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  • 1
    Publication Date: 2015-08-11
    Description: Using a mathematical programming model of Norwegian agriculture, we explore interconnections between trade liberalization and reductions in greenhouse gas (GHG) emissions. We show that the Doha Round proposals for a new agreement on agriculture through the World Trade Organization would not generate significant reductions in emissions. Further trade liberalization would reduce emissions by cutting agricultural production but would not change production methods. Imposing a carbon tax would lead both to a reduction in output and the extensification of production. In contrast, if farmers are allowed to claim a credit for carbon sequestration the effect is to intensify agricultural production.
    Keywords: F18 - Trade and Environment, Q17 - Agriculture in International Trade, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 2
    Publication Date: 2016-07-09
    Description: Large rural-urban wage gaps observed in many developing countries are suggestive of barriers to migration that keep potential migrants in rural areas. Using long panel data spanning nearly two decades, I study the extent to which migration rates are constrained by liquidity constraints in rural Tanzania. The analysis begins by quantifying the impact of weather variation on household welfare. The results show how household consumption co-moves with temperature, rendering households vulnerable to local weather events. These temperature-induced income shocks are then found to inhibit long-term migration among men, thus preventing them from tapping into the opportunities brought about by geographical mobility.
    Keywords: O12 - Microeconomic Analyses of Economic Development, O15 - Human Resources ; Human Development ; Income Distribution ; Migration, Q54 - Climate ; Natural Disasters ; Global Warming, R23 - Regional Migration ; Regional Labor Markets ; Population
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 3
    Publication Date: 2016-06-21
    Description: Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by the Hi-C technology, but also provide additional novel details of chromosomal organizations. We predicted the chromatin interaction frequencies, topological domains and their states (e.g. active or repressive) for 98 additional cell types from Roadmap Epigenomics and ENCODE projects. A total of 131 protein-coding genes located near 78 preserved boundaries among 100 cell types are found to be significantly enriched in functional categories of the nucleosome organization and chromatin assembly. CITD and its predicted results can be used for complementing the topological domains derived from limited Hi-C data and facilitating the understanding of spatial principles underlying the chromosomal organization.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2016-07-09
    Description: Dam identification (DamID) is a powerful technique to generate genome-wide maps of chromatin protein binding. Due to its high sensitivity, it is particularly suited to study the genome interactions of chromatin proteins in small tissue samples in model organisms such as Drosophila . Here, we report an intein-based approach to tune the expression level of Dam and Dam-fusion proteins in Drosophila by addition of a ligand to fly food. This helps to suppress possible toxic effects of Dam. In addition, we describe a strategy for genetically controlled expression of Dam in a specific cell type in complex tissues. We demonstrate the utility of the latter by generating a glia-specific map of Polycomb in small samples of brain tissue. These new DamID tools will be valuable for the mapping of binding patterns of chromatin proteins in Drosophila tissues and especially in cell lineages.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2013-04-02
    Description: DNA methylation is one of the most important epigenetic alterations involved in the control of gene expression. Bisulfite sequencing of genomic DNA is currently the only method to study DNA methylation patterns at single-nucleotide resolution. Hence, next-generation sequencing of bisulfite-converted DNA is the method of choice to investigate DNA methylation profiles at the genome-wide scale. Nevertheless, whole genome sequencing for analysis of human methylomes is expensive, and a method for targeted gene analysis would provide a good alternative in many cases where the primary interest is restricted to a set of genes. Here, we report the successful use of a custom Agilent SureSelect Target Enrichment system for the hybrid capture of bisulfite-converted DNA. We prepared bisulfite-converted next-generation sequencing libraries, which are enriched for the coding and regulatory regions of 174 ADME genes (i.e. genes involved in the metabolism and distribution of drugs). Sequencing of these libraries on Illumina’s HiSeq2000 revealed that the method allows a reliable quantification of methylation levels of CpG sites in the selected genes, and validation of the method using pyrosequencing and the Illumina 450K methylation BeadChips revealed good concordance.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2015-04-14
    Description: Our article contributes to the emerging micro-level strand of the literature on the link between local variations in weather shocks and conflicts by focusing on a pixel-level analysis for North and South Sudan between 1997 and 2009. Temperature anomalies are found to strongly affect the risk of conflict, whereas the risk is expected to magnify in a range of 24–31% in the future under a median scenario. Our analysis also sheds light on the competition over natural resources, in particular water, as the main driver of such relationship in a region where pastoralism constitutes the dominant livelihood.
    Keywords: D74 - Conflict ; Conflict Resolution ; Alliances, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q54 - Climate ; Natural Disasters ; Global Warming, R11 - Regional Economic Activity: Growth, Development, and Changes
    Print ISSN: 1468-2702
    Electronic ISSN: 1468-2710
    Topics: Geography , Economics
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  • 7
    Publication Date: 2015-04-18
    Description: Climate change will most likely confront agricultural producers with natural, economic, and political conditions that have not previously been observed and are largely uncertain. As a consequence, extrapolation from past data reaches its limits, and a process-based analysis of farmer adaptation is required. Simulation of changes in crop yields using crop growth models is a first step in that direction. However, changes in crop yields are only one pathway through which climate change affects agricultural production. A meaningful process-based analysis of farmer adaptation requires a whole-farm analysis at the farm level. We use a highly disaggregated mathematical programming model to analyze farm-level climate change adaptation for a mountainous area in southwest Germany. Regional-level results are obtained by simulating each full-time farm holding in the study area. We address parameter uncertainty and model underdetermination using a cautious calibration approach and a comprehensive uncertainty analysis. We deal with the resulting computational burden using efficient experimental designs and high-performance computing. We show that in our study area, shifted crop management time slots can have potentially significant effects on agricultural supply, incomes, and various policy objectives promoted under German and European environmental policy schemes. The simulated effects are robust against model uncertainty and underline the importance of a comprehensive assessment of climate change impacts beyond merely looking at crop yield changes. Our simulations demonstrate how farm-level models can contribute to a process-based analysis of climate change adaptation if they are embedded into a systematic framework for treating inherent model uncertainty.
    Keywords: C61 - Optimization Techniques ; Programming Models ; Dynamic Analysis, C63 - Computational Techniques, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 8
    Publication Date: 2015-12-13
    Description: This article uses the 2007 Farm and Ranch Irrigation Survey database developed by the U.S. Department of Agriculture to assess the impact of water scarcity and climate on irrigation decisions for producers of specialty crops, wheat, and forage crops. We estimate an irrigation management model for major crops in the West Coast (California, Oregon, and Washington), which includes a farm-level equation of irrigated share and crop-specific equations of technology adoption and water application rate (orchard/vineyard, vegetable, wheat, alfalfa, hay, and pasture). We find that economic and physical water scarcity, climate, and extreme weather, such as frost, extreme heat, and drought, significantly impact producers’ irrigation decisions. Producers use sprinkler technologies or additional water applications to mitigate risk of crop damage from extreme weather. Water application rates are least responsive to surface water cost or groundwater well depth for producers of orchard/vineyard. Water supply institutions influence producers’ irrigation decisions. Producers who receive water from federal agencies use higher water application rates and are less likely to adopt water-saving irrigation technologies for some crops. Institutional arrangements, including access to distinct water sources (surface or ground) and whether surface water cost is fee based, also affect the responsiveness of water application rates to changes in surface water cost. The analysis provides valuable information about how producers in irrigated agricultural production systems would respond and adapt to water pricing policies and climate change.
    Keywords: Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q16 - R&D ; Agricultural Technology ; Agricultural Extension Services, Q18 - Agricultural Policy ; Food Policy, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 9
    Publication Date: 2015-07-18
    Description: How important is the Green Paradox? We address this question in three ways. First, we present a simple model explaining how announcing a future climate policy may increase carbon emissions today – the Green Paradox effect. This effect is a result of fossil fuel producers increasing their extraction today as a response to a reduction in future resource rents. Second, we examine the theoretical and empirical literature to assess whether green paradoxes are likely to occur, and if they are, whether they are big enough to be of concern for policy makers. We consider several factors that affect the existence of the green paradox, including long-term extraction costs, short-term extraction capacities, the mix of policy instruments, and potential spatial carbon leakage to countries that have no climate policy. We find that these and other factors can sometimes strengthen, but mostly weaken, the case for concern about the green paradox. Third, we identify the lessons the literature offers for policy makers. We argue that in designing climate policy, policy makers need to consider the supply side of the fossil fuel market.
    Keywords: H23 - Externalities ; Redistributive Effects ; Environmental Taxes and Subsidies, Q31 - Demand and Supply, Q38 - Government Policy, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 10
    Publication Date: 2015-07-18
    Description: Why have policies aimed at reducing the demand for carbon not succeeded in slowing down global carbon extraction and CO 2 emissions, and why have carbon prices failed to increase over the last three decades? This comment argues that this is because of the Green Paradox, that is, the anticipation of sales by resource owners who try to preempt the destruction of their markets by green policies. Reviewing some of the conditions under which strong and weak versions of the Green Paradox may emerge, it is argued that there is little hope that green replacement technologies will impose hard price constraints that would keep long-run extraction within a fixed carbon budget and that, therefore, even strong versions of the paradox cannot easily be avoided.
    Keywords: O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, Q32 - Exhaustible Resources and Economic Development, Q54 - Climate ; Natural Disasters ; Global Warming, H23 - Externalities ; Redistributive Effects ; Environmental Taxes and Subsidies
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 11
    Publication Date: 2015-07-18
    Description: This article examines how, in a world with incomplete coordination among countries, well-intentioned unilateral environmental policies may actually harm the global environment. This outcome is known as the "Green Paradox." The incentives for free-riding and the challenge of achieving an effective international environmental agreement are reviewed. I examine the various channels that lead to carbon leakage in static models of open economies, and report some simulation results. This is complemented by a review of the potential for Green Paradox outcomes in dynamic open-economy models in which forward-looking firms exploit an exhaustible resource. I show that border tax adjustments can lead to Green Paradox outcomes. I also discuss priorities for future research on environmental policies in a trading world that lacks a central enforcement agency.
