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Sample records for hotspots rare genomic

  1. Genomic hotspots but few recurrent fusion genes in breast cancer.

    Science.gov (United States)

    Fimereli, Danai; Fumagalli, Debora; Brown, David; Gacquer, David; Rothé, Françoise; Salgado, Roberto; Larsimont, Denis; Sotiriou, Christos; Detours, Vincent

    2018-02-13

    The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations. Overall, 370 fusions were detected across the majority of the samples. HER2+ samples had significantly more fusions than triple negative and luminal subtypes. The number of fusions was correlated with histological grade, Ki67 and tumor size. Clusters of fusion genes were observed across the genome and a significant correlation of fusions with copy number aberrations and more specifically amplifications was also revealed. Despite the large number of fusion events, only a few were recurrent, while recurrent individual genes forming fusions with different partners were also detected including the estrogen receptor 1 gene in the previously detected ESR1 - CCDC170 fusion. Overall we detected novel gene fusion events while we confirmed previously reported fusions. Genomic hotspots of fusion genes, differences between subtypes and small number of recurrent fusions are the most relevant characteristics of these events in breast cancer. Further investigation is necessary to comprehend the biological significance of these fusions. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  2. Drosophila duplication hotspots are associated with late-replicating regions of the genome.

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    Margarida Cardoso-Moreira

    2011-11-01

    Full Text Available Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulans-Drosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is

  3. Genomic features shaping the landscape of meiotic double-strand-break hotspots in maize.

    Science.gov (United States)

    He, Yan; Wang, Minghui; Dukowic-Schulze, Stefanie; Zhou, Adele; Tiang, Choon-Lin; Shilo, Shay; Sidhu, Gaganpreet K; Eichten, Steven; Bradbury, Peter; Springer, Nathan M; Buckler, Edward S; Levy, Avraham A; Sun, Qi; Pillardy, Jaroslaw; Kianian, Penny M A; Kianian, Shahryar F; Chen, Changbin; Pawlowski, Wojciech P

    2017-11-14

    Meiotic recombination is the most important source of genetic variation in higher eukaryotes. It is initiated by formation of double-strand breaks (DSBs) in chromosomal DNA in early meiotic prophase. The DSBs are subsequently repaired, resulting in crossovers (COs) and noncrossovers (NCOs). Recombination events are not distributed evenly along chromosomes but cluster at recombination hotspots. How specific sites become hotspots is poorly understood. Studies in yeast and mammals linked initiation of meiotic recombination to active chromatin features present upstream from genes, such as absence of nucleosomes and presence of trimethylation of lysine 4 in histone H3 (H3K4me3). Core recombination components are conserved among eukaryotes, but it is unclear whether this conservation results in universal characteristics of recombination landscapes shared by a wide range of species. To address this question, we mapped meiotic DSBs in maize, a higher eukaryote with a large genome that is rich in repetitive DNA. We found DSBs in maize to be frequent in all chromosome regions, including sites lacking COs, such as centromeres and pericentromeric regions. Furthermore, most DSBs are formed in repetitive DNA, predominantly Gypsy retrotransposons, and only one-quarter of DSB hotspots are near genes. Genic and nongenic hotspots differ in several characteristics, and only genic DSBs contribute to crossover formation. Maize hotspots overlap regions of low nucleosome occupancy but show only limited association with H3K4me3 sites. Overall, maize DSB hotspots exhibit distribution patterns and characteristics not reported previously in other species. Understanding recombination patterns in maize will shed light on mechanisms affecting dynamics of the plant genome.

  4. Seeds as emerging hotspot for maintenance of genome stability

    Czech Academy of Sciences Publication Activity Database

    Diaz, Mariana; Pečinka, Aleš

    2017-01-01

    Roč. 82, č. 5 (2017), s. 467-470 ISSN 0011-4545 Institutional support: RVO:61389030 Keywords : Chromatin * Chromosome * DNA damage repair * Genome stability * Seed * Structural maintenance of chromosome Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 0.913, year: 2016

  5. The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

    Science.gov (United States)

    Lesecque, Yann; Glémin, Sylvain; Lartillot, Nicolas; Mouchiroud, Dominique; Duret, Laurent

    2014-11-01

    Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

  6. The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

    Directory of Open Access Journals (Sweden)

    Yann Lesecque

    2014-11-01

    Full Text Available Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC, which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

  7. Rare variant density across the genome and across populations

    OpenAIRE

    Raska Paola; Zhu Xiaofeng

    2011-01-01

    Abstract Next-generation sequencing allows for a new focus on rare variant density for conducting analyses of association to disease and for narrowing down the genomic regions that show evidence of functionality. In this study we use the 1000 Genomes Project pilot data as distributed by Genetic Analysis Workshop 17 to compare rare variant densities across seven populations. We made the comparisons using regressions of rare variants on total variant counts per gene for each population and Taji...

  8. Human and non-human primate genomes share hotspots of positive selection.

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    David Enard

    2010-02-01

    Full Text Available Among primates, genome-wide analysis of recent positive selection is currently limited to the human species because it requires extensive sampling of genotypic data from many individuals. The extent to which genes positively selected in human also present adaptive changes in other primates therefore remains unknown. This question is important because a gene that has been positively selected independently in the human and in other primate lineages may be less likely to be involved in human specific phenotypic changes such as dietary habits or cognitive abilities. To answer this question, we analysed heterozygous Single Nucleotide Polymorphisms (SNPs in the genomes of single human, chimpanzee, orangutan, and macaque individuals using a new method aiming to identify selective sweeps genome-wide. We found an unexpectedly high number of orthologous genes exhibiting signatures of a selective sweep simultaneously in several primate species, suggesting the presence of hotspots of positive selection. A similar significant excess is evident when comparing genes positively selected during recent human evolution with genes subjected to positive selection in their coding sequence in other primate lineages and identified using a different test. These findings are further supported by comparing several published human genome scans for positive selection with our findings in non-human primate genomes. We thus provide extensive evidence that the co-occurrence of positive selection in humans and in other primates at the same genetic loci can be measured with only four species, an indication that it may be a widespread phenomenon. The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution.

  9. Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process.

    Science.gov (United States)

    Alanazi, Ibrahim O; Ebrahimie, Esmaeil

    2016-07-01

    Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

  10. Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in Heliconius erato.

    Directory of Open Access Journals (Sweden)

    Brian A Counterman

    2010-02-01

    Full Text Available Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD, and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as "supergenes." Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative

  11. The substantial first impact of bottom fishing on rare biodiversity hotspots: a dilemma for evidence-based conservation.

    Science.gov (United States)

    Cook, Robert; Fariñas-Franco, Jose M; Gell, Fiona R; Holt, Rohan H F; Holt, Terry; Lindenbaum, Charles; Porter, Joanne S; Seed, Ray; Skates, Lucie R; Stringell, Thomas B; Sanderson, William G

    2013-01-01

    This study describes the impact of the first passage of two types of bottom-towed fishing gear on rare protected shellfish-reefs formed by the horse mussel Modiolus modiolus (L.). One of the study sites was trawled and the other was scallop-dredged. Divers collected HD video imagery of epifauna from quadrats at the two study sites and directed infaunal samples from one site. The total number of epifaunal organisms was significantly reduced following a single pass of a trawl (90%) or scallop dredge (59%), as was the diversity of the associated community and the total number of M. modiolus at the trawled site. At both sites declines in anthozoans, hydrozoans, bivalves, echinoderms and ascidians accounted for most of the change. A year later, no recovery was evident at the trawled site and significantly fewer infaunal taxa (polychaetes, malacostracans, bivalves and ophuroids) were recorded in the trawl track. The severity of the two types of impact reflected the undisturbed status of the habitats compared to previous studies. As a 'priority habitat' the nature of the impacts described on M. modiolus communities are important to the development of conservation management policy and indicators of condition in Marine Protected Areas (EU Habitats Directive) as well as indicators of 'Good Environmental Status' under the European Union Marine Strategy Framework Directive. Conservation managers are under pressure to support decisions with good quality evidence. Elsewhere, indirect studies have shown declines of M. modiolus biogenic communities in fishing grounds. However, given the protected status of the rare habitat, premeditated demonstration of direct impact is unethical or illegal in Marine Protected Areas. This study therefore provides a unique opportunity to investigate the impact from fishing gear whilst at the same time reflecting on the dilemma of evidence-based conservation management.

  12. The substantial first impact of bottom fishing on rare biodiversity hotspots: a dilemma for evidence-based conservation.

    Directory of Open Access Journals (Sweden)

    Robert Cook

    Full Text Available This study describes the impact of the first passage of two types of bottom-towed fishing gear on rare protected shellfish-reefs formed by the horse mussel Modiolus modiolus (L.. One of the study sites was trawled and the other was scallop-dredged. Divers collected HD video imagery of epifauna from quadrats at the two study sites and directed infaunal samples from one site. The total number of epifaunal organisms was significantly reduced following a single pass of a trawl (90% or scallop dredge (59%, as was the diversity of the associated community and the total number of M. modiolus at the trawled site. At both sites declines in anthozoans, hydrozoans, bivalves, echinoderms and ascidians accounted for most of the change. A year later, no recovery was evident at the trawled site and significantly fewer infaunal taxa (polychaetes, malacostracans, bivalves and ophuroids were recorded in the trawl track. The severity of the two types of impact reflected the undisturbed status of the habitats compared to previous studies. As a 'priority habitat' the nature of the impacts described on M. modiolus communities are important to the development of conservation management policy and indicators of condition in Marine Protected Areas (EU Habitats Directive as well as indicators of 'Good Environmental Status' under the European Union Marine Strategy Framework Directive. Conservation managers are under pressure to support decisions with good quality evidence. Elsewhere, indirect studies have shown declines of M. modiolus biogenic communities in fishing grounds. However, given the protected status of the rare habitat, premeditated demonstration of direct impact is unethical or illegal in Marine Protected Areas. This study therefore provides a unique opportunity to investigate the impact from fishing gear whilst at the same time reflecting on the dilemma of evidence-based conservation management.

  13. From Agrobacterium to viral vectors: genome modification of plant cells by rare cutting restriction enzymes.

    Science.gov (United States)

    Marton, Ira; Honig, Arik; Omid, Ayelet; De Costa, Noam; Marhevka, Elena; Cohen, Barry; Zuker, Amir; Vainstein, Alexander

    2013-01-01

    Researchers and biotechnologists require methods to accurately modify the genome of higher eukaryotic cells. Such modifications include, but are not limited to, site-specific mutagenesis, site-specific insertion of foreign DNA, and replacement and deletion of native sequences. Accurate genome modifications in plant species have been rather limited, with only a handful of plant species and genes being modified through the use of early genome-editing techniques. The development of rare-cutting restriction enzymes as a tool for the induction of site-specific genomic double-strand breaks and their introduction as a reliable tool for genome modification in animals, animal cells and human cell lines have paved the way for the adaptation of rare-cutting restriction enzymes to genome editing in plant cells. Indeed, the number of plant species and genes which have been successfully edited using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and engineered homing endonucleases is on the rise. In our review, we discuss the basics of rare-cutting restriction enzyme-mediated genome-editing technology with an emphasis on its application in plant species.

  14. Genome sequences of rare, uncultured bacteria obtained by differential coverage binning of multiple metagenomes

    DEFF Research Database (Denmark)

    Albertsen, Mads; Hugenholtz, Philip; Skarshewski, Adam

    2013-01-01

    Reference genomes are required to understand the diverse roles of microorganisms in ecology, evolution, human and animal health, but most species remain uncultured. Here we present a sequence composition–independent approach to recover high-quality microbial genomes from deeply sequenced...... metagenomes. Multiple metagenomes of the same community, which differ in relative population abundances, were used to assemble 31 bacterial genomes, including rare (genomes were assembled into complete or near-complete chromosomes....... Four belong to the candidate bacterial phylum TM7 and represent the most complete genomes for this phylum to date (relative abundances, 0.06–1.58%). Reanalysis of published metagenomes reveals that differential coverage binning facilitates recovery of more complete and higher fidelity genome bins than...

  15. Rare and common regulatory variation in population-scale sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Stephen B Montgomery

    2011-07-01

    Full Text Available Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.

  16. Pan-Cancer Analysis of Mutation Hotspots in Protein Domains.

    Science.gov (United States)

    Miller, Martin L; Reznik, Ed; Gauthier, Nicholas P; Aksoy, Bülent Arman; Korkut, Anil; Gao, Jianjiong; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

    2015-09-23

    In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain mutation analysis also sharpens the functional interpretation of the impact of mutations, as domains more succinctly embody function than entire genes. By mapping mutations in 22 different tumor types to equivalent positions in multiple sequence alignments of domains, we confirm well-known functional mutation hotspots, identify uncharacterized rare variants in one gene that are equivalent to well-characterized mutations in another gene, detect previously unknown mutation hotspots, and provide hypotheses about molecular mechanisms and downstream effects of domain mutations. With the rapid expansion of cancer genomics projects, protein domain hotspot analysis will likely provide many more leads linking mutations in proteins to the cancer phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Hotspot advance speed - hotspot size/core-hotspot distance relation ...

    African Journals Online (AJOL)

    We examined the evolution of extragalactic radio sources using the observed corehotspot distance and hotspot size. Analysis indicates a fairly strong positive correlation in the ratio of core-hotspot distance to hotspot size between that of the approaching arm and the receding arm with a correlation coefficient of r ~ 0.7.

  18. Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

    Science.gov (United States)

    Schorn, Michelle A.; Alanjary, Mohammad M.; Aguinaldo, Kristen; Korobeynikov, Anton; Podell, Sheila; Patin, Nastassia; Lincecum, Tommie; Jensen, Paul R.; Ziemert, Nadine

    2016-01-01

    Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for exploration, as they are relatively unstudied, and their relatives are historically rich in secondary metabolites. PMID:27902408

  19. Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters.

    Science.gov (United States)

    Schorn, Michelle A; Alanjary, Mohammad M; Aguinaldo, Kristen; Korobeynikov, Anton; Podell, Sheila; Patin, Nastassia; Lincecum, Tommie; Jensen, Paul R; Ziemert, Nadine; Moore, Bradley S

    2016-12-01

    Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for exploration, as they are relatively unstudied, and their relatives are historically rich in secondary metabolites.

  20. GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases.

    Science.gov (United States)

    Koile, Daniel; Cordoba, Marta; de Sousa Serro, Maximiliano; Kauffman, Marcelo Andres; Yankilevich, Patricio

    2018-01-27

    GenIO is a novel web-server, designed to assist clinical genomics researchers and medical doctors in the diagnostic process of rare genetic diseases. The tool identifies the most probable variants causing a rare disease, using the genomic and clinical information provided by a medical practitioner. Variants identified in a whole-genome, whole-exome or target sequencing studies are annotated, classified and filtered by clinical significance. Candidate genes associated with the patient's symptoms, suspected disease and complementary findings are identified to obtain a small manageable number of the most probable recessive and dominant candidate gene variants associated with the rare disease case. Additionally, following the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and recommendations, all potentially pathogenic variants that might be contributing to disease and secondary findings are identified. A retrospective study was performed on 40 patients with a diagnostic rate of 40%. All the known genes that were previously considered as disease causing were correctly identified in the final inherit model output lists. In previously undiagnosed cases, we had no additional yield. This unique, intuitive and user-friendly tool to assists medical doctors in the clinical genomics diagnostic process is openly available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .

  1. Molecular architecture of transcription factor hotspots in early adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Baek, Songjoon; Rabiee, Atefeh

    2014-01-01

    Transcription factors have recently been shown to colocalize in hotspot regions of the genome, which are further clustered into super-enhancers. However, the detailed molecular organization of transcription factors at hotspot regions is poorly defined. Here, we have used digital genomic footprint......Transcription factors have recently been shown to colocalize in hotspot regions of the genome, which are further clustered into super-enhancers. However, the detailed molecular organization of transcription factors at hotspot regions is poorly defined. Here, we have used digital genomic...

  2. Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in the Heliconius melpomene clade.

    Directory of Open Access Journals (Sweden)

    Simon W Baxter

    2010-02-01

    Full Text Available Wing patterning in Heliconius butterflies is a longstanding example of both Müllerian mimicry and phenotypic radiation under strong natural selection. The loci controlling such patterns are "hotspots" for adaptive evolution with great allelic diversity across different species in the genus. We characterise nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium, and candidate gene expression at two loci and across multiple hybrid zones in Heliconius melpomene and relatives. Alleles at HmB control the presence or absence of the red forewing band, while alleles at HmYb control the yellow hindwing bar. Across HmYb two regions, separated by approximately 100 kb, show significant genotype-by-phenotype associations that are replicated across independent hybrid zones. In contrast, at HmB a single peak of association indicates the likely position of functional sites at three genes, encoding a kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb and HmB there is evidence for enhanced linkage disequilibrium (LD between associated sites separated by up to 14 kb, suggesting that multiple sites are under selection. However, there was no evidence for reduced variation or deviations from neutrality that might indicate a recent selective sweep, consistent with these alleles being relatively old. Of the three genes showing an association with the HmB locus, the kinesin shows differences in wing disc expression between races that are replicated in the co-mimic, Heliconius erato, providing striking evidence for parallel changes in gene expression between Müllerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show a haplotype structure maintained by selection, but no evidence for a recent selective sweep. The complex genetic pattern contrasts with the simple genetic basis of many adaptive traits studied previously, but may provide a better model for most adaptation in natural populations

  3. The effect of rare alleles on estimated genomic relationships from whole genome sequence data

    NARCIS (Netherlands)

    Eynard, S.E.; Windig, J.J.; Leroy, G.; Binsbergen, van R.; Calus, M.P.L.

    2015-01-01

    Relationships between individuals and inbreeding coefficients are commonly used for breeding decisions, but may be affected by the type of data used for their estimation. The proportion of variants with low Minor Allele Frequency (MAF) is larger in whole genome sequence (WGS) data compared to Single

  4. A GENOME-WIDE ASSOCIATION STUDY OF BRONCHODILATOR RESPONSE IN LATINOS IMPLICATES RARE VARIANTS

    Science.gov (United States)

    Drake, Katherine A.; Torgerson, Dara G.; Gignoux, Christopher R.; Galanter, Joshua M.; Roth, Lindsey A.; Huntsman, Scott; Eng, Celeste; Oh, Sam S.; Yee, Sook Wah; Lin, Lawrence; Bustamante, Carlos D.; Moreno-Estrada, Andrés; Sandoval, Karla; Davis, Adam; Borrell, Luisa N.; Farber, Harold J.; Kumar, Rajesh; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Chapela, Rocio; Ford, Jean G.; LeNoir, Michael A.; Lurmann, Fred; Meade, Kelley; Serebrisky, Denise; Thyne, Shannon; Rodríguez-Cintrón, William; Sen, Saunak; Rodríguez-Santana, José R.; Hernandez, Ryan D.; Giacomini, Kathleen M.; Burchard, Esteban G.

    2013-01-01

    Rationale The primary rescue medication to treat acute asthma exacerbation is short-acting β2- adrenergic receptor (β2AR) agonists (SABAs), however there is variation in how well an individual responds to treatment. Although these differences may be due to environmental factors, there is mounting evidence for a genetic contribution to variability in bronchodilator drug response (BDR). Methods We performed a genome-wide association study (GWAS) for BDR in 1,782 Latino children with asthma using standard linear regression, adjusting for genetic ancestry and ethnicity, and performed replication studies in an additional 531 Latinos. We also performed admixture mapping across the genome by testing for an association between local European, African, and Native American ancestry and BDR, adjusting for genomic ancestry and ethnicity. Results We identified seven genetic variants associated with BDR at a genome-wide significant threshold (p<5×10−8), all of which had frequencies below 5%. Furthermore, we observed an excess of small p-values driven by rare variants (frequency < 5%), and by variants in the proximity of solute carrier (SLC) genes. Admixture mapping identified five significant peaks; fine mapping within these peaks identified two rare variants in SLC22A15 as being associated with increased BDR in Mexicans. Quantitative PCR and immunohistochemistry identified SLC22A15 as being expressed in the lung and bronchial epithelial cells. Conclusion Our results suggest that rare variation contributes to individual differences in response to albuterol in Latinos, notably in solute carrier genes that include membrane transport proteins involved in the transport of endogenous metabolites and xenobiotics. Resequencing in larger, multi-ethnic population samples and additional functional studies are required to further understand the role of rare variation in BDR. PMID:23992748

  5. Performance characteristics of the AmpliSeq Cancer Hotspot panel v2 in combination with the Ion Torrent Next Generation Sequencing Personal Genome Machine.

    Science.gov (United States)

    Butler, Kimberly S; Young, Megan Y L; Li, Zhihua; Elespuru, Rosalie K; Wood, Steven C

    2016-02-01

    Next-Generation Sequencing is a rapidly advancing technology that has research and clinical applications. For many cancers, it is important to know the precise mutation(s) present, as specific mutations could indicate or contra-indicate certain treatments as well as be indicative of prognosis. Using the Ion Torrent Personal Genome Machine and the AmpliSeq Cancer Hotspot panel v2, we sequenced two pancreatic cancer cell lines, BxPC-3 and HPAF-II, alone or in mixtures, to determine the error rate, sensitivity, and reproducibility of this system. The system resulted in coverage averaging 2000× across the various amplicons and was able to reliably and reproducibly identify mutations present at a rate of 5%. Identification of mutations present at a lower rate was possible by altering the parameters by which calls were made, but with an increase in erroneous, low-level calls. The panel was able to identify known mutations in these cell lines that are present in the COSMIC database. In addition, other, novel mutations were also identified that may prove clinically useful. The system was assessed for systematic errors such as homopolymer effects, end of amplicon effects and patterns in NO CALL sequence. Overall, the system is adequate at identifying the known, targeted mutations in the panel. Published by Elsevier Inc.

  6. Genome sequence of a diabetes-prone rodent reveals a mutation hotspot around the ParaHox gene cluster

    DEFF Research Database (Denmark)

    Hargreaves, Adam D.; Zhou, Long; Christensen, Josef

    2017-01-01

    The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing...... Pdx1 has been grossly affected by GC-biased mutation, leading to the highest divergence observed for this gene across the Bilateria. In addition to genomic insights into restricted caloric intake in a desert species, the discovery of a localized chromosomal region subject to elevated mutation suggests...

  7. Comprehensive genomic profiling of a rare thyroid follicular dendritic cell sarcoma

    Directory of Open Access Journals (Sweden)

    Jaime I. Davila

    2017-09-01

    Full Text Available We previously reported an extremely rare case of follicular dendritic cell sarcoma (FDCS presented as a thyroid mass. Given the rarity of this disease, there are no personalized and molecularly targeted treatment options due to the lack of knowledge in the genomic makeup of the tumor. A 44- year-old white woman was diagnosed with an extranodal FDCS in thyroid. The patient underwent a total thyroidectomy, central compartment dissection, parathyroid reimplantation, and adjuvant radiation therapy. Tumor DNA sequencing of 236 genes by FoundationOne panel found truncating mutations in PTEN and missense mutations in RET and TP53. However, patientmatched germline DNA was not sequenced which is critical for identification of true somatic mutations. Furthermore, the FoundationOne panel doesn’t measure genomic rearrangements which have been shown to be abundant in sarcomas and are associated with sarcoma tumorigenesis and progression. In the current study, we carried out comprehensive genomic sequencing of the tumor, adjacent normal tissues, and patient-matched blood, in an effort to understand the genomic makeup of this rare extranodal FDCS and to identify potential therapeutic targets. Eighty-one somatic point mutations were identified in tumor but not in adjacent normal tissues or blood. A clonal truncating mutation in the CLTCL1 gene, which stabilizes the mitotic spindle, was likely a driver mutation of tumorigenesis and could explain the extensive copy number aberrations (CNAs and genomic rearrangements in the tumor including a chr15/chr17 local chromothripsis resulted in 6 expressed fusion genes. The fusion gene HDGFRP3→SHC4 led to a 200-fold increase in the expression of oncogene SHC4 which is a potential target of the commercial drug Dasatinib. Missense mutations in ATM and splice-site mutation in VEGFR1 were also detected in addition to the TP53 missense mutation reported by FoundationOne.

  8. Reconstructing Rare Soil Microbial Genomes using in situ Enrichments and Metagenomics

    Directory of Open Access Journals (Sweden)

    Tom O Delmont

    2015-04-01

    Full Text Available Despite extensive direct sequencing efforts and advanced analytical tools, reconstructing microbial genomes from soil using metagenomics have been challenging due to the tremendous diversity and relatively uniform distribution of genomes found in this system. Here we used enrichment techniques in an attempt to decrease the complexity of a soil microbiome prior to sequencing by submitting it to a range of physical and chemical stresses in 23 separate microcosms for four months. The metagenomic analysis of these microcosms at the end of the treatment yielded 540Mb of assembly using standard de novo assembly techniques (a total of 559,555 genes and 29,176 functions, from which we could recover novel bacterial genomes, plasmids and phages. The recovered genomes belonged to Leifsonia (n=2, Rhodanobacter (n=5, Acidobacteria (n=2, Sporolactobacillus (n=2, novel nitrogen fixing taxon, Ktedonobacter (n=1, second representative of the family Ktedonobacteraceae, Streptomyces (n=3, novel polyketide synthase modules and Burkholderia (n=2, includes mega-plasmids conferring mercury resistance. Assembled genomes averaged to 5.9Mb, with relative abundances ranging from rare (0.01% in the original soil microbiome. Furthermore, we detected them in samples collected from geographically distant locations, particularly more in temperate soils compared to samples originating from high-latitude soils and deserts. To the best of our knowledge, this study is the first successful attempt to assemble multiple bacterial genomes directly from a soil sample. Our findings demonstrate that developing pertinent enrichment conditions can stimulate environmental genomic discoveries that would have been impossible to achieve with canonical approaches that focus solely upon post-sequencing data treatment.

  9. Reconstructing rare soil microbial genomes using in situ enrichments and metagenomics.

    Science.gov (United States)

    Delmont, Tom O; Eren, A Murat; Maccario, Lorrie; Prestat, Emmanuel; Esen, Özcan C; Pelletier, Eric; Le Paslier, Denis; Simonet, Pascal; Vogel, Timothy M

    2015-01-01

    Despite extensive direct sequencing efforts and advanced analytical tools, reconstructing microbial genomes from soil using metagenomics have been challenging due to the tremendous diversity and relatively uniform distribution of genomes found in this system. Here we used enrichment techniques in an attempt to decrease the complexity of a soil microbiome prior to sequencing by submitting it to a range of physical and chemical stresses in 23 separate microcosms for 4 months. The metagenomic analysis of these microcosms at the end of the treatment yielded 540 Mb of assembly using standard de novo assembly techniques (a total of 559,555 genes and 29,176 functions), from which we could recover novel bacterial genomes, plasmids and phages. The recovered genomes belonged to Leifsonia (n = 2), Rhodanobacter (n = 5), Acidobacteria (n = 2), Sporolactobacillus (n = 2, novel nitrogen fixing taxon), Ktedonobacter (n = 1, second representative of the family Ktedonobacteraceae), Streptomyces (n = 3, novel polyketide synthase modules), and Burkholderia (n = 2, includes mega-plasmids conferring mercury resistance). Assembled genomes averaged to 5.9 Mb, with relative abundances ranging from rare (0.01%) in the original soil microbiome. Furthermore, we detected them in samples collected from geographically distant locations, particularly more in temperate soils compared to samples originating from high-latitude soils and deserts. To the best of our knowledge, this study is the first successful attempt to assemble multiple bacterial genomes directly from a soil sample. Our findings demonstrate that developing pertinent enrichment conditions can stimulate environmental genomic discoveries that would have been impossible to achieve with canonical approaches that focus solely upon post-sequencing data treatment.

  10. Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy.

    Science.gov (United States)

    Oudejans, Cees; Poutsma, Ankie; Michel, Omar; Mulders, Joyce; Visser, Allerdien; van Dijk, Marie; Nauta, Tessa; Bokslag, Anouk; Paulus, Walter; de Haas, Andreas; Koolwijk, Pieter; de Groot, Christianne J M

    2016-01-01

    The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia. We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters. The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.

  11. Klebsiella pneumoniae asparagine tDNAs are integration hotspots for different genomic islands encoding microcin E492 production determinants and other putative virulence factors present in hypervirulent strains

    Directory of Open Access Journals (Sweden)

    Andrés Esteban Marcoleta

    2016-06-01

    Full Text Available Due to the developing of multi-resistant and invasive hypervirulent strains, Klebsiella pneumoniae has become one of the most urgent bacterial pathogen threats in the last years. Genomic comparison of a growing number of sequenced isolates has allowed the identification of putative virulence factors, proposed to be acquirable mainly through horizontal gene transfer. In particular, those related with synthesizing the antibacterial peptide microcin E492 (MccE492 and salmochelin siderophores were found to be highly prevalent among hypervirulent strains. The determinants for the production of both molecules were first reported as part of a 13-kbp segment of K. pneumoniae RYC492 chromosome, and were cloned and characterized in E. coli. However, the genomic context of this segment in K. pneumoniae remained uncharacterized.In this work we provided experimental and bioinformatics evidence indicating that the MccE492 cluster is part of a highly conserved 23-kbp genomic island (GI named GIE492, that was integrated in a specific asparagine-tRNA gene (asn-tDNA and was found in a high proportion of isolates from liver abscesses sampled around the world. This element resulted to be unstable and its excision frequency increased after treating bacteria with mytomicin C and upon the overexpression of the island-encoded integrase. Besides the MccE492 genetic cluster, it invariably included an integrase-coding gene, at least 7 protein-coding genes of unknown function, and a putative transfer origin that possibly allows this GI to be mobilized through conjugation. In addition, we analyzed the asn-tDNA loci of all the available K. pneumoniae assembled chromosomes to evaluate them as GI-integration sites. Remarkably, 73% of the strains harbored at least one GI integrated in one of the four asn-tDNA present in this species, confirming them as integration hotspots. Each of these tDNAs was occupied with different frequencies, although they were 100% identical. Also, we

  12. The pheV phenylalanine tRNA gene Klebsiella pneumoniae clinical isolates is an integration hotspot for possible niche-adaptation genomic islands.

    Science.gov (United States)

    Chen, Nan; Ou, Hong-Yu; van Aartsen, Jon Jurriaan; Jiang, XiaoFei; Li, Min; Yang, ZeHua; Wei, QuHao; Chen, XiaoYun; He, Xinyi; Deng, Zixin; Rajakumar, Kumar; Lu, Yuan

    2010-03-01

    Horizontally acquired genomic islands may allow bacteria to conquer and colonize previously uncharted niches. Four Klebsiella pneumoniae tRNA gene insertion hotspots (arg6, asn34, met56, and pheV) in 101 clinical isolates derived from blood, sputum, wound, bile or urine specimens were screened by long-range PCR for the presence or absence of integrated islands. The pheV phenylalanine tRNA gene was the most frequently occupied site and harbored at least three entirely distinct types of islands: (1) KpGI-1, a 3.7 kb island coding for four proteins, three of which showed high similarity to two hypothetical proteins and a Gcn5-related N-acetyltransferase in Salmonella enterica, (2) KpGI-2, a 6.4 kb island coding for five proteins including a truncated phage-like integrase, two helicase-related proteins, and a homolog of the functionally elusive Fic protein, and (3) KpGI-3, a 12.6 kb island which carried seven fimbriae-related genes, first identified in MGH78578. Consistent with the niche-adaptation hypothesis, KpGI-1-like islands which coded for the putative acetyltransferase were significantly over-represented in sputum isolates as compared to urine (P coded for Fic were also found at undefined locations in six other clinical isolates, though none possessed the other KpGI-2 genes. We propose that the pheV-associated islands described in this study may contribute to fine tuning and adaptation of K. pneumoniae strains toward preferred infection and/or colonization pathways.

  13. Genomic Resources of Three Pulsatilla Species Reveal Evolutionary Hotspots, Species-Specific Sites and Variable Plastid Structure in the Family Ranunculaceae

    Directory of Open Access Journals (Sweden)

    Monika Szczecińska

    2015-09-01

    Full Text Available Background: The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the continent. Most plants of the genus Pulsatilla are rare and endangered, which is why most research efforts focused on their biology, ecology and hybridization. The objective of this study was to develop genomic resources, including complete plastid genomes and nuclear rRNA clusters, for three sympatric Pulsatilla species that are most commonly found in Central Europe. The results will supply valuable information about genetic variation, which can be used in the process of designing primers for population studies and conservation genetics research. The complete plastid genomes together with the nuclear rRNA cluster can serve as a useful tool in hybridization studies. Methodology/principal findings: Six complete plastid genomes and nuclear rRNA clusters were sequenced from three species of Pulsatilla using the Illumina sequencing technology. Four junctions between single copy regions and inverted repeats and junctions between the identified locally-collinear blocks (LCB were confirmed by Sanger sequencing. Pulsatilla genomes of 120 unique genes had a total length of approximately 161–162 kb, and 21 were duplicated in the inverted repeats (IR region. Comparative plastid genomes of newly-sequenced Pulsatilla and the previously-identified plastomes of Aconitum and Ranunculus species belonging to the family Ranunculaceae revealed several variations in the structure of the genome, but the gene content remained constant. The nuclear rRNA cluster (18S-ITS1-5.8S-ITS2-26S of studied Pulsatilla species is 5795 bp long. Among five analyzed regions of the rRNA cluster, only Internal Transcribed Spacer 2 (ITS2 enabled the molecular delimitation of closely-related Pulsatilla

  14. Insights from early experience of a Rare Disease Genomic Medicine Multidisciplinary Team: a qualitative study.

    Science.gov (United States)

    Ormondroyd, Elizabeth; Mackley, Michael P; Blair, Edward; Craft, Jude; Knight, Julian C; Taylor, John; Taylor, Jenny C; Wilkie, Andrew Om; Watkins, Hugh

    2017-06-01

    Whole-exome/whole-genome sequencing (WES/WGS) has the potential to enhance genetic diagnosis of rare disease, and is increasingly becoming part of routine clinical care in mainstream medicine. Effective translation will require ongoing efforts in a number of areas including: selection of appropriate patients, provision of effective consent, pre- and post-test genetic counselling, improving variant interpretation algorithms and practices, and management of secondary findings including those found incidentally and those actively sought. Allied to this is the need for an effective education programme for all members of clinical teams involved in care of patients with rare disease, as well as to maintain public confidence in the use of these technologies. We established a Genomic Medicine Multidisciplinary Team (GM-MDT) in 2014 to build on the experiences of earlier successful research-based WES/WGS studies, to address these needs and to review results including pertinent and secondary findings. Here we report on a qualitative study of decision-making in the GM-MDT combined with analysis of semi-structured interviews with GM-MDT members. Study findings show that members appreciate the clinical and scientific diversity of the GM-MDT and value it for education and oversight. To date, discussions have focussed on case selection including the extent and interpretation of clinical and family history information required to establish likely monogenic aetiology and inheritance model. Achieving a balance between effective use of WES/WGS - prioritising cases in a diverse and highly complex patient population where WES/WGS will be tractable - and meeting the recruitment targets of a large project is considered challenging.

  15. Identifying Rare Variation in Cases of Schizophrenia in the Isolated Population of the Faroe Islands using Whole-genome Sequencing

    DEFF Research Database (Denmark)

    Als, Thomas Damm; Lescai, Francesco; Dahl, Hans

    The allelic architecture of schizophrenia (SZ) is likely to be underlined by a combination of multiple common and rare variants. Genome-wide association studies (GWAS) and large-scale consortia meta-analysis of GWAS have successfully been applied in the search for common variants affecting the risk...... influencing susceptibility to schizophrenia using whole genome sequencing of Faroese case-control samples. We will conduct association testing based on IBD information (IBD association testing) by analysing genome-wide association of shared IBD segments identified by the method implemented in GERMLINE...... and clustered using the DASH algorithm. Genomic regions with evidence for shared ancestral polymorphisms and/or genetic linkage co-segregation will thus be prioritized. We hypothesize greater degree of IBD sharing of rare haplotypes in cases compared to controls for regions harbouring disease susceptibility...

  16. Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.

    Science.gov (United States)

    Girirajan, Santhosh; Dennis, Megan Y; Baker, Carl; Malig, Maika; Coe, Bradley P; Campbell, Catarina D; Mark, Kenneth; Vu, Tiffany H; Alkan, Can; Cheng, Ze; Biesecker, Leslie G; Bernier, Raphael; Eichler, Evan E

    2013-02-07

    Rare copy-number variants (CNVs) have been implicated in autism and intellectual disability. These variants are large and affect many genes but lack clear specificity toward autism as opposed to developmental-delay phenotypes. We exploited the repeat architecture of the genome to target segmental duplication-mediated rearrangement hotspots (n = 120, median size 1.78 Mbp, range 240 kbp to 13 Mbp) and smaller hotspots flanked by repetitive sequence (n = 1,247, median size 79 kbp, range 3-96 kbp) in 2,588 autistic individuals from simplex and multiplex families and in 580 controls. Our analysis identified several recurrent large hotspot events, including association with 1q21 duplications, which are more likely to be identified in individuals with autism than in those with developmental delay (p = 0.01; OR = 2.7). Within larger hotspots, we also identified smaller atypical CNVs that implicated CHD1L and ACACA for the 1q21 and 17q12 deletions, respectively. Our analysis, however, suggested no overall increase in the burden of smaller hotspots in autistic individuals as compared to controls. By focusing on gene-disruptive events, we identified recurrent CNVs, including DPP10, PLCB1, TRPM1, NRXN1, FHIT, and HYDIN, that are enriched in autism. We found that as the size of deletions increases, nonverbal IQ significantly decreases, but there is no impact on autism severity; and as the size of duplications increases, autism severity significantly increases but nonverbal IQ is not affected. The absence of an increased burden of smaller CNVs in individuals with autism and the failure of most large hotspots to refine to single genes is consistent with a model where imbalance of multiple genes contributes to a disease state. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. Integrative analysis of functional genomic annotations and sequencing data to identify rare causal variants via hierarchical modeling

    Directory of Open Access Journals (Sweden)

    Marinela eCapanu

    2015-05-01

    Full Text Available Identifying the small number of rare causal variants contributing to disease has beena major focus of investigation in recent years, but represents a formidable statisticalchallenge due to the rare frequencies with which these variants are observed. In thiscommentary we draw attention to a formal statistical framework, namely hierarchicalmodeling, to combine functional genomic annotations with sequencing data with theobjective of enhancing our ability to identify rare causal variants. Using simulations weshow that in all configurations studied, the hierarchical modeling approach has superiordiscriminatory ability compared to a recently proposed aggregate measure of deleteriousness,the Combined Annotation-Dependent Depletion (CADD score, supportingour premise that aggregate functional genomic measures can more accurately identifycausal variants when used in conjunction with sequencing data through a hierarchicalmodeling approach

  18. Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Bassett, Anne S; Lowther, Chelsea; Merico, Daniele; Costain, Gregory; Chow, Eva W C; van Amelsvoort, Therese; McDonald-McGinn, Donna; Gur, Raquel E; Swillen, Ann; Van den Bree, Marianne; Murphy, Kieran; Gothelf, Doron; Bearden, Carrie E; Eliez, Stephan; Kates, Wendy; Philip, Nicole; Sashi, Vandana; Campbell, Linda; Vorstman, Jacob; Cubells, Joseph; Repetto, Gabriela M; Simon, Tony; Boot, Erik; Heung, Tracy; Evers, Rens; Vingerhoets, Claudia; van Duin, Esther; Zackai, Elaine; Vergaelen, Elfi; Devriendt, Koen; Vermeesch, Joris R; Owen, Michael; Murphy, Clodagh; Michaelovosky, Elena; Kushan, Leila; Schneider, Maude; Fremont, Wanda; Busa, Tiffany; Hooper, Stephen; McCabe, Kathryn; Duijff, Sasja; Isaev, Karin; Pellecchia, Giovanna; Wei, John; Gazzellone, Matthew J; Scherer, Stephen W; Emanuel, Beverly S; Guo, Tingwei; Morrow, Bernice E; Marshall, Christian R

    2017-11-01

    Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.

  19. Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions

    Science.gov (United States)

    Raychaudhuri, Soumya; Plenge, Robert M.; Rossin, Elizabeth J.; Ng, Aylwin C. Y.; Purcell, Shaun M.; Sklar, Pamela; Scolnick, Edward M.; Xavier, Ramnik J.; Altshuler, David; Daly, Mark J.

    2009-01-01

    Translating a set of disease regions into insight about pathogenic mechanisms requires not only the ability to identify the key disease genes within them, but also the biological relationships among those key genes. Here we describe a statistical method, Gene Relationships Among Implicated Loci (GRAIL), that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts. We first evaluated GRAIL by assessing its ability to identify subsets of highly related genes in common pathways from validated lipid and height SNP associations from recent genome-wide studies. We then tested GRAIL, by assessing its ability to separate true disease regions from many false positive disease regions in two separate practical applications in human genetics. First, we took 74 nominally associated Crohn's disease SNPs and applied GRAIL to identify a subset of 13 SNPs with highly related genes. Of these, ten convincingly validated in follow-up genotyping; genotyping results for the remaining three were inconclusive. Next, we applied GRAIL to 165 rare deletion events seen in schizophrenia cases (less than one-third of which are contributing to disease risk). We demonstrate that GRAIL is able to identify a subset of 16 deletions containing highly related genes; many of these genes are expressed in the central nervous system and play a role in neuronal synapses. GRAIL offers a statistically robust approach to identifying functionally related genes from across multiple disease regions—that likely represent key disease pathways. An online version of this method is available for public use (http://www.broad.mit.edu/mpg/grail/). PMID:19557189

  20. Genome-wide Polygenic Burden of Rare Deleterious Variants in Sudden Unexpected Death in Epilepsy

    Directory of Open Access Journals (Sweden)

    Costin Leu

    2015-09-01

    Full Text Available Sudden unexpected death in epilepsy (SUDEP represents the most severe degree of the spectrum of epilepsy severity and is the commonest cause of epilepsy-related premature mortality. The precise pathophysiology and the genetic architecture of SUDEP remain elusive. Aiming to elucidate the genetic basis of SUDEP, we analysed rare, protein-changing variants from whole-exome sequences of 18 people who died of SUDEP, 87 living people with epilepsy and 1479 non-epilepsy disease controls. Association analysis revealed a significantly increased genome-wide polygenic burden per individual in the SUDEP cohort when compared to epilepsy (P = 5.7 × 10−3 and non-epilepsy disease controls (P = 1.2 × 10−3. The polygenic burden was driven both by the number of variants per individual, and over-representation of variants likely to be deleterious in the SUDEP cohort. As determined by this study, more than a thousand genes contribute to the observed polygenic burden within the framework of this study. Subsequent gene-based association analysis revealed five possible candidate genes significantly associated with SUDEP or epilepsy, but no one single gene emerges as common to the SUDEP cases. Our findings provide further evidence for a genetic susceptibility to SUDEP, and suggest an extensive polygenic contribution to SUDEP causation. Thus, an overall increased burden of deleterious variants in a highly polygenic background might be important in rendering a given individual more susceptible to SUDEP. Our findings suggest that exome sequencing in people with epilepsy might eventually contribute to generating SUDEP risk estimates, promoting stratified medicine in epilepsy, with the eventual aim of reducing an individual patient's risk of SUDEP.

  1. Identification and analysis of mutational hotspots in oncogenes and tumour suppressors.

    Science.gov (United States)

    Baeissa, Hanadi; Benstead-Hume, Graeme; Richardson, Christopher J; Pearl, Frances M G

    2017-03-28

    The key to interpreting the contribution of a disease-associated mutation in the development and progression of cancer is an understanding of the consequences of that mutation both on the function of the affected protein and on the pathways in which that protein is involved. Protein domains encapsulate function and position-specific domain based analysis of mutations have been shown to help elucidate their phenotypes. In this paper we examine the domain biases in oncogenes and tumour suppressors, and find that their domain compositions substantially differ. Using data from over 30 different cancers from whole-exome sequencing cancer genomic projects we mapped over one million mutations to their respective Pfam domains to identify which domains are enriched in any of three different classes of mutation; missense, indels or truncations. Next, we identified the mutational hotspots within domain families by mapping small mutations to equivalent positions in multiple sequence alignments of protein domainsWe find that gain of function mutations from oncogenes and loss of function mutations from tumour suppressors are normally found in different domain families and when observed in the same domain families, hotspot mutations are located at different positions within the multiple sequence alignment of the domain. By considering hotspots in tumour suppressors and oncogenes independently, we find that there are different specific positions within domain families that are particularly suited to accommodate either a loss or a gain of function mutation. The position is also dependent on the class of mutation.We find rare mutations co-located with well-known functional mutation hotspots, in members of homologous domain superfamilies, and we detect novel mutation hotspots in domain families previously unconnected with cancer. The results of this analysis can be accessed through the MOKCa database (http://strubiol.icr.ac.uk/extra/MOKCa).

  2. Meeting summary: Ethical aspects of whole exome and whole genome sequencing studies (WES/WGS) in rare diseases, Tel Aviv, Israel, January 2013.

    Science.gov (United States)

    Farberov, Luba; Gilam, Avital; Isakov, Ofer; Shomron, Noam

    2013-06-01

    A recent E-Rare workshop reviewed the ethical aspects of whole exome and whole genome-sequencing studies (WES and WGS, respectively) in rare diseases. Leveraging new genomic technologies, which output vast amounts of known and novel genetic variants, researchers are learning more about the genetic basis and mechanisms involved in rare diseases. In some cases, these findings are translated into diagnostic tools for the benefit of rare disease patients. Among the disclosed data, which can assist in treatment management, incidental findings await, bringing with them ethical concerns for the clinicians, researchers and patients.

  3. Rare pathogenic microdeletions and tandem duplications are microhomology-mediated and stimulated by local genomic architecture.

    NARCIS (Netherlands)

    Vissers, L.E.L.M.; Bhatt, S.S.; Janssen, I.M.; Xia, Z.; Lalani, S.R.; Pfundt, R.P.; Derwinska, K.; Vries, L.B.A. de; Gilissen, C.F.H.A.; Hoischen, A.; Nesteruk, M.; Wisniowiecka-Kowalnik, B.; Smyk, M.; Brunner, H.G.; Cheung, S.W.; Geurts van Kessel, A.H.M.; Veltman, J.A.; Stankiewicz, P.

    2009-01-01

    Genomic copy number variation (CNV) plays a major role in various human diseases as well as in normal phenotypic variability. For some recurrent disease-causing CNVs that convey genomic disorders, the causative mechanism is meiotic, non-allelic, homologous recombination between breakpoint regions

  4. Defining persistent hotspots

    DEFF Research Database (Denmark)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H.

    2017-01-01

    , investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs...... and contrast the outcomes of these analyses. Our intent is to showhowthe samedataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever...... using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare...

  5. Observed climate change hotspots

    Science.gov (United States)

    Turco, M.; Palazzi, E.; Hardenberg, J.; Provenzale, A.

