Parallelisation and application of AD3 as a method for solving large scale combinatorial auctions

Auctions, and combinatorial auctions (CAs), have been successfully employed to solve coordination problems in a wide range of application domains. However, the scale of CAs that can be optimally solved is small because of the complexity of the winner determination problem (WDP), namely of finding the bids that maximise the auctioneer’s revenue. A way of approximating the solution of a WDP is to solve its linear programming relaxation. The recently proposed Alternate Direction Dual Decomposition algorithm (AD3) has been shown to ef- ficiently solve large-scale LP relaxations. Hence, in this paper we show how to encode the WDP so that it can be approximated by means of AD3. Moreover, we present PAR-AD3, the first parallel implementation of AD3. PAR-AD3 shows to be up to 12.4 times faster than CPLEX in a single-thread execution, and up to 23 times faster than parallel CPLEX in an 8-core architecture. Therefore PAR- AD3 becomes the algorithm of choice to solve large-scale WDP LP relaxations for hard instances. Furthermore, PAR-AD3 has potential when considering large- scale coordination problems that must be solved as optimisation problems.Research supported by MICINN projects TIN2011-28689-C02-01, TIN2013-45732-C4-4-P and TIN2012-38876-C02-01Peer reviewe

Zippin’ up my boots, goin’ back to my roots: Radical left parties in Southern Europe

Radical left parties actively encourage the participation of their members in internal decision-making and insist on promoting organised links to trade unions and social movements. As a party family, they deviate from what is considered to be the trend in which Western political parties have turned their backs on their social roots. Drawing on the experience of South European radical left parties from the fall of the Berlin Wall until the recent financial crisis, we argue that ideology, electoral incentives, party competition and external events explain the radical left's pronounced emphasis on linkage, while organisational trajectory explains variation within the party family in terms of the linkage strategies pursued

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

N-Cadherin in Neuroblastoma Disease: Expression and Clinical Significance

One of the first and most important steps in the metastatic cascade is the loss of cell-cell and cell-matrix interactions. N-cadherin, a crucial mediator of homotypic and heterotypic cell-cell interactions, might play a central role in the metastasis of neuroblastoma (NB), a solid tumor of neuroectodermal origin. Using Reverse Transcription Quantitative PCR (RT-qPCR), Western blot, immunocytochemistry and Tissue MicroArrays (TMA) we demonstrate the expression of N-cadherin in neuroblastoma tumors and cell lines. All neuroblastic tumors (n = 356) and cell lines (n = 10) expressed various levels of the adhesion protein. The N-cadherin mRNA expression was significantly lower in tumor samples from patients suffering metastatic disease. Treatment of NB cell lines with the N-cadherin blocking peptide ADH-1 (Exherin, Adherex Technologies Inc.), strongly inhibited tumor cell proliferation in vitro by inducing apoptosis. Our results suggest that N-cadherin signaling may play a role in neuroblastoma disease, marking involvement of metastasis and determining neuroblastoma cell viability

A Herbivorous Mite Down-Regulates Plant Defence and Produces Web to Exclude Competitors

Herbivores may interact with each other through resource competition, but also through their impact on plant defence. We recently found that the spider mite Tetranychus evansi down-regulates plant defences in tomato plants, resulting in higher rates of oviposition and population growth on previously attacked than on unattacked leaves. The danger of such down-regulation is that attacked plants could become a more profitable resource for heterospecific competitors, such as the two-spotted spider mite Tetranychus urticae. Indeed, T. urticae had an almost 2-fold higher rate of oviposition on leaf discs on which T. evansi had fed previously. In contrast, induction of direct plant defences by T. urticae resulted in decreased oviposition by T. evansi. Hence, both herbivores affect each other through induced plant responses. However, when populations of T. evansi and T. urticae competed on the same plants, populations of the latter invariably went extinct, whereas T. evansi was not significantly affected by the presence of its competitor. This suggests that T. evansi can somehow prevent its competitor from benefiting from the down-regulated plant defence, perhaps by covering it with a profuse web. Indeed, we found that T. urticae had difficulties reaching the leaf surface to feed when the leaf was covered with web produced by T. evansi. Furthermore, T. evansi produced more web when exposed to damage or other cues associated with T. urticae. We suggest that the silken web produced by T. evansi serves to prevent competitors from profiting from down-regulated plant defences

