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High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species.sup.1-4. To address this issue, the international Genome 10K (G10K) consortium.sup.5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences. The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights., Author(s): Arang Rhie [sup.1] , Shane A. McCarthy [sup.2] [sup.3] , Olivier Fedrigo [sup.4] , Joana Damas [sup.5] , Giulio Formenti [sup.4] [sup.6] , Sergey Koren [sup.1] , Marcela Uliano-Silva [...]

Canada is exposed to rare but potentially destructive earthquakes that threaten densely settled metropolitan centers in many parts of the country. To assess the impacts and consequences of future natural-hazard events and help advance policy goals and objectives of the Sendai Framework for Disaster Risk Reduction, Natural Resources Canada, through a collaborative partnership with the Global Earthquake Model Foundation, produced a national seismic risk model. Developing this model has required the creation of a national exposure inventory, Canadian-specific fragility and vulnerability curves, and significant simplification of the Canadian Seismic Hazard Model which forms the basis for the design seismic hazard values of the National Building Code of Canada. Using the Global Earthquake Model Foundation's OpenQuake Engine, probabilistic stochastic risk modeling is completed under baseline and simulated retrofit conditions to assess seismic risk at the neighborhood level for all settled areas in Canada. Output risk metrics include the expected immediate physical impacts of earthquake events such as building damage, casualties, and direct economic losses. This article documents the technical details of the modeling approach including a description of novel data sets in use, a summary of the extensive sensitivity testing undertaken, and characterization of quality control implemented in the absence of usable validating earthquake loss data. The results from this model, such as loss exceedance curves and annual average losses, provide an open, accessible and quantitative base of evidence for decision-making at local, regional, and national levels. As a large country with a complex seismic hazard model and dispersed populations, this Canadian study is unique. However, the challenges faced and solutions offered are likely to be of interest to other nations pursuing similar programs. [ABSTRACT FROM AUTHOR]

Numerous novel adaptations characterise the radiation of notothenioids, the dominant fish group in the freezing seas of the Southern Ocean. To improve understanding of the evolution of this iconic fish group, here we generate and analyse new genome assemblies for 24 species covering all major subgroups of the radiation, including five long-read assemblies. We present a new estimate for the onset of the radiation at 10.7 million years ago, based on a time-calibrated phylogeny derived from genome-wide sequence data. We identify a two-fold variation in genome size, driven by expansion of multiple transposable element families, and use the long-read data to reconstruct two evolutionarily important, highly repetitive gene family loci. First, we present the most complete reconstruction to date of the antifreeze glycoprotein gene family, whose emergence enabled survival in sub-zero temperatures, showing the expansion of the antifreeze gene locus from the ancestral to the derived state. Second, we trace the loss of haemoglobin genes in icefishes, the only vertebrates lacking functional haemoglobins, through complete reconstruction of the two haemoglobin gene clusters across notothenioid families. Both the haemoglobin and antifreeze genomic loci are characterised by multiple transposon expansions that may have driven the evolutionary history of these genes. The notothenioid radiation is a remarkable group of fish adapted to life in the icy waters of the Southern Ocean. This study investigates the evolutionary history of this group and the basis of their adaption to cold environments through genomic analysis of 24 new genome assemblies. [ABSTRACT FROM AUTHOR]

An attempt to robustify the Bayesian vector autoregression is discussed by studying the innovative outliers. A summary of the result of outlier identification is presented.

Background The tufted duck is a non-model organism that experiences high mortality in highly pathogenic avian influenza outbreaks. It belongs to the same bird family (Anatidae) as the mallard, one of the best-studied natural hosts of low-pathogenic avian influenza viruses. Studies in non-model bird species are crucial to disentangle the role of the host response in avian influenza virus infection in the natural reservoir. Such endeavour requires a high-quality genome assembly and transcriptome. Findings This study presents the first high-quality, chromosome-level reference genome assembly of the tufted duck using the Vertebrate Genomes Project pipeline. We sequenced RNA (complementary DNA) from brain, ileum, lung, ovary, spleen, and testis using Illumina short-read and Pacific Biosciences long-read sequencing platforms, which were used for annotation. We found 34 autosomes plus Z and W sex chromosomes in the curated genome assembly, with 99.6% of the sequence assigned to chromosomes. Functional annotation revealed 14,099 protein-coding genes that generate 111,934 transcripts, which implies a mean of 7.9 isoforms per gene. We also identified 246 small RNA families. Conclusions This annotated genome contributes to continuing research into the host response in avian influenza virus infections in a natural reservoir. Our findings from a comparison between short-read and long-read reference transcriptomics contribute to a deeper understanding of these competing options. In this study, both technologies complemented each other. We expect this annotation to be a foundation for further comparative and evolutionary genomic studies, including many waterfowl relatives with differing susceptibilities to avian influenza viruses. [ABSTRACT FROM AUTHOR]