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, Q42 - Alternative Energy Sources
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 12
    Publication Date: 2015-07-18
    Description: Climate change—and, by extension, climate policy—is beset with unknowns and unknowables. This "Reflections" article presents an overview of approaches to managing climate uncertainties, in the hopes of providing guidance for current policy decisions as well as future research. We propose the following guidance for policy makers: Treat climate change as a risk management problem; recognize that benefit-cost analysis is only the first of many steps in deciding on optimal climate policy; in assessing abatement choices, use a discount rate that declines over time; recognize the importance of framing, evidence, and connecting the dots; reward modesty. We suggest the following questions for consideration by researchers: Can we improve forecasting? Can we improve the way we address nonlinearities and possible irreversibilities? What other (sub)disciplines merit a closer look? How can we create the right incentives for updating and expanding economic damage functions and climate-economy models? What alternative decision criteria merit further exploration? What does ‘not knowing’ tell us?
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, D81 - Criteria for Decision-Making under Risk and Uncertainty
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 13
    Publication Date: 2016-08-20
    Description: A multi-year drought has taken a severe toll on the agricultural economy of California’s Central Valley. Index insurance is an instrument with the potential to protect water users from economic losses due to periodic water shortages. An index insurance product based on the Sacramento Index and adapted to the Central Valley Project water supply is proposed. To address the potential for intertemporal adverse selection, three product designs are suggested: (1) "early bird" insurance; (2) variable premium insurance; and (3) variable deductible insurance. The performance of the designs are assessed using loss functions from the Westlands Water District in the San Joaquin Valley.
    Keywords: Q14 - Agricultural Finance, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 14
    Publication Date: 2015-12-16
    Description: Many cancers comprise heterogeneous populations of cells at primary and metastatic sites throughout the body. The presence or emergence of distinct subclones with drug-resistant genetic and epigenetic phenotypes within these populations can greatly complicate therapeutic intervention. Liquid biopsies of peripheral blood from cancer patients have been suggested as an ideal means of sampling intratumor genetic and epigenetic heterogeneity for diagnostics, monitoring and therapeutic guidance. However, current molecular diagnostic and sequencing methods are not well suited to the routine assessment of epigenetic heterogeneity in difficult samples such as liquid biopsies that contain intrinsically low fractional concentrations of circulating tumor DNA (ctDNA) and rare epigenetic subclonal populations. Here we report an alternative approach, deemed DREAMing (Discrimination of Rare EpiAlleles by Melt), which uses semi-limiting dilution and precise melt curve analysis to distinguish and enumerate individual copies of epiallelic species at single-CpG-site resolution in fractions as low as 0.005%, providing facile and inexpensive ultrasensitive assessment of locus-specific epigenetic heterogeneity directly from liquid biopsies. The technique is demonstrated here for the evaluation of epigenetic heterogeneity at p14 ARF and BRCA1 gene-promoter loci in liquid biopsies obtained from patients in association with non-small cell lung cancer (NSCLC) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 15
    Publication Date: 2015-12-16
    Description: Bisulfite sequencing is a key methodology in epigenetics. However, the standard workflow of bisulfite sequencing involves heat and strongly basic conditions to convert the intermediary product 5,6-dihydrouridine-6-sulfonate (dhU6S) (generated by reaction of bisulfite with deoxycytidine (dC)) to uracil (dU). These harsh conditions generally lead to sample loss and DNA damage while milder conditions may result in incomplete conversion of intermediates to uracil. Both can lead to poor recovery of bisulfite-treated DNA by the polymerase chain reaction (PCR) as either damaged DNA and/or intermediates of bisulfite treatment are poor substrate for standard DNA polymerases. Here we describe an engineered DNA polymerase (5D4) with an enhanced ability to replicate and PCR amplify bisulfite-treated DNA due to an ability to bypass both DNA lesions and bisulfite intermediates, allowing significantly milder conversion conditions and increased sensitivity in the PCR amplification of bisulfite-treated DNA. Incorporation of the 5D4 DNA polymerase into the bisulfite sequencing workflow thus promises significant sensitivity and efficiency gains.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 16
    Publication Date: 2016-09-03
    Description: Nucleosomes, the fundamental subunits of eukaryotic chromatin, are organized with respect to transcriptional start sites. A major challenge to the persistence of this organization is the disassembly of nucleosomes during DNA replication. Here, we use complimentary approaches to map the locations of nucleosomes on recently replicated DNA. We find that nucleosomes are substantially realigned with promoters during the minutes following DNA replication. As a result, the nucleosomal landscape is largely re-established before newly replicated chromosomes are partitioned into daughter cells and can serve as a platform for the re-establishment of gene expression programmes. When the supply of histones is disrupted through mutation of the chaperone Caf1, a promoter-based architecture is generated, but with increased inter-nucleosomal spacing. This indicates that the chromatin remodelling enzymes responsible for spacing nucleosomes are capable of organizing nucleosomes with a range of different linker DNA lengths.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
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    Topics: Biology
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  • 17
    Publication Date: 2016-09-20
    Description: DNA methylation plays an important role in many biological processes. Existing epigenome-wide association studies (EWAS) have successfully identified aberrantly methylated genes in many diseases and disorders with most studies focusing on analysing methylation sites one at a time. Incorporating prior biological information such as biological networks has been proven to be powerful in identifying disease-associated genes in both gene expression studies and genome-wide association studies (GWAS) but has been under studied in EWAS. Although recent studies have noticed that there are differences in methylation variation in different groups, only a few existing methods consider variance signals in DNA methylation studies. Here, we present a network-assisted algorithm, NEpiC, that combines both mean and variance signals in searching for differentially methylated sub-networks using the protein–protein interaction (PPI) network. In simulation studies, we demonstrate the power gain from using both the prior biological information and variance signals compared to using either of the two or neither information. Applications to several DNA methylation datasets from the Cancer Genome Atlas (TCGA) project and DNA methylation data on hepatocellular carcinoma (HCC) from the Columbia University Medical Center (CUMC) suggest that the proposed NEpiC algorithm identifies more cancer-related genes and generates better replication results.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 18
    Publication Date: 2016-08-20
    Description: To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 19
    Publication Date: 2016-07-09
    Description: Climate change affects agriculture by altering not only output quantity, but also crop quality. We quantify the economic impacts of climate change on agriculture through changes in both quantity and quality, where quality is measured by crop grades. Our model controls for methodological issues regarding sample selection, aggregation, phenology, and nonlinearity. The empirical application to Japanese rice production indicates that temperature effects are asymmetric: quantity is especially vulnerable to cold, whereas quality is vulnerable to extremely high temperature. Using these results, we simulate the effect of global warming, and we find that warming (a 3 °C increase) increases farm revenues by improving yield but decreases revenues as a result of deteriorating quality. The net effect is negative, suggesting that quality matters more than quantity. The negative effect, however, can be mitigated by shifting cultivation periods and/or regions. Overall, our results suggest that the estimated impacts of climate change and adaptation strategies could be severely misleading unless quality is considered.
    Keywords: L15 - Information and Product Quality ; Standardization and Compatibility, Q10 - General, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 20
    Publication Date: 2015-05-21
    Description: Relying on census data collected in 2002 and historical weather data for Uganda, we estimate the impact of weather-induced internal migration on the probability for non-migrants living in the destination regions to be employed. Consistent with the prediction of a simple theoretical model, our results reveal a larger negative impact than the one documented for developed countries. They further show that this negative impact is significantly stronger in Ugandan regions with lower road density and therefore less conducive to capital mobility: a 10 percentage points increase in the net in-migration rate in these areas decreases the probability of being employed of non-migrants by more than 10 percentage points.
    Keywords: E24 - Employment ; Unemployment ; Wages ; Intergenerational Income Distribution, J21 - Labor Force and Employment, Size, and Structure, J61 - Geographic Labor Mobility ; Immigrant Workers, Q54 - Climate ; Natural Disasters ; Global Warming, R23 - Regional Migration ; Regional Labor Markets ; Population
    Print ISSN: 0258-6770
    Electronic ISSN: 1564-698X
    Topics: Economics
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  • 21
    Publication Date: 2015-04-18
    Description: This article explores the reduction potential of greenhouse gases for major pollution-emitting countries of the world using nonparametric productivity measurement methods and directional distance functions. In contrast to the existing literature, we apply optimization methods to endogenously determine optimal directions for the efficiency analysis. These directions represent the compromise of output enhancement and emissions reduction. The results show that for reasonable directions the adoption of best practices would lead to sizable emission reductions in a range of approximately 20% compared with current levels.