    2015-05-01

    We quantify climate change hotspots from observations, taking into account the differences in precipitation and temperature statistics (mean, variability, and extremes) between 1981-2010 and 1951-1980. Areas in the Amazon, the Sahel, tropical West Africa, Indonesia, and central eastern Asia emerge as primary observed hotspots. The main contributing factors are the global increase in mean temperatures, the intensification of extreme hot-season occurrence in low-latitude regions and the decrease of precipitation over central Africa. Temperature and precipitation variability have been substantially stable over the past decades, with only a few areas showing significant changes against the background climate variability. The regions identified from the observations are remarkably similar to those defined from projections of global climate models under a "business-as-usual" scenario, indicating that climate change hotspots are robust and persistent over time. These results provide a useful background to develop global policy decisions on adaptation and mitigation priorities over near-time horizons.

  6. A scan statistic to extract causal gene clusters from case-control genome-wide rare CNV data

    Directory of Open Access Journals (Sweden)

    Scherer Stephen W

    2011-05-01

    Full Text Available Abstract Background Several statistical tests have been developed for analyzing genome-wide association data by incorporating gene pathway information in terms of gene sets. Using these methods, hundreds of gene sets are typically tested, and the tested gene sets often overlap. This overlapping greatly increases the probability of generating false positives, and the results obtained are difficult to interpret, particularly when many gene sets show statistical significance. Results We propose a flexible statistical framework to circumvent these problems. Inspired by spatial scan statistics for detecting clustering of disease occurrence in the field of epidemiology, we developed a scan statistic to extract disease-associated gene clusters from a whole gene pathway. Extracting one or a few significant gene clusters from a global pathway limits the overall false positive probability, which results in increased statistical power, and facilitates the interpretation of test results. In the present study, we applied our method to genome-wide association data for rare copy-number variations, which have been strongly implicated in common diseases. Application of our method to a simulated dataset demonstrated the high accuracy of this method in detecting disease-associated gene clusters in a whole gene pathway. Conclusions The scan statistic approach proposed here shows a high level of accuracy in detecting gene clusters in a whole gene pathway. This study has provided a sound statistical framework for analyzing genome-wide rare CNV data by incorporating topological information on the gene pathway.

  7. Regional differences in recombination hotspots between two chicken populations

    NARCIS (Netherlands)

    Elferink, M.G.; As, van P.; Veenendaal, A.; Crooijmans, R.P.M.A.; Groenen, M.A.M.

    2010-01-01

    Background Although several genetic linkage maps of the chicken genome have been published, the resolution of these maps is limited and does not allow the precise identification of recombination hotspots. The availability of more than 3.2 million SNPs in the chicken genome and the recent advances in

  8. Mitochondrial genome sequences illuminate maternal lineages of conservation concern in a rare carnivore

    Science.gov (United States)

    Brian J. Knaus; Richard Cronn; Aaron Liston; Kristine Pilgrim; Michael K. Schwartz

    2011-01-01

    Science-based wildlife management relies on genetic information to infer population connectivity and identify conservation units. The most commonly used genetic marker for characterizing animal biodiversity and identifying maternal lineages is the mitochondrial genome. Mitochondrial genotyping figures prominently in conservation and management plans, with much of the...

  9. The use of whole genome sequence data to estimate genetic relationships including rare alleles information

    NARCIS (Netherlands)

    Eynard, S.E.; Windig, J.J.; Leroy, G.; Verrier, E.; Hiemstra, S.J.; Binsbergen, van R.; Calus, M.P.L.

    2014-01-01

    Whole genome sequencing technologies are rapidly developing. In some ways, the speed of this development has outstripped our capacity to use this type of data in selection strategies, especially in livestock diversity conservation. In this study, relationship matrices were computed for 118 Holstein

  10. Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

    Science.gov (United States)

    Carss, Keren J; Arno, Gavin; Erwood, Marie; Stephens, Jonathan; Sanchis-Juan, Alba; Hull, Sarah; Megy, Karyn; Grozeva, Detelina; Dewhurst, Eleanor; Malka, Samantha; Plagnol, Vincent; Penkett, Christopher; Stirrups, Kathleen; Rizzo, Roberta; Wright, Genevieve; Josifova, Dragana; Bitner-Glindzicz, Maria; Scott, Richard H; Clement, Emma; Allen, Louise; Armstrong, Ruth; Brady, Angela F; Carmichael, Jenny; Chitre, Manali; Henderson, Robert H H; Hurst, Jane; MacLaren, Robert E; Murphy, Elaine; Paterson, Joan; Rosser, Elisabeth; Thompson, Dorothy A; Wakeling, Emma; Ouwehand, Willem H; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Raymond, F Lucy

    2017-01-05

    Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease. Copyright © 2017. Published by Elsevier Inc.

  11. Rare genomic variants link bipolar disorder to CREB regulated intracellular signaling pathways

    Directory of Open Access Journals (Sweden)

    Berit eKerner

    2013-11-01

    Full Text Available Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood stabilizing drugs, such as tricyclic antidepressants, lithium and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder.

  12. Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

    Science.gov (United States)

    Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

  13. The complete maternal mitochondrial genome of rare Chinese freshwater mussel Lepidodesma languilati (Bivalvia: Unionidae: Unioninae).

    Science.gov (United States)

    Zhou, Chun-Hua; Ouyang, Shan; Wu, Xiao-Ping; Ding, Mei-Huang

    2016-11-01

    Lepidodesma languilati is considered threatened because of the influence of human activities in China. The complete F-type mitochondrial genome of L. languilati was determined in this study (GenBank accession no. KT381195). It is a 15 754-bp-long circular molecule that consists of 37 genes that are typically found in other invertebrates. The overall base composition of the entire sequence is as follows: A (39.1%), T (25.7%), C (23.4%), and G (11.8%). Except for cox1 (TTG), cob (ATT), nad1 (ATT), nad6 (ATA), nad4 (TTG), and atp8 (GTG), 7 of the 13 protein-coding genes initiate with orthodox ATG start codon. All the 13 protein-coding genes have complete termination codon TAA or TAG. Phylogenetic tree indicates that L. languilati belongs to Unioninae. The newly sequenced complete mitogenome can provide basic data for comparative studies on mitochondrial genomes of Unionidae. It could also lay the important theoretical foundation for phylogenetics, population genetics, germplasm resources protection, sustainable, and reasonable utilization.

  14. High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.

    Science.gov (United States)

    Islam, Md Tarikul; Sarkar, Suprovath Kumar; Sultana, Nusrat; Begum, Mst Noorjahan; Bhuyan, Golam Sarower; Talukder, Shezote; Muraduzzaman, A K M; Alauddin, Md; Islam, Mohammad Sazzadul; Biswas, Pritha Promita; Biswas, Aparna; Qadri, Syeda Kashfi; Shirin, Tahmina; Banu, Bilquis; Sadya, Salma; Hussain, Manzoor; Sarwardi, Golam; Khan, Waqar Ahmed; Mannan, Mohammad Abdul; Shekhar, Hossain Uddin; Chowdhury, Emran Kabir; Sajib, Abu Ashfaqur; Akhteruzzaman, Sharif; Qadri, Syed Saleheen; Qadri, Firdausi; Mannoor, Kaiissar

    2018-01-02

    Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh. Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result. Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and

  15. A discrete class of intergenic DNA dictates meiotic DNA break hotspots in fission yeast.

    Directory of Open Access Journals (Sweden)

    Gareth A Cromie

    2007-08-01

    Full Text Available Meiotic recombination is initiated by DNA double-strand breaks (DSBs made by Spo11 (Rec12 in fission yeast, which becomes covalently linked to the DSB ends. Like recombination events, DSBs occur at hotspots in the genome, but the genetic factors responsible for most hotspots have remained elusive. Here we describe in fission yeast the genome-wide distribution of meiosis-specific Rec12-DNA linkages, which closely parallel DSBs measured by conventional Southern blot hybridization. Prominent DSB hotspots are located approximately 65 kb apart, separated by intervals with little or no detectable breakage. Most hotspots lie within exceptionally large intergenic regions. Thus, the chromosomal architecture responsible for hotspots in fission yeast is markedly different from that of budding yeast, in which DSB hotspots are much more closely spaced and, in many regions of the genome, occur at each promoter. Our analysis in fission yeast reveals a clearly identifiable chromosomal feature that can predict the majority of recombination hotspots across a whole genome and provides a basis for searching for the chromosomal features that dictate hotspots of meiotic recombination in other organisms, including humans.

  16. Rare copy number alterations and copy-neutral loss of heterozygosity revealed in ameloblastomas by high-density whole-genome microarray analysis

    DEFF Research Database (Denmark)

    Diniz, Marina Gonçalves; Duarte, Alessandra Pires; Villacis, Rolando A

    2017-01-01

    BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their d......BACKGROUND: Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account......: Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors....

  17. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia

    Science.gov (United States)

    Legge, S E; Hamshere, M L; Ripke, S; Pardinas, A F; Goldstein, J I; Rees, E; Richards, A L; Leonenko, G; Jorskog, L F; Goldstein, Jacqueline I; Jarskog, L Fredrik; Hilliard, Chris; Alfirevic, Ana; Duncan, Laramie; Fourches, Denis; Huang, Hailiang; Lek, Monkol; Neale, Benjamin M; Ripke, Stephan; Shianna, Kevin; Szatkiewicz, Jin P; Tropsha, Alexander; van den Oord, Edwin JCG; Cascorbi, Ingolf; Dettling, Michael; Gazit, Ephraim; Goff, Donald C; Holden, Arthur L; Kelly, Deanna L; Malhotra, Anil K; Nielsen, Jimmi; Pirmohamed, Munir; Rujescu, Dan; Werge, Thomas; Levy, Deborah L; Josiassen, Richard C; Kennedy, James L; Lieberman, Jeffrey A; Daly, Mark J; Sullivan, Patrick F; Chambert, K D; Collier, D A; Genovese, G; Giegling, I; Holmans, P; Jonasdottir, A; Kirov, G; McCarroll, S A; MacCabe, J H; Mantripragada, K; Moran, J L; Neale, B M; Stefansson, H; Rujescu, D; Daly, M J; Sullivan, P F; Owen, M J; O'Donovan, M C; Walters, J T R

    2017-01-01

    The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (odds ratio (OR)=4.32, P=1.79 × 10−8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P=0.015, positive predictive value=35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID:27400856

  18. Absence of the TAP2 human recombination hotspot in chimpanzees.

    Directory of Open Access Journals (Sweden)

    Susan E Ptak

    2004-06-01

    Full Text Available Recent experiments using sperm typing have demonstrated that, in several regions of the human genome, recombination does not occur uniformly but instead is concentrated in "hotspots" of 1-2 kb. Moreover, the crossover asymmetry observed in a subset of these has led to the suggestion that hotspots may be short-lived on an evolutionary time scale. To test this possibility, we focused on a region known to contain a recombination hotspot in humans, TAP2, and asked whether chimpanzees, the closest living evolutionary relatives of humans, harbor a hotspot in a similar location. Specifically, we used a new statistical approach to estimate recombination rate variation from patterns of linkage disequilibrium in a sample of 24 western chimpanzees (Pan troglodytes verus. This method has been shown to produce reliable results on simulated data and on human data from the TAP2 region. Strikingly, however, it finds very little support for recombination rate variation at TAP2 in the western chimpanzee data. Moreover, simulations suggest that there should be stronger support if there were a hotspot similar to the one characterized in humans. Thus, it appears that the human TAP2 recombination hotspot is not shared by western chimpanzees. These findings demonstrate that fine-scale recombination rates can change between very closely related species and raise the possibility that rates differ among human populations, with important implications for linkage-disequilibrium based association studies.

  19. Generation of mutation hotspots in ageing bacterial colonies

    DEFF Research Database (Denmark)

    Sekowska, Agnieszka; Wendel, Sofie; Christian Fischer, Emil

    2016-01-01

    : most mutations were located in just a few hotspots in the genome, and over time, mutations increasingly were consistent with the involvement of 8-oxo-guanosine, formed exclusively on the transcribed strand. This work provides strong support for retromutagenesis as a general process creating adaptive...... mutations during ageing....

  20. Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.

    Science.gov (United States)

    Dapper, Amy L; Payseur, Bret A

    2017-10-17

    In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot are sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Methodology for the analysis of rare genetic variation in genome-wide association and re-sequencing studies of complex human traits.

    Science.gov (United States)

    Moutsianas, Loukas; Morris, Andrew P

    2014-09-01

    Genome-wide association studies have been successful in identifying common variants that impact complex human traits and diseases. However, despite this success, the joint effects of these variants explain only a small proportion of the genetic variance in these phenotypes, leading to speculation that rare genetic variation might account for much of the 'missing heritability'. Consequently, there has been an exciting period of research and development into the methodology for the analysis of rare genetic variants, typically by considering their joint effects on complex traits within the same functional unit or genomic region. In this review, we describe a general framework for modelling the joint effects of rare genetic variants on complex traits in association studies of unrelated individuals. We summarise a range of widely used association tests that have been developed from this model and provide an overview of the relative performance of these approaches from published simulation studies. © The Author 2014. Published by Oxford University Press.

  2. VT Biodiversity Project - Biological Hotspots

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This dataset is the result of an effort to map biological "hotspots" in Vermont based on the "element occurrences" in the Nongame and Natural...

  3. Sequence requirement of the ade6-4095 meiotic recombination hotspot in Schizosaccharomyces pombe.

    Science.gov (United States)

    Foulis, Steven J; Fowler, Kyle R; Steiner, Walter W

    2018-02-01

    Homologous recombination occurs at a greatly elevated frequency in meiosis compared to mitosis and is initiated by programmed double-strand DNA breaks (DSBs). DSBs do not occur at uniform frequency throughout the genome in most organisms, but occur preferentially at a limited number of sites referred to as hotspots. The location of hotspots have been determined at nucleotide-level resolution in both the budding and fission yeasts, and while several patterns have emerged regarding preferred locations for DSB hotspots, it remains unclear why particular sites experience DSBs at much higher frequency than other sites with seemingly similar properties. Short sequence motifs, which are often sites for binding of transcription factors, are known to be responsible for a number of hotspots. In this study we identified the minimum sequence required for activity of one of such motif identified in a screen of random sequences capable of producing recombination hotspots. The experimentally determined sequence, GGTCTRGACC, closely matches the previously inferred sequence. Full hotspot activity requires an effective sequence length of 9.5 bp, whereas moderate activity requires an effective sequence length of approximately 8.2 bp and shows significant association with DSB hotspots. In combination with our previous work, this result is consistent with a large number of different sequence motifs capable of producing recombination hotspots, and supports a model in which hotspots can be rapidly regenerated by mutation as they are lost through recombination.

  4. Identification of chromosomal translocation hotspots via scan statistics.

    Science.gov (United States)

    Silva, Israel T; Rosales, Rafael A; Holanda, Adriano J; Nussenzweig, Michel C; Jankovic, Mila

    2014-09-15

    The detection of genomic regions unusually rich in a given pattern is an important undertaking in the analysis of next-generation sequencing data. Recent studies of chromosomal translocations in activated B lymphocytes have identified regions that are frequently translocated to c-myc oncogene. A quantitative method for the identification of translocation hotspots was crucial to this study. Here we improve this analysis by using a simple probabilistic model and the framework provided by scan statistics to define the number and location of translocation breakpoint hotspots. A key feature of our method is that it provides a global chromosome-wide nominal control level to clustering, as opposed to previous methods based on local criteria. While being motivated by a specific application, the detection of unusual clusters is a widespread problem in bioinformatics. We expect our method to be useful in the analysis of data from other experimental approaches such as of ChIP-seq and 4C-seq. The analysis of translocations from B lymphocytes with the method described here reveals the presence of longer hotspots when compared with those defined previously. Further, we show that the hotspot size changes substantially in the absence of DNA repair protein 53BP1. When 53BP1 deficiency is combined with overexpression of activation-induced cytidine deaminase, the hotspot length increases even further. These changes are not detected by previous methods that use local significance criteria for clustering. Our method is also able to identify several exclusive translocation hotspots located in genes of known tumor supressors. The detection of translocation hotspots is done with hot_scan, a program implemented in R and Perl. Source code and documentation are freely available for download at https://github.com/itojal/hot_scan. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Methodology and software to detect viral integration site hot-spots

    Directory of Open Access Journals (Sweden)

    Kim Namshin

    2011-09-01

    Full Text Available Abstract Background Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or 'common insertion sites' (CIS are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100 kb region, which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. Results We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1 Mb 'bins' of the genome. The first method 'z-threshold' tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method 'BCP' applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy, CGD (chronic granulomatous disease and SCID-X1 (X-linked severe combined immunodeficiency trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS and combined (2401 VIS resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap

  6. HIV protein sequence hotspots for crosstalk with host hub proteins.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

  7. Hotspots within hotspots? Hammerhead shark movements around Wolf Island, Galapagos Marine Reserve.

    Science.gov (United States)

    Hearn, Alex; Ketchum, James; Klimley, A Peter; Espinoza, Eduardo; Peñaherrera, Cesar

    2010-01-01

    Are pelagic species such as sharks and tuna distributed homogenously or heterogeneously in the oceans? Large assemblages of these species have been observed at seamounts and offshore islands in the eastern tropical Pacific, which are considered hotspots of pelagic biodiversity. Is the species distribution uniform at these hotspots or do species aggregate at a finer spatial scale at these sites? We employed three techniques to demonstrate that the aggregations of scalloped hammerhead sharks, Sphyrna lewini, and other pelagic species were confined to the southeastern corner of Wolf Island in the Galapagos Marine Reserve. Coded ultrasonic transmitters were placed on individuals at this site and at another aggregation site at Darwin Island, separated from Wolf by 40 km, and they were detected by monitors moored at the southeastern corner of Wolf Island and rarely by monitors deployed at other sites around the island. Hammerhead sharks, carrying depth-sensing continual transmitters, were tracked for two-day periods in a vessel and shown to reside a disproportionately large fraction of their time at the southeastern corner. Visual censuses were carried out seasonally at the eight monitor sites at Wolf Island, recording the abundance of one species of tuna, four species of jacks, and a number of other species. The highest diversity and abundance of these species occurred in the southeastern corner of the island. Our results support the use of hammerhead sharks as indicator and umbrella species for pelagic hotspots on a fine scale.

  8. The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions

    OpenAIRE

    Bamshad, Michael J.; Shendure, Jay A.; Rieder, Mark J.; Valle, David; Hamosh, Ada; James R Lupski; Gibbs, Richard A.; Boerwinkle, Eric; Lifton, Rick P.; Gerstein, Mark; Gunel, Murat; Mane, Shrikant; Nickersonon, Deborah A.

    2012-01-01

    Next generation exome sequencing (ES) and whole genome sequencing (WGS) are new powerful tools for discovering the gene(s) that underlie Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Disorders at Yale University; and the Baylor-Johns Hopkins Center for Mendelian Genomics at Baylor College of Medicine ...

  9. Applying Hotspot Detection Methods in Forestry: A Case Study of Chestnut Oak Regeneration

    Directory of Open Access Journals (Sweden)

    Songlin Fei

    2010-01-01

    Full Text Available Hotspot detection has been widely adopted in health sciences for disease surveillance, but rarely in natural resource disciplines. In this paper, two spatial scan statistics (SaTScan and ClusterSeer and a nonspatial classification and regression trees method were evaluated as techniques for identifying chestnut oak (Quercus Montana regeneration hotspots among 50 mixed-oak stands in the central Appalachian region of the eastern United States. Hotspots defined by the three methods had a moderate level of conformity and revealed similar chestnut oak regeneration site affinity. Chestnut oak regeneration hotspots were positively associated with the abundance of chestnut oak trees in the overstory and a moderate cover of heather species (Vaccinium and Gaylussacia spp. but were negatively associated with the abundance of hayscented fern (Dennstaedtia punctilobula and mountain laurel (Kalmia latiforia. In general, hotspot detection is a viable tool for assisting natural resource managers with identifying areas possessing significantly high or low tree regeneration.

  10. Detecting Biosphere anomalies hotspots

    Science.gov (United States)

    Guanche-Garcia, Yanira; Mahecha, Miguel; Flach, Milan; Denzler, Joachim

    2017-04-01

    The current amount of satellite remote sensing measurements available allow for applying data-driven methods to investigate environmental processes. The detection of anomalies or abnormal events is crucial to monitor the Earth system and to analyze their impacts on ecosystems and society. By means of a combination of statistical methods, this study proposes an intuitive and efficient methodology to detect those areas that present hotspots of anomalies, i.e. higher levels of abnormal or extreme events or more severe phases during our historical records. Biosphere variables from a preliminary version of the Earth System Data Cube developed within the CAB-LAB project (http://earthsystemdatacube.net/) have been used in this study. This database comprises several atmosphere and biosphere variables expanding 11 years (2001-2011) with 8-day of temporal resolution and 0.25° of global spatial resolution. In this study, we have used 10 variables that measure the biosphere. The methodology applied to detect abnormal events follows the intuitive idea that anomalies are assumed to be time steps that are not well represented by a previously estimated statistical model [1].We combine the use of Autoregressive Moving Average (ARMA) models with a distance metric like Mahalanobis distance to detect abnormal events in multiple biosphere variables. In a first step we pre-treat the variables by removing the seasonality and normalizing them locally (μ=0,σ=1). Additionally we have regionalized the area of study into subregions of similar climate conditions, by using the Köppen climate classification. For each climate region and variable we have selected the best ARMA parameters by means of a Bayesian Criteria. Then we have obtained the residuals by comparing the fitted models with the original data. To detect the extreme residuals from the 10 variables, we have computed the Mahalanobis distance to the data's mean (Hotelling's T^2), which considers the covariance matrix of the joint

  11. A framework for identifying carbon hotspots and forest management drivers.

    Science.gov (United States)

    Timilsina, Nilesh; Escobedo, Francisco J; Cropper, Wendell P; Abd-Elrahman, Amr; Brandeis, Thomas J; Delphin, Sonia; Lambert, Samuel

    2013-01-15

    Spatial analyses of ecosystem system services that are directly relevant to both forest management decision making and conservation in the subtropics are rare. Also, frameworks that identify and map carbon stocks and corresponding forest management drivers using available regional, national, and international-level forest inventory datasets could provide insights into key forest structural characteristics and management practices that are optimal for carbon storage. To address this need we used publicly available USDA Forest Service Forest Inventory and Analysis data and spatial analyses to develop a framework for mapping "carbon hotspots" (i.e. areas of significantly high tree and understory aboveground carbon stocks) across a range of forest types using the state of Florida, USA as an example. We also analyzed influential forest management variables (e.g. forest types, fire, hurricanes, tenure, management activities) using generalized linear mixed modeling to identify drivers associated with these hotspots. Most of the hotspots were located in the northern third of the state some in peri-urban areas, and there were no identifiable hotspots in South Florida. Forest silvicultural treatments (e.g. site preparation, thinning, logging, etc) were not significant predictors of hotspots. Forest types, site quality, and stand age were however significant predictors. Higher site quality and stand age increased the probability of forests being classified as a hotspot. Disturbance type and time since disturbance were not significant predictors in our analyses. This framework can use globally available forest inventory datasets to analyze and map ecosystems service provision areas and bioenergy supplies and identify forest management practices that optimize these services in forests. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. The Centers for Mendelian Genomics: a new large-scale initiative to identify the genes underlying rare Mendelian conditions.

    Science.gov (United States)

    Bamshad, Michael J; Shendure, Jay A; Valle, David; Hamosh, Ada; Lupski, James R; Gibbs, Richard A; Boerwinkle, Eric; Lifton, Richard P; Gerstein, Mark; Gunel, Murat; Mane, Shrikant; Nickerson, Deborah A

    2012-07-01

    Next generation exome sequencing (ES) and whole genome sequencing (WGS) are new powerful tools for discovering the gene(s) that underlie Mendelian disorders. To accelerate these discoveries, the National Institutes of Health has established three Centers for Mendelian Genomics (CMGs): the Center for Mendelian Genomics at the University of Washington; the Center for Mendelian Genomics at Yale University; and the Baylor-Johns Hopkins Center for Mendelian Genomics at Baylor College of Medicine and Johns Hopkins University. The CMGs will provide ES/WGS and extensive analysis expertise at no cost to collaborating investigators where the causal gene(s) for a Mendelian phenotype has yet to be uncovered. Over the next few years and in collaboration with the global human genetics community, the CMGs hope to facilitate the identification of the genes underlying a very large fraction of all Mendelian disorders; see http://mendelian.org. Copyright © 2012 Wiley Periodicals, Inc.

  13. Hot-spots in tapwaterleidingen

    NARCIS (Netherlands)

    Wolferen, J. van; Sluis, S.M. van der

    2002-01-01

    ln opdracht van de VNI is een aantal berekeningen uitgevoerd voor het vaststellen van aanvullende richtlijnen in verband met hot-spots in tapwaterleidingen. Hierbij is deels voortgebouwd op berekeningen die reeds eerder in opdracht van Novem zijn uitgevoerd t.b.v. ISSO publicatie 55.1, Handleiding

  14. Are hotspots of evolutionary potential adequately protected in southern California?

    Science.gov (United States)

    Vandergast, A.G.; Bohonak, A.J.; Hathaway, S.A.; Boys, J.; Fisher, R.N.

    2008-01-01

    Reserves are often designed to protect rare habitats, or "typical" exemplars of ecoregions and geomorphic provinces. This approach focuses on current patterns of organismal and ecosystem-level biodiversity, but typically ignores the evolutionary processes that control the gain and loss of biodiversity at these and other levels (e.g., genetic, ecological). In order to include evolutionary processes in conservation planning efforts, their spatial components must first be identified and mapped. We describe a GIS-based approach for explicitly mapping patterns of genetic divergence and diversity for multiple species (a "multi-species genetic landscape"). Using this approach, we analyzed mitochondrial DNA datasets from 21 vertebrate and invertebrate species in southern California to identify areas with common phylogeographic breaks and high intrapopulation diversity. The result is an evolutionary framework for southern California within which patterns of genetic diversity can be analyzed in the context of historical processes, future evolutionary potential and current reserve design. Our multi-species genetic landscapes pinpoint six hotspots where interpopulation genetic divergence is consistently high, five evolutionary hotspots within which genetic connectivity is high, and three hotspots where intrapopulation genetic diversity is high. These 14 hotspots can be grouped into eight geographic areas, of which five largely are unprotected at this time. The multi-species genetic landscape approach may provide an avenue to readily incorporate measures of evolutionary process into GIS-based systematic conservation assessment and land-use planning.

  15. SEQSpark: A Complete Analysis Tool for Large-Scale Rare Variant Association Studies Using Whole-Genome and Exome Sequence Data.

    Science.gov (United States)

    Zhang, Di; Zhao, Linhai; Li, Biao; He, Zongxiao; Wang, Gao T; Liu, Dajiang J; Leal, Suzanne M

    2017-07-06

    Massively parallel sequencing technologies provide great opportunities for discovering rare susceptibility variants involved in complex disease etiology via large-scale imputation and exome and whole-genome sequence-based association studies. Due to modest effect sizes, large sample sizes of tens to hundreds of thousands of individuals are required for adequately powered studies. Current analytical tools are obsolete when it comes to handling these large datasets. To facilitate the analysis of large-scale sequence-based studies, we developed SEQSpark which implements parallel processing based on Spark to increase the speed and efficiency of performing data quality control, annotation, and association analysis. To demonstrate the versatility and speed of SEQSpark, we analyzed whole-genome sequence data from the UK10K, testing for associations with waist-to-hip ratios. The analysis, which was completed in 1.5 hr, included loading data, annotation, principal component analysis, and single variant and rare variant aggregate association analysis of >9 million variants. For rare variant aggregate analysis, an exome-wide significant association (p analysis of a quantitative trait using several rare variant aggregate association methods. Additionally, the performance of SEQSpark was compared to Variant Association Tools and PLINK/SEQ. SEQSpark was always faster and in some situations computation was reduced to a hundredth of the time. SEQSpark will empower large sequence-based epidemiological studies to quickly elucidate genetic variation involved in the etiology of complex traits. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. A Possible Mechanism of Zika Virus Associated Microcephaly: Imperative Role of Retinoic Acid Response Element (RARE Consensus Sequence Repeats in the Viral Genome.

    Directory of Open Access Journals (Sweden)

    Ashutosh Kumar

    2016-08-01

    Full Text Available Owing to the reports of microcephaly as a consistent outcome in the foetuses of pregnant women infected with ZIKV in Brazil, Zika virus (ZIKV - microcephaly etiomechanistic relationship has recently been implicated. Researchers, however, are still struggling to establish an embryological basis for this interesting causal handcuff. The present study reveals robust evidence in favour of a plausible ZIKV-microcephaly cause-effect liaison. The rationale is based on: (1 sequence homology between ZIKV genome and the response element of an early neural tube developmental marker ‘retinoic acid’ in human DNA and (2 comprehensive similarities between the details of brain defects in ZIKV-microcephaly and retinoic acid embryopathy. Retinoic acid is considered as the earliest factor for regulating anteroposterior axis of neural tube and positioning of structures in developing brain through retinoic acid response elements (RARE consensus sequence (5′–AGGTCA–3′ in promoter regions of retinoic acid-dependent genes. We screened genomic sequences of already reported virulent ZIKV strains (including those linked to microcephaly and other viruses available in National Institute of Health genetic sequence database (GenBank for the RARE consensus repeats and obtained results strongly bolstering our hypothesis that ZIKV strains associated with microcephaly may act through precipitation of dysregulation in retinoic acid-dependent genes by introducing extra stretches of RARE consensus sequence repeats in the genome of developing brain cells. Additional support to our hypothesis comes from our findings that screening of other viruses for RARE consensus sequence repeats is positive only for those known to display neurotropism and cause foetal brain defects (for which maternal-foetal transmission during developing stage may be required. The numbers of RARE sequence repeats appeared to match with the virulence of screened positive viruses. Although bioinformatic

  17. Recombination Hotspot/Coldspot Identification Combining Three Different Pseudocomponents via an Ensemble Learning Approach

    Directory of Open Access Journals (Sweden)

    Bingquan Liu

    2016-01-01

    Full Text Available Recombination presents a nonuniform distribution across the genome. Genomic regions that present relatively higher frequencies of recombination are called hotspots while those with relatively lower frequencies of recombination are recombination coldspots. Therefore, the identification of hotspots/coldspots could provide useful information for the study of the mechanism of recombination. In this study, a new computational predictor called SVM-EL was proposed to identify hotspots/coldspots across the yeast genome. It combined Support Vector Machines (SVMs and Ensemble Learning (EL based on three features including basic kmer (Kmer, dinucleotide-based auto-cross covariance (DACC, and pseudo dinucleotide composition (PseDNC. These features are able to incorporate the nucleic acid composition and their order information into the predictor. The proposed SVM-EL achieves an accuracy of 82.89% on a widely used benchmark dataset, which outperforms some related methods.

  18. PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.

    Directory of Open Access Journals (Sweden)

    Christopher L Baker

    2015-01-01

    Full Text Available Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB. The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.

  19. PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.

    Science.gov (United States)

    Baker, Christopher L; Kajita, Shimpei; Walker, Michael; Saxl, Ruth L; Raghupathy, Narayanan; Choi, Kwangbom; Petkov, Petko M; Paigen, Kenneth

    2015-01-01

    Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.

  20. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

    Science.gov (United States)

    Fritsche, Lars G.; Igl, Wilmar; Cooke Bailey, Jessica N.; Grassmann, Felix; Sengupta, Sebanti; Bragg-Gresham, Jennifer L.; Burdon, Kathryn P.; Hebbring, Scott J.; Wen, Cindy; Gorski, Mathias; Kim, Ivana K.; Cho, David; Zack, Donald; Souied, Eric; Scholl, Hendrik P. N.; Bala, Elisa; Lee, Kristine E.; Hunter, David J.; Sardell, Rebecca J.; Mitchell, Paul; Merriam, Joanna E.; Cipriani, Valentina; Hoffman, Joshua D.; Schick, Tina; Lechanteur, Yara T. E.; Guymer, Robyn H.; Johnson, Matthew P.; Jiang, Yingda; Stanton, Chloe M.; Buitendijk, Gabriëlle H. S.; Zhan, Xiaowei; Kwong, Alan M.; Boleda, Alexis; Brooks, Matthew; Gieser, Linn; Ratnapriya, Rinki; Branham, Kari E.; Foerster, Johanna R.; Heckenlively, John R.; Othman, Mohammad I.; Vote, Brendan J.; Liang, Helena Hai; Souzeau, Emmanuelle; McAllister, Ian L.; Isaacs, Timothy; Hall, Janette; Lake, Stewart; Mackey, David A.; Constable, Ian J.; Craig, Jamie E.; Kitchner, Terrie E.; Yang, Zhenglin; Su, Zhiguang; Luo, Hongrong; Chen, Daniel; Ouyang, Hong; Flagg, Ken; Lin, Danni; Mao, Guanping; Ferreyra, Henry; Stark, Klaus; von Strachwitz, Claudia N.; Wolf, Armin; Brandl, Caroline; Rudolph, Guenther; Olden, Matthias; Morrison, Margaux A.; Morgan, Denise J.; Schu, Matthew; Ahn, Jeeyun; Silvestri, Giuliana; Tsironi, Evangelia E.; Park, Kyu Hyung; Farrer, Lindsay A.; Orlin, Anton; Brucker, Alexander; Li, Mingyao; Curcio, Christine; Mohand-Saïd, Saddek; Sahel, José-Alain; Audo, Isabelle; Benchaboune, Mustapha; Cree, Angela J.; Rennie, Christina A.; Goverdhan, Srinivas V.; Grunin, Michelle; Hagbi-Levi, Shira; Campochiaro, Peter; Katsanis, Nicholas; Holz, Frank G.; Blond, Frédéric; Blanché, Hélène; Deleuze, Jean-François; Igo, Robert P.; Truitt, Barbara; Peachey, Neal S.; Meuer, Stacy M.; Myers, Chelsea E.; Moore, Emily L.; Klein, Ronald; Hauser, Michael A.; Postel, Eric A.; Courtenay, Monique D.; Schwartz, Stephen G.; Kovach, Jaclyn L.; Scott, William K.; Liew, Gerald; Tƒan, Ava G.; Gopinath, Bamini; Merriam, John C.; Smith, R. Theodore; Khan, Jane C.; Shahid, Humma; Moore, Anthony T.; McGrath, J. Allie; Laux, Reneé; Brantley, Milam A.; Agarwal, Anita; Ersoy, Lebriz; Caramoy, Albert; Langmann, Thomas; Saksens, Nicole T. M.; de Jong, Eiko K.; Hoyng, Carel B.; Cain, Melinda S.; Richardson, Andrea J.; Martin, Tammy M.; Blangero, John; Weeks, Daniel E.; Dhillon, Bal; van Duijn, Cornelia M.; Doheny, Kimberly F.; Romm, Jane; Klaver, Caroline C. W.; Hayward, Caroline; Gorin, Michael B.; Klein, Michael L.; Baird, Paul N.; den Hollander, Anneke I.; Fauser, Sascha; Yates, John R. W.; Allikmets, Rando; Wang, Jie Jin; Schaumberg, Debra A.; Klein, Barbara E. K.; Hagstrom, Stephanie A.; Chowers, Itay; Lotery, Andrew J.; Léveillard, Thierry; Zhang, Kang; Brilliant, Murray H.; Hewitt, Alex W.; Swaroop, Anand; Chew, Emily Y.; Pericak-Vance, Margaret A.; DeAngelis, Margaret; Stambolian, Dwight; Haines, Jonathan L.; Iyengar, Sudha K.; Weber, Bernhard H. F.; Abecasis, Gonçalo R.; Heid, Iris M.

    2016-01-01

    Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. Here, we report on a study of >12 million variants including 163,714 directly genotyped, most rare, protein-altering variant. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5×10–8) distributed across 34 loci. While wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first signal specific to wet AMD, near MMP9 (difference-P = 4.1×10–10). Very rare coding variants (frequency < 0.1%) in CFH, CFI, and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes. PMID:26691988

  1. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

    NARCIS (Netherlands)

    L.G. Fritsche (Lars G.); W. Igl (Wilmar); J.N.C. Bailey (Jessica N. Cooke); F. Grassmann (Felix); S. Sengupta (Sebanti); J.L. Bragg-Gresham (Jennifer L.); K.P. Burdon (Kathryn); S.J. Hebbring (Scott J.); C. Wen (Cindy); M. Gorski (Mathias); I.K. Kim (Ivana K.); D. Cho (David); D.J. Zack (Donald); E.H. Souied (Eric); H.P.N. Scholl (Hendrik); E. Bala (Elisa); K. ELee (Kristine); D.J. Hunter (David J.); R.J. Sardell (Rebecca J.); P. Mitchell (Paul); J.E. Merriam (Joanna E.); F. Cipriani (Francesco); J.D. Hoffman (Joshua D.); T. Schick (Tina); Y.T.E. Lechanteur (Yara T.E.); R.H. Guymer (Robyn); M.P. Johnson (Matthew); Y. Jiang (Yingda); C.M. Stanton (Chloe M.); G.H.S. Buitendijk (Gabrielle); X. Zhan (Xiaowei); A.M. Kwong (Alan M.); A. Boleda (Alexis); M. Brooks (Matthew); L. Gieser (Linn); R. Ratna Priya (Rinki); K.E. Branham (Kari E.); J.R. Foerster (Johanna R.); J.R. Heckenlively (John R.); M.I. Othman (Mohammad I.); B.J. Vote (Brendan J.); H.H. Liang (Helena Hai); E. Souzeau (Emmanuelle); I.L. McAllister (Ian L.); T. Isaacs (Timothy); J. Hall (Janette); S. Lake (Stewart); D.A. Mackey (David A.); I.J. Constable (Ian J.); J.E. Craig (Jamie E.); T.E. Kitchner (Terrie E.); Z. Yang (Zhenglin); Z. Su (Zhiguang); H. Luo (Hongrong); D. Chen (Daniel); H. Ouyang (Hong); K. Flagg (Ken); D. Lin (Danni); G. Mao (Guanping); H.A. Ferreyra (Henry); K. Stark (Klaus); C. von Strachwitz (Claudia); A. Wolf (Armin); C. Brandl (Caroline); G. Rudolph (Guenther); M. Olden (Matthias); M.A. Morrison (Margaux A.); D.J. Morgan (Denise); M. Schu (Matthew); J. Ahn (Jeeyun); G. Silvestri (Giuliana); E. ETsironi (Evangelia); K.H. Park (Kyu Hyung); L.A. Farrer (Lindsay); A. Orlin (Anton); A. Brucker (Alexander); M. Li (Mingyao); C.A. Curcio (Christine A.); S. Mohand-Sa'd (Saddek); J.-A. Sahel (José-Alain); I. Audo (Isabelle); M. Benchaboune (Mustapha); A.J. Cree (Angela); C.A. Rennie (Christina A.); S.V. Goverdhan (Srinivas V.); M. Grunin (Michelle); S. Hagbi-Levi (Shira); P. Campochiaro (Peter); N. Katsanis (Nicholas); F.G. Holz (Frank G.); F. Blond (Frédéric); H. Blanché (Hél'ne); J.-F. Deleuze (Jean-Fran'ois); R.P. Igo Jr. (Robert); B.J. Truitt (Barbara); N.S. Peachey (Neal S.); S.M. Meuer (Stacy M.); C.E. Myers (Chelsea E.); E.L. Moore (Emily L.); R. Klein (Ronald); M.A. Hauser (Michael A.); E.A. Postel (Eric A.); M.D. Courtenay (Monique D.); S.M. Schwartz (Stephen); J.L. Kovach (Jaclyn); W.K. Scott (William); G. Liew (Gerald); A.G. Tan (Ava G.); B. Gopinath (Bamini); J.C. Merriam (John C.); R.T. Smith (R Theodore); J.C. Khan (Jane C.); M. Shahid (Mohammad); A.T. Moore (Anthony T.); J.A. McGrath (J Allie); R. Laux (Reneé); M.A. Brantley (Milam A.); A. Agarwal (Anita); L. Ersoy (Lebriz); A. Caramoy (Albert); T. Langmann (Thomas); N.T.M. Saksens (Nicole T.); E.K. Jong (Eiko Kde); C.B. Hoyng (Carel B.); M.S. Cain (Melinda S.); A.J. Richardson (Andrea J.); T.M. Martin (Tammy M.); J. Blangero (John); D.E. Weeks (Daniel E.); B. Dhillon (Bal); C.M. van Duijn (Cornelia); K.F. Doheny (Kimberly F.); J. Romm (Jane); C.C.W. Klaver (Caroline); C. Hayward (Caroline); M.B. Gorin (Michael B.); M.L. Klein (Michael); P.N. Baird (Paul N.); A.I. Den Hollander (Anneke I.); S. Fauser (Sascha); J.R. WYates (John R.); R. Allikmets (Rando); J.J. Wang (Jie Jin); D.A. Schaumberg (Debra A.); B.E.K. Klein (Barbara); S.A. Hagstrom (Stephanie A.); Y. Chowers (Yehuda); A.J. Lotery (Andrew); T. Léveillard (Thierry); K. Zhang (Kang); M.H. Brilliant (Murray H.); A.W. Hewit (Alex); A. Swaroop (Anand); E.Y. Chew (Emily Y.); M.A. Pericak-Vance (Margaret); M.M. DeAngelis (Margaret); D. Stambolian (Dwight); J.L. Haines (Jonathan L.); S.K. Iyengar (Sudha K.); B.H.F. Weber (Bernhard); G.R. Abecasis (Gonçalo); I.M. Heid (Iris)

    2016-01-01

    textabstractAdvanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients

  2. Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions

    NARCIS (Netherlands)

    Kasperavičiūtė, Dalia; Catarino, Claudia B.; Chinthapalli, Krishna; Clayton, Lisa M. S.; Thom, Maria; Martinian, Lillian; Cohen, Hannah; Adalat, Shazia; Bockenhauer, Detlef; Pope, Simon A.; Lench, Nicholas; Koltzenburg, Martin; Duncan, John S.; Hammond, Peter; Hennekam, Raoul C. M.; Land, John M.; Sisodiya, Sanjay M.

    2011-01-01

    Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained. We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic

  3. Rare CNVs in Suicide Attempt include Schizophrenia-Associated Loci and Neurodevelopmental Genes: A Pilot Genome-Wide and Family-Based Study.

    Directory of Open Access Journals (Sweden)

    Marcus Sokolowski

    Full Text Available Suicidal behavior (SB has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs, as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA in offspring as main outcome (n = 660 trios. We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (100 kb CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having

  4. Detection of a Distinctive Genomic Signature in Rhabdoid Glioblastoma, A Rare Disease Entity Identified by Whole Exome Sequencing and Whole Transcriptome Sequencing

    Directory of Open Access Journals (Sweden)

    Youngil Koh

    2015-08-01

    Full Text Available We analyzed the genome of a rhabdoid glioblastoma (R-GBM tumor, a very rare variant of GBM. A surgical specimen of R-GBM from a 20-year-old woman was analyzed using whole exome sequencing (WES, whole transcriptome sequencing (WTS, single nucleotide polymorphism array, and array comparative genomic hybridization. The status of gene expression in R-GBM tissue was compared with that of normal brain tissue and conventional GBM tumor tissue. We identified 23 somatic non-synonymous small nucleotide variants with WES. We identified the BRAF V600E mutation and possible functional changes in the mutated genes, ISL1 and NDRG2. Copy number alteration analysis revealed gains of chromosomes 3, 7, and 9. We found loss of heterozygosity and focal homozygous deletion on 9q21, which includes CDKN2A and CDKN2B. In addition, WTS revealed that CDK6, MET, EZH2, EGFR, and NOTCH1, which are located on chromosomes 7 and 9, were over-expressed, whereas CDKN2A/2B were minimally expressed. Fusion gene analysis showed 14 candidate genes that may be functionally involved in R-GBM, including TWIST2, and UPK3BL. The BRAF V600E mutation, CDKN2A/2B deletion, and EGFR/MET copy number gain were observed. These simultaneous alterations are very rarely found in GBM. Moreover, the NDRG2 mutation was first identified in this study as it has never been reported in GBM. We observed a unique genomic signature in R-GBM compared to conventional GBM, which may provide insight regarding R-GBM as a distinct disease entity among the larger group of GBMs.

  5. In search of rare variants: Preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes

    Science.gov (United States)

    VRIEZE, SCOTT I.; MALONE, STEPHEN M.; VAIDYANATHAN, UMA; KWONG, ALAN; KANG, HYUN MIN; ZHAN, XIAOWEI; FLICKINGER, MATTHEW; IRONS, DANIEL; JUN, GOO; LOCKE, ADAM E.; PISTIS, GIORGIO; PORCU, ELEONORA; LEVY, SHAWN; MYERS, RICHARD M.; OETTING, WILLIAM; MCGUE, MATT; ABECASIS, GONCALO; IACONO, WILLIAM G.

    2014-01-01

    Whole genome sequencing was completed on 1,325 individuals from 602 families, identifying 27 million autosomal variants. Genetic association tests were conducted for those individuals who had been assessed for one or more of 17 endophenotypes (N range = 802–1,185). No significant associations were found. These 27 million variants were then imputed into the full sample of individuals with psychophysiological data (N range = 3,088–4,469) and again tested for associations with the 17 endophenotypes. No association was significant. Using a gene-based variable threshold burden test of nonsynonymous variants, we obtained five significant associations. These findings are preliminary and call for additional analysis of this rich sample. We argue that larger samples, alternative study designs, and additional bioinformatics approaches will be necessary to discover associations between these endophenotypes and genomic variation. PMID:25387710

  6. Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions.

    Directory of Open Access Journals (Sweden)

    Dalia Kasperavičiūtė

    Full Text Available Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained.We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients.Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.

  7. [Assessment of a new hotspot for plant biodiversity in the Mediterranean basin (North Africa)].

    Science.gov (United States)

    Véla, Errol; Benhouhou, Salima

    2007-08-01

    The concept of biodiversity hotspot at the regional and global scale has contributed to the improvement of the conservation strategies. The need for precise evaluation is often hampered by lapses of knowledge in some Mediterranean regional hotspots. The objective of the present work is to analyse the diversity of endemic and rare flora in the northern part of Algeria. According to the bibliographical data that are available, the most remarkable areas for endemism are the Oran's coast, the Great Kabylia, and the Small Kabylia. As far as rare species are concerned, coastal Numidia comes first, then the Algiers surroundings. This group 'Kabylias-Numidia-Kroumiria' comprises an unrecognised regional hotspot, made of forests, mountains and coastal ecosystems and threatened by human activities. In the face of growing threats, it is urgent to reinforce national and international policies of conservation and to cooperate for a better floristic knowledge of all the areas mentioned above.

  8. The Red Queen theory of recombination hotspots.

    Science.gov (United States)

    Ubeda, F; Wilkins, J F

    2011-03-01

    Recombination hotspots are small chromosomal regions, where meiotic crossover events happen with high frequency. Recombination is initiated by a double-strand break (DSB) that requires the intervention of the molecular repair mechanism. The DSB repair mechanism may result in the exchange of homologous chromosomes (crossover) and the conversion of the allelic sequence that breaks into the one that does not break (biased gene conversion). Biased gene conversion results in a transmission advantage for the allele that does not break, thus preventing recombination and rendering recombination hotspots transient. How is it possible that recombination hotspots persist over evolutionary time (maintaining the average chromosomal crossover rate) when they are self-destructive? This fundamental question is known as the recombination hotspot paradox and has attracted much attention in recent years. Yet, that attention has not translated into a fully satisfactory answer. No existing model adequately explains all aspects of the recombination hotspot paradox. Here, we formulate an intragenomic conflict model resulting in Red Queen dynamics that fully accounts for all empirical observations regarding the molecular mechanisms of recombination hotspots, the nonrandom targeting of the recombination machinery to hotspots and the evolutionary dynamics of hotspot turnover. © 2010 The Authors. Journal of Evolutionary Biology © 2010 European Society For Evolutionary Biology.

