Multiple centrality assessment in Parma : a network analysis of paths and open spaces

One of the largest of Europe, the recently realized university campus 'Area of the Sciences' in Parma, northern Italy, has been planned for a comprehensive programme of renovation and revitalization with a special focus on vehicular accessibility and the quality of open spaces. As part of the problem setting phase, the authors, with Rivi Engineering, applied Multiple Centrality Assessment (MCA) - a process of network analysis based on primal graphs, a set of different centrality indices and the metric computation of distances - in order to understand why the existent system of open spaces and pedestrian paths is so scarcely experienced by students as well as faculty and staff members and why it appears so poorly supportive of social life and human exchange. In the problem-solving phase MCA was also applied, turning out to offer a relevant contribution to the comparative evaluation of two alternative proposed scenarios, leading to the identification of one final solution of urban design. In the present paper, the first professional application of MCA, an innovative approach to the network analysis of geographic complex systems, is presented and its relevance in the context of a problem of urban design illustrated

LOCATING CRITICAL LINES IN HIGH-VOLTAGE ELECTRICAL POWER GRIDS

Electrical power grids are among the infrastructures that are attracting a great deal of attention because of their intrinsic criticality. Here we analyze the topological vulnerability and improvability of the spanish 400 kV, the french 400 kV and the italian 380 kV power transmission grids. For each network we detect the most critical lines and suggest how to improve the connectivity

Centrality Measures in Spatial Networks of Urban Streets

We study centrality in urban street patterns of different world cities represented as networks in geographical space. The results indicate that a spatial analysis based on a set of four centrality indices allows an extended visualization and characterization of the city structure. Planned and self-organized cities clearly belong to two different universality classes. In particular, self-organized cities exhibit scale-free properties similar to those found in the degree distributions of non-spatial networks.Comment: 4 pages, 3 figure

A model for cascading failures in complex networks

Large but rare cascades triggered by small initial shocks are present in most of the infrastructure networks. Here we present a simple model for cascading failures based on the dynamical redistribution of the flow on the network. We show that the breakdown of a single node is sufficient to collapse the efficiency of the entire system if the node is among the ones with largest load. This is particularly important for real-world networks with an highly hetereogeneous distribution of loads as the Internet and electrical power grids.Comment: 4 pages, 4 figure

Efficiency of Scale-Free Networks: Error and Attack Tolerance

The concept of network efficiency, recently proposed to characterize the properties of small-world networks, is here used to study the effects of errors and attacks on scale-free networks. Two different kinds of scale-free networks, i.e. networks with power law P(k), are considered: 1) scale-free networks with no local clustering produced by the Barabasi-Albert model and 2) scale-free networks with high clustering properties as in the model by Klemm and Eguiluz, and their properties are compared to the properties of random graphs (exponential graphs). By using as mathematical measures the global and the local efficiency we investigate the effects of errors and attacks both on the global and the local properties of the network. We show that the global efficiency is a better measure than the characteristic path length to describe the response of complex networks to external factors. We find that, at variance with random graphs, scale-free networks display, both on a global and on a local scale, a high degree of error tolerance and an extreme vulnerability to attacks. In fact, the global and the local efficiency are unaffected by the failure of some randomly chosen nodes, though they are extremely sensititive to the removal of the few nodes which play a crucial role in maintaining the network's connectivity.Comment: 23 pages, 10 figure

