ALBERT

Description: Tandem repeats (TRs) are often present in proteins with crucial functions, responsible for resistance, pathogenicity and associated with infectious or neurodegenerative diseases. This motivates numerous studies of TRs and their evolution, requiring accurate multiple sequence alignment. TRs may be lost or inserted at any position of a TR region by replication slippage or recombination, but current methods assume fixed unit boundaries, and yet are of high complexity. We present a new global graph-based alignment method that does not restrict TR unit indels by unit boundaries. TR indels are modeled separately and penalized using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of reconstructed alignments, disentangling TRs and measuring indel events and rates in a biologically meaningful way. Our method detects not only duplication events but also all changes in TR regions owing to recombination, strand slippage and other events inserting or deleting TR units. We evaluate our method by simulation incorporating TR evolution, by either sampling TRs from a profile hidden Markov model or by mimicking strand slippage with duplications. The new method is illustrated on a family of type III effectors, a pathogenicity determinant in agriculturally important bacteria Ralstonia solanacearum. We show that TR indel rate variation contributes to the diversification of this protein family.

Description: The introduction of next generation sequencing methods in genome studies has made it possible to shift research from a gene-centric approach to a genome wide view. Although methods and tools to detect single nucleotide polymorphisms are becoming more mature, methods to identify and visualize structural variation (SV) are still in their infancy. Most genome browsers can only compare a given sequence to a reference genome; therefore, direct comparison of multiple individuals still remains a challenge. Therefore, the implementation of efficient approaches to explore and visualize SVs and directly compare two or more individuals is desirable. In this article, we present a visualization approach that uses space-filling Hilbert curves to explore SVs based on both read-depth and pair-end information. An interactive open-source Java application, called Meander , implements the proposed methodology, and its functionality is demonstrated using two cases. With Meander , users can explore variations at different levels of resolution and simultaneously compare up to four different individuals against a common reference. The application was developed using Java version 1.6 and Processing.org and can be run on any platform. It can be found at http://homes.esat.kuleuven.be/~bioiuser/meander .

Description: A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/ .

Description: We present high-resolution tomographic images in source areas of 26 large crustal earthquakes ( M 6.0–7.2) which occurred in Northeast Japan (Tohoku) during the past 120 yr from 1894 to 2014. Prominent low-velocity (low- V ) and high Poisson's ratio (high- ) anomalies are revealed in the crust and mantle wedge under the source areas. Beneath the volcanic front and backarc areas, the low- V and high- zones reflect arc-magma related high-temperature anomalies which are produced by joint effects of corner flow in the mantle wedge and fluids from dehydration of the subducting Pacific slab. The hot anomalies cause locally thinning and weakening of the brittle seismogenic layer above them. Low-frequency micro-earthquakes are observed in the lower crust and uppermost mantle in or around the low- V zones, which reflect ascending of arc magma and fluids from the mantle wedge to the crust. No volcano and magma exist in the forearc area due to low temperature there, hence the low- V zones in the forearc reflect fluids from the slab dehydration. The ascending fluids may have produced a ‘water wall’ in the mantle wedge and crust beneath the forearc area. When the water enters active faults in the crust, the fault-zone friction is reduced and so large earthquakes can be induced. These results indicate that the nucleation of a large earthquake is not entirely a mechanical process, but is closely associated with subduction dynamics and physical and chemical properties of rocks in the crust and upper mantle. In particular, arc magma and fluids play an important role in the seismogenesis.

Description: It is now known that unwanted noise and unmodeled artifacts such as batch effects can dramatically reduce the accuracy of statistical inference in genomic experiments. These sources of noise must be modeled and removed to accurately measure biological variability and to obtain correct statistical inference when performing high-throughput genomic analysis. We introduced surrogate variable analysis (sva) for estimating these artifacts by (i) identifying the part of the genomic data only affected by artifacts and (ii) estimating the artifacts with principal components or singular vectors of the subset of the data matrix. The resulting estimates of artifacts can be used in subsequent analyses as adjustment factors to correct analyses. Here I describe a version of the sva approach specifically created for count data or FPKMs from sequencing experiments based on appropriate data transformation. I also describe the addition of supervised sva (ssva) for using control probes to identify the part of the genomic data only affected by artifacts. I present a comparison between these versions of sva and other methods for batch effect estimation on simulated data, real count-based data and FPKM-based data. These updates are available through the sva Bioconductor package and I have made fully reproducible analysis using these methods available from: https://github.com/jtleek/svaseq .

Description: High-throughput techniques have considerably increased the potential of comparative genomics whilst simultaneously posing many new challenges. One of those challenges involves efficiently mining the large amount of data produced and exploring the landscape of both conserved and idiosyncratic genomic regions across multiple genomes. Domains of application of these analyses are diverse: identification of evolutionary events, inference of gene functions, detection of niche-specific genes or phylogenetic profiling. Insyght is a comparative genomic visualization tool that combines three complementary displays: (i) a table for thoroughly browsing amongst homologues, (ii) a comparator of orthologue functional annotations and (iii) a genomic organization view designed to improve the legibility of rearrangements and distinctive loci. The latter display combines symbolic and proportional graphical paradigms. Synchronized navigation across multiple species and interoperability between the views are core features of Insyght. A gene filter mechanism is provided that helps the user to build a biologically relevant gene set according to multiple criteria such as presence/absence of homologues and/or various annotations. We illustrate the use of Insyght with scenarios. Currently, only Bacteria and Archaea are supported. A public instance is available at http://genome.jouy.inra.fr/Insyght . The tool is freely downloadable for private data set analysis.

Description: The 54 promoters are unique in prokaryotic genome and responsible for transcripting carbon and nitrogen-related genes. With the avalanche of genome sequences generated in the postgenomic age, it is highly desired to develop automated methods for rapidly and effectively identifying the 54 promoters. Here, a predictor called ‘ iPro54-PseKNC ’ was developed. In the predictor, the samples of DNA sequences were formulated by a novel feature vector called ‘pseudo k -tuple nucleotide composition’, which was further optimized by the incremental feature selection procedure. The performance of iPro54-PseKNC was examined by the rigorous jackknife cross-validation tests on a stringent benchmark data set. As a user-friendly web-server, iPro54-PseKNC is freely accessible at http://lin.uestc.edu.cn/server/iPro54-PseKNC . For the convenience of the vast majority of experimental scientists, a step-by-step protocol guide was provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics that were presented in this paper just for its integrity. Meanwhile, we also discovered through an in-depth statistical analysis that the distribution of distances between the transcription start sites and the translation initiation sites were governed by the gamma distribution, which may provide a fundamental physical principle for studying the 54 promoters.

Description: We present a discriminative learning method for pattern discovery of binding sites in nucleic acid sequences based on hidden Markov models. Sets of positive and negative example sequences are mined for sequence motifs whose occurrence frequency varies between the sets. The method offers several objective functions, but we concentrate on mutual information of condition and motif occurrence. We perform a systematic comparison of our method and numerous published motif-finding tools. Our method achieves the highest motif discovery performance, while being faster than most published methods. We present case studies of data from various technologies, including ChIP-Seq, RIP-Chip and PAR-CLIP, of embryonic stem cell transcription factors and of RNA-binding proteins, demonstrating practicality and utility of the method. For the alternative splicing factor RBM10, our analysis finds motifs known to be splicing-relevant. The motif discovery method is implemented in the free software package Discrover. It is applicable to genome- and transcriptome-scale data, makes use of available repeat experiments and aside from binary contrasts also more complex data configurations can be utilized.

Description: This study presents evidence from a survey and choice experiment on the preferences of Hispanic immigrants who entered the United States illegally for different immigration reform proposal attributes. Key components of the current competing US Senate and House immigration reform bills are considered including pathways to legal permanent residence, temporary work visas, family visitation rights, and access to medical care. The results quantify the value Hispanic immigrants place on different policy attributes and suggest that longer-term work visas are highly valued. Ability to legally work in the United States and a pathway to citizenship are substantially more valued than social services such as medical care and social security benefits.

Description: Sometimes, authorities are unable to rapidly identify the origin of a tainted product. In such cases, recalls or warnings often apply to all suppliers, even to those that had not contributed to the contamination. Traceability enables more targeted recalls by identifying the product's origin more specifically. In this article, we show how increased traceability protects the reputation of industries by limiting the size of recalls. We show the relationships between traceability and the level of food safety with many identical small farms in a competitive industry and for an industry using collective action to set rules and standards.

Description: While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription factories; however, a generalized systematic test has hitherto not been described. Here we reveal transcription factories using a rigorous definition of genomic structure based on Saccharomyces cerevisiae chromosome conformation capture data, coupled with an experimental design controlling for the primary gene order. We develop a data-driven method for the interpolation and the embedding of such datasets and introduce statistics that enable the comparison of the spatial and genomic densities of genes. Combining these, we report evidence that co-regulated genes are clustered in space, beyond their observed clustering in the context of gene order along the genome and show this phenomenon is significant for 64 out of 117 transcription factors. Furthermore, we show that those transcription factors with high spatially co-localized targets are expressed higher than those whose targets are not spatially clustered. Collectively, our results support the notion that, at a given time, the physical density of genes is intimately related to regulatory activity.

Description: Pan-genome ortholog clustering tool ( PanOCT ) is a tool for pan-genomic analysis of closely related prokaryotic species or strains. PanOCT uses conserved gene neighborhood information to separate recently diverged paralogs into orthologous clusters where homology-only clustering methods cannot. The results from PanOCT and three commonly used graph-based ortholog-finding programs were compared using a set of four publicly available strains of the same bacterial species. All four methods agreed on ~70% of the clusters and ~86% of the proteins. The clusters that did not agree were inspected for evidence of correctness resulting in 85 high-confidence manually curated clusters that were used to compare all four methods.

Description: A novel ab initio parameter-tuning-free system to identify transcriptional factor (TF) binding motifs (TFBMs) in genome DNA sequences was developed. It is based on the comparison of two types of frequency distributions with respect to the TFBM candidates in the target DNA sequences and the non-candidates in the background sequence, with the latter generated by utilizing the intergenic sequences. For benchmark tests, we used DNA sequence datasets extracted by ChIP-on-chip and ChIP-seq techniques and identified 65 yeast and four mammalian TFBMs, with the latter including gaps. The accuracy of our system was compared with those of other available programs (i.e. MEME, Weeder, BioProspector, MDscan and DME) and was the best among them, even without tuning of the parameter set for each TFBM and pre-treatment/editing of the target DNA sequences. Moreover, with respect to some TFs for which the identified motifs are inconsistent with those in the references, our results were revealed to be correct, by comparing them with other existing experimental data. Thus, our identification system does not need any other biological information except for gene positions, and is also expected to be applicable to genome DNA sequences to identify unknown TFBMs as well as known ones.

Description: MicroRNAs (miRNAs) are major regulators of gene expression in multicellular organisms. They recognize their targets by sequence complementarity and guide them to cleavage or translational arrest. It is generally accepted that plant miRNAs have extensive complementarity to their targets and their prediction usually relies on the use of empirical parameters deduced from known miRNA–target interactions. Here, we developed a strategy to identify miRNA targets which is mainly based on the conservation of the potential regulation in different species. We applied the approach to expressed sequence tags datasets from angiosperms. Using this strategy, we predicted many new interactions and experimentally validated previously unknown miRNA targets in Arabidopsis thaliana . Newly identified targets that are broadly conserved include auxin regulators, transcription factors and transporters. Some of them might participate in the same pathways as the targets known before, suggesting that some miRNAs might control different aspects of a biological process. Furthermore, this approach can be used to identify targets present in a specific group of species, and, as a proof of principle, we analyzed Solanaceae -specific targets. The presented strategy can be used alone or in combination with other approaches to find miRNA targets in plants.