  9. Capturing Hotspots For Constrained Indoor Movement

    DEFF Research Database (Denmark)

    Ahmed, Tanvir; Pedersen, Torben Bach; Lu, Hua

    2013-01-01

    Finding the hotspots in large indoor spaces is very important for getting overloaded locations, security, crowd management, indoor navigation and guidance. The tracking data coming from indoor tracking are huge in volume and not readily available for finding hotspots. This paper presents a graph...

  10. High-resolution characterization of CPD hotspot formation in human fibroblasts.

    Science.gov (United States)

    Zavala, Anamaria G; Morris, Robert T; Wyrick, John J; Smerdon, Michael J

    2014-01-01

    Repair of DNA lesions must occur within the chromatin landscape and is associated with alterations in histone modifications and nucleosome rearrangement. To directly associate these chromatin features with DNA damage and repair, it is necessary to be able to map DNA adducts. We have developed a cyclobutane pyrimidine dimer (CPD)-specific immunoprecipitation method and mapped ultraviolet damage hotspots across human chromosomes 1 and 6. CPD hotspots occur almost equally in genic and intergenic regions. However, these hotspots are significantly more prevalent adjacent to repeat elements, especially Alu repeats. Nucleosome mapping studies indicate that nucleosomes are consistently positioned at Alu elements where CPD hotspots form, but by 2 h post-irradiation, these same regions are significantly depleted of nucleosomes. These results indicate that nucleosomes associated with hotspots of CPD formation are readily rearranged, potentially making them accessible to DNA repair machinery. Our results represent the first chromosome scale map of ultraviolet-induced DNA lesions in the human genome, and reveal the sequence features and dynamic chromatin changes associated with CPD hotspots.

  11. Evaluating Temporal Consistency in Marine Biodiversity Hotspots

    Science.gov (United States)

    Barner, Allison K.; Benkwitt, Cassandra E.; Boersma, Kate S.; Cerny-Chipman, Elizabeth B.; Ingeman, Kurt E.; Kindinger, Tye L.; Lindsley, Amy J.; Nelson, Jake; Reimer, Jessica N.; Rowe, Jennifer C.; Shen, Chenchen; Thompson, Kevin A.; Heppell, Selina S.

    2015-01-01

    With the ongoing crisis of biodiversity loss and limited resources for conservation, the concept of biodiversity hotspots has been useful in determining conservation priority areas. However, there has been limited research into how temporal variability in biodiversity may influence conservation area prioritization. To address this information gap, we present an approach to evaluate the temporal consistency of biodiversity hotspots in large marine ecosystems. Using a large scale, public monitoring dataset collected over an eight year period off the US Pacific Coast, we developed a methodological approach for avoiding biases associated with hotspot delineation. We aggregated benthic fish species data from research trawls and calculated mean hotspot thresholds for fish species richness and Shannon’s diversity indices over the eight year dataset. We used a spatial frequency distribution method to assign hotspot designations to the grid cells annually. We found no areas containing consistently high biodiversity through the entire study period based on the mean thresholds, and no grid cell was designated as a hotspot for greater than 50% of the time-series. To test if our approach was sensitive to sampling effort and the geographic extent of the survey, we followed a similar routine for the northern region of the survey area. Our finding of low consistency in benthic fish biodiversity hotspots over time was upheld, regardless of biodiversity metric used, whether thresholds were calculated per year or across all years, or the spatial extent for which we calculated thresholds and identified hotspots. Our results suggest that static measures of benthic fish biodiversity off the US West Coast are insufficient for identification of hotspots and that long-term data are required to appropriately identify patterns of high temporal variability in biodiversity for these highly mobile taxa. Given that ecological communities are responding to a changing climate and other

  12. Evaluating Temporal Consistency in Marine Biodiversity Hotspots.

    Science.gov (United States)

    Piacenza, Susan E; Thurman, Lindsey L; Barner, Allison K; Benkwitt, Cassandra E; Boersma, Kate S; Cerny-Chipman, Elizabeth B; Ingeman, Kurt E; Kindinger, Tye L; Lindsley, Amy J; Nelson, Jake; Reimer, Jessica N; Rowe, Jennifer C; Shen, Chenchen; Thompson, Kevin A; Heppell, Selina S

    2015-01-01

    With the ongoing crisis of biodiversity loss and limited resources for conservation, the concept of biodiversity hotspots has been useful in determining conservation priority areas. However, there has been limited research into how temporal variability in biodiversity may influence conservation area prioritization. To address this information gap, we present an approach to evaluate the temporal consistency of biodiversity hotspots in large marine ecosystems. Using a large scale, public monitoring dataset collected over an eight year period off the US Pacific Coast, we developed a methodological approach for avoiding biases associated with hotspot delineation. We aggregated benthic fish species data from research trawls and calculated mean hotspot thresholds for fish species richness and Shannon's diversity indices over the eight year dataset. We used a spatial frequency distribution method to assign hotspot designations to the grid cells annually. We found no areas containing consistently high biodiversity through the entire study period based on the mean thresholds, and no grid cell was designated as a hotspot for greater than 50% of the time-series. To test if our approach was sensitive to sampling effort and the geographic extent of the survey, we followed a similar routine for the northern region of the survey area. Our finding of low consistency in benthic fish biodiversity hotspots over time was upheld, regardless of biodiversity metric used, whether thresholds were calculated per year or across all years, or the spatial extent for which we calculated thresholds and identified hotspots. Our results suggest that static measures of benthic fish biodiversity off the US West Coast are insufficient for identification of hotspots and that long-term data are required to appropriately identify patterns of high temporal variability in biodiversity for these highly mobile taxa. Given that ecological communities are responding to a changing climate and other

  13. Identifying infection hotspots early on.

    Science.gov (United States)

    Shabha, Ghasson

    2012-04-01

    According to many published studies, 'ducting in ventilation and air-conditioning are largely overlooked and ignored, as they are out of sight and out of mind', despite mounting evidence indicating a higher risk in spreading airborne infections'. So says Ghasson Shabha BSc (Arch) MSc, PhD (Arch), MBIFM, Associate CIBSE, PG Cert Ed, of the Faculty of Technology, Engineering and the Environment (TEE), at the Birmingham School of the Built Environment (BSBE) at Birmingham City University, who adds that CIBSE estimates that fewer than 5% of buildings with air-conditioning systems above 12 kW have been inspected so far. Here he argues that incorporating 3D building information modelling software into existing computer-aided facilities management software systems will enable hospitals' 'infection hotspots' to be far more quickly identified, and subsequently monitored, to prevent future problems.

  14. Rare, high-affinity anti-pathogen antibodies from human repertoires, discovered using microfluidics and molecular genomics.

    Science.gov (United States)

    Adler, Adam S; Mizrahi, Rena A; Spindler, Matthew J; Adams, Matthew S; Asensio, Michael A; Edgar, Robert C; Leong, Jackson; Leong, Renee; Roalfe, Lucy; White, Rebecca; Goldblatt, David; Johnson, David S

    Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These antibodies are often excellent candidates for therapeutic monoclonal antibodies. However, mining natural human antibody repertoires is a challenge. In this study, we demonstrate a new method that uses microfluidics, yeast display, and deep sequencing to identify 247 natively paired anti-pathogen single-chain variable fragments (scFvs), which were initially as rare as 1 in 100,000 in the human repertoires. Influenza A vaccination increased the frequency of influenza A antigen-binding scFv within the peripheral B cell repertoire from <0.1% in non-vaccinated donors to 0.3-0.4% in vaccinated donors, whereas pneumococcus vaccination did not increase the frequency of antigen-binding scFv. However, the pneumococcus scFv binders from the vaccinated library had higher heavy and light chain Replacement/Silent mutation (R/S) ratios, a measure of affinity maturation, than the pneumococcus binders from the corresponding non-vaccinated library. Thus, pneumococcus vaccination may increase the frequency of affinity-matured antibodies in human repertoires. We synthesized 10 anti-influenza A and nine anti-pneumococcus full-length antibodies that were highly abundant among antigen-binding scFv. All 10 anti-influenza A antibodies bound the appropriate antigen at KD<10 nM and neutralized virus in cellular assays. All nine anti-pneumococcus full-length antibodies bound at least one polysaccharide serotype, and 71% of the anti-pneumococcus antibodies that we tested were functional in cell killing assays. Our approach has future application in a variety of fields, including the development of therapeutic antibodies for emerging viral diseases, autoimmune disorders, and cancer.

  15. HD-CNV: hotspot detector for copy number variants.

    Science.gov (United States)

    Butler, Jenna L; Osborne Locke, Marjorie Elizabeth; Hill, Kathleen A; Daley, Mark

    2013-01-15

    Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software or by automated graph analysis, is useful in identifying genomic regions of interest for further study. HD-CNV is an open source Java code and is freely available, with tutorials and sample data from http://daleylab.org. jcamer7@uwo.ca

  16. Coral Reef Watch, Hotspots, 50 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA Coral Reef Watch provides Coral Bleaching hotspot maps derived from NOAA's Polar Operational Environmental Satellites (POES). This data provides global area...

  17. Absence of ras-gene hot-spot mutations in canine fibrosarcomas and melanomas.

    Science.gov (United States)

    Murua Escobar, Hugo; Günther, Kathrin; Richter, Andreas; Soller, Jan T; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

    2004-01-01

    Point mutations within ras proto-oncogenes, particularly within the mutational hot-spot codons 12, 13 and 61, are frequently detected in human malignancies and in different types of experimentally-induced tumours in animals. So far little is known about ras mutations in naturally occurring canine fibrosarcomas or K-ras mutations in canine melanomas. To elucidate whether ras mutations exist in these naturally occurring tumours in dogs, in the present study we screened 13 canine fibrosarcomas, 2 feline fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot-spots, making this the first study to investigate a large number of canine fibrosarcomas. None of the samples showed a K- or N-ras hot spot mutation. Thus, our data strongly suggest that ras mutations at the hot-spot loci are very rare and do not play a major role in the pathogenesis of the spontaneously occurring canine tumours investigated.

  18. Cis- and trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot.

    Directory of Open Access Journals (Sweden)

    Frédéric Baudat

    2007-06-01

    Full Text Available In most eukaryotes, the prophase of the first meiotic division is characterized by a high level of homologous recombination between homologous chromosomes. Recombination events are not distributed evenly within the genome, but vary both locally and at large scale. Locally, most recombination events are clustered in short intervals (a few kilobases called hotspots, separated by large intervening regions with no or very little recombination. Despite the importance of regulating both the frequency and the distribution of recombination events, the genetic factors controlling the activity of the recombination hotspots in mammals are still poorly understood. We previously characterized a recombination hotspot located close to the Psmb9 gene in the mouse major histocompatibility complex by sperm typing, demonstrating that it is a site of recombination initiation. With the goal of uncovering some of the genetic factors controlling the activity of this initiation site, we analyzed this hotspot in both male and female germ lines and compared the level of recombination in different hybrid mice. We show that a haplotype-specific element acts at distance and in trans to activate about 2,000-fold the recombination activity at Psmb9. Another haplotype-specific element acts in cis to repress initiation of recombination, and we propose this control to be due to polymorphisms located within the initiation zone. In addition, we describe subtle variations in the frequency and distribution of recombination events related to strain and sex differences. These findings show that most regulations observed act at the level of initiation and provide the first analysis of the control of the activity of a meiotic recombination hotspot in the mouse genome that reveals the interactions of elements located both in and outside the hotspot.

  19. A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge?

    Science.gov (United States)

    Banerjee, Priyanka; Mondal, Rajiv Kumar; Nandi, Madhuparna; Ghosh, Sumantra; Khatun, Mousumi; Chakraborty, Nabendu; Bhattacharya, Swatilekha; RoyChoudhury, Arindam; Banerjee, Soma; Santra, Amal; Sil, Samir; Chowdhury, Abhijit; Bhaumik, Pradip; Datta, Simanti

    2014-01-01

    Background/Aims HBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura. Methods From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. Results HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. Conclusions IndD4 has potential to undermine vaccination programs or anti

  20. Predator diversity hotspots in the blue ocean.

    Science.gov (United States)

    Worm, Boris; Lotze, Heike K; Myers, Ransom A

    2003-08-19

    Concentrations of biodiversity, or hotspots, represent conservation priorities in terrestrial ecosystems but remain largely unexplored in marine habitats. In the open ocean, many large predators such as tunas, sharks, billfishes, and sea turtles are of current conservation concern because of their vulnerability to overfishing and ecosystem role. Here we use scientific-observer records from pelagic longline fisheries in the Atlantic and Pacific Oceans to show that oceanic predators concentrate in distinct diversity hotspots. Predator diversity consistently peaks at intermediate latitudes (20-30 degrees N and S), where tropical and temperate species ranges overlap. Individual hotspots are found close to prominent habitat features such as reefs, shelf breaks, or seamounts and often coincide with zooplankton and coral reef hotspots. Closed-area models in the northwest Atlantic predict that protection of hotspots outperforms other area closures in safeguarding threatened pelagic predators from ecological extinction. We conclude that the seemingly monotonous landscape of the open ocean shows rich structure in species diversity and that these features should be used to focus future conservation efforts.

  1. Plate tectonics and hotspots: the third dimension.

    Science.gov (United States)

    Anderson, D L; Tanimoto, T; Zhang, Y S

    1992-06-19

    High-resolution seismic tomographic models of the upper mantle provide powerful new constraints on theories of plate tectonics and hotspots. Midocean ridges have extremely low seismic velocities to a depth of 100 kilometers. These low velocities imply partial melting. At greater depths, low-velocity and high-velocity anomalies record, respectively, previous positions of migrating ridges and trenches. Extensional, rifting, and hotspot regions have deep (> 200 kilometers) low-velocity anomalies. The upper mantle is characterized by vast domains of high temperature rather than small regions surrounding hotspots; the asthenosphere is not homogeneous or isothermal. Extensive magmatism requires a combination of hot upper mantle and suitable lithospheric conditions. High-velocity regions of the upper 200 kilometers of the mantle correlate with Archean cratons.

  2. Are hot-spots occluded from water?

    Science.gov (United States)

    Moreira, Irina Sousa; Ramos, Rui Miguel; Martins, Joao Miguel; Fernandes, Pedro Alexandrino; Ramos, Maria João

    2014-01-01

    Protein-protein interactions are the basis of many biological processes and are governed by focused regions with high binding affinities, the warm- and hot-spots. It was proposed that these regions are surrounded by areas with higher packing density leading to solvent exclusion around them - "the O-ring theory." This important inference still lacks sufficient demonstration. We have used Molecular Dynamics (MD) simulations to investigate the validity of the O-ring theory in the context of the conformational flexibility of the proteins, which is critical for function, in general, and for interaction with water, in particular. The MD results were analyzed for a variety of solvent-accessible surface area (SASA) features, radial distribution functions (RDFs), protein-water distances, and water residence times. The measurement of the average solvent-accessible surface area features for the warm- and hot-spots and the null-spots, as well as data for corresponding RDFs, identify distinct properties for these two sets of residues. Warm- and hot-spots are found to be occluded from the solvent. However, it has to be borne in mind that water-mediated interactions have significant power to construct an extensive and strongly bonded interface. We observed that warm- and hot-spots tend to form hydrogen bond (H-bond) networks with water molecules that have an occupancy around 90%. This study provides strong evidence in support of the O-ring theory and the results show that hot-spots are indeed protected from the bulk solvent. Nevertheless, the warm- and hot-spots still make water-mediated contacts, which are also important for protein-protein binding.

  3. Recombination hotspots and population structure in Plasmodium falciparum.

    Science.gov (United States)

    Mu, Jianbing; Awadalla, Philip; Duan, Junhui; McGee, Kate M; Joy, Deirdre A; McVean, Gilean A T; Su, Xin-zhuan

    2005-10-01

    Understanding the influences of population structure, selection, and recombination on polymorphism and linkage disequilibrium (LD) is integral to mapping genes contributing to drug resistance or virulence in Plasmodium falciparum. The parasite's short generation time, coupled with a high cross-over rate, can cause rapid LD break-down. However, observations of low genetic variation have led to suggestions of effective clonality: selfing, population admixture, and selection may preserve LD in populations. Indeed, extensive LD surrounding drug-resistant genes has been observed, indicating that recombination and selection play important roles in shaping recent parasite genome evolution. These studies, however, provide only limited information about haplotype variation at local scales. Here we describe the first (to our knowledge) chromosome-wide SNP haplotype and population recombination maps for a global collection of malaria parasites, including the 3D7 isolate, whose genome has been sequenced previously. The parasites are clustered according to continental origin, but alternative groupings were obtained using SNPs at 37 putative transporter genes that are potentially under selection. Geographic isolation and highly variable multiple infection rates are the major factors affecting haplotype structure. Variation in effective recombination rates is high, both among populations and along the chromosome, with recombination hotspots conserved among populations at chromosome ends. This study supports the feasibility of genome-wide association studies in some parasite populations.

  4. Recombination hotspots and population structure in Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Jianbing Mu

    2005-10-01

    Full Text Available Understanding the influences of population structure, selection, and recombination on polymorphism and linkage disequilibrium (LD is integral to mapping genes contributing to drug resistance or virulence in Plasmodium falciparum. The parasite's short generation time, coupled with a high cross-over rate, can cause rapid LD break-down. However, observations of low genetic variation have led to suggestions of effective clonality: selfing, population admixture, and selection may preserve LD in populations. Indeed, extensive LD surrounding drug-resistant genes has been observed, indicating that recombination and selection play important roles in shaping recent parasite genome evolution. These studies, however, provide only limited information about haplotype variation at local scales. Here we describe the first (to our knowledge chromosome-wide SNP haplotype and population recombination maps for a global collection of malaria parasites, including the 3D7 isolate, whose genome has been sequenced previously. The parasites are clustered according to continental origin, but alternative groupings were obtained using SNPs at 37 putative transporter genes that are potentially under selection. Geographic isolation and highly variable multiple infection rates are the major factors affecting haplotype structure. Variation in effective recombination rates is high, both among populations and along the chromosome, with recombination hotspots conserved among populations at chromosome ends. This study supports the feasibility of genome-wide association studies in some parasite populations.

  5. Hotspot Mainport Schiphol : midterm review report

    NARCIS (Netherlands)

    Döpp, S.; Brink, van den P.; Hartogensis, O.K.; Jacobs, A.; Homan, C.; Sondij, J.

    2012-01-01

    The focus of Knowledge for Climate (KfC) research in Hotspot Schiphol Mainport is to optimize the contribution of meteorological services to a sustainable operation and reliable operation of Schiphol airport. Three research projects have been carried out in the first tranche of the Knowledge for

  6. Eliminating "Hotspots" in Digital Image Processing

    Science.gov (United States)

    Salomon, P. M.

    1984-01-01

    Signals from defective picture elements rejected. Image processing program for use with charge-coupled device (CCD) or other mosaic imager augmented with algorithm that compensates for common type of electronic defect. Algorithm prevents false interpretation of "hotspots". Used for robotics, image enhancement, image analysis and digital television.

  7. Biogeographic methods identify gymnosperm biodiversity hotspots.

    Science.gov (United States)

    Contreras-Medina, R; Morrone, J J; Lunz Vega, I

    2001-10-01

    A remarkable congruence among areas of endemism, panbiogeographic nodes, and refugia in western North America, Japan, south-western China, Tasmania, and New Caledonia indicates that these areas deserve special status for conservation. Here we propose that areas identified by different biogeographic methods are significant candidates for designation as hotspots.

  8. The unusual Samoan hotspot: A "hotspot highway" juxtaposed with a trench

    Science.gov (United States)

    Jackson, M. G.; Konter, J. G.; Koppers, A. A.

    2011-12-01

    Oceanic hotspots are fed by (relatively) stationary, upwelling mantle plumes that melt beneath mobile tectonic plates. This mechanism results in the generation of a linear chain of volcanoes exhibiting a clear age progression: the islands and seamounts should be increasingly older with increasing distance from the inferred location of the mantle plume. Located in the southwest Pacific, the Cook-Austral volcanic islands and seamounts were long thought to lack a clear age progression, and it has been argued that the Cook-Austral volcanic chain is an example of a hotspot not fed by a mantle plume. However, work by Chauvel et al (1997) showed that the Cook-Austral volcanoes have been generated by three distinct, co-linear mantle plumes spaced by ~1000 km, resulting in 3 overlapping hotspot tracks. Critically, the volcanoes generated by each hotspot exhibit a clear age progression that emerges from its respective plume. Using plate motion models, the reconstructed tracks of the three Cook-Austral hotspots backtrack through the region of the Pacific plate now occupied by the Samoan hotspot between 10 and 40 Ma (Konter et al., 2008). Owing to the unusual number of hotspots (Samoa is the fourth) that have been hosted in the region, we refer to this corridor of the Pacific plate as the "hotspot highway." The Samoan hotspot is burning through and thus crosscutting the trails of the older Cook-Austral hotspots. Consistent with this hypothesis, Jackson et al. (2010) reported volcanic features from the Cook-Austral hotspots in the Samoan region, including three seamounts and one atoll with geochemical affinities to the Cook-Austral hotspot. The Pacific lithosphere was likely "preconditioned" (metasomatized) by the three Cook-Australs hotspots before the arrival of the Samoan plume into the region, yet geochemical signatures associated with the Cook-Austral hotspot pedigrees are not evident in Samoan shield lavas. However, Samoan rejuvenated lavas exhibit a clear EMI (enriched

  9. Genetic and Rare Diseases Information Center (GARD)

    Data.gov (United States)

    Federal Laboratory Consortium — NCATS collaborates with the National Human Genome Research Institute (NHGRI) to support GARD, a center designed to provide comprehensive information about rare and...

  10. Hotspots within hotspots? Hammerhead shark movements around Wolf Island, Galapagos Marine Reserve

    OpenAIRE

    Hearn, Alex; Ketchum, James; Klimley, A. Peter; Espinoza, Eduardo; Peñaherrera, Cesar

    2010-01-01

    Are pelagic species such as sharks and tuna distributed homogenously or heterogeneously in the oceans? Large assemblages of these species have been observed at seamounts and offshore islands in the eastern tropical Pacific, which are considered hotspots of pelagic biodiversity. Is the species distribution uniform at these hotspots or do species aggregate at a finer spatial scale at these sites? We employed three techniques to demonstrate that the aggregations of scalloped hammerhead sharks, S...

  11. HOTSPOT Health Physics codes for the PC

    Energy Technology Data Exchange (ETDEWEB)

    Homann, S.G.

    1994-03-01

    The HOTSPOT Health Physics codes were created to provide Health Physics personnel with a fast, field-portable calculation tool for evaluating accidents involving radioactive materials. HOTSPOT codes are a first-order approximation of the radiation effects associated with the atmospheric release of radioactive materials. HOTSPOT programs are reasonably accurate for a timely initial assessment. More importantly, HOTSPOT codes produce a consistent output for the same input assumptions and minimize the probability of errors associated with reading a graph incorrectly or scaling a universal nomogram during an emergency. The HOTSPOT codes are designed for short-term (less than 24 hours) release durations. Users requiring radiological release consequences for release scenarios over a longer time period, e.g., annual windrose data, are directed to such long-term models as CAPP88-PC (Parks, 1992). Users requiring more sophisticated modeling capabilities, e.g., complex terrain; multi-location real-time wind field data; etc., are directed to such capabilities as the Department of Energy`s ARAC computer codes (Sullivan, 1993). Four general programs -- Plume, Explosion, Fire, and Resuspension -- calculate a downwind assessment following the release of radioactive material resulting from a continuous or puff release, explosive release, fuel fire, or an area contamination event. Other programs deal with the release of plutonium, uranium, and tritium to expedite an initial assessment of accidents involving nuclear weapons. Additional programs estimate the dose commitment from the inhalation of any one of the radionuclides listed in the database of radionuclides; calibrate a radiation survey instrument for ground-survey measurements; and screen plutonium uptake in the lung (see FIDLER Calibration and LUNG Screening sections).

  12. The detection of thermophilous forest hotspots in Poland using geostatistical interpolation of plant richness

    Directory of Open Access Journals (Sweden)

    Marcin Kiedrzyński

    2014-07-01

    Full Text Available Attempts to study biodiversity hotspots on a regional scale should combine compositional and functionalist criteria. The detection of hotspots in this study uses one ecologically similar group of high conservation value species as hotspot indicators, as well as focal habitat indicators, to detect the distribution of suitable environmental conditions. The method is assessed with reference to thermophilous forests in Poland – key habitats for many rare and relict species. Twenty-six high conservation priority species were used as hotspot indicators, and ten plant taxa characteristic of the Quercetalia pubescenti-petraeae phytosociological order were used as focal habitat indicators. Species distribution data was based on a 10 × 10 km grid. The number of species per grid square was interpolated by the ordinary kriging geostatistical method. Our analysis largely determined the distribution of areas with concentration of thermophilous forest flora, but also regional disjunctions and geographical barriers. Indicator species richness can be interpreted as a reflection of the actual state of habitat conditions. It can also be used to determine the location of potential species refugia and possible past and future migration routes.

  13. Magnetic and electric hotspots with silicon nanodimers.

    Science.gov (United States)

    Bakker, Reuben M; Permyakov, Dmitry; Yu, Ye Feng; Markovich, Dmitry; Paniagua-Domínguez, Ramón; Gonzaga, Leonard; Samusev, Anton; Kivshar, Yuri; Luk'yanchuk, Boris; Kuznetsov, Arseniy I

    2015-03-11

    The study of the resonant behavior of silicon nanostructures provides a new route for achieving efficient control of both electric and magnetic components of light. We demonstrate experimentally and numerically that enhancement of localized electric and magnetic fields can be achieved in a silicon nanodimer. For the first time, we experimentally observe hotspots of the magnetic field at visible wavelengths for light polarized across the nanodimer's primary axis, using near-field scanning optical microscopy.

  14. Integration Preferences of Wildtype AAV-2 for Consensus Rep-Binding Sites at Numerous Loci in the Human Genome

    Science.gov (United States)

    Hüser, Daniela; Gogol-Döring, Andreas; Lutter, Timo; Weger, Stefan; Winter, Kerstin; Hammer, Eva-Maria; Cathomen, Toni; Reinert, Knut; Heilbronn, Regine

    2010-01-01

    Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome. PMID:20628575

  15. Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome.

    Directory of Open Access Journals (Sweden)

    Daniela Hüser

    Full Text Available Adeno-associated virus type 2 (AAV is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome.

  16. Integration preferences of wildtype AAV-2 for consensus rep-binding sites at numerous loci in the human genome.

    Science.gov (United States)

    Hüser, Daniela; Gogol-Döring, Andreas; Lutter, Timo; Weger, Stefan; Winter, Kerstin; Hammer, Eva-Maria; Cathomen, Toni; Reinert, Knut; Heilbronn, Regine

    2010-07-08

    Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome.

  17. Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; John, Sam

    2011-01-01

    Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I...... hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides...... with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPβ and -δ) to transcription factor 'hotspots'. Our results demonstrate that C/EBPβ marks a large number of these transcription factor 'hotspots' before induction of differentiation...

  18. Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies.

    Directory of Open Access Journals (Sweden)

    Heather C Mefford

    2010-05-01

    Full Text Available Epilepsy is one of the most common neurological disorders in humans with a prevalence of 1% and a lifetime incidence of 3%. Several genes have been identified in rare autosomal dominant and severe sporadic forms of epilepsy, but the genetic cause is unknown in the vast majority of cases. Copy number variants (CNVs are known to play an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID, autism, and schizophrenia. Genome-wide studies of copy number variation in epilepsy have not been performed. We have applied whole-genome oligonucleotide array comparative genomic hybridization to a cohort of 517 individuals with various idiopathic, non-lesional epilepsies. We detected one or more rare genic CNVs in 8.9% of affected individuals that are not present in 2,493 controls; five individuals had two rare CNVs. We identified CNVs in genes previously implicated in other neurodevelopmental disorders, including two deletions in AUTS2 and one deletion in CNTNAP2. Therefore, our findings indicate that rare CNVs are likely to contribute to a broad range of generalized and focal epilepsies. In addition, we find that 2.9% of patients carry deletions at 15q11.2, 15q13.3, or 16p13.11, genomic hotspots previously associated with ID, autism, or schizophrenia. In summary, our findings suggest common etiological factors for seemingly diverse diseases such as ID, autism, schizophrenia, and epilepsy.

  19. HOTSPOT: The Snake River Scientifi c Drilling Project— Tracking the Yellowstone Hotspot Through Space and Time

    Directory of Open Access Journals (Sweden)

    Douglas F. Williams

    2006-09-01

    Full Text Available The project “HOTSPOT: Scientifi c Drilling of the Snake River Plain” held its inaugural workshop in Twin Falls, Idaho, U.S.A. on 18–21 May 2006. This inter-disciplinary workshop, sponsored by the International Continental Scientifi c Drilling Program (ICDP, explored the major scientifi c and logistical issues central to a transect of boreholes along the hotspot track and addressing the geochemical evolution of continental lithosphere in response to interaction with deepseated mantle hotspots or plumes. A series of four to six bore holes is envisioned, each about 1.5–2.0 km deep and located along the axis of the Snake River Plain. The holes will specific ally target the origin and evolution of hotspot-related volcanism in space and time. To accomplish scientific and logistical planning, sixty scientists from six countries attended the workshop.

  20. The emergence of motives in liminal hotspots

    DEFF Research Database (Denmark)

    Nissen, Morten; Sørensen, Kathrine Solgaard

    2017-01-01

    as part of an ongoing collaboration with counselors who experiment with different ways of helping young drug users without taking motivation as premise, in the sense of a prerequisite, for interventions. Data from recorded counseling sessions are analyzed and rearticulated, first in terms of the classical...... motivation–resistance contradiction; then through pragmatic approaches in counseling, i.e., the prevalent cognitive-client-centered form and the “solution-focused brief therapy” approach—and finally as motives emergent in liminal hotspots....

  1. The emergence of motives in liminal hotspots

    DEFF Research Database (Denmark)

    Nissen, Morten; Sørensen, Kathrine Solgaard

    2017-01-01

    The concept of “motivation” commonly constructs as a psychological essence what is really the paradoxical imposition of a required desire. While the resulting impasse blocked theoretical development for around four decades, pragmatic motivational techniques evolved regardless. These could...... be (probably to no avail) dismissed for not taking account of the deep theoretical problems. This article suggests instead to rearticulate them with the conceptual repertoire of liminal hotspots, which directs attention to the emergent nature of activities and collectives, and thus motives. This is done...

  2. Rare Decays

    Science.gov (United States)

    Bryman, Douglas

    1998-04-01

    Fifty years after the discovery of the strange quark and the first search for lepton flavor violation in muon decay, extraordinary experimental progress continues to be made on measurements and searches for rare kaon and muon decays. Several important new rare kaon decay channels, including the second order weak flavor-changing-neutral-current process K^+arrowπ^+ν\\overlineν, have been reported recently, and further significant advances are anticipated. Although only null results have been found so far in the quest for lepton flavor violation, there are promising prospects for additional gains in sensitivity of orders of magnitude on such processes as μ→ e γ, nuclear μ → e conversion, K^0_Larrowμ e and Karrowπμ^+e^-. In this presentation, the status of experiments on selected rare decays of kaons and muons will be reviewed.

  3. Geographic Hotspots of Critical National Infrastructure.

    Science.gov (United States)

    Thacker, Scott; Barr, Stuart; Pant, Raghav; Hall, Jim W; Alderson, David

    2017-06-12

    Failure of critical national infrastructures can result in major disruptions to society and the economy. Understanding the criticality of individual assets and the geographic areas in which they are located is essential for targeting investments to reduce risks and enhance system resilience. Within this study we provide new insights into the criticality of real-life critical infrastructure networks by integrating high-resolution data on infrastructure location, connectivity, interdependence, and usage. We propose a metric of infrastructure criticality in terms of the number of users who may be directly or indirectly disrupted by the failure of physically interdependent infrastructures. Kernel density estimation is used to integrate spatially discrete criticality values associated with individual infrastructure assets, producing a continuous surface from which statistically significant infrastructure criticality hotspots are identified. We develop a comprehensive and unique national-scale demonstration for England and Wales that utilizes previously unavailable data from the energy, transport, water, waste, and digital communications sectors. The testing of 200,000 failure scenarios identifies that hotspots are typically located around the periphery of urban areas where there are large facilities upon which many users depend or where several critical infrastructures are concentrated in one location. © 2017 Society for Risk Analysis.

  4. An examination of the relationship between hotspots and recombination associated with chromosome 21 nondisjunction.

    Directory of Open Access Journals (Sweden)

    Tiffany Renee Oliver

    Full Text Available Trisomy 21, resulting in Down Syndrome (DS, is the most common autosomal trisomy among live-born infants and is caused mainly by nondisjunction of chromosome 21 within oocytes. Risk factors for nondisjunction depend on the parental origin and type of meiotic error. For errors in the oocyte, increased maternal age and altered patterns of recombination are highly associated with nondisjunction. Studies of normal meiotic events in humans have shown that recombination clusters in regions referred to as hotspots. In addition, GC content, CpG fraction, Poly(A/Poly(T fraction and gene density have been found to be significant predictors of the placement of sex-averaged recombination in the human genome. These observations led us to ask whether the altered patterns of recombination associated with maternal nondisjunction of chromosome 21 could be explained by differences in the relationship between recombination placement and recombination-related genomic features (i.e., GC content, CpG fraction, Poly(A/Poly(T fraction or gene density on 21q or differential hot-spot usage along the nondisjoined chromosome 21. We found several significant associations between our genomic features of interest and recombination, interestingly, these results were not consistent among recombination types (single and double proximal or distal events. We also found statistically significant relationships between the frequency of hotspots and the distribution of recombination along nondisjoined chromosomes. Collectively, these findings suggest that factors that affect the accessibility of a specific chromosome region to recombination may be altered in at least a proportion of oocytes with MI and MII errors.

  5. MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer.

    Science.gov (United States)

    Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L

    2016-01-04

    The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Whole genome sequencing of a rare rotavirus from archived stool sample demonstrates independent zoonotic origin of human G8P[14] strains in Hungary.

    Science.gov (United States)

    Marton, Szilvia; Dóró, Renáta; Fehér, Enikő; Forró, Barbara; Ihász, Katalin; Varga-Kugler, Renáta; Farkas, Szilvia L; Bányai, Krisztián

    2017-01-02

    Genotype P[14] rotaviruses in humans are thought to be zoonotic strains originating from bovine or ovine host species. Over the past 30 years only few genotype P[14] strains were identified in Hungary totaling<0.1% of all human rotaviruses whose genotype had been determined. In this study we report the genome sequence and phylogenetic analysis of a human genotype G8P[14] strain, RVA/Human-wt/HUN/182-02/2001/G8P[14]. The whole genome constellation (G8-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3) of this strain was shared with another Hungarian zoonotic G8P[14] strain, RVA/Human-wt/HUN/BP1062/2004/G8P[14], although phylogenetic analyses revealed the two rotaviruses likely had different progenitors. Overall, our findings indicate that human G8P[14] rotavirus detected in Hungary in the past originated from independent zoonotic events. Further studies are needed to assess the public health risk associated with infections by various animal rotavirus strains. Copyright © 2016. Published by Elsevier B.V.

  7. Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers.

    Science.gov (United States)

    Lee, Ha Youn; Lee, Se Hoon; Won, Jae Kyung; Lee, Dong Soo; Kwon, Nak Jung; Choi, Sun Mi; Lee, Jinwoo; Lee, Chang Hoon; Lee, Sang Min; Yim, Jae Joon; Yoo, Chul Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

    2017-03-01

    Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57-73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.

  8. Imbalance aware lithography hotspot detection: a deep learning approach

    Science.gov (United States)

    Yang, Haoyu; Luo, Luyang; Su, Jing; Lin, Chenxi; Yu, Bei

    2017-07-01

    With the advancement of very large scale integrated circuits (VLSI) technology nodes, lithographic hotspots become a serious problem that affects manufacture yield. Lithography hotspot detection at the post-OPC stage is imperative to check potential circuit failures when transferring designed patterns onto silicon wafers. Although conventional lithography hotspot detection methods, such as machine learning, have gained satisfactory performance, with the extreme scaling of transistor feature size and layout patterns growing in complexity, conventional methodologies may suffer from performance degradation. For example, manual or ad hoc feature extraction in a machine learning framework may lose important information when predicting potential errors in ultra-large-scale integrated circuit masks. We present a deep convolutional neural network (CNN) that targets representative feature learning in lithography hotspot detection. We carefully analyze the impact and effectiveness of different CNN hyperparameters, through which a hotspot-detection-oriented neural network model is established. Because hotspot patterns are always in the minority in VLSI mask design, the training dataset is highly imbalanced. In this situation, a neural network is no longer reliable, because a trained model with high classification accuracy may still suffer from a high number of false negative results (missing hotspots), which is fatal in hotspot detection problems. To address the imbalance problem, we further apply hotspot upsampling and random-mirror flipping before training the network. Experimental results show that our proposed neural network model achieves comparable or better performance on the ICCAD 2012 contest benchmark compared to state-of-the-art hotspot detectors based on deep or representative machine leaning.

  9. A rare homozygous MFSD8 single-base-pair deletion and frameshift in the whole genome sequence of a Chinese Crested dog with neuronal ceroid lipofuscinosis.

    Science.gov (United States)

    Guo, Juyuan; O'Brien, Dennis P; Mhlanga-Mutangadura, Tendai; Olby, Natasha J; Taylor, Jeremy F; Schnabel, Robert D; Katz, Martin L; Johnson, Gary S

    2015-01-03

    The neuronal ceroid lipofuscinoses are heritable lysosomal storage diseases characterized by progressive neurological impairment and the accumulation of autofluorescent storage granules in neurons and other cell types. Various forms of human neuronal ceroid lipofuscinosis have been attributed to mutations in at least 13 different genes. So far, mutations in the canine orthologs of 7 of these genes have been identified in DNA from dogs with neuronal ceroid lipofuscinosis. The identification of new causal mutations could lead to the establishment of canine models to investigate the pathogenesis of the corresponding human neuronal ceroid lipofuscinoses and to evaluate and optimize therapeutic interventions for these fatal human diseases. We obtained blood and formalin-fixed paraffin-embedded brain sections from a rescue dog that was reported to be a young adult Chinese Crested. The dog was euthanized at approximately 19 months of age as a consequence of progressive neurological decline that included blindness, anxiety, and cognitive impairment. A diagnosis of neuronal ceroid lipofuscinosis was made based on neurological signs, magnetic resonance imaging of the brain, and fluorescence microscopic and electron microscopic examination of brain sections. We isolated DNA from the blood and used it to generate a whole genome sequence with 33-fold average coverage. Among the 7.2 million potential sequence variants revealed by aligning the sequence reads to the canine genome reference sequence was a homozygous single base pair deletion in the canine ortholog of one of 13 known human NCL genes: MFSD8:c.843delT. MFSD8:c.843delT is predicted to cause a frame shift and premature stop codon resulting in a truncated protein, MFSD8:p.F282Lfs13*, missing its 239 C-terminal amino acids. The MFSD8:c.843delT allele is absent from the whole genome sequences of 101 healthy canids or dogs with other diseases. The genotyping of archived DNA from 1478 Chinese Cresteds did not identify any

  10. Severe fluoropyrimidine toxicity due to novel and rare DPYD missense mutations, deletion and genomic amplification affecting DPD activity and mRNA splicing

    DEFF Research Database (Denmark)

    van Kuilenburg, André B P; Meijer, Judith; Maurer, Dirk

    2017-01-01

    in 9 cancer patients presenting with severe fluoropyrimidine-associated toxicity. All patients possessed a strongly reduced DPD activity, ranging from 9 to 53% of controls. Analysis of the DPD gene (DPYD) showed the presence of 21 variable sites including 4 novel and 4 very rare aberrations: 3 missense.......G284V mutation showed residual DPD activities of 30% and 0.5%, respectively. Analysis of a DPD homology model indicated that the p.I948T and p.G284V mutations may affect electron transfer and the binding of FAD, respectively. cDNA analysis showed that the c.321+1G>A mutation in DPYD leads to skipping...

  11. Future hotspots of terrestrial mammal loss

    Science.gov (United States)

    Visconti, Piero; Pressey, Robert L.; Giorgini, Daniele; Maiorano, Luigi; Bakkenes, Michel; Boitani, Luigi; Alkemade, Rob; Falcucci, Alessandra; Chiozza, Federica; Rondinini, Carlo

    2011-01-01

    Current levels of endangerment and historical trends of species and habitats are the main criteria used to direct conservation efforts globally. Estimates of future declines, which might indicate different priorities than past declines, have been limited by the lack of appropriate data and models. Given that much of conservation is about anticipating and responding to future threats, our inability to look forward at a global scale has been a major constraint on effective action. Here, we assess the geography and extent of projected future changes in suitable habitat for terrestrial mammals within their present ranges. We used a global earth-system model, IMAGE, coupled with fine-scale habitat suitability models and parametrized according to four global scenarios of human development. We identified the most affected countries by 2050 for each scenario, assuming that no additional conservation actions other than those described in the scenarios take place. We found that, with some exceptions, most of the countries with the largest predicted losses of suitable habitat for mammals are in Africa and the Americas. African and North American countries were also predicted to host the most species with large proportional global declines. Most of the countries we identified as future hotspots of terrestrial mammal loss have little or no overlap with the present global conservation priorities, thus confirming the need for forward-looking analyses in conservation priority setting. The expected growth in human populations and consumption in hotspots of future mammal loss mean that local conservation actions such as protected areas might not be sufficient to mitigate losses. Other policies, directed towards the root causes of biodiversity loss, are required, both in Africa and other parts of the world. PMID:21844048

  12. Methane Hotspots in the Los Angeles Megacity

    Science.gov (United States)

    Hopkins, F. M.; Randerson, J. T.; Bush, S.; Ehleringer, J. R.; Lai, C.; Kort, E. A.; Blake, D. R.

    2013-12-01

    Airborne observations show that Los Angeles (LA) is a large source of methane to the atmosphere, yet the sources of excess methane from the urban area are poorly constrained. We used a mobile laboratory, a Ford Transit van equipped with cavity ring down spectrometers (Picarro, Inc.), to measure greenhouse gases (CH4, CO2, and CO) mole fractions in LA. On-road surveys across the LA Basin were conducted seasonally to determine patterns of CH4 enrichment in space and over time, with a focus on quantifying methane leaks from known sources. We found fugitive leaks and elevated CH4 concentrations throughout the LA Basin. Some were associated with known sources, such as landfills, wastewater treatment, and oil and gas infrastructure, while others had an unknown origin. Urban CH4 enrichment varied over the course of the year, largely due to seasonal changes in meteorological conditions. Nevertheless, our mobile surveys revealed CH4 hotspots (>200 ppb elevated with respect to background levels) that persisted among seasons. High CH4 concentrations were most easily predicted by proximity to methane sources, particularly near the coast, while elevated CH4 levels were more evenly dispersed in inland areas. CH4 hotspots had a disproportionate impact on excess methane relative to the area they accounted for, typically providing more than a quarter of excess methane measured on a transect. These data improve estimates of the relative roles of specific leaks and emission sectors to LA's excess methane. Depending on the cost of reducing these CH4 leaks, a focus on CH4 emissions may prove an effective way to reduce LA's greenhouse gas emissions in the near term.

  13. Imbalance aware lithography hotspot detection: a deep learning approach

    Science.gov (United States)

    Yang, Haoyu; Luo, Luyang; Su, Jing; Lin, Chenxi; Yu, Bei

    2017-03-01

    With the advancement of VLSI technology nodes, light diffraction caused lithographic hotspots have become a serious problem affecting manufacture yield. Lithography hotspot detection at the post-OPC stage is imperative to check potential circuit failures when transferring designed patterns onto silicon wafers. Although conventional lithography hotspot detection methods, such as machine learning, have gained satisfactory performance, with extreme scaling of transistor feature size and more and more complicated layout patterns, conventional methodologies may suffer from performance degradation. For example, manual or ad hoc feature extraction in a machine learning framework may lose important information when predicting potential errors in ultra-large-scale integrated circuit masks. In this paper, we present a deep convolutional neural network (CNN) targeting representative feature learning in lithography hotspot detection. We carefully analyze impact and effectiveness of different CNN hyper-parameters, through which a hotspot-detection-oriented neural network model is established. Because hotspot patterns are always minorities in VLSI mask design, the training data set is highly imbalanced. In this situation, a neural network is no longer reliable, because a trained model with high classification accuracy may still suffer from high false negative results (missing hotspots), which is fatal in hotspot detection problems. To address the imbalance problem, we further apply minority upsampling and random-mirror flipping before training the network. Experimental results show that our proposed neural network model achieves highly comparable or better performance on the ICCAD 2012 contest benchmark compared to state-of-the-art hotspot detectors based on deep or representative machine leaning.

  14. Support vector machine for classification of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae based on codon composition

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2006-04-01

    Full Text Available Abstract Background Meiotic double-strand breaks occur at relatively high frequencies in some genomic regions (hotspots and relatively low frequencies in others (coldspots. Hotspots and coldspots are receiving increasing attention in research into the mechanism of meiotic recombination. However, predicting hotspots and coldspots from DNA sequence information is still a challenging task. Results We present a novel method for classification of hot and cold ORFs located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using support vector machine (SVM, which relies on codon composition differences. This method has achieved a high classification accuracy of 85.0%. Since codon composition is a fusion of codon usage bias and amino acid composition signals, the ability of these two kinds of sequence attributes to discriminate hot ORFs from cold ORFs was also investigated separately. Our results indicate that neither codon usage bias nor amino acid composition taken separately performed as well as codon composition. Moreover, our SVM based method was applied to the full genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of recombination rate. We found that the performance of our method for predicting cold ORFs is not as good as that for predicting hot ORFs. Besides, we also observed a considerable correlation between meiotic recombination rate and amino acid composition of certain residues, which probably reflects the structural and functional dissimilarity between the hot and cold groups. Conclusion We have introduced a SVM-based novel method to discriminate hot ORFs from cold ones. Applying codon composition as sequence attributes, we have achieved a high classification accuracy, which suggests that codon composition has strong potential to be used as sequence attributes in the prediction of hot and cold ORFs.

  15. Stability predicts genetic diversity in the Brazilian Atlantic forest hotspot.

    Science.gov (United States)

    Carnaval, Ana Carolina; Hickerson, Michael J; Haddad, Célio F B; Rodrigues, Miguel T; Moritz, Craig

    2009-02-06

    Biodiversity hotspots, representing regions with high species endemism and conservation threat, have been mapped globally. Yet, biodiversity distribution data from within hotspots are too sparse for effective conservation in the face of rapid environmental change. Using frogs as indicators, ecological niche models under paleoclimates, and simultaneous Bayesian analyses of multispecies molecular data, we compare alternative hypotheses of assemblage-scale response to late Quaternary climate change. This reveals a hotspot within the Brazilian Atlantic forest hotspot. We show that the southern Atlantic forest was climatically unstable relative to the central region, which served as a large climatic refugium for neotropical species in the late Pleistocene. This sets new priorities for conservation in Brazil and establishes a validated approach to biodiversity prediction in other understudied, species-rich regions.

