Beyond energy efficiency in evaluating sustainable development in planning and the built environment

The EU has set the policy target of reducing energy use by 20% by the year 2020. Therefore, a substantial consumption decrease is needed in the built environment sector. Despite the great energy efficiency improvements in households, recent energy consumption data analyses show that these targets will unlikely be reached. The general aim of this study is to point out the need to define new indicators and evaluation approaches in urban planning and the built environment which are based on the concept of ‘energy subsidiarity', focusing on local renewable resources rather than on current approaches based on energy efficiency. This concept correlates energy consumption with the energy supply from local renewable resources and is here proposed as the new urban planning evaluation approach toward a sustainable built environment. In the paper, the ‘Jevons Paradox' concept and the ‘energy rebound effect' phenomenon are used to demonstrate how current approaches based on energy efficiency, alone, cannot lead to a remarkable reduction of energy consumption. This is also supported by data on European energy consumption and European energy efficiency in the built environment. Finally, a number of well-known European ecological districts (‘eco-districts') are analysed in terms of sustainable energy strategy as well as energy efficiency and energy balance. This study shows that there is a contradiction between the purpose of some of the eco-districts to be low consumption (or low impacts), and the district renewable energy balance. Only a few of the analysed eco-districts are able to cover energy needs by using renewable energy obtained in the surrounding area. In most of the cases, the focus of the districts' activities is on energy efficiency. According to the ‘Jevons Paradox' and ‘energy rebound effect' paradigm, energy efficiency alone will unlikely lead to an effective reduction in resources' consumption. These results point out the need for a radical shift toward the development of new approaches in the assessment and management of the built environment for sustainabilit

Modern cities modelled as “super-cells” rather than multicellular organisms: Implications for industry, goods and services

The structure and “metabolism” (movement and conversion of goods and energy) of urban areas has caused cities to be identified as “super-organisms”, placed between ecosystems and the biosphere, in the hierarchy of living systems. Yet most such analogies are weak, and render the super-organism model ineffective for sustainable development of cities. Via a cluster analysis of 15 shared traits of the hierarchical living system, we found that industrialized cities are more similar to eukaryotic cells than to multicellular organisms; enclosed systems, such as factories and greenhouses, paralleling organelles in eukaryotic cells. We further developed a “super-cell” industrialized city model: a “eukarcity” with citynucleus (urban area) as a regulating centre, and organaras (enclosed systems, which provide the majority of goods and services) as the functional components, and cityplasm (natural ecosystems and farmlands) as the matrix. This model may improve the vitality and sustainability of cities through planning and management

Mobilising Urban Policies: The Policy Transfer of US Business Improvement Districts to England and Wales

This paper examines the ways in which policies are transferred between places: how they are disembedded from, and re-embedded into, new political, economic and social contexts. To do this, the paper will draw upon a case study of the transfer of Business Improvement Districts (BIDs) from the US to England and Wales. Within this, the paper demonstrates how they were a response to fiscal problems facing city-centre management in England and Wales; how US BIDs were socially constructed as `successful' and `transferable'; and how the BID `model' was reshaped prior to and following its rolling-out in England and Wales. The paper concludes by stressing six wider conceptual points about the nature of urban policy transfer

Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory

The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans

Small Change: Economics and the British coin-tree

This is the accepted manuscript for the following article: Ceri Houlbrook, “Small Change: Economics and the British coin-tree”, Post Medieval Archaeology, Vol. 49(1), June 2015. The final published version can be found at: http://www.tandfonline.com/doi/full/10.1179/0079423615Z.00000000074 © Society for Post-Medieval Archaeology 2015Throughout the c.2000 year period coins have been circulated in Britain, they have also been ritually employed, most notably as votive deposits. Focusing specifically on the understudied custom of the British coin-tree, whereby coins are ritually embedded into the barks of trees, this paper considers the coin’s role and applicability as a deposit. It aims to demonstrate that our understanding of the coin’s past, present, and future ritual employment is not only aided by a consideration of economics and the coin’s secular function; it would be utterly incomplete without it.Peer reviewedFinal Accepted Versio

Misbehaviour of XIST RNA in Breast Cancer Cells

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors

Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk

Coding variants represent many of the strongest associations between genotype and phenotype; however, they exhibit interindividual differences in effect, termed 'variable penetrance'. Here, we study how cis-regulatory variation modifies the penetrance of coding variants. Using functional genomic and genetic data from the Genotype-Tissue Expression Project (GTEx), we observed that in the general population, purifying selection has depleted haplotype combinations predicted to increase pathogenic coding variant penetrance. Conversely, in cancer and autism patients, we observed an enrichment of penetrance increasing haplotype configurations for pathogenic variants in disease-implicated genes, providing evidence that regulatory haplotype configuration of coding variants affects disease risk. Finally, we experimentally validated this model by editing a Mendelian single-nucleotide polymorphism (SNP) using CRISPR/Cas9 on distinct expression haplotypes with the transcriptome as a phenotypic readout. Our results demonstrate that joint regulatory and coding variant effects are an important part of the genetic architecture of human traits and contribute to modified penetrance of disease-causing variants.Peer reviewe

Successful Inhibition of Tumor Development by Specific Class-3 Semaphorins Is Associated with Expression of Appropriate Semaphorin Receptors by Tumor Cells

The class-3 semaphorins (sema3s) include seven family members. Six of them bind to neuropilin-1 (np1) or neuropilin-2 (np2) receptors or to both, while the seventh, sema3E, binds to the plexin-D1 receptor. Sema3B and sema3F were previously characterized as tumor suppressors and as inhibitors of tumor angiogenesis. To determine if additional class-3 semaphorins such as sema3A, sema3D, sema3E and sema3G possess anti-angiogenic and anti-tumorigenic properties, we expressed the recombinant full length semaphorins in four different tumorigenic cell lines expressing different combinations of class-3 semaphorin receptors. We show for the first time that sema3A, sema3D, sema3E and sema3G can function as potent anti-tumorigenic agents. All the semaphorins we examined were also able to reduce the concentration of tumor associated blood vessels although the potencies of the anti-angiogenic effects varied depending on the tumor cell type. Surprisingly, there was little correlation between the ability to inhibit tumor angiogenesis and their anti-tumorigenic activity. None of the semaphorins inhibited the adhesion of the tumor cells to plastic or fibronectin nor did they modulate the proliferation of tumor cells cultured in cell culture dishes. However, various semaphorins were able to inhibit the formation of soft agar colonies from tumor cells expressing appropriate semaphorin receptors, although in this case too the inhibitory effect was not always correlated with the anti-tumorigenic effect. In contrast, the anti-tumorigenic effect of each of the semaphorins correlated very well with tumor cell expression of specific signal transducing receptors for particular semaphorins. This correlation was not broken even in cases in which the tumor cells expressed significant concentrations of endogenous semaphorins. Our results suggest that combinations of different class-3 semaphorins may be more effective than single semaphorins in cases in which tumor cells express more than one type of semaphorin receptors