Description: This paper analyses the impact of the recent decision by the European Union to ‘decouple’ agricultural support payments from agricultural production on Irish farmers' land market decisions. The land market participation decisions of Irish farmers are modelled using a dynamic probit model, while the extent of participation decisions is modelled using a dynamic tobit model. Decoupling does not appear to have significantly altered farmers' land market decisions. One likely explanation for this is the cross-compliance obligation for farmers to maintain land in a state fit for agricultural production in order to receive their full payments.

Description: We address the challenge of regulatory sequence alignment with a new method, Pro-Coffee, a multiple aligner specifically designed for homologous promoter regions. Pro-Coffee uses a dinucleotide substitution matrix estimated on alignments of functional binding sites from TRANSFAC. We designed a validation framework using several thousand families of orthologous promoters. This dataset was used to evaluate the accuracy for predicting true human orthologs among their paralogs. We found that whereas other methods achieve on average 73.5% accuracy, and 77.6% when trained on that same dataset, the figure goes up to 80.4% for Pro-Coffee. We then applied a novel validation procedure based on multi-species ChIP-seq data. Trained and untrained methods were tested for their capacity to correctly align experimentally detected binding sites. Whereas the average number of correctly aligned sites for two transcription factors is 284 for default methods and 316 for trained methods, Pro-Coffee achieves 331, 16.5% above the default average. We find a high correlation between a method's performance when classifying orthologs and its ability to correctly align proven binding sites. Not only has this interesting biological consequences, it also allows us to conclude that any method that is trained on the ortholog data set will result in functionally more informative alignments.

Description: MCScan is an algorithm able to scan multiple genomes or subgenomes in order to identify putative homologous chromosomal regions, and align these regions using genes as anchors. The MCScanX toolkit implements an adjusted MCScan algorithm for detection of synteny and collinearity that extends the original software by incorporating 14 utility programs for visualization of results and additional downstream analyses. Applications of MCScanX to several sequenced plant genomes and gene families are shown as examples. MCScanX can be used to effectively analyze chromosome structural changes, and reveal the history of gene family expansions that might contribute to the adaptation of lineages and taxa. An integrated view of various modes of gene duplication can supplement the traditional gene tree analysis in specific families. The source code and documentation of MCScanX are freely available at http://chibba.pgml.uga.edu/mcscan2/ .

Description: Cytosines in genomic DNA are sometimes methylated. This affects many biological processes and diseases. The standard way of measuring methylation is to use bisulfite, which converts unmethylated cytosines to thymines, then sequence the DNA and compare it to a reference genome sequence. We describe a method for the critical step of aligning the DNA reads to the correct genomic locations. Our method builds on classic alignment techniques, including likelihood-ratio scores and spaced seeds. In a realistic benchmark, our method has a better combination of sensitivity, specificity and speed than nine other high-throughput bisulfite aligners. This study enables more accurate and rational analysis of DNA methylation. It also illustrates how to adapt general-purpose alignment methods to a special case with distorted base patterns: this should be informative for other special cases such as ancient DNA and AT-rich genomes.

Description: Prophages are phages in lysogeny that are integrated into, and replicated as part of, the host bacterial genome. These mobile elements can have tremendous impact on their bacterial hosts’ genomes and phenotypes, which may lead to strain emergence and diversification, increased virulence or antibiotic resistance. However, finding prophages in microbial genomes remains a problem with no definitive solution. The majority of existing tools rely on detecting genomic regions enriched in protein-coding genes with known phage homologs, which hinders the de novo discovery of phage regions. In this study, a weighted phage detection algorithm, PhiSpy was developed based on seven distinctive characteristics of prophages, i.e. protein length, transcription strand directionality, customized AT and GC skew, the abundance of unique phage words, phage insertion points and the similarity of phage proteins. The first five characteristics are capable of identifying prophages without any sequence similarity with known phage genes. PhiSpy locates prophages by ranking genomic regions enriched in distinctive phage traits, which leads to the successful prediction of 94% of prophages in 50 complete bacterial genomes with a 6% false-negative rate and a 0.66% false-positive rate.

Description: Messenger RNA sequences possess specific nucleotide patterns distinguishing them from non-coding genomic sequences. In this study, we explore the utilization of modified Markov models to analyze sequences up to 44 bp, far beyond the 8-bp limit of conventional Markov models, for exon/intron discrimination. In order to analyze nucleotide sequences of this length, their information content is first reduced by conversion into shorter binary patterns via the application of numerous abstraction schemes. After the conversion of genomic sequences to binary strings, homogenous Markov models trained on the binary sequences are used to discriminate between exons and introns. We term this approach the Binary Abstraction Markov Model (BAMM). High-quality abstraction schemes for exon/intron discrimination are selected using optimization algorithms on supercomputers. The best MM classifiers are then combined using support vector machines into a single classifier. With this approach, over 95% classification accuracy is achieved without taking reading frame into account. With further development, the BAMM approach can be applied to sequences lacking the genetic code such as ncRNAs and 5'-untranslated regions.

Description: Insertional mutagenesis screens in mice are used to identify individual genes that drive tumor formation. In these screens, candidate cancer genes are identified if their genomic location is proximal to a common insertion site (CIS) defined by high rates of transposon or retroviral insertions in a given genomic window. In this article, we describe a new method for defining CISs based on a Poisson distribution, the Poisson Regression Insertion Model, and show that this new method is an improvement over previously described methods. We also describe a modification of the method that can identify pairs and higher orders of co-occurring common insertion sites. We apply these methods to two data sets, one generated in a transposon-based screen for gastrointestinal tract cancer genes and another based on the set of retroviral insertions in the Retroviral Tagged Cancer Gene Database. We show that the new methods identify more relevant candidate genes and candidate gene pairs than found using previous methods. Identification of the biologically relevant set of mutations that occur in a single cell and cause tumor progression will aid in the rational design of single and combinatorial therapies in the upcoming age of personalized cancer therapy.

Description: This paper evaluates the farm-level supply and income effects from removing milk quotas and reducing producer prices with increasing direct compensatory payments. Using a panel of Belgian dairy farms, we first estimate a multi-output multi-input flexible cost function that generates a U-shaped marginal cost curve for each farm of the sample. We then embed each farm cost function in a profit-maximisation programming model that is built and calibrated for each farm in the sample. Accounting for farm heterogeneity, the simulations show how dairy farms without quotas may respond differently to changes in prices and structural changes that may take place within the dairy sector. A quota removal with a 20 per cent reduction in milk prices keeps aggregate milk supply and farm income at about the same level of the 2006 reference year.

Description: This paper analyses the impact of milk quotas on the size structure of dairy herds in two major EU milk-producing member states, Germany and the Netherlands, using Markov chain models. Four mobility indicators characterising structural change are developed and calculated. Structural change in the dairy sector as measured by the mobility measures is found to be affected by the milk quota scheme. In the quota period, mobility out of dairying is lower, but the overall and upward mobility increase. This effect is stronger in the Netherlands than in West Germany.

Description: We use a stochastic dynamic programming model to simulate the market implications of alternative foot and mouth disease scenarios in the Finnish pig sector. The model considers the dynamics of animal stock adjustment and price movements when the duration of export disruptions is unknown. Explicit treatment of these issues is crucial in the economic analysis of livestock epidemics, especially if there is a risk of a prolonged export ban. Results suggest that the risk of a prolonged ban increases disease losses considerably. It also increases economic benefits from production adjustments.

Description: Consumers' preferences for food safety characteristics are investigated with a particular focus on the existence of an embedding effect. Embedding exists if consumer valuation of food safety is insensitive to scope. We conduct between-attribute external tests for embedding in two choice experiments concerning the value of food safety attributes in minced pork and chicken breasts. We find no evidence of embedding neither when using food safety attributes that are not close substitutes and which exhibit both private and public good characteristics, nor when using food safety attributes that are closer substitutes and which have primarily private good characteristics.

Description: In this article, we present one of the first real-world empirical applications of state-contingent production theory. Our state-contingent behavioural model allows us to analyse production under both inefficiency and uncertainty without regard to the nature of producer risk preferences. Using farm data for Finland, we estimate a flexible production model that permits substitutability between state-contingent outputs. We test empirically and reject an assumption that has been implicit in almost all efficiency studies conducted in the last three decades, namely that the production technology is output-cubical, i.e. that outputs are not substitutable between states of nature.

Description: In this paper, a modelling approach is developed for the treatment of ‘don't know’(DK) responses, within choice experiments (CEs). A DK option is motivated by the need to allow respondents the opportunity to express uncertainty. Our model explains a DK using an entropy measure of the similarity between options given to respondents within the CE. We illustrate our model by applying it to a CE examining consumer preferences for nutrient contents in food. We find that similarity between options in a given choice set does explain the tendency for respondents to report DK.

Description: Economists frequently use choice experiments (CEs) to evaluate demand for new attributes in food products. Using a split-sample experimental design focused on demand for pork chop attributes, we find consumer inferences regarding food safety and quality to impact estimates of marginal willingness to pay, market participation, policy appropriateness and consumer welfare effects. Our results suggest that interpretation of findings should be noted as conditional on attributes included in original analyses. A split-sample experimental approach involving multiple CE designs is described and suggested to practitioners to better consider consumer inference effects in future studies.

Description: Economists have long relied on utilitarian principles in carrying out cost–benefit analysis, but such utilitarianism is typically limited to the well-being of humans. Some prominent philosophers have argued such an approach is unjustifiably speciesist, but what are the consequences of including animal well-being in cost–benefit analysis? This paper considers this question in the context of human altruism towards animals in which people's concerns for the well-being of animals create an externality. After uncovering some conceptual challenges involved in carrying out cost–benefit analysis on animal welfare policies, we report the results of a novel experiment used to measure the public-good value of farm animal welfare, and show that although the average value in our sample is quite large, the result is due to the preferences of only a small subset of the subjects.

Description: Crop insurance is similar to flood and hurricane insurance in that spatially correlated weather tends to cause violations of the independence assumption. Ideally, one would seek to pool uncorrelated risk drawn from the same distribution in crop insurance. This article proposes a testing procedure for the cross-sectional pooling of group units, and empirically analyzes whether the proposed test improves out-of-sample rating performance. We utilize a balanced panel of U.S. county-level corn yields for 510 counties, and the results of an out-of-sample crop insurance rating performance exercise provide economic significance to the proposed pooling methodology and results.

Description: Is low input use by poor, smallholder farmers caused by time-inconsistent behavior or by limited ability to buy inputs? Are input subsidies the best solution to stimulate input demand or are there smarter solutions? These issues are investigated by combining survey data, stated preference questions, and randomized experiments in Malawi. The demand for fertilizer at harvest time and at planting time, farm gate shadow prices for fertilizer, and the gap between the willingness-to-accept (WTA) and willingness-to-pay (WTP) prices for a standard input package were investigated. Significant effects of timing and of cash constraints were found, suggesting the possibility that smarter designs exist, such as distribution of smaller packages from harvest time to planting time.

Description: This paper studies the effect of political regime transitions on public policy using a new data set on global agricultural and food policies over a 50-year period (including data from 74 developing and developed countries over the 1955–2005 period). We find evidence that democratization leads to a reduction of agricultural taxation, an increase in agricultural subsidization, or both. The empirical findings are consistent with the predictions of the median voter model because political transitions occurred primarily in countries with a majority of farmers. The results are robust to different specifications, estimation approaches, and variable definitions.

Description: In times of highly volatile commodity markets, governments often try to protect their populations from rapidly rising food prices, which can be particularly harmful for the poor. A potential solution for food-deficit countries is to hold strategic reserves that can be called on when international prices spike. But how large should strategic stockpiles be, and what rules should govern their release? In this paper, we develop a dynamic competitive storage model for wheat in the Middle East and North Africa region, where imported wheat is the most significant component of the average diet. We analyze a strategy that sets aside wheat stockpiles, which can be used to keep domestic prices below a targeted price. Our analysis shows that if the target price is set high and reserves are adequate, the strategy can be effective and robust. Contrary to most interventions, strategic storage policies are counter-cyclical, and when the importing region is sufficiently large, a regional policy can smooth global prices. Simulations indicate that this is the case for the Middle East and North Africa region. Nevertheless, the policy is more costly than a procyclical policy similar to food stamps that uses targeted transfers to directly offset high prices with a subsidy.