  16. HD-CNV: hotspot detector for copy number variants

    National Research Council Canada - National Science Library

    Butler, Jenna L; Osborne Locke, Marjorie Elizabeth; Hill, Kathleen A; Daley, Mark

    2013-01-01

    ... (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input...

  17. Pervasive defaunation of forest remnants in a tropical biodiversity hotspot

    National Research Council Canada - National Science Library

    Canale, Gustavo R; Peres, Carlos A; Guidorizzi, Carlos E; Gatto, Cassiano A Ferreira; Kierulff, Maria Cecília M

    2012-01-01

    ... in unprotected forest remnants remain poorly explained. Here, we report unprecedented rates of local extinctions of medium to large-bodied mammals in one of the world's most important tropical biodiversity hotspot...

  18. Transportation conformity particulate matter hot-spot air quality modeling.

    Science.gov (United States)

    2013-07-01

    In light of the new development in particulate matter (PM) hot-spot regulations and Illinois Department : of Transportation (IDOT)s National Environmental Policy Act (NEPA) documentation requirements, : this project is intended to (1) perform and ...

  19. Background heatflow on hotspot planets - Io and Venus

    Science.gov (United States)

    Stevenson, David J.; Mcnamara, Sean C.

    1988-01-01

    It is suggested that there is no simple relationship between lithospheric thickness and heatflow on planets where volcanism dominates the heatflow. This applies locally and globally, even away from regions of volcanic activity. This indicates that there is no basis for the assumption that the Io heatflow is as low as (or lower than) the hotspot component alone would suggest. A model is presented to describe the heatflow on hotspot planets. The model is applied to Io and Venus.

  20. Hotspots Detection in Photovoltaic Modules Using Infrared Thermography

    Directory of Open Access Journals (Sweden)

    Salazar April M.

    2016-01-01

    Full Text Available An increased interest on generating power from renewable sources has led to an increase in solar photovoltaic (PV system installations worldwide. Power generation of such systems is affected by factors that can be identified early on through efficient monitoring techniques. This study developed a non-invasive technique that can detect localized heating and quantify the area of the hotspots, a potential cause of degradation in photovoltaic systems. This is done by the use of infrared thermography, a well-accepted non-destructive evaluation technique that allows contactless, real-time inspection. In this approach, thermal images or thermograms of an operating PV module were taken using an infrared camera. These thermograms were analyzed by a Hotspot Detection algorithm implemented in MATLAB. Prior to image processing, images were converted to CIE L*a*b color space making k-means clustering implementation computationally efficient. K-means clustering is an iterative technique that segments data into k clusters which was used to isolate hotspots. The devised algorithm detected hotspots in the modules being observed. In addition, average temperature and relative area is provided to quantify the hotspot. Various features and conditions leading to hotspots such as crack, junction box and shading were investigated in this study.

  1. Driver gene mutations of non-small-cell lung cancer are rare in primary carcinoids of the lung: NGS study by ion Torrent.

    Science.gov (United States)

    Armengol, Gemma; Sarhadi, Virinder Kaur; Rönty, Mikko; Tikkanen, Milja; Knuuttila, Aija; Knuutila, Sakari

    2015-04-01

    Lung carcinoids are rare neuroendocrine tumors of the lung. Very little is known about the genetic background of these tumors. We applied Ion Torrent Ampliseq next-generation technology to study hotspot mutations of 22 lung cancer-related genes from typical and atypical lung carcinoid tumors. DNA isolated from 25 formalin-fixed, paraffin-embedded carcinoid tumors were amplified to prepare barcoded libraries covering 507 mutations included in 90 amplicons. The libraries were pooled, purified, enriched, and sequenced on ion personal genome machine. The sequences were aligned and checked for known and novel variations using Torrent Suite Software v.4.0.2. One out of 25 patients had mutations in the targeted regions sequenced. This patient had mutations in BRAF, SMAD4, PIK3CA, and KRAS. All these mutations were confirmed as somatic and are previously known mutations. In summary, mutations in genes commonly mutated in non-small-cell lung cancer are not common in lung carcinoids.

  2. Deep whole-genome sequencing of 100 southeast Asian Malays.

    Science.gov (United States)

    Wong, Lai-Ping; Ong, Rick Twee-Hee; Poh, Wan-Ting; Liu, Xuanyao; Chen, Peng; Li, Ruoying; Lam, Kevin Koi-Yau; Pillai, Nisha Esakimuthu; Sim, Kar-Seng; Xu, Haiyan; Sim, Ngak-Leng; Teo, Shu-Mei; Foo, Jia-Nee; Tan, Linda Wei-Lin; Lim, Yenly; Koo, Seok-Hwee; Gan, Linda Seo-Hwee; Cheng, Ching-Yu; Wee, Sharon; Yap, Eric Peng-Huat; Ng, Pauline Crystal; Lim, Wei-Yen; Soong, Richie; Wenk, Markus Rene; Aung, Tin; Wong, Tien-Yin; Khor, Chiea-Chuen; Little, Peter; Chia, Kee-Seng; Teo, Yik-Ying

    2013-01-10

    Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. Paleocene on-spreading-axis hotspot volcanism along the Ninetyeast Ridge: An interaction between the Kerguelen hotspot and the Wharton spreading center

    Digital Repository Service at National Institute of Oceanography (India)

    Krishna, K.S.; Gopala Rao, D.; SubbaRaju, L.V.; Chaubey, A.K.; Shcherbakov, V.S.; Pilipenko, A.I.; Murthy, I.V.R.

    Investigations of three plausible tectonic settings of the Kerguelen hotspot relative to the Wharton spreading center evoke the on-spreading-axis hotspot volcanism of Paleocene (60-54 Ma) age along the Ninetyeast Ridge. The hypothesis is consistent...

  4. Hybridization hotspots at bat swarming sites.

    Directory of Open Access Journals (Sweden)

    Wiesław Bogdanowicz

    Full Text Available During late summer and early autumn in temperate zones of the Northern Hemisphere, thousands of bats gather at caves, mainly for the purpose of mating. We demonstrated that this swarming behavior most probably leads not only to breeding among bats of the same species but also interbreeding between different species. Using 14 nuclear microsatellites and three different methods (the Bayesian assignment approaches of STRUCTURE and NEWHYBRIDS and a principal coordinate analysis of pairwise genetic distances, we analyzed 375 individuals belonging to three species of whiskered bats (genus Myotis at swarming sites across their sympatric range in southern Poland. The overall hybridization rate varied from 3.2 to 7.2%. At the species level, depending on the method used, these values ranged from 2.1-4.6% in M. mystacinus and 3.0-3.7% in M. brandtii to 6.5-30.4% in M. alcathoe. Hybrids occurred in about half of the caves we studied. In all three species, the sex ratio of hybrids was biased towards males but the observed differences did not differ statistically from those noted at the population level. In our opinion, factors leading to the formation of these admixed individuals and their relatively high frequency are: i swarming behaviour at swarming sites, where high numbers of bats belonging to several species meet; ii male-biased sex ratio during the swarming period; iii the fact that all these bats are generally polygynous. The highly different population sizes of different species at swarming sites may also play some role. Swarming sites may represent unique hybrid hotspots, which, as there are at least 2,000 caves in the Polish Carpathians alone, may occur on a massive scale not previously observed for any group of mammal species in the wild. Evidently, these sites should be treated as focal points for the conservation of biodiversity and evolutionary processes.

  5. Cannabis cultivation in Quebec: between space-time hotspots and coldspots.

    Science.gov (United States)

    Chadillon-Farinacci, Véronique; Apparicio, Philippe; Morselli, Carlo

    2015-03-01

    Cannabis cultivation has become increasingly localized, whether soil-based or hydroponic growing methods are used. Characteristics of a given location, such as its climate and the equipment it requires may influence general accessibility or attract different types of offenders based on potential profits. The location of crops, especially hydroponic crops, suggests a certain proximity to the consumer market via semi-urban and urban environments, while making it possible to avoid detection. This article examines the cannabis market through its cultivation. The stability of temporal and spatial clusters of cannabis cultivation, hotspots, and coldspots between 2001 and 2009 in the province of Quebec, Canada, are addressed. Studying the geography of crime is not a new endeavor, but coldspots are rarely documented in drug market research. Using arrests and general population data, as well as Kulldorff's scan statistics, results show that the temporal distribution of cannabis cultivation is highly seasonal for soil-based methods. Hydroponic production shows adaptation to its soil-based counterpart. Stable patterns are found for both spatial distributions. Hotspots for soil-based cultivation are found near several urban centers and the Ontario border. For hydroponic cannabis cultivation, a new hotspot suggests the emergence of an American demand for Quebec-grown cannabis between 2007 and 2009. Curiously, the region surrounding Montreal, the largest urban center in Quebec, is a recurrent and stable coldspot for both methods of cultivation. For all periods, spatial clusters are stronger for soil-based methods than in the hydroponic context. Temporal differences and spatial similarities between soil-based cultivation and hydroponic cultivation are discussed. The role of the metropolis is also addressed. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Thermally-Driven Mantle Plumes Reconcile Hot-spot Observations

    Science.gov (United States)

    Davies, D.; Davies, J.

    2008-12-01

    Hot-spots are anomalous regions of magmatism that cannot be directly associated with plate tectonic processes (e.g. Morgan, 1972). They are widely regarded as the surface expression of upwelling mantle plumes. Hot-spots exhibit variable life-spans, magmatic productivity and fixity (e.g. Ito and van Keken, 2007). This suggests that a wide-range of upwelling structures coexist within Earth's mantle, a view supported by geochemical and seismic evidence, but, thus far, not reproduced by numerical models. Here, results from a new, global, 3-D spherical, mantle convection model are presented, which better reconcile hot-spot observations, the key modification from previous models being increased convective vigor. Model upwellings show broad-ranging dynamics; some drift slowly, while others are more mobile, displaying variable life-spans, intensities and migration velocities. Such behavior is consistent with hot-spot observations, indicating that the mantle must be simulated at the correct vigor and in the appropriate geometry to reproduce Earth-like dynamics. Thermally-driven mantle plumes can explain the principal features of hot-spot volcanism on Earth.

  7. Borneo and Indochina are major evolutionary hotspots for Southeast Asian biodiversity.

    Science.gov (United States)

    de Bruyn, Mark; Stelbrink, Björn; Morley, Robert J; Hall, Robert; Carvalho, Gary R; Cannon, Charles H; van den Bergh, Gerrit; Meijaard, Erik; Metcalfe, Ian; Boitani, Luigi; Maiorano, Luigi; Shoup, Robert; von Rintelen, Thomas

    2014-11-01

    Tropical Southeast (SE) Asia harbors extraordinary species richness and in its entirety comprises four of the Earth's 34 biodiversity hotspots. Here, we examine the assembly of the SE Asian biota through time and space. We conduct meta-analyses of geological, climatic, and biological (including 61 phylogenetic) data sets to test which areas have been the sources of long-term biological diversity in SE Asia, particularly in the pre-Miocene, Miocene, and Plio-Pleistocene, and whether the respective biota have been dominated by in situ diversification, immigration and/or emigration, or equilibrium dynamics. We identify Borneo and Indochina, in particular, as major "evolutionary hotspots" for a diverse range of fauna and flora. Although most of the region's biodiversity is a result of both the accumulation of immigrants and in situ diversification, within-area diversification and subsequent emigration have been the predominant signals characterizing Indochina and Borneo's biota since at least the early Miocene. In contrast, colonization events are comparatively rare from younger volcanically active emergent islands such as Java, which show increased levels of immigration events. Few dispersal events were observed across the major biogeographic barrier of Wallace's Line. Accelerated efforts to conserve Borneo's flora and fauna in particular, currently housing the highest levels of SE Asian plant and mammal species richness, are critically required. © The Author(s) 2014. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Extensive chromatin remodelling and establishment of transcription factor ‘hotspots' during early adipogenesis

    Science.gov (United States)

    Siersbæk, Rasmus; Nielsen, Ronni; John, Sam; Sung, Myong-Hee; Baek, Songjoon; Loft, Anne; Hager, Gordon L; Mandrup, Susanne

    2011-01-01

    Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBPβ and -δ) to transcription factor ‘hotspots'. Our results demonstrate that C/EBPβ marks a large number of these transcription factor ‘hotspots' before induction of differentiation and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled C/EBP-binding sites persists throughout differentiation and is later occupied by PPARγ, indicating that early C/EBP family members, in addition to their well-established role in activation of PPARγ transcription, may act as pioneering factors for PPARγ binding. PMID:21427703

  9. Punctuated Distribution of Recombination Hotspots and Demarcation of Pericentromeric Regions in Phaseolus vulgaris L.

    Science.gov (United States)

    Bhakta, Mehul S.; Jones, Valerie A.; Vallejos, C. Eduardo

    2015-01-01

    High density genetic maps are a reliable tool for genetic dissection of complex plant traits. Mapping resolution is often hampered by the variable crossover and non-crossover events occurring across the genome, with pericentromeric regions (pCENR) showing highly suppressed recombination rates. The efficiency of linkage mapping can further be improved by characterizing and understanding the distribution of recombinational activity along individual chromosomes. In order to evaluate the genome wide recombination rate in common beans (Phaseolus vulgaris L.) we developed a SNP-based linkage map using the genotype-by-sequencing approach with a 188 recombinant inbred line family generated from an inter gene pool cross (Andean x Mesoamerican). We identified 1,112 SNPs that were subsequently used to construct a robust linkage map with 11 groups, comprising 513 recombinationally unique marker loci spanning 943 cM (LOD 3.0). Comparative analysis showed that the linkage map spanned >95% of the physical map, indicating that the map is almost saturated. Evaluation of genome-wide recombination rate indicated that at least 45% of the genome is highly recombinationally suppressed, and allowed us to estimate locations of pCENRs. We observed an average recombination rate of 0.25 cM/Mb in pCENRs as compared to the rest of genome that showed 3.72 cM/Mb. However, several hot spots of recombination were also detected with recombination rates reaching as high as 34 cM/Mb. Hotspots were mostly found towards the end of chromosomes, which also happened to be gene-rich regions. Analyzing relationships between linkage and physical map indicated a punctuated distribution of recombinational hot spots across the genome. PMID:25629314

  10. Efficient Assessment of Social Hotspots in the Supply Chains of 100 Product Categories Using the Social Hotspots Database

    Directory of Open Access Journals (Sweden)

    Catherine Benoît Norris

    2014-10-01

    Full Text Available Data collection, or the inventory step, is often the most labor-intensive phase of any Life Cycle Assessment (LCA study. The S-LCA Guidelines and numerous authors have recommended generic assessment in this first phase of an S-LCA. In an effort to identify the social hotspots in the supply chains of 100 product categories during just a few months’ time, adopting a streamlined approach was essential. The Social Hotspots Database system was developed by New Earth over 5 years. It includes a Global Input Output (IO model derived from the Global Trade Analysis Project, a Worker Hours Model constructed using annual wage payments and wage rates by country and sector, and Social Theme Tables covering 22 themes within five Social Impact Categories—Labor Rights and Decent Work, Health and Safety, Human Rights, Governance and Community Impacts. The data tables identify social risks for over 100 indicators. Both the ranking of worker hour intensity and the risk levels across multiple social themes for the Country Specific Sectors (CSS within a product category supply chain are used to calculate Social Hotspots Indexes (SHI using an additive weighting method. The CSS with the highest SHI are highlighted as social hotspots within the supply chain of the product in question. This system was tested in seven case studies in 2011. In order to further limit the number of hotspots, a set of prioritization rules was applied. This paper will review the method implemented to study the social hotspots of the 100 product categories and provide one detailed example. Limitations of the approach and recommended research avenues will be outlined.

  11. Handwritten Character Classification using the Hotspot Feature Extraction Technique

    NARCIS (Netherlands)

    Surinta, Olarik; Schomaker, Lambertus; Wiering, Marco

    2012-01-01

    Feature extraction techniques can be important in character recognition, because they can enhance the efficacy of recognition in comparison to featureless or pixel-based approaches. This study aims to investigate the novel feature extraction technique called the hotspot technique in order to use it

  12. The problems with multi-species conservation: do hotspots, ideal ...

    African Journals Online (AJOL)

    The investigation of six vertebrate taxa (viz freshwater fish, frogs, tortoises and terrapins, snakes, birds, and various mammal orders) at a national scale reveals that hotspots are not coincident within taxa. Centres of richness are concentrated in the north-eastern areas of the country, whereas endemism is concentrated in the ...

  13. Identifying biodiversity hotspots for threatened mammal species in Iran

    NARCIS (Netherlands)

    Farashi, Azita; Shariati Najafabadi, Mitra; Hosseini, Mahshid

    2017-01-01

    Conservation biology has much more attention for biodiversity hot spots than before. In order to recognize the hotspots for Iranian terrestrial mammal species that are listed in any red list, nationally or globally, ten Species Distribution Models (SDMs) have been applied. The SDMs evaluation

  14. The making of a productivity hotspot in the coastal ocean.

    Directory of Open Access Journals (Sweden)

    Dana K Wingfield

    Full Text Available BACKGROUND: Highly productive hotspots in the ocean often occur where complex physical forcing mechanisms lead to aggregation of primary and secondary producers. Understanding how hotspots persist, however, requires combining knowledge of the spatio-temporal linkages between geomorphology, physical forcing, and biological responses with the physiological requirements and movement of top predators. METHODOLOGY/PRINCIPAL FINDINGS: Here we integrate remotely sensed oceanography, ship surveys, and satellite telemetry to show how local geomorphology interacts with physical forcing to create a region with locally enhanced upwelling and an adjacent upwelling shadow that promotes retentive circulation, enhanced year-round primary production, and prey aggregation. These conditions provide an area within the upwelling shadow where physiologically optimal water temperatures can be found adjacent to a region of enhanced prey availability, resulting in a foraging hotspot for loggerhead sea turtles (Caretta caretta off the Baja California peninsula, Mexico. SIGNIFICANCE/CONCLUSIONS: We have identified the set of conditions that lead to a persistent top predator hotspot, which increases our understanding of how highly migratory species exploit productive regions of the ocean. These results will aid in the development of spatially and environmentally explicit management strategies for marine species of conservation concern.

  15. The Yellowstone hotspot, Greater Yellowstone ecosystem, and human geography

    Science.gov (United States)

    Pierce, Kenneth L.; Despain, D.G.; Morgan, Lisa A.; Good, John M.; Morgan Morzel, Lisa Ann

    2007-01-01

    Active geologic processes associated with the Yellowstone hotspot are fundamental in shaping the landscapes of the greater Yellowstone ecosystem (GYE), a high volcanic plateau flanked by a crescent of still higher mountainous terrain. The processes associated with the Yellowstone hotspot are volcanism, faulting, and uplift and are observed in the geology at the surface. We attribute the driving forces responsible for the northeastward progression of these processes to a thermal plume rising through the Earth’s mantle into the base of the southwest-moving North American plate. This progression began 16 million years ago (Ma) near the Nevada-Oregon border and arrived at Yellowstone about 2 Ma. Before arrival of the hotspot, an older landscape existed, particularly mountains created during the Laramide orogeny about 70–50 Ma and volcanic terrain formed by Absaroka andesitic volcanism mostly between 50–45 Ma. These landscapes were more muted than the present, hotspot-modified landscape because the Laramide-age mountains had worn down and an erosion surface of low relief had developed on the Absaroka volcanic terrain.

  16. Ideas from the global climate change hotspot research | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-05-09

    May 9, 2017 ... So what are the major findings from the research happening in the three climate change hotspot areas? In the semi-arid regions of Africa and Asia, the research confirms that vulnerability to climate stresses, and capacity to respond, is due to a mix of social, economic and political factors, closely coupled ...

  17. The Complete Plastome Sequences of Four Orchid Species: Insights into the Evolution of the Orchidaceae and the Utility of Plastomic Mutational Hotspots.

    Science.gov (United States)

    Niu, Zhitao; Xue, Qingyun; Zhu, Shuying; Sun, Jing; Liu, Wei; Ding, Xiaoyu

    2017-01-01

    Orchidaceae (orchids) is the largest family in the monocots, including about 25,000 species in 880 genera and five subfamilies. Many orchids are highly valued for their beautiful and long-lasting flowers. However, the phylogenetic relationships among the five orchid subfamilies remain unresolved. The major dispute centers on whether the three one-stamened subfamilies, Epidendroideae, Orchidoideae, and Vanilloideae, are monophyletic or paraphyletic. Moreover, structural changes in the plastid genome (plastome) and the effective genetic loci at the species-level phylogenetics of orchids have rarely been documented. In this study, we compared 53 orchid plastomes, including four newly sequenced ones, that represent four remote genera: Dendrobium, Goodyera, Paphiopedilum, and Vanilla. These differ from one another not only in their lengths of inverted repeats and small single copy regions but also in their retention of ndh genes. Comparative analyses of the plastomes revealed that the expansion of inverted repeats in Paphiopedilum and Vanilla is associated with a loss of ndh genes. In orchid plastomes, mutational hotspots are genus specific. After having carefully examined the data, we propose that the three loci 5'trnK-rps16, trnS-trnG, and rps16-trnQ might be powerful markers for genera within Epidendroideae, and clpP-psbB and rps16-trnQ might be markers for genera within Cypripedioideae. After analyses of a partitioned dataset, we found that our plastid phylogenomic trees were congruent in a topology where two one-stamened subfamilies (i.e., Epidendroideae and Orchidoideae) were sisters to a multi-stamened subfamily (i.e., Cypripedioideae) rather than to the other one-stamened subfamily (Vanilloideae), suggesting that the living one-stamened orchids are paraphyletic.

  18. The Complete Plastome Sequences of Four Orchid Species: Insights into the Evolution of the Orchidaceae and the Utility of Plastomic Mutational Hotspots

    Directory of Open Access Journals (Sweden)

    Zhitao Niu

    2017-05-01

    Full Text Available Orchidaceae (orchids is the largest family in the monocots, including about 25,000 species in 880 genera and five subfamilies. Many orchids are highly valued for their beautiful and long-lasting flowers. However, the phylogenetic relationships among the five orchid subfamilies remain unresolved. The major dispute centers on whether the three one-stamened subfamilies, Epidendroideae, Orchidoideae, and Vanilloideae, are monophyletic or paraphyletic. Moreover, structural changes in the plastid genome (plastome and the effective genetic loci at the species-level phylogenetics of orchids have rarely been documented. In this study, we compared 53 orchid plastomes, including four newly sequenced ones, that represent four remote genera: Dendrobium, Goodyera, Paphiopedilum, and Vanilla. These differ from one another not only in their lengths of inverted repeats and small single copy regions but also in their retention of ndh genes. Comparative analyses of the plastomes revealed that the expansion of inverted repeats in Paphiopedilum and Vanilla is associated with a loss of ndh genes. In orchid plastomes, mutational hotspots are genus specific. After having carefully examined the data, we propose that the three loci 5′trnK-rps16, trnS-trnG, and rps16-trnQ might be powerful markers for genera within Epidendroideae, and clpP-psbB and rps16-trnQ might be markers for genera within Cypripedioideae. After analyses of a partitioned dataset, we found that our plastid phylogenomic trees were congruent in a topology where two one-stamened subfamilies (i.e., Epidendroideae and Orchidoideae were sisters to a multi-stamened subfamily (i.e., Cypripedioideae rather than to the other one-stamened subfamily (Vanilloideae, suggesting that the living one-stamened orchids are paraphyletic.

  19. Death of PRDM9 coincides with stabilization of the recombination landscape in the dog genome.

    Science.gov (United States)

    Axelsson, Erik; Webster, Matthew T; Ratnakumar, Abhirami; Ponting, Chris P; Lindblad-Toh, Kerstin

    2012-01-01

    Analysis of diverse eukaryotes has revealed that recombination events cluster in discrete genomic locations known as hotspots. In humans, a zinc-finger protein, PRDM9, is believed to initiate recombination in >40% of hotspots by binding to a specific DNA sequence motif. However, the PRDM9 coding sequence is disrupted in the dog genome assembly, raising questions regarding the nature and control of recombination in dogs. By analyzing the sequences of PRDM9 orthologs in a number of dog breeds and several carnivores, we show here that this gene was inactivated early in canid evolution. We next use patterns of linkage disequilibrium using more than 170,000 SNP markers typed in almost 500 dogs to estimate the recombination rates in the dog genome using a coalescent-based approach. Broad-scale recombination rates show good correspondence with an existing linkage-based map. Significant variation in recombination rate is observed on the fine scale, and we are able to detect over 4000 recombination hotspots with high confidence. In contrast to human hotspots, 40% of canine hotspots are characterized by a distinct peak in GC content. A comparative genomic analysis indicates that these peaks are present also as weaker peaks in the panda, suggesting that the hotspots have been continually reinforced by accelerated and strongly GC biased nucleotide substitutions, consistent with the long-term action of biased gene conversion on the dog lineage. These results are consistent with the loss of PRDM9 in canids, resulting in a greater evolutionary stability of recombination hotspots. The genetic determinants of recombination hotspots in the dog genome may thus reflect a fundamental process of relevance to diverse animal species.

  20. Prdm9, a major determinant of meiotic recombination hotspots, is not functional in dogs and their wild relatives, wolves and coyotes.

    Directory of Open Access Journals (Sweden)

    Violeta Muñoz-Fuentes

    Full Text Available Meiotic recombination is a fundamental process needed for the correct segregation of chromosomes during meiosis in sexually reproducing organisms. In humans, 80% of crossovers are estimated to occur at specific areas of the genome called recombination hotspots. Recently, a protein called PRDM9 was identified as a major player in determining the location of genome-wide meiotic recombination hotspots in humans and mice. The origin of this protein seems to be ancient in evolutionary time, as reflected by its fairly conserved structure in lineages that diverged over 700 million years ago. Despite its important role, there are many animal groups in which Prdm9 is absent (e.g. birds, reptiles, amphibians, diptera and it has been suggested to have disruptive mutations and thus to be a pseudogene in dogs. Because of the dog's history through domestication and artificial selection, we wanted to confirm the presence of a disrupted Prdm9 gene in dogs and determine whether this was exclusive of this species or whether it also occurred in its wild ancestor, the wolf, and in a close relative, the coyote. We sequenced the region in the dog genome that aligned to the last exon of the human Prdm9, containing the entire zinc finger domain, in 4 dogs, 17 wolves and 2 coyotes. Our results show that the three canid species possess mutations that likely make this gene non functional. Because these mutations are shared across the three species, they must have appeared prior to the split of the wolf and the coyote, millions of years ago, and are not related to domestication. In addition, our results suggest that in these three canid species recombination does not occur at hotspots or hotspot location is controlled through a mechanism yet to be determined.

  1. Prdm9, a major determinant of meiotic recombination hotspots, is not functional in dogs and their wild relatives, wolves and coyotes.

    Science.gov (United States)

    Muñoz-Fuentes, Violeta; Di Rienzo, Anna; Vilà, Carles

    2011-01-01

    Meiotic recombination is a fundamental process needed for the correct segregation of chromosomes during meiosis in sexually reproducing organisms. In humans, 80% of crossovers are estimated to occur at specific areas of the genome called recombination hotspots. Recently, a protein called PRDM9 was identified as a major player in determining the location of genome-wide meiotic recombination hotspots in humans and mice. The origin of this protein seems to be ancient in evolutionary time, as reflected by its fairly conserved structure in lineages that diverged over 700 million years ago. Despite its important role, there are many animal groups in which Prdm9 is absent (e.g. birds, reptiles, amphibians, diptera) and it has been suggested to have disruptive mutations and thus to be a pseudogene in dogs. Because of the dog's history through domestication and artificial selection, we wanted to confirm the presence of a disrupted Prdm9 gene in dogs and determine whether this was exclusive of this species or whether it also occurred in its wild ancestor, the wolf, and in a close relative, the coyote. We sequenced the region in the dog genome that aligned to the last exon of the human Prdm9, containing the entire zinc finger domain, in 4 dogs, 17 wolves and 2 coyotes. Our results show that the three canid species possess mutations that likely make this gene non functional. Because these mutations are shared across the three species, they must have appeared prior to the split of the wolf and the coyote, millions of years ago, and are not related to domestication. In addition, our results suggest that in these three canid species recombination does not occur at hotspots or hotspot location is controlled through a mechanism yet to be determined.

  2. Recombination hotspots and host susceptibility modulate the adaptive value of recombination during maize streak virus evolution

    Directory of Open Access Journals (Sweden)

    Monjane Adérito L

    2011-12-01

    Full Text Available Abstract Background Maize streak virus -strain A (MSV-A; Genus Mastrevirus, Family Geminiviridae, the maize-adapted strain of MSV that causes maize streak disease throughout sub-Saharan Africa, probably arose between 100 and 200 years ago via homologous recombination between two MSV strains adapted to wild grasses. MSV recombination experiments and analyses of natural MSV recombination patterns have revealed that this recombination event entailed the exchange of the movement protein - coat protein gene cassette, bounded by the two genomic regions most prone to recombination in mastrevirus genomes; the first surrounding the virion-strand origin of replication, and the second around the interface between the coat protein gene and the short intergenic region. Therefore, aside from the likely adaptive advantages presented by a modular exchange of this cassette, these specific breakpoints may have been largely predetermined by the underlying mechanisms of mastrevirus recombination. To investigate this hypothesis, we constructed artificial, low-fitness, reciprocal chimaeric MSV genomes using alternating genomic segments from two MSV strains; a grass-adapted MSV-B, and a maize-adapted MSV-A. Between them, each pair of reciprocal chimaeric genomes represented all of the genetic material required to reconstruct - via recombination - the highly maize-adapted MSV-A genotype, MSV-MatA. We then co-infected a selection of differentially MSV-resistant maize genotypes with pairs of reciprocal chimaeras to determine the efficiency with which recombination would give rise to high-fitness progeny genomes resembling MSV-MatA. Results Recombinants resembling MSV-MatA invariably arose in all of our experiments. However, the accuracy and efficiency with which the MSV-MatA genotype was recovered across all replicates of each experiment depended on the MSV susceptibility of the maize genotypes used and the precise positions - in relation to known recombination hotspots

  3. Comparative genomic analysis of Tropheryma whipplei strains reveals that diversity among clinical isolates is mainly related to the WiSP proteins.

    Science.gov (United States)

    La, My-Van; Crapoulet, Nicolas; Barbry, Pascal; Raoult, Didier; Renesto, Patricia

    2007-10-02

    The aim of this study was to analyze the genomic diversity of several Tropheryma whipplei strains by microarray-based comparative genomic hybridization. Fifteen clinical isolates originating from biopsy samples recovered from different countries were compared with the T. whipplei Twist strain. For each isolate, the genes were defined as either present or absent/divergent using the GACK analysis software. Genomic changes were then further characterized by PCR and sequencing. The results revealed a limited genetic variation among the T. whipplei isolates, with at most 2.24% of the probes exhibiting differential hybridization against the Twist strain. The main variation was found in genes encoding the WiSP membrane protein family. This work also demonstrated a 19.2 kb-pair deletion within the T. whipplei DIG15 strain. This deletion occurs in the same region as the previously described large genomic rearrangement between Twist and TW08/27. Thus, this can be considered as a major hot-spot for intra-specific T. whipplei differentiation. Analysis of this deleted region confirmed the role of WND domains in generating T. whipplei diversity. This work provides the first comprehensive genomic comparison of several T. whipplei isolates. It reveals that clinical isolates originating from various geographic and biological sources exhibit a high conservation rate, indicating that T. whipplei rarely interacts with exogenous DNA. Remarkably, frequent inter-strain variations were dicovered that affected members of the WiSP family.

  4. Comparative genomic analysis of Tropheryma whipplei strains reveals that diversity among clinical isolates is mainly related to the WiSP proteins

    Directory of Open Access Journals (Sweden)

    Raoult Didier

    2007-10-01

    Full Text Available Abstract Background The aim of this study was to analyze the genomic diversity of several Tropheryma whipplei strains by microarray-based comparative genomic hybridization. Fifteen clinical isolates originating from biopsy samples recovered from different countries were compared with the T. whipplei Twist strain. For each isolate, the genes were defined as either present or absent/divergent using the GACK analysis software. Genomic changes were then further characterized by PCR and sequencing. Results The results revealed a limited genetic variation among the T. whipplei isolates, with at most 2.24% of the probes exhibiting differential hybridization against the Twist strain. The main variation was found in genes encoding the WiSP membrane protein family. This work also demonstrated a 19.2 kb-pair deletion within the T. whipplei DIG15 strain. This deletion occurs in the same region as the previously described large genomic rearrangement between Twist and TW08/27. Thus, this can be considered as a major hot-spot for intra-specific T. whipplei differentiation. Analysis of this deleted region confirmed the role of WND domains in generating T. whipplei diversity. Conclusion This work provides the first comprehensive genomic comparison of several T. whipplei isolates. It reveals that clinical isolates originating from various geographic and biological sources exhibit a high conservation rate, indicating that T. whipplei rarely interacts with exogenous DNA. Remarkably, frequent inter-strain variations were dicovered that affected members of the WiSP family.

  5. Decongestion of urban areas with hotspot-pricing

    CERN Document Server

    Solé-Ribalta, Albert; Arenas, Alex

    2016-01-01

    The rapid growth of population in urban areas is jeopardizing the mobility and air quality worldwide. One of the most notable problems arising is that of traffic congestion which in turn affects air pollution. With the advent of technologies able to sense real-time data about cities, and its public distribution for analysis, we are in place to forecast scenarios valuable to ameliorate and control congestion. Here, we propose a local congestion pricing scheme, hotspot-pricing, that surcharges vehicles traversing congested junctions. The proposed tax is computed from the estimation of the evolution of congestion at local level, and the expected response of users to the tax (elasticity). Results on cities' road networks, considering real-traffic data, show that the proposed hotspot-pricing scheme would be more effective than current mechanisms to decongest urban areas, and paves the way towards sustainable congestion in urban areas.

  6. Driver KIT mutations in melanoma cluster in four hotspots.

    Science.gov (United States)

    Dumaz, Nicolas; André, Jocelyne; Sadoux, Aurélie; Laugier, Florence; Podgorniak, Marie Pierre; Mourah, Samia; Lebbé, Céleste

    2015-02-01

    There has been a great deal of interest in understanding the role of KIT in melanoma since the discovery of KIT mutations in a subset of melanoma. Although a significant proportion of these melanomas respond to KIT inhibitors, the presence of a KIT mutation does not guarantee a response to KIT inhibitors. Because recent data seem to indicate that only melanoma with specific KIT mutations respond to KIT inhibitors, we investigated which KIT mutations are driver mutations in melanoma and are therefore therapeutically relevant. We established that 70% of KIT mutations in melanoma are located in four hotspots (L576, K642, W557-V560, and D816-A829) and that these mutations are oncogenic in melanocytes and are bona-fide driver mutations. Testing for KIT mutations should therefore concentrate on these four hotspots, which can be targeted therapeutically.

  7. Recent hotspot volcanism on Venus from VIRTIS emissivity data.

    Science.gov (United States)

    Smrekar, Suzanne E; Stofan, Ellen R; Mueller, Nils; Treiman, Allan; Elkins-Tanton, Linda; Helbert, Joern; Piccioni, Giuseppe; Drossart, Pierre

    2010-04-30

    The questions of whether Venus is geologically active and how the planet has resurfaced over the past billion years have major implications for interior dynamics and climate change. Nine "hotspots"--areas analogous to Hawaii, with volcanism, broad topographic rises, and large positive gravity anomalies suggesting mantle plumes at depth--have been identified as possibly active. This study used variations in the thermal emissivity of the surface observed by the Visible and Infrared Thermal Imaging Spectrometer on the European Space Agency's Venus Express spacecraft to identify compositional differences in lava flows at three hotspots. The anomalies are interpreted as a lack of surface weathering. We estimate the flows to be younger than 2.5 million years and probably much younger, about 250,000 years or less, indicating that Venus is actively resurfacing.

  8. Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission.

    Science.gov (United States)

    Rice, Benjamin L; Golden, Christopher D; Anjaranirina, Evelin Jean Gasta; Botelho, Carolina Mastella; Volkman, Sarah K; Hartl, Daniel L

    2016-12-20

    Encouraging advances in the control of Plasmodium falciparum malaria have been observed across much of Africa in the past decade. However, regions of high relative prevalence and transmission that remain unaddressed or unrecognized provide a threat to this progress. Difficulties in identifying such localized hotspots include inadequate surveillance, especially in remote regions, and the cost and labor needed to produce direct estimates of transmission. Genetic data can provide a much-needed alternative to such empirical estimates, as the pattern of genetic variation within malaria parasite populations is indicative of the level of local transmission. Here, genetic data were used to provide the first empirical estimates of P. falciparum malaria prevalence and transmission dynamics for the rural, remote Makira region of northeastern Madagascar. Longitudinal surveys of a cohort of 698 total individuals (both sexes, 0-74 years of age) were performed in two communities bordering the Makira Natural Park protected area. Rapid diagnostic tests, with confirmation by molecular methods, were used to estimate P. falciparum prevalence at three seasonal time points separated by 4-month intervals. Genomic loci in a panel of polymorphic, putatively neutral markers were genotyped for 94 P. falciparum infections and used to characterize genetic parameters known to correlate with transmission levels. Overall, 27.8% of individuals tested positive for P. falciparum over the 10-month course of the study, a rate approximately sevenfold higher than the countrywide average for Madagascar. Among those P. falciparum infections, a high level of genotypic diversity and a high frequency of polygenomic infections (68.1%) were observed, providing a pattern consistent with high and stable transmission. Prevalence and genetic diversity data indicate that the Makira region is a hotspot of P. falciparum transmission in Madagascar. This suggests that the area should be highlighted for future

  9. The Red Queen model of recombination hot-spot evolution: a theoretical investigation.

    Science.gov (United States)

    Latrille, Thibault; Duret, Laurent; Lartillot, Nicolas

    2017-12-19

    In humans and many other species, recombination events cluster in narrow and short-lived hot spots distributed across the genome, whose location is determined by the Zn-finger protein PRDM9. To explain these fast evolutionary dynamics, an intra-genomic Red Queen model has been proposed, based on the interplay between two antagonistic forces: biased gene conversion, mediated by double-strand breaks, resulting in hot-spot extinction, followed by positive selection favouring new PRDM9 alleles recognizing new sequence motifs. Thus far, however, this Red Queen model has not been formalized as a quantitative population-genetic model, fully accounting for the intricate interplay between biased gene conversion, mutation, selection, demography and genetic diversity at the PRDM9 locus. Here, we explore the population genetics of the Red Queen model of recombination. A Wright-Fisher simulator was implemented, allowing exploration of the behaviour of the model (mean equilibrium recombination rate, diversity at the PRDM9 locus or turnover rate) as a function of the parameters (effective population size, mutation and erosion rates). In a second step, analytical results based on self-consistent mean-field approximations were derived, reproducing the scaling relations observed in the simulations. Empirical fit of the model to current data from the mouse suggests both a high mutation rate at PRDM9 and strong biased gene conversion on its targets.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. © 2017 The Authors.

  10. Chronic kidney disease hotspots in developing countries in South Asia

    OpenAIRE

    Abraham, Georgi; Varughese, Santosh; Thandavan, Thiagarajan; IYENGAR, ARPANA; Fernando, Edwin; Naqvi, S. A. Jaffar; Sheriff, Rezvi; Ur-Rashid, Harun; Gopalakrishnan, Natarajan; Kafle, Rishi Kumar

    2015-01-01

    In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinc...

  11. Hotspot temperature calculation and quench analysis on ITER busbar

    Energy Technology Data Exchange (ETDEWEB)

    Rong, J., E-mail: jianrong@mail.ustc.edu.cn [University of Science and Technology of China, Hefei 230027 (China); Huang, X.Y.; Song, Y.T.; Wu, S.T. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2014-12-15

    Highlights: • The hotspot temperature is calculated in the case of different extra copper in this paper. • The MQE (minimum quench energy) is carried out as the external heating to trigger a quench in busbar. • The temperature changes after quench is analyzed by Gandalf code in the case of different extra copper and no helium. • The normal length is carried out in the case of different extra copper by Gandalf code. - Abstract: This paper describes the analysis of ITER feeder busbar, the hotspot temperature of busbar is calculated by classical method in the case of 0%, 50%, 75% and 100% extra copper (copper strands). The quench behavior of busbar is simulated by 1-D Gandalf code, and the MQE (minimum quench energy) is estimated in classical method as initial external heat in Gandalf input file. The temperature and the normal length of conductor are analyzed in the case of 0%, 50% and 100% extra copper and no helium. By hotspot temperature, conductor temperature and normal length are contrasted in different extra copper cases, it is shown that the extra copper play an important role in quench protecting.

  12. On localised hotspots of an urban crime model

    Science.gov (United States)

    Lloyd, David J. B.; O'Farrell, Hayley

    2013-06-01

    We investigate stationary, spatially localised crime hotspots on the real line and the plane of an urban crime model of Short et al. [M. Short, M. DÓrsogna, A statistical model of criminal behavior, Mathematical Models and Methods in Applied Sciences 18 (2008) 1249-1267]. Extending the weakly nonlinear analysis of Short et al., we show in one-dimension that localised hotspots should bifurcate off the background spatially homogeneous state at a Turing instability provided the bifurcation is subcritical. Using path-following techniques, we continue these hotspots and show that the bifurcating pulses can undergo the process of homoclinic snaking near the singular limit. We analyse the singular limit to explain the existence of spike solutions and compare the analytical results with the numerical computations. In two-dimensions, we show that localised radial spots should also bifurcate off the spatially homogeneous background state. Localised planar hexagon fronts and hexagon patches are found and depending on the proximity to the singular limit these solutions either undergo homoclinic snaking or act like “multi-spot” solutions. Finally, we discuss applications of these localised patterns in the urban crime context and the full agent-based model.

  13. Towards biodiversity hotspots effective for conserving mammals with small geographic ranges

    Science.gov (United States)

    Carrara, Rodolfo; San Blas, Germán; Agrain, Federico; Roig-Juñent, Sergio

    2017-01-01

    The main goal of using global biodiversity hotspots for conservation purposes is to protect taxa with small geographic ranges because these are highly vulnerable to extinction. However, the extent to what different hotspots types are effective for meeting this goal remains controversial because hotspots have been previously defined as either the richest or most threatened and richest sites in terms of total, endemic or threatened species. In this regard, the use of species richness to set conservation priorities is widely discussed because strategies focused on this diversity measure tend to miss many of the taxa with small geographic ranges. Here we use data on global terrestrial mammal distributions to show that, hotspots of total species, endemism and threat defined in terms of species richness are effective in including 27%, 29% and 11% respectively, of the taxa with small geographic ranges. Whilst, the same hotspot types defined in terms of a simple diversity index, which is a function of species richness and range-size rarity, include 68%, 44% and 90% respectively, of these taxa. In addition, we demonstrate that index hotspot types are highly efficient because they conserve 79% of mammal species (21% more species than richness hotspot types), with 59% of species shared by three hotspot types (31% more than richness hotspot types). These results suggest that selection of different diversity measures to define hotspots may strongly affect the achievement of conservation goals.

  14. Network Dynamic Connectivity for Identifying Hotspots of Fluvial Geomorphic Change

    Science.gov (United States)

    Czuba, J. A.; Foufoula-Georgiou, E.

    2014-12-01

    The hierarchical branching structure of a river network serves as a template upon which environmental fluxes of water, sediment, nutrients, etc. are conveyed and organized both spatially and temporally within a basin. Dynamical processes occurring on a river network tend to heterogeneously distribute fluxes on the network, often concentrating them into "clusters," i.e., places of excess flux accumulation. Here, we put forward the hypothesis that places in the network predisposed (due to process dynamics and network topology) to accumulate excess bed-material sediment over a considerable river reach and over a considerable period of time reflect locations where a local imbalance in sediment flux may occur thereby highlighting a susceptibility to potential fluvial geomorphic change. We have developed a framework where we are able to track fluxes on a "static" river network using a simplified Lagrangian transport model and use the spatial-temporal distribution of that flux to form a new "dynamic" network of the flux that evolves over time. From this dynamic network we can quantify the dynamic connectivity of the flux and integrate emergent "clusters" over time through a cluster persistence index (CPI) to assess the persistence of mass throughout the network. The framework was applied to sand transport on the Greater Blue Earth River Network in Minnesota where three hotspots of fluvial geomorphic change have been defined based on high rates of channel migration observed from aerial photographic analysis. Locations within the network with high CPI coincided with two of these hotspots, possibly suggesting that channel migration here is driven by sediment deposition "pushing" the stream into and thus eroding the opposite bank. The third hotspot was not identified by high CPI, but instead is believed to be a hotspot of streamflow-driven change based on additional information and the fact that high bed shear stress coincided with this hotspot. The proposed network

  15. RARE DISEASES AND GENETIC DISCRIMINATION

    Directory of Open Access Journals (Sweden)

    Mariela Yaneva – Deliverska

    2011-04-01

    physicians (not enough physicians involved in rare diseases clinical trials, and the absence of treatment consensus recommendations.It is fundamental to realise that rare diseases can affect any family at any time. It is not just “something terrible that happens to other people”. It is a very cruel reality that can happen to anyone, either when having a child or in the course of one’s own life.In fact, the terminology “rare diseases” only highlights the characteristic of rarity of the complex and heterogeneous mosaic of an estimated 7,000 life-threatening and heavily debilitating conditions.The rare diseases for which a simple and effective preventive treatment is available are being screened for, as part of public health policy. But this is not enough, and it is essential for public authorities to consider rare diseases as a Public Health priority and take action to concretely support patients and families affected by rare diseases.As underlined in the Background Paper on Orphan Diseases for the World Health Organisation Report on Priority Medicines for Europe and the World, “despite the growing public awareness of rare diseases in the last one or two decades, there are still many gaps in knowledge related to the development of treatment for rare diseases. Policymakers have to realise that rare diseases are a crucial health issue for about 30 million people in the EU”.A good medication for rare disease patients is a medication that is both available in the country where they live and affordable. If one of these two factors is missing, the drug is of little use.Personalized medicine however is an emerging term for a medical philosophy that uses a person’s individual clinical, genetic, genomic, and environmental information to tailor a treatment plan that will maximize efficacy and safety for that individual. While the technology offers much promise, it also is also challenged by some ethical and social questions in both its clinical application and in its

  16. Evolution of a transposon in Daphnia hybrid genomes

    Directory of Open Access Journals (Sweden)

    Vergilino Roland

    2013-02-01

    Full Text Available Abstract Background Transposable elements play a major role in genome evolution. Their capacity to move and/or multiply in the genome of their host may have profound impacts on phenotypes, and may have dramatic consequences on genome structure. Hybrid and polyploid clones have arisen multiple times in the Daphnia pulex complex and are thought to reproduce by obligate parthenogenesis. Our study examines the evolution of a DNA transposable element named Pokey in the D. pulex complex. Results Portions of Pokey elements inserted in the 28S rRNA genes from various Daphnia hybrids (diploids and polyploids were sequenced and compared to sequences from a previous study to understand the evolutionary history of the elements. Pokey sequences show a complex phylogenetic pattern. We found evidence of recombination events in numerous Pokey alleles from diploid and polyploid hybrids and also from non-hybrid diploids. The recombination rate in Pokey elements is comparable to recombination rates previously estimated for 28S rRNA genes in the congener, Daphnia obtusa. Some recombinant Pokey alleles were encountered in Daphnia isolates from multiple locations and habitats. Conclusions Phylogenetic and recombination analyses showed that recombination is a major force that shapes Pokey evolution. Based on Pokey phylogenies, reticulation has played and still plays an important role in shaping the diversity of the D. pulex complex. Horizontal transfer of Pokey seems to be rare and hybrids often possess Pokey elements derived from recombination among alleles encountered in the putative parental species. The insertion of Pokey in hotspots of recombination may have important impacts on the diversity and fitness of this transposable element.