    Keywords: C14 - Semiparametric and Nonparametric Methods, D24 - Production ; Cost ; Capital and Total Factor Productivity ; Capacity, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 22
    Publication Date: 2015-02-18
    Description: The large number of chemical modifications that are found on the histone proteins of eukaryotic cells form multiple complex combinations, which can act as recognition signals for reader proteins. We have used peptide capture in conjunction with super-SILAC quantification to carry out an unbiased high-throughput analysis of the composition of protein complexes that bind to histone H3K9/S10 and H3K27/S28 methyl-phospho modifications. The accurate quantification allowed us to perform Weighted correlation network analysis (WGCNA) to obtain a systems-level view of the histone H3 histone tail interactome. The analysis reveals the underlying modularity of the histone reader network with members of nuclear complexes exhibiting very similar binding signatures, which suggests that many proteins bind to histones as part of pre-organized complexes. Our results identify a novel complex that binds to the double H3K9me3/S10ph modification, which includes Atrx, Daxx and members of the FACT complex. The super-SILAC approach allows comparison of binding to multiple peptides with different combinations of modifications and the resolution of the WGCNA analysis is enhanced by maximizing the number of combinations that are compared. This makes it a useful approach for assessing the effects of changes in histone modification combinations on the composition and function of bound complexes.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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  • 23
    Publication Date: 2015-01-29
    Description: The United States and Canada have seen a competitive and technological revolution in unconventional natural gas production in the 21 st Century—dramatically lowering the price of gas and displacing high-carbon coal with low-carbon gas for power generation. This gas revolution came from an earlier revolution in the regulation of gas pipelines, which ended the obstruction of gas markets by pipeline interests. Neither revolution has spread to Europe, where increasingly protectionist EU legislation has effectively blocked competitive pipeline entry and related gas markets. As a result, unconventional gas is untapped, coal displaces gas for power generation, and oil-linked gas prices have cost EU consumers a staggering $425 billion more than their US counterparts have paid since 2009 for about the same quantity of gas. Europe faces a serious institutional challenge to adopting the kind of pipeline regulation that facilitates the competitive flow of natural gas supplies and the accompanying lower carbon emissions. ( JEL : D23, K23, L14, L51, L95, N70, Q54)
    Keywords: D23 - Organizational Behavior ; Transaction Costs ; Property Rights, K23 - Regulated Industries and Administrative Law, L14 - Transactional Relationships ; Contracts and Reputation ; Networks, L51 - Economics of Regulation, L95 - Gas Utilities ; Pipelines ; Water Utilities, N70 - General, International, or Comparative, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 24
    Publication Date: 2015-01-29
    Description: Natural gas plays an important role in the global energy system as an input to power generation, heating, and industry. This article identifies key drivers and uncertainties for natural gas markets in the coming decades. These include the availability of natural gas from conventional and unconventional sources, the role of international trade, and the impact of climate policies. We build on model-based research as well as an up-to-date survey of natural gas resource availability. We find that natural gas is an abundant fossil fuel and that the Asia-Pacific region will be most important in future global natural gas markets, especially under stringent international climate change mitigation. This means that an increasingly large share of future natural gas trade flows and infrastructure expansions will be directed to the Asia-Pacific region and that the role of liquefied natural gas will continue to increase globally. ( JEL : C61, L71, Q33, Q37, Q54)
    Keywords: C61 - Optimization Techniques ; Programming Models ; Dynamic Analysis, L71 - Mining, Extraction, and Refining: Hydrocarbon Fuels, Q33 - Resource Booms, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 25
    Publication Date: 2015-01-29
    Description: Natural disasters may constitute a major shock to public finances and debt sustainability because of their impact on output and the need for government response with reconstruction and relief expenses. The question arises of whether governments can use financial development policy as the means to mitigate or insure against this negative fiscal impact. This paper uses a panel vector autoregressive model, estimated on annual data for high- and middle-income countries over 1975–2008, to study the role of debt market development and insurance penetration in enabling fiscal response after catastrophes. The authors find that countries with higher debt market development suffer smaller real consequences from disasters but that their deficits expand further following the mitigating fiscal response. Disasters in countries with high insurance penetration also experience smaller real consequences of disasters but without the need for further deficit expansions. From an ex-post perspective, the availability of insurance could offer the best mitigation approach against the real and fiscal consequences of disasters.
    Keywords: E32 - Business Fluctuations ; Cycles, H50 - General, H60 - General, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0258-6770
    Electronic ISSN: 1564-698X
    Topics: Economics
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  • 26
    Publication Date: 2014-11-28
    Description: Genome-wide assessment of protein–DNA interaction by chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) is a key technology for studying transcription factor (TF) localization and regulation of gene expression. Signal-to-noise-ratio and signal specificity in ChIP-seq studies depend on many variables, including antibody affinity and specificity. Thus far, efforts to improve antibody reagents for ChIP-seq experiments have focused mainly on generating higher quality antibodies. Here we introduce KOIN (knockout implemented normalization) as a novel strategy to increase signal specificity and reduce noise by using TF knockout mice as a critical control for ChIP-seq data experiments. Additionally, KOIN can identify ‘hyper ChIPable regions’ as another source of false-positive signals. As the use of the KOIN algorithm reduces false-positive results and thereby prevents misinterpretation of ChIP-seq data, it should be considered as the gold standard for future ChIP-seq analyses, particularly when developing ChIP-assays with novel antibody reagents.
    Keywords: Chromatin and Epigenetics
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  • 27
    Publication Date: 2015-07-10
    Description: We develop a general equilibrium framework, based on a specific-factors trade model, to quantify the medium-term household welfare impacts of global warming in rural India. Using an hedonic approach grounded in the theory combined with detailed microdata, we estimate that three decades of warming will reduce agricultural productivity in the range of 7%–13%, with the arid northwest of India especially hard hit. Our analysis shows that the proportional welfare cost of climate change is likely to be both modest and evenly distributed across percentiles of the per capita income distribution, but this latter conclusion emerges only when the flexibility of rural wages is taken into account.
    Keywords: Q17 - Agriculture in International Trade, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 28
    Publication Date: 2015-07-12
    Description: We present a capture-based approach for bisulfite-converted DNA that allows interrogation of pre-defined genomic locations, allowing quantitative and qualitative assessments of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) at CG dinucleotides and in non-CG contexts (CHG, CHH) in mammalian and plant genomes. We show the technique works robustly and reproducibly using as little as 500 ng of starting DNA, with results correlating well with whole genome bisulfite sequencing data, and demonstrate that human DNA can be tested in samples contaminated with microbial DNA. This targeting approach will allow cell type-specific designs to maximize the value of 5mC and 5hmC sequencing.
    Keywords: Chromatin and Epigenetics
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  • 29
    Publication Date: 2015-07-12
    Description: Androgen receptor (AR) variants (AR-Vs) expressed in prostate cancer (PCa) lack the AR ligand binding domain (LBD) and function as constitutively active transcription factors. AR-V expression in patient tissues or circulating tumor cells is associated with resistance to AR-targeting endocrine therapies and poor outcomes. Here, we investigated the mechanisms governing chromatin binding of AR-Vs with the goal of identifying therapeutic vulnerabilities. By chromatin immunoprecipitation and sequencing (ChIP-seq) and complementary biochemical experiments, we show that AR-Vs display a binding preference for the same canonical high-affinity androgen response elements (AREs) that are preferentially engaged by AR, albeit with lower affinity. Dimerization was an absolute requirement for constitutive AR-V DNA binding and transcriptional activation. Treatment with the bromodomain and extraterminal (BET) inhibitor JQ1 resulted in inhibition of AR-V chromatin binding and impaired AR-V driven PCa cell growth in vitro and in vivo . Importantly, this was associated with a novel JQ1 action of down-regulating AR-V transcript and protein expression. Overall, this study demonstrates that AR-Vs broadly restore AR chromatin binding events that are otherwise suppressed during endocrine therapy, and provides pre-clinical rationale for BET inhibition as a strategy for inhibiting expression and chromatin binding of AR-Vs in PCa.
    Keywords: Chromatin and Epigenetics
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  • 30
    Publication Date: 2016-02-03
    Description: The availability of practical mechanisms for comparing domestic efforts aimed at mitigating global climate change is important for the stability, equity, and efficiency of international climate agreements. We examine a variety of metrics that could be used to compare countries’ climate change mitigation efforts and illustrate their potential application to large developed and developing countries. Because there is no single, comprehensive, measurable metric that could be applied to all countries, we suggest using a set of indicators to characterize and compare mitigation effort, akin to using a set of economic statistics to indicate the health of the macroeconomy. Given the iterative pledge-and-review approach that is emerging in the current climate change negotiations, participation, commitment, and compliance could be enhanced if this set of indicators is able to show that all parties are doing their "fair share," both prospectively and retrospectively. The latter, in particular, highlights the need for a well-functioning policy surveillance regime. ( JEL : Q54, Q58, F55)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, Q58 - Government Policy, F55 - International Institutional Arrangements
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 31
    Publication Date: 2016-02-03
    Description: In this article, we provide an overview of the extensive literature on the impact of weather and climate on grapes and wine, with the goal of identifying how climate change is likely to affect their production. We first discuss the physical impact of weather on vine phenology (i.e., the timing of biological events such as bud break or flowering), berry composition, and yields. Then we examine the economic literature that measures the effects of temperature on wine quality, prices, costs, and profits and, based on this review, infer how climate change will affect these variables. We also describe what has been learned thus far about possible adaptation strategies for grape growers that would allow them to mitigate the economic effects of climate change. We conclude that climate change is likely to produce both winners and losers, with the winners being those located closer to the North and South Poles. There are also likely to be some substantial short-run costs as growers adapt to climate change. Nevertheless, wine making has survived through thousands of years of recorded history, a history that has included significant climate changes. ( JEL : Q13, Q18, Q54)
    Keywords: Q13 - Agricultural Markets and Marketing ; Cooperatives ; Agribusiness, Q18 - Agricultural Policy ; Food Policy, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 32
    Publication Date: 2016-02-03
    Description: This article reviews the recent literature on ex post evaluation of the impacts of the European Union (EU) Emissions Trading Scheme (ETS) on regulated firms in the industrial and power sectors. We summarize the findings from original research papers concerning three broadly defined impacts: carbon dioxide emissions, economic performance and competitiveness, and innovation. We conclude by highlighting gaps in the current literature and suggesting priorities for future research on this landmark policy. ( JEL : Q52, Q54, Q58)
    Keywords: Q52 - Pollution Control Costs ; Distributional Effects ; Employment Effects, Q54 - Climate ; Natural Disasters ; Global Warming, Q58 - Government Policy
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 33
    Publication Date: 2016-02-03
    Description: This article provides an introduction to the European Union (EU) Emissions Trading System (ETS). First we describe the legislative development of the EU ETS, its evolution from free allocation to auctioning and centralized allocation rules, its relationship to the Kyoto Protocol and other trading systems, and its relationship to other EU climate and energy policies. This is followed by an assessment of the performance of the EU ETS, which focuses in particular on emissions, allowance prices, and the use of offsets. We conclude with a discussion of the current debate about the future of the EU ETS and proposals for changes to both the EU ETS and the climate policy environment in which it operates. ( JEL : Q54, Q58)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, Q58 - Government Policy
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 34
    Publication Date: 2016-02-03
    Description: The December 2015 Conference of the Parties (COP) to the United Nations Framework Convention on Climate Change meetings in Paris are likely to yield a global agreement that will slow the world’s growth of greenhouse gas emissions, but this agreement is unlikely to guarantee a decline in global emissions in the near future. Given this reality, climate change adaptation is an increasingly important topic for discussion and study. Although much research has focused on the macroeconomic relationship between economic growth and temperature at the national and/or annual level, microeconomic analysis also offers valuable insights. This Reflections discusses recent work on household and firm responses to three climate change challenges: increased summer heat, higher food prices, and increased natural disaster risk. ( JEL : Q54)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 35
    Publication Date: 2016-02-20
    Description: Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/T-rich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10°C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to ‘phasing’ off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequence-dependent models.