Description: Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant ( P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients’ molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification.

Description: The ability to correlate chromosome conformation and gene expression gives a great deal of information regarding the strategies used by a cell to properly regulate gene activity. 4C-Seq is a relatively new and increasingly popular technology where the set of genomic interactions generated by a single point in the genome can be determined. 4C-Seq experiments generate large, complicated data sets and it is imperative that signal is properly distinguished from noise. Currently, there are a limited number of methods for analyzing 4C-Seq data. Here, we present a new method, fourSig , which in addition to being precise and simple to use also includes a new feature that prioritizes detected interactions. Our results demonstrate the efficacy of fourSig with previously published and novel 4C-Seq data sets and show that our significance prioritization correlates with the ability to reproducibly detect interactions among replicates.

Description: The Minnesota Food Network is a limited liability company comprised of 52 farmers producing a variety of high-quality, sustainably produced agricultural products in southern Minnesota. The network's goal is to develop a regional food system to provide locally grown food at a price that "is fair" to both consumers and producers. This case outlines the challenges that the network faces in their efforts to expand to take advantage of a market opportunity. One of their biggest challenges is that they face high operating costs because of their disaggregated distribution system and need to purchase a distribution and storage facility and two vehicles. They will fund the purchase of a building through an angel investor. An angel investor is necessary because the network cannot sustain traditional loan payments in its current form. Students are asked to consider a number of questions pertaining to the decisions in this case outlined in the final section of the case study.

Description: Simulated prices from a stochastic storage model are used to examine the price impacts of speculation by rational investors who diversify their financial portfolios by holding agricultural commodity futures. The main result is that rather than destabilizing commodity prices, as is commonly believed, portfolio speculation actually reduces price volatility. Portfolio speculation can potentially destabilize a commodity's price because the additional demand for long futures by speculators is expected to drive up the cash price during both periods of low net demand, when the cash price is below average, and periods of high net demand, when the cash price is above average. Our theoretical analysis demonstrates that the higher level of inventory that is associated with portfolio speculation results in a larger release of stocks during periods of high net demand. The price simulations reveal that this stock adjustment effect is strong since overall price volatility is smaller rather than larger with portfolio speculation.

Description: Alternative transcript processing is an important mechanism for generating functional diversity in genes. However, little is known about the precise functions of individual isoforms. In fact, proteins (translated from transcript isoforms), not genes, are the function carriers. By integrating multiple human RNA-seq data sets, we carried out the first systematic prediction of isoform functions, enabling high-resolution functional annotation of human transcriptome. Unlike gene function prediction, isoform function prediction faces a unique challenge: the lack of the training data—all known functional annotations are at the gene level. To address this challenge, we modelled the gene–isoform relationships as multiple instance data and developed a novel label propagation method to predict functions. Our method achieved an average area under the receiver operating characteristic curve of 0.67 and assigned functions to 15 572 isoforms. Interestingly, we observed that different functions have different sensitivities to alternative isoform processing, and that the function diversity of isoforms from the same gene is positively correlated with their tissue expression diversity. Finally, we surveyed the literature to validate our predictions for a number of apoptotic genes. Strikingly, for the famous ‘TP53’ gene, we not only accurately identified the apoptosis regulation function of its five isoforms, but also correctly predicted the precise direction of the regulation.

Description: This paper uses framed choice experiments to examine the preferences of smallholder farmers in Malawi regarding alternative policy-based incentives to adopt conservation practices that reduce soil erosion and increase yields. The policy incentives offered in the choice experiments included an ideal index-based crop insurance contract, an index insurance contract with basis risk, cash payments, and fertilizer subsidies. Prior to implementing the choice experiments, the farmers participated in a workshop utilizing small group-based dynamic learning games that demonstrated how index-based crop insurance contracts function. The choice experiment results indicate that most farmers preferred cash payments to index insurance contracts, even when the insurance contracts offered substantially higher expected returns. Further, more risk averse farmers were more likely to prefer cash payments than less risk averse and risk loving farmers.

Description: We develop a dynamic model to assess the effects of policy expectations on crop supply and illustrate the approach with estimates of the effects of base updating in U.S. crop programs. For corn and soybeans in the Corn Belt, the effect of base updating is relatively small because relevant crop alternatives are subject to similar policies and the alternatives are substitutes in production. Increasing acreage of one program crop to capture future payments from base updating reduces future payments from the alternative crop. We also use our model to assess the effect of base updating on acreage response to prices.

Description: A substantial share of U.S. hog producers incorporate antimicrobial drugs into their livestock's feed or water at sub-therapeutic levels to promote feed efficiency and weight gain. Recently, in response to concerns that the overuse of antibiotics in livestock could promote the development of antimicrobial drug-resistant bacteria, the U.S. Food and Drug Administration adopted a strategy to phase out the use of antibiotics for production purposes. This study uses a stochastic frontier model and data from the 2009 USDA Agricultural Resource Management Survey of feeder-to-finish hog producers to estimate the potential effects on hog output and output variability resulting from a ban on antibiotics used for growth promotion. We use propensity score nearest neighbor matching to create a balanced sample of sub-therapeutic antibiotic (STA) users and nonusers. We estimate the frontier model for the pooled sample and separately for users and non-users—which allows for a flexible interaction between STA use and the production technology. Point estimates for the matched sample indicate that STA use has a small positive effect on productivity and production risk, increasing output by 1.0–1.3% and reducing the standard deviation of unexplained output by 1.4%. The results indicate that improvements in productivity resulted exclusively from technological improvement rather than from an increase in technical efficiency.

Description: Broadly, computational approaches for ortholog assignment is a three steps process: (i) identify all putative homologs between the genomes, (ii) identify gene anchors and (iii) link anchors to identify best gene matches given their order and context. In this article, we engineer two methods to improve two important aspects of this pipeline [specifically steps (ii) and (iii)]. First, computing sequence similarity data [step (i)] is a computationally intensive task for large sequence sets, creating a bottleneck in the ortholog assignment pipeline. We have designed a fast and highly scalable sort-join method (afree) based on k -mer counts to rapidly compare all pairs of sequences in a large protein sequence set to identify putative homologs. Second, availability of complex genomes containing large gene families with prevalence of complex evolutionary events, such as duplications, has made the task of assigning orthologs and co-orthologs difficult. Here, we have developed an iterative graph matching strategy where at each iteration the best gene assignments are identified resulting in a set of orthologs and co-orthologs. We find that the afree algorithm is faster than existing methods and maintains high accuracy in identifying similar genes. The iterative graph matching strategy also showed high accuracy in identifying complex gene relationships. Standalone afree available from http://vbc.med.monash.edu.au/~kmahmood/afree . EGM2, complete ortholog assignment pipeline (including afree and the iterative graph matching method) available from http://vbc.med.monash.edu.au/~kmahmood/EGM2 .

Description: With the availability of next-generation sequencing (NGS) technology, it is expected that sequence variants may be called on a genomic scale. Here, we demonstrate that a deeper understanding of the distribution of the variant call frequencies at heterozygous loci in NGS data sets is a prerequisite for sensitive variant detection. We model the crucial steps in an NGS protocol as a stochastic branching process and derive a mathematical framework for the expected distribution of alleles at heterozygous loci before measurement that is sequencing. We confirm our theoretical results by analyzing technical replicates of human exome data and demonstrate that the variance of allele frequencies at heterozygous loci is higher than expected by a simple binomial distribution. Due to this high variance, mutation callers relying on binomial distributed priors are less sensitive for heterozygous variants that deviate strongly from the expected mean frequency. Our results also indicate that error rates can be reduced to a greater degree by technical replicates than by increasing sequencing depth.

Description: An approach to infer the unknown microbial population structure within a metagenome is to cluster nucleotide sequences based on common patterns in base composition, otherwise referred to as binning. When functional roles are assigned to the identified populations, a deeper understanding of microbial communities can be attained, more so than gene-centric approaches that explore overall functionality. In this study, we propose an unsupervised, model-based binning method with two clustering tiers, which uses a novel transformation of the oligonucleotide frequency-derived error gradient and GC content to generate coarse groups at the first tier of clustering; and tetranucleotide frequency to refine these groups at the secondary clustering tier. The proposed method has a demonstrated improvement over PhyloPythia, S-GSOM, TACOA and TaxSOM on all three benchmarks that were used for evaluation in this study. The proposed method is then applied to a pyrosequenced metagenomic library of mud volcano sediment sampled in southwestern Taiwan, with the inferred population structure validated against complementary sequencing of 16S ribosomal RNA marker genes. Finally, the proposed method was further validated against four publicly available metagenomes, including a highly complex Antarctic whale-fall bone sample, which was previously assumed to be too complex for binning prior to functional analysis.

Description: We investigate farm size inequality in France using agricultural censuses and farm structure surveys at the NUTS3 level (‘départements’) during the period 1970–2007. Using calculated Gini coefficients, we show that farm size inequality has not systematically increased in France. An econometric analysis of the determinants of farm size inequality reveals that policy measures significantly affected farm size inequality, with most of the measures considered decreasing it. Empirical results suggest that the main contributor was the activity of the SAFER (Société d'Aménagement Foncier et d'Etablissement Rural), a specific feature of the French farm structural policy aimed at regulating rural land management. Besides, this research highlights the great complexity of the dynamics underlying the evolution of farm size distribution.

Description: This paper analyses implementation policies of environmental quota trade, with the Flemish nutrient production rights as an example. Implementation policies concern the transaction quantity, quota reduction and prevention of speculation. They are analysed with a static and a dynamic multi-agent quota trade model. The static model with discrete non-auctioned quota trade shows that the obligation for quota sellers to entirely stop their production stimulates structural change. The dynamic model version indicates that a flat rate reduction on traded quota and measures taken to prevent speculation combined with too low penalties for overuse stimulate the total production.

Description: European cattle markets have recently undergone significant change. We explore the simultaneous impacts of agricultural policy reform and the occurrence of an animal health crisis on spatial interdependencies of calf prices of four major European Union markets. The markets are found to be integrated. Price shocks are rapidly absorbed. We find that the member state specific implementations of the 2003 Common Agricultural Policy reforms significantly affected prices of both the national market and of other member states. The blue tongue disease further induced structural change. Using counterfactual scenarios, we show that the decoupling of payments from production led to reduced calf prices.

Description: We apply a spatial price equilibrium model of the world sugar market to simulate an abolition of the European Union (EU) quota system in 2015/16. To overcome the normative nature of the approach, we calibrate the model by attaching a non-linear cost term to each trade flow. This is in some regards similar to positive mathematical programming. We suggest an economic interpretation and an econometric specification of the cost term. EU sugar production is simulated to increase from 13.3 to 15.5 million tons in case of quota abolition by 2019/20. Ten member states increase production, nine reduce it. Preferential imports are significantly reduced. Simulated effects are found to be more pronounced the higher the world market price.

Description: We introduce the software tool NTRFinder to search for a complex repetitive structure in DNA we call a nested tandem repeat (NTR). An NTR is a recurrence of two or more distinct tandem motifs interspersed with each other. We propose that NTRs can be used as phylogenetic and population markers. We have tested our algorithm on both real and simulated data, and present some real NTRs of interest. NTRFinder can be downloaded from http://www.maths.otago.ac.nz/~aamatroud/ .