The European union’s 2010 target: Putting rare species in focus

P. 167-185The European Union has adopted the ambitious target of halting the loss of biodiversity by 2010. Several indicators have been proposed to assess progress towards the 2010 target, two of them addressing directly the issue of species decline. In Europe, the Fauna Europaea database gives an insight into the patterns of distribution of a total dataset of 130,000 terrestrial and freshwater species without taxonomic bias, and provide a unique opportunity to assess the feasibility of the 2010 target. It shows that the vast majority of European species are rare, in the sense that they have a restricted range. Considering this, the paper discusses whether the 2010 target indicators really cover the species most at risk of extinction. The analysis of a list of 62 globally extinct European taxa shows that most contemporary extinctions have affected narrow-range taxa or taxa with strict ecological requirements. Indeed, most European species listed as threatened in the IUCN Red List are narrow-range species. Conversely, there are as many wide-range species as narrow-range endemics in the list of protected species in Europe (Bird and Habitat Directives). The subset of biodiversity captured by the 2010 target indicators should be representative of the whole biodiversity in terms of patterns of distribution and abundance. Indicators should not overlook a core characteristic of biodiversity, i.e. the large number of narrow-range species and their intrinsic vulnerability. With ill-selected indicator species, the extinction of narrowrange endemics would go unnoticedS

Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets

Tuberculosis (TB) is a disease that the World Health Organisation (WHO) regards as a global pandemic. There is a great need for new drugs to combat this threat. Drug resistant strains of the causative agent, Mycobacterium tuberculosis (Mtb), have increased the urgency of this quest for novel anti-mycobacterial medicines. Publication of the Mtb genome sequence revealed a large number of cytochrome P450 (CYP) enzymes [Cole, S. T. et al. 1998]. These mono-oxygenase enzymes have been studied for many years and are responsible for metabolic functions in every kingdom of life. Research on the Mtb P450s to date has highlighted several of them as having critcal roles within the organism. CYP121 and CYP128 have been implicated as essential through gene knockout studies. It has been demonstrated that CYP125 is not essential for viability. However, it is part of a gene cluster highly important for Mtb infectivity and virulence. Due to the prospective importance of P450s to Mtb, this group of enzymes is under investigation as a source of novel drug targets. CYP142 was discovered as a potential drug target after it was located to a gene cluster involved in cholesterol catabolism during Mtb dormancy. As part of this PhD project, it was demonstrated that CYP142 performs an almost identical role to that reported for CYP125. These enzymes both perform C27 hydroxylation and carboxylation of the cholesterol side chain. However, variations in the level of oxidation have been identified, dependent upon the redox system with which these P450s are associated. A crystal structure of CYP142 showing high similarity in active site architecture to CYP125 supports the physiological role of CYP142 in cholesterol catabolism. Combining this with in vitro data which demonstrates that CYP142 possesses high affinity for a range of azole anti-fungal agents [Ahmad, Z. et al. 2005, 2006] supports the suggestion that it is a candidate target for the next generation of anti-mycobacterial drugs. CYP144 was highlighted as being important during the latent phase of Mtb growth, a phase that is not targeted by any of the current antimycobacterials. Work performed as part of this PhD has shown that many characteristics of CYP144 are highly comparable to those reported for other MtbP450s. CYP144 shows high affinity and specificity towards many azole molecules. Econazole, clotrimazole and miconazole have repeatedly been shown to bind to MtbP450s, including CYP144 and CYP142, with high affinity and are excellent potential candidates as novel anti-mycobacterial agents. An N-terminally truncated form of CYP144, CYP144-T, has been investigated in the pursuit of a CYP144 crystal structure. It is hoped that this will enable the elucidation of a physiological role for CYP144. Both CYP142 and CYP144 have demonstrated biochemical and biophysical characteristics that contribute to our knowledge of P450 enzymes. This PhD has established that CYP142 exhibits an equilibrium between P450 and P420 species in its CO-bound, ferrous form. A conversion from P420, and stabilisation of P450, upon substrate binding was also demonstrated. CYP144 displays unusual azole coordination characteristics when examined by EPR and removal of the CYP144 gene from Mtb increased sensitivity of the strain to clotrimazole. Studies of these enzymes has advanced knowledge of P450 and Mtb redox chemistry, established roles for the MtbP450 cohort and identified the potential of anti-mycobacterial drugs and associated targets.EThOS - Electronic Theses Online ServiceGBUnited Kingdo