Open-ended evolution to discover analogue circuits for beyond conventional applications

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10710-012-9163-8. Copyright @ Springer 2012.Analogue circuits synthesised by means of open-ended evolutionary algorithms often have unconventional designs. However, these circuits are typically highly compact, and the general nature of the evolutionary search methodology allows such designs to be used in many applications. Previous work on the evolutionary design of analogue circuits has focused on circuits that lie well within analogue application domain. In contrast, our paper considers the evolution of analogue circuits that are usually synthesised in digital logic. We have developed four computational circuits, two voltage distributor circuits and a time interval metre circuit. The approach, despite its simplicity, succeeds over the design tasks owing to the employment of substructure reuse and incremental evolution. Our findings expand the range of applications that are considered suitable for evolutionary electronics

Homeodomain Interacting Protein Kinase 2 Activation Compromises Endothelial Cell Response to Laminar Flow: Protective Role of p21waf1,cip1,sdi1

BACKGROUND: In the cardiovascular system, laminar shear stress (SS) is one of the most important source of endothelial protecting signals. Physical and chemical agents, however, including ionising radiations and anticancer drugs, may injure endothelial cells determining an increase in oxidative stress and genotoxic damage. Whether the SS protective function remains intact in the presence of strong oxidants or DNA damage is currently unclear. METHODS AND RESULTS: To investigate this aspect a series of experiments were performed in which HUVEC were exposed to sub-lethal doses of the radio-mimetic compound Bleomycin (Bleo; 10 microg/ml) which generated free radicals (ROS) without significantly compromising cell survival. Remarkably, the application of a SS of 12 dyne/cm(2) did not protect endothelial cells but markedly accelerated apoptosis compared to controls kept in static culture and in the presence of Bleo. Experiments with the inducible nitric oxide synthase (iNOS) inhibitor GW274150 significantly reduced the SS-dependent apoptosis indicating that the production of NO was relevant for this effect. At molecular level, the ataxia-telangectasia-mutated (ATM) kinase, the homeodomain-interacting protein kinase-2 (HIPK2) and p53 were found activated along a pro-apoptotic signalling pathway while p21(waf1,cip1,sdi1) was prevented from its protective action. RNA interference experiments revealed that HIPK2 and p53 were both important for this process, however, only the forced expression p21(waf1,cip1,sdi1) fully restored the SS-dependent pro-survival function. CONCLUSIONS: This study provides the first evidence that, in the presence of genotoxic damage, laminar flow contributes to endothelial toxicity and death and identifies molecular targets potentially relevant in endothelial dysfunction and cardiovascular disease pathogenesis

On the equivalence between hierarchical segmentations and ultrametric watersheds

We study hierarchical segmentation in the framework of edge-weighted graphs. We define ultrametric watersheds as topological watersheds null on the minima. We prove that there exists a bijection between the set of ultrametric watersheds and the set of hierarchical segmentations. We end this paper by showing how to use the proposed framework in practice in the example of constrained connectivity; in particular it allows to compute such a hierarchy following a classical watershed-based morphological scheme, which provides an efficient algorithm to compute the whole hierarchy.Comment: 19 pages, double-colum

On morphological hierarchical representations for image processing and spatial data clustering

Hierarchical data representations in the context of classi cation and data clustering were put forward during the fties. Recently, hierarchical image representations have gained renewed interest for segmentation purposes. In this paper, we briefly survey fundamental results on hierarchical clustering and then detail recent paradigms developed for the hierarchical representation of images in the framework of mathematical morphology: constrained connectivity and ultrametric watersheds. Constrained connectivity can be viewed as a way to constrain an initial hierarchy in such a way that a set of desired constraints are satis ed. The framework of ultrametric watersheds provides a generic scheme for computing any hierarchical connected clustering, in particular when such a hierarchy is constrained. The suitability of this framework for solving practical problems is illustrated with applications in remote sensing

Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652

A Computational Algebraic Topology Model for the Deformation of Curves

A new method for the deformation of curves is presented. It is based upon a decomposition of the linear elasticity problem into basic physical laws

P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation by nε-lysine acetylation of contractile proteins

OBJECTIVE-: To address the role of epigenetic enzymes in the process of arterial vasorelaxation and nitrate tolerance, in vitro and in vivo experiments were performed in the presence or absence of glyceryl trinitrate (GTN) or histone deacetylases/histone acetylases modulators. METHODS AND RESULTS-: In vitro single GTN administration rapidly increased cGMP synthesis and protein N-lysine acetylation in rat smooth muscle cells, including myosin light chain and smooth muscle actin. This phenomenon determined a decrease in myosin light chain phosphorylation and actomyosin formation. These effects were abolished by prolonged exposure to GTN and rescued by treatment with trichostatin A. In vivo, adult male rats were treated for 72 hours with subcutaneous injections of GTN alone or in combination with the histone deacetylases inhibitors trichostatin A, suberoylanilide hydroxamic acid, MS-27-275, or valproic acid. Ex vivo experiments performed on aortic rings showed that the effect of tolerance was reversed by all proacetylation drugs, including the p300/CREB binding protein-associated factor activator pentadecylidenemalonate 1b (SPV106). Any response to GTN was abolished by anacardic acid, a potent histone acetylases inhibitor. CONCLUSION-: This study establishes the following points: (1) GTN treatment increases histone acetylases activity; (2) GTN-activated p300/CREB binding protein-associated factor increases protein N-lysine acetylation; (3) N-lysine acetylation of contractile proteins influences GTN-dependent vascular response. Hence, combination of epigenetic drugs and nitroglycerin may be envisaged as a novel treatment strategy for coronary artery disease symptoms and other cardiovascular accidents of ischemic origin. © 2012 American Heart Association, Inc