    Keywords: Chromatin and Epigenetics
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  • 36
    Publication Date: 2016-02-20
    Description: The Illumina HumanMethylation450 BeadChip is increasingly utilized in epigenome-wide association studies, however, this array-based measurement of DNA methylation is subject to measurement variation. Appropriate data preprocessing to remove background noise is important for detecting the small changes that may be associated with disease. We developed a novel background correction method, ENmix, that uses a mixture of exponential and truncated normal distributions to flexibly model signal intensity and uses a truncated normal distribution to model background noise. Depending on data availability, we employ three approaches to estimate background normal distribution parameters using (i) internal chip negative controls, (ii) out-of-band Infinium I probe intensities or (iii) combined methylated and unmethylated intensities. We evaluate ENmix against other available methods for both reproducibility among duplicate samples and accuracy of methylation measurement among laboratory control samples. ENmix out-performed other background correction methods for both these measures and substantially reduced the probe-design type bias between Infinium I and II probes. In reanalysis of existing EWAS data we show that ENmix can identify additional CpGs, and results in smaller P -value estimates for previously-validated CpGs. We incorporated the method into R package ENmix , which is freely available from Bioconductor website.
    Keywords: Chromatin and Epigenetics
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  • 37
    Publication Date: 2016-02-20
    Description: In the estimation of Ricardian models the endogeneity of adaptation measures is typically ignored. In this article we propose a new estimation strategy that explicitly recognises the endogeneity of the farm type and irrigation to climate. Based on the latest census data on over 270,000 farms in Germany, we estimate a cross-sectional, spatial-IV model that decomposes the effects of climate on farm profitability into direct (unmediated) and indirect (mediated by the variables that reflect adaptation). Our results show that neglecting the endogenous nature of adaptation measures may substantially bias the magnitude of the total effect of climate on farm profitability.
    Keywords: C21 - Cross-Sectional Models ; Spatial Models ; Treatment Effect Models, C25 - Discrete Regression and Qualitative Choice Models, C36- Instrumental Variables (IV) Estimation, Q18 - Agricultural Policy ; Food Policy, Q51 - Valuation of Environmental Effects, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 38
    Publication Date: 2015-12-02
    Description: DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Recent developments in whole genome bisulfite sequencing (WGBS) technology have enabled genome-wide measurements of DNA methylation at single base pair resolution. Many experiments have been conducted to compare DNA methylation profiles under different biological contexts, with the goal of identifying differentially methylated regions (DMRs). Due to the high cost of WGBS experiments, many studies are still conducted without biological replicates. Methods and tools available for analyzing such data are very limited. We develop a statistical method, DSS-single, for detecting DMRs from WGBS data without replicates. We characterize the count data using a rigorous model that accounts for the spatial correlation of methylation levels, sequence depth and biological variation. We demonstrate that using information from neighboring CG sites, biological variation can be estimated accurately even without replicates. DMR detection is then carried out via a Wald test procedure. Simulations demonstrate that DSS-single has greater sensitivity and accuracy than existing methods, and an analysis of H1 versus IMR90 cell lines suggests that it also yields the most biologically meaningful results. DSS-single is implemented in the Bioconductor package DSS.
    Keywords: Chromatin and Epigenetics
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  • 39
    Publication Date: 2015-12-13
    Description: We investigate the effect of crop price and climate variables on rainfed corn and soybean yields and acreage in the United States using a large panel dataset for the 1977–2007 period. Instrumental variables are used to control for endogeneity of prices in yield and acreage regressions, while allowing for spatially auto-correlated errors. We find that an increase in corn price has a statistically significant positive impact on corn yield, but the effect of soybean price on soybean yields is not statistically significant. The estimated price elasticities of corn yield and acreage are 0.23 and 0.45, respectively. Of the increase in corn supply caused by an increase in corn price, we find that 33.8% is due to price-induced yield enhancement and 66.2% is due to price-induced acreage expansion. We also find that the impact of climate change on corn production ranges from $-$ 7% to $-$ 41% and on soybean ranges from $-$ 8% to $-$ 45%, depending on the climate change scenarios, time horizon, and global climate models used to predict climate change. We show that the aggregate net impact of omitting price variables is an overestimation of the effect of climate change on corn yield by up to 9% and on soybean yield by up to 15%.
    Keywords: Q11 - Aggregate Supply and Demand Analysis ; Prices, Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 40
    Publication Date: 2011-11-24
    Description: Looking into the future of agriculture raises three challenging questions: How can agriculture deal with an uncertain future? How do local vulnerabilities and global disparities respond to this uncertain future? How should we prioritise adaptation to overcome the resulting future risks? This paper analyses the broad question of how climate change science may provide some insights into these issues. The data provided for the analysis are the product of our new research on global impacts of climate change in agriculture. The questions are analysed across world regions to provide some thoughts on policy development.
    Keywords: N50 - General, International, or Comparative, Q18 - Agricultural Policy ; Food Policy, Q54 - Climate ; Natural Disasters ; Global Warming
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 41
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    Oxford University Press
    Publication Date: 2014-01-22
    Description: This literature review focuses on the relationships between population, poverty, and climate change. Developed countries are largely responsible for global warming, but the brunt of the fallout will be borne by developing countries in forms such as lower agricultural output, poorer health, and more frequent natural disasters. Although carbon emissions per capita have leveled off in developed countries, they are projected to rise rapidly in developing countries because of economic growth and population growth. Unfortunately, the latter will rise most notably in the poorest countries, combining with climate change to slow poverty reduction. These countries have many incentives to lower fertility. Previous studies indicate that in high fertility settings, fertility decline facilitates economic growth and poverty reduction. It also reduces the pressure on livelihoods and frees resources that can be used to cope with climate change. Moreover, slowing population growth helps avert some of the projected global warming, which will benefit the poorest countries far more than it will benefit developed countries that lie at higher latitudes and/or have more resources to cope with climate change. Natural experiments indicate that family-planning programs are effective and highly pro-poor in their impact. While the rest of the world wrestles with the complexities of reducing emissions, the poorest countries will benefit from simple programs to lower fertility.
    Keywords: Q56 - Environment and Development ; Environment and Trade ; Sustainability ; Environmental Accounting ; , Q54 - Climate ; Natural Disasters ; Global Warming, J13 - Fertility ; Family Planning ; Child Care ; Children ; Youth, J18 - Public Policy
    Print ISSN: 0257-3032
    Electronic ISSN: 1564-6971
    Topics: Economics
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  • 42
    Publication Date: 2013-12-07
    Description: The epigenetic modification of 5-hydroxymethylcytosine (5hmC) is receiving great attention due to its potential role in DNA methylation reprogramming and as a cell state identifier. Given this interest, it is important to identify reliable and cost-effective methods for the enrichment of 5hmC marked DNA for downstream analysis. We tested three commonly used affinity-based enrichment techniques; (i) antibody, (ii) chemical capture and (iii) protein affinity enrichment and assessed their ability to accurately and reproducibly report 5hmC profiles in mouse tissues containing high (brain) and lower (liver) levels of 5hmC. The protein-affinity technique is a poor reporter of 5hmC profiles, delivering 5hmC patterns that are incompatible with other methods. Both antibody and chemical capture-based techniques generate highly similar genome-wide patterns for 5hmC, which are independently validated by standard quantitative PCR (qPCR) and glucosyl-sensitive restriction enzyme digestion (gRES-qPCR). Both antibody and chemical capture generated profiles reproducibly link to unique chromatin modification profiles associated with 5hmC. However, there appears to be a slight bias of the antibody to bind to regions of DNA rich in simple repeats. Ultimately, the increased specificity observed with chemical capture-based approaches makes this an attractive method for the analysis of locus-specific or genome-wide patterns of 5hmC.
