PCSK9 Induces Tissue Factor Expression by Activation of TLR4/NFkB Signaling

Proprotein convertase subtilisin kexin 9 (PCSK9) increases LDL cholesterol (C) concentration by accelerating the hepatic degradation of the LDL receptor (R) thus promoting atherogenesis. The molecule, however, also exerts proinflammatory effects independent of circulating LDL-C by enhancing local cytokine production and activation of NFkB, a process that might involve Toll-like receptor 4 (TLR4), a crucial component of the innate immunity system. Tissue factor (TF), a glycoprotein which plays an essential role in coagulation and inflammation, is rapidly induced by circulating monocytes stimulated by proinflammatory agents through NFkB-dependent mechanisms. The aims of our study were (1) to assess whether PCSK9 may induce monocytic TF expression and (2) to evaluate whether the TLR4/NFkB signaling pathway may contribute to that effect. Experiments were carried out in peripheral blood mononuclear cells (PBMCs), THP-1 cells, and HEK293 cells transfected with plasmids encoding the human TLR4 complex. PCSK9 increased procoagulant activity (PCA), mRNA and TF protein expression in both PBMCs and THP-1 cultures. Pre-treatment with inhibitors of TLR4/NFkB signaling such as LPS-RS, CLI-095, and BAY 11-7082, downregulated PCSK9-induced TF expression. A similar effect was obtained by incubating cell cultures with anti-PCSK9 human monoclonal antibody. In TLR4-HEK293 cells, PCSK9 activated the TLR4/NFkB signaling pathway to an extent comparable to LPS, the specific agonist of TLR4s and quantitative confocal microscopy documented the colocalization of PCSK9 and TLR4s. In conclusion, PCSK9 induces TF expression through activation of TLR4/NFkB signaling.     

Possibility of improving the quality characteristics of olive‐pomace oil and enhancing its differentiation from refined olive‐pomace oil

An investigation was carried out to evaluate the oxidative and hydrolytic degradation of 37 olive‐pomace oils marketed in southern Italy and to compare the results with those obtained from 10 deodorised olive‐pomace oils representative of large stocks of oil obtained after the final step of refining. One aim of the research was to ascertain the quality characteristics of commercial olive‐pomace oils; another was to verify whether the legally prescribed addition of virgin olive oil to refined pomace oil, so that the final product may be classified commercially as olive‐pomace oil, was actually sufficient to justify upgrading. The analytical methods used were silica gel column chromatography and high‐performance size exclusion chromatography. The data obtained showed that the final retail olive‐pomace oils had a lower degree of oxidative degradation than the refined oils, as indicated by the lower values obtained when summing the proportions of triglyceride oligopolymers and oxidised triglycerides. Conversely, hydrolytic degradation, which was evaluated by determining diglycerides, proved to be the same in the two categories of oil. The proportions of virgin olive oil added are small, as indicated by the statistically indistinguishable values of triglyceride oligopolymers and free fatty acids obtained. The possibility of setting a limit to the amount of triglyceride oligopolymers present in the commercial category of olive‐pomace oil has been considered. This limit would ensure standardisation of the level of oxidation and, consequently, of the quality of marketed oils and would enhance differentiation between olive‐pomace oil and refined olive‐pomace oil. © 2000 Society of Chemical Industry     

A review of metrics on permutations for search landscape analysis

Search landscape analysis has become a central tool for analysing the dependency of the performance of stochastic local search algorithms on structural aspects of the spaces being searched. Central to search landscape analysis is the notion of distance between candidate solutions. This distance depends on some underlying basic operator and it is defined as the minimum number of operations that need to be applied to one candidate solution for transforming it into another one. For operations on candidate solutions that are represented by permutations, in almost all researches on search landscape analysis surrogate distance measures are applied, although efficient algorithms exist in many cases for computing the exact distances. This discrepancy is probably due to the fact that these efficient algorithms are not very widely known. In this article, we review algorithms for computing distances on permutations for the most widely applied operators and present simulation results that compare the exact distances to commonly used approximations.     

An Interconnect Strategy for a Heterogeneous, Reconfigurable SoC

Editor's note:The diversification of the SoC market has increased the need for domain-specific programmable platforms that can be tailored to postfabrication products. This article presents a design case study on the interconnect for such a programmable platform, as part of the Morpheus project.—Li-Shiuan Peh, Princeton University     

Inverse scattering from phaseless measurements of the total field on a closed curve

A new approach for quantitative electromagnetic imaging of scatterers located in free space from phaseless data is proposed and discussed. The procedure splits the problem into two steps. In the first one, we solve a phase-retrieval problem for the total field, thus estimating the amplitude and phase of the scattered field. Careful analysis of properties and possible representations of both scattered and incident fields allow us to introduce a criterion for an optimal choice of the measurement setup and a successful retrieval. Then the complex permittivity profile is reconstructed in the second step by use of the estimated scattered field. Numerical examples are provided to check the whole chain in the presence of noise-corrupted data.     

Synthesis and characterization of lanthanum bonded agar-carbomer hydrogel:a promising tool for biomedical research

Agar-Carbomer(branched poly(acrylic acid)) hydrogel,an injectable bio-resorbable scaffold with a controlled nanostructure specifically designed for neural cell housing,was developed together with a new protocol for building three dimensional biohybrid cell/hydrogel systems.In order to overcome classic structural analysis inconveniences due to the high water amount,which affects instruments results and reliability,agar-Carbomer hydrogels were synthesized by microwave-assisted block copolymerization together with La3+ salts.Propylene glycol,glycerol and buffered saline solution were used as cross-linking agents and solvent,respectively.Biomaterial properties were not affected by the presence of lanthanum,and were checked via swelling and rheological analysis.Moreover,the presence of La3+ within the polymeric network was characterized by thermogravimetric analysis,environmental scanning electron microscopy and Fourier transformed infrared spectroscopy.The results showed that the rare earth presented uniform distribution in the hydrogel network due to the formation of chemical bonds after polymerization without being modified its luminescence emission spectrum that allowed hydrogel detection.These results made the obtained host-guest system a useful tool for analytical research studies concerning regenerative medical applications that could also be potentially taken up with in vivo experiments.