  17. Twenty-First Century Diseases: Commonly Rare and Rarely Common?

    Science.gov (United States)

    Daunert, Sylvia; Sittampalam, Gurusingham Sitta; Goldschmidt-Clermont, Pascal J

    2017-09-20

    Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.

  18. The Eucalyptus grandis NBS-LRR gene family: physical clustering and expression hotspots

    Directory of Open Access Journals (Sweden)

    Nanette eChristie

    2016-01-01

    Full Text Available Eucalyptus grandis is a commercially important hardwood species and is known to be susceptible to a number of pests and pathogens. Determining mechanisms of defense is therefore a research priority. The published genome for E. grandis has aided the identification of one important class of resistance (R genes that incorporate nucleotide binding sites and leucine-rich repeat domains (NBS-LRR. Using an iterative search process we identified NBS-LRR gene models within the E. grandis genome. We characterized the gene models and identified their genomic arrangement. The gene expression patterns were examined in E. grandis clones, challenged with a fungal pathogen (Chrysoporthe austroafricana and insect pest (Leptocybe invasa. 1215 putative NBS-LRR coding sequences were located which aligned into two large classes, Toll or interleukin-1 receptor (TIR and coiled-coil (CC based on NB-ARC domains. NBS-LRR gene-rich regions were identified with 76% organized in clusters of three or more genes. A further 272 putative incomplete resistance genes were also identified. We determined that E. grandis has a higher ratio of TIR to CC classed genes compared to other woody plant species as well as a smaller percentage of single NBS-LRR genes. Transcriptome profiles indicated expression hotspots, within physical clusters, including expression of many incomplete genes. The clustering of putative NBS-LRR genes correlates with differential expression responses in resistant and susceptible plants indicating functional relevance for the physical arrangement of this gene family. This analysis of the repertoire and expression of E. grandis putative NBS-LRR genes provides an important resource for the identification of novel and functional R-genes; a key objective for strategies to enhance resilience.

  19. Identifying hotspots and management of critical ecosystem services in rapidly urbanizing Yangtze River Delta Region, China.

    Science.gov (United States)

    Cai, Wenbo; Gibbs, David; Zhang, Lang; Ferrier, Graham; Cai, Yongli

    2017-04-15

    Rapid urbanization has altered many ecosystems, causing a decline in many ecosystem services, generating serious ecological crisis. To cope with these challenges, we presented a comprehensive framework comprising five core steps for identifying and managing hotspots of critical ecosystem services in a rapid urbanizing region. This framework was applied in the case study of the Yangtze River Delta (YRD) Region. The study showed that there was large spatial heterogeneity in the hotspots of ecosystem services in the region, hotspots of supporting services and regulating services aggregately distributing in the southwest mountainous areas while hotspots of provisioning services mainly in the northeast plain, and hotspots of cultural services widespread in the waterbodies and southwest mountainous areas. The regionalization of the critical ecosystem services was made through the hotspot analysis. This study provided valuable information for environmental planning and management in a rapid urbanizing region and helped improve China's ecological redlines policy at regional scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Mapping copy number variation by population-scale genome sequencing

    DEFF Research Database (Denmark)

    Mills, Ryan E.; Walter, Klaudia; Stewart, Chip

    2011-01-01

    , copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications...... differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies....

  1. Overlooked Mountain Rock Pools in Deserts Are Critical Local Hotspots of Biodiversity

    OpenAIRE

    Vale, C?ndida Gomes; Pimm, Stuart L.; Brito, Jos? Carlos

    2015-01-01

    Background The world is undergoing exceptional biodiversity loss. Most conservation efforts target biodiversity hotspots at large scales. Such approach overlooks small-sized local hotspots, which may be rich in endemic and highly threatened species. We explore the importance of mountain rock pools (gueltas) as local biodiversity hotspots in the Sahara-Sahel. Specifically, we considered how many vertebrates (total and endemics) use gueltas, what factors predict species richness, and which guel...

  2. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids.

    Science.gov (United States)

    Bazelet, Corinna S; Thompson, Aileen C; Naskrecki, Piotr

    2016-01-01

    The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species' natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms.

  3. Sampling effects on the identification of roadkill hotspots: Implications for survey design.

    Science.gov (United States)

    Santos, Sara M; Marques, J Tiago; Lourenço, André; Medinas, Denis; Barbosa, A Márcia; Beja, Pedro; Mira, António

    2015-10-01

    Although locating wildlife roadkill hotspots is essential to mitigate road impacts, the influence of study design on hotspot identification remains uncertain. We evaluated how sampling frequency affects the accuracy of hotspot identification, using a dataset of vertebrate roadkills (n = 4427) recorded over a year of daily surveys along 37 km of roads. "True" hotspots were identified using this baseline dataset, as the 500-m segments where the number of road-killed vertebrates exceeded the upper 95% confidence limit of the mean, assuming a Poisson distribution of road-kills per segment. "Estimated" hotspots were identified likewise, using datasets representing progressively lower sampling frequencies, which were produced by extracting data from the baseline dataset at appropriate time intervals (1-30 days). Overall, 24.3% of segments were "true" hotspots, concentrating 40.4% of roadkills. For different groups, "true" hotspots accounted from 6.8% (bats) to 29.7% (small birds) of road segments, concentrating from 60% (lizards, lagomorphs, carnivores) of roadkills. Spatial congruence between "true" and "estimated" hotspots declined rapidly with increasing time interval between surveys, due primarily to increasing false negatives (i.e., missing "true" hotspots). There were also false positives (i.e., wrong "estimated" hotspots), particularly at low sampling frequencies. Spatial accuracy decay with increasing time interval between surveys was higher for smaller-bodied (amphibians, reptiles, small birds, small mammals) than for larger-bodied species (birds of prey, hedgehogs, lagomorphs, carnivores). Results suggest that widely used surveys at weekly or longer intervals may produce poor estimates of roadkill hotspots, particularly for small-bodied species. Surveying daily or at two-day intervals may be required to achieve high accuracy in hotspot identification for multiple species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Exploiting the Genome

    Science.gov (United States)

    1998-09-11

    closing gaps left by Celera’s sequencing efforts and may be applicable to the sequencing of other eucaryotic genomes. 3. Transition to capillary gel...how those functions differ in different cell states, cell types, individuals, and organisms. Functional genomics is most mean- ingful when viewed...individuals who have expertise in both eucaryotic taxonomy and molecular aspects of gene expression (such individuals are rare). The goal would be to

  5. Detecting Malaria Hotspots: A Comparison of Rapid Diagnostic Test, Microscopy, and Polymerase Chain Reaction.

    Science.gov (United States)

    Mogeni, Polycarp; Williams, Thomas N; Omedo, Irene; Kimani, Domtila; Ngoi, Joyce M; Mwacharo, Jedida; Morter, Richard; Nyundo, Christopher; Wambua, Juliana; Nyangweso, George; Kapulu, Melissa; Fegan, Gregory; Bejon, Philip

    2017-11-27

    Malaria control strategies need to respond to geographical hotspots of transmission. Detection of hotspots depends on the sensitivity of the diagnostic tool used. We conducted cross-sectional surveys in 3 sites within Kilifi County, Kenya, that had variable transmission intensities. Rapid diagnostic test (RDT), microscopy, and polymerase chain reaction (PCR) were used to detect asymptomatic parasitemia, and hotspots were detected using the spatial scan statistic. Eight thousand five hundred eighty-one study participants were surveyed in 3 sites. There were statistically significant malaria hotspots by RDT, microscopy, and PCR for all sites except by microscopy in 1 low transmission site. Pooled data analysis of hotspots by PCR overlapped with hotspots by microscopy at a moderate setting but not at 2 lower transmission settings. However, variations in degree of overlap were noted when data were analyzed by year. Hotspots by RDT were predictive of PCR/microscopy at the moderate setting, but not at the 2 low transmission settings. We observed long-term stability of hotspots by PCR and microscopy but not RDT. Malaria control programs may consider PCR testing to guide asymptomatic malaria hotspot detection once the prevalence of infection falls.

  6. Impact of metric and sample size on determining malaria hotspot boundaries.

    Science.gov (United States)

    Stresman, Gillian H; Giorgi, Emanuele; Baidjoe, Amrish; Knight, Phil; Odongo, Wycliffe; Owaga, Chrispin; Shagari, Shehu; Makori, Euniah; Stevenson, Jennifer; Drakeley, Chris; Cox, Jonathan; Bousema, Teun; Diggle, Peter J

    2017-04-12

    The spatial heterogeneity of malaria suggests that interventions may be targeted for maximum impact. It is unclear to what extent different metrics lead to consistent delineation of hotspot boundaries. Using data from a large community-based malaria survey in the western Kenyan highlands, we assessed the agreement between a model-based geostatistical (MBG) approach to detect hotspots using Plasmodium falciparum parasite prevalence and serological evidence for exposure. Malaria transmission was widespread and highly heterogeneous with one third of the total population living in hotspots regardless of metric tested. Moderate agreement (Kappa = 0.424) was observed between hotspots defined based on parasite prevalence by polymerase chain reaction (PCR)- and the prevalence of antibodies to two P. falciparum antigens (MSP-1, AMA-1). While numerous biologically plausible hotspots were identified, their detection strongly relied on the proportion of the population sampled. When only 3% of the population was sampled, no PCR derived hotspots were reliably detected and at least 21% of the population was needed for reliable results. Similar results were observed for hotspots of seroprevalence. Hotspot boundaries are driven by the malaria diagnostic and sample size used to inform the model. These findings warn against the simplistic use of spatial analysis on available data to target malaria interventions in areas where hotspot boundaries are uncertain.

  7. Dynamic placement of plasmonic hotspots for super-resolution surface-enhanced Raman scattering.

    Science.gov (United States)

    Ertsgaard, Christopher T; McKoskey, Rachel M; Rich, Isabel S; Lindquist, Nathan C

    2014-10-28

    In this paper, we demonstrate dynamic placement of locally enhanced plasmonic fields using holographic laser illumination of a silver nanohole array. To visualize these focused "hotspots", the silver surface was coated with various biological samples for surface-enhanced Raman spectroscopy (SERS) imaging. Due to the large field enhancements, blinking behavior of the SERS hotspots was observed and processed using a stochastic optical reconstruction microscopy algorithm enabling super-resolution localization of the hotspots to within 10 nm. These hotspots were then shifted across the surface in subwavelength (super-resolution chemical imaging.

  8. The genome of Eucalyptus grandis

    Energy Technology Data Exchange (ETDEWEB)

    Myburg, Alexander A.; Grattapaglia, Dario; Tuskan, Gerald A.; Hellsten, Uffe; Hayes, Richard D.; Grimwood, Jane; Jenkins, Jerry; Lindquist, Erika; Tice, Hope; Bauer, Diane; Goodstein, David M.; Dubchak, Inna; Poliakov, Alexandre; Mizrachi, Eshchar; Kullan, Anand R. K.; Hussey, Steven G.; Pinard, Desre; van der Merwe, Karen; Singh, Pooja; van Jaarsveld, Ida; Silva-Junior, Orzenil B.; Togawa, Roberto C.; Pappas, Marilia R.; Faria, Danielle A.; Sansaloni, Carolina P.; Petroli, Cesar D.; Yang, Xiaohan; Ranjan, Priya; Tschaplinski, Timothy J.; Ye, Chu-Yu; Li, Ting; Sterck, Lieven; Vanneste, Kevin; Murat, Florent; Soler, Marçal; Clemente, Hélène San; Saidi, Naijib; Cassan-Wang, Hua; Dunand, Christophe; Hefer, Charles A.; Bornberg-Bauer, Erich; Kersting, Anna R.; Vining, Kelly; Amarasinghe, Vindhya; Ranik, Martin; Naithani, Sushma; Elser, Justin; Boyd, Alexander E.; Liston, Aaron; Spatafora, Joseph W.; Dharmwardhana, Palitha; Raja, Rajani; Sullivan, Christopher; Romanel, Elisson; Alves-Ferreira, Marcio; Külheim, Carsten; Foley, William; Carocha, Victor; Paiva, Jorge; Kudrna, David; Brommonschenkel, Sergio H.; Pasquali, Giancarlo; Byrne, Margaret; Rigault, Philippe; Tibbits, Josquin; Spokevicius, Antanas; Jones, Rebecca C.; Steane, Dorothy A.; Vaillancourt, René E.; Potts, Brad M.; Joubert, Fourie; Barry, Kerrie; Pappas, Georgios J.; Strauss, Steven H.; Jaiswal, Pankaj; Grima-Pettenati, Jacqueline; Salse, Jérôme; Van de Peer, Yves; Rokhsar, Daniel S.; Schmutz, Jeremy

    2014-06-11

    Eucalypts are the world s most widely planted hardwood trees. Their broad adaptability, rich species diversity, fast growth and superior multipurpose wood, have made them a global renewable resource of fiber and energy that mitigates human pressures on natural forests. We sequenced and assembled >94% of the 640 Mbp genome of Eucalyptus grandis into its 11 chromosomes. A set of 36,376 protein coding genes were predicted revealing that 34% occur in tandem duplications, the largest proportion found thus far in any plant genome. Eucalypts also show the highest diversity of genes for plant specialized metabolism that act as chemical defence against biotic agents and provide unique pharmaceutical oils. Resequencing of a set of inbred tree genomes revealed regions of strongly conserved heterozygosity, likely hotspots of inbreeding depression. The resequenced genome of the sister species E. globulus underscored the high inter-specific genome colinearity despite substantial genome size variation in the genus. The genome of E. grandis is the first reference for the early diverging Rosid order Myrtales and is placed here basal to the Eurosids. This resource expands knowledge on the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.

  9. Global diversity hotspots and conservation priorities for sharks.

    Directory of Open Access Journals (Sweden)

    Luis O Lucifora

    Full Text Available Sharks are one of the most threatened groups of marine animals, as high exploitation rates coupled with low resilience to fishing pressure have resulted in population declines worldwide. Designing conservation strategies for this group depends on basic knowledge of the geographic distribution and diversity of known species. So far, this information has been fragmented and incomplete. Here, we have synthesized the first global shark diversity pattern from a new database of published sources, including all 507 species described at present, and have identified hotspots of shark species richness, functional diversity and endemicity from these data. We have evaluated the congruence of these diversity measures and demonstrate their potential use in setting priority areas for shark conservation. Our results show that shark diversity across all species peaks on the continental shelves and at mid-latitudes (30-40 degrees N and S. Global hotspots of species richness, functional diversity and endemicity were found off Japan, Taiwan, the East and West coasts of Australia, Southeast Africa, Southeast Brazil and Southeast USA. Moreover, some areas with low to moderate species richness such as Southern Australia, Angola, North Chile and Western Continental Europe stood out as places of high functional diversity. Finally, species affected by shark finning showed different patterns of diversity, with peaks closer to the Equator and a more oceanic distribution overall. Our results show that the global pattern of shark diversity is uniquely different from land, and other well-studied marine taxa, and may provide guidance for spatial approaches to shark conservation. However, similar to terrestrial ecosystems, protected areas based on hotspots of diversity and endemism alone would provide insufficient means for safeguarding the diverse functional roles that sharks play in marine ecosystems.

  10. The Matchmaker Exchange: a platform for rare disease gene discovery

    NARCIS (Netherlands)

    Philippakis, A.A.; Azzariti, D.R.; Beltran, S.; Brookes, A.J.; Brownstein, C.A.; Brudno, M.; Brunner, H.G.; Buske, O.J.; Carey, K.; Doll, C.; Dumitriu, S.; Dyke, S.O.M.; Dunnen, J.T. den; Firth, H.V.; Gibbs, R.A.; Girdea, M.; Gonzalez, M.; Haendel, M.A.; Hamosh, A.; Holm, I.A.; Huang, L.; Hurles, M.E.; Hutton, B.; Krier, J.B.; Misyura, A.; Mungall, C.J.; Paschall, J.; Paten, B.; Robinson, P.N.; Schiettecatte, F.; Sobreira, N.L.; Swaminathan, G.J.; Taschner, P.E.M.; Terry, S.F.; Washington, N.L.; Zuchner, S.; Boycott, K.M.; Rehm, H.L.

    2015-01-01

    There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of

  11. French Polynesia Hotspot Swells Explained By Dynamic Topography

    Science.gov (United States)

    Adam, C.; Yoshida, M.; Isse, T.; Suetsugu, D.; Shiobara, H.; Sugioka, H.; Kanazawa, T.; Fukao, Y.; Barruol, G.

    2007-12-01

    Situated on the South Pacific Superswell, French Polynesia is a region characterized by numerous geophysical anomalies among which a high volcanism concentration. Seven hotspots are required to explain the observed chains, volcanism ages and geochemical trends. Many open questions still remain on the origin of these hotspot chains: are they created by passive uplift of magma due to discontinuities in the structure of the lithosphere or by the ascent of mantle plumes? In this case, at which depth do these plumes initiate in the mantle? Many geophysical observations (bathymetry, gravity, magnetism, volcanism ages..) are used to understand the unique phenomenon occurring on this region. The most useful information may come from tomography models since they provide a 3D view of the mantle. Until recently, the tomography models over the region were quite inaccurate because of the sparse location of the seismic stations. The deployment of two new seismic stations networks (BBOBS and temporary island stations) has lately remedied this failing. The resulting tomography model obtained through the inversion of Rayleigh waves provides the most accurate view of the shallowest part of the mantle (depths ≤ 240 km) beneath French Polynesia. Indeed, for the first time the accuracy of a tomography model is good enough to provide information about plume phenomenology in this complex region. In order to quantify the plumes effect on the seafloor, we compute the dynamic topography through an instantaneous flow model. The general trend of the observed depths anomalies (highs and lows) is well recovered. For example the amplitude, location and extension of the swells associated with the Society, Macdonald and Rarotonga are accurately described by the dynamic model. We also find that dynamic uplift is associated with the Tuamotu archipelago which means that a part of the observed swell is due to the present day action of plumes. Since no volcanism ages are available over this chain

  12. Ecosystem characteristics and processes facilitating persistent macrobenthic biomass hotspots and associated benthivory in the Pacific Arctic

    Science.gov (United States)

    Grebmeier, Jacqueline M.; Bluhm, Bodil A.; Cooper, Lee W.; Danielson, Seth L.; Arrigo, Kevin R.; Blanchard, Arny L.; Clarke, Janet T.; Day, Robert H.; Frey, Karen E.; Gradinger, Rolf R.; Kędra, Monika; Konar, Brenda; Kuletz, Kathy J.; Lee, Sang H.; Lovvorn, James R.; Norcross, Brenda L.; Okkonen, Stephen R.

    2015-08-01

    The northern Bering and Chukchi Seas are areas in the Pacific Arctic characterized by high northward advection of Pacific Ocean water, with seasonal variability in sea ice cover, water mass characteristics, and benthic processes. In this review, we evaluate the biological and environmental factors that support communities of benthic prey on the continental shelves, with a focus on four macrofaunal biomass "hotspots." For the purpose of this study, we define hotspots as macrofaunal benthic communities with high biomass that support a corresponding ecological guild of benthivorous seabird and marine mammal populations. These four benthic hotspots are regions within the influence of the St. Lawrence Island Polynya (SLIP), the Chirikov Basin between St. Lawrence Island and Bering Strait (Chirikov), north of Bering Strait in the southeast Chukchi Sea (SECS), and in the northeast Chukchi Sea (NECS). Detailed benthic macrofaunal sampling indicates that these hotspot regions have been persistent over four decades of sampling due to annual reoccurrence of seasonally consistent, moderate-to-high water column production with significant export of carbon to the underlying sediments. We also evaluate the usage of the four benthic hotspot regions by benthic prey consumers to illuminate predator-prey connectivity. In the SLIP hotspot, spectacled eiders and walruses are important winter consumers of infaunal bivalves and polychaetes, along with epibenthic gastropods and crabs. In the Chirikov hotspot, gray whales have historically been the largest summer consumers of benthic macrofauna, primarily feeding on ampeliscid amphipods in the summer, but they are also foraging further northward in the SECS and NECS hotspots. Areas of concentrated walrus foraging occur in the SLIP hotspot in winter and early spring, the NECS hotspot in summer, and the SECS hotspot in fall. Bottom up forcing by hydrography and food supply to the benthos influences persistence and composition of benthic prey

  13. Dynamics of reactive microbial hotspots in concentration gradients

    Science.gov (United States)

    Hubert, Antoine; Farasin, Julien; Tabuteau, Hervé; Méheust, Yves; Le Borgne, Tanguy

    2017-04-01

    In subsurface environments, bacteria play a major role in controlling the kinetics of a broad range of biogeochemical reactions. In such environments, nutrients fluxes and solute concentrations needed for bacteria metabolism may be highly variable in space and intermittent in time. This can lead to the formation of reactive hotspots where and when conditions are favorable to particular microorganisms, hence inducing biogeochemical reaction kinetics that differ significantly from those measured in homogeneous model environments. To investigate the impact of chemical gradients on the spatial structure and temporal dynamics of subsurface microorganism populations, we develop microfluidic cells allowing for a precise control of flow and chemical gradient conditions, as well as a quantitative monitoring of the bacteria's spatial distribution and biofilm development. Using the non-motile Escherichia coli JW1908-1 strain and Gallionella as model organisms, we investigate the behavior and development of bacteria over a range of single and double concentration gradients in the concentrations of nutrients, electron donors and electron acceptors. To quantify bacterial activity we use Fluorescein Diacetate (FDA) hydrolysis by bacterial enzymes which transforms FDA into Fluorescein, whose local concentration is measured optically. We thus measure bacterial activity locally from the time derivative of the measured fluorescence. This approach allows time-resolved monitoring of the location and intensity of reactive hotspots in micromodels as a function of the flow and chemical gradient conditions. We discuss consequences for the formation and temporal dynamics of biofilms in the subsurface.

  14. Can we detect oceanic biodiversity hotspots from space?

    Science.gov (United States)

    De Monte, Silvia; Soccodato, Alice; Alvain, Séverine; d'Ovidio, Francesco

    2013-10-01

    Understanding the variability of marine biodiversity is a central issue in microbiology. Current observational programs are based on in situ studies, but their implementation at the global scale is particularly challenging, owing to the ocean extent, its temporal variability and the heterogeneity of the data sources on which compilations are built. Here, we explore the possibility of identifying phytoplanktonic biodiversity hotspots from satellite. We define a Shannon entropy index based on patchiness in ocean color bio-optical anomalies. This index provides a high resolution (1 degree) global coverage. It shows a relation to temperature and mid-latitude maxima in accordance with those previously evidenced in microbiological biodiversity model and observational studies. Regional maxima are in remarkable agreement with several known biodiversity hotspots for plankton organisms and even for higher levels of the marine trophic chain, as well as with some in situ planktonic biodiversity estimates (from Atlantic Meridional Transect cruise). These results encourage to explore marine biodiversity with a coordinated effort of the molecular, ecological and remote sensing communities.

  15. Avian Haemosporidian blood parasite infections at a migration hotspot in Eilat, Israel

    Directory of Open Access Journals (Sweden)

    Paperna Ilan

    2016-06-01

    Full Text Available Haemosporidian blood parasites are frequent amongst passerines. Though they often do not cause detectable consequences to host health, however, their presence or absence and also their prevalence across host populations may potentially carry meaningful information about the health, stress, body condition and viability of bird individuals or populations. The study of migratory birds captured in Eilat, Israel, allowed us to evaluate the prevalence of blood parasite infections in a wide range of both migrant and resident species in spring (N = 1,950 and autumn (N = 538 of 2004 and 2005. According to blood film microscopy, Haemoproteus spp. and Leucocytozoon spp. were more prevalent in the spring than in the autumn (0.289, 0.082 vs. 0.132, 0.033, respectively, whilst Plasmodium spp. exhibited a slight opposite trend (0.034, 0.056. All other parasites (such as trypanosomes, microfilaria and haemococcidians were rare. During the spring seasons, prevalences were significantly higher in migrant than in resident species, whilst this difference was only marginally significant in the autumn. Given that Eilat is a migration hotspot for several Palearctic passerine species, the present descriptive study may hopefully serve to set the baseline values for future long-term epidemiological monitoring.

  16. Global Hotspots of Conflict Risk between Food Security and Biodiversity Conservation

    Directory of Open Access Journals (Sweden)

    Amy Molotoks

    2017-10-01

    Full Text Available The global challenges of food security and biodiversity are rarely addressed together, though recently there has been an increasing awareness that the two issues are closely related. The majority of land available for agriculture is already used for food production, but despite the productivity gains, one in nine people worldwide are classified as food insecure. There is an increasing risk that addressing food insecurity through methods such as agricultural expansion or intensification could lead to biodiversity loss through destruction of habitats important for conservation. This analysis uses various indicators of biodiversity at a global scale, including biodiversity hotspots, total species richness, and threatened and endemic species richness. Areas where high biodiversity coexists with high food insecurity or a high risk of agricultural expansion, were examined and found to mainly occur in the tropics, with Madagascar standing out in particular. The areas identified are especially at risk of biodiversity loss, and so are global priorities for further research and for policy development to address food insecurity and biodiversity loss together.

  17. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch.

    Science.gov (United States)

    Oakes, Benjamin L; Nadler, Dana C; Flamholz, Avi; Fellmann, Christof; Staahl, Brett T; Doudna, Jennifer A; Savage, David F

    2016-06-01

    The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated protein Cas9 from Streptococcus pyogenes is an RNA-guided DNA endonuclease with widespread utility for genome modification. However, the structural constraints limiting the engineering of Cas9 have not been determined. Here we experimentally profile Cas9 using randomized insertional mutagenesis and delineate hotspots in the structure capable of tolerating insertions of a PDZ domain without disruption of the enzyme's binding and cleavage functions. Orthogonal domains or combinations of domains can be inserted into the identified sites with minimal functional consequence. To illustrate the utility of the identified sites, we construct an allosterically regulated Cas9 by insertion of the estrogen receptor-α ligand-binding domain. This protein showed robust, ligand-dependent activation in prokaryotic and eukaryotic cells, establishing a versatile one-component system for inducible and reversible Cas9 activation. Thus, domain insertion profiling facilitates the rapid generation of new Cas9 functionalities and provides useful data for future engineering of Cas9.

  18. Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot.

    Science.gov (United States)

    Suzuki, Hitoshi; Aoki, Yoshitsugu; Kameyama, Toshiki; Saito, Takashi; Masuda, Satoru; Tanihata, Jun; Nagata, Tetsuya; Mayeda, Akila; Takeda, Shin'ichi; Tsukahara, Toshifumi

    2016-10-13

    Duchenne muscular dystrophy (DMD) is a severe muscular disorder. It was reported that multiple exon skipping (MES), targeting exon 45-55 of the DMD gene, might improve patients' symptoms because patients who have a genomic deletion of all these exons showed very mild symptoms. Thus, exon 45-55 skipping treatments for DMD have been proposed as a potential clinical cure. Herein, we detected the expression of endogenous exons 44-56 connected mRNA transcript of the DMD using total RNAs derived from human normal skeletal muscle by reverse transcription polymerase chain reaction (RT-PCR), and identified a total of eight types of MES products around the hotspot. Surprisingly, the 5' splice sites of recently reported post-transcriptional introns (remaining introns after co-transcriptional splicing) act as splicing donor sites for MESs. We also tested exon combinations to generate DMD circular RNAs (circRNAs) and determined the preferential splice sites of back-splicing, which are involved not only in circRNA generation, but also in MESs. Our results fit the current circRNA-generation model, suggesting that upstream post-transcriptional introns trigger MES and generate circRNA because its existence is critical for the intra-intronic interaction or for extremely distal splicing.

  19. How hot are drosophila hotspots? examining recombination rate variation and associations with nucleotide diversity, divergence, and maternal age in Drosophila pseudoobscura.

    Directory of Open Access Journals (Sweden)

    Brenda Manzano-Winkler

    Full Text Available Fine scale meiotic recombination maps have uncovered a large amount of variation in crossover rate across the genomes of many species, and such variation in mammalian and yeast genomes is concentrated to <5kb regions of highly elevated recombination rates (10-100x the background rate called "hotspots." Drosophila exhibit substantial recombination rate heterogeneity across their genome, but evidence for these highly-localized hotspots is lacking. We assayed recombination across a 40Kb region of Drosophila pseudoobscura chromosome 2, with one 20kb interval assayed every 5Kb and the adjacent 20kb interval bisected into 10kb pieces. We found that recombination events across the 40kb stretch were relatively evenly distributed across each of the 5kb and 10kb intervals, rather than concentrated in a single 5kb region. This, in combination with other recent work, indicates that the recombination landscape of Drosophila may differ from the punctate recombination pattern observed in many mammals and yeast. Additionally, we found no correlation of average pairwise nucleotide diversity and divergence with recombination rate across the 20kb intervals, nor any effect of maternal age in weeks on recombination rate in our sample.

  20. Reconstruction of gross avian genome structure, organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor.

    Science.gov (United States)

    Romanov, Michael N; Farré, Marta; Lithgow, Pamela E; Fowler, Katie E; Skinner, Benjamin M; O'Connor, Rebecca; Fonseka, Gothami; Backström, Niclas; Matsuda, Yoichi; Nishida, Chizuko; Houde, Peter; Jarvis, Erich D; Ellegren, Hans; Burt, David W; Larkin, Denis M; Griffin, Darren K

    2014-12-11

    The availability of multiple avian genome sequence assemblies greatly improves our ability to define overall genome organization and reconstruct evolutionary changes. In birds, this has previously been impeded by a near intractable karyotype and relied almost exclusively on comparative molecular cytogenetics of only the largest chromosomes. Here, novel whole genome sequence information from 21 avian genome sequences (most newly assembled) made available on an interactive browser (Evolution Highway) was analyzed. Focusing on the six best-assembled genomes allowed us to assemble a putative karyotype of the dinosaur ancestor for each chromosome. Reconstructing evolutionary events that led to each species' genome organization, we determined that the fastest rate of change occurred in the zebra finch and budgerigar, consistent with rapid speciation events in the Passeriformes and Psittaciformes. Intra- and interchromosomal changes were explained most parsimoniously by a series of inversions and translocations respectively, with breakpoint reuse being commonplace. Analyzing chicken and zebra finch, we found little evidence to support the hypothesis of an association of evolutionary breakpoint regions with recombination hotspots but some evidence to support the hypothesis that microchromosomes largely represent conserved blocks of synteny in the majority of the 21 species analyzed. All but one species showed the expected number of microchromosomal rearrangements predicted by the haploid chromosome count. Ostrich, however, appeared to retain an overall karyotype structure of 2n=80 despite undergoing a large number (26) of hitherto un-described interchromosomal changes. Results suggest that mechanisms exist to preserve a static overall avian karyotype/genomic structure, including the microchromosomes, with widespread interchromosomal change occurring rarely (e.g., in ostrich and budgerigar lineages). Of the species analyzed, the chicken lineage appeared to have undergone

  1. Hotspot trails in the South Atlantic controlled by plume and plate tectonic processes

    NARCIS (Netherlands)

    O'Connor, J.M.; Jokat, W.; Le Roex, A.; Class, C.; Wijbrans, J.R.; Kessling, S.; Kuiper, K.F.; Nebel, O.

    2012-01-01

    The origin of hotspot trails is controversial. Explanations range from deep mantle plumes rising from the core-mantle boundary (CMB) to shallow plate cracking. However, these mechanisms cannot explain uniquely the scattered hotspot trails distributed across a 2,000-km-wide swell in the sea floor of

  2. Biodiversity hotspots on the Dutch Continental Shelf: a marine strategy framework directive perspective

    NARCIS (Netherlands)

    Bos, O.G.; Witbaard, R.; Lavaleye, M.S.S.; Moorsel, G.W.N.M.; Teal, L.R.; Hal, van R.; Hammen, van der T.; Hofstede, ter R.; Bemmelen, van R.S.A.; Witte, R.H.; Geelhoed, S.C.V.; Dijkman, E.M.

    2011-01-01

    This report presenst hotspots of biodiversity for benthos, fish, birds, marine mammals and habitats on the Dutch Continental Shelf. These hotspots are based on a spatial application of biodiversity metrics developed in this study for the GES(Good Environmental Status)-descriptor 1 ‘Biological

  3. The Ig heavy chain switch region is a hotspot for insertion of transfected DNA

    Energy Technology Data Exchange (ETDEWEB)

    Baar, J.; Shulman, M.J. [Univ. of Toronto, Ontario (Canada)

    1995-08-15

    The Ig heavy chain switch usually occurs by breaking and rejoining DNA in the switch (S) regions, which consist of tandemly repeated sequences 5{prime} of the constant region exons. Various studies have suggested that S DNA can also recombine with non-S sequences. To measure the frequency of such recombination events, the hybridoma cell line igm692, a deletion mutant that lacks the C{mu}1 and C{mu}2 exons and the 3{prime} end of the S{mu} region, was transfected with a fragment bearing the C{mu}1-2 exons, but no S{mu} DNA. Insertion of this fragment into the residual VDJ-C{mu} intron of igm692 can restore a functional {mu} gene, yielding a transformant that is detected as a plaque-forming cell (PFC). PFCs comprise {approximately}8 x 10{sup -7} of the surviving transfected cells. In 10 of 12 PFCs, the C{mu}1-2 fragment inserted into the 2.5-kb residual S{mu} region, whereas insertion in two cases occurred in the 3.5-kb segment 5{prime} of S{mu}. Using a PCR assay to measure the frequency of insertion of the tranferred fragment elsewhere in the hybridoma genome, we found that {approximately}9% of the surviving tranfected cells had stably acquired the C{mu}1-2 fragment. These results indicate that the S{mu} region is {approximately}100-fold more recombinogenic than the average genomic site, and {approximately}7-fold more recombinogenic than the non-S{mu} segment of the residual VDJ-C{mu}, i.e., the S{mu} region is a hotspot for insertion of transfected DNA.

  4. ANALISIS HUBUNGAN KODE-KODE SPBK (SISTEM PERINGKAT BAHAYA KEBAKARAN) DAN HOTSPOT DENGAN KEBAKARAN HUTAN DAN LAHAN DI KALIMANTAN TENGAH

    National Research Council Canada - National Science Library

    Indah Prasasti; Rizaldi Boer; Muhammad Ardiansyah; Agus Buono; Lailan Syaufina; Yenni Vetrita

    2012-01-01

    ...) to develop the estimation model of burned area from hotspot and FDRS codes. The result of this research showed that burned area can not be estimated by using number of hotspots. The drought code (DC...

  5. Rare cancers: Challenges & issues

    Directory of Open Access Journals (Sweden)

    Raveendran K Pillai

    2017-01-01

    Full Text Available Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients' evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers.

  6. Rare cancers: Challenges & issues

    Science.gov (United States)

    Pillai, Raveendran K.; Jayasree, K.

    2017-01-01

    Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients’ evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers. PMID:28574010

  7. Current plate velocities relative to the hotspots incorporating the NUVEL-1 global plate motion model

    Science.gov (United States)

    Gripp, Alice E.; Gordon, Richard G.

    1990-01-01

    The NUVEL-1 model of current global relative plate velocities is presently incorporated into HS2-NUVEL1, a global model for plate velocities relative to hotspots; the results thus obtained are compared with those of the AM1-2 model of hotspot-relative plate velocities. While there are places in which plate velocities relative to the hotspots differ between HS2-NUVEL1 and AM1-2 by tens of degrees in direction and 15 mm/yr in speed, the hotspot Euler vectors differ with 95 percent confidence only for the Arabian and Indian plates. Plates attached to subducting slabs move faster relative to the hotspots than do plates without slabs.

  8. Current plate velocities relative to the hotspots incorporating the NUVEL-1 global plate motion model

    Science.gov (United States)

    Gripp, Alice E.; Gordon, Richard G.

    1990-07-01

    The NUVEL-1 model of current global relative plate velocities is presently incorporated into HS2-NUVEL1, a global model for plate velocities relative to hotspots; the results thus obtained are compared with those of the AM1-2 model of hotspot-relative plate velocities. While there are places in which plate velocities relative to the hotspots differ between HS2-NUVEL1 and AM1-2 by tens of degrees in direction and 15 mm/yr in speed, the hotspot Euler vectors differ with 95 percent confidence only for the Arabian and Indian plates. Plates attached to subducting slabs move faster relative to the hotspots than do plates without slabs.

  9. Paleo-drainage basin connectivity predicts evolutionary relationships across three Southeast Asian biodiversity hotspots.

    Science.gov (United States)

    de Bruyn, Mark; Rüber, Lukas; Nylinder, Stephan; Stelbrink, Björn; Lovejoy, Nathan R; Lavoué, Sébastien; Tan, Heok Hui; Nugroho, Estu; Wowor, Daisy; Ng, Peter K L; Siti Azizah, M N; Von Rintelen, Thomas; Hall, Robert; Carvalho, Gary R

    2013-05-01

    Understanding factors driving diversity across biodiversity hotspots is critical for formulating conservation priorities in the face of ongoing and escalating environmental deterioration. While biodiversity hotspots encompass a small fraction of Earth's land surface, more than half the world's plants and two-thirds of terrestrial vertebrate species are endemic to these hotspots. Tropical Southeast (SE) Asia displays extraordinary species richness, encompassing four biodiversity hotspots, though disentangling multiple potential drivers of species richness is confounded by the region's dynamic geological and climatic history. Here, we use multilocus molecular genetic data from dense multispecies sampling of freshwater fishes across three biodiversity hotspots, to test the effect of Quaternary climate change and resulting drainage rearrangements on aquatic faunal diversification. While Cenozoic geological processes have clearly shaped evolutionary history in SE Asian halfbeak fishes, we show that paleo-drainage re-arrangements resulting from Quaternary climate change played a significant role in the spatiotemporal evolution of lowland aquatic taxa, and provide priorities for conservation efforts.

  10. Genomic management of animal genetic diversity

    NARCIS (Netherlands)

    Oldenbroek, Kor

    2017-01-01

    Recently developed genomic tools, like SNP-genotyping and whole genome sequencing, and their analysis, offer great opportunities for the conservation and utilisation of animal genetic diversity, both among and within breeds. These genomic tools can be used to detect potentially valuable rare alleles

  11. Scope of Silicic Magmatism Associated With the Snake River Plain-Yellowstone (SRPY) "Hotspot" Track

    Science.gov (United States)

    Leeman, W. P.

    2007-12-01

    Eruptive volumes of silicic volcanic rocks provide indirect albeit minimal indications of the scale of magmatism associated with the SRPY hotspot track. Coherent eruptive centers at Yellowstone produced ca. 6000 km3 of high silica rhyolite over &~2 m.y. whereas the Bruneau-Jarbidge center in the central SRP produced as much as 10,000 km3 between 12.7 and 8 Ma. Total magma volumes could be significantly larger. About half erupted as 'supervolcano class` ignimbrites (i.e., exceeding 103 km3). Implicitly, such volumes must be on-tap at least periodically during the lifetime of an eruptive center but heterogeneities in mineral populations imply that magma may be derived from a plexus of isolated pockets in the crust (`crustal sponge`) rather than a well-mixed chamber. Magmatism was strongly bimodal - 'A-type' high silica rhyolite and basalt - intermediate composition lavas are rare. Moreover, each center produced rhyolite for 2-3 m.y. prior to the onset of basaltic volcanism which dominated subsequent activity. Nearly all SRPY rhyolites carry anhydrous mineral assemblages and mineral thermometry indicates high magmatic temperatures (typically >850-900°C). Radiogenic isotopes (Sr-Nd-Pb), trace element patterns, and low 18O in many SRPY rhyolites implicate a crustal source, although Nd isotopic data preclude large contributions from Archean crust. Silicic volcanism initiated in N-central Nevada ca. 16 Ma and migrated to Yellowstone by 2 Ma. However, the pattern of silicic eruptions was not simply progressive in space and time. Between 11.5-10 Ma major silicic eruptions occurred over a swath of more than 400 km - signifying availability of diverse rhyolite magmas beneath much of the SRP. Assuming that crustal melting was driven by basaltic intrusions, such magmas must have been generated beneath much of the province prior to 10 Ma - in part, well in advance of the postulated position of the Yellowstone hotspot at that time. The quantity of basalt needed to power SRPY

  12. A novel Bayesian hierarchical model for road safety hotspot prediction.

    Science.gov (United States)

    Fawcett, Lee; Thorpe, Neil; Matthews, Joseph; Kremer, Karsten

    2017-02-01

    In this paper, we propose a Bayesian hierarchical model for predicting accident counts in future years at sites within a pool of potential road safety hotspots. The aim is to inform road safety practitioners of the location of likely future hotspots to enable a proactive, rather than reactive, approach to road safety scheme implementation. A feature of our model is the ability to rank sites according to their potential to exceed, in some future time period, a threshold accident count which may be used as a criterion for scheme implementation. Our model specification enables the classical empirical Bayes formulation - commonly used in before-and-after studies, wherein accident counts from a single before period are used to estimate counterfactual counts in the after period - to be extended to incorporate counts from multiple time periods. This allows site-specific variations in historical accident counts (e.g. locally-observed trends) to offset estimates of safety generated by a global accident prediction model (APM), which itself is used to help account for the effects of global trend and regression-to-mean (RTM). The Bayesian posterior predictive distribution is exploited to formulate predictions and to properly quantify our uncertainty in these predictions. The main contributions of our model include (i) the ability to allow accident counts from multiple time-points to inform predictions, with counts in more recent years lending more weight to predictions than counts from time-points further in the past; (ii) where appropriate, the ability to offset global estimates of trend by variations in accident counts observed locally, at a site-specific level; and (iii) the ability to account for unknown/unobserved site-specific factors which may affect accident counts. We illustrate our model with an application to accident counts at 734 potential hotspots in the German city of Halle; we also propose some simple diagnostics to validate the predictive capability of our

  13. Heterogeneity in tuberculosis transmission and the role of geographic hotspots in propagating epidemics

    Science.gov (United States)

    Dowdy, David W.; Golub, Jonathan E.; Chaisson, Richard E.; Saraceni, Valeria

    2012-01-01

    The importance of high-incidence “hotspots” to population-level tuberculosis (TB) incidence remains poorly understood. TB incidence varies widely across countries, but within smaller geographic areas (e.g., cities), TB transmission may be more homogeneous than other infectious diseases. We constructed a steady-state compartmental model of TB in Rio de Janeiro, replicating nine epidemiological variables (e.g., TB incidence) within 1% of their observed values. We estimated the proportion of TB transmission originating from a high-incidence hotspot (6.0% of the city’s population, 16.5% of TB incidence) and the relative impact of TB control measures targeting the hotspot vs. the general community. If each case of active TB in the hotspot caused 0.5 secondary transmissions in the general community for each within-hotspot transmission, the 6.0% of people living in the hotspot accounted for 35.3% of city-wide TB transmission. Reducing the TB transmission rate (i.e., number of secondary infections per infectious case) in the hotspot to that in the general community reduced city-wide TB incidence by 9.8% in year 5, and 29.7% in year 50—an effect similar to halving time to diagnosis for the remaining 94% of the community. The importance of the hotspot to city-wide TB control depended strongly on the extent of TB transmission from the hotspot to the general community. High-incidence hotspots may play an important role in propagating TB epidemics. Achieving TB control targets in a hotspot containing 6% of a city’s population can have similar impact on city-wide TB incidence as achieving the same targets throughout the remaining community. PMID:22645356

  14. Current Absolute Plate Velocities Inferred from Hotspot Tracks, Comparison with Absolute Velocities Inferred from Seismic Anisotropy, and Bounds on Rates of Motion Between Groups of Hotspots

    Science.gov (United States)

    Wang, C.; Gordon, R. G.; Zheng, L.

    2015-12-01

    Hotspot tracks have been widely used to estimate the velocities of the plate relative to the lower mantle. Here we analyze the hotspot azimuth data set of Morgan and Phipps Morgan [2007] and show that the errors in plate velocity azimuths inferred from hotspot tracks in any one plate are correlated with the errors of other azimuths in the same plate. We use a two-tier analysis to account for this correlated error. First, we determine an individual best-fitting pole for each plate. Second, we determine the absolute plate velocity by minimizing the misfit while constrained by the MORVEL relative plate velocities [DeMets et al. 2010]. Our preferred model, HS4-MORVEL, uses azimuths from 9 major plates, which are weighted equally. We find that the Pacific plate rotates 0.860.016°Ma-1 right handed about 63.3°S, 96.1°E. Angular velocities of four plates (Amur, Eurasia, Yangtze and Antarctic) differ insignificantly from zero. The net rotation of the lithosphere is 0.24°±0.014° Ma-1 right handed about 52.3S, 56.9E. The angular velocities differ insignificantly from the absolute angular velocities inferred from the orientation of seismic anisotropy [Zheng et al. 2014]. The within-plate dispersion of hotspot track azimuths is 14°, which is comparable to the within-plate dispersion found from orientations of seismic anisotropy. The between-plate dispersion is 6.9±2.4° (95% confidence limits), which is smaller than that found from seismic anisotropy. The between-plate dispersion of 4.5° to 9.3° can be used to place bounds on how fast hotspots under one plate move relative to hotspots under another plate. For an average plate absolute speed of ≈50 mm/yr, the between-plate dispersion indicates a rate of motion of 4 mm/yr to 8 mm/yr for the component of hotspot motion perpendicular to plate motion. This upper bound is consistent with prior work that indicated upper bounds on motion between Pacific hotspots and Indo-Atlantic hotspots over the past 48 Ma of 8-13 mm

  15. A rare opportunity beckons

    Energy Technology Data Exchange (ETDEWEB)

    Gschneidner, K

    2011-02-01

    There is a great deal of uncertainty for the future of rare-earth production. Rare-earths are a collection of 17 chemical elements in the periodic table, which include scandium and yttrium as well as the 15 lanthanides, such as dysprosium and ytterbium. China has a stranglehold on today's rare-earth market, which was worth about $3bn in 2010, with the country accounting for about 95% of worldwide production. Yet China's future actions can only be guessed at best. In September it halted shipments of rare-earth elements to Japan over a diplomatic spat concerning the detention of a Chinese trawler captain. Although the ban was later lifted, the episode raised concerns around the world about China's rare-earth monopoly and its use in diplomacy. China has already warned that it will not export any rare-earth material in the coming years as it expects its own consumption of rare-earth metals to increase. The country has introduced export taxes as well as production and export quotas, and also refused to grant any new rare-earth mining licences. Furthermore, because its reserves are limited and China's internal markets are growing so rapidly, the country has suggested it will no longer export products that require rare-earth elements, especially those that need heavy rare-earth elements, such as terbium and dysprosium. China's actions have led to huge rises in the cost of rare-earth materials and products. Dysprosium oxide, for example, has shot up from $36 per kilogram in 2005 to a massive $305 per kilogram by late last year. This could have a huge impact on much of today's electronics industry, given that rare-earth elements are ubiquitous in electric motors, computers, batteries, liquid-crystal displays (LCDs) and mobile phones. Neodymium-iron-boron permanent magnets, for example, are used as computer spindle drives. The question is: what can be done to ensure that China's dominance of the rare-earth industry does not affect the

  16. RAS gene hot-spot mutations in canine neoplasias.

    Science.gov (United States)

    Richter, A; Murua Escobar, H; Günther, K; Soller, J T; Winkler, S; Nolte, I; Bullerdiek, J

    2005-01-01

    Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs.