    Keywords: Chromatin and Epigenetics
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  • 43
    Publication Date: 2013-10-19
    Description: Methylation-specific fluorescence in situ hybridization (MeFISH) was developed for microscopic visualization of DNA methylation status at specific repeat sequences in individual cells. MeFISH is based on the differential reactivity of 5-methylcytosine and cytosine in target DNA for interstrand complex formation with osmium and bipyridine-containing nucleic acids (ICON). Cell nuclei and chromosomes hybridized with fluorescence-labeled ICON probes for mouse major and minor satellite repeats were treated with osmium for crosslinking. After denaturation, fluorescent signals were retained specifically at satellite repeats in wild-type, but not in DNA methyltransferase triple-knockout (negative control) mouse embryonic stem cells. Moreover, using MeFISH, we successfully detected hypomethylated satellite repeats in cells from patients with immunodeficiency, centromeric instability and facial anomalies syndrome and 5-hydroxymethylated satellite repeats in male germ cells, the latter of which had been considered to be unmethylated based on anti-5-methylcytosine antibody staining. MeFISH will be suitable for a wide range of applications in epigenetics research and medical diagnosis.
    Keywords: Chromatin and Epigenetics
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  • 44
    Publication Date: 2014-05-01
    Description: DNA methylation is an important epigenetic modification that has essential roles in cellular processes including gene regulation, development and disease and is widely dysregulated in most types of cancer. Recent advances in sequencing technology have enabled the measurement of DNA methylation at single nucleotide resolution through methods such as whole-genome bisulfite sequencing and reduced representation bisulfite sequencing. In DNA methylation studies, a key task is to identify differences under distinct biological contexts, for example, between tumor and normal tissue. A challenge in sequencing studies is that the number of biological replicates is often limited by the costs of sequencing. The small number of replicates leads to unstable variance estimation, which can reduce accuracy to detect differentially methylated loci (DML). Here we propose a novel statistical method to detect DML when comparing two treatment groups. The sequencing counts are described by a lognormal-beta-binomial hierarchical model, which provides a basis for information sharing across different CpG sites. A Wald test is developed for hypothesis testing at each CpG site. Simulation results show that the proposed method yields improved DML detection compared to existing methods, particularly when the number of replicates is low. The proposed method is implemented in the Bioconductor package DSS.
    Keywords: Chromatin and Epigenetics
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  • 45
    Publication Date: 2014-04-03
    Description: Epigenetic regulation of gene expression involves, besides DNA and histone modifications, the relative positioning of DNA sequences within the nucleus. To trace specific DNA sequences in living cells, we used programmable sequence-specific DNA binding of designer transcription activator-like effectors (dTALEs). We designed a recombinant dTALE (msTALE) with variable repeat domains to specifically bind a 19-bp target sequence of major satellite DNA. The msTALE was fused with green fluorescent protein (GFP) and stably expressed in mouse embryonic stem cells. Hybridization with a major satellite probe (3D-fluorescent in situ hybridization) and co-staining for known cellular structures confirmed in vivo binding of the GFP-msTALE to major satellite DNA present at nuclear chromocenters. Dual tracing of major satellite DNA and the replication machinery throughout S-phase showed co-localization during mid to late S-phase, directly demonstrating the late replication timing of major satellite DNA. Fluorescence bleaching experiments indicated a relatively stable but still dynamic binding, with mean residence times in the range of minutes. Fluorescently labeled dTALEs open new perspectives to target and trace DNA sequences and to monitor dynamic changes in subnuclear positioning as well as interactions with functional nuclear structures during cell cycle progression and cellular differentiation.
    Keywords: Chromatin and Epigenetics
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  • 46
    Publication Date: 2014-04-03
    Description: Coupling bisulfite conversion with next-generation sequencing (Bisulfite-seq) enables genome-wide measurement of DNA methylation, but poses unique challenges for mapping. However, despite a proliferation of Bisulfite-seq mapping tools, no systematic comparison of their genomic coverage and quantitative accuracy has been reported. We sequenced bisulfite-converted DNA from two tissues from each of two healthy human adults and systematically compared five widely used Bisulfite-seq mapping algorithms: Bismark, BSMAP, Pash, BatMeth and BS Seeker. We evaluated their computational speed and genomic coverage and verified their percentage methylation estimates. With the exception of BatMeth, all mappers covered 〉70% of CpG sites genome-wide and yielded highly concordant estimates of percentage methylation ( r 2 ≥ 0.95). Fourfold variation in mapping time was found between BSMAP (fastest) and Pash (slowest). In each library, 8–12% of genomic regions covered by Bismark and Pash were not covered by BSMAP. An experiment using simulated reads confirmed that Pash has an exceptional ability to uniquely map reads in genomic regions of structural variation. Independent verification by bisulfite pyrosequencing generally confirmed the percentage methylation estimates by the mappers. Of these algorithms, Bismark provides an attractive combination of processing speed, genomic coverage and quantitative accuracy, whereas Pash offers considerably higher genomic coverage.
    Keywords: Chromatin and Epigenetics
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  • 47
    Publication Date: 2014-04-05
    Description: It appears that news media and some pro-environmental organizations have the tendency to accentuate or even exaggerate the damage caused by climate change. This article provides a rationale for this tendency by using a modified International Environmental Agreement (IEA) model with asymmetric information. We find that the information manipulation has an instrumental value, as it ex post induces more countries to participate in an IEA, which will eventually enhance global welfare. From the ex ante perspective, however, the impact that manipulating information has on the level of participation in an IEA and on welfare is ambiguous.
    Keywords: D82 - Asymmetric and Private Information, L82 - Entertainment ; Media, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 48
    Publication Date: 2014-09-17
    Description: Three-dimensional organization of chromatin is fundamental for transcriptional regulation. Tissue-specific transcriptional programs are orchestrated by transcription factors and epigenetic regulators. The RUNX2 transcription factor is required for differentiation of precursor cells into mature osteoblasts. Although organization and control of the bone-specific Runx2-P1 promoter have been studied extensively, long-range regulation has not been explored. In this study, we investigated higher-order organization of the Runx2-P1 promoter during osteoblast differentiation. Mining the ENCODE database revealed interactions between Runx2-P1 and  Supt3h promoters in several non-mesenchymal human cell lines. Supt3h is a ubiquitously expressed gene located within the first intron of Runx2 . These two genes show shared synteny across species from humans to sponges. Chromosome conformation capture analysis in the murine pre-osteoblastic MC3T3-E1 cell line revealed increased contact frequency between Runx2-P1 and Supt3h promoters during differentiation. This increase was accompanied by enhanced DNaseI hypersensitivity along with RUNX2 and CTCF binding at the Supt3h promoter. Furthermore, interplasmid-3C and luciferase reporter assays showed that the Supt3h promoter can modulate Runx2-P1 activity via direct association. Taken together, our data demonstrate physical proximity between Runx2-P1 and Supt3h promoters, consistent with their syntenic nature. Importantly, we identify the Supt3h promoter as a potential regulator of the bone-specific Runx2-P1 promoter .
    Keywords: Chromatin and Epigenetics
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  • 49
    Publication Date: 2014-07-03
    Description: In this paper, after a review of the evolution of the literature on climate change economics in agriculture, I present some evidence of the impact of different moments of the distribution of rainfall on farmers risk aversion. It is found that while more rainfall is negatively associated with the probability of observing risk aversion, rainfall variability is positively correlated. This result highlights an important behavioural dimension of climatic factors.
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, Q56 - Environment and Development ; Environment and Trade ; Sustainability ; Environmental Accounting
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 50
    Publication Date: 2014-11-12
    Description: Understanding the role of a given transcription factor (TF) in regulating gene expression requires precise mapping of its binding sites in the genome. Chromatin immunoprecipitation-exo, an emerging technique using exonuclease to digest TF unbound DNA after ChIP, is designed to reveal transcription factor binding site (TFBS) boundaries with near-single nucleotide resolution. Although ChIP-exo promises deeper insights into transcription regulation, no dedicated bioinformatics tool exists to leverage its advantages. Most ChIP-seq and ChIP-chip analytic methods are not tailored for ChIP-exo, and thus cannot take full advantage of high-resolution ChIP-exo data. Here we describe a novel analysis framework, termed MACE (model-based analysis of ChIP-exo) dedicated to ChIP-exo data analysis. The MACE workflow consists of four steps: (i) sequencing data normalization and bias correction; (ii) signal consolidation and noise reduction; (iii) single-nucleotide resolution border peak detection using the Chebyshev Inequality and (iv) border matching using the Gale-Shapley stable matching algorithm. When applied to published human CTCF, yeast Reb1 and our own mouse ONECUT1/HNF6 ChIP-exo data, MACE is able to define TFBSs with high sensitivity, specificity and spatial resolution, as evidenced by multiple criteria including motif enrichment, sequence conservation, direct sequence pileup, nucleosome positioning and open chromatin states. In addition, we show that the fundamental advance of MACE is the identification of two boundaries of a TFBS with high resolution, whereas other methods only report a single location of the same event. The two boundaries help elucidate the in vivo binding structure of a given TF, e.g. whether the TF may bind as dimers or in a complex with other co-factors.
    Keywords: Chromatin and Epigenetics
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  • 51
    Publication Date: 2016-05-20
    Description: Epigenetic modifications of histone tails play an essential role in the regulation of eukaryotic transcription. Writer and eraser enzymes establish and maintain the epigenetic code by creating or removing posttranslational marks. Specific binding proteins, called readers, recognize the modifications and mediate epigenetic signalling. Here, we present a versatile assay platform for the investigation of the interaction between methyl lysine readers and their ligands. This can be utilized for the screening of small-molecule inhibitors of such protein–protein interactions and the detailed characterization of the inhibition. Our platform is constructed in a modular way consisting of orthogonal in vitro binding assays for ligand screening and verification of initial hits and biophysical, label-free techniques for further kinetic characterization of confirmed ligands. A stability assay for the investigation of target engagement in a cellular context complements the platform. We applied the complete evaluation chain to the Tudor domain containing protein Spindlin1 and established the in vitro test systems for the double Tudor domain of the histone demethylase JMJD2C. We finally conducted an exploratory screen for inhibitors of the interaction between Spindlin1 and H3K4me3 and identified A366 as the first nanomolar small-molecule ligand of a Tudor domain containing methyl lysine reader.