A Quorum Sensing Regulated Small Volatile Molecule Reduces Acute Virulence and Promotes Chronic Infection Phenotypes

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections

Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 Activation

The main purpose of the present study is to envisage the molecular mechanism of inhibitory action ofdehydrocostuslactone (DCE) andcostunolide (CS), two naturally occurring sesquiterpene lactones, towards the activation of signal transducer and activator of transcription 3 (STAT3). We report that, in human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of 10 µM with concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an α-β-unsatured carbonyl moiety and function as potent Michael reaction acceptor, induce a rapid drop in intracellular glutathione (GSH) concentration by direct interaction with it, thereby triggering S-glutathionylation of STAT3. Dehydrocostunolide (HCS), the reduced form of CS lacking only the α-β-unsaturated carbonyl group, fails to exert any inhibitory action. Finally, the glutathione ethylene ester (GEE), the cell permeable GSH form, reverts the inhibitory action of DCE and CS on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene lactones are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function

Spider mite web mediates anti-predator behaviour

Herbivores suffer significant mortality from predation and are therefore subject to natural selection on traits promoting predator avoidance and resistance. They can employ an array of strategies to reduce predation, for example through changes in behaviour, morphology and life history. So far, the anti-predator response studied most intensively in spider mites has been the avoidance of patches with high predation risk. Less attention has been given to the dense web produced by spider mites, which is a complex structure of silken threads that is thought to hinder predators. Here, we investigate the effects of the web produced by the red spider mite, Tetranychus evansi Baker & Pritchard, on its interactions with the predatory mite, Phytoseiulus longipes Evans. We tested whether female spider mites recognize predator cues and whether these can induce the spider mites to produce denser web. We found that the prey did not produce denser web in response to such cues, but laid more eggs suspended in the web, away from the leaf surface. These suspended eggs suffered less from predation by P. longipes than eggs that were laid on the leaf surface under the web. Thus, by altering their oviposition behaviour in response to predator cues, females of T. evansi protect their offspring

H3K9me-Independent Gene Silencing in Fission Yeast Heterochromatin by Clr5 and Histone Deacetylases

Nucleosomes in heterochromatic regions bear histone modifications that distinguish them from euchromatic nucleosomes. Among those, histone H3 lysine 9 methylation (H3K9me) and hypoacetylation have been evolutionarily conserved and are found in both multicellular eukaryotes and single-cell model organisms such as fission yeast. In spite of numerous studies, the relative contributions of the various heterochromatic histone marks to the properties of heterochromatin remain largely undefined. Here, we report that silencing of the fission yeast mating-type cassettes, which are located in a well-characterized heterochromatic region, is hardly affected in cells lacking the H3K9 methyltransferase Clr4. We document the existence of a pathway parallel to H3K9me ensuring gene repression in the absence of Clr4 and identify a silencing factor central to this pathway, Clr5. We find that Clr5 controls gene expression at multiple chromosomal locations in addition to affecting the mating-type region. The histone deacetylase Clr6 acts in the same pathway as Clr5, at least for its effects in the mating-type region, and on a subset of other targets, notably a region recently found to be prone to neo-centromere formation. The genomic targets of Clr5 also include Ste11, a master regulator of sexual differentiation. Hence Clr5, like the multi-functional Atf1 transcription factor which also modulates chromatin structure in the mating-type region, controls sexual differentiation and genome integrity at several levels. Globally, our results point to histone deacetylases as prominent repressors of gene expression in fission yeast heterochromatin. These deacetylases can act in concert with, or independently of, the widely studied H3K9me mark to influence gene silencing at heterochromatic loci