/CH)4 capsules using a pH-driven method and released by decreasing pH. Biocompatible tannic acid/chitosan films and capsules have advantages toward capsules made of synthetic polyelectrolytes for drug encapsulation and as delivery and depot systems. Incorporating a layer of tannic acid with proved antioxidant and antimicrobial properties into capsule walls, provides defense for encapsulated materials.     

A numerical green's function approach for boundary elements applied to fracture mechanics

The most accurate boundary element formulation to deal with fracture mechanics problems is obtained with the implementation of the associated Green's function acting as the fundamental solution. Consequently, the range of applications of this formulation is dependent on the availability of the appropriate Green's function for actual crack geometry. Analytical Green's functions have been presented for a few single crack configurations in 2-D applications and require complex variable theory. This work extends the applicability of the formulation through the introduction of efficient numerical means of computing the Green's function components for single or multiple crack problems, of general geometry, including the implementation to 3-D problems as a future development. Also, the approach uses real variables only and well-established boundary integral equations.     

Layer-by-layer nanocoating of lignocellulose fibers for enhanced paper properties

The systematic modification of the surface charge of lignocellulose fibers was performed with a polyelectrolyte layer-by-layer (LbL) nanocoating process to produce negatively and positively charged fibers. The fibers were coated with 20-50 nm thick polymer surface layers which subsequently increased interaction between the fibers during paper formation. The modified fibers were added to standard fibers at varying proportions to produce paper with corresponding variation in properties such as strength and electrical conductivity. Paper strength was doubled by manipulating the surface charge and coating thickness of the LbL-treated pulp fibers. It is demonstrated that the LbL coating process increased the fiber interactions and that these interactions enhanced the paper properties. This process, when applied to a simulated sample of recycle grade of fibers, produce paper with an increase in tear strength as compared with untreated fiber paper. Nanocoating fibers with polythiophene/polyallylamine multilayers produced marginally conductive pulp and paper. Paper electrical conductivity was proportional to the number of the bilayers deposited.     

Contactless Stimulation and Control of Biomimetic Nanotubes by Calcium Ion Gradients

Membrane tubular structures are important communication pathways between cells and cellular compartments. Studying these structures in their native environment is challenging, due to the complexity of membranes and varying chemical conditions within and outside of the cells. This work demonstrates that a calcium ion gradient, applied to a synthetic lipid nanotube, triggers lipid flow directed toward the application site, resulting in the formation of a bulge aggregate. This bulge can be translated in a contactless manner by moving a calcium ion source along the lipid nanotube. Furthermore, entrapment of polystyrene nanobeads within the bulge does not tamper the bulge movement and allows transporting of the nanoparticle cargo along the lipid nanotube. In addition to the synthetic lipid nanotubes, the response of cell plasma membrane tethers to local calcium ion stimulation is investigated. The directed membrane transport in these tethers is observed, but with slower kinetics in comparison to the synthetic lipid nanotubes. The findings of this work demonstrate a novel and contactless mode of transport in lipid nanotubes, guided by local exposure to calcium ions. The observed lipid nanotube behavior can advance the current understanding of the cell membrane tubular structures, which are constantly reshaped during dynamic cellular processes.     

On the modularization and reuse of exception handling with aspects

This paper presents an in‐depth study of the adequacy of the AspectJ language for modularizing and reusing exception‐handling code. The study consisted of refactoring existing applications so that the code responsible for implementing error‐handling strategies was moved to newly created exception handler aspects. We have performed quantitative assessments of five systems—four object‐oriented and one aspect‐oriented—based on four key quality attributes, namely separation of concerns, coupling, cohesion, and conciseness. Our investigation also included a multi‐perspective analysis of the refactored systems, including (i) the extent to which error‐handling aspects can be reused, (ii) the beneficial and harmful aspectization scenarios for exception handling, and (iii) the scalability of AOP to support the modularization of exception handling in the presence of other aspects. Copyright © 2009 John Wiley & Sons, Ltd.