The reed warbler (Acrocephalus scirpaceus) is a long-distance migrant passerine with a wide distribution across Eurasia. This species has fascinated researchers for decades, especially its role as host of a brood parasite, and its capacity for rapid phenotypic change in the face of climate change. Currently, it is expanding its range northwards in Europe, and is altering its migratory behavior in certain areas. Thus, there is great potential to discover signs of recent evolution and its impact on the genomic composition of the reed warbler. Here, we present a high-quality reference genome for the reed warbler, based on PacBio, 10×, and Hi-C sequencing. The genome has an assembly size of 1,075,083,815 bp with a scaffold N50 of 74,438,198 bp and a contig N50 of 12,742,779 bp. BUSCO analysis using aves_odb10 as a model showed that 95.7% of BUSCO genes were complete. We found unequivocal evidence of two separate macrochromosomal fusions in the reed warbler genome, in addition to the previously identified fusion between chromosome Z and a part of chromosome 4A in the Sylvioidea superfamily. We annotated 14,645 protein-coding genes, and a BUSCO analysis of the protein sequences indicated 97.5% completeness. This reference genome will serve as an important resource, and will provide new insights into the genomic effects of evolutionary drivers such as coevolution, range expansion, and adaptations to climate change, as well as chromosomal rearrangements in birds. [ABSTRACT FROM AUTHOR]

Abstract Background The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest. Results We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced. Conclusions We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves the loss of a single hemoglobin gene cluster after the whole genome duplication (WGD) at the base of the teleost radiation but prior to the salmonid-specific WGD, which then produced the duplicated copies seen today. We also propose that the relatively high number of hemoglobin genes as well as the presence of non-Bohr β hemoglobin genes may be due to the dynamic life history of salmon and the diverse environmental conditions that the species encounters. Data deposition: BACs S0155C07 and S0079J05 (fps135): GenBank GQ898924; BACs S0055H05 and S0014B03 (fps1046): GenBank GQ898925

The vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline for more than 20 years resulting from inadvertent deaths due to the increasing use of large‐mesh gillnets. To understand the evolutionary and demographic history of the vaquita, we used combined long‐read sequencing and long‐range scaffolding methods with long‐ and short‐read RNA sequencing to generate a near error‐free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome‐length autosome scaffolds and the X‐chromosome scaffold, with a scaffold N50 of 115 Mb. Genome‐wide heterozygosity is the lowest (0.01%) of any mammalian species analysed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long‐term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long‐term population stability at less than 5,000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health. see also the Perspective by Annabel Whibley [ABSTRACT FROM AUTHOR]

Abstract Background With a whole genome duplication event and wealth of biological data, salmonids are excellent model organisms for studying evolutionary processes, fates of duplicated genes and genetic and physiological processes associated with complex behavioral phenotypes. It is surprising therefore, that no salmonid genome has been sequenced. Atlantic salmon (Salmo salar) is a good representative salmonid for sequencing given its importance in aquaculture and the genomic resources available. However, the size and complexity of the genome combined with the lack of a sequenced reference genome from a closely related fish makes assembly challenging. Given the cost and time limitations of Sanger sequencing as well as recent improvements to next generation sequencing technologies, we examined the feasibility of using the Genome Sequencer (GS) FLX pyrosequencing system to obtain the sequence of a salmonid genome. Eight pooled BACs belonging to a minimum tiling path covering ~1 Mb of the Atlantic salmon genome were sequenced by GS FLX shotgun and Long Paired End sequencing and compared with a ninth BAC sequenced by Sanger sequencing of a shotgun library. Results An initial assembly using only GS FLX shotgun sequences (average read length 248.5 bp) with ~30× coverage allowed gene identification, but was incomplete even when 126 Sanger-generated BAC-end sequences (~0.09× coverage) were incorporated. The addition of paired end sequencing reads (additional ~26× coverage) produced a final assembly comprising 175 contigs assembled into four scaffolds with 171 gaps. Sanger sequencing of the ninth BAC (~10.5× coverage) produced nine contigs and two scaffolds. The number of scaffolds produced by the GS FLX assembly was comparable to Sanger-generated sequencing; however, the number of gaps was much higher in the GS FLX assembly. Conclusion These results represent the first use of GS FLX paired end reads for de novo sequence assembly. Our data demonstrated that this improved the GS FLX assemblies; however, with respect to de novo sequencing of complex genomes, the GS FLX technology is limited to gene mining and establishing a set of ordered sequence contigs. Currently, for a salmonid reference sequence, it appears that a substantial portion of sequencing should be done using Sanger technology.

