The Network Analysis of Urban Streets: A Primal Approach

The network metaphor in the analysis of urban and territorial cases has a long tradition especially in transportation/land-use planning and economic geography. More recently, urban design has brought its contribution by means of the "space syntax" methodology. All these approaches, though under different terms like accessibility, proximity, integration,connectivity, cost or effort, focus on the idea that some places (or streets) are more important than others because they are more central. The study of centrality in complex systems,however, originated in other scientific areas, namely in structural sociology, well before its use in urban studies; moreover, as a structural property of the system, centrality has never been extensively investigated metrically in geographic networks as it has been topologically in a wide range of other relational networks like social, biological or technological. After two previous works on some structural properties of the dual and primal graph representations of urban street networks (Porta et al. cond-mat/0411241; Crucitti et al. physics/0504163), in this paper we provide an in-depth investigation of centrality in the primal approach as compared to the dual one, with a special focus on potentials for urban design.Comment: 19 page, 4 figures. Paper related to the paper "The Network Analysis of Urban Streets: A Dual Approach" cond-mat/041124

The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Preserves Endothelial Function in Mesenteric Arteries from Type 1 Diabetic Rats without Decreasing Plasma Glucose.

The aim of the study was to investigate the effect of the DPP-4 inhibitor linagliptin on the mechanism(s) of endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and diabetic animals received linagliptin (2 mg/kg) daily by oral gavage for a period of 4 weeks. To measure superoxide generation in mesenteric arteries, lucigenin-enhanced chemiluminescence was used. ACh-induced relaxation of mesenteric arteries was assessed using organ bath techniques and Western blotting was used to investigate protein expression. Pharmacological tools (1 μM TRAM-34, 1 μM apamin, 100 nM Ibtx, 100 μM L-NNA, 10 μM ODQ) were used to distinguish between NO and EDH-mediated relaxation. Linagliptin did not affect plasma glucose, but did decrease vascular superoxide levels. Diabetes reduced responses to ACh but did not affect endothelium-independent responses to SNP. Linagliptin improved endothelial function indicated by a significant increase in responses to ACh. Diabetes impaired the contribution of both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation and linagliptin treatment significantly enhanced the contribution of both relaxing factors. Western blotting demonstrated that diabetes also increased expression of Nox2 and decreased expression and dimerization of endothelial NO synthase, effects that were reversed by linagliptin. These findings demonstrate treatment of type 1 diabetic rats with linagliptin significantly reduced vascular superoxide levels and preserved both NO and EDH-mediated relaxation indicating that linagliptin can improve endothelial function in diabetes independently of any glucose lowering activity

Plasma glucose concentrations measured from 1–10 weeks after administration of STZ (50 mg/kg IV).

<p>Linagliptin treatment (2 mg/kg po per day) commenced 6 weeks after STZ administration. Linagliptin did not affect plasma glucose in normal or STZ treated rats.</p

Mean body weight, blood glucose and HbA_1c levels at the end of the experiment of normal and diabetic rats with or without treatment with linagliptin (2 mg/kg oral gavage daily for 4 weeks) 10 weeks after vehicle or STZ treatment.

<p>n = the number of rats.</p><p>^a Significantly different to normal group, p<0.05, Tukey’s test</p><p>^b Significantly different to diabetic group, P<0.05, Tukey’s test</p><p>^c Significantly different to normal+linagliptin group, P<0.05, Tukey’s test.</p><p>Results are shown as mean±SEM.</p><p>Mean body weight, blood glucose and HbA_1c levels at the end of the experiment of normal and diabetic rats with or without treatment with linagliptin (2 mg/kg oral gavage daily for 4 weeks) 10 weeks after vehicle or STZ treatment.</p

ROS measurement in intact mesenteric arteries.

<p>NADPH activity was elevated in diabetic mesenteric arteries and this was attenuated by linagliptin treatment or by DPI (5 μM), a flavoprotein inhibitor that inhibits NADPH oxidase. Results are shown as mean±SEM. n = 7–10 experiments. *P<0.05 vs normal, ^#P<0.05 vs diabetic.</p

Relative contribution of NO and EDH to endothelium-dependent relaxation.

<p>NO and EDH-mediated relaxation in isolated mesenteric arteries from normal (a), diabetic (b), normal+linagliptin (c), diabetic+linagliptin (d) rats. In each group of experiments, arteries were precontracted with PE to similar levels: 63±2 (a), 65±0.6 (b), 65±1 (c), 63±1 (d) %KPSS, n = 8–9 experiments. Results are shown as mean±SEM. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143941#pone.0143941.t002" target="_blank">Table 2</a> for pEC₅₀ and R_max values derived from this data. *P<0.05 vs normal.</p

Western blot analysis of protein expression of eNOS (a, 130 kDa), eNOS dimers and monomers (b, 260 kDa) and Nox2 Nox2 (c, 58 kDa) in the normal and diabetic mesenteric arteries with or without linagliptin treatment.

<p>In diabetic mesenteric arteries, the expression of eNOS significantly reduced and the proportion of eNOS expressed as the dimer reduced, and the expression of Nox2 increased. Treatment with linagliptin increased the expression of eNOS significantly and reduced Nox2 expression and increased the proportion of eNOS expressed as the dimer. Representative blots are shown on each of the corresponding graphs. n = 6 experiments. Results are shown as mean±s.e.m. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.</p

Cumulative concentration-response curves to ACh (a), SNP (b), and basal NO release (c) in endothelium-intact mesenteric arteries.

<p>In each group (a, b), mesenteric arteries were prcontracted with PE to a similar levels: (a) normal 66±2, normal+linagliptin 64±1, diabetic 65±1, diabetic+linagliptin 66±1, (b) normal 64±1, normal+linagliptin 64±1, diabetic 61±6, diabetic+linagliptin 66±1%KPSS, n = 7–10 experiments. Results are shown as mean±SEM. **P<0.01, ***P<0.001 See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143941#pone.0143941.t002" target="_blank">Table 2</a> or results section for pEC₅₀ and R_max values derived from this data.</p

Effect of L-NNA, ODQ and potassium channel blockers on ACh-induced relaxation of mesenteric arteries from normal and diabetic rats with or without linagliptin (2 mg/kg oral gavage daily for 4 weeks) treatment in the presence of indomethacin.

<p>A comparison of the sensitivity (pEC₅₀) and maximum relaxation (R_max) to ACh in the absence (control), or the presence of TRAM-34 (1 μM)</p><p>+apamin (1 μM), L-NNA (100 μM)+ODQ (10 μM), L-NNA (100 μM)+ODQ (10 μM)+ TRAM-34 (1 μM) +apamin (1 μM) or L-NNA (100 μM)</p><p>+ODQ (10 μM)+TRAM-34 (1 μM) +apamin (1 μM)+Ibtx (100 nM) in endothelium intact mesenteric arteries. All experiments were performed in the presence of indomethacin (10 μM). n = the number of experiments.</p><p>^a Significantly different to control within each group, P<0.05, Tukey’s test</p><p>^b Significantly different to normal within inhibitor group, P<0.05, Tukey’s test</p><p>^c Significantly different to normal+linagliptin within inhibitor group, P<0.05, Tukey’s test</p><p>^d Significantly different to diabetic within inhibitor group, P<0.05, Tukey’s test. Results are shown as mean±SEM</p><p>ND = not determined.</p><p>Effect of L-NNA, ODQ and potassium channel blockers on ACh-induced relaxation of mesenteric arteries from normal and diabetic rats with or without linagliptin (2 mg/kg oral gavage daily for 4 weeks) treatment in the presence of indomethacin.</p