Description: For a period of about 1 yr between the summers of 2010 and 2011, 25 broad-band seismographs were deployed in a roughly linear array across the eastern end of the Qaidam basin and the Qilian Shan in the northeastern Tibetan plateau. This region is probably the most suitable place to study the ongoing convergence interaction between the high Tibetan plateau and the main Asian continental plate. Low-frequency P receiver function analysis of the data provides an image of the crust and mantle down to 700 km depth. In addition to the Moho at 45–65 km depth beneath the profile, the 410 and 660 km discontinuities bounding the mantle transition zone can be identified at 400–410 and 650–660 km depths, respectively. A possible increase in temperature in the upper mantle thought to exist beneath the northern part of the high Tibetan plateau is thus confined to this part of the plateau and lower upper-mantle temperatures similar to those beneath southern Tibet occur beneath the Qaidam basin and Qilian Shan. When higher frequencies are included in the P receiver function analysis, a positive Ps converter dipping down to the south from 70–75 km depth at 37.9°N to about 110 km depth at 36°N is imaged. As this feature is only seen in high-frequency images and not in the low-frequency image, it is modelled as the positive Ps conversion from the base of an approximately 5-km-thick anisotropic layer at the top of the Asian mantle lithosphere which is currently subducting. This south-dipping converter continues to the south on the INDEPTH IV profile. S receiver function analysis completes the image of the structure below the Qilian Shan profile with the identification of the lithosphere–asthenosphere boundary (LAB). The LAB of the Asian Plate is identified for a reference slowness of 6.4 s deg –1 at 12–14 s (105–125 km depth) between 38 and 41°N below the northern part of the S receiver function profile. To the south it increases in depth such that it is at about 19 s (170 km depth) between 34 and 35°N at the southern end of the profile. The LAB of the Asian Plate occurs at similar depths on the INDEPTH IV profile at the latitudes where the INDEPTH IV and Qilian Shan profiles overlap. As on the INDEPTH IV profile to the south, between 34 and 35°N at the southern end of the Qilian Shan profile there is evidence from the S receiver functions for the LAB of a separate Tibetan Plate.

Description: Parallel analysis of RNA ends (PARE) is a technique utilizing high-throughput sequencing to profile uncapped, mRNA cleavage or decay products on a genome-wide basis. Tools currently available to validate miRNA targets using PARE data employ only annotated genes, whereas important targets may be found in unannotated genomic regions. To handle such cases and to scale to the growing availability of PARE data and genomes, we developed a new tool, ‘ sPARTA ’ (small RNA-PARE target analyzer) that utilizes a built-in, plant-focused target prediction module (aka ‘ miRferno ’). sPARTA not only exhibits an unprecedented gain in speed but also it shows greater predictive power by validating more targets, compared to a popular alternative. In addition, the novel ‘seed-free’ mode, optimized to find targets irrespective of complementarity in the seed-region, identifies novel intergenic targets. To fully capitalize on the novelty and strengths of sPARTA , we developed a web resource, ‘ comPARE ’, for plant miRNA target analysis; this facilitates the systematic identification and analysis of miRNA-target interactions across multiple species, integrated with visualization tools. This collation of high-throughput small RNA and PARE datasets from different genomes further facilitates re-evaluation of existing miRNA annotations, resulting in a ‘cleaner’ set of microRNAs.

Description: Identification of three-dimensional (3D) interactions between regulatory elements across the genome is crucial to unravel the complex regulatory machinery that orchestrates proliferation and differentiation of cells. ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. However, determining the significance of the observed interaction frequencies in such datasets is challenging, and few methods have been proposed. Despite the fact that regions that are close in linear genomic distance have a much higher tendency to interact by chance, no methods to date are capable of taking such dependency into account. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall. Using both real and simulated data, we show that the previously proposed statistical test, based on Fisher's exact test, leads to invalid results when data are dependent on genomic distance. We also evaluate our method on previously validated cell-line specific and constitutive 3D interactions, and show that relevant interactions are significant, while avoiding over-estimating the significance of short nearby interactions.

Description: Viral sequence classification has wide applications in clinical, epidemiological, structural and functional categorization studies. Most existing approaches rely on an initial alignment step followed by classification based on phylogenetic or statistical algorithms. Here we present an ultrafast alignment-free subtyping tool for human immunodeficiency virus type one (HIV-1) adapted from Prediction by Partial Matching compression. This tool, named COMET, was compared to the widely used phylogeny-based REGA and SCUEAL tools using synthetic and clinical HIV data sets (1 090 698 and 10 625 sequences, respectively). COMET's sensitivity and specificity were comparable to or higher than the two other subtyping tools on both data sets for known subtypes. COMET also excelled in detecting and identifying new recombinant forms, a frequent feature of the HIV epidemic. Runtime comparisons showed that COMET was almost as fast as USEARCH. This study demonstrates the advantages of alignment-free classification of viral sequences, which feature high rates of variation, recombination and insertions/deletions. COMET is free to use via an online interface.

Description: Lower and upper bounds for present deformation rates across faults in central California between the San Andreas Fault and Pacific coast are estimated from a new Global Positioning System (GPS) velocity field for central, western California in light of geodetic evidence presented in a companion paper for slow, but significant deformation within the Pacific Plate between young seafloor in the eastern Pacific and older seafloor elsewhere on the plate. Transects of the GPS velocity field across the San Andreas Fault between Parkfield and San Juan Buatista, where fault slip is dominated by creep and the velocity field thus reveals the off-fault deformation, show that GPS sites in westernmost California move approximately parallel to the fault at an average rate of 3.4 ± 0.4 mm yr –1 relative to the older interior of the Pacific Plate, but only 1.8 ± 0.6 mm yr –1 if the Pacific Plate frame of reference is corrected for deformation within the plate. Modelled interseismic elastic deformation from the weakly coupled creeping segment of the San Andreas Fault is an order-of-magnitude too small to explain the southeastward motions of coastal sites in western California. Similarly, models that maximize residual viscoelastic deformation from the 1857 Fort Tejon and 1906 San Francisco earthquakes mismatch both the rates and directions of GPS site motions in central California relative to the Pacific Plate. Neither thus explains the site motions southwest of the San Andreas fault, indicating that the site motions measure deformation across faults and folds outboard of the San Andreas Fault. The non-zero site velocities thus constitute strong evidence for active folding and faulting outboard from the creeping segment of the San Andreas Fault and suggest limits of 0–2 mm yr –1 for the Rinconada Fault slip rate and 1.8 ± 0.6 to 3.4 ± 0.4 mm yr –1 for the slip rates integrated across near-coastal faults such as the Hosgri, San Gregorio and San Simeon faults.

Description: We combine new, well-determined GPS velocities from Clarion, Guadalupe and Socorro islands on young seafloor in the eastern Pacific basin with newly estimated velocities for 26 GPS sites from older seafloor in the central, western and southern parts of the Pacific Plate to test for deformation within the interior of the Pacific Plate and estimate the viscosity of the asthenosphere below the plate. Relative to a Pacific Plate reference frame defined from the velocities of the 26 GPS sites in other areas of the Pacific Plate, GPS sites on Clarion and Guadalupe islands in the eastern Pacific move 1.2 ± 0.6 mm yr –1 (1) towards S09°W ± 38° and 1.9 ± 0.3 mm yr –1 towards S19°E ± 10°, respectively. The two velocities, which are consistent within their 95 per cent uncertainties, both differ significantly from Pacific Plate motion. Transient volcanic deformation related to a 1993–1996 eruption of the Socorro Island shield volcano renders our GPS velocity from that island unreliable for the tectonic analysis although its motion is also southward like those of Clarion and Guadalupe islands. We test but reject the possibilities that drift of Earth's origin in ITRF2008 or unmodelled elastic offsets due to large-magnitude earthquakes around the Pacific rim since 1993 can be invoked to explain the apparent slow southward motions of Clarion and Guadalupe islands. Similarly, corrections to the Pacific Plate GPS velocity field for possible viscoelastic deformation triggered by large-magnitude earthquakes since 1950 also fail to explain the southward motions of the two islands. Viscoelastic models with prescribed asthenospheric viscosities lower than 1  x 10 19 Pa s instead introduce statistically significant inconsistencies into the Pacific Plate velocity field, suggesting that the viscosity of the asthenosphere below the plate is higher than 1  x 10 19 Pa s. Elastic deformation from locked Pacific–North America Plate boundary faults is also too small to explain the southward motions of the two islands. Horizontal thermal contraction of the plate interior may explain the motion observed at Clarion and Guadalupe islands, as might long-term tectonic deformation of the plate interior.

Description: In this study, a new method for computing the sensitivity of the glacial isostatic adjustment (GIA) forward solution with respect to the Earth's mantle viscosity, the so-called the forward sensitivity method (FSM), and a method for computing the gradient of data misfit with respect to viscosity parameters, the so-called adjoint-state method (ASM), are presented. These advanced formal methods complement each other in the inverse modelling of GIA-related observations. When solving this inverse problem, the first step is to calculate the forward sensitivities by the FSM and use them to fix the model parameters that do not affect the forward model solution, as well as identifying and removing redundant parts of the inferred viscosity structure. Once the viscosity model is optimized in view of the forward sensitivities, the minimization of the data misfit with respect to the viscosity parameters can be carried out by a gradient technique which makes use of the ASM. The aim is this paper is to derive the FSM and ASM in the forms that are closely associated with the forward solver of GIA developed by Martinec. Since this method is based on a continuous form of the forward model equations, which are then discretized by spectral and finite elements, we first derive the continuous forms of the FSM and ASM and then discretize them by the spectral and finite elements used in the discretization of the forward model equations. The advantage of this approach is that all three methods (forward, FSM and ASM) have the same matrix of equations and use the same methodology for the implementation of the time evolution of stresses. The only difference between the forward method and the FSM and ASM is that the different numerical differencing schemes for the time evolution of the Maxwell and generalized Maxwell viscous stresses are applied in the respective methods. However, it requires only a little extra computational time for carrying out the FSM and ASM numerically. An straightforward approach to compute the gradient of the data misfit is the brute-force method, whereby the partial derivatives of the misfit with respect to model parameters are approximated by the centred difference of two forward model runs. Although the brute-force method is useful for computing the gradient of the data misfit with respect to a small number of model parameters, it becomes expensive for a viscosity model with a large number of parameters. The ASM offers an efficient alternative for computing the gradient of the misfit since the computational time of the ASM is independent of the number of viscosity parameters. The ASM is thus highly efficient for calculating the gradient of the misfit for models with large numbers of parameters. However, the forward-model solution for each time step must be stored, hence the memory demands scale linearly with the number of time steps. This is the main drawback of the ASM.

Description: This paper deals with the determinants of out-farm migration across the European Union (EU) regions focusing on the role played by CAP payments. We add to the existing literature in three main directions. First, our analysis has broad coverage (150 EU regions over the 1990–2009 period); second, we work on the entire portfolio of CAP instruments; third, we rely on modern panel data methods. Results show that standard drivers, such as the relative income and the relative labour share, are important determinants of out-farm migration. Overall, CAP payments significantly contributed to maintain job in agriculture, though the magnitude of the economic effect has been quite moderate and heterogeneous across policy instruments. Pillar I subsidies exerted an effect more than two times greater than that of Pillar II payments.

Description: Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE ( http://mips.helmholtz-muenchen.de/cogere ), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient 2 (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research.

Description: Decoupled direct payments to farmers were introduced in the European Union (EU) in the form of the Single Payment Scheme (SPS) in 2005. The 2013 Common Agriculture Policy (CAP) reform changed both the implementation of the SPS and its budget. We assess the possible effects of the 2013 CAP reform on EU land markets, particularly the capitalization of the SPS in land rental values. Our analyses suggest that the implementation details of the 2013 CAP reform will largely determine the impact of the SPS on land markets. The key considerations are the reference period for entitlement allocation, regionalization, payment differentiation, and budgetary changes. Our analysis also implies that a number of relatively minor policy changes could have substantial impacts on land markets.

Description: We examine the effect that investments in education have on household expenditure on fruits and vegetables using a two-stage model that accounts for differences in ability and heterogeneous returns to education. For this, we use the 2008 Consumer Expenditure Survey for the United States. We find that higher levels of education contribute to greater household expenditures on both fresh and processed fruits and vegetables. We find a nonlinear effect on fresh fruits and vegetables, indicating that education impacts the quality of purchases as well. Although nutritional education is often touted as important for a healthful diet, these results highlight how investments in human capital via formal education can potentially improve dietary quality as well.