Genome sequence assemblies provide the basis for our understanding of biology. Generating error-free assemblies is therefore the ultimate, but sadly still unachieved goal of a multitude of research projects. Despite the ever-advancing improvements in data generation, assembly algorithms and pipelines, no automated approach has so far reliably generated near error-free genome assemblies for eukaryotes. Whilst working towards improved datasets and fully automated pipelines, assembly evaluation and curation is actively used to bridge this shortcoming and significantly reduce the number of assembly errors. In addition to this increase in product value, the insights gained from assembly curation are fed back into the automated assembly strategy and contribute to notable improvements in genome assembly quality. We describe our tried and tested approach for assembly curation using gEVAL, the genome evaluation browser. We outline the procedures applied to genome curation using gEVAL and also our recommendations for assembly curation in a gEVAL-independent context to facilitate the uptake of genome curation in the wider community. [ABSTRACT FROM AUTHOR]

This paper presents three approaches to minimize and eliminate scrap from stamping a single shape arranged in a single row or double rows on strip raw materials. In the first approach, interlocking shapes are generated. Although such shapes are scrap-free, they require congruent lines in the design. At the early stages of the design process, a skilful designer can compromise between functional features and symmetric features to improve nesting. The second approach is to characterize a shape by parallel lines bounding it. Specifically, the method to find a minimum area parallelogram that encloses a given convex shape is discussed. The result, gives the optimum arrangement of a convex shape in single row. The third approach involves the nesting of a given shape in a specified pattern. Three computational algorithms for the single and double row arrangements are given. The double row arrangement includes a half-turn or a mirror reflection. The three approaches are all based on the concept of interlocking shapes and they can readily be implemented on a small computer. Depending on the design environment and the piece shape, one of the approaches can be used. [ABSTRACT FROM AUTHOR]

This study examines the relationship between financial development and economic growth across Chinese provinces with switching causality. Four states are considered: bidirectional causality (state 1); one-way causality from growth to finance (state 2); one-way causality from finance to growth (state 3); and non-causality (state 4). While state 3 dominates in developed regions, states 1 and 3 occur intermittently in other regions. This implies that the demand for financial services induced by local economic growth plays a stronger role in driving financial development in under-developed regions. Consistent with prior research, bank loans negatively affect economic growth in China. [ABSTRACT FROM AUTHOR]

The issue of house price convergence in 34 Chinese cities is investigated. We augmented the convergence model with contemporaneous spatial dependence in house prices and found that price convergence and positive spatial spillover are both present. We explicitly addressed the endogeneity problem by introducing a Bayesian instrumental variable setup, which was estimated with particle filtering techniques. From a growth poles perspective, the empirical evidence indicates that the spread effect in regional house prices outweighs the backwash effect. The identified positive spatial spillover has two effects on the growth of house prices in Chinese cities. First, the spillover elevates the trajectories of the steady-state growth paths of house prices. Second, the spillover narrows the gaps between the growth paths of house prices in neighbouring cities. Shocks to the socio-economic variables of a city generate their own effects on domestic house prices that dominate the effects arising from cross-city price feedbacks, thus mitigating the prospect of level convergence. Our findings also suggest a collaborating role between time and spatial dependence parameters. The identification of inter-city spillover, which is a conditioning factor for regional house price convergence, offers implications to policies that are most likely to be effective in reducing regional disparity. [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

We prospectively evaluated the accuracy of the 2007 World Health Organization (WHO) criteria for diagnosing polycythemia vera (PV), especially in "early-stage" patients. A total of 28 of 30 patients were diagnosed as PV owing to an elevated Cr-51 red cell mass (RCM), JAK2 positivity, and at least 1 minor criterion. A total of 18 PV patients did not meet the WHO criterion for an increased hemoglobin value and 8 did not meet the WHO criterion for an increased hematocrit value. Bone marrow morphology was very valuable for diagnosis. Low serum erythropoietin (EPO) values were specific for PV, but normal EPO values were found at presentation (20%). We recommend revision of the WHO criteria, especially to distinguish early-stage PV from essential thrombocythemia. Major criteria remain JAK2 positivity and increased red cell volume, but Cr-51 RCM is mandatory for patients who do not meet the defined elevated hemoglobin or hematocrit value (>18.5 g/dL and 60% in men and >16.5 g/dL and 56% in women, respectively). Minor criteria remain bone marrow histology or a low serum EPO value. For patients with a normal EPO value, marrow examination is mandatory for diagnostic confirmation. Because the therapies for myeloproliferative disorders differ, our data have major clinical implications [ABSTRACT FROM AUTHOR]