  17. Hotspots in clinical management of severe liver diseases

    Directory of Open Access Journals (Sweden)

    LYU Jiayu

    2017-09-01

    Full Text Available Severe liver diseases such as liver failure and acute decompensated cirrhosis have critical conditions and high mortality rates, and the prognosis of such patients is closely associated with early warning, timely dynamic assessment, and comprehensive and effective therapy. The patients require a series of effective clinical management measures for elimination of causative factors, organ support, and prevention and treatment of complications. Medical treatment-artificial liver-liver transplantation is an important modality for severe liver diseases. Granulocyte colony-stimulating factor, stem cell therapy, and bioartificial liver have a promising future, while there are still controversies over non-selective β-blocker. This article reviews the hotspots in the clinical management of severe liver diseases.

  18. Urban rivers as hotspots of regional nitrogen pollution.

    Science.gov (United States)

    Zhang, Xiaohong; Wu, Yiyun; Gu, Baojing

    2015-10-01

    Excess nitrogen inputs to terrestrial ecosystems via human activities have deteriorated water qualities on regional scales. Urban areas as settlements of over half global population, however, were usually not considered in the analysis of regional water pollution. Here, we used a 72-month monitoring data of water qualities in Hangzhou, China to test the role of urban rives in regional nitrogen pollution and how they response to the changes of human activities. Concentrations of ammonium nitrogen in urban rivers were 3-5 times higher than that in regional rivers. Urban rivers have become pools of reactive nitrogen and hotspots of regional pollution. Moreover, this river pollution is not being measured by current surface water monitoring networks that are designed to measure broader regional patterns, resulting in an underestimation of regional pollution. This is crucial to urban environment not only in China, but also in other countries, where urban rivers are seriously polluted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Future of endemic flora of biodiversity hotspots in India.

    Science.gov (United States)

    Chitale, Vishwas Sudhir; Behera, Mukund Dev; Roy, Partha Sarthi

    2014-01-01

    India is one of the 12 mega biodiversity countries of the world, which represents 11% of world's flora in about 2.4% of global land mass. Approximately 28% of the total Indian flora and 33% of angiosperms occurring in India are endemic. Higher human population density in biodiversity hotspots in India puts undue pressure on these sensitive eco-regions. In the present study, we predict the future distribution of 637 endemic plant species from three biodiversity hotspots in India; Himalaya, Western Ghats, Indo-Burma, based on A1B scenario for year 2050 and 2080. We develop individual variable based models as well as mixed models in MaxEnt by combining ten least co-related bioclimatic variables, two disturbance variables and one physiography variable as predictor variables. The projected changes suggest that the endemic flora will be adversely impacted, even under such a moderate climate scenario. The future distribution is predicted to shift in northern and north-eastern direction in Himalaya and Indo-Burma, while in southern and south-western direction in Western Ghats, due to cooler climatic conditions in these regions. In the future distribution of endemic plants, we observe a significant shift and reduction in the distribution range compared to the present distribution. The model predicts a 23.99% range reduction and a 7.70% range expansion in future distribution by 2050, while a 41.34% range reduction and a 24.10% range expansion by 2080. Integration of disturbance and physiography variables along with bioclimatic variables in the models improved the prediction accuracy. Mixed models provide most accurate results for most of the combinations of climatic and non-climatic variables as compared to individual variable based models. We conclude that a) regions with cooler climates and higher moisture availability could serve as refugia for endemic plants in future climatic conditions; b) mixed models provide more accurate results, compared to single variable based

  20. Future of endemic flora of biodiversity hotspots in India.

    Directory of Open Access Journals (Sweden)

    Vishwas Sudhir Chitale

    Full Text Available India is one of the 12 mega biodiversity countries of the world, which represents 11% of world's flora in about 2.4% of global land mass. Approximately 28% of the total Indian flora and 33% of angiosperms occurring in India are endemic. Higher human population density in biodiversity hotspots in India puts undue pressure on these sensitive eco-regions. In the present study, we predict the future distribution of 637 endemic plant species from three biodiversity hotspots in India; Himalaya, Western Ghats, Indo-Burma, based on A1B scenario for year 2050 and 2080. We develop individual variable based models as well as mixed models in MaxEnt by combining ten least co-related bioclimatic variables, two disturbance variables and one physiography variable as predictor variables. The projected changes suggest that the endemic flora will be adversely impacted, even under such a moderate climate scenario. The future distribution is predicted to shift in northern and north-eastern direction in Himalaya and Indo-Burma, while in southern and south-western direction in Western Ghats, due to cooler climatic conditions in these regions. In the future distribution of endemic plants, we observe a significant shift and reduction in the distribution range compared to the present distribution. The model predicts a 23.99% range reduction and a 7.70% range expansion in future distribution by 2050, while a 41.34% range reduction and a 24.10% range expansion by 2080. Integration of disturbance and physiography variables along with bioclimatic variables in the models improved the prediction accuracy. Mixed models provide most accurate results for most of the combinations of climatic and non-climatic variables as compared to individual variable based models. We conclude that a regions with cooler climates and higher moisture availability could serve as refugia for endemic plants in future climatic conditions; b mixed models provide more accurate results, compared to single

  1. Knowledge and practice of household mosquito breeding control measures between a dengue hotspot and non-hotspot in Singapore.

    Science.gov (United States)

    Ong, Dave Q R; Sitaram, Neela; Rajakulendran, Mohana; Koh, Gerald C H; Seow, Adeline L H; Ong, Evan S L; Pang, Fung Yin

    2010-02-01

    The aim of this study was to compare the knowledge and practices of household mosquito-breeding control measures between a dengue hotspot (HS) and a non-hotspot (NHS). Eight hundred households were randomly sampled from HS and NHS areas, and an National Environment Agency (NEA) questionnaire was administered to heads of the households. Interviewers were blinded to the dengue status of households. We included subjects aged above 16 years, who were communicative and currently living in the household. Chi-square test was used to compare proportions and multiple logistic regression was used to adjust for socio-demographic differences between both areas. The overall response rate was 59.0% (n = 472). There were significant differences in gender, educational level, employment status and housing type between HS and NHS (all P <0.05). NHS residents were less knowledgeable in 6 out of 8 NEA-recommended anti-mosquito breeding actions: changing water in vase/bowls [AOR (adjusted OR), 0.20; CI, 0.08-0.47; P <0.01], adding sand granular insecticide to water [AOR, 0.49; CI, 0.31-0.71; P <0.01], turning over pails when not in use [AOR, 0.39; CI, 0.17-0.89; P = 0.02], removing flower pot/plates [AOR, 0.35; CI, 0.18-0.67; P <0.01], removing water in flower pot/plates [AOR, 0.36; CI, 0.17-0.75; P <0.01] and putting insecticide in roof gutters [AOR 0.36; CI, 0.13-0.98; P = 0.04]. Hotspot residents reported better practice of only 2 out of 8 NEA-recommended mosquito-breeding control measures: changing water in vases or bowls on alternate days [AOR, 2.74; CI, 1.51-4.96; P <0.01] and removing water from flower pot plates on alternate days [AOR, 1.95; CI, 1.01-3.77; P = 0.05]. More HS residents were knowledgeable and reported practicing mosquito-breeding control measures compared to NHS residents. However, a knowledge-practice gap still existed.

  2. Analysis of rare categories

    CERN Document Server

    He, Jingrui

    2012-01-01

    This book focuses on rare category analysis where the majority classes have smooth distributions and the minority classes exhibit the compactness property. It focuses on challenging cases where the support regions of the majority and minority classes overlap.

  3. Monitoring the trajectory of urban nighttime light hotspots using a Gaussian volume model

    Science.gov (United States)

    Zheng, Qiming; Jiang, Ruowei; Wang, Ke; Huang, Lingyan; Ye, Ziran; Gan, Muye; Ji, Biyong

    2018-03-01

    Urban nighttime light hotspot is an ideal representation of the spatial heterogeneity of human activities within a city, which is sensitive to regional urban expansion pattern. However, most of previous studies related to nighttime light imageries focused on extracting urban extent, leaving the spatial variation of radiance intensity insufficiently explored. With the help of global radiance calibrated DMSP-OLS datasets (NTLgrc), we proposed an innovative framework to explore the spatio-temporal trajectory of polycentric urban nighttime light hotspots. Firstly, NTLgrc was inter-annually calibrated to improve the consistency. Secondly, multi-resolution segmentation and region-growing SVM classification were employed to remove blooming effect and to extract potential clusters. At last, the urban hotspots were identified by a Gaussian volume model, and the resulting parameters were used to quantitatively depict hotspot features (i.e., intensity, morphology and centroid dynamics). The result shows that our framework successfully captures hotspots in polycentric urban area, whose Ra2 are over 0.9. Meanwhile, the spatio-temporal dynamics of the hotspot features intuitively reveal the impact of the regional urban growth pattern and planning strategies on human activities. Compared to previous studies, our framework is more robust and offers an effective way to describe hotspot pattern. Also, it provides a more comprehensive and spatial-explicit understanding regarding the interaction between urbanization pattern and human activities. Our findings are expected to be beneficial to governors in term of sustainable urban planning and decision making.

  4. Landscape-scale analyses suggest both nutrient and antipredator advantages to Serengeti herbivore hotspots.

    Science.gov (United States)

    Anderson, T Michael; Hopcraft, J Grant C; Eby, Stephanie; Ritchie, Mark; Grace, James B; Olff, Han

    2010-05-01

    Mechanistic explanations of herbivore spatial distribution have focused largely on either resource-related (bottom-up) or predation-related (top-down) factors. We studied direct and indirect influences on the spatial distributions of Serengeti herbivore hotspots, defined as temporally stable areas inhabited by mixed herds of resident grazers. Remote sensing and variation in landscape features were first used to create a map of the spatial distribution of hotspots, which was tested for accuracy against an independent data set of herbivore observations. Subsequently, we applied structural equation modeling to data on soil fertility and plant quality and quantity across a range of sites. We found that hotspots in Serengeti occur in areas that are relatively flat and located away from rivers, sites where ungulates are less susceptible to predation. Further, hotspots tend to occur in areas where hydrology and rainfall create conditions of relatively low-standing plant biomass, which, coupled with grazing, increases forage quality while decreasing predation risk. Low-standing biomass and higher leaf concentrations of N, Na, and Mg were strong direct predictors of hotspot occurrence. Soil fertility had indirect effects on hotspot occurrence by promoting leaf Na and Mg. The results indicate that landscape features contribute in direct and indirect ways to influence the spatial distribution of hotspots and that the best models incorporated both resource- and predation-related factors. Our study highlights the collective and simultaneous role of bottom-up and top-down factors in determining ungulate spatial distributions.

  5. Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System

    Directory of Open Access Journals (Sweden)

    Jinjian Jiang

    2017-07-01

    Full Text Available Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences.

  6. Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System

    Science.gov (United States)

    Jiang, Jinjian; Wang, Nian; Chen, Peng; Zheng, Chunhou; Wang, Bing

    2017-01-01

    Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences. PMID:28718782

  7. Hotspots Detection from Trajectory Data Based on Spatiotemporal Data Field Clustering

    Science.gov (United States)

    Qin, K.; Zhou, Q.; Wu, T.; Xu, Y. Q.

    2017-09-01

    City hotspots refer to the areas where residents visit frequently, and large traffic flow exist, which reflect the people travel patterns and distribution of urban function area. Taxi trajectory data contain abundant information about urban functions and citizen activities, and extracting interesting city hotspots from them can be of importance in urban planning, traffic command, public travel services etc. To detect city hotspots and discover a variety of changing patterns among them, we introduce a data field-based cluster analysis technique to the pick-up and drop-off points of taxi trajectory data and improve the method by introducing the time weight, which has been normalized to estimate the potential value in data field. Thus, in the light of the new potential function in data field, short distance and short time difference play a powerful role. So the region full of trajectory points, which is regarded as hotspots area, has a higher potential value, while the region with thin trajectory points has a lower potential value. The taxi trajectory data of Wuhan city in China on May 1, 6 and 9, 2015, are taken as the experimental data. From the result, we find the sustaining hotspots area and inconstant hotspots area in Wuhan city based on the spatiotemporal data field method. Further study will focus on optimizing parameter and the interaction among hotspots area.

  8. HOTSPOTS DETECTION FROM TRAJECTORY DATA BASED ON SPATIOTEMPORAL DATA FIELD CLUSTERING

    Directory of Open Access Journals (Sweden)

    K. Qin

    2017-09-01

    Full Text Available City hotspots refer to the areas where residents visit frequently, and large traffic flow exist, which reflect the people travel patterns and distribution of urban function area. Taxi trajectory data contain abundant information about urban functions and citizen activities, and extracting interesting city hotspots from them can be of importance in urban planning, traffic command, public travel services etc. To detect city hotspots and discover a variety of changing patterns among them, we introduce a data field-based cluster analysis technique to the pick-up and drop-off points of taxi trajectory data and improve the method by introducing the time weight, which has been normalized to estimate the potential value in data field. Thus, in the light of the new potential function in data field, short distance and short time difference play a powerful role. So the region full of trajectory points, which is regarded as hotspots area, has a higher potential value, while the region with thin trajectory points has a lower potential value. The taxi trajectory data of Wuhan city in China on May 1, 6 and 9, 2015, are taken as the experimental data. From the result, we find the sustaining hotspots area and inconstant hotspots area in Wuhan city based on the spatiotemporal data field method. Further study will focus on optimizing parameter and the interaction among hotspots area.

  9. En studie i dyslektikers kommunikativa och känslomässiga interaktion med användandet av specialgjorda datorprogram : Genom forskning med användare/elever på en gymnasienivå och enligt specialpedagog/speciallärare

    OpenAIRE

    Gullström, Wictor

    2008-01-01

    Den här C-uppsatsen är en studie om dyslektikers kommunikativa interaktion med kompenserande specialgjorda datorprogram för träning i sitt användande av att skriva olika sorters texter. Ämnets olika nyckelord är det som är relevant för denna C-uppsats.   Denna studies undersökningar har skett genom intervjuer med en speciallärare och en specialpedagog som är en form av experter på detta område och kan extra fakta om de olika eleverna (respondenterna). De har intervjuats för att få koll på vad...

  10. Application of GIS to predict malaria hotspots based on Anopheles arabiensis habitat suitability in Southern Africa

    Science.gov (United States)

    Gwitira, Isaiah; Murwira, Amon; Zengeya, Fadzai M.; Shekede, Munyaradzi Davis

    2018-02-01

    Malaria remains a major public health problem and a principal cause of morbidity and mortality in most developing countries. Although malaria still presents health problems, significant successes have been recorded in reducing deaths resulting from the disease. As malaria transmission continues to decline, control interventions will increasingly depend on the ability to define high-risk areas known as malaria hotspots. Therefore, there is urgent need to use geospatial tools such as geographic information system to detect spatial patterns of malaria and delineate disease hot spots for better planning and management. Thus, accurate mapping and prediction of seasonality of malaria hotspots is an important step towards developing strategies for effective malaria control. In this study, we modelled seasonal malaria hotspots as a function of habitat suitability of Anopheles arabiensis (A. Arabiensis) as a first step towards predicting likely seasonal malaria hotspots that could provide guidance in targeted malaria control. We used Geographical information system (GIS) and spatial statistic methods to identify seasonal hotspots of malaria cases at the country level. In order to achieve this, we first determined the spatial distribution of seasonal malaria hotspots using the Getis Ord Gi* statistic based on confirmed positive malaria cases recorded at health facilities in Zimbabwe over four years (1996-1999). We then used MAXENT technique to model habitat suitability of A. arabiensis from presence data collected from 1990 to 2002 based on bioclimatic variables and altitude. Finally, we used autologistic regression to test the extent to which malaria hotspots can be predicted using A. arabiensis habitat suitability. Our results show that A. arabiensis habitat suitability consistently and significantly (p malaria hotspots from 1996 to 1999. Overall, our results show that malaria hotspots can be predicted using A. arabiensis habitat suitability, suggesting the possibility of

  11. Computational analysis of hot-spot formation by quasi-steady deformation waves in porous explosive

    Science.gov (United States)

    Gilbert, John; Chakravarthy, Sunada; Gonthier, Keith A.

    2013-05-01

    The impact and shock sensitivity of porous (granular) high-explosives is related to the formation of small mass regions of elevated temperature within the material called hot-spots by dissipative mechanisms such as plastic and friction work. Because of their small size, hot-spots are difficult to experimentally interrogate, particularly for high volumetric strain rates (ɛ˙V>10,000 s-1). In this study, simulations are performed for large ensembles of deformable particles (≈4000 particles) using a combined finite and discrete element technique to characterize statistical distributions of hot-spot intensity, geometry, and spatial proximity within and behind quasi-steady, piston supported uniaxial waves in granular HMX (C4H8N8O8). Emphasis is placed on examining how the material's initial particle packing density, characterized by its effective solid volume fraction ϕ¯s ,0, affects hot-spot statistics for pressure dominated waves corresponding to piston speeds within the range 300≤Up≤500 m /s. Predictions indicate that hot-spot intensity is only marginally affected by initial porosity (1-ϕ¯s ,0) for all piston speeds, whereas hot-spot size, number density, volume fraction, and volume specific surface area appreciably increase with porosity and exponentially increase with piston speed. Minor variations in particle shape are predicted to be largely inconsequential. Joint distributions of hot-spot intensity and size are combined with thermal explosion data to identify and examine critical hot-spots that quickly react behind waves. These results indicate that the observed increase in sensitivity with initial porosity for sustained loading is likely due to an increase in hot-spot size and number rather than intensity.

  12. Long-lived but Discontinuous Hotspot Volcanism of the South Pacific Mantle

    Science.gov (United States)

    Koppers, A.; Staudigel, H.; Wijbrans, J.; Pringle, M.

    2001-12-01

    Hotspots of the South Pacific have been operating since the Early Cretaceous. We present evidence that their heterogeneous geochemical character and, hence, their respective HIMU-EMI-EMII mantle sources, can be traced back into the West Pacific Seamount Province (WPSP) using plate tectonic reconstructions. This implies that the HIMU, EMI and EMII mantle components are enduring features within the Earth's mantle, at least, for the last 140 Myr. These correlations are eminent on the scale of the WPSP and the South Pacific Thermal and Isotopic Anomaly (SOPITA) although the evolution of individual hotspots emerges notably more complicated. Hotspots in the WPSP and SOPITA mantle regions typically display intermittent volcanic activity, longevities shorter than 70 Myr, superposition of hotspot volcanism, and indirectly the motion of their mantle plumes through time. In our plate tectonic reconstructions, we use 40Ar/39Ar seamount ages and Sr-Nd-Pb isotopic signatures to map out Cretaceous hotspot volcanism in the WPSP and to characterize its evolution with respect to the currently active hotspots in the SOPITA region. EM-type Magellan, Anewetak, Ralik and Ratak seamount trails can be traced back to the magmatic activity of the Macdonald, Rurutu and Rarotonga hotspots during the Cretaceous; the HIMU-type seamounts within the Southern Wake seamount trail (97-120 Ma) most likely originated from the Mangaia-Rurutu "hot-line" in the Cook-Austral Islands. The Typhoon and Japanese guyots terminated their volcanism during the Early Cretaceous and have no presently active hot spot. However, the currently active Samoan, Society, Pitcairn and Marquesas hotspots may be traced back only to about 30-70 Myr and lack long-lived counterparts in the WPSP. These hotspots may have become active over the last 30-70 Myr only. All in all hotspot volcanism in the South Pacific seems to be controlled by a "superplume" type of mantle convection giving rise to multiple weak mantle plumes, each

  13. How and when plume zonation appeared during the 132 Myr evolution of the Tristan Hotspot

    OpenAIRE

    Hoernle, Kaj; Rohde, Joana; Hauff, Folkmar; Garbe-Schönberg, Dieter; Homrighausen, Stephan; Werner, Reinhard; Morgan, Jason P.

    2015-01-01

    Increasingly, spatial geochemical zonation, present as geographically distinct, subparallel trends, is observed along hotspot tracks, such as Hawaii and the Galapagos. The origin of this zonation is currently unclear. Recently zonation was found along the last ∼70 Myr of the Tristan-Gough hotspot track. Here we present new Sr–Nd–Pb–Hf isotope data from the older parts of this hotspot track (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the Etendeka and Parana flood bas...

  14. CONSERVATION. Genetic assignment of large seizures of elephant ivory reveals Africa's major poaching hotspots.

    Science.gov (United States)

    Wasser, S K; Brown, L; Mailand, C; Mondol, S; Clark, W; Laurie, C; Weir, B S

    2015-07-03

    Poaching of elephants is now occurring at rates that threaten African populations with extinction. Identifying the number and location of Africa's major poaching hotspots may assist efforts to end poaching and facilitate recovery of elephant populations. We genetically assign origin to 28 large ivory seizures (≥0.5 metric tons) made between 1996 and 2014, also testing assignment accuracy. Results suggest that the major poaching hotspots in Africa may be currently concentrated in as few as two areas. Increasing law enforcement in these two hotspots could help curtail future elephant losses across Africa and disrupt this organized transnational crime. Copyright © 2015, American Association for the Advancement of Science.

  15. Gene copy number variations in adaptive evolution: The genomic distribution of gene copy number variations revealed by genetic mapping and their adaptive role in an undomesticated species, white spruce (Picea glauca).

    Science.gov (United States)

    Prunier, Julien; Caron, Sébastien; Lamothe, Manuel; Blais, Sylvie; Bousquet, Jean; Isabel, Nathalie; MacKay, John

    2017-11-01

    Gene copy number variation (CNV) has been associated with phenotypic variability in animals and plants, but a genomewide understanding of their impacts on phenotypes is largely restricted to human and agricultural systems. As such, CNVs have rarely been considered in investigations of the genomic architecture of adaptation in wild species. Here, we report on the genetic mapping of gene CNVs in white spruce, which lacks a contiguous assembly of its large genome (~20 Gb), and their relationships with adaptive phenotypic variation. We detected 3,911 gene CNVs including de novo structural variations using comparative genome hybridization on arrays (aCGH) in a large progeny set. We inferred the heterozygosity at CNV loci within parents by comparing haploid and diploid tissues and genetically mapped 82 gene CNVs. Our analysis showed that CNVs were distributed over 10 linkage groups and identified four CNV hotspots that we predict to occur in other species of the Pinaceae. Significant relationships were found between 29 of the gene CNVs and adaptive traits based on regression analyses with timings of bud set and bud flush, and height growth, suggesting a role for CNVs in climate adaptation. The importance of CNVs in adaptive evolution of white spruce was also indicated by functional gene annotations and the clustering of 31% of the mapped adaptive gene CNVs in CNV hotspots. Taken together, these results illustrate the feasibility of studying CNVs in undomesticated species and represent a major step towards a better understanding of the roles of CNVs in adaptive evolution. © 2017 John Wiley & Sons Ltd.

  16. Genomic Testing

    Science.gov (United States)

    ... Counseling Genomic Testing Pathogen Genomics Epidemiology Resources Genomic Testing Recommend on Facebook Tweet Share Compartir Fact Sheet: ... Page The Need for Reliable Information on Genetic Testing In 2008, the former Secretary’s Advisory Committee on ...

  17. Implications of salinity pollution hotspots on agricultural production

    Science.gov (United States)

    Floerke, Martina; Fink, Julia; Malsy, Marcus; Voelker, Jeanette; Alcamo, Joseph

    2016-04-01

    , large metropolitan regions are initially loading hotspots and pollution, too, and prevention becomes important as point sources are dependent on sewer connection rates and treatment levels. In conclusion, this study provides a detailed picture of the spatial and temporal distribution of salinity pollution and identifies hotspot areas as well as the dominant sources. Furthermore, impacts of water quality degradation on agricultural production and food security are quantified, which aim for a better understanding of the risks for food security caused by water quality impairment.

  18. Plumes, Hotspot & Slabs Imaged by Global Adjoint Tomography

    Science.gov (United States)

    Bozdag, E.; Lefebvre, M. P.; Lei, W.; Peter, D. B.; Smith, J. A.; Komatitsch, D.; Tromp, J.

    2015-12-01

    We present the "first generation" global adjoint tomography model based on 3D wave simulations, which is the result of 15 conjugate-gradient iterations with confined transverse isotropy to the upper mantle. Our starting model is the 3D mantle and crustal models S362ANI (Kustowski et al. 2008) and Crust2.0 (Bassin et al. 2000), respectively. We take into account the full nonlinearity of wave propagation in numerical simulations including attenuation (both in forward and adjoint simulations), topography/bathymetry, etc., using the GPU version of the SPECFEM3D_GLOBE package. We invert for crust and mantle together without crustal corrections to avoid any bias in mantle structure. We started with an initial selection of 253 global CMT events within the magnitude range 5.8 ≤ Mw ≤ 7.0 with numerical simulations having resolution down to 27 s combining 30-s body and 60-s surface waves. After the 12th iteration we increased the resolution to 17 s, including higher-frequency body waves as well as going down to 45 s in surface-wave measurements. We run 180-min seismograms and assimilate all minor- and major-arc body and surface waves. Our 15th iteration model update shows a tantalisingly enhanced image of the Tahiti plume as well as various other plumes and hotspots, such as Caroline, Galapagos, Yellowstone, Erebus, etc. Furthermore, we see clear improvements in slab resolution along the Hellenic and Japan Arcs, as well as subduction along the East of Scotia Plate, which does not exist in the initial model. Point-spread function tests (Fichtner & Trampert 2011) suggest that we are close to the resolution of continental-scale studies in our global inversions and able to confidently map features, for instance, at the scale of the Yellowstone hotspot. This is a clear consequence of our multi-scale smoothing strategy, in which we define our smoothing operator as a function of the approximate Hessian kernel and smooth our gradients less wherever we have good ray coverage

  19. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  20. Neurolipoma: A rare entity

    Directory of Open Access Journals (Sweden)

    Banyameen Iqbal

    2014-01-01

    Full Text Available A lipoma is a common type of benign tumor and a neurolipoma is one of its variants. It is also referred to as neural fibrolipoma, fibrolipomatous hamartoma, intramural lipoma, and lipomatosis of nerve. The most common sites of presentation are the volar aspects of the hands, wrists, and forearms of young persons. The median nerve is most commonly involved. Lower-extremity cases are extremely rare. We report here a rare case involving the median nerve without any skeletal deformity occurring in a male patient. It usually presents with swelling associated with pain and tenderness.

  1. Rare carpometacarpal dislocations.

    Science.gov (United States)

    Lefere, M; Dallaudière, B; Omoumi, P; Cyteval, C; Larbi, A

    2016-10-01

    Posttraumatic carpal and carpometacarpal dislocations represent a heterogeneous group of disorders resulting from high-energy wrist trauma. Perilunate injury is the most common and best-known manifestation of carpal dislocation, typically occurring after hyperextension trauma. Other forms are very rare and have different causative mechanisms. Carpometacarpal (CMC) dislocations are also uncommon and may affect isolated or multiple CMC joints. These lesions are prone to wrist instability if not treated promptly. The aim of this article is to provide a systematic radiologic approach to the evaluation of wrist injury and to present two acute cases of rare CMC dislocations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Rare (Earth Elements [score

    Directory of Open Access Journals (Sweden)

    Camilo Méndez

    2014-12-01

    Full Text Available Rare (Earth Elements is a cycle of works for solo piano. The cycle was inspired by James Dillon’s Book of Elements (Vol. I-V. The complete cycle will consist of 14 pieces; one for each selected rare (earth element. The chosen elements are Neodymium, Erbium, Tellurium, Hafnium, Tantalum, Technetium, Indium, Dysprosium, Lanthanium, Cerium, Europium, Terbium, Yttrium and Darmstadtium. These elements were selected due to their special atomic properties that in many cases make them extremely valuable for the development of new technologies, and also because of their scarcity. To date, only 4 works have been completed Yttrium, Technetium, Indium and Tellurium.

  3. Marine caves of the Mediterranean Sea: a sponge biodiversity reservoir within a biodiversity hotspot.

    Science.gov (United States)

    Gerovasileiou, Vasilis; Voultsiadou, Eleni

    2012-01-01

    Marine caves are widely acknowledged for their unique biodiversity and constitute a typical feature of the Mediterranean coastline. Herein an attempt was made to evaluate the ecological significance of this particular ecosystem in the Mediterranean Sea, which is considered a biodiversity hotspot. This was accomplished by using Porifera, which dominate the rocky sublittoral substrata, as a reference group in a meta-analytical approach, combining primary research data from the Aegean Sea (eastern Mediterranean) with data derived from the literature. In total 311 species from all poriferan classes were recorded, representing 45.7% of the Mediterranean Porifera. Demospongiae and Homoscleromorpha are highly represented in marine caves at the family (88%), generic (70%), and species level (47.5%), the latter being the most favored group along with Dictyoceratida and Lithistida. Several rare and cave-exclusive species were reported from only one or few caves, indicating the fragmentation and peculiarity of this unique ecosystem. Species richness and phylogenetic diversity varied among Mediterranean areas; the former was positively correlated with research effort, being higher in the northern Mediterranean, while the latter was generally higher in caves than in the overall sponge assemblages of each area. Resemblance analysis among areas revealed that cavernicolous sponge assemblages followed a pattern quite similar to that of the overall Mediterranean assemblages. The same pattern was exhibited by the zoogeographic affinities of cave sponges: species with Atlanto-Mediterranean distribution and Mediterranean endemics prevailed (more than 40% each), 70% of them having warm-water affinities, since most caves were studied in shallow waters. According to our findings, Mediterranean marine caves appear to be important sponge biodiversity reservoirs of high representativeness and great scientific interest, deserving further detailed study and protection.

  4. Pneumococcal Capsule Synthesis Locus cps as Evolutionary Hotspot with Potential to Generate Novel Serotypes by Recombination.

    Science.gov (United States)

    Mostowy, Rafal J; Croucher, Nicholas J; De Maio, Nicola; Chewapreecha, Claire; Salter, Susannah J; Turner, Paul; Aanensen, David M; Bentley, Stephen D; Didelot, Xavier; Fraser, Christophe

    2017-10-01

    Diversity of the polysaccharide capsule in Streptococcus pneumoniae-main surface antigen and the target of the currently used pneumococcal vaccines-constitutes a major obstacle in eliminating pneumococcal disease. Such diversity is genetically encoded by almost 100 variants of the capsule biosynthesis locus, cps. However, the evolutionary dynamics of the capsule remains not fully understood. Here, using genetic data from 4,519 bacterial isolates, we found cps to be an evolutionary hotspot with elevated substitution and recombination rates. These rates were a consequence of relaxed purifying selection and positive, diversifying selection acting at this locus, supporting the hypothesis that the capsule has an increased potential to generate novel diversity compared with the rest of the genome. Diversifying selection was particularly evident in the region of wzd/wze genes, which are known to regulate capsule expression and hence the bacterium's ability to cause disease. Using a novel, capsule-centered approach, we analyzed the evolutionary history of 12 major serogroups. Such analysis revealed their complex diversification scenarios, which were principally driven by recombination with other serogroups and other streptococci. Patterns of recombinational exchanges between serogroups could not be explained by serotype frequency alone, thus pointing to nonrandom associations between co-colonizing serotypes. Finally, we discovered a previously unobserved mosaic serotype 39X, which was confirmed to carry a viable and structurally novel capsule. Adding to previous discoveries of other mosaic capsules in densely sampled collections, these results emphasize the strong adaptive potential of the bacterium by its ability to generate novel antigenic diversity by recombination. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Poverty, livelihoods and the conservation of nature in biodiversity hotspots around the world

    CSIR Research Space (South Africa)

    Bouma, J

    2013-01-01

    Full Text Available The high incidence of poverty in biodiversity hotspots around the world has given rise to a debate about the potential of integrated development-conservation approaches to help alleviate poverty and protect biodiversity at the same time...

  6. Identification of Hotspots of Genetic Risk for Type 2 Diabetes Using GIS Methods

    Science.gov (United States)

    BACKGROUND: Having the ability to scan the entire country for potential "hotspots" with increased risk of developing chronic diseases due to various environmental, demographic, and genetic susceptibility factors may inform risk management decisions and enable better env...

  7. Tracking Long-lived Hotspots to Constrain Temporal Mantle Compositional Evolution

    Science.gov (United States)

    Konter, J. G.; Jackson, M. G.; Koppers, A. A.

    2011-12-01

    Linear chains of intraplate volcanoes provide a record of the geochemical composition of the mantle through geologic time. Their geochemical compositions characterize the mantle source material that melted and place constraints on the geodynamic origin of the source, and thereby the dynamic character of the mantle. In particular, long-lived volcanic chains provide strong constraints, since they require large volumes of mantle source material and provide the best way to evaluate hotspot source stability. Some of the longest-lived volcanic chains are anchored by the current Cook-Austral Islands continuing into the Western Pacific, where their tracks are complicated by cross-cutting volcanic chains and isolated seamounts. The connection between recent volcanism in the Cook-Austral Islands and Cretaceous volcanism in the Western Pacific is revealed by a combination of ages and isotopic compositions, suggesting three simultaneously erupting hotspot locations. The ages of the Western Pacific volcanoes fit with three predicted hotspot tracks, while the isotopic compositions along each track have a limited range and are largely distinct from each other. However, until recently no data existed on volcanoes in the 30-60 Ma age range for these hotspot chains. New data collected on samples from volcanoes in Samoa and Tuvalu are now starting to provide a more complete geochemical record through time. In the Tuvalu Islands very limited dredging only provided a small number of samples. Isotopic compositions for these volcanoes correspond very well to the range in compositions observed for the Rurutu hotspot in the Cook-Austral Islands, and the Tuvalu Islands lie along the predicted hotspot track for the Rurutu hotspot. Similarly, a number of volcanoes with similar composition are found along the Samoan chain of volcanoes. Since plate motion models predicts that the Pacific Plate around Samoa passed over the Rurutu hotspot, the Samoan region represents a complex area of

  8. Proofreading neutralizes potential error hotspots in genetic code translation by transfer RNAs

    National Research Council Canada - National Science Library

    Zhang, Jingji; Ieong, Ka-Weng; Mellenius, Harriet; Ehrenberg, Måns

    2016-01-01

    .... Anomalously high initial misreading in vitro of near-cognate codons by tRNA(His) and tRNA(Glu) suggested potential error hotspots in protein synthesis, but in vivo data suggested their partial neutralization...

  9. HotSpot Wizard: a web server for identification of hot spots in protein engineering

    National Research Council Canada - National Science Library

    Pavelka, Antonin; Chovancova, Eva; Damborsky, Jiri

    2009-01-01

    HotSpot Wizard is a web server for automatic identification of 'hot spots' for engineering of substrate specificity, activity or enantioselectivity of enzymes and for annotation of protein structures...

  10. Characterizing local biological hotspots in the Gulf of Maine using remote sensing data

    Science.gov (United States)

    Ribera, Marta M.

    Researchers increasingly advocate the use of ecosystem-based management (EBM) for managing complex marine ecosystems. This approach requires managers to focus on processes and cross-scale interactions, rather than individual components. However, they often lack appropriate tools and data sources to pursue this change in management approach. One method that has been proposed to understand the ecological complexity inherent in marine ecosystems is the study of biological hotspots. Biological hotspots are locations where organisms from different trophic levels aggregate to feed on abundant supplies, and they are considered a first step toward understanding the processes driving spatial and temporal heterogeneity in marine systems. Biological hotspots are supported by phytoplankton aggregations, which are characterized by high spatial and temporal variability. As a result, methods developed to locate biological hotspots in relatively stable terrestrial systems are not well suited for more dynamic marine ecosystems. The main objective of this thesis is thus to identify and characterize local-scale biological hotspots in the western side of the Gulf of Maine. The first chapter describes a new methodological framework with the steps needed to locate these types of hotspots in marine ecosystems using remote sensing datasets. Then, in the second chapter these hotspots are characterized using a novel metric that uses time series information and spatial statistics to account for both the temporal variability and spatial structure of these marine aggregations. This metric redefines biological hotspots as areas with a high probability of exhibiting positive anomalies of productivity compared to the expected regional seasonal pattern. Finally, the third chapter compares the resulting biological hotspots to fishery-dependent abundance indices of surface and benthic predators to determine the effect of the location and magnitude of phytoplankton aggregations on the rest of the

  11. Secondary Hotspots in the South Pacific as a Result of Mantle Plumelets and Lithospheric Extension?

    Science.gov (United States)

    Koppers, A.; Staudigel, H.; Wijbrans, J.; Pringle, M.

    2003-12-01

    By far the largest number of secondary hotspots (cf. Courtillet et al., 2003) can be found in the "South Pacific Thermal and Isotopic Anomaly" (SOPITA) or "Superswell" region. Its Cretaceous counterpart is preserved in a large range of seamounts and guyots found in the "West Pacific Seamount Province" (WPSP). The seamounts in these regions display very distinct and long-lived isotopic signatures (Staudigel et al., 1991; Koppers et al., 2003) that can be used to combine source region chemistry and seamount geochronology to map out mantle melting anomalies over geological time. These mappings may resolve many important questions regarding the stationary character, continuity and longevity of the melting anomalies in the South Pacific mantle - and its secondary hotspots. Of all secondary hotspots that are currently active in the SOPITA we could identify only two hotspots that appear to be long-lived and that have Cretaceous counterparts in the WPSP. Plate reconstructions show that the "HIMU-type" Southern Wake seamounts may have originated from the Mangaia-Rurutu "hotline" in the Cook-Austral Islands, whereas the "EMI-type" Magellan seamounts may have originated from the Rarotonga hotspot. All other hotspots in the SOPITA and WPSP are short-lived (or intermittently active) as evidenced by the presence of numerous seamount trail "segments" representing no more than 10-40 Myr of volcanism. Our observations violate one or more assumptions of the classical Wilson-Morgan hotspot hypothesis: (1) none of the South Pacific hotspots are continuously active, (2) most are short-lived, (3) some show evidence of hotspot motion, and (4) most of them have poor linear age progressions, if any at all. On top of this we have evidence for volcanism along "hotlines" and the "superposition" of hotspots. The simple and elegant "hotspot" model, therefore, seems insufficient to explain the age distribution and source region characteristics of intra-plate volcanoes in the South Pacific. This

  12. Identification of a Hawaiian-Emperor Style Bend in the Tuvalu Segment of the Rurutu Hotspot

    Science.gov (United States)

    Finlayson, V.; Konter, J. G.; Konrad, K.; Price, A. A.; Koppers, A. A. P.; Jackson, M. G.

    2016-12-01

    Absolute plate motion (APM) models continue to improve with better characterization of drift of the two primary hotspots: Hawaii and Louisville. While APM models are more reliable from 50 Ma to modern times, uncertainty is introduced prior to 50 Ma due to hotspot track mismatch, uncertain location of the Louisville hotspot, and inter-hotspot drift as deduced from paleolatitude data [1,2]. Hawaiian hotspot drift contributed to a sharp 50 Ma Hawaiian-Emperor Bend (HEB) not reflected by the Louisville track. Adding a third HEB to the known long-lived hotspot tracks allows evaluation of APM uncertainty and hotspot drift. We present Pb-Sr-Nd-Hf isotopes and 40Ar/39Ar ages that complement existing Rurutu data [3], and for the first time trace the hotspot through its HEB back to 100 Ma. Our results reveal that the Tuvalu chain and some western Samoa seamounts define an age-progressive 63-42 Ma segment of the Rurutu track. The segment displays various mixtures between extreme endmember HIMU (206Pb/204Pb ≥ 20) and compositionally common FOZO [4,5] typical of Rurutu volcanism [3,6]. Other compositions also occur, differing in age and origin. In addition to the Rurutu-related seamounts, three seamounts were also sampled that have depleted mid-ocean ridge basalt compositions and ages that coincide with the opening of the underlying ocean basin. While distinct from the Rurutu hotspot, Samoan volcanoes overlapping 50-42 Ma Rurutu seamounts prevent straightforward identification of the HEB. Using age, composition, and location data, we project the Rurutu track with a moving hotspot APM model [7] from each age-dated seamount, defining the likeliest location with a cluster of projected HEBs. We find the Rurutu HEB occurs near the intersection of Tuvalu and western Samoa, providing a key constraint required to evaluate APM and inter-hotspot drift. 1. Koppers et al., (2012) doi:10.1038/ngeo1638 2. Tarduno et al., (2003) doi:10.1126/science.1086442 3. Konter et al., (2008) doi:10

  13. Sites for priority biodiversity conservation in the Caribbean Islands Biodiversity Hotspot

    OpenAIRE

    V. Anadon-Irizarry; D.C. Wege; A. Upgren; Young, R; Boom, B.; Leon, Y.M.; Y Arias; Koenig, K.; Morales, A.L.; Burke, W

    2012-01-01

    The Caribbean Islands Biodiversity Hotspot is exceptionally important for global biodiversity conservation due to high levels of species endemism and threat. A total of 755 Caribbean plant and vertebrate species are considered globally threatened, making it one of the top Biodiversity Hotspots in terms of threat levels. In 2009, Key Biodiversity Areas (KBAs) were identified for the Caribbean Islands through a regional-level analysis of accessible data and literature, followed by extensive nat...

  14. Re-evaluating the NO 2 hotspot over the South African Highveld

    Directory of Open Access Journals (Sweden)

    Alexandra S.M. Lourens

    2012-10-01

    Full Text Available Globally, numerous pollution hotspots have been identified using satellite-based instruments. One of these hotspots is the prominent NO2hotspot over the South African Highveld. The tropospheric NO2column density of this area is comparable to that observed for central and northern Europe, eastern North America and south-east Asia. The most well-known pollution source in this area is a large array of coal-fired power stations. Upon closer inspection, long-term means of satellite observations also show a smaller area, approximately 100 km west of the Highveld hotspot, with a seemingly less substantial NO2column density. This area correlates with the geographical location of the Johannesburg–Pretoria conurbation or megacity, one of the 40 largest metropolitan areas in the world. Ground-based measurements indicate that NO2concentrations in the megacity have diurnal peaks in the early morning and late afternoon, which coincide with peak traffic hours and domestic combustion. During these times, NO2concentrations in the megacity are higher than those in the Highveld hotspot. These diurnal NO2 peaks in the megacity have generally been overlooked by satellite observations because the satellites have fixed local overpass times that do not coincide with these peak periods. Consequently, the importance of NO2 over the megacity has been underestimated. We examined the diurnal cycles of NO2 ground-based measurements for the two areas – the megacity and the Highveld hotspot – and compared them with the satellite-based NO2 observations. Results show that the Highveld hotspot is accompanied by a second hotspot over the megacity, which is of significance for the more than 10 million people living in this megacity.

  15. Genetic assignment of large seizures of elephant ivory reveals Africa’s major poaching hotspots

    OpenAIRE

    Wasser, S. K.; Brown, L.; Mailand, C.; Mondol, S.; Clark, W.; Laurie, C.; Weir, B. S.

    2015-01-01

    Poaching of elephants is now occurring at rates that threaten African populations with extinction. Identifying the number and location of Africa’s major poaching hotspots may assist efforts to end poaching and facilitate recovery of elephant populations. We genetically assign origin to 28 large ivory seizures (≥0.5 metric tons) made between 1996 and 2014, also testing assignment accuracy. Results suggest that the major poaching hotspots in Africa may be currently concentrated in as few as two...

  16. Hydrologic and Undernourisment Trends In Food Insecurity Hotspots

    Science.gov (United States)

    Funk, C. C.; Mishra, V.; Davenport, F.

    2011-12-01

    As food prices rise, per capita harvested area diminishes and competition for limited resources mounts, the number of undernourished people has risen to more than a billion people. In this study, we target 80 potentially food insecure countries, examining hydrologic and undernourishment trends. For each country, primary cultivation areas are identified, and hydrologic variables extracted from simulations based on the Variable Infiltration Capacity model driven with the Princeton University climate data. Trends in runoff, soil moisture, precipitation, evapotranspiration, and temperature are evaluated. In addition to precipitation driven-aridity, the analysis also evaluates possible temperature-related shifts in sensible versus latent heat fluxes during energy-limited portions of the growing seasons. Changes in the timing and magnitude of streamflow are also investigated. The undernourishment trends are explored using the FAO percent under-nourished formulation, which determines the fraction of the population falling below a critical caloric threshold by using national food balance sheets (quantity) and a caloric distribution based on economic equality. Trends in quantity and equity, and their effects on undernourishment are evaluated, and vulnerability to price volatility quantified. Finally, a sub-set of countries facing both hydrologic declines and undernourishment increases are identified as food security hotspots.

  17. Atmospheric gravity waves in the Red Sea: a new hotspot

    KAUST Repository

    Magalhaes, J. M.

    2011-02-03

    The region of the Middle East around the Red Sea (between 32° E and 44° E longitude and 12° N and 28° N latitude) is a currently undocumented hotspot for atmospheric gravity waves (AGWs). Satellite imagery shows evidence that this region is prone to relatively high occurrence of AGWs compared to other areas in the world, and reveals the spatial characteristics of these waves. The favorable conditions for wave propagation in this region are illustrated with three typical cases of AGWs propagating in the lower troposphere over the sea. Using weakly nonlinear long wave theory and the observed characteristic wavelengths we obtain phase speeds which are consistent with those observed and typical for AGWs, with the Korteweg-de Vries theory performing slightly better than Benjamin-Davis-Acrivos-Ono theory as far as phase speeds are concerned. ERS-SAR and Envisat-ASAR satellite data analysis between 1993 and 2008 reveals signatures consistent with horizontally propagating large-scale internal waves. These signatures cover the entire Red Sea and are more frequently observed between April and September, although they also occur during the rest of the year. The region\\'s (seasonal) propagation conditions for AGWs, based upon average vertical atmospheric stratification profiles suggest that many of the signatures identified in the satellite images are atmospheric internal waves. © Author(s) 2011.

