Adaptive Tunning of All Parameters in a Multi- Swarm Particle Swarm Optimization Algorithm : An Application to the Probabilistic Traveling Salesman Problem

One of the main issues in the application of a Particle SwarmOptimization (PSO) algorithm and of every evolutionary opti-mization algorithm is the finding of the suitable parameters ofthe algorithm. In this paper, we use a parameter free version of aMulti-Swarm PSO algorithm where random values are assignedin the initialization of all parameters (including the number ofswarms) of the algorithm and, then, during the iterations theparameters are optimized together and simultaneously with theoptimization of the objective function of the problem. This ideais used for the solution of the Probabilistic Traveling SalesmanProblem (PTSP). The PTSP is a variation of the classic Trav-eling Salesman Problem (TSP) and one of the most significantstochastic routing problems. In the PTSP, only a subset of poten-tial customers needs to be visited on any given instance of theproblem. The number of customers to be visited each time is arandom variable. The proposed algorithm is tested on numer-ous benchmark problems from TSPLIB with very satisfactoryresults. It is compared with other algorithms from the literature,and, mainly with a Multi-Swarm Particle Swarm Optimizationwith parameters calculated with a classic trial - and - error pro-cedure and they are the same for all instances.Godkänd; 2014; 20141124 (athmig

c-erbB2–induced Disruption of Matrix Adhesion and Morphogenesis Reveals a Novel Role for Protein Kinase B as a Negative Regulator of α(2)β(1) Integrin Function

Overexpression of the growth factor receptor subunit c-erbB2, leading to its ligand-independent homodimerization and activation, has been implicated in the pathogenesis of mammary carcinoma. Here, we have examined the effects of c-erbB2 on the adhesive properties of a mammary epithelial cell line, HB2/tnz34, in which c-erbB2 homodimerization can be induced by means of a transfected hybrid “trk-neu” construct. trk-neu consists of the extracellular domain of the trkA nerve growth factor (NGF) receptor fused to the transmembrane and cytoplasmic domains of c-erbB2, allowing NGF-induced c-erbB2 homodimer signaling. Both spreading and adhesion on collagen surfaces were impaired on c-erbB2 activation in HB2/tnz34 cells. Antibody-mediated stimulation of α(2)β(1) integrin function restored adhesion, suggesting a direct role for c-erbB2 in integrin inactivation. Using pharmacological inhibitors and transient transfections, we identified signaling pathways required for suppression of integrin function by c-erbB2. Among these was the MEK-ERK pathway, previously implicated in integrin inactivation. However, we could also show that downstream of phosphoinositide-3-kinase (PI3K), protein kinase B (PKB) acted as a previously unknown, potent inhibitor of integrin function and mediator of the disruptive effects of c-erbB2 on adhesion and morphogenesis. The integrin-linked kinase, previously identified as a PKB coactivator, was also found to be required for integrin inactivation by c-erbB2. In addition, the PI3K-dependent mTOR/S6 kinase pathway was shown to mediate c-erbB2–induced inhibition of adhesion (but not spreading) independently of PKB. Overexpression of MEK1 or PKB suppressed adhesion without requirement for c-erbB2 activation, suggesting that these two pathways partake in integrin inhibition by targeting common downstream effectors. These results demonstrate a major novel role for PI3K and PKB in regulation of integrin function

Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake

In multicellular organisms, constituent cells depend on extracellular signals for growth, proliferation, and survival. When cells are withdrawn from growth factors, they undergo apoptosis. Expression of constitutively active forms of the serine/threonine kinase Akt/PKB can prevent apoptosis upon growth factor withdrawal. Akt-mediated survival depends in part on the maintenance of glucose metabolism, suggesting that reduced glucose utilization contributes to growth factor withdrawal-induced death. However, it is unclear how restricting access to extracellular glucose alone would lead to the metabolic collapse observed after growth factor withdrawal. We report herein that growth factor withdrawal results in the loss of surface transporters for not only glucose but also amino acids, low-density lipoprotein, and iron. This coordinated decline in transporters and receptors for extracellular molecules creates a catabolic state characterized by atrophy and a decline in the mitochondrial membrane potential. Activated forms of Akt maintained these transporters on the cell surface in the absence of growth factor through an mTOR-dependent mechanism. The mTOR inhibitor rapamycin diminished Akt-mediated increases in cell size, mitochondrial membrane potential, and cell survival. These results suggest that growth factors control cellular growth and survival by regulating cellular access to extracellular nutrients in part by modulating the activity of Akt and mTOR