Do institutional arrangements make a difference to transport policy and implementation? Lessons for Britain

This paper describes local government decision-making in transport in three areas of the UK, London, West Yorkshire and Edinburgh, in which major changes in local government decision-making structures have taken place over the last decade, and between which arrangements are now very different. The research discusses whether institutional change has had a beneficial or adverse effect, and whether any of the current structures provides a more effective framework for policy development and implementation. The results show that although the sites share a broadly common set of objectives there are differences in devolved responsibilities and in the extent to which various policy options are within the control of the bodies charged with transport policy delivery. The existence of several tiers of government, coupled with the many interactions required between these public sector bodies and the predominantly private sector public transport operators appears to create extra transactional barriers and impedes the implementation of the most effective measures for cutting congestion. There is, however, a compelling argument for the presence of an overarching tier of government to organise travel over a spatial scale compatible with that of major commuter patterns. The extent to which such arrangements currently appear to work is a function of the range of powers and the funding levels afforded to the co-ordinating organisation

A procedure for the change point problem in parametric models based on phi-divergence test-statistics

This paper studies the change point problem for a general parametric, univariate or multivariate family of distributions. An information theoretic procedure is developed which is based on general divergence measures for testing the hypothesis of the existence of a change. For comparing the accuracy of the new test-statistic a simulation study is performed for the special case of a univariate discrete model. Finally, the procedure proposed in this paper is illustrated through a classical change-point example

Transport poverty meets the digital divide : accessibility and connectivity in rural communities

Peer reviewedPublisher PD

Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD-95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD-95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K+ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage-dependent K+ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease

Olympic legacy and cultural tourism: Exploring the facets of Athens' Olympic heritage

This study examines the effects of the Olympic Games on Athens’ cultural tourism and the city’s potential to leverage the Olympic legacy in synergy with its rich heritage in order to enhance its tourism product during the post-Games period. In doing so, a qualitative and interpretive approach was employed. This includes a literature review on Athens’ 2004 Olympics to identify the sport facilities and regeneration projects, which constitute the Olympic legacy and heritage. Based on that, an empirical analysis was undertaken, by collecting official documents about the 2004 Olympics, and conducting five semi-structured interviews with tourism/administrative officials. The findings indicate that the Olympiad contributed significantly to Athens’ built and human heritage, revealing the dimensions of new venues/facilities, infrastructure, transportation and aesthetic image of the city, and human capital enhancement. Hence, the Games affected to the multifaceted representation and reconstruction of the city’s identity and cultural heritage. However, the potential afforded from the post-Olympic Athens remains unrealised due to lack of strategic planning/management. The study concludes that there is a need to develop cross-leveraging synergies between the Olympic legacy and cultural tourism for the host city. Finally, a strategic planning framework for leveraging post-Games Olympic tourism is suggested in order to maximise the benefits of Olympic legacy and heritage in a host city’s tourism development

Genomic and transcriptomic landscape of conjunctival melanoma.

Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM

Comprehensive Genetic Landscape of Uveal Melanoma by Whole-Genome Sequencing.

Uveal melanoma (UM) is a rare intraocular tumor that, similar to cutaneous melanoma, originates from melanocytes. To gain insights into its genetics, we performed whole-genome sequencing at very deep coverage of tumor-control pairs in 33 samples (24 primary and 9 metastases). Genome-wide, the number of coding mutations was rather low (only 17 variants per tumor on average; range 7-28), thus radically different from cutaneous melanoma, where hundreds of exonic DNA insults are usually detected. Furthermore, no UV light-induced mutational signature was identified. Recurrent coding mutations were found in the known UM drivers GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Other genes, i.e., TP53BP1, CSMD1, TTC28, DLK2, and KTN1, were also found to harbor somatic mutations in more than one individual, possibly indicating a previously undescribed association with UM pathogenesis. De novo assembly of unmatched reads from non-coding DNA revealed peculiar copy-number variations defining specific UM subtypes, which in turn could be associated with metastatic transformation. Mutational-driven comparison with other tumor types showed that UM is very similar to pediatric tumors, characterized by very few somatic insults and, possibly, important epigenetic changes. Through the analysis of whole-genome sequencing data, our findings shed new light on the molecular genetics of uveal melanoma, delineating it as an atypical tumor of the adult for which somatic events other than mutations in exonic DNA shape its genetic landscape and define its metastatic potential