  18. Lead Polluted Hotspot: Environmental Implication of Unplanned Industrial Development

    Directory of Open Access Journals (Sweden)

    Rikta Sharmin Yousuf

    2016-06-01

    Full Text Available In Rayer Bazaar, different industries like tannery, plastic, textile, battery recycling industry etc. are increasing rapidly without considering the environmental issues and deterioration. Since chromium (Cr pollution of this area has been widely investigated due to the presence of tannery industries, this study was focused on examining other environmental factors. Field visits and analytical results of semi-quantitative and quantitative analysis as well as three dimensional excitation emission matrix spectroscopy (3DEEM of water, soil and vegetative tissues indicated that, the area is highly polluted in term of different environmental parameters and metal content. The extremely high lead (Pb content of the soil (1171.7 mg/kg in summer, 2157.1 mg/kg in winter and blackish materials of vegetative tissues (6585.6 mg/kg in summer, 1974.1 mg/kg in winter indicates excessive lead deposition of this area that makes it a lead polluted hotspot. One of the possible sources of the extremely high lead concentration is adjacent battery recycling industry and/or other industries surrounding this area. So it is urgent to take necessary steps to find out immediate options for possible mitigation.

  19. Isotopic identification of nitrogen hotspots across natural terrestrial ecosystems

    Directory of Open Access Journals (Sweden)

    E. Bai

    2012-08-01

    Full Text Available Nitrogen (N influences local biological processes, ecosystem productivity, the composition of the atmospheric-climate system, and the human endeavour as a whole. Here we use natural variations in N isotopes, coupled with two models, to trace global pathways of N loss from the land to the water and atmosphere. We show that denitrification accounts for approximately 35 % of total N losses from the natural soil, with NO, N2O, and N2 fluxes equal to 15.7 ± 4.7 Tg N yr−1, 10.2 ± 3.0 Tg N yr−1, and 21.0 ± 6.1 Tg N yr−1, respectively. Our analysis points to tropical regions as the major "hotspot" of nitrogen export from the terrestrial biosphere, accounting for 71 % of global N losses from the natural land surface. The poorly studied Congo Basin is further identified as one of the major natural sources of atmospheric N2O. Extra-tropical areas, by contrast, lose a greater fraction of N via leaching pathways (~77 % of total N losses than do tropical biomes, likely contributing to N limitations of CO2 uptake at higher latitudes. Our results provide an independent constraint on global models of the N cycle among different regions of the unfertilized biosphere.

  20. Automatic Hotspot and Sun Glint Detection in UAV Multispectral Images

    Directory of Open Access Journals (Sweden)

    Damian Ortega-Terol

    2017-10-01

    Full Text Available Last advances in sensors, photogrammetry and computer vision have led to high-automation levels of 3D reconstruction processes for generating dense models and multispectral orthoimages from Unmanned Aerial Vehicle (UAV images. However, these cartographic products are sometimes blurred and degraded due to sun reflection effects which reduce the image contrast and colour fidelity in photogrammetry and the quality of radiometric values in remote sensing applications. This paper proposes an automatic approach for detecting sun reflections problems (hotspot and sun glint in multispectral images acquired with an Unmanned Aerial Vehicle (UAV, based on a photogrammetric strategy included in a flight planning and control software developed by the authors. In particular, two main consequences are derived from the approach developed: (i different areas of the images can be excluded since they contain sun reflection problems; (ii the cartographic products obtained (e.g., digital terrain model, orthoimages and the agronomical parameters computed (e.g., normalized vegetation index-NVDI are improved since radiometric defects in pixels are not considered. Finally, an accuracy assessment was performed in order to analyse the error in the detection process, getting errors around 10 pixels for a ground sample distance (GSD of 5 cm which is perfectly valid for agricultural applications. This error confirms that the precision in the detection of sun reflections can be guaranteed using this approach and the current low-cost UAV technology.

  1. Predicting foraging hotspots for Yelkouan Shearwater in the Black Sea

    Science.gov (United States)

    Pérez-Ortega, María; İsfendiyaroğlu, Süreyya

    2017-07-01

    The Yelkouan shearwater (Puffinus yelkouan) is a vulnerable species endemic to the Mediterranean Region, but there is little information of its ecology particularly when at sea. In this study, we assessed the habitat use by Yelkouan shearwater in the Black Sea during the breeding (March-July) and non-breeding (August-February) periods of 2013, using boat-based surveys and shore-based counts. We created a species distribution model (SDM) based on the environmental variables that most accurately reflected the oceanographic habitat of this species in order to delineate foraging hotspots. Our habitat modelling analyses suggest that Yelkouan shearwaters respond to complex bio-physical coupling, as evidenced by their association with oceanographic variables. Foraging Yelkouan shearwaters mainly occurred on the western Black Sea continental shelf, indicating that Yelkouan shearwaters were foraging in shallow, cold and coastal waters. In the non-breeding period, Yelkouan Shearwater occurred beyond the Black Sea continental shelf, a wide pelagic extension of sea, indicating that shearwaters foraged in deep, warm and pelagic waters. These results are consistent with earlier studies, which identified the Black Sea as an important congregation site for Mediterranean Yelkouan shearwater populations outside the breeding season. This study demonstrates how the integration of boat-based survey data, shore-based counts and modelling can provide a wider understanding of the linkage between marine ecosystems that is mediated by marine megafauna such as pelagic seabirds.

  2. Kitobo Forest of Kenya, a unique hotspot of herpetofaunal diversity

    Directory of Open Access Journals (Sweden)

    Patrick K. Malonza

    2011-12-01

    Full Text Available Herpetologically, the remoteness of Kitobo forest in south-eastern Kenya has partly contributed to it remaining virtually un-explored until 2007. Three surveys were conducted in December 2007, December 2009 and April 2010 aimed at generating a comprehensive list of the forest amphibians and reptiles. Using largely timed-species count method, 13 species of amphibians representing eight families and 32 reptiles belonging to 11 families were recorded. Overall species diversity was highest during the 2007 sampling. The richness and abundance of amphibians was highest during the April 2010 sampling period when the amount of rainfall was also highest. The results of species accumulation curves of the three sampling periods did not plateau demonstrating that more species occur in this forest. Pressure on this forest fragment from the adjacent local people is high which in addition to the annual floods threatens its long-term survival. For example the distribution and abundance of some forest associated species such as the tree frogs Leptopelis flavomaculatus and Hyperolius puncticulatus appear to fluctuate with flood events and may decline in future. Considering the forest associated herpetofanua recorded, Kitobo forest is zoogeographically assignable to the East African coastal forest biodiversity hotspot. The documentation of high species richness and diversity in this small forest fragment strongly highlight its biodiversity importance and place it among the most important sites for the conservation of reptiles and amphibians in Kenya.

  3. Conservation businesses and conservation planning in a biological diversity hotspot.

    Science.gov (United States)

    Di Minin, Enrico; Macmillan, Douglas Craig; Goodman, Peter Styan; Escott, Boyd; Slotow, Rob; Moilanen, Atte

    2013-08-01

    The allocation of land to biological diversity conservation competes with other land uses and the needs of society for development, food, and extraction of natural resources. Trade-offs between biological diversity conservation and alternative land uses are unavoidable, given the realities of limited conservation resources and the competing demands of society. We developed a conservation-planning assessment for the South African province of KwaZulu-Natal, which forms the central component of the Maputaland-Pondoland-Albany biological diversity hotspot. Our objective was to enhance biological diversity protection while promoting sustainable development and providing spatial guidance in the resolution of potential policy conflicts over priority areas for conservation at risk of transformation. The conservation-planning assessment combined spatial-distribution models for 646 conservation features, spatial economic-return models for 28 alternative land uses, and spatial maps for 4 threats. Nature-based tourism businesses were competitive with other land uses and could provide revenues of >US$60 million/year to local stakeholders and simultaneously help meeting conservation goals for almost half the conservation features in the planning region. Accounting for opportunity costs substantially decreased conflicts between biological diversity, agricultural use, commercial forestry, and mining. Accounting for economic benefits arising from conservation and reducing potential policy conflicts with alternative plans for development can provide opportunities for successful strategies that combine conservation and sustainable development and facilitate conservation action. © 2013 Society for Conservation Biology.

  4. Pervasive defaunation of forest remnants in a tropical biodiversity hotspot.

    Science.gov (United States)

    Canale, Gustavo R; Peres, Carlos A; Guidorizzi, Carlos E; Gatto, Cassiano A Ferreira; Kierulff, Maria Cecília M

    2012-01-01

    Tropical deforestation and forest fragmentation are among the most important biodiversity conservation issues worldwide, yet local extinctions of millions of animal and plant populations stranded in unprotected forest remnants remain poorly explained. Here, we report unprecedented rates of local extinctions of medium to large-bodied mammals in one of the world's most important tropical biodiversity hotspots. We scrutinized 8,846 person-years of local knowledge to derive patch occupancy data for 18 mammal species within 196 forest patches across a 252,669-km(2) study region of the Brazilian Atlantic Forest. We uncovered a staggering rate of local extinctions in the mammal fauna, with only 767 from a possible 3,528 populations still persisting. On average, forest patches retained 3.9 out of 18 potential species occupancies, and geographic ranges had contracted to 0-14.4% of their former distributions, including five large-bodied species that had been extirpated at a regional scale. Forest fragments were highly accessible to hunters and exposed to edge effects and fires, thereby severely diminishing the predictive power of species-area relationships, with the power model explaining only ~9% of the variation in species richness per patch. Hence, conventional species-area curves provided over-optimistic estimates of species persistence in that most forest fragments had lost species at a much faster rate than predicted by habitat loss alone.

  5. Pervasive defaunation of forest remnants in a tropical biodiversity hotspot.

    Directory of Open Access Journals (Sweden)

    Gustavo R Canale

    Full Text Available Tropical deforestation and forest fragmentation are among the most important biodiversity conservation issues worldwide, yet local extinctions of millions of animal and plant populations stranded in unprotected forest remnants remain poorly explained. Here, we report unprecedented rates of local extinctions of medium to large-bodied mammals in one of the world's most important tropical biodiversity hotspots. We scrutinized 8,846 person-years of local knowledge to derive patch occupancy data for 18 mammal species within 196 forest patches across a 252,669-km(2 study region of the Brazilian Atlantic Forest. We uncovered a staggering rate of local extinctions in the mammal fauna, with only 767 from a possible 3,528 populations still persisting. On average, forest patches retained 3.9 out of 18 potential species occupancies, and geographic ranges had contracted to 0-14.4% of their former distributions, including five large-bodied species that had been extirpated at a regional scale. Forest fragments were highly accessible to hunters and exposed to edge effects and fires, thereby severely diminishing the predictive power of species-area relationships, with the power model explaining only ~9% of the variation in species richness per patch. Hence, conventional species-area curves provided over-optimistic estimates of species persistence in that most forest fragments had lost species at a much faster rate than predicted by habitat loss alone.

  6. Near-island biological hotspots in barren ocean basins

    Science.gov (United States)

    Gove, Jamison M.; McManus, Margaret A.; Neuheimer, Anna B.; Polovina, Jeffrey J.; Drazen, Jeffrey C.; Smith, Craig R.; Merrifield, Mark A.; Friedlander, Alan M.; Ehses, Julia S.; Young, Charles W.; Dillon, Amanda K.; Williams, Gareth J.

    2016-01-01

    Phytoplankton production drives marine ecosystem trophic-structure and global fisheries yields. Phytoplankton biomass is particularly influential near coral reef islands and atolls that span the oligotrophic tropical oceans. The paradoxical enhancement in phytoplankton near an island-reef ecosystem—Island Mass Effect (IME)—was first documented 60 years ago, yet much remains unknown about the prevalence and drivers of this ecologically important phenomenon. Here we provide the first basin-scale investigation of IME. We show that IME is a near-ubiquitous feature among a majority (91%) of coral reef ecosystems surveyed, creating near-island ‘hotspots' of phytoplankton biomass throughout the upper water column. Variations in IME strength are governed by geomorphic type (atoll vs island), bathymetric slope, reef area and local human impacts (for example, human-derived nutrient input). These ocean oases increase nearshore phytoplankton biomass by up to 86% over oceanic conditions, providing basal energetic resources to higher trophic levels that support subsistence-based human populations. PMID:26881874

  7. Automatic Hotspot and Sun Glint Detection in UAV Multispectral Images.

    Science.gov (United States)

    Ortega-Terol, Damian; Hernandez-Lopez, David; Ballesteros, Rocio; Gonzalez-Aguilera, Diego

    2017-10-15

    Last advances in sensors, photogrammetry and computer vision have led to high-automation levels of 3D reconstruction processes for generating dense models and multispectral orthoimages from Unmanned Aerial Vehicle (UAV) images. However, these cartographic products are sometimes blurred and degraded due to sun reflection effects which reduce the image contrast and colour fidelity in photogrammetry and the quality of radiometric values in remote sensing applications. This paper proposes an automatic approach for detecting sun reflections problems (hotspot and sun glint) in multispectral images acquired with an Unmanned Aerial Vehicle (UAV), based on a photogrammetric strategy included in a flight planning and control software developed by the authors. In particular, two main consequences are derived from the approach developed: (i) different areas of the images can be excluded since they contain sun reflection problems; (ii) the cartographic products obtained (e.g., digital terrain model, orthoimages) and the agronomical parameters computed (e.g., normalized vegetation index-NVDI) are improved since radiometric defects in pixels are not considered. Finally, an accuracy assessment was performed in order to analyse the error in the detection process, getting errors around 10 pixels for a ground sample distance (GSD) of 5 cm which is perfectly valid for agricultural applications. This error confirms that the precision in the detection of sun reflections can be guaranteed using this approach and the current low-cost UAV technology.

  8. Pervasive Defaunation of Forest Remnants in a Tropical Biodiversity Hotspot

    Science.gov (United States)

    Canale, Gustavo R.; Peres, Carlos A.; Guidorizzi, Carlos E.; Gatto, Cassiano A. Ferreira; Kierulff, Maria Cecília M.

    2012-01-01

    Tropical deforestation and forest fragmentation are among the most important biodiversity conservation issues worldwide, yet local extinctions of millions of animal and plant populations stranded in unprotected forest remnants remain poorly explained. Here, we report unprecedented rates of local extinctions of medium to large-bodied mammals in one of the world's most important tropical biodiversity hotspots. We scrutinized 8,846 person-years of local knowledge to derive patch occupancy data for 18 mammal species within 196 forest patches across a 252,669-km2 study region of the Brazilian Atlantic Forest. We uncovered a staggering rate of local extinctions in the mammal fauna, with only 767 from a possible 3,528 populations still persisting. On average, forest patches retained 3.9 out of 18 potential species occupancies, and geographic ranges had contracted to 0–14.4% of their former distributions, including five large-bodied species that had been extirpated at a regional scale. Forest fragments were highly accessible to hunters and exposed to edge effects and fires, thereby severely diminishing the predictive power of species-area relationships, with the power model explaining only ∼9% of the variation in species richness per patch. Hence, conventional species-area curves provided over-optimistic estimates of species persistence in that most forest fragments had lost species at a much faster rate than predicted by habitat loss alone. PMID:22905103

  9. Rare Decays With LHCb

    CERN Document Server

    Mancinelli, Giampiero

    2012-01-01

    Rare decays involving leptons or photons in the final states are studied using 1.0 fb^{-1} of pp collisions at a centre-of-mass energy of sqrt{s}=7TeV collected by the LHCb experiment in 2011. We present results of measurements of branching ratios, angular distributions, and isospin asymmetries obtained using this data sample.

  10. Afganistan and rare earths

    Directory of Open Access Journals (Sweden)

    Emilian M. Dobrescu

    2013-05-01

    Full Text Available On our planet, over a quarter of new technologies for the economic production of industrial goods, are using rare earths, which are also called critical minerals and industries that rely on these precious items being worth of an estimated nearly five trillion dollars, or 5 percent of world gross domestic product. In the near future, competition will increase for the control of rare earth minerals embedded in high-tech products. Rare minerals are in the twenty-first century what oil accounted for in the twentieth century and coal in the nineteenth century: the engine of a new industrial revolution. Future energy will be produced increasingly by more sophisticated technological equipment based not just on steel and concrete, but incorporating significant quantities of metals and rare earths. Widespread application of these technologies will result in an exponential increase in demand for such minerals, and what is worrying is that minerals of this type are almost nowhere to be found in Europe and in other industrialized countries in the world, such as U.S. and Japan, but only in some Asian countries, like China and Afghanistan.

  11. Rare Kaon Decays

    Science.gov (United States)

    Bryman, Douglas

    2010-06-01

    The prospects for measuring the ultra-rare decays K^ + -> π ^ + ν /line ν and KL0 -> π 0 ν /line ν are discussed. Several new experiments are being constructed or have been proposed at existing facilities and ideas for reaching very high precision experiments at a future high intensity proton source like Project X ICD2 are under discussion.

  12. Surveillance of rare cancers

    NARCIS (Netherlands)

    van der Zwan, Johannes Martinus

    2016-01-01

    The widespread incidence and effects of cancer have led to a growing development in cancer prevention in the form of screening and research programs and cancer registries. Because of the low number of patients with rare cancers this improvement is not applied to the same extent to all cancer

  13. Magnetic rare earth superlattices

    DEFF Research Database (Denmark)

    Majkrzak, C.F.; Kwo, J.; Hong, M.

    1991-01-01

    Advances in molecular beam epitaxy deposition techniques have recently made it possible to grow, an atomic plane at a time, single crystalline superlattices composed of alternating layers of a magnetic rare earth, such as Gd, Dy, Ho, or Er, and metallic Y, which has an identical chemical structure...

  14. A physical map of the papaya genome with integrated genetic map and genome sequence

    Directory of Open Access Journals (Sweden)

    Luo Ming-Cheng

    2009-08-01

    Full Text Available Abstract Background Papaya is a major fruit crop in tropical and subtropical regions worldwide and has primitive sex chromosomes controlling sex determination in this trioecious species. The papaya genome was recently sequenced because of its agricultural importance, unique biological features, and successful application of transgenic papaya for resistance to papaya ringspot virus. As a part of the genome sequencing project, we constructed a BAC-based physical map using a high information-content fingerprinting approach to assist whole genome shotgun sequence assembly. Results The physical map consists of 963 contigs, representing 9.4× genome equivalents, and was integrated with the genetic map and genome sequence using BAC end sequences and a sequence-tagged high-density genetic map. The estimated genome coverage of the physical map is about 95.8%, while 72.4% of the genome was aligned to the genetic map. A total of 1,181 high quality overgo (overlapping oligonucleotide probes representing conserved sequences in Arabidopsis and genetically mapped loci in Brassica were anchored on the physical map, which provides a foundation for comparative genomics in the Brassicales. The integrated genetic and physical map aligned with the genome sequence revealed recombination hotspots as well as regions suppressed for recombination across the genome, particularly on the recently evolved sex chromosomes. Suppression of recombination spread to the adjacent region of the male specific region of the Y chromosome (MSY, and recombination rates were recovered gradually and then exceeded the genome average. Recombination hotspots were observed at about 10 Mb away on both sides of the MSY, showing 7-fold increase compared with the genome wide average, demonstrating the dynamics of recombination of the sex chromosomes. Conclusion A BAC-based physical map of papaya was constructed and integrated with the genetic map and genome sequence. The integrated map facilitated

  15. How and when plume zonation appeared during the 132 Myr evolution of the Tristan Hotspot

    Science.gov (United States)

    Hoernle, Kaj; Rohde, Joana; Hauff, Folkmar; Garbe-Schönberg, Dieter; Homrighausen, Stephan; Werner, Reinhard; Morgan, Jason P.

    2015-07-01

    Increasingly, spatial geochemical zonation, present as geographically distinct, subparallel trends, is observed along hotspot tracks, such as Hawaii and the Galapagos. The origin of this zonation is currently unclear. Recently zonation was found along the last ~70 Myr of the Tristan-Gough hotspot track. Here we present new Sr-Nd-Pb-Hf isotope data from the older parts of this hotspot track (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the Etendeka and Parana flood basalts erupted at the initiation of the hotspot track. We show that only the enriched Gough, but not the less-enriched Tristan, component is present in the earlier (70-132 Ma) history of the hotspot. Here we present a model that can explain the temporal evolution and origin of plume zonation for both the Tristan-Gough and Hawaiian hotspots, two end member types of zoned plumes, through processes taking place in the plume sources at the base of the lower mantle.

  16. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

    DEFF Research Database (Denmark)

    Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.

    2014-01-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells ...... [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04–21.37; validation data: HR, 1.59, 95% CI, 1.05–2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution.......The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...

  17. Full genome characterization of human influenza A/H3N2 isolates from Asian countries reveals a rare amantadine resistance-conferring mutation and novel PB1-F2 polymorphisms

    Directory of Open Access Journals (Sweden)

    Hassan eZaraket

    2016-03-01

    Full Text Available Influenza A viruses evolve at a high rate requiring continuous monitoring to maintain the efficacy of vaccines and antiviral drugs. We performed next generation sequencing analysis of 100 influenza A/H3N2 isolates collected in four Asian countries (Japan, Lebanon, Myanmar, and Vietnam during 2012-2015. Phylogenetic analysis revealed several reassortment events leading to the circulation of multiple clades within the same season. This was particularly evident during the 2013 and 2013/2014 seasons. Importantly, our data showed that certain lineages appeared to be fitter and were able to persist into the following season. The majority of A/H3N2 viruses continued to harbor the M2-S31N mutation conferring amantadine-resistance. In addition, an S31D mutation in the M2-protein, conferring a similar level of resistance as the S31N mutation, was detected in three isolates obtained in Japan during the 2014/2015 season. None of the isolates possessed the NA-H274Y mutation conferring oseltamivir-resistance, though a few isolates were found to contain mutations at the catalytic residue 151 (D151A/G/N or V of the NA protein. These variations did not alter the susceptibility to neuraminidase inhibitors and were not detected in the original clinical specimens, suggesting that they had been acquired during their passage in MDCK cells. Novel polymorphisms were detected in the PB1-F2 open-reading frame resulting in truncations in the protein of 24-34 aminoacids in length. Thus, this study has demonstrated the utility of monitoring the full genome of influenza viruses to allow the detection of the potentially fittest lineages. This enhances our ability to predict the strain(s most likely to persist into the following seasons and predict the potential degree of vaccine match or mismatch with the seasonal influenza season for that year. This will enable the public health and clinical teams to prepare for any related healthcare burden, depending on whether the vaccine

  18. The research progress of genomic selection in livestock.

    Science.gov (United States)

    Li, Hong-wei; Wang, Rui-jun; Wang, Zhi-ying; Li, Xue-wu; Wang, Zhen-yu; Yanjun, Zhang; Rui, Su; Zhihong, Liu; Jinquan, Li

    2017-05-20

    With the development of gene chip and breeding technology, genomic selection in plants and animals has become research hotspots in recent years. Genomic selection has been extensively applied to all kinds of economic livestock, due to its high accuracy, short generation intervals and low breeding costs. In this review, we summarize genotyping technology and the methods for genomic breeding value estimation, the latter including the least square method, RR-BLUP, GBLUP, ssGBLUP, BayesA and BayesB. We also cover basic principles of genomic selection and compare their genetic marker ranges, genomic selection accuracy and operational speed. In addition, we list common indicators, methods and influencing factors that are related to genomic selection accuracy. Lastly, we discuss latest applications and the current problems of genomic selection at home and abroad. Importantly, we envision future status of genomic selection research, including multi-trait and multi-population genomic selection, as well as impact of whole genome sequencing and dominant effects on genomic selection. This review will provide some venues for other breeders to further understand genome selection.

  19. Rare Decays at LHCb

    Science.gov (United States)

    Hall, Sam

    2014-04-01

    Rare decays of beauty and charm hadrons provide an effective method of testing the Standard Model and probing possible new physics scenarios. The LHCb experiment has published a variety of interesting results in this field, some of which are presented here. In particular the measurements of the branching fractions of B(s)0 → μ+μ- which, in combination with CMS, resulted in the first observation of the Bs0 → μ+μ- decay. Other topics include searches for the rare decay D0 → μ+μ-, the lepton flavour violating decays B(s)0 → e±μ∓, and the observation of the ψ(4160) resonance in the region of low recoil in B+ → K+μ+μ- decay. New results on the angular analysis of the decay B0 → K*0μ+μ- with form factor independent observables are also shown.

  20. Rare Decays at LHCb

    Directory of Open Access Journals (Sweden)

    Hall Sam

    2014-04-01

    Full Text Available Rare decays of beauty and charm hadrons provide an effective method of testing the Standard Model and probing possible new physics scenarios. The LHCb experiment has published a variety of interesting results in this field, some of which are presented here. In particular the measurements of the branching fractions of B(s0 → μ+μ− which, in combination with CMS, resulted in the first observation of the Bs0 → μ+μ− decay. Other topics include searches for the rare decay D0 → μ+μ−, the lepton flavour violating decays B(s0 → e±μ∓, and the observation of the ψ(4160 resonance in the region of low recoil in B+ → K+μ+μ− decay. New results on the angular analysis of the decay B0 → K*0μ+μ− with form factor independent observables are also shown.

  1. Rainfall-induced landslides in Europe: hotspots and thresholds (Invited)

    Science.gov (United States)

    Cepeda, J.; Jaedicke, C.; Nadim, F.; Kalsnes, B.

    2010-12-01

    This contribution presents preliminary results of the European project SafeLand. SafeLand is a large-scale integrating collaborative research project on landslide risks in Europe, funded by the Seventh Framework Programme for research and technological development (FP7) of the European Commission. SafeLand was launched in May 2009 and will run for three years. The project team, which comprises 27 institutions from 12 European countries, is coordinated by the International Centre for Geohazards (ICG) in Norway. SafeLand aims to develop and implement an integrated and comprehensive approach to help and guide decision-making in connection with mitigation of landslide risks. Quantifying the effects of global change (changes in demography and climate change) on evolution of landslide risk in Europe is one of the main goals of SafeLand. The methodologies are tested in selected hazard and risk "hotspots” in Europe, in turn improving knowledge, methodologies and integration strategies for the management of landslide risk. The present contribution is focused on two components of SafeLand: (1) the identification of landslide hazard and risk hotspots and (2) the estimation and assessment of rainfall thresholds for triggering of landslides. Hotspots of landslide hazard and risk were identified by an objective GIS-based analysis. The results show clearly where landslide pose the largest hazard in Europe and the objective approach allows a ranking of the countries by exposed area and population. In absolute numbers, Italy is the country with the highest amount of area and population exposed. Relative to absolute number of inhabitants and area, small alpine countries such as Lichtenstein and Montenegro score highest where as much as 40% of the population could be exposed. It is obvious that the type and quality of the input data are decisive for the quality of the results. Especially the estimation of extreme precipitation events needs improvement. These preliminary results are

  2. Multisectoral Climate Impact Hotspots in a Warming World

    Science.gov (United States)

    Piontek, Franziska; Mueller, Christoph; Pugh, Thomas A. M.; Clark, Douglas B.; Deryng, Delphine; Elliott, Joshua; deJesusColonGonzalez, Felipe; Floerke, Martina; Folberth, Christian; Franssen, Wietse; hide

    2014-01-01

    The impacts of global climate change on different aspects of humanity's diverse life-support systems are complex and often difficult to predict. To facilitate policy decisions on mitigation and adaptation strategies, it is necessary to understand, quantify, and synthesize these climate-change impacts, taking into account their uncertainties. Crucial to these decisions is an understanding of how impacts in different sectors overlap, as overlapping impacts increase exposure, lead to interactions of impacts, and are likely to raise adaptation pressure. As a first step we develop herein a framework to study coinciding impacts and identify regional exposure hotspots. This framework can then be used as a starting point for regional case studies on vulnerability and multifaceted adaptation strategies. We consider impacts related to water, agriculture, ecosystems, and malaria at different levels of global warming. Multisectoral overlap starts to be seen robustly at a mean global warming of 3 degC above the 1980-2010 mean, with 11% of the world population subject to severe impacts in at least two of the four impact sectors at 4 degC. Despite these general conclusions, we find that uncertainty arising from the impact models is considerable, and larger than that from the climate models. In a low probability-high impact worst-case assessment, almost the whole inhabited world is at risk for multisectoral pressures. Hence, there is a pressing need for an increased research effort to develop a more comprehensive understanding of impacts, as well as for the development of policy measures under existing uncertainty.

  3. Fish ladders: safe fish passage or hotspot for predation?

    Directory of Open Access Journals (Sweden)

    Angelo Antonio Agostinho

    Full Text Available Fish ladders are a strategy for conserving biodiversity, as they can provide connectivity between fragmented habitats and reduce predation on shoals that accumulate immediately below dams. Although the impact of predation downstream of reservoirs has been investigated, especially in juvenile salmonids during their downstream movements, nothing is known about predation on Neotropical fish in the attraction and containment areas commonly found in translocation facilities. This study analysed predation in a fish passage system at the Lajeado Dam on the Tocantins River in Brazil. The abundance, distribution, and the permanence (time spent of large predatory fish along the ladder, the injuries imposed by piranhas during passage and the presence of other vertebrate predators were investigated. From December 2002 to October 2003, sampling was conducted in four regions (downstream, along the ladder, in the forebay, and upstream of the reservoir using gillnets, cast nets and counts or visual observations. The captured fish were tagged with thread and beads, and any mutilations were registered. Fish, birds and dolphins were the main predator groups observed, with a predominance of the first two groups. The entrance to the ladder, in the downstream region, was the area with the highest number of large predators and was the only region with relevant non-fish vertebrates. The main predatory fish species were Rhaphiodon vulpinus, Hydrolycus armatus, and Serrasalmus rhombeus. Tagged individuals were detected predating along the ladder for up to 90 days. Mutilations caused by Serrasalmus attacks were noted in 36% of species and 4% of individuals at the top of the ladder. Our results suggested that the high density of fish in the restricted ladder environment, which is associated with injuries suffered along the ladder course and the presence of multiple predator groups with different predation strategies, transformed the fish corridor into a hotspot for

  4. A framework for identifying carbon hotspots and forest management drivers

    Science.gov (United States)

    Nilesh Timilsina; Francisco J. Escobedo; Wendell P. Cropper; Amr Abd-Elrahman; Thomas Brandeis; Sonia Delphin; Samuel Lambert

    2013-01-01

    Spatial analyses of ecosystem system services that are directly relevant to both forest management decision making and conservation in the subtropics are rare. Also, frameworks that identify and map carbon stocks and corresponding forest management drivers using available regional, national, and international-level forest inventory datasets could provide insights into...

  5. Generation of mutation hotspots in ageing bacterial colonies

    DEFF Research Database (Denmark)

    Sekowska, Agnieszka; Wendel, Sofie; Nørholm, Morten

    How do ageing bacterial colonies generate adaptive mutants? Over a period of two months, we isolated on ageing colonies outgrowing mutants able to use a new carbon source, and sequenced their genomes. This allowed us to uncover exquisite details on the molecular mechanism behind their adaptation:...

  6. Predictable hotspots and foraging habitat of the endangered short-tailed albatross (Phoebastria albatrus) in the North Pacific: Implications for conservation

    Science.gov (United States)

    Piatt, John F.; Wetzel, J.; Bell, K.; DeGange, A.R.; Balogh, G.R.; Drew, G.S.; Geernaert, T.; Ladd, C.; Byrd, G.V.

    2006-01-01

    The short-tailed albatross (Phoebastria albatrus) is a rare and endangered seabird that ranges widely over the northern North Pacific. Populations are slowly recovering but birds face several threats at sea, in particular the incidental capture of birds in long-line fisheries. Conservation efforts are hampered by a lack of information about the at-sea distribution of this species, especially knowledge of where it may predictably co-occur with long-line fishing effort. During 18 years of transiting the Aleutian Islands Unit of the Alaska Maritime National Wildlife Refuge on a research vessel, we observed short-tailed albatross on 65 occasions. They were consistently observed near Ingenstrem Rocks (Buldir Pass) in the western Aleutians and near Seguam Pass in the central Aleutians. Based on the oceanographic characteristics of the locations where we saw most of the birds, we hypothesized that short-tailed albatross “hotspots” were located where tidal currents and steep bottom topography generate strong vertical mixing along the Aleutian Archipelago. As a test of this hypothesis, we analyzed a database containing 1432 opportunistic observations of 2463 short-tailed albatross at sea in the North Pacific. These data showed that short-tailed albatross were closely associated with shelf-edge habitats throughout the northern Gulf of Alaska and Bering Sea. In addition to Ingenstrem Rocks and Seguam Pass, important hotspots for short-tailed albatross in the Aleutians included Near Strait, Samalga Pass, and the shelf-edge south of Umnak/Unalaska islands. In the Bering Sea, hotspots were located along margins of Zhemchug, St. Matthews and Pervenets canyons. Because these short-tailed albatross hotspots are predictable, they are also protectable by regulation of threatening activities at local spatial scales.

  7. Evolutionary melting pots: a biodiversity hotspot shaped by ring diversifications around the Black Sea in the Eastern tree frog (Hyla orientalis).

    Science.gov (United States)

    Dufresnes, Christophe; Litvinchuk, Spartak N; Leuenberger, Julien; Ghali, Karim; Zinenko, Oleksandr; Stöck, Matthias; Perrin, Nicolas

    2016-09-01

    Hotspots of intraspecific genetic diversity, which are of primary importance for the conservation of species, have been associated with glacial refugia, that is areas where species survived the Quaternary climatic oscillations. However, the proximate mechanisms generating these hotspots remain an open issue. Hotspots may reflect the long-term persistence of large refugial populations; alternatively, they may result from allopatric differentiation between small and isolated populations, that later admixed. Here, we test these two scenarios in a widely distributed species of tree frog, Hyla orientalis, which inhabits Asia Minor and southeastern Europe. We apply a fine-scale phylogeographic survey, combining fast-evolving mitochondrial and nuclear markers, with a dense sampling throughout the range, as well as ecological niche modelling, to understand what shaped the genetic variation of this species. We documented an important diversity centre around the Black Sea, composed of multiple allopatric and/or parapatric diversifications, likely driven by a combination of Pleistocene climatic fluctuations and complex regional topography. Remarkably, this diversification forms a ring around the Black Sea, from the Caucasus through Anatolia and eastern Europe, with terminal forms coming into contact and partially admixing in Crimea. Our results support the view that glacial refugia generate rather than host genetic diversity and can also function as evolutionary melting pots of biodiversity. Moreover, we report a new case of ring diversification, triggered by a large, yet cohesive dispersal barrier, a very rare situation in nature. Finally, we emphasize the Black Sea region as an important centre of intraspecific diversity in the Palearctic with implications for conservation. © 2016 John Wiley & Sons Ltd.

  8. Where the wild things are: Predicting hotspots of seabird aggregations in the California Current System

    Science.gov (United States)

    Nur, N.; Jahncke, J.; Herzog, M.P.; Howar, J.; Hyrenbach, K.D.; Zamon, J.E.; Ainley, D.G.; Wiens, J.A.; Morgan, K.; Balance, L.T.; Stralberg, D.

    2011-01-01

    Marine Protected Areas (MPAs) provide an important tool for conservation of marine ecosystems. To be most effective, these areas should be strategically located in a manner that supports ecosystem function. To inform marine spatial planning and support strategic establishment of MPAs within the California Current System, we identified areas predicted to support multispecies aggregations of seabirds ("hotspot????). We developed habitat-association models for 16 species using information from at-sea observations collected over an 11-year period (1997-2008), bathymetric data, and remotely sensed oceanographic data for an area from north of Vancouver Island, Canada, to the USA/Mexico border and seaward 600 km from the coast. This approach enabled us to predict distribution and abundance of seabirds even in areas of few or no surveys. We developed single-species predictive models using a machine-learning algorithm: bagged decision trees. Single-species predictions were then combined to identify potential hotspots of seabird aggregation, using three criteria: (1) overall abundance among species, (2) importance of specific areas ("core area????) to individual species, and (3) predicted persistence of hotspots across years. Model predictions were applied to the entire California Current for four seasons (represented by February, May, July, and October) in each of 11 years. Overall, bathymetric variables were often important predictive variables, whereas oceanographic variables derived from remotely sensed data were generally less important. Predicted hotspots often aligned with currently protected areas (e.g., National Marine Sanctuaries), but we also identified potential hotspots in Northern California/Southern Oregon (from Cape Mendocino to Heceta Bank), Southern California (adjacent to the Channel Islands), and adjacent to Vancouver Island, British Columbia, that are not currently included in protected areas. Prioritization and identification of multispecies hotspots

  9. Identifying ecosystem service hotspots for environmental management in Durban, South Africa

    Directory of Open Access Journals (Sweden)

    Rashieda Davids

    2016-11-01

    Full Text Available Background: Despite considerable research into the importance of ecosystem services, little has been achieved in translating such research into management action. In an urban context where numerous pressures on ecosystem services exist, the identification and management of priority ecosystem services areas are vital to ensure the ongoing provision of these services.Method: To identify opportunities for securing a sustainable supply of ecosystem services for the city of Durban, this paper identifies ecosystem service priority areas, called hotspots, and assesses their spatial congruence with critical biodiversity areas (CBAs, conservation areas, the Durban Metropolitan Open Space System (D’MOSS and land ownership categories, using spatial overlap and correlation analyses. Hotspots for 13 ecosystem services were identified and analysed, including carbon storage, nutrient retention, sediment retention, water supply and flood attenuation.Results: The study found generally weak correlations between ecosystem service hotspots and CBAs and conservation areas. On average, 30% of the 13 ecosystem services hotspots were located within terrestrial CBAs, 51% within the D’MOSS, with nominal overlaps of 0.3%, 3.9% and 5.07% within estuaries and freshwater CBAs and conservation areas, respectively. The majority of ecosystem service hotspots were located within communally (41% or privately owned (27% lands.Conclusion: The results indicated that substantial portions of hotspot areas lie outside of formally regulated and managed conservation areas and remain vulnerable to human impact and habitat degradation. The study identified management areas and options that could yield maximum benefits; including the need for the development of an ecosystem services management and protection strategy, the selection of areas for co-management of ecosystem service hotspots and CBAs and the need for collaborative management.

  10. Hotspots of species richness, threat and endemism for terrestrial vertebrates in SW Europe

    Science.gov (United States)

    Pascual, López-López; Luigi, Maiorano; Alessandra, Falcucci; Emilio, Barba; Luigi, Boitani

    2011-09-01

    The Mediterranean basin, and the Iberian Peninsula in particular, represent an outstanding "hotspot" of biological diversity with a long history of integration between natural ecosystems and human activities. Using deductive distribution models, and considering both Spain and Portugal, we downscaled traditional range maps for terrestrial vertebrates (amphibians, breeding birds, mammals and reptiles) to the finest possible resolution with the data at hand, and we identified hotspots based on three criteria: i) species richness; ii) vulnerability, and iii) endemism. We also provided a first evaluation of the conservation status of biodiversity hotspots based on these three criteria considering both existing and proposed protected areas (i.e., Natura 2000). For the identification of hotspots, we used a method based on the cumulative distribution functions of species richness values. We found no clear surrogacy among the different types of hotspots in the Iberian Peninsula. The most important hotspots (considering all criteria) are located in the western and southwestern portions of the study area, in the Mediterranean biogeographical region. Existing protected areas are not specifically concentrated in areas of high species richness, with only 5.2% of the hotspots of total richness being currently protected. The Natura 2000 network can potentially constitute an important baseline for protecting vertebrate diversity in the Iberian Peninsula although further improvements are needed. We suggest taking a step forward in conservation planning in the Mediterranean basin, explicitly considering the history of the region as well as its present environmental context. This would allow moving from traditional reserve networks (conservation focused on "patterns") to considerations about the "processes" that generated present biodiversity.

  11. Comparative genomics in chicken and Pekin duck using FISH mapping and microarray analysis

    Directory of Open Access Journals (Sweden)

    Fowler Katie E

    2009-08-01

    Full Text Available Abstract Background The availability of the complete chicken (Gallus gallus genome sequence as well as a large number of chicken probes for fluorescent in-situ hybridization (FISH and microarray resources facilitate comparative genomic studies between chicken and other bird species. In a previous study, we provided a comprehensive cytogenetic map for the turkey (Meleagris gallopavo and the first analysis of copy number variants (CNVs in birds. Here, we extend this approach to the Pekin duck (Anas platyrhynchos, an obvious target for comparative genomic studies due to its agricultural importance and resistance to avian flu. Results We provide a detailed molecular cytogenetic map of the duck genome through FISH assignment of 155 chicken clones. We identified one inter- and six intrachromosomal rearrangements between chicken and duck macrochromosomes and demonstrated conserved synteny among all microchromosomes analysed. Array comparative genomic hybridisation revealed 32 CNVs, of which 5 overlap previously designated "hotspot" regions between chicken and turkey. Conclusion Our results suggest extensive conservation of avian genomes across 90 million years of evolution in both macro- and microchromosomes. The data on CNVs between chicken and duck extends previous analyses in chicken and turkey and supports the hypotheses that avian genomes contain fewer CNVs than mammalian genomes and that genomes of evolutionarily distant species share regions of copy number variation ("CNV hotspots". Our results will expedite duck genomics, assist marker development and highlight areas of interest for future evolutionary and functional studies.

  12. Hotspots trails below Arabia and the Horn of Africa: new insight about the initiation of the Red Sea rift

    Science.gov (United States)

    de Gouveia, Sophie Vicente; Besse, Jean; Frizon de Lamotte, Dominique; Greff-Lefftz, Marianne; Gueydan, Frédéric; Lescanne, Marc; Leparmentier, François

    2017-04-01

    The past trajectories followed by three present-day hotspots, Afar, East-Africa and Lake-Victoria were computed using a hotspot reference frame. The tracks are most of time situated under continental crust, which is known to strongly filter surface plume activity. We thus look for surface markers of their ancient existence, such as volcanism, doming, geochemistry and finally by a compilation of heat flow data issued from petroleum wells. Hence, the East-Africa hotspot is episodically warranted up to at least 110 Ma, the Afar one to about 90 Ma and the Lake-Victoria hotspot activity appears more recent and is attested until the Cenozoic. According to the hotspot trajectories, two important issues are addressed. Firstly, the Afar hotspot was situated 1000 km on the north-east of the Ethiopian-Yemen traps at 32 Ma, too far to be responsible for it. The trigger was most probably the East-Africa hotspot situated at the right location at that time. Secondly, we address the question of the Arabian Plate formation as the result of the coeval opening of both the Gulf of Aden and the Red Sea in a context characterized by extensional forces linked to the Neo-Tethys slab-pull: (1) the Gulf of Aden overlaps on inherited Mesozoic extensional basin between two weak zones, the Carlsberg ridge's end and a hotspot heated area; while (2) the Red Sea develops on the previous hotspot track location suggesting a causal relationship between a thermal weakening of the lithosphere and the rift initiation. To test this idea, we performed a numerical simulation in order to describe the lithosphere strength evolution when exposed to a hotspot heating combined with tectonic forces along the East-Africa hotspot track from 110 Ma until the beginning of the rifting at early Oligocene time. Preliminary results suggest that the Red Sea rift was compelled to evolve in a specific area pre-weakened by a hotspot impact.

  13. Five-way smoking status classification using text hot-spot identification and error-correcting output codes

    National Research Council Canada - National Science Library

    Cohen, Aaron M

    2008-01-01

    .... Our submission included several techniques that we compared and studied, including hot-spot identification, zero-vector filtering, inverse class frequency weighting, error-correcting output codes...

  14. Rare kidney tumor provides insight on metabolic changes

    Science.gov (United States)

    Researchers in The Cancer Genome Atlas (TCGA) Network have uncovered a number of new findings about the biology and development of a rare form of kidney cancer. They found that the disease – chromophobe renal cell carcinoma – stems in part from alteratio

  15. Genomic alterations detected by comparative genomic hybridization in ovarian endometriomas

    Directory of Open Access Journals (Sweden)

    L.C. Veiga-Castelli

    2010-08-01

    Full Text Available Endometriosis is a complex and multifactorial disease. Chromosomal imbalance screening in endometriotic tissue can be used to detect hot-spot regions in the search for a possible genetic marker for endometriosis. The objective of the present study was to detect chromosomal imbalances by comparative genomic hybridization (CGH in ectopic tissue samples from ovarian endometriomas and eutopic tissue from the same patients. We evaluated 10 ovarian endometriotic tissues and 10 eutopic endometrial tissues by metaphase CGH. CGH was prepared with normal and test DNA enzymatically digested, ligated to adaptors and amplified by PCR. A second PCR was performed for DNA labeling. Equal amounts of both normal and test-labeled DNA were hybridized in human normal metaphases. The Isis FISH Imaging System V 5.0 software was used for chromosome analysis. In both eutopic and ectopic groups, 4/10 samples presented chromosomal alterations, mainly chromosomal gains. CGH identified 11q12.3-q13.1, 17p11.1-p12, 17q25.3-qter, and 19p as critical regions. Genomic imbalances in 11q, 17p, 17q, and 19p were detected in normal eutopic and/or ectopic endometrium from women with ovarian endometriosis. These regions contain genes such as POLR2G, MXRA7 and UBA52 involved in biological processes that may lead to the establishment and maintenance of endometriotic implants. This genomic imbalance may affect genes in which dysregulation impacts both eutopic and ectopic endometrium.

  16. Use of local statistics to reveal hidden information of pollution hotspots in urban soil geochemistry

    Science.gov (United States)

    Zhang, Chaosheng

    2017-04-01

    The identification of pollution hotspots is an important approach for a better understanding of spatial distribution patterns and the exploration for their influencing factors in environmental studies. One of the most often asked questions in an environmental investigation is: Where are the pollution hotspots? This presentation explains one of the popularly used methodologies called local index of spatial association (LISA) and its applications in urban geochemical studies in Galway, Ireland and London of the UK. The LISA is a useful tool for identifying pollution hotspots and classifying them into spatial clusters and spatial outliers. The results were affected by the definition of weight function, data transformation and existence of extreme values, and it is suggested that all these influencing factors should be considered until reasonable and reliable results are obtained. This method has been applied to identify Pb pollution in Galway, polluted areas in bonfires sites, elevated P and REE concentrations in London. Hotspots in identified in urban soils are related to locations of high road density, traditional festival bonfires, industries and other human activities. The results of hotspots analysis provide useful information for the management of urban soils.

  17. Genotype heterogeneity of Mycobacterium tuberculosis within geospatial hotspots suggests foci of imported infection in Sydney, Australia.

    Science.gov (United States)

    Gurjav, Ulziijargal; Jelfs, Peter; Hill-Cawthorne, Grant A; Marais, Ben J; Sintchenko, Vitali

    2016-06-01

    In recent years the State of New South Wales (NSW), Australia, has maintained a low tuberculosis incidence rate with little evidence of local transmission. Nearly 90% of notified tuberculosis cases occurred in people born in tuberculosis-endemic countries. We analyzed geographic, epidemiological and genotypic data of all culture-confirmed tuberculosis cases to identify the bacterial and demographic determinants of tuberculosis hotspot areas in NSW. Standard 24-loci mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-24) typing was performed on all isolates recovered between 2009 and 2013. In total 1692/1841 (91.9%) cases with confirmed Mycobacterium tuberculosis infection had complete MIRU-24 and demographic data and were included in the study. Despite some year-to-year variability, spatio-temporal analysis identified four tuberculosis hotspots. The incidence rate and the relative risk of tuberculosis in these hotspots were 2- to 10-fold and 4- to 8-fold higher than the state average, respectively. MIRU-24 profiles of M. tuberculosis isolates associated with these hotspots revealed high levels of heterogeneity. This suggests that these spatio-temporal hotspots, within this low incidence setting, can represent areas of predominantly imported infection rather than clusters of cases due to local transmission. These findings provide important epidemiological insight and demonstrate the value of combining tuberculosis genotyping and spatiotemporal data to guide better-targeted public health interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Indirect-direct hybrid-drive work-dominated hotspot ignition for inertial confinement fusion

    CERN Document Server

    He, X T; Li, J W; Liu, J; Lan, K; Wu, J F; Wang, L F; Ye, W H

    2015-01-01

    An indirect-direct hybrid-drive work-dominated hotspot ignition scheme for inertial confinement fusion is proposed: a layered fuel capsule inside a spherical hohlraum with an octahedral symmetry is compressed first by indirect-drive soft-x rays (radiation) and then by direct-drive lasers in last pulse duration. In this scheme, an enhanced shock and a follow-up compression wave for ignition with pressure far greater than the radiation ablation pressure are driven by the direct-drive lasers, and provide large pdV work to the hotspot to perform the work-dominated ignition. The numerical simulations show that the enhanced shock stops the reflections of indirect-drive shock at the main fuel-hotspot interface, and therefore significantly suppresses the hydrodynamic instabilities and asymmetry. Based on the indirect-drive implosion dynamics the hotspot is further compressed and heated by the enhanced shock and follow-up compression wave, resulting in the work-dominated hotspot ignition and burn with a maximal implos...

