local buzz, global pipelines and the process of knowledge creation

The version of record [Bathelt, H., Malmberg, A., & Maskell, P. (2004). Clusters and knowledge: Local buzz, global pipelines and the process of knowledge creation. Progress in Human Geography, 28(1), 31-56.] is available online at: http://phg.sagepub.com/content/28/1/31 [doi: 10.1191/0309132504ph469oa]The paper is concerned with spatial clustering of economic activity and its relation to the spatiality of knowledge creation in interactive learning processes. It questions the view that tacit knowledge transfer is confined to local milieus whereas codified knowledge may roam the globe almost frictionlessly. The paper highlights the conditions under which both tacit and codified knowledge can be exchanged locally and globally. A distinction is made between, on the one hand, the learning processes taking place among actors embedded in a community by just being there dubbed buzz and, on the other, the knowledge attained by investing in building channels of communication called pipelines to selected providers located outside the local milieu. It is argued that the co-existence of high levels of buzz and many pipelines may provide firms located in outward-looking and lively clusters with a string of particular advantages not available to outsiders. Finally, some policy implications, stemming from this argument, are identified

A circulating microRNA profile is associated with late-stage neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs) which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV) AMD (hsa-mir-301-3p, pcorrected = 5.6*10−5, hsa-mir-361-5p, pcorrected = 8.0*10−4 and hsa-mir-424-5p, pcorrected = 9.6*10−3). A combined profile of the three miRNAs revealed an area under the curve (AUC) value of 0.727 and was highly associated with NV AMD (p = 1.2*10−8). To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA) were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005). Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay

<i>In vitro</i> tube formation assays in human endothelial cells.

<p>HUVEC cells were transfected with antagomirs for hsa-mir-301a-3p, hsa-mir-361-5p or hsa-mir-424-5p or with control antagomirs (see <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107461#pone.0107461.s002" target="_blank">Figure S2</a></b>) and seeded on Geltrex/Matrigel. Cumulative tube length was quantified with Angiogenesis Analyzer implemented in ImageJ. Each measurement point indicates one independent transfection. Low Serum Growth Supplements (Life) were used as a positive inducer control. Representative images are shown in <b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107461#pone.0107461.s003" target="_blank">Figure S3</a></b>. Significant differences between means are indicated by asterix. * = p_corrected<0.05; *** = p_corrected<0.0005.</p

Summary characteristics of the study.

<p>Summary characteristics of the study.</p

Association of circulating microRNAs with AMD in the Regensburg discovery study (9 NV cases and 9 controls).

<p>Association of circulating microRNAs with AMD in the Regensburg discovery study (9 NV cases and 9 controls).</p

Pathway enrichment analysis performed with miRSystem and mirPATH2.

1<p>genetic associations were reported in or near genes in this pathway by genome wide association studies.</p><p>²KEGG pathway ID (<a href="http://www.genome.jp/kegg/" target="_blank">http://www.genome.jp/kegg/</a>).</p><p>Pathway enrichment analysis performed with miRSystem and mirPATH2.</p

Sensitivity analysis in the Regensburg study by multiple logistic regression models.

1<p>strong increase in association signal by adjusting for glaucoma as a covariate.</p><p>*statistically significant association (p<0.05).</p><p>Sensitivity analysis in the Regensburg study by multiple logistic regression models.</p

Expression analysis of three cmiRNAs (hsa-mir-301a-3p, hsa-mir-361-5p and hsa-mir-424-5p) in 129 NV AMD cases, 59 GA AMD cases and 147 healthy controls.

<p>Expression values for all samples were normalized by the median expression value in controls. Broad horizontal bars represent the mean value in each group (NV cases, GA cases or controls) for each cmiRNA. Smaller horizontal bars represent the 95% confidence intervals for each mean (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107461#pone.0107461.s004" target="_blank">Table S1</a>). Significant differences between means are indicated by asterix. * = p_corrected<0.05; ** = p_corrected<0.005; *** = p_corrected<0.0005.</p