Description: In this article, we explore how using imputed income data in the Survey of Income and Program Participation affects the observed relationship between household income volatility and food insufficiency. We find that measuring income volatility using imputed income data substantially understates the association between large drops in household income and food insufficiency. After excluding observations with imputed income, large drops in income are associated with a 2.1–percentage point increased probability of food insufficiency, or a 31% higher likelihood of food insufficiency.

Description: This research explores the viability of an alternative design for crop insurance based upon farmer-owned savings accounts that are regulated, monitored, and marginally assisted by the government. Such accounts could be an effective risk management tool for many farmers and could operate without major government subsidization. Relative to the current program, the proposed design should exhibit minimal moral hazard and adverse selection problems, and since farm-level risk does not have to be priced, the proposed design eliminates the premium rating difficulties that weaken actuarial soundness and trigger the need for substantial external subsidies. In addition, administrative costs should be considerably lower.

Description: The recent spikes of global food prices induced a rapid increase in mass media coverage, public policy attention, and donor funding for food security and for agriculture and rural poverty. This has occurred while the shift from low to high food prices has induced a shift in (demographic or social) location of the hunger and poverty effects, but the total number of undernourished and poor people has declined over the same period. We suggest that the observed pattern can be explained by the presence of a global urban bias on agriculture and food policy in developing countries, and we discuss whether this global urban bias may actually benefit poor farmers. We argue that the food price spikes have succeeded where others have failed in the past: to move the problems of poor and hungry farmers to the top of the policy agenda and to induce development and donor strategies to help them.

Description: Relative to the gravitational potential energy of the Earth's monopole, the multipole energy has received far less attention. In this paper, we recapitulate the basic physics from first principles and derive the formulas for multipole energies in analogy to classical electrostatic theory. We focus on the zonal quadrupole energy associated with the Earth's oblateness, the dominant term in Earth's gravity field apart from the monopole. We find the gravitational energy E oblateness 10 –6 | E monopole | = +2.5 x 10 26 J. We examine the implications of E oblateness and its changes associated with long-term ‘secular’ decreases in the oblateness parameter J 2 . We find the rate of loss of E oblateness due to the Earth rounding induced by the present-day GIA is about –200 GW, an amount quite significant in the kinetic energy budget of the mantle heat engine that drives the plate tectonics that has been estimated to be ~1 TW. We also assert that the tidal braking and the global earthquake dislocations, both resulting in Earth rounding on long-term geological timescales, are accompanied with a secular decrease of E oblateness at nearly the same rate of several GW.

Description: Large-scale chemical lateral heterogeneities are inferred in the Earth's lowermost mantle by seismological studies. We explore the model space of thermochemical convection that can maintain reservoirs of dense material for a long period of time, by using similar analysis in 3-D spherical geometry. In this study, we focus on the parameters thought to be important in controlling the stability and structure of primordial dense reservoirs in the lower mantle, including the chemical density contrast between the primordial dense material and the regular mantle material (buoyancy ratio), thermal and chemical viscosity contrasts, volume fraction of primordial dense material and the Clapeyron slope of the phase transition at 660 km depth. We find that most of the findings from the 3-D Cartesian study still apply to 3-D spherical cases after slight modifications. Varying buoyancy ratio leads to different flow patterns, from rapid upwelling to stable layering; and large thermal viscosity contrasts are required to generate long wavelength chemical structures in the lower mantle. Chemical viscosity contrasts in a reasonable range have a second-order role in modifying the stability of the dense anomalies. The volume fraction of the initial primordial dense material does not effect the results with large thermal viscosity contrasts, but has significant effects on calculations with intermediate and small thermal viscosity contrasts. The volume fraction of dense material at which the flow pattern changes from unstable to stable depends on buoyancy ratio and thermal viscosity contrast. An endothermic phase transition at 660 km depth acts as a ‘filter’ allowing cold slabs to penetrate while blocking most of the dense material from penetrating to the upper mantle.

Description: Relative sea level curves contain coupled information about absolute sea level change and vertical lithospheric movement. Such curves may be constructed based on, for example tide gauge data for the most recent times and different types of geological data for ancient times. Correct account for vertical lithospheric movement is essential for estimation of reliable values of absolute sea level change from relative sea level data and vise versa. For modern times, estimates of vertical lithospheric movement may be constrained by data (e.g. GPS-based measurements), which are independent from the relative sea level data. Similar independent data do not exist for ancient times. The purpose of this study is to test two simple inversion approaches for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates for ancient times in areas where a dense coverage of relative sea level data exists and well-constrained average lithospheric movement values are known from, for example glacial isostatic adjustment (GIA) models. The inversion approaches are tested and used for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates in southwest Scandinavia from modern relative sea level data series that cover the period from 1900 to 2000. In both approaches, a priori information is required to solve the inverse problem. A priori information about the average vertical lithospheric movement in the area of interest is critical for the quality of the obtained results. The two tested inversion schemes result in estimated absolute sea level rise of ~1.2/1.3 mm yr –1 and vertical uplift rates ranging from approximately –1.4/–1.2 mm yr –1 (subsidence) to about 5.0/5.2 mm yr –1 if an a priori value of 1 mm yr –1 is used for the vertical lithospheric movement throughout the study area. In case the studied time interval is broken into two time intervals (before and after 1970), absolute sea level rise values of ~0.8/1.2 mm yr –1 (before 1970) and ~2.0 mm yr –1 (after 1970) are found. The uplift patterns resulting from the different inversions suggest that the lithospheric post-GIA response changes near the border between the Danish Basin and the Fennoscandian Shield. The obtained patterns of vertical lithospheric movement rates are comparable to results from other studies based on different and similar data types. Main differences between the inversion results and the results from other studies are caused by factors such as the simplifications included in the inversion approach, such as neglecting local sea level variation caused by the dominant wind patterns, and the a priori values chosen for the vertical uplift rates. The tests of the inversion schemes reveal that realistic values of absolute sea level rise and lithospheric uplift may be simultaneously estimated provided that reliable prior knowledge regarding the overall lithospheric uplift in the study area is available beforehand. In the presented parametrizations, only one absolute sea level change rate value is estimated for each studied time interval while several vertical movement rates are found, and the inverse estimate of absolute sea level change rate is practically insensitive with respect to the choice of a priori value of absolute sea level change, as long as the uncertainty assigned to this a priori value is kept sufficiently high.

Description: In 1356, a magnitude 6–7 earthquake occurred near Basel, in Switzerland. But recent compilations of GPS measurements reveal that measured horizontal deformation rates in northwestern continental Europe are smaller than error bars on the measurements, proving present tectonic activity, if any, is very small in this area. We propose to reconcile these apparently antinomic observations with a mechanical model of the lithosphere that takes into account the geometry of the lithosphere–asthenosphere boundary, assuming that the only loading mechanism is gravity. The lithosphere is considered to be an elastoplastic material satisfying a Von Mises plasticity criterion. The model, which is 400 km long, 360 km wide and 230 km thick, is centred near Belfort in eastern France, with its width oriented parallel to the N145°E direction. It also takes into account the real topography of both the ground surface and that of the Moho discontinuity. Not only does the model reproduce observed principal stress directions orientations, it also identifies a plastic zone that fits roughly the most seismically active domain of the region. Interestingly, a somewhat similar stress map may be produced by considering an elastic lithosphere and an ad-hoc horizontal ‘tectonic’ stress field. However, for the latter model, examination of the plasticity criterion suggests that plastic deformation should have taken place. It is concluded that the present-day stress field in this region is likely controlled by gravity and rheology, rather than by active Alpine tectonics.

Description: We have investigated variations in transition zone thickness under the Borborema Province of NE Brazil by migrating and stacking teleseismic P -wave receiver functions at 32 seismic stations in the region. The Borborema Province represents the western portion of a larger Neoproterozoic mobile belt that occupied much of northern Gondwana, where extensional processes in the Mesozoic lead to the formation of a number of intracontinental basins and ultimately continental breakup. Episodes of intraplate volcanism and uplift marked the evolution of the Province during the Cenozoic, but it is unclear whether those episodes originated from shallow or deep-seated magmatic sources. On one hand, the elliptical shape of the uplifted area, the stress pattern of the Cenozoic deformation and the time overlap between uplift and volcanism suggest doming from thermal activation due to a deep-seated mantle plume. On the other hand, geochronological dates of volcanic bodies in the Province are better understood if resulting from lithospheric erosion by a shallow, small-scale convection cell. Large temperature anomalies are expected to be associated with mantle upwellings, and constraints on the depth extent of the upwellings can be obtained from transition zone thickness. Thinning of the transition zone with respect to its nominal 250 km value is considered diagnostic for positive temperature anomalies, while thickening is considered diagnostic for negative anomalies. Our results show that transition zone thickness is normal, around 250 km, throughout the Province and suggest that thermal perturbations—if present—are confined to the upper mantle. We argue that our results are consistent with a local, shallow magmatic source for the Cenozoic intraplate volcanism of the Borborema Province, although other proposed scenarios—such as channeling of upwelling plume material along lithospheric thin spots—cannot be ruled out with our analysis.

Description: Non-coding RNAs (ncRNAs) are known to play important functional roles in the cell. However, their identification and recognition in genomic sequences remains challenging. In silico methods, such as classification tools, offer a fast and reliable way for such screening and multiple classifiers have already been developed to predict well-defined subfamilies of RNA. So far, however, out of all the ncRNAs, only tRNA, miRNA and snoRNA can be predicted with a satisfying sensitivity and specificity. We here present ptRNApred , a tool to detect and classify subclasses of non-coding RNA that are involved in the regulation of post-transcriptional modifications or DNA replication, which we here call post-transcriptional RNA (ptRNA). It (i) detects RNA sequences coding for post-transcriptional RNA from the genomic sequence with an overall sensitivity of 91% and a specificity of 94% and (ii) predicts ptRNA-subclasses that exist in eukaryotes: snRNA, snoRNA, RNase P, RNase MRP, Y RNA or telomerase RNA. AVAILABILITY: The ptRNApred software is open for public use on http://www.ptrnapred.org/ .

Description: Rapid development of next generation sequencing technology has enabled the identification of genomic alterations from short sequencing reads. There are a number of software pipelines available for calling single nucleotide variants from genomic DNA but, no comprehensive pipelines to identify, annotate and prioritize expressed SNVs (eSNVs) from non-directional paired-end RNA-Seq data. We have developed the eSNV-Detect, a novel computational system, which utilizes data from multiple aligners to call, even at low read depths, and rank variants from RNA-Seq. Multi-platform comparisons with the eSNV-Detect variant candidates were performed. The method was first applied to RNA-Seq from a lymphoblastoid cell-line, achieving 99.7% precision and 91.0% sensitivity in the expressed SNPs for the matching HumanOmni2.5 BeadChip data. Comparison of RNA-Seq eSNV candidates from 25 ER+ breast tumors from The Cancer Genome Atlas (TCGA) project with whole exome coding data showed 90.6–96.8% precision and 91.6–95.7% sensitivity. Contrasting single-cell mRNA-Seq variants with matching traditional multicellular RNA-Seq data for the MD-MB231 breast cancer cell-line delineated variant heterogeneity among the single-cells. Further, Sanger sequencing validation was performed for an ER+ breast tumor with paired normal adjacent tissue validating 29 out of 31 candidate eSNVs. The source code and user manuals of the eSNV-Detect pipeline for Sun Grid Engine and virtual machine are available at http://bioinformaticstools.mayo.edu/research/esnv-detect/ .

