Rail Connected City-Regions: the Significance of Concerted Policies and Alternative Funding Options

One should not be enthusiastic of Far East mega-cities easily sustaining urban rail systems to understand that high densities slow down land consumption and increase ridership. An objective of the paper is to investigate the case of a mutually supportive land use and urban rail planning in two European cities. A parallel objective is to demonstrate that singular measures like urban rail stations or dense mixed uses are not sufficient to achieve a sustainable growth. The macro-connectivity of the city-region by rail as well as local parking constraints are important factors for successful sustainability. A particular (chrono-)logical planning sequence of action packages is suggested, in order to maximize the desired impacts. Next to the conceptual part, two relevant case studies are demonstrated. First, the Swiss City-Rail project of Bern. It concerns the two employment poles Ausserholligen west of, and Wankdorf east of the Central Station, where suburban rail interchanges are planned. Each pole will contain a development of 600.000 sq.m. Gross Floor Area of mixed uses, staged up to 2020. The wide range of concerted policies effectuated is analysed. Second, the case of Athens, one of the seven European mega-cities with more than 4 mi. inhabitants is discussed. Within the framework of the Metro Development Study (MDS), a multimodal transportation plan for Athens with the horizon 2020 has been developed. A calibrated Garin-Lowry land use – transportation model forecasts job and population figures at the level of 1230 traffic zones. The MDS 2020 plan contains 106 km metro, 46 km tramway, and 328 km suburban rail. High urban rail investments have already taken place in Athens, also in view of the Olympic Games. The paper discusses planning opportunities for concentrated service development at suitable rail interchanges proposed by the MDS. Two types of structural actions are considered. First, upzoning and new development around three suburban rail interchanges, especially along the suburban rail corridor leading from Athens to the Airport. A recent mall development in one of these interchanges is critically discussed. Rail use is better suited for employees and people seeking entertainment than shopping in this respect. Second, rezoning and recycled development at built-up areas around three peripheral metro interchanges, while protecting the existing housing. Finally, a comparative review of the planning frameworks in Bern and in Athens is performed, with a special emphasis on revealed planning deficits.

Rail Connected City-Regions: the Significance of Concerted Policies and Alternative Funding Options

One should not be enthusiastic of Far East mega-cities easily sustaining urban rail systems to understand that high densities slow down land consumption and increase ridership. An objective of the paper is to investigate the case of a mutually supportive land use and urban rail planning in two European cities. A parallel objective is to demonstrate that singular measures like urban rail stations or dense mixed uses are not sufficient to achieve a sustainable growth. The macro-connectivity of the city-region by rail as well as local parking constraints are important factors for successful sustainability. A particular (chrono-)logical planning sequence of action packages is suggested, in order to maximize the desired impacts. Next to the conceptual part, two relevant case studies are demonstrated. First, the Swiss City-Rail project of Bern. It concerns the two employment poles Ausserholligen west of, and Wankdorf east of the Central Station, where suburban rail interchanges are planned. Each pole will contain a development of 600.000 sq.m. Gross Floor Area of mixed uses, staged up to 2020. The wide range of concerted policies effectuated is analysed. Second, the case of Athens, one of the seven European mega-cities with more than 4 mi. inhabitants is discussed. Within the framework of the Metro Development Study (MDS), a multimodal transportation plan for Athens with the horizon 2020 has been developed. A calibrated Garin-Lowry land use – transportation model forecasts job and population figures at the level of 1230 traffic zones. The MDS 2020 plan contains 106 km metro, 46 km tramway, and 328 km suburban rail. High urban rail investments have already taken place in Athens, also in view of the Olympic Games. The paper discusses planning opportunities for concentrated service development at suitable rail interchanges proposed by the MDS. Two types of structural actions are considered. First, upzoning and new development around three suburban rail interchanges, especially along the suburban rail corridor leading from Athens to the Airport. A recent mall development in one of these interchanges is critically discussed. Rail use is better suited for employees and people seeking entertainment than shopping in this respect. Second, rezoning and recycled development at built-up areas around three peripheral metro interchanges, while protecting the existing housing. Finally, a comparative review of the planning frameworks in Bern and in Athens is performed, with a special emphasis on revealed planning deficits

Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies

Summary: Genevar (GENe Expression VARiation) is a database and Java tool designed to integrate multiple datasets, and provides analysis and visualization of associations between sequence variation and gene expression. Genevar allows researchers to investigate expression quantitative trait loci (eQTL) associations within a gene locus of interest in real time. The database and application can be installed on a standard computer in database mode and, in addition, on a server to share discoveries among affiliations or the broader community over the Internet via web services protocols. Availability: http://www.sanger.ac.uk/resources/software/genevar Contact: [email protected]

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a ~410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPARγ, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids

Genetically determined height and coronary artery disease.

BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)

Differences in the localization and morphology of chromosomes in the human nucleus

Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Genome-wide associations of gene expression variation in humans

The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs) with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis-) to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I) HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level