    Keywords: Chromatin and Epigenetics
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  • 52
    Publication Date: 2016-04-24
    Description: We construct a stochastic dynamic dual model to investigate the structural adjustment of two aggregate output and three aggregate input categories in US agriculture under stochastic climatic change. More than a century of national annual data (1910–2011) is used in the empirical analysis. No constraints on asset fixity are imposed. Results indicate that, with rational expectations, both output categories as well as all input categories exhibit quasi-fixity in response to market change and stochastic climate change. Crops adjust more than twice as fast as livestock—49% versus 20% of the way toward their long-run equilibrium in one year. Fertilizer adjusts most rapidly toward equilibrium levels (88% in one year), and capital adjusts most slowly (5% in one year). Labor oscillates rather than converging smoothly toward equilibrium; its distance from equilibrium is the same as if it adjusted 59% of the way toward its optimal level in one year. Failing to anticipate climate change dramatically slows the estimated rate of adjustment for two netputs and modestly speeds the rate for two others, thus likely increasing overall adjustment costs. Failing to account for uncertainty in anticipated climate change has little impact on adjustment rates.
    Keywords: Q11 - Aggregate Supply and Demand Analysis ; Prices, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 53
    Publication Date: 2016-04-08
    Description: The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons—GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.
    Keywords: Chromatin and Epigenetics
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  • 54
    Publication Date: 2016-04-21
    Description: Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a key technique in chromatin research. Although heavily applied, existing ChIP-seq protocols are often highly fine-tuned workflows, optimized for specific experimental requirements. Especially the initial steps of ChIP-seq, particularly chromatin shearing, are deemed to be exceedingly cell-type-specific, thus impeding any protocol standardization efforts. Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (NEXSON: Nuclei EXtraction by SONication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. By including NEXSON in ChIP-seq workflows, we completely eliminate the need for extensive optimization and sample-dependent adjustments. Apart from this significant simplification, our approach also provides the basis for a fully standardized ChIP-seq and yields highly reproducible transcription factor and histone modifications maps for a wide range of different cell types. Even small cell numbers (~10 000 cells per ChIP) can be easily processed without application of modified chromatin or library preparation protocols.
    Keywords: Chromatin and Epigenetics
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  • 55
    Publication Date: 2016-02-10
    Description: This study quantifies how leakage behavior from afforesting agricultural land affects the intensification of agricultural production. In particular, we examine the leakage percentage from carbon offset allowance at specific southern regions in the United States as a part of a carbon market. We use the Forest and Agriculture Sector Optimization Model-Greenhouse Gases model to examine responses between sectors as part of the regional afforestation policy analysis. Regional characteristics and a policy's time frame are found to play important roles in achieving net gains, in terms of greenhouse gases stored, from such regional policies. In some cases, however, leakage greater than 100% is evident.
    Keywords: Q23 - Forestry, Q54 - Climate ; Natural Disasters ; Global Warming, R14 - Land Use Patterns
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 56
    Publication Date: 2012-06-28
    Description: Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) is a halogenated nucleotide of low toxicity commonly used to monitor DNA replication. It is considered a valuable tool for in vitro and in vivo studies, including the detection of the small population of neural stem cells (NSC) in the mammalian brain. Here, we show that NSC grown in self-renewing conditions in vitro , when exposed to BrdU, lose the expression of stem cell markers like Nestin, Sox2 and Pax6 and undergo glial differentiation, strongly up-regulating the astrocytic marker GFAP. The onset of GFAP expression in BrdU exposed NSC was paralleled by a reduced expression of key DNA methyltransferases (DNMT) and a rapid loss of global DNA CpG methylation, as we determined by our specially developed analytic assay. Remarkably, a known DNA demethylating compound, 5-aza-2'-deoxycytidine (Decitabine), had similar effect on demethylation and differentiation of NSC. Since our key findings apply also to NSC derived from murine forebrain, our observations strongly suggest more caution in BrdU uses in stem cells research. We also propose that BrdU and its related substances may also open new opportunities for differentiation therapy in oncology.
    Keywords: Chromatin and Epigenetics
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  • 57
    Publication Date: 2012-06-28
    Description: In Escherichia coli , the SeqA protein binds specifically to GATC sequences which are methylated on the A of the old strand but not on the new strand. Such hemimethylated DNA is produced by progression of the replication forks and lasts until Dam methyltransferase methylates the new strand. It is therefore believed that a region of hemimethylated DNA covered by SeqA follows the replication fork. We show that this is, indeed, the case by using global ChIP on Chip analysis of SeqA in cells synchronized regarding DNA replication. To assess hemimethylation, we developed the first genome-wide method for methylation analysis in bacteria. Since loss of the SeqA protein affects growth rate only during rapid growth when cells contain multiple replication forks, a comparison of rapid and slow growth was performed. In cells with six replication forks per chromosome, the two old forks were found to bind surprisingly little SeqA protein. Cell cycle analysis showed that loss of SeqA from the old forks did not occur at initiation of the new forks, but instead occurs at a time point coinciding with the end of SeqA-dependent origin sequestration. The finding suggests simultaneous origin de-sequestration and loss of SeqA from old replication forks.
    Keywords: Chromatin and Epigenetics
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  • 58
    Publication Date: 2012-08-23
    Description: Live-cell measurement of protein binding to chromatin allows probing cellular biochemistry in physiological conditions, which are difficult to mimic in vitro . However, different studies have yielded widely discrepant predictions, and so it remains uncertain how to make the measurements accurately. To establish a benchmark we measured binding of the transcription factor p53 to chromatin by three approaches: fluorescence recovery after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS) and single-molecule tracking (SMT). Using new procedures to analyze the SMT data and to guide the FRAP and FCS analysis, we show how all three approaches yield similar estimates for both the fraction of p53 molecules bound to chromatin (only about 20%) and the residence time of these bound molecules (~1.8 s). We also apply these procedures to mutants in p53 chromatin binding. Our results support the model that p53 locates specific sites by first binding at sequence-independent sites.
    Keywords: Chromatin and Epigenetics
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  • 59
    Publication Date: 2013-11-22
    Description: Following the failure of legislative proposals for a multi-sector greenhouse gas (GHG) cap-and-trade policy, the shift in focus to energy sector policies ignores the perhaps substantial potential for GHG mitigation from agriculture/forestry. We review estimates of the current U.S. agriculture sector contribution to GHG mitigation from a portfolio of existing sector policies in bioenergy, conservation, and research and development to compare accomplishments across programs. We then consider what opportunities and challenges may exist for increasing sector GHG mitigation by retargeting and/or expanding current programs—or for bioenergy-related mitigation, implementing proposed new programs—to serve as an alternative to cap-and-trade.
    Keywords: Q16 - R&D ; Agricultural Technology ; Agricultural Extension Services, Q42 - Alternative Energy Sources, Q54 - Climate ; Natural Disasters ; Global Warming, Q58 - Government Policy
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 60
    Publication Date: 2013-11-22
    Description: This paper explores federal policies, other than a carbon price, for reducing emissions from the electric power sector. These policies fall into two major categories: policies that encourage the development of non- or low-emitting energy sources, and regulatory policies under existing legal authority (primarily the Clean Air Act). The paper provides an overview of policy options and a few concrete proposals, along with a summary of insights from economists on their advantages and disadvantages. Economists generally disfavor investment subsidies, but comparing other policy options, including regulatory approaches, technology mandates, and production subsidies, is complex. Excluding existing clean generation from incentive policies is tempting but can lead to perverse outcomes.
    Keywords: L94 - Electric Utilities, Q54 - Climate ; Natural Disasters ; Global Warming
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    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 61
    Publication Date: 2016-12-01
    Description: The study of changes in protein–DNA interactions measured by ChIP-seq on dynamic systems, such as cell differentiation, response to treatments or the comparison of healthy and diseased individuals, is still an open challenge. There are few computational methods comparing changes in ChIP-seq signals with replicates. Moreover, none of these previous approaches addresses ChIP-seq specific experimental artefacts arising from studies with biological replicates. We propose THOR, a Hidden Markov Model based approach, to detect differential peaks between pairs of biological conditions with replicates. THOR provides all pre- and post-processing steps required in ChIP-seq analyses. Moreover, we propose a novel normalization approach based on housekeeping genes to deal with cases where replicates have distinct signal-to-noise ratios. To evaluate differential peak calling methods, we delineate a methodology using both biological and simulated data. This includes an evaluation procedure that associates differential peaks with changes in gene expression as well as histone modifications close to these peaks. We evaluate THOR and seven competing methods on data sets with distinct characteristics from in vitro studies with technical replicates to clinical studies of cancer patients. Our evaluation analysis comprises of 13 comparisons between pairs of biological conditions. We show that THOR performs best in all scenarios.