Description: Standard techniques for computed tomography imaging are not directly applicable to a carbonate rock because of the geometric complexity of its pore space. In this study, we first characterized the pore structure in Majella limestone with 30 per cent porosity. Microtomography data acquired on this rock was partitioned into three distinct domains: macropores, solid grains, and an intermediate domain made up of voxels of solid embedded with micropores below the resolution. A morphological analysis of the microtomography images shows that in Majella limestone both the solid and intermediate domains are interconnected in a manner similar to that reported previously in a less porous limestone. We however show that the macroporosity in Majella limestone is fundamentally different, in that it has a percolative backbone which may contribute significantly to its permeability. We then applied for the first time 3-D-volumetric digital image correlation (DIC) to characterize the mode of mechanical failure in this limestone. Samples were triaxially deformed over a wide range of confining pressures. Tomography imaging was performed on these samples before and after deformation. Inelastic compaction was observed at all tested pressures associated with both brittle and ductile behaviors. Our DIC analysis reveals the structure of compacting shear bands in Majella limestone deformed in the transitional regime. It also indicates an increase of geometric complexity with increasing confinement—from a planar shear band, to a curvilinear band, and ultimately to a diffuse multiplicity of bands, before shear localization is inhibited as the failure mode completes the transition to delocalized cataclastic flow.

Description: Are labels good or bad for consumers and firms? The answer may seem straightforward since labels improve information, yet economic theory reveals situations where their introduction reduces the welfare of at least some market participants. This essay reviews the theoretical literature on labels in order to identify and explain the main reasons that may cause labeling to produce undesirable side-effects. In contrast to earlier reviews that either concentrate on narrow topics or treat the subject in a more or less informal way, we bring together the main results from all the relevant topics by presenting and discussing the assumptions and model-building techniques that underpin them. The advantage of this approach is that it identifies the origin of the differences between results, thus allowing the synthesis of results that sometimes appear even to be contradictory. We focus on "quality labels" and examine the impact of labeling on market structure, the side-effects of costly certification, issues related to the label's trustworthiness, the rationale for mandatory vs. voluntary labeling, the level at which the label's standard is set according to the agency that selects it, the political economy of labels, that is, pro- or anti-label lobbying, lobbying to affect the label's standard, and lobbying in favor or against the label's mandatory imposition. These topics cover a wide range of applications, including Genetically Modified Organism (GMOs), organic produce, geographic indicators, controlled origin, eco-labels, etc. We conclude by identifying topics that require further research.

Description: Can food prices cause social unrest? Throughout history, riots have frequently broken out, ostensibly as a consequence of high food prices. Using monthly data at the international level, this article studies the impact of food prices – food price levels as well as food price volatility – on social unrest. Because food prices and social unrest are jointly determined, data on natural disasters are used to identify the causal relationship flowing from food price levels to social unrest. Results indicate that for the period 1990–2011, food price increases have led to increases in social unrest, whereas food price volatility has not been associated with increases in social unrest. These results are robust to alternative definitions of social unrest, to using real or nominal prices, to using commodity-specific price indices instead of aggregated price indices, to alternative definitions of the instrumental variable, to alternative definitions of volatility, and to controlling for non-food-related social unrest.

Description: Wide-angle reflection/refraction seismic profiles were recorded across the Cyprus Arc, the plate boundary between the African Plate and the Aegean–Anatolian microplate, from the Eratosthenes Seamount to the Hecataeus Rise immediately south of Cyprus. The resultant models were able to resolve detail of significant lateral velocity variations, though the deepest crust and Moho are not well resolved from the seismic data alone. Conclusions from the modelling suggest that (i) Eratosthenes Seamount consists of continental crust but exhibits a laterally variable velocity structure with a thicker middle crust and thinner lower crust to the northeast; (ii) the Hecataeus Rise has a thick sedimentary rock cover on an indeterminate crust (likely continental) and the crust is significantly thinner than Eratosthenes Seamount based on gravity modelling; (iii) high velocity basement blocks, coincident with highs in the magnetic field, occur in the deep water between Eratosthenes and Hecataeus, and are separated and bounded by deep low-velocity troughs and (iv) one of the high velocity blocks runs parallel to the Cyprus Arc, while the other two appear linked based on the magnetic data and run NW–SE, parallel to the margin of the Hecataeus Rise. The high velocity block beneath the edge of Eratosthenes Seamount is interpreted as an older magmatic intrusion while the linked high velocity blocks along Hecataeus Rise are interpreted as deformed remnant Tethyan oceanic crust or mafic intrusives from the NNW–SSE oriented transform margin marking the northern boundary of Eratosthenes Seamount. Eratosthenes Seamount, the northwestern limit of rifted continental crust from the Levant Margin, is part of a jagged rifted margin transected by transform faults on the northern edge of the lower African Plate that is being obliquely subducted under the Aegean–Anatolian upper plate. The thicker crust of Eratosthenes Seamount may be acting as an asperity on the subducting slab, locally locking up subduction of the Cyprus Arc on its northern margin, while deformed Tethyan oceanic crust remains trapped between its northeastern margin and the Hecataeus Rise.

Description: We present an up-to-date high resolution picture of the ongoing crustal deformation field of Italy, based on an extensive combination of permanent and non-permanent GPS observations carried out since 1994. In addition, we present an updated map of contemporary S Hmax orientations computed by a multidisciplinary data set of well-constrained stress indicators, including both published results and novel analyses. The comparison of stress and geodetic strain-rates directions reveals that both patterns are near-parallel over a large part of the investigated area, highlighting that crustal stress and surface deformation are driven by the same mechanism. The comparison of the azimuthal patterns of surface strain and mantle deformation shows a modest correlation on the Alps and a low correlation along the Apennines chain and the Calabro-Peloritan Arc. Along the Apennines chain, this feature suggests the occurrence of significant strain partitioning and crust–mantle mechanical decoupling. Along the Calabro-Peloritan Arc, the apparent low correlation reflects a different mantle–crust mechanism of deformation to the ongoing subduction and rollback of the Ionian slab. In addition, the superposition of regional/local effects related to second-order sources (crustal lateral density changes, strength contrasts), which at regional/local scale modulate the crustal stress/strain-rate pattern, cannot be ruled out.

Description: A series of linear analysis was performed on the onset of thermal convection of highly compressible fluids, in order to deepen the fundamental insights into the mantle convection of massive super-Earths in the presence of strong adiabatic compression. We consider the temporal evolution (growth or decay) of an infinitesimal perturbation superimposed to a highly compressible fluid which is in a hydrostatic (motionless) and conductive state in a basally heated horizontal layer. As a model of pressure-dependence in material properties, we employed an exponential decrease in thermal expansivity α and exponential increase in (reference) density with depth. The linearized equations for conservation of mass, momentum and internal (thermal) energy are numerically solved for the critical Rayleigh number as well as the vertical profiles of eigenfunctions for infinitesimal perturbations. The above calculations are repeatedly carried out by systematically varying (i) the dissipation number (Di), (ii) the temperature at the top surface and (iii) the magnitude of pressure-dependence in α and . Our analysis demonstrated that the onset of thermal convection is strongly affected by the adiabatic compression, in response to the changes in the static stability of thermal stratification in the fluid layer. For sufficiently large Di where a thick sublayer of stable stratification develops in the layer, for example, the critical Rayleigh number explosively increases with Di, together with drastic decreases in the length scales of perturbations both in vertical and horizontal directions. In particular, for very large Di, a thick ‘stratosphere’ occurs in the fluid layer where the vertical motion is significantly suppressed, resulting in a shrink of the incipient convection in a thin sublayer of unstable thermal stratification. In addition, when Di exceeds a threshold value above which a thermal stratification becomes stable in the entire layer, no perturbation is allowed to grow with time regardless of the Rayleigh number and/or the horizontal wavelength. We also found that the effect of adiabatic compression becomes prominent for higher temperature at the top surface of the fluid layer. These findings may imply the crucial importance of adiabatic compression in understanding the dynamics and evolution of the mantles of massive super-Earths, particularly for those orbiting their parent stars very closely.

Description: In this paper, we propose an approach to compute the coseismic Earth's volume change based on a spherical-Earth elastic dislocation theory. We present a general expression of the Earth's volume change for three typical dislocations: the shear, tensile and explosion sources. We conduct a case study for the 2004 Sumatra earthquake ( M w 9.3), the 2010 Chile earthquake ( M w 8.8), the 2011 Tohoku-Oki earthquake ( M w 9.0) and the 2013 Okhotsk Sea earthquake ( M w 8.3). The results show that mega-thrust earthquakes make the Earth expand and earthquakes along a normal fault make the Earth contract. We compare the volume changes computed for finite fault models and a point source of the 2011 Tohoku-Oki earthquake ( M w 9.0). The big difference of the results indicates that the coseismic changes in the Earth's volume (or the mean radius) are strongly dependent on the earthquakes’ focal mechanism, especially the depth and the dip angle. Then we estimate the cumulative volume changes by historical earthquakes ( M w ≥ 7.0) since 1960, and obtain an Earth mean radius expanding rate about 0.011 mm yr –1 .

Description: We present the crustal resistivity structure of the Pamir and Southern Tian Shan orogenic belts at the northwestern promontory of the India–Asia collision zone. The magnetotelluric (MT) data were recorded along a roughly north–south trending, 350 km long corridor from the Pamir Plateau in southern Tajikistan across the Pamir frontal ranges, the Alai Valley and the southwestern Tian Shan to Osh in the Kyrgyz part of the Fergana Basin. In total, we measured at 178 sites, whereof 26 combine broad band and long period recordings. One of the most intriguing features of the 2-D and 3-D inversion results is a laterally extended zone of high electrical conductivity below the Pamir Plateau, with resistivities below 1 m, starting at a depth of ~10–15 km. The high conductivity can be explained with the presence of partially molten rocks at middle to lower crustal levels, possibly related to ongoing migmatization and/or middle/lower crustal flow underneath the Southern Pamir. This interpretation is consistent with a low velocity zone found from local earthquake tomography, relatively high v p / v s ratios, elevated surface heat flow, and thermomechanical modelling suggesting that melting temperatures are reached in the felsic middle crust. In the upper crust of the Pamir and Tian Shan, the Palaeozoic–Mesozoic suture zones appear as electrically conductive, whereas the compact metamorphic rocks of the Muskol-Shatput Dome of the Central Pamir are highly resistive. The intra-montane basin of the Alai Valley—sandwiched between the Pamir and Tian Shan—exhibits a generally conductive upper crust that bifurcates into two conductors at depth. One of them connects to the active Main Pamir Thrust, which is absorbing most of today's convergence between the Pamir and the Tian Shan. Several deeper zones of high conductivity in the middle and lower crust of Central and Northern Pamir likely record fluid release due to metamorphism associated with active continental subduction/delamination.

