194 research outputs found

    Climate change: Sustainable growth, markets, and institutions

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    human development, climate change

    Introduction..

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    In committing itself to providing a 30-year framework for air transport policy, the government recognised that the existing approach of ad hoc interventions, delayed decisions and the consequent congestion could not be allowed to continue indefinitely. A ten-year transport strategy had been set out for the railways (DETR, 2000); a new energy policy was eventually produced at the end of a lengthy consultation period (DTI, 2003); and a longer-term framework for water published too (Defra, 2002). The government recognised that markets and competition, though important, would not be sufficient for the development of core infrastructure.

    Water regulation: the periodic review

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    Since the privatisation of the water industry in 1989, issues relating to the pricing of water, charging structures and the conduct of the water regulators have rarely been out of public attention. Water prices have increased ahead of inflation, in some cases by more than 10 per cent per annum, profits have been high, construction costs have fallen dramatically in the recession and the investment requirements to meet EC Directives have been revised upwards. In the first years following privatisation, the Director General (DG) of the Office of Water Services (OFWAT), the economic regulator of the industry, has, in the face of major shocks, used his discretion to intervene in the pricing and investment arrangements repeatedly. Indeed, the shocks have been so large that the DG has brought forward the review of the regulatory formula governing prices from 1999-2000 to 1994-95. It is this review of the price limits (called the Periodic Review) which is the subject of this paper. The review will be far reaching, involving decisions about the appropriate cost of capital for the industry, the valuation of existing assets, the capital expenditures required to meet environmental quality targets, and the level of operating costs and efficiency. To date, the DG has issued a series of consultation papers, culminating in Setting Price Limits for Water and Sewerage Services: The Framework and Approach to the 1994 Periodic Review, published in November 1993, which details his approach to the Periodic Review. The aim of this paper is to examine the economic principles underlying the DG’s approach and to consider the implications for the future of water regulation. The structure of the paper is as follows. Section II provides an overview of the current regulatory regime, which was set up at privatisation. Section III considers how the regulatory framework has developed since 1989, with particular focus on the capital expenditure out-turn, shareholder returns and the revisions to the process instigated by the DG. Section IV analyses the DG’s approach to the Periodic Review and describes the ways in which pressure has been brought to bear on the various components of the capital expenditure, cost of capital, asset valuation and operating expenditure to reduce the rate of increase in prices. Section V provides an assessment of the prospects for the success of the DG’s approach. Finally, in Section VI, we summarise our main conclusions.

    The Reverse Transcription Signature of N-\u3csub\u3e1\u3c/sub\u3e-Methyladenosine in RNA-Seq is Sequence Dependent

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    The combination of Reverse Transcription (RT) and high-throughput sequencing has emerged as a powerful combination to detect modified nucleotides in RNA via analysis of either abortive RT-products or of the incorporation of mismatched dNTPs into cDNA. Here we simultaneously analyze both parameters in detail with respect to the occurrence of N-1-methyladenosine (m1A) in the template RNA. This naturally occurring modification is associated with structural effects, but it is also known as a mediator of antibiotic resistance in ribosomal RNA. In structural probing experiments with dimethylsulfate, m1A is routinely detected by RT-arrest. A specifically developed RNA-Seq protocol was tailored to the simultaneous analysis of RT-arrest and misincorporation patterns. By application to a variety of native and synthetic RNA preparations, we found a characteristic signature of m1A, which, in addition to an arrest rate, features misincorporation as a significant component. Detailed analysis suggests that the signature depends on RNA structure and on the nature of the nucleotide 3’ of m1A in the template RNA, meaning it is sequence dependent. The RT-signature ofm1Awas used for inspection and confirmation of suspected modification sites and resulted in the identification of hitherto unknown m1A residues in trypanosomal tRNA

    Effect of 3D-scaffold formation on differentiation and survival in human neural progenitor cells

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    <p>Abstract</p> <p>Background</p> <p>3D-scaffolds have been shown to direct cell growth and differentiation in many different cell types, with the formation and functionalisation of the 3D-microenvironment being important in determining the fate of the embedded cells. Here we used a hydrogel-based scaffold to investigate the influences of matrix concentration and functionalisation with laminin on the formation of the scaffolds, and the effect of these scaffolds on human neural progenitor cells cultured within them.</p> <p>Methods</p> <p>In this study we used different concentrations of the hydrogel-based matrix PuraMatrix. In some experiments we functionalised the matrix with laminin I. The impact of concentration and treatment with laminin on the formation of the scaffold was examined with atomic force microscopy. Cells from a human fetal neural progenitor cell line were cultured in the different matrices, as well as in a 2D culture system, and were subsequently analysed with antibody stainings against neuronal markers. In parallel, the survival rate of the cells was determined by a live/dead assay.</p> <p>Results</p> <p>Atomic force microscopy measurements demonstrated that the matrices are formed by networks of isolated PuraMatrix fibres and aggregates of fibres. An increase of the hydrogel concentration led to a decrease in the mesh size of the scaffolds and functionalisation with laminin promoted aggregation of the fibres (bundle formation), which further reduces the density of isolated fibres. We showed that laminin-functionalisation is essential for human neural progenitor cells to build up 3D-growth patterns, and that proliferation of the cells is also affected by the concentration of matrix. In addition we found that 3D-cultures enhanced neuronal differentiation and the survival rate of the cells compared to 2D-cultures.</p> <p>Conclusions</p> <p>Taken together, we have demonstrated a direct influence of the 3D-scaffold formation on the survival and neuronal differentiation of human neural progenitor cells. These findings emphasize the importance of optimizing 3D-scaffolds protocols prior to <it>in vivo </it>engraftment of stem and progenitor cells in the context of regenerative medicine.</p

    Universal ultrafast detector for short optical pulses based on graphene

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    Graphene has unique optical and electronic properties that make it attractive as an active material for broadband ultrafast detection. We present here a graphene-based detector that shows 40-picosecond electrical rise time over a spectral range that spans nearly three orders of magnitude, from the visible to the far-infrared. The detector employs a large area graphene active region with interdigitated electrodes that are connected to a log-periodic antenna to improve the long-wavelength collection efficiency, and a silicon carbide substrate that is transparent throughout the visible regime. The detector exhibits a noise-equivalent power of approximately 100 &#x00B5;W&#x00B7;Hz&#x2013;&#x00BD; and is characterized at wavelengths from 780 nm to 500 &#x00B5;m

    Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function

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    TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor–binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support
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