    Keywords: Chromatin and Epigenetics
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  • 62
    Publication Date: 2016-12-04
    Description: Recently, a number of advances have been implemented into the core ChIP-seq (chromatin immunoprecipitation coupled with next-generation sequencing) methodology to streamline the process, reduce costs or improve data resolution. Several of these emerging ChIP-based methods perform additional chemical steps on bead-bound immunoprecipitated chromatin, posing a challenge for generating similarly treated input controls required for artifact removal during bioinformatics analyses. Here we present a versatile method for producing technique-specific input controls for ChIP-based methods that utilize additional bead-bound processing steps. This reported method, termed protein attached chromatin capture (PAtCh-Cap), relies on the non-specific capture of chromatin-bound proteins via their carboxylate groups, leaving the DNA accessible for subsequent chemical treatments in parallel with chromatin separately immunoprecipitated for the target protein. Application of this input strategy not only significantly enhanced artifact removal from ChIP-exo data, increasing confidence in peak identification and allowing for de novo motif searching, but also afforded discovery of a novel CTCF binding motif.
    Keywords: Chromatin and Epigenetics
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  • 63
    Publication Date: 2014-03-07
    Description: Within the European Union, it is agreed that watershed-based management of water quality problems is more efficient than centralised arrangements. In this study, a mechanism for allocating international funds to watershed authorities for nitrogen abatement in the presence of moral hazard is investigated. The results show that when there is a risk of climate change, the cost of moral hazard to the international funding agency can be high if there is a moderate likelihood of climate change and the watershed authority is guaranteed a high minimum compensation.
    Keywords: Q53 - Air Pollution ; Water Pollution ; Noise ; Hazardous Waste ; Solid Waste ; Recycling, Q54 - Climate ; Natural Disasters ; Global Warming, Q58 - Government Policy
    Print ISSN: 0165-1587
    Electronic ISSN: 1464-3618
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 64
    Publication Date: 2014-07-23
    Description: In the United States, climate change is likely to increase average daily temperatures and the frequency of heat waves, which can reduce meat and milk production in animals. Methods that livestock producers use to mitigate thermal stress—including modifications to animal management or housing—tend to increase production costs. We use operation-level economic data coupled with finely-scaled climate data to estimate how the local thermal environment affects the technical efficiency of dairies across the United States. We then use this information to estimate the possible decline in milk production in 2030 resulting from climate change-induced heat stress under the simplifying assumptions that the production technology, location of production, and other factors are held constant. For four climate model scenarios, the results indicate modest heat-stress-related production declines by 2030, with the largest declines occurring in the southern states.
    Keywords: D24 - Production ; Cost ; Capital and Total Factor Productivity ; Capacity, Q12 - Micro Analysis of Farm Firms, Farm Households, and Farm Input Markets, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 65
    Publication Date: 2014-07-23
    Description: A growing body of evidence shows a causal relationship between extreme weather events and civil conflict incidence at the global level. We find that this causality is also valid for droughts and local violent conflicts in a within-country setting over a short time frame in the case of Somalia. We estimate that a one standard deviation increase in drought intensity and length raises the likelihood of conflict by 62%. We also find that drought affects conflict through livestock price changes, establishing livestock markets as the primary channel of transmission in Somalia.
    Keywords: D74 - Conflict ; Conflict Resolution ; Alliances, O12 - Microeconomic Analyses of Economic Development, Q11 - Aggregate Supply and Demand Analysis ; Prices, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 66
    Publication Date: 2014-07-23
    Description: Due to the failure of international efforts to limit atmospheric concentrations of greenhouse gases, consideration is now being given to solar geoengineering—a deliberate intervention to limit global warming without altering the atmospheric concentration of greenhouse gases. In contrast to emission cuts, geoengineering is expected to be cheap, quick to lower temperature, and feasible through the use of a single intervention. However, geoengineering is an imperfect substitute for emission reductions and will likely have undesirable side effects, only some of which can be anticipated before geoengineering is deployed. Most importantly, because geoengineering can be undertaken unilaterally, it creates issues of governance: Who gets to decide if, when, and how geoengineering should be attempted? This article provides an introduction to the key issues surrounding the governance of this unprecedented technology. ( JEL : Q54, F53, K33)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming, F53 - International Agreements and Observance ; International Organizations, K33 - International Law
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 67
    Publication Date: 2014-07-23
    Description: Climate engineering measures are designed to either reduce atmospheric carbon concentration (by growing trees or spreading iron in the ocean, for example) or directly influence the radiation reaching or leaving the earth (by injecting sulfur into the stratosphere or modifying cloud formations, for example) to compensate for greenhouse gas–induced warming. The former measures are termed carbon dioxide removal (CDR), which we characterize as a low-leverage causative approach, and the latter are termed radiation management (RM), which we characterize as a high-leverage symptomatic approach. There are similarities between CDR and emission control. Accordingly, benefit-cost analysis can be used to assess certain CDR measures. By contrast, high-leverage RM represents a genuinely new option in the climate change response portfolio, at first glance promising insurance against fat-tail climate change risks. However, the persistent intrinsic uncertainties of RM suggest that any cautious climate risk management approach should consider RM as a complement to (rather than a substitute for) emission control at best. Moreover, the complexity of the earth system imposes major limitations on the ability of research to reduce these uncertainties. Thus we argue that a research strategy is needed that focuses on increasing our basic understanding of the earth system and conducting comprehensive assessments of the risk(s) associated with both climate change and the deployment of climate engineering. ( JEL : Q52, Q54, Q55)
    Keywords: Q52 - Pollution Control Costs ; Distributional Effects ; Employment Effects, Q54 - Climate ; Natural Disasters ; Global Warming, Q55 - Technological Innovation
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 68
    Publication Date: 2014-07-23
    Description: Climate scientists, and natural scientists more generally, believe that climate change is a major, perhaps the most important, problem facing humankind this century, and that it is increasingly linked to extreme weather events. However, the impression one gets from much of the economic literature, particularly simulations from integrated assessment models used in policy analysis, is that the potential impacts of climate change are not large enough to warrant aggressive mitigation efforts in the near term. Although these models represent an important step in the needed interdisciplinary analysis of climate change by elucidating the links between climate and economy, we argue that they grossly underestimate potential impacts and associated damages because they (and the related policy analyses) fail to adequately capture extreme conditions, catastrophic events, and tipping points that trigger irreversible changes in the climate system, as well as impacts on the natural environment that cannot be monetized. Because the most severe impacts are expected in the later years of this century and beyond, discounting is crucial, and we argue that the appropriate rate is well below market rates. Moreover, we show that in the uniquely long period relevant to climate policy, the irreversibility of climate changes and impacts is more serious than the irreversibility of proposed mitigation measures. We conclude that an aggressive mitigation policy is warranted, one that holds further increases in global mean temperature to the scientific consensus on what is required to avoid the worst impacts, and that such a policy can be achieved at a cost that is well below potential damages. ( JEL : Q54)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 69
    Publication Date: 2013-01-20
    Description: Genomic deletions induced by imprecise excision of transposons have been used to disrupt gene functions in Drosophila . To determine the excision properties of Tol2 , a popular transposon in zebrafish, we took advantage of two transgenic zebrafish lines Et(gata2a:EGFP)pku684 and Et(gata2a:EGFP)pku760 , and mobilized the transposon by injecting transposase mRNA into homozygous transgenic embryos. Footprint analysis showed that the Tol2 transposons were excised in either a precise or an imprecise manner. Furthermore, we identified 1093-bp and 1253-bp genomic deletions in Et(gata2a:EGFP)pku684 founder embryos flanking the 5' end of the original Tol2 insertion site, and a 1340-bp deletion in the Et(gata2a:EGFP)pku760 founder embryos flanking the 3' end of the insertion site. The mosaic Et(gata2a:EGFP)pku684 embryos were raised to adulthood and screened for germline transmission of Tol2 excision in their F 1 progeny. On average, ~42% of the F 1 embryos displayed loss or altered EGFP patterns, demonstrating that this transposon could be efficiently excised from the zebrafish genome in the germline. Furthermore, from 59 founders, we identified one that transmitted the 1093-bp genomic deletion to its offspring. These results suggest that imprecise Tol2 transposon excision can be used as an alternative strategy to achieve gene targeting in zebrafish.
    Keywords: Chromatin and Epigenetics
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  • 70
    Publication Date: 2012-09-27
    Description: DNA methylation plays a key role in epigenetic regulation of eukaryotic genomes. Hence the genome-wide distribution of 5-methylcytosine, or the methylome, has been attracting intense attention. In recent years, whole-genome bisulfite sequencing (WGBS) has enabled methylome analysis at single-base resolution. However, WGBS typically requires microgram quantities of DNA as well as global PCR amplification, thereby precluding its application to samples of limited amounts. This is presumably because bisulfite treatment of adaptor-tagged templates, which is inherent to current WGBS methods, leads to substantial DNA fragmentation. To circumvent the bisulfite-induced loss of intact sequencing templates, we conceived an alternative method termed Post-Bisulfite Adaptor Tagging (PBAT) wherein bisulfite treatment precedes adaptor tagging by two rounds of random primer extension. The PBAT method can generate a substantial number of unamplified reads from as little as subnanogram quantities of DNA. It requires only 100 ng of DNA for amplification-free WGBS of mammalian genomes. Thus, the PBAT method will enable various novel applications that would not otherwise be possible, thereby contributing to the rapidly growing field of epigenomics.