Description: A new model of the deglaciation history of Antarctica over the past 25 kyr has been developed, which we refer to herein as ICE-6G_C (VM5a). This revision of its predecessor ICE-5G (VM2) has been constrained to fit all available geological and geodetic observations, consisting of: (1) the present day uplift rates at 42 sites estimated from GPS measurements, (2) ice thickness change at 62 locations estimated from exposure-age dating, (3) Holocene relative sea level histories from 12 locations estimated on the basis of radiocarbon dating and (4) age of the onset of marine sedimentation at nine locations along the Antarctic shelf also estimated on the basis of 14 C dating. Our new model fits the totality of these data well. An additional nine GPS-determined site velocities are also estimated for locations known to be influenced by modern ice loss from the Pine Island Bay and Northern Antarctic Peninsula regions. At the 42 locations not influenced by modern ice loss, the quality of the fit of postglacial rebound model ICE-6G_C (VM5A) is characterized by a weighted root mean square residual of 0.9 mm yr –1 . The Southern Antarctic Peninsula is inferred to be rising at 2 mm yr –1 , requiring there to be less Holocene ice loss there than in the prior model ICE-5G (VM2). The East Antarctica coast is rising at approximately 1 mm yr –1 , requiring ice loss from this region to have been small since Last Glacial Maximum. The Ellsworth Mountains, at the base of the Antarctic Peninsula, are inferred to be rising at 5–8 mm yr –1 , indicating large ice loss from this area during deglaciation that is poorly sampled by geological data. Horizontal deformation of the Antarctic Plate is minor with two exceptions. First, O'Higgins, at the tip of the Antarctic Peninsula, is moving southeast at a significant 2 mm yr –1 relative to the Antarctic Plate. Secondly, the margins of the Ronne and Ross Ice Shelves are moving horizontally away from the shelf centres at an approximate rate of 0.8 mm yr –1 , in viscous response to the early Holocene unloading of ice from the current locations of the ice shelf centers. ICE-6G_C (VM5A) fits the horizontal observations well (wrms residual speed of 0.7 mm yr –1 ), there being no need to invoke any influence of lateral variation in mantle viscosity. ICE-6G_C (VM5A) differs in several respects from the recently published W12A model of Whitehouse et al. First, the upper-mantle viscosity in VM5a is 5 10 20 Pa s, half that in W12A. The VM5a profile, which is identical to that inferred on the basis of the Fennoscandian relaxation spectrum, North American relative sea level histories and Earth rotation constraints, when coupled with the revised ICE-6G_C deglaciation history, fits all of the available constraints. Secondly, the net contribution of Antarctica ice loss to global sea level rise is 13.6 m, 2/3 greater than the 8 m in W12A. Thirdly, ice loss occurs quickly from 12 to 5 ka, and the contribution to global sea level rise during Meltwater Pulse 1B (11.5 ka) is large (5 m), consistent with sedimentation constraints from cores from the Antarctica ice shelf. Fourthly, in ICE-6G_C there is no ice gain in the East Antarctica interior, as there is in W12A. Finally, the new model of Antarctic deglaciation reconciles the global constraint upon the global mass loss during deglaciation provided by the Barbados record of relative sea level history when coupled with the Northern Hemisphere counterpart of this new model.

Description: Up to now, most nutritional policies have been set up to inform consumers about the health benefits induced by more balanced diets. Reviews of the impacts of these policies show that the effects are often modest. This has led governments to implement, in more recent times, policies focused on the market environment, especially on the characteristics of the food supply. The goal of this paper is to review theoretical and empirical studies focusing on changes in the food supply induced by alternative policies, and to attempt to draw from them policy guidelines and conjectures to test in future research.

Description: The Himalaya is the result of the on-going convergence and collision of India and Asia. The internal configuration and processes that govern the rise of the Himalayan Mountains and Tibetan Plateau are crucial to understand continental collision zones. However, knowledge of the prior configuration of the colliding plates is equally important, since inherited (pre-orogenic/basement) structures can undeniably influence the development of the orogenic architecture throughout the orogen's cycle of collision and eventual collapse. Three northeast-trending palaeotopographic ridges of faulted Precambrian Indian basement underlie the Ganga basin south of the Himalaya. Our paper illustrates a crustal-scale fault origin for these ridges and succeeds in determining how far north beneath the Himalayan system they extend and how they ultimately govern the location of upper crustal faults in southern Tibet. Spectrally filtered EGM2008 Bouguer gravity data and edges in its horizontal gradient at different source depths (‘gravity worms’) over northern Peninsular India, the Himalaya and southern Tibet reveal several continuous Himalayan cross-strike discontinuities interpreted to represent crustal faults. Gravity lineaments in Peninsular India coincide with edges of the Precambrian basement ridges and megakinks up to 100 km wide develop in foreland cover sequences between the interpreted basement faults. The interpreted basement faults project northward beneath the Himalayan system and southern Tibet. Our results suggest that several active Himalayan cross-strike faults, such as the ones related to many graben in southern Tibet, are rooted in the underplated Indian lower crust or step en échelon along interpreted basement faults. Our interpretation thus suggests that south Tibet graben are spatially related to deep-seated crustal-scale faults rooted in the underplated Indian crust. These major discontinuities partition the Himalayan range into distinct zones, and could ultimately contribute to lateral variability in tectonic evolution along the orogen's strike.

Description: We explore the impact of deep ductile shear zones on post-seismic deformation following a finite length strike-slip earthquake. We show that the pattern of post-seismic vertical surface deformation surrounding the fault is a discriminant for the existence of high viscosities immediately below the seismogenic layer, regardless of whether the model contains purely distributed creep or also includes a component of localized creep at subseismogenic depths. Post-seismic deformation characterized by initially fast relaxation followed by a slower relaxation is predicted by models that include both localized creep in a subseismogenic shear zone and distributed creep in the surrounding region, even if they only contain steady Maxwell viscoelasticity. This post-seismic deformation is similar to that in models that approximate the ductile lithosphere and/or asthenosphere with Burgers viscoelasticity. We find that the post-seismic deformation following the 1997 M w 7.6 Manyi, China, earthquake, is consistent with a post-seismic model composed of a lower Maxwell viscoelastic region with viscosity 10 19 Pa s and a 5 km wide, Maxwell viscoelastic shear zone with viscosity 10 18 Pa s beneath the fault.

Description: The Amundsen Sea Embayment of West Antarctica represents a key component in the tectonic history of Antarctic–New Zealand continental breakup. The region played a major role in the plate-kinematic development of the southern Pacific from the inferred collision of the Hikurangi Plateau with the Gondwana subduction margin at approximately 110–100 Ma to the evolution of the West Antarctic Rift System. However, little is known about the crustal architecture and the tectonic processes creating the embayment. During two ‘RV Polarstern’ expeditions in 2006 and 2010 a large geophysical data set was collected consisting of seismic-refraction and reflection data, ship-borne gravity and helicopter-borne magnetic measurements. Two P -wave velocity–depth models based on forward traveltime modelling of nine ocean bottom hydrophone recordings provide an insight into the lithospheric structure beneath the Amundsen Sea Embayment. Seismic-reflection data image the sedimentary architecture and the top-of-basement. The seismic data provide constraints for 2-D gravity modelling, which supports and complements P -wave modelling. Our final model shows 10–14-km-thick stretched continental crust at the continental rise that thickens to as much as 28 km beneath the inner shelf. The homogenous crustal architecture of the continental rise, including horst and graben structures are interpreted as indicating that wide-mode rifting affected the entire region. We observe a high-velocity layer of variable thickness beneath the margin and related it, contrary to other ‘normal volcanic type margins’, to a proposed magma flow along the base of the crust from beneath eastern Marie Byrd Land—West Antarctica to the Marie Byrd Seamount province. Furthermore, we discuss the possibility of upper mantle serpentinization by seawater penetration at the Marie Byrd Seamount province. Hints of seaward-dipping reflectors indicate some degree of volcanism in the area after break-up. A set of gravity anomaly data indicate several phases of fully developed and failed rift systems, including a possible branch of the West Antarctic Rift System in the Amundsen Sea Embayment.

Description: Geophysical data are the main source of information about the subsurface. Geophysical techniques are, however, highly non-unique in determining specific physical parameters and boundaries of subsurface objects. To obtain actual physical information, an inversion process is often applied, in which measurements at or above the Earth surface are inverted into a 2- or 3-D subsurface spatial distribution of the physical property. Interpreting these models into structural objects, related to physical processes, requires a priori knowledge and expert analysis which is susceptible to subjective choices and is therefore often non-repeatable. In this research, we implemented a recently introduced object-based approach to interpret the 3-D inversion results of a single geophysical technique using the available a priori information and the physical and geometrical characteristics of the interpreted objects. The introduced methodology is semi-automatic and repeatable, and allows the extraction of subsurface structures using 3-D object-oriented image analysis (3-D OOA) in an objective knowledge–based classification scheme. The approach allows for a semi-objective setting of thresholds that can be tested and, if necessary, changed in a very fast and efficient way. These changes require only changing the thresholds used in a so-called ruleset, which is composed of algorithms that extract objects from a 3-D data cube. The approach is tested on a synthetic model, which is based on a priori knowledge on objects present in the study area (Tanzania). Object characteristics and thresholds were well defined in a 3-D histogram of velocity versus depth, and objects were fully retrieved. The real model results showed how 3-D OOA can deal with realistic 3-D subsurface conditions in which the boundaries become fuzzy, the object extensions become unclear and the model characteristics vary with depth due to the different physical conditions. As expected, the 3-D histogram of the real data was substantially more complex. Still, the 3-D OOA-derived objects were extracted based on their velocity and their depth location. Spatially defined boundaries, based on physical variations, can improve the modelling with spatially dependent parameter information. With 3-D OOA, the non-uniqueness on the location of objects and their physical properties can be potentially significantly reduced.

Description: We estimate Eurasia-North America Plate motion rotations at ~1-Myr intervals for the past 20 Myr from more than 11 000 crossings of 21 magnetic reversals from Chron 1n (0.78 Ma) to C6no (19.72 Ma) and flow lines digitized from the Charlie Gibbs, Bight and Molloy fracture zones and transform faults. Adjusted for outward displacement, the 21 best-fitting rotations determined from a simultaneous inversion of the numerous kinematic data reconstruct the reversal crossings with weighted root mean square misfits of only 1–2 km and 0.2–7 km for the transform fault and fracture zone crossings. The new rotations clearly define a ~1000 km southward shift of the rotation pole and 20 per cent slowdown in seafloor spreading rates between 7 and 6 Ma, preceded by apparently steady plate motion from 19.7 to ~7 Ma. Data for times since C3An.2 (6.7 Ma) are well fit by a stationary pole of rotation and constant rate of angular opening, consistent with steady motion since 6.7 Ma. The southward shift of the rotation pole at 7–6 Ma implies that Eurasia-North America motion in northeastern Asia changed from slowly convergent before 7 Ma to slowly divergent afterward. Crossings of magnetic reversals C1n through C3An.1 (6.0 Ma) are well fit everywhere in the Arctic basin and south to the Azores triple junction, indicating that the Eurasia and North America plates have not deformed along their mutual boundary since at least 6.0 Ma. However, the new rotations systematically overrotate magnetic lineations older than C3An.1 (6.0 Ma) within 200 km of the Azores triple junction and also overrotate lineations older than C5n along the Gakkel Ridge in the Arctic Basin. Barring misidentifications of the magnetic anomalies in those areas, the pattern and magnitude of the systematic misfits imply that slow (~1 mm yr –1 ) distributed or microplate deformation occurred in one or both regions.

Description: Here we inverted the GPS data to infer the coseismic slip of the Tohoku-Oki earthquake and the time-dependent afterslip distribution in the 4 months following the main shock. The Tohoku-Oki earthquake showed an unexpected magnitude and a characteristic depth-dependent differentiation of seismic energy radiation. In this context the estimation and comparison of the distribution of the fault portions that slip coseismically and post-seismically contribute to a better understanding of the variation of frictional characteristics of the plate interface. The inferred coseismic slip extends in a relatively compact region located updip from the hypocentre and reaches its highest value (about 60 m) near the trench. Afterslip occurs mostly outside the coseismic rupture and is distributed in two main modal centres. It reaches its largest values in an area located downdip of the coseismic slip and extends to a depth of 80 km. In the depth range between 30 and 50 km afterslip overlaps the portion of the fault that experienced historical moderate earthquakes, high-frequency seismic radiation and thrust-type aftershocks. The behaviour of this area can be explained by a rheologically heterogeneous region made of a ductile fault matrix interspersed with compact brittle asperities. On the contrary, the region beneath 50–60 km depth is probably characterized by a fully velocity strengthening behaviour. Southern afterslip, located off-Chiba Prefecture, is probably related to the M w 7.9 Ibaraki-Oki aftershock. The northward extension of the afterslip stops at a latitude of about 40°N, just south of the off-Aomori region. This may be related to three large events occurred in this area during the last century and the consequent strong coupling or complete depletion of the accumulated strain that characterize this region.

