A multiobjective routing model for Multiprotocol Label Switching networks with multiple service types and traffic splitting is presented in this paper.The routing problem is formulated as a multiobjective mixed-integer program,where the considered objectives are the minimization of the bandwidth routing cost and the minimization of the load cost in the network links with a constraint on the maximal splitting of traffic trunks.Two different exact methods are developed for solving the formulated problem,one based on the classical constraint method and another based on a modified constraint method.Avery extensive experimental study,with results on network performance measures in various reference test networks and in randomly generated networks,is also presented and its results are discussed. 相似文献
Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.
Polarity is a fundamental feature of cells. Protein complexes, including the PAR3–PAR6–aPKC complex, have conserved roles in establishing polarity across a number of eukaryotic cell types. In neurons, polarity is evident as distinct axonal versus dendritic domains. The PAR3, PAR6, and aPKC proteins also play important roles in neuronal polarization. During this process, either aPKC kinase activity, the assembly of the PAR3–PAR6–aPKC complex or the localization of these proteins is regulated downstream of a number of signaling pathways. In turn, the PAR3, PAR6, and aPKC proteins control various effector molecules to establish neuronal polarity. Herein, we discuss the many signaling mechanisms and effector functions that have been linked to PAR3, PAR6, and aPKC during the establishment of neuronal polarity. 相似文献
ABSTRACTThe island of New Guinea has been identified as biologically megadiverse but many taxa are still poorly known. This is especially the case for many of the island’s snakes, which by their very nature can be difficult to collect and study. Here we examine the phylogenetic and phylogeographic structure of a poorly studied snake genus, Stegonotus, focusing on the species of New Guinea; until now, Stegonotus has never been examined using modern phylogenetic methods. Using molecular data from 49 individuals representing eight of the ten described species, and including all New Guinea taxa, we estimate a multilocus phylogeny and examine population structure to help identify undescribed taxa. We use morphological data from the corresponding museum vouchered specimens (where available) and also examine additional specimens for taxa not included in the molecular data set to determine morphological differences among putative taxa. We find molecular evidence for four new species of Stegonotus, both morphologically obvious and cryptic, and describe them herein. The recognition of these four species indicates that Stegonotus diversity has been previously underestimated and also suggests that there are likely additional undescribed taxa within the genus. These four taxa increase the number of described species by 40% and further confirm New Guinea as the centre of diversity for the genus.www.zoobank.org/urn:lsid:zoobank.org:pub:9E21390E-3FD4-40EB-9442-31BC92A76B4F相似文献