    Keywords: Chromatin and Epigenetics
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  • 71
    Publication Date: 2012-11-04
    Description: The mammalian thymine DNA glycosylase (TDG) is implicated in active DNA demethylation via the base excision repair pathway. TDG excises the mismatched base from G:X mismatches, where X is uracil, thymine or 5-hydroxymethyluracil (5hmU). These are, respectively, the deamination products of cytosine, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). In addition, TDG excises the Tet protein products 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) but not 5hmC and 5mC, when paired with a guanine. Here we present a post-reactive complex structure of the human TDG domain with a 28-base pair DNA containing a G:5hmU mismatch. TDG flips the target nucleotide from the double-stranded DNA, cleaves the N -glycosidic bond and leaves the C1' hydrolyzed abasic sugar in the flipped state. The cleaved 5hmU base remains in a binding pocket of the enzyme. TDG allows hydrogen-bonding interactions to both T/U-based (5hmU) and C-based (5caC) modifications, thus enabling its activity on a wider range of substrates. We further show that the TDG catalytic domain has higher activity for 5caC at a lower pH (5.5) as compared to the activities at higher pH (7.5 and 8.0) and that the structurally related Escherichia coli mismatch uracil glycosylase can excise 5caC as well. We discuss several possible mechanisms, including the amino-imino tautomerization of the substrate base that may explain how TDG discriminates against 5hmC and 5mC.
    Keywords: Chromatin and Epigenetics
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  • 72
    Publication Date: 2013-08-28
    Description: Combinations of histone modifications have significant biological roles, such as maintenance of pluripotency and cancer development, but cannot be analyzed at the single cell level. Here, we visualized a combination of histone modifications by applying the in situ proximity ligation assay, which detects two proteins in close vicinity (~30 nm). The specificity of the method [designated as imaging of a combination of histone modifications (iChmo)] was confirmed by positive signals from H3K4me3/acetylated H3K9, H3K4me3/RNA polymerase II and H3K9me3/H4K20me3, and negative signals from H3K4me3/H3K9me3. Bivalent modification was clearly visualized by iChmo in wild-type embryonic stem cells (ESCs) known to have it, whereas rarely in Suz12 knockout ESCs and mouse embryonic fibroblasts known to have little of it. iChmo was applied to analysis of epigenetic and phenotypic changes of heterogeneous cell population, namely, ESCs at an early stage of differentiation, and this revealed that the bivalent modification disappeared in a highly concerted manner, whereas phenotypic differentiation proceeded with large variations among cells. Also, using this method, we were able to visualize a combination of repressive histone marks in tissue samples. The application of iChmo to samples with heterogeneous cell population and tissue samples is expected to clarify unknown biological and pathological significance of various combinations of epigenetic modifications.
    Keywords: Chromatin and Epigenetics
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  • 73
    Publication Date: 2013-03-13
    Description: Nucleosome positioning on the chromatin strand plays a critical role in regulating accessibility of DNA to transcription factors and chromatin modifying enzymes. Hence, detailed information on nucleosome depletion or movement at cis -acting regulatory elements has the potential to identify predicted binding sites for trans -acting factors. Using a novel method based on enrichment of mononucleosomal DNA by bacterial artificial chromosome hybridization, we mapped nucleosome positions by deep sequencing across 250 kb, encompassing the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. CFTR shows tight tissue-specific regulation of expression, which is largely determined by cis -regulatory elements that lie outside the gene promoter. Although multiple elements are known, the repertoire of transcription factors that interact with these sites to activate or repress CFTR expression remains incomplete. Here, we show that specific nucleosome depletion corresponds to well-characterized binding sites for known trans -acting factors, including hepatocyte nuclear factor 1, Forkhead box A1 and CCCTC-binding factor. Moreover, the cell-type selective nucleosome positioning is effective in predicting binding sites for novel interacting factors, such as BAF155. Finally, we identify transcription factor binding sites that are overrepresented in regions where nucleosomes are depleted in a cell-specific manner. This approach recognizes the glucocorticoid receptor as a novel trans -acting factor that regulates CFTR expression in vivo .
    Keywords: Chromatin and Epigenetics
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  • 74
    Publication Date: 2013-11-02
    Description: Here, we describe an approach to isolate native chromatin sections without genomic engineering for label-free proteomic identification of associated proteins and histone post-translational modifications. A transcription activator-like (TAL) protein A fusion protein was designed to recognize a unique site in the yeast GAL1 promoter. The TAL-PrA fusion enabled chromatin affinity purification (ChAP) of a small section of native chromatin upstream from the GAL1 locus, permitting mass spectrometric (MS) identification of proteins and histone post-translational modifications regulating galactose-induced transcription. This TAL-ChAP-MS approach allows the biochemical isolation of a specific native genomic locus for proteomic studies and will provide for unprecedented objective insight into protein and epigenetic mechanisms regulating site-specific chromosome metabolism.
    Keywords: Chromatin and Epigenetics
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  • 75
    Publication Date: 2014-01-28
    Description: Uncertainty is intrinsic to climate change: we know that the climate is changing but not precisely how fast or in what ways. Nor do we understand fully the social and economic consequences of these changes or the options that will be available for reducing climate change. Furthermore, the uncertainty about these issues is not readily quantified in probabilistic terms: we are facing deep uncertainty rather than known risks. We argue that this may render the classical expected utility framework for decision making under uncertainty of limited value for informing climate policy. We review the sources of uncertainty about all aspects of climate change, separate these into scientific and socioeconomic components, and examine their relative importance. Then we review decision-making frameworks that may be more appropriate in the absence of unique probabilities including nonprobabilistic approaches and those based on multiple priors, and we discuss their application in the context of climate change economics. ( JEL : D81, Q54)
    Keywords: D81 - Criteria for Decision-Making under Risk and Uncertainty, Q54 - Climate ; Natural Disasters ; Global Warming
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 76
    Publication Date: 2015-11-17
    Description: Sequencing DNA fragments associated with proteins following in vivo cross-linking with formaldehyde (known as ChIP-seq) has been used extensively to describe the distribution of proteins across genomes. It is not widely appreciated that this method merely estimates a protein's distribution and cannot reveal changes in occupancy between samples. To do this, we tagged with the same epitope orthologous proteins in Saccharomyces cerevisiae and Candida glabrata , whose sequences have diverged to a degree that most DNA fragments longer than 50 bp are unique to just one species. By mixing defined numbers of C. glabrata cells (the calibration genome) with S. cerevisiae samples (the experimental genomes) prior to chromatin fragmentation and immunoprecipitation, it is possible to derive a quantitative measure of occupancy (the occupancy ratio – OR) that enables a comparison of occupancies not only within but also between genomes. We demonstrate for the first time that this ‘internal standard’ calibration method satisfies the sine qua non for quantifying ChIP-seq profiles, namely linearity over a wide range. Crucially, by employing functional tagged proteins, our calibration process describes a method that distinguishes genuine association within ChIP-seq profiles from background noise. Our method is applicable to any protein, not merely highly conserved ones, and obviates the need for the time consuming, expensive, and technically demanding quantification of ChIP using qPCR, which can only be performed on individual loci. As we demonstrate for the first time in this paper, calibrated ChIP-seq represents a major step towards documenting the quantitative distributions of proteins along chromosomes in different cell states, which we term biological chromodynamics.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 77
    Publication Date: 2015-08-18
    Description: Stochastic epigenetic changes drive biological processes, such as development, aging and disease. Yet, epigenetic information is typically collected from millions of cells, thereby precluding a more precise understanding of cell-to-cell variability and the pathogenic history of epimutations. Here we present a novel procedure for directly detecting epimutations in DNA methylation patterns using single-cell, locus-specific bisulfite sequencing (SLBS). We show that within gene promoter regions of mouse hepatocytes the epimutation rate is two orders of magnitude higher than the mutation rate.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 78
    Publication Date: 2016-01-09
    Description: Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 79
    Publication Date: 2016-12-07
    Description: Much attention has been paid to the potential role that climate and food security has on conflict, especially in the Middle East. However, there has been little critical examination beyond the statistical correlation of events, which demonstrates whether a causal link exists and if it does, what can be done about it. This paper explores the conceptual linkages between food and conflict and attempts to draw attention to the opportunity cost of conflict as the nexus for decision-making in this context.
    Keywords: D74 - Conflict ; Conflict Resolution ; Alliances, Q18 - Agricultural Policy ; Food Policy, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 80
    Publication Date: 2016-12-07
    Description: What are second-generation (2G) biofuel technologies worth to global society? A dynamic, economic model is used to assess the impact that introducing 2G biofuels technology has on crops, livestock, biofuels, forestry, and environmental services, as well as greenhouse gas emissions. Under baseline conditions, this amounts to $64 billion and is $84 billion under the optimistic technology case, suggesting that investing in 2G technology could be appropriate. Under greenhouse gas regulation, global valuation more than doubles to $139 and $174 billion, respectively. A flat energy price scenario eliminates the value of 2G technology to society.
    Keywords: Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q42 - Alternative Energy Sources, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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  • 81
    Publication Date: 2017-01-05
    Description: The system of prior appropriation in the Western Unites States prioritizes property rights for water based on the establishment of beneficial use, creating a hierarchy where rights initiated first are more secure. I estimate the demand for security in water rights through their capitalization in agricultural property markets in the Yakima River Basin, a major watershed in Washington State. All water rights are satisfied in an average year, so the relative value of secure property rights is a function of water supply volatility and the costs of droughts are predominantly born by those with weak rights. In aggregate, security in water rights does not capitalize into property values at the irrigation district level; however, there is heterogeneity in the premium for secure water rights. The lack of a premium for district-level water security is robust to a variety of econometric methods to account for correlated district unobservables, and the null result produces an economically significant upper bound on the value to water security for the district. The ability for farmers to adapt to water supply volatility, as well as expectations about water markets and government infrastructure investment, are leading explanations for the lack of an aggregate premium. These explanations are supported by the pattern of heterogeneity in the water security premium.
    Keywords: Q15 - Land Ownership and Tenure ; Land Reform ; Land Use ; Irrigation, Q21 - Demand and Supply, Q24 - Land, Q25 - Water, Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 0002-9092
    Electronic ISSN: 1467-8276
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
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