Description: With the rise of behavioural economics has come the belief that decision-making biases justify paternalistic policies. Such views challenge the notion of consumer sovereignty and the validity of traditional approaches of economic welfare analysis. While behavioural economics might improve the effectiveness of policies that are already justified on some other market-failure grounds, this article argues that the existence of cognitive failures, alone, do not justify government regulation. If one abandons the idea that consumers know what is in their best interest, judging the merits of policies becomes arbitrary and reflects only what a paternalist wants for others. The typical behavioural economic experiment occurs with college students devoid of real-world context. The biases found in such setting may not extrapolate well to conditions where people have more experience and knowledge, and where they can learn from past mistakes. Even when behavioural biases persist in the ‘real world’, consumers face incentives to engage in activities that protect them from the adverse consequences of the biases, and public policies that shield people from such consequences reduce incentives to self-regulate. The article concludes with some ideas for future research and a discussion of the merits of freedom of choice.

Description: Heterogeneity in genetic networks across different signaling molecular contexts can suggest molecular regulatory mechanisms. Here we describe a comparative chi-square analysis (CP 2 ) method, considerably more flexible and effective than other alternatives, to screen large gene expression data sets for conserved and differential interactions. CP 2 decomposes interactions across conditions to assess homogeneity and heterogeneity. Theoretically, we prove an asymptotic chi-square null distribution for the interaction heterogeneity statistic. Empirically, on synthetic yeast cell cycle data, CP 2 achieved much higher statistical power in detecting differential networks than alternative approaches. We applied CP 2 to Drosophila melanogaster wing gene expression arrays collected under normal conditions, and conditions with overexpressed E2F and Cabut, two transcription factor complexes that promote ectopic cell cycling. The resulting differential networks suggest a mechanism by which E2F and Cabut regulate distinct gene interactions, while still sharing a small core network. Thus, CP 2 is sensitive in detecting network rewiring, useful in comparing related biological systems.

Description: In consequence of strong changes in general economic conditions, adjustments in the agricultural sector can be expected. To date, however, there are only few policy impact analyses on agricultural investments in a dynamic-stochastic context. The objective of this paper is to develop a real options market model which allows the impact assessment of different political schemes. The model combines genetic algorithms and stochastic simulation. Simulations of the model show that investment subsidies and production ceilings are preferable to price floors because the welfare is less reduced for a given stimulation of the willingness to invest.

Description: The aim of this paper is to study farmers' participation in rural development policy (RDP) measures. We investigate to what extent regional RDP priorities are driven by regional characteristics and moreover, whether regional-level policy priorities help to explain farmers' participation in RDP measures. We estimate a multilevel binary choice model that includes both farm-level and regional-level explanatory variables. We conclude that regional governments select RDP priorities based on the specific features of their region. Regional policy priorities play an important role in explaining farmers' participation in agri-environmental schemes but not in measures aimed at improving farmer competitiveness.

Description: The distinction between single farm payments (SFP) and counter-cyclical payments (CCPs) is mainly based on theory. Due to a lack of empirical comparative studies between these payments, it is difficult to confirm the claim that CCPs are more distorting. This paper provides a comparative analysis of these payments and quantifies the impact of such payments in the presence of debt constraints. The main findings are that CCPs are more distorting than SFP. However, the magnitude of the impact estimates is not as large as suggested by the different treatment received by both support programmes in the WTO negotiations.

Description: Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ~10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors’ websites: e.g. http://www.cs.toronto.edu/~wkc/kmerHMM .

Description: Sequence similarity search is a fundamental way of analyzing nucleotide sequences. Despite decades of research, this is not a solved problem because there exist many similarities that are not found by current methods. Search methods are typically based on a seed-and-extend approach, which has many variants (e.g. spaced seeds, transition seeds), and it remains unclear how to optimize this approach. This study designs and tests seeding methods for inter-mammal and inter-insect genome comparison. By considering substitution patterns of real genomes, we design sets of multiple complementary transition seeds, which have better performance (sensitivity per run time) than previous seeding strategies. Often the best seed patterns have more transition positions than those used previously. We also point out that recent computer memory sizes (e.g. 60 GB) make it feasible to use multiple (e.g. eight) seeds for whole mammal genomes. Interestingly, the most sensitive settings achieve diminishing returns for human–dog and melanogaster–pseudoobscura comparisons, but not for human–mouse, which suggests that we still miss many human–mouse alignments. Our optimized heuristics find ~20 000 new human–mouse alignments that are missing from the standard UCSC alignments. We tabulate seed patterns and parameters that work well so they can be used in future research.

Description: Identifying differential features between conditions is a popular approach to understanding molecular features and their mechanisms underlying a biological process of particular interest. Although many tests for identifying differential expression of gene or gene sets have been proposed, there was limited success in developing methods for differential interactions of genes between conditions because of its computational complexity. We present a method for Evaluation of Dependency DifferentialitY (EDDY), which is a statistical test for differential dependencies of a set of genes between two conditions. Unlike previous methods focused on differential expression of individual genes or correlation changes of individual gene–gene interactions, EDDY compares two conditions by evaluating the probability distributions of dependency networks from genes. The method has been evaluated and compared with other methods through simulation studies, and application to glioblastoma multiforme data resulted in informative cancer and glioblastoma multiforme subtype-related findings. The comparison with Gene Set Enrichment Analysis, a differential expression-based method, revealed that EDDY identifies the gene sets that are complementary to those identified by Gene Set Enrichment Analysis. EDDY also showed much lower false positives than Gene Set Co-expression Analysis, a method based on correlation changes of individual gene–gene interactions, thus providing more informative results. The Java implementation of the algorithm is freely available to noncommercial users. Download from: http://biocomputing.tgen.org/software/EDDY .

Description: We present a revised interpretation of magnetic anomalies and fracture zones on the Southwest Indian Ridge (SWIR; Africa–Antarctica) and the Southeast Indian Ridge (SEIR; Capricorn–Antarctica) and use them to calculate 2-plate finite rotations for anomalies 34 to 20 (84 to 43 Ma). Central Indian Ridge (CIR; Capricorn–Africa) rotations are calculated by summing the SWIR and SEIR rotations. These rotations provide a high-resolution record of changes in the motion of India and Africa at the time of the onset of the Reunion plume head. An analysis of the relative velocities of India, Africa and Antarctica leads to a refinement of previous observations that the speedup of India relative to the mantle was accompanied by a slowdown of Africa. The most rapid slowdown of Africa occurs around Chron 32Ay (71 Ma), the time when India's motion relative to Africa notably starts to accelerate. Using the most recent Geomagnetic Polarity Timescale (GTS12) we show that India's velocity relative to Africa was characterized by an acceleration from roughly 60 to 180 mm yr –1 between 71 and 66 Ma, a short pulse of superfast motion (~180 mm yr –1 ) between 66 and 63 Ma, an abrupt slowdown to 120 mm yr –1 between 63 and 62 Ma, and then a long period (63 to 47 Ma) of gradual slowing, but still fast motion (~100 mm yr –1 ), which ends with a rapid slowdown after Chron 21o (47 Ma). Changes in the velocities of Africa and India with respect to the mantle follow a similar pattern. The fastest motion of India relative to the mantle, ~220 mm yr –1 , occurs during Chron 29R. The SWIR rotations constrain three significant changes in the migration path of the Africa–Antarctic stage poles: following Chron 33y (73 Ma), following Chron 31y (68 Ma), and following Chron 24o (54 Ma). The change in the migration path of the SWIR stage poles following Chron 33y is coincident with the most rapid slowdown in Africa's motion. The change in the migration path after Chron 31y, although coincident with the most rapid acceleration of India's northward motion, may be related to changes in ridge push forces on the SWIR associated with the onset of extension along the Bain transform fault zone. The initial slowdown in India's motion relative to Africa between 63 and 62 Ma is more abrupt than predictions based on published plume head force models, suggesting it might have been caused by a change in plate boundary forces. The abrupt change in the migration path of the SWIR stage poles after Chron 24o is not associated with major changes in the velocities of either Africa or India and may reflect Atlantic basin plate motion changes associated with the arrival at the Earth's surface of the Iceland plume head. The abruptness of India's slowdown after Chron 21o is consistent with a collision event.

Description: Thin plate flexure theory provides an accurate model for the response of the lithosphere to vertical loads on horizontal length scales ranging from tens to hundreds of kilometres. Examples include flexure at seamounts, fracture zones, sedimentary basins and subduction zones. When applying this theory to real world situations, most studies assume a locally uniform plate thickness to enable simple Fourier transform solutions. However, in cases where the amplitude of the flexure is prominent, such as subduction zones, or there are rapid variations in seafloor age, such as fracture zones, these models are inadequate. Here we present a computationally efficient algorithm for solving the thin plate flexure equation for non-uniform plate thickness and arbitrary vertical load. The iterative scheme takes advantage of the 2-D fast Fourier transform to perform calculations in both the spatial and spectral domains, resulting in an accurate and computationally efficient solution. We illustrate the accuracy of the method through comparisons with known analytic solutions. Finally, we present results from three simple models demonstrating the differences in trench outer rise flexure when 2-D variations in plate rigidity and applied bending moment are taken into account. Although we focus our analysis on ocean trench flexure, the method is applicable to other 2-D flexure problems having spatial rigidity variations such as seamount loading of a thermally eroded lithosphere or flexure across the continental–oceanic crust boundary.

Description: Theory has been long established for computing the elastic response of a spherically symmetric terrestrial planetary body to both body tide and surface loading forces. However, for a planet with laterally heterogeneous mantle structure, the response is usually computed using a fully numerical approach. In this paper, we develop a semi-analytic method based on perturbation theory to solve for the elastic response of a planetary body with lateral heterogeneities in its mantle. We present a derivation of the governing equations for our second-order perturbation method and use them to study the high-order tidal effects caused by mode coupling between degree-2 body tide forcing and the laterally heterogeneous elastic structure of the mantle. We test our method by applying it to the Moon in which small long-wavelength lateral heterogeneities are assumed to exist in the elastic moduli of the lunar mantle. The tidal response of the Moon is determined mode by mode, for lateral heterogeneities with different depth ranges within the mantle and different horizontal scales. Our perturbation method solutions are compared with numerical results, showing remarkable agreement between the two methods. We conclude that our perturbation method provides accurate results and can be adapted to address a variety of forward and inverse response problems.

Description: We examine enrollment in the U.S. Medicaid and Supplemental Nutrition Assistance Programs (SNAP) and find that while SNAP-eligible adults in poor physical health and with multiple chronic conditions are more likely to jointly enroll in SNAP and Medicaid, they are less likely to enroll in SNAP alone. We also find that the conditional probability of SNAP enrollment given Medicaid participation is higher for individuals with multiple chronic conditions. As a result, the expansion of Medicaid and state policies that promote enrollment coordination between SNAP and Medicaid are expected to increase the number of individuals in SNAP with chronic medical conditions.

Description: At odds with a vast body of economic evidence reporting exceptionally high rates of return to investments in agricultural research and development (R&D), growth in public R&D spending for food and agriculture has slowed in numerous, especially rich, countries worldwide. The observed R&D spending behavior is consistent with a determination that the reported rates of return are perceived as implausible by policy makers. We examine this notion by scrutinizing 2,242 investment evaluations reported in 372 separate studies from 1958 to 2011. We find that the internal rate of return (IRR) is the predominant summary measure of investment performance used in the literature despite methodological criticisms dating back more than a half century. The reported IRRs imply rates of return that are implausibly high. We investigate the reasons for these implausibly high estimates by analytically comparing the IRR to the modified internal rate of return (MIRR). The MIRR addresses several methodological concerns with using the IRR, has the intuitive interpretation as the annual compounding interest rate paid by an investment, and is directly related to the benefit–cost ratio. To obtain more credible rate of return estimates, we then develop a novel method for recalibrating previously reported IRR estimates using the MIRR when there is limited information on an investment's stream of benefits and costs. Our recalibrated estimates of the rate of return are more modest (median of 9.8% versus 39% per year); however, they are still substantial enough to question the current scaling back of public agricultural R&D spending in many countries.