Motivation: For most research approaches, genome analyses are dependent on the existence of a high quality genome reference assembly. However, the local accuracy of an assembly remains difficult to assess and improve. The gEVAL browser allows the user to interrogate an assembly in any region of the genome by comparing it to different datasets and evaluating the concordance. These analyses include: a wide variety of sequence alignments, comparative analyses of multiple genome assemblies, and consistency with optical and other physical maps. gEVAL highlights allelic variations, regions of low complexity, abnormal coverage, and potential sequence and assembly errors, and offers strategies for improvement. Although gEVAL focuses primarily on sequence integrity, it can also display arbitrary annotation including from Ensembl or TrackHub sources. We provide gEVAL web sites for many human, mouse, zebrafish and chicken assemblies to support the Genome Reference Consortium, and gEVAL is also downloadable to enable its use for any organism and assembly. [ABSTRACT FROM AUTHOR]

Background: With a whole genome duplication event and wealth of biological data, salmonids are excellent model organisms for studying evolutionary processes, fates of duplicated genes and genetic and physiological processes associated with complex behavioral phenotypes. It is surprising therefore, that no salmonid genome has been sequenced. Atlantic salmon (Salmo salar) is a good representative salmonid for sequencing given its importance in aquaculture and the genomic resources available. However, the size and complexity of the genome combined with the lack of a sequenced reference genome from a closely related fish makes assembly challenging. Given the cost and time limitations of Sanger sequencing as well as recent improvements to next generation sequencing technologies, we examined the feasibility of using the Genome Sequencer (GS) FLX pyrosequencing system to obtain the sequence of a salmonid genome. Eight pooled BACs belonging to a minimum tiling path covering ~1 Mb of the Atlantic salmon genome were sequenced by GS FLX shotgun and Long Paired End sequencing and compared with a ninth BAC sequenced by Sanger sequencing of a shotgun library. Results: An initial assembly using only GS FLX shotgun sequences (average read length 248.5 bp) with ~30x coverage allowed gene identification, but was incomplete even when 126 Sanger-generated BAC-end sequences (~0.09x coverage) were incorporated. The addition of paired end sequencing reads (additional ~26x coverage) produced a final assembly comprising 175 contigs assembled into four scaffolds with 171 gaps. Sanger sequencing of the ninth BAC (~10.5x coverage) produced nine contigs and two scaffolds. The number of scaffolds produced by the GS FLX assembly was comparable to Sanger-generated sequencing; however, the number of gaps was much higher in the GS FLX assembly. Conclusion: These results represent the first use of GS FLX paired end reads for de novo sequence assembly. Our data demonstrated that this improved the GS FLX assemblies; however, with respect to de novo sequencing of complex genomes, the GS FLX technology is limited to gene mining and establishing a set of ordered sequence contigs. Currently, for a salmonid reference sequence, it appears that a substantial portion of sequencing should be done using Sanger technology. [ABSTRACT FROM AUTHOR]

This paper studies the use of patent statistics in identifying four aspects of technological structure, namely, the potential knowledge pool, cumulativeness, inter-firm homogeneity in technology levels, and the scope of innovations. The firms are sampled from the chemical (CHEM), the computer (COM) and the electrical and electronic (EE) industries worldwide. Using the proxies defined, we find that (i) the contributions of intra-industry spillover are low, at 12%, 10%, and 9% for the three industries respectively; (ii) they can internalize 15%, 19% and 13% of their previous research efforts respectively; and (iii) a positive relationship between knowledge spillover and technology overlap, and between scope of innovation and number of patents being cited in future. [ABSTRACT FROM AUTHOR]

Investigates investment strategy books and their effectiveness in providing readers with trading strategies. Classification of several investment books; Discussion of the trading rule discussed in the book 'What Works on Wall Street,' by James P. O'Shaughnessy; Result of a test on the effectiveness of the rule discussed in the book in the London equity market of England.

Having shown at the end of the 19th century interest in Western ideas about individualism, Chinese reformers and liberal intellectuals by the 1920's had proceeded from general misunderstanding of both liberalism and individualism - as in the works of Yan Fu (1853-1921) and Liang Qichao (1873-1929) - to an adequate interpretation of these ideas by Zhou Zuoren (1885-1967).