  19. Environmental niche conservatism explains the accumulation of species richness in Mediterranean-hotspot plant genera.

    Science.gov (United States)

    Skeels, Alexander; Cardillo, Marcel

    2017-03-01

    The causes of exceptionally high plant diversity in Mediterranean-climate biodiversity hotspots are not fully understood. We asked whether a mechanism similar to the tropical niche conservatism hypothesis could explain the diversity of four large genera (Protea, Moraea, Banksia, and Hakea) with distributions within and adjacent to the Greater Cape Floristic Region (South Africa) or the Southwest Floristic Region (Australia). Using phylogenetic and spatial data we estimated the environmental niche of each species, and reconstructed the mode and dynamics of niche evolution, and the geographic history, of each genus. For three genera, there were strong positive relationships between the diversity of clades within a region and their inferred length of occupation of that region. Within genera, there was evidence for strong evolutionary constraint on niche axes associated with climatic seasonality and aridity, with different niche optima for hotspot and nonhotspot clades. Evolutionary transitions away from hotspots were associated with increases in niche breadth and elevated rates of niche evolution. Our results point to a process of "hotspot niche conservatism" whereby the accumulation of plant diversity in Mediterranean-type ecosystems results from longer time for speciation, with dispersal away from hotspots limited by narrow and phylogenetically conserved environmental niches. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  20. Climate Change Hotspots Identification in China through the CMIP5 Global Climate Model Ensemble

    Directory of Open Access Journals (Sweden)

    Huanghe Gu

    2014-01-01

    Full Text Available China is one of the countries vulnerable to adverse climate changes. The potential climate change hotspots in China throughout the 21st century are identified in this study by using a multimodel, multiscenario climate model ensemble that includes Phase Five of the Coupled Model Intercomparison Project (CMIP5 atmosphere-ocean general circulation models. Both high (RCP8.5 and low (RCP4.5 greenhouse gas emission trajectories are tested, and both the mean and extreme seasonal temperature and precipitation are considered in identifying regional climate change hotspots. Tarim basin and Tibetan Plateau in West China are identified as persistent regional climate change hotspots in both the RCP4.5 and RCP8.5 scenarios. The aggregate impacts of climate change increase throughout the 21st century and are more significant in RCP8.5 than in RCP4.5. Extreme hot event and mean temperature are two climate variables that greatly contribute to the hotspots calculation in all regions. The contribution of other climate variables exhibits a notable subregional variability. South China is identified as another hotspot based on the change of extreme dry event, especially in SON and DJF, which indicates that such event will frequently occur in the future. Our results can contribute to the designing of national and cross-national adaptation and mitigation policies.

  1. Classification Model for Forest Fire Hotspot Occurrences Prediction Using ANFIS Algorithm

    Science.gov (United States)

    Wijayanto, A. K.; Sani, O.; Kartika, N. D.; Herdiyeni, Y.

    2017-01-01

    This study proposed the application of data mining technique namely Adaptive Neuro-Fuzzy inference system (ANFIS) on forest fires hotspot data to develop classification models for hotspots occurrence in Central Kalimantan. Hotspot is a point that is indicated as the location of fires. In this study, hotspot distribution is categorized as true alarm and false alarm. ANFIS is a soft computing method in which a given inputoutput data set is expressed in a fuzzy inference system (FIS). The FIS implements a nonlinear mapping from its input space to the output space. The method of this study classified hotspots as target objects by correlating spatial attributes data using three folds in ANFIS algorithm to obtain the best model. The best result obtained from the 3rd fold provided low error for training (error = 0.0093676) and also low error testing result (error = 0.0093676). Attribute of distance to road is the most determining factor that influences the probability of true and false alarm where the level of human activities in this attribute is higher. This classification model can be used to develop early warning system of forest fire.

  2. Persistence of trophic hotspots and relation to human impacts within an upwelling marine ecosystem.

    Science.gov (United States)

    Santora, Jarrod A; Sydeman, William J; Schroeder, Isaac D; Field, John C; Miller, Rebecca R; Wells, Brian K

    2017-03-01

    Human impacts (e.g., fishing, pollution, and shipping) on pelagic ecosystems are increasing, causing concerns about stresses on marine food webs. Maintaining predator-prey relationships through protection of pelagic hotspots is crucial for conservation and management of living marine resources. Biotic components of pelagic, plankton-based, ecosystems exhibit high variability in abundance in time and space (i.e., extreme patchiness), requiring investigation of persistence of abundance across trophic levels to resolve trophic hotspots. Using a 26-yr record of indicators for primary production, secondary (zooplankton and larval fish), and tertiary (seabirds) consumers, we show distributions of trophic hotspots in the southern California Current Ecosystem result from interactions between a strong upwelling center and a productive retention zone with enhanced nutrients, which concentrate prey and predators across multiple trophic levels. Trophic hotspots also overlap with human impacts, including fisheries extraction of coastal pelagic and groundfish species, as well as intense commercial shipping traffic. Spatial overlap of trophic hotspots with fisheries and shipping increases vulnerability of the ecosystem to localized depletion of forage fish, ship strikes on marine mammals, and pollution. This study represents a critical step toward resolving pelagic areas of high conservation interest for planktonic ecosystems and may serve as a model for other ocean regions where ecosystem-based management and marine spatial planning of pelagic ecosystems is warranted. © 2016 by the Ecological Society of America.

  3. Analisa Kecepatan Transfer Data Pada Perancangan Hotspot Sederhana Dengan System Single Sign On Di Perkantoran

    Directory of Open Access Journals (Sweden)

    Bela Neziah Arum Pangesti

    2017-05-01

    Full Text Available The problems office in the utilization of wireless technology has widely used but sometimes without take into the number of users, so it is not mangkus. The networking system for small office can be use wireless simple system. Most of the office has applied hotspot but that is old system, one account for all people using internet access. Single sign-on is a system services of hotspot, this system verifying an account for each user so people have different and username dan a password. The methodology used is literature review, analysis, design, implementation, testing and analysis of the data transfer rate. The hotspot with a single sign-on system using mikrotik, and access point, the connected with networking devices in the office. Winbox tools is used to configuration. Testing with the user had been connected to the hotspot system single sign on. Methods of test to user login on the system single sign-on is the black box texting. Testing the speed of data transfer is used staff user and guest user who uploaded three types of files to the drive with diffrent bandwidth. Then the network sniffing is used tools wireshark. The results from this study is simple hotspot service with single sign-on system for office and from the analysis of the data transfer rate was known the data transfer rate on the staff user and guest user to the three types of file is a type of word files greater than PDF and PPT.

  4. A Practical Approach to Screening Potential Environmental Hotspots of Different Impact Categories in Supply Chains

    Directory of Open Access Journals (Sweden)

    Jun Nakatani

    2015-08-01

    Full Text Available Identification of environmental hotspots becomes a pressing issue for companies pursuing sustainable supply chain management. In particular, excessive dependence on water resources outside the country may put the supply chain at unanticipated risk of water shortage. This article presents a practical approach to screening potential environmental hotspots of different impact categories that occur in the supply chain using environmental input-output analysis. First, the amounts of domestic and foreign potential impacts of global warming, terrestrial acidification, and water resource consumption, induced through supply chains were calculated for 403 sectors of Japanese products. Thereafter, with a focus on potential impacts induced through the import of raw materials, a framework for screening foreign potential hotspots was presented. The results showed that the sectoral potential impacts of water resource consumption had high rates of foreign impacts at deeper tiers of the supply chains for some sectors, which indicated that there exist hidden water hotspots outside the country. In the case study of fiber yarns, impacts on water resource consumption induced as a result of the import of crops, as well as that induced in silviculture as a result of the import of wood chips, were found to be the foreign potential hotspots.

  5. Kernel density estimation and K-means clustering to profile road accident hotspots.

    Science.gov (United States)

    Anderson, Tessa K

    2009-05-01

    Identifying road accident hotspots is a key role in determining effective strategies for the reduction of high density areas of accidents. This paper presents (1) a methodology using Geographical Information Systems (GIS) and Kernel Density Estimation to study the spatial patterns of injury related road accidents in London, UK and (2) a clustering methodology using environmental data and results from the first section in order to create a classification of road accident hotspots. The use of this methodology will be illustrated using the London area in the UK. Road accident data collected by the Metropolitan Police from 1999 to 2003 was used. A kernel density estimation map was created and subsequently disaggregated by cell density to create a basic spatial unit of an accident hotspot. Appended environmental data was then added to the hotspot cells and using K-means clustering, an outcome of similar hotspots was deciphered. Five groups and 15 clusters were created based on collision and attribute data. These clusters are discussed and evaluated according to their robustness and potential uses in road safety campaigning.

  6. First Results from HOTSPOT: The Snake River Plain Scientific Drilling Project, Idaho, U.S.A.

    Directory of Open Access Journals (Sweden)

    John W. Shervais

    2013-03-01

    Full Text Available HOTSPOT is an international collaborative effort to understand the volcanic history of the Snake River Plain (SRP. The SRP overlies a thermal anomaly, the Yellowstone-Snake River hotspot, that is thought to represent a deep-seated mantle plume under North America. Theprimary goal of this project is to document the volcanic and stratigraphic history of the SRP, which represents the surface expression of this hotspot, and to understand how it affected the evolution of continental crust and mantle. An additional goal is to evaluate the geothermal potential of southern Idaho.Project HOTSPOT has completed three drill holes. (1 The Kimama site is located along the central volcanic axis of the SRP; our goal here was to sample a long-term record of basaltic volcanism in the wake of the SRP hotspot. (2 The Kimberly site is located near the margin of the plain; our goal here was to sample a record of high-temperaturerhyolite volcanism associated with the underlying plume. This site was chosen to form a nominally continuous record of volcanism when paired with the Kimama site. (3 The Mountain Home site is located in the western plain; our goal here was to sample the Pliocene-Pleistocene transition in lake sediments at this site and to sample older basalts that underlie the sediments.We report here on our initial results for each site, and on some of the geophysical logging studies carried out as part of this project.

  7. The characterization of twenty sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Kimberly Pelak

    2010-09-01

    Full Text Available We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

  8. Structural health management of aerospace hotspots under fatigue loading

    Science.gov (United States)

    Soni, Sunilkumar

    Sustainability and life-cycle assessments of aerospace systems, such as aircraft structures and propulsion systems, represent growing challenges in engineering. Hence, there has been an increasing demand in using structural health monitoring (SHM) techniques for continuous monitoring of these systems in an effort to improve safety and reduce maintenance costs. The current research is part of an ongoing multidisciplinary effort to develop a robust SHM framework resulting in improved models for damage-state awareness and life prediction, and enhancing capability of future aircraft systems. Lug joints, a typical structural hotspot, were chosen as the test article for the current study. The thesis focuses on integrated SHM techniques for damage detection and characterization in lug joints. Piezoelectric wafer sensors (PZTs) are used to generate guided Lamb waves as they can be easily used for onboard applications. Sensor placement in certain regions of a structural component is not feasible due to the inaccessibility of the area to be monitored. Therefore, a virtual sensing concept is introduced to acquire sensor data from finite element (FE) models. A full three dimensional FE analysis of lug joints with piezoelectric transducers, accounting for piezoelectrical-mechanical coupling, was performed in Abaqus and the sensor signals were simulated. These modeled sensors are called virtual sensors. A combination of real data from PZTs and virtual sensing data from FE analysis is used to monitor and detect fatigue damage in aluminum lug joints. Experiments were conducted on lug joints under fatigue loads and sensor signals collected were used to validate the simulated sensor response. An optimal sensor placement methodology for lug joints is developed based on a detection theory framework to maximize the detection rate and minimize the false alarm rate. The placement technique is such that the sensor features can be directly correlated to damage. The technique accounts for a

  9. A rare sight

    CERN Multimedia

    Antonella Del Rosso and The LHCb Collaboration

    2012-01-01

    Today, at the Hadron Collider Physics Symposium in Kyoto, the LHCb collaboration has presented the evidence of a very rare B decay, the rarest ever seen. The result further shrinks the region in which scientists can still look for supersymmetry.   The graph showing evidence of the Bs0 → μ+ μ- decay. The result was presented Monday 12 November at the HCP Conference in Kyoto (photo courtesy of the LHCb Collaboration). Particle decays tell us about the inner properties and functioning of Nature’s physics processes. By studying them and their occurrence, physicists infer the rules that control them. Often, it turns out that some rare decays, which are very difficult to observe, are those in which Nature could reveal the presence of new physics. This is the case of some decays of the Bs0 particle (a particle made of a bottom anti-quark bound to a strange quark), and in particular Bs0 → μ+ μ- whose...

  10. Rare B decays at LEP

    CERN Document Server

    Kluit, P M

    2001-01-01

    The results of the LEP experiments for rare B decays will be reviewed, covering hadronic final states, radiative and other rare decays and results for the inclusive charmless branching ratio. (8 refs).

  11. Demography and the age of rare variants.

    Science.gov (United States)

    Mathieson, Iain; McVean, Gil

    2014-08-01

    Large whole-genome sequencing projects have provided access to much rare variation in human populations, which is highly informative about population structure and recent demography. Here, we show how the age of rare variants can be estimated from patterns of haplotype sharing and how these ages can be related to historical relationships between populations. We investigate the distribution of the age of variants occurring exactly twice (ƒ(2) variants) in a worldwide sample sequenced by the 1000 Genomes Project, revealing enormous variation across populations. The median age of haplotypes carrying ƒ(2) variants is 50 to 160 generations across populations within Europe or Asia, and 170 to 320 generations within Africa. Haplotypes shared between continents are much older with median ages for haplotypes shared between Europe and Asia ranging from 320 to 670 generations. The distribution of the ages of ƒ(2) haplotypes is informative about their demography, revealing recent bottlenecks, ancient splits, and more modern connections between populations. We see the effect of selection in the observation that functional variants are significantly younger than nonfunctional variants of the same frequency. This approach is relatively insensitive to mutation rate and complements other nonparametric methods for demographic inference.

  12. Comparative Genomics

    Indian Academy of Sciences (India)

    tory motifs and other non-coding DNA motifs, and genome flux and dynamics. Finally the article describes how the information one can extract from a comparative analysis of genomes depends to a large extent, on the specific aspect of the genomes that is being compared and the phylogenetic distances of the organisms ...

  13. Cancer genomics

    DEFF Research Database (Denmark)

    Norrild, Bodil; Guldberg, Per; Ralfkiær, Elisabeth Methner

    2007-01-01

    Almost all cells in the human body contain a complete copy of the genome with an estimated number of 25,000 genes. The sequences of these genes make up about three percent of the genome and comprise the inherited set of genetic information. The genome also contains information that determines whe...

  14. Hotspot detection using space-time scan statistics on children under five years of age in Depok

    Science.gov (United States)

    Verdiana, Miranti; Widyaningsih, Yekti

    2017-03-01

    Some problems that affect the health level in Depok is the high malnutrition rates from year to year and the more spread infectious and non-communicable diseases in some areas. Children under five years old is a vulnerable part of population to get the malnutrition and diseases. Based on this reason, it is important to observe the location and time, where and when, malnutrition in Depok happened in high intensity. To obtain the location and time of the hotspots of malnutrition and diseases that attack children under five years old, space-time scan statistics method can be used. Space-time scan statistic is a hotspot detection method, where the area and time of information and time are taken into account simultaneously in detecting the hotspots. This method detects a hotspot with a cylindrical scanning window: the cylindrical pedestal describes the area, and the height of cylinder describe the time. Cylinders formed is a hotspot candidate that may occur, which require testing of hypotheses, whether a cylinder can be summed up as a hotspot. Hotspot detection in this study carried out by forming a combination of several variables. Some combination of variables provides hotspot detection results that tend to be the same, so as to form groups (clusters). In the case of infant health level in Depok city, Beji health care center region in 2011-2012 is a hotspot. According to the combination of the variables used in the detection of hotspots, Beji health care center is most frequently as a hotspot. Hopefully the local government can take the right policy to improve the health level of children under five in the city of Depok.

  15. Detecting fluorescence hot-spots using mosaic maps generated from multimodal endoscope imaging

    Science.gov (United States)

    Yang, Chenying; Soper, Timothy D.; Seibel, Eric J.

    2013-03-01

    Fluorescence labeled biomarkers can be detected during endoscopy to guide early cancer biopsies, such as high-grade dysplasia in Barrett's Esophagus. To enhance intraoperative visualization of the fluorescence hot-spots, a mosaicking technique was developed to create full anatomical maps of the lower esophagus and associated fluorescent hot-spots. The resultant mosaic map contains overlaid reflectance and fluorescence images. It can be used to assist biopsy and document findings. The mosaicking algorithm uses reflectance images to calculate image registration between successive frames, and apply this registration to simultaneously acquired fluorescence images. During this mosaicking process, the fluorescence signal is enhanced through multi-frame averaging. Preliminary results showed that the technique promises to enhance the detectability of the hot-spots due to enhanced fluorescence signal.

  16. Research on Hotspot Discovery in Internet Public Opinions Based on Improved -Means

    Directory of Open Access Journals (Sweden)

    Gensheng Wang

    2013-01-01

    Full Text Available How to discover hotspot in the Internet public opinions effectively is a hot research field for the researchers related which plays a key role for governments and corporations to find useful information from mass data in the Internet. An improved -means algorithm for hotspot discovery in internet public opinions is presented based on the analysis of existing defects and calculation principle of original -means algorithm. First, some new methods are designed to preprocess website texts, select and express the characteristics of website texts, and define the similarity between two website texts, respectively. Second, clustering principle and the method of initial classification centers selection are analyzed and improved in order to overcome the limitations of original -means algorithm. Finally, the experimental results verify that the improved algorithm can improve the clustering stability and classification accuracy of hotspot discovery in internet public opinions when used in practice.

  17. Hot-spot mix in ignition-scale inertial confinement fusion targets.

    Science.gov (United States)

    Regan, S P; Epstein, R; Hammel, B A; Suter, L J; Scott, H A; Barrios, M A; Bradley, D K; Callahan, D A; Cerjan, C; Collins, G W; Dixit, S N; Döppner, T; Edwards, M J; Farley, D R; Fournier, K B; Glenn, S; Glenzer, S H; Golovkin, I E; Haan, S W; Hamza, A; Hicks, D G; Izumi, N; Jones, O S; Kilkenny, J D; Kline, J L; Kyrala, G A; Landen, O L; Ma, T; MacFarlane, J J; MacKinnon, A J; Mancini, R C; McCrory, R L; Meezan, N B; Meyerhofer, D D; Nikroo, A; Park, H-S; Ralph, J; Remington, B A; Sangster, T C; Smalyuk, V A; Springer, P T; Town, R P J

    2013-07-26

    Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. Low neutron yields and hot-spot mix mass between 34(-13,+50)  ng and 4000(-2970,+17 160)  ng are observed.

  18. Effects of Hot-Spot Geometry on Backscattering and Down-Scattering Neutron Spectra

    Science.gov (United States)

    Mohamed, Z. L.; Mannion, O. M.; Forrest, C. J.; Knauer, J. P.; Anderson, K. S.; Radha, P. B.

    2017-10-01

    The measured neutron spectrum produced by a fusion experiment plays a key role in inferring observable quantities. One important observable is the areal density of an implosion, which is inferred by measuring the scattering of neutrons. This project seeks to use particle-transport simulations to model the effects of hot-spot geometry on backscattering and down-scattering neutron spectra along different lines of sight. Implosions similar to those conducted at the Laboratory of Laser Energetics are modeled by neutron transport through a DT plasma and a DT ice shell using the particle transport codes MCNP and IRIS. Effects of hot-spot geometry are obtained by ``detecting'' scattered neutrons along different lines of sight. This process is repeated for various hot-spot geometries representing known shape distortions between the hot spot and the shell. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  19. Optimally designed gold nanorattles with strong built-in hotspots and weak polarization dependence

    Science.gov (United States)

    Zhang, Xuemin; Wang, Tieqiang; Li, Yunong; Fu, Yu; Guo, Lei

    2017-12-01

    Localized electromagnetic fields generated by interparticle plasmon coupling suffer greatly from nonreproducibility because they are extremely sensitive to the nanoparticle aggregation status and the incident polarization. Here, we synthesize gold nanorattles that exhibit inherent aggregation-insensitive hotspots due to the intraparticle core–shell plasmon coupling, and investigate the structural effect on the intraparticle coupling strength and its polarization dependence. Through optimizing the structural parameters, we successfully synthesize gold nanorattles with strong built-in hotspots and weak polarization dependence. These aggregation-insensitive and weakly polarization-dependent hotspots make the Raman enhancement from nanorattle aggregates show an unusual weak dependence on the particle aggregation status, which therefore affords the opportunity to fabricate uniform and reproducible surface enhanced Raman scattering substrates.

  20. Comparative phylogeography reveals deep lineages and regional evolutionary hotspots in the Mojave and Sonoran Deserts

    Science.gov (United States)

    Wood, Dustin A.; Vandergast, Amy G.; Barr, Kelly R.; Inman, Richard D.; Esque, Todd C.; Nussear, Kenneth E.; Fisher, Robert N.

    2013-01-01

    Aim: We explored lineage diversification within desert-dwelling fauna. Our goals were (1) to determine whether phylogenetic lineages and population expansions were consistent with younger Pleistocene climate fluctuation hypotheses or much older events predicted by pre-Pleistocene vicariance hypotheses, (2) to assess concordance in spatial patterns of genetic divergence and diversity among species and (3) to identify regional evolutionary hotspots of divergence and diversity and assess their conservation status. Location: Mojave, Colorado, and Sonoran Deserts, USA. Methods: We analysed previously published gene sequence data for twelve species. We used Bayesian gene tree methods to estimate lineages and divergence times. Within each lineage, we tested for population expansion and age of expansion using coalescent approaches. We mapped interpopulation genetic divergence and intra-population genetic diversity in a GIS to identify hotspots of highest genetic divergence and diversity and to assess whether protected lands overlapped with evolutionary hotspots. Results: In seven of the 12 species, lineage divergence substantially predated the Pleistocene. Historical population expansion was found in eight species, but expansion events postdated the Last Glacial Maximum (LGM) in only four. For all species assessed, six hotspots of high genetic divergence and diversity were concentrated in the Colorado Desert, along the Colorado River and in the Mojave/Sonoran ecotone. At least some proportion of the land within each recovered hotspot was categorized as protected, yet four of the six also overlapped with major areas of human development. Main conclusions: Most of the species studied here diversified into distinct Mojave and Sonoran lineages prior to the LGM – supporting older diversification hypotheses. Several evolutionary hotspots were recovered but are not strategically paired with areas of protected land. Long-term preservation of species-level biodiversity would

  1. Threatened Plants in China’s Sanjiang Plain: Hotspot Distributions and Gap Analysis

    Directory of Open Access Journals (Sweden)

    Baojia Du

    2018-01-01

    Full Text Available Global biodiversity is markedly decreasing in response to climate change and human disturbance. Sanjiang Plain is recognized as a biodiversity hotspot in China due to its high forest and wetland coverage, but species are being lost at an unprecedented rate, induced by anthropogenic activities. Identifying hotspot distributions and conservation gaps of threatened species is of particular significance for enhancing the conservation of biodiversity. Specifically, we integrated the principles and methods of spatial hotspot inspection, geographic information system (GIS technology and spatial autocorrelation analysis along with fieldwork to determine the spatial distribution patterns and unprotected hotspots of vulnerable and endangered plants in Sanjiang Plain. A gap analysis of the conservation status of vulnerable and endangered plants was conducted. Our results indicate that six nationally-protected plants were not observed in nature reserves or were without any protection, while the protection rates were <10% for 10 other nationally-protected plants. Protected areas (PAs cover <5% of the distribution areas for 31 threatened plant species, while only five species are covered by national nature reserves (NNRs within >50% of the distribution areas. We found 30 hotspots with vulnerable and endangered plants in the study area, but the area covered by NNRs is very limited. Most of the hotspots were located in areas with a high-high aggregation of plant species. Therefore, it is necessary to expand the area of existing nature reserves, establish miniature protection plots and create new PAs and ecological corridors to link the existing PAs. Our findings can contribute to the design of a PA network for botanical conservation.

  2. Next-generation invaders? Hotspots for naturalised sleeper weeds in Australia under future climates.

    Science.gov (United States)

    Duursma, Daisy Englert; Gallagher, Rachael V; Roger, Erin; Hughes, Lesley; Downey, Paul O; Leishman, Michelle R

    2013-01-01

    Naturalised, but not yet invasive plants, pose a nascent threat to biodiversity. As climate regimes continue to change, it is likely that a new suite of invaders will emerge from the established pool of naturalised plants. Pre-emptive management of locations that may be most suitable for a large number of potentially invasive plants will help to target monitoring, and is vital for effective control. We used species distribution models (SDM) and invasion-hotspot analysis to determine where in Australia suitable habitat may occur for 292 naturalised plants. SDMs were built in MaxEnt using both climate and soil variables for current baseline conditions. Modelled relationships were projected onto two Representative Concentration Pathways for future climates (RCP 4.5 and 8.5), based on seven global climate models, for two time periods (2035, 2065). Model outputs for each of the 292 species were then aggregated into single 'hotspot' maps at two scales: continental, and for each of Australia's 37 ecoregions. Across Australia, areas in the south-east and south-west corners of the continent were identified as potential hotspots for naturalised plants under current and future climates. These regions provided suitable habitat for 288 and 239 species respectively under baseline climates. The areal extent of the continental hotspot was projected to decrease by 8.8% under climates for 2035, and by a further 5.2% by 2065. A similar pattern of hotspot contraction under future climates was seen for the majority of ecoregions examined. However, two ecoregions - Tasmanian temperate forests and Australian Alps montane grasslands - showed increases in the areal extent of hotspots of >45% under climate scenarios for 2065. The alpine ecoregion also had an increase in the number of naturalised plant species with abiotically suitable habitat under future climate scenarios, indicating that this area may be particularly vulnerable to future incursions by naturalised plants.

  3. Next-generation invaders? Hotspots for naturalised sleeper weeds in Australia under future climates.

    Directory of Open Access Journals (Sweden)

    Daisy Englert Duursma

    Full Text Available Naturalised, but not yet invasive plants, pose a nascent threat to biodiversity. As climate regimes continue to change, it is likely that a new suite of invaders will emerge from the established pool of naturalised plants. Pre-emptive management of locations that may be most suitable for a large number of potentially invasive plants will help to target monitoring, and is vital for effective control. We used species distribution models (SDM and invasion-hotspot analysis to determine where in Australia suitable habitat may occur for 292 naturalised plants. SDMs were built in MaxEnt using both climate and soil variables for current baseline conditions. Modelled relationships were projected onto two Representative Concentration Pathways for future climates (RCP 4.5 and 8.5, based on seven global climate models, for two time periods (2035, 2065. Model outputs for each of the 292 species were then aggregated into single 'hotspot' maps at two scales: continental, and for each of Australia's 37 ecoregions. Across Australia, areas in the south-east and south-west corners of the continent were identified as potential hotspots for naturalised plants under current and future climates. These regions provided suitable habitat for 288 and 239 species respectively under baseline climates. The areal extent of the continental hotspot was projected to decrease by 8.8% under climates for 2035, and by a further 5.2% by 2065. A similar pattern of hotspot contraction under future climates was seen for the majority of ecoregions examined. However, two ecoregions - Tasmanian temperate forests and Australian Alps montane grasslands - showed increases in the areal extent of hotspots of >45% under climate scenarios for 2065. The alpine ecoregion also had an increase in the number of naturalised plant species with abiotically suitable habitat under future climate scenarios, indicating that this area may be particularly vulnerable to future incursions by naturalised plants.

  4. [A rare endolaryngeal tumor].

    Science.gov (United States)

    Ngo, Carine; Albert, Sébastien; Barry, Beatrix; Copie-Bergman, Christiane; Couvelard, Anne; Hourseau, Muriel

    2017-10-01

    We report the case of a 65-year-old woman who presented with a dysphonia. ENT tomography and laryngoscopy showed an endolaryngeal tumoral lesion extended to the right supraglottis. Biopsy of the lesion revealed dense lymphoid infiltrate in the lamina propria, without necrosis or ulceration of the mucosa. The infiltrate showed many CD3+, CD5+, CD4+, CD8+ lymphocytes and plasmocytes. Larger lymphoid cells with cytologic atypia expressed CD56 and cytotoxicity markers such as TIA1 and granzyme B. In situ hybridization for EBV revealed numerous positive cells. The diagnosis of extranodal NK/T cell lymphoma was proposed. The primary laryngeal localization of this disease is exceptionally rare. Heavy admixture of inflammatory cells may mimic inflammatory process and delay the diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Seed plant phylogenetic diversity and species richness in conservation planning within a global biodiversity hotspot in eastern Asia.

    Science.gov (United States)

    Li, Rong; Kraft, Nathan J B; Yu, Haiying; Li, Heng

    2015-12-01

    One of the main goals of conservation biology is to understand the factors shaping variation in biodiversity across the planet. This understanding is critical for conservation planners to be able to develop effective conservation strategies. Although many studies have focused on species richness and the protection of rare and endemic species, less attention has been paid to the protection of the phylogenetic dimension of biodiversity. We explored how phylogenetic diversity, species richness, and phylogenetic community structure vary in seed plant communities along an elevational gradient in a relatively understudied high mountain region, the Dulong Valley, in southeastern Tibet, China. As expected, phylogenetic diversity was well correlated with species richness among the elevational bands and among communities. At the community level, evergreen broad-leaved forests had the highest levels of species richness and phylogenetic diversity. Using null model analyses, we found evidence of nonrandom phylogenetic structure across the region. Evergreen broad-leaved forests were phylogenetically overdispersed, whereas other vegetation types tended to be phylogenetically clustered. We suggest that communities with high species richness or overdispersed phylogenetic structure should be a focus for biodiversity conservation within the Dulong Valley because these areas may help maximize the potential of this flora to respond to future global change. In biodiversity hotspots worldwide, we suggest that the phylogenetic structure of a community may serve as a useful measure of phylogenetic diversity in the context of conservation planning. © 2015 Society for Conservation Biology.

  6. The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen-Goldberg syndrome.

    Science.gov (United States)

    Schepers, Dorien; Doyle, Alexander J; Oswald, Gretchen; Sparks, Elizabeth; Myers, Loretha; Willems, Patrick J; Mansour, Sahar; Simpson, Michael A; Frysira, Helena; Maat-Kievit, Anneke; Van Minkelen, Rick; Hoogeboom, Jeanette M; Mortier, Geert R; Titheradge, Hannah; Brueton, Louise; Starr, Lois; Stark, Zornitza; Ockeloen, Charlotte; Lourenco, Charles Marques; Blair, Ed; Hobson, Emma; Hurst, Jane; Maystadt, Isabelle; Destrée, Anne; Girisha, Katta M; Miller, Michelle; Dietz, Harry C; Loeys, Bart; Van Laer, Lut

    2015-02-01

    Shprintzen-Goldberg syndrome (SGS) is a rare, systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations that show a significant overlap with the features observed in the Marfan (MFS) and Loeys-Dietz syndrome (LDS). A distinguishing observation in SGS patients is the presence of intellectual disability, although not all patients in this series present this finding. Recently, SGS was shown to be due to mutations in the SKI gene, encoding the oncoprotein SKI, a repressor of TGFβ activity. Here, we report eight recurrent and three novel SKI mutations in eleven SGS patients. All were heterozygous missense mutations located in the R-SMAD binding domain, except for one novel in-frame deletion affecting the DHD domain. Adding our new findings to the existing data clearly reveals a mutational hotspot, with 73% (24 out of 33) of the hitherto described unrelated patients having mutations in a stretch of five SKI residues (from p.(Ser31) to p.(Pro35)). This implicates that the initial molecular testing could be focused on mutation analysis of the first half of exon 1 of SKI. As the majority of the known mutations are located in the R-SMAD binding domain of SKI, our study further emphasizes the importance of TGFβ signaling in the pathogenesis of SGS.

  7. SRSF2-p95 hotspot mutation is highly associated with advanced forms of mastocytosis and mutations in epigenetic regulator genes.

    Science.gov (United States)

    Hanssens, Katia; Brenet, Fabienne; Agopian, Julie; Georgin-Lavialle, Sophie; Damaj, Gandhi; Cabaret, Laure; Chandesris, Maria Olivia; de Sepulveda, Paulo; Hermine, Olivier; Dubreuil, Patrice; Soucie, Erinn

    2014-05-01

    Mastocytosis is a rare and chronic disease with phenotypes ranging from indolent to severe. Prognosis for this disease is variable and very few biomarkers to predict disease evolution or outcome are currently known. We have performed comprehensive screening in our large cohort of mastocytosis patients for mutations previously found in other myeloid diseases and that could serve as prognostic indicators. KIT, SRSF2-P95 and TET2 mutations were by far the most frequent, detected in 81%, 24% and 21% of patients, respectively. Where TET2 and SRSF2-P95 mutation both correlated with advanced disease phenotypes, SRSF2-P95 hotspot mutation was found almost exclusively in patients diagnosed with associated clonal hematologic non-mast cell disease. Statistically, TET2 and SRSF2-P95 mutations were highly associated, suggesting a mechanistic link between these two factors. Finally, analysis of both clonal and sorted cell populations from patients confirms the presence of these mutations in the mast cell component of the disease, suggests an ontological mutation hierarchy and provides evidence for the expansion of multiple clones. This highlights the prognostic potential of such approaches, if applied systematically, for delineating the roles of specific mutations in predisposing and/or driving distinct disease phenotypes.

  8. The SMAD-binding domain of SKI: a hotspot for de novo mutations causing Shprintzen–Goldberg syndrome

    Science.gov (United States)

    Schepers, Dorien; Doyle, Alexander J; Oswald, Gretchen; Sparks, Elizabeth; Myers, Loretha; Willems, Patrick J; Mansour, Sahar; Simpson, Michael A; Frysira, Helena; Maat-Kievit, Anneke; Van Minkelen, Rick; Hoogeboom, Jeanette M; Mortier, Geert R; Titheradge, Hannah; Brueton, Louise; Starr, Lois; Stark, Zornitza; Ockeloen, Charlotte; Lourenco, Charles Marques; Blair, Ed; Hobson, Emma; Hurst, Jane; Maystadt, Isabelle; Destrée, Anne; Girisha, Katta M; Miller, Michelle; Dietz, Harry C; Loeys, Bart; Van Laer, Lut

    2015-01-01

    Shprintzen–Goldberg syndrome (SGS) is a rare, systemic connective tissue disorder characterized by craniofacial, skeletal, and cardiovascular manifestations that show a significant overlap with the features observed in the Marfan (MFS) and Loeys–Dietz syndrome (LDS). A distinguishing observation in SGS patients is the presence of intellectual disability, although not all patients in this series present this finding. Recently, SGS was shown to be due to mutations in the SKI gene, encoding the oncoprotein SKI, a repressor of TGFβ activity. Here, we report eight recurrent and three novel SKI mutations in eleven SGS patients. All were heterozygous missense mutations located in the R-SMAD binding domain, except for one novel in-frame deletion affecting the DHD domain. Adding our new findings to the existing data clearly reveals a mutational hotspot, with 73% (24 out of 33) of the hitherto described unrelated patients having mutations in a stretch of five SKI residues (from p.(Ser31) to p.(Pro35)). This implicates that the initial molecular testing could be focused on mutation analysis of the first half of exon 1 of SKI. As the majority of the known mutations are located in the R-SMAD binding domain of SKI, our study further emphasizes the importance of TGFβ signaling in the pathogenesis of SGS. PMID:24736733

  9. Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

    Energy Technology Data Exchange (ETDEWEB)

    Hasin-Brumshtein, Yehudit; Khan, Arshad H.; Hormozdiari, Farhad; Pan, Calvin; Parks, Brian W.; Petyuk, Vladislav A.; Piehowski, Paul D.; Brümmer, Anneke; Pellegrini, Matteo; Xiao, Xinshu; Eskin, Eleazar; Smith, Richard D.; Lusis, Aldons J.; Smith, Desmond J.

    2016-09-13

    Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals bothlocalandtransexpression Quantitative Trait Loci (eQTLs) demonstrating 2transeQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation.

  10. Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes

    Science.gov (United States)

    Hasin-Brumshtein, Yehudit; Khan, Arshad H; Hormozdiari, Farhad; Pan, Calvin; Parks, Brian W; Petyuk, Vladislav A; Piehowski, Paul D; Brümmer, Anneke; Pellegrini, Matteo; Xiao, Xinshu; Eskin, Eleazar; Smith, Richard D; Lusis, Aldons J; Smith, Desmond J

    2016-01-01

    Previous studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation. DOI: http://dx.doi.org/10.7554/eLife.15614.001 PMID:27623010

  11. Bos taurus genome assembly.

    Science.gov (United States)

    Liu, Yue; Qin, Xiang; Song, Xing-Zhi Henry; Jiang, Huaiyang; Shen, Yufeng; Durbin, K James; Lien, Sigbjørn; Kent, Matthew Peter; Sodeland, Marte; Ren, Yanru; Zhang, Lan; Sodergren, Erica; Havlak, Paul; Worley, Kim C; Weinstock, George M; Gibbs, Richard A

    2009-04-24

    We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS) only assembly used for many other animal genomes including the rhesus macaque. The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information.Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5%) of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly. The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.

  12. Bos taurus genome assembly

    Directory of Open Access Journals (Sweden)

    Sodergren Erica

    2009-04-01

    Full Text Available Abstract Background We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS only assembly used for many other animal genomes including the rhesus macaque. Results The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information. Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5% of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly. Conclusion The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.

  13. Identifying ecosystem service hotspots for environmental management in Durban, South Africa

    Directory of Open Access Journals (Sweden)

    Rashieda Davids

    2016-12-01

    Conclusion: The results indicated that substantial portions of hotspot areas lie outside of formally regulated and managed conservation areas and remain vulnerable to human impact and habitat degradation. The study identified management areas and options that could yield maximum benefits; including the need for the development of an ecosystem services management and protection strategy, the selection of areas for co-management of ecosystem service hotspots and CBAs and the need for collaborative management.

  14. Pedestrian injury and the built environment: an environmental scan of hotspots

    Directory of Open Access Journals (Sweden)

    Crooks Valorie A

    2009-07-01

    Full Text Available Abstract Background Pedestrian injury frequently results in devastating and costly injuries and accounts for 11% of all road user fatalities. In the United States in 2006 there were 4,784 fatalities and 61,000 injuries from pedestrian injury, and in 2007 there were 4,654 fatalities and 70,000 injuries. In Canada, injury is the leading cause of death for those under 45 years of age and the fourth most common cause of death for all ages Traumatic pedestrian injury results in nearly 4000 hospitalizations in Canada annually. These injuries result from the interplay of modifiable environmental factors. The objective of this study was to determine links between the built environment and pedestrian injury hotspots in Vancouver. Methods Data were obtained from the Insurance Corporation of British Columbia (ICBC for the 6 year period from 2000 to 2005 and combined with pedestrian injury data extracted from the British Columbia Trauma Registry (BCTR for the same period. High incident locations (hotspots for pedestrian injury in the City of Vancouver were identified and mapped using geographic information systems (GIS, and the characteristics of the built environment at each of the hotspot locations were examined by a team of researchers. Results The analysis highlighted 32 pedestrian injury hotspot locations in Vancouver. 31 of 32 hotspots were situated on major roads. Likewise, the majority of hotspots were located on downtown streets. The 'downtown eastside' was identified as an area with multiple high-incident locations, including the 2 highest ranked pedestrian injury hotspots. Bars were present at 21 of the hotspot locations, with 11 of these locations being judged to have high alcohol establishment density. Conclusion This study highlighted the disproportionate burden of pedestrian injury centred on the downtown eastside area of Vancouver. The environmental scan revealed that important passive pedestrian safety countermeasures were only present at a

  15. Rare cancers are not so rare: The rare cancer burden in Europe

    NARCIS (Netherlands)

    Gatta, Gemma; van der Zwan, Jan Maarten; Casali, Paolo G.; Siesling, Sabine; Dei Tos, Angelo Paolo; Kunkler, Ian; Otter, Renee; Licitra, Lisa

    2011-01-01

    Purpose: Epidemiologic information on rare cancers is scarce. The project Surveillance of Rare Cancers in Europe (RARECARE) provides estimates of the incidence, prevalence and survival of rare cancers in Europe based on a new and comprehensive list of these diseases. Materials and methods: RARECARE

  16. New constraints on the Yellowstone hotspot's dynamical agent

    Science.gov (United States)

    Dueker, K. G.; Schutt, D.; Yuan, H.

    2006-12-01

    Recent teleseismic results from the 2000-2001 PASSCAL Yellowstone and Billings arrays reveal the following. The P-wave velocity tomogram requires a 100 km diameter pipe extending from beneath Yellowstone Park to 400-500 km depth. This pipe is tilted at about 15° from vertical towards the NW. We show that the image of the low velocity pipe in the 200-400 km depth range is robust (our array apature and teleseismic earthquake distribution is better than Iceland arrays). Ignoring the possibility of a wet non-thermal upwelling pipe, a mantle plume is the only process capable of producing the >200 km extension of the low velocity pipe. Independent confirmation that a warm pipe exists is provided by a 14 km depression of the 410 km discontinuity where the tomographic image of the pipe crosses the 410. Noteworthy is that the 660 km discontinuity does not show evidence for a plume: consistent with our tomographic image. Less visually stimulating, but equally compelling evidence for the occurrence of a plume beneath Yellowstone is provided by Rayleigh wave phase velocity modeling. The most remarkable aspect of this modeling is that a shear-wave velocity minimum of 3.8-3.9 km/s is required below the eastern Snake River Plain (ESRP) at 70-80 km depth (normal sub-solidus adiabatic mantle is 4.1-4.2 km/s). Simple parametric modeling of the phase velocity data is performed in which the independent parameters are: temperature, grain size, attenuation, and melt-velocity scaling. Equilibrium melt porosities of 0.1-0.4% were constrained by a 1-D Darcy flow suggesting that most of the velocity reduction is not controlled by melt porosity (using Kreutzmann et al., (2004) melt- velocity scaling of 2.1% dVs per 1% melt). This modeling requires a minimum excess temperature of 90° with respect to a 1320° potential temperature mantle. A plume flux rate estimate is provided by integrating the volume of low velocity plume layer beneath the last 8 Ma of the hotspot track; this finds a very

  17. A lithography aware design optimization using foundry-certified models and hotspot detection

    Science.gov (United States)

    Karklin, L.; Arkhipov, A.; Blakely, D.; Dingenen, M.; Mehrotra, A.; Watson, B.; Zelnik, C.; Cote, M.; Hurat, P.

    2007-10-01

    An automated litho-aware design migration solution has been implemented to enable designers to port existing IP layouts (custom, library, and block) to nanometer technologies while optimizing layout printability and silicon yield. With rapidly shrinking technology nodes, the industry consolidation toward fabless or fab-lite manufacturing, demand for second-sourcing and dramatic increase in cost of IP development, the automation of "vertical" (between nodes) and 'horizontal" (between chip manufacturers) migration becomes a very important task. The challenge comes from the fact that even within the same technology node design and process-induced rules deviate substantially among different IDMs and foundries, which leads to costly, error-prone and time consuming design modifications. At the same time, fast and reliable adjustments to design and ability to switch between processes and chip manufacturers could represent significant improvement to TTM, and respectively improving ROI. Using conservative rules (or restricted design rules) is not always a viable option because of the area, performance and yield penalties. The difficulty of migration is augmented by the fact that design rules are not sufficient to guaranty good printability, maximum process window and high yield. Model-based detection of lithography-induced systematic yield-limiting defects (a.k.a. hotspots) is becoming a vital part of the design-for-manufacturing flow for advanced technology nodes at 65nm and below. Driven by customer demand, a collaborative effort between EDA vendors provides a complete design-for-manufacturing migration solution that allows sub-65 nanometer designers to comprehensively address the impact of manufacturing variations on design yield and performance during layout migration. First, the physical hard IP is migrated from its existing 90nm process to a more advanced 65 and 45 nm processes, resulting in an area-optimized DRC-clean 65nm design retaining the original hierarchy to

  18. A Globally Self-Consistent Model of Plate Motions Relative to the Hotspots for the Past 48 Million Years

    Science.gov (United States)

    Koivisto, E.; Gordon, R. G.

    2012-04-01

    Hotspots are volcanic anomalies, either in an intraplate setting or in the form of excessive volcanism along the plate boundaries, not explained by classic plate tectonics. In the early 70's, along with a deep mantle origin, hotspots were proposed to move so slowly relative to one another such that they could be used as a reference frame fixed in the deep mantle for describing plate motions in an "absolute" sense. Ever since the idea was first introduced, however, the rates of relative hotspot motion, and thus the limits of the hotspot frame of reference, have remained a source of heated debate with suggestions ranging from apparent fixity to rapid motion between the hotspots. The question of inter-hotspot motion is closely related to the estimation of true polar wander—rotation of the whole solid earth relative to the spin axis. A fundamental problem of global tectonics and paleomagnetism is determining which part of apparent polar wander—the apparent movement of age-progressive paleomagnetic poles relative to the continent in question—is due to plate motion, and which part is due to true polar wander. One approach for separating these is available if the hotspots are indeed tracking the motion of the mantle beneath the asthenosphere and are moving slowly relative to one another. In this case, a model of plate motion relative to the hotspots can be used to predict the positions of past paleomagnetic poles relative to the spin axis and thus estimate the amount of true polar wander. Cumulative improvements in the age progression along the hotspot tracks, the geomagnetic reversal time scale, and relative plate reconstructions lead to significant changes in earlier results. In this study, we build on a new method for objectively estimating plate-hotspot rotations and their uncertainties, and on our recent results that have demonstrated no significant motion between the Pacific and Indo-Atlantic hotspots since 48 Ma, and present a globally self-consistent model

  19. PEX Genes in Fungal Genomes : Common, Rare or Redundant

    NARCIS (Netherlands)

    Kiel, Jan A.K.W.; Veenhuis, Marten; Klei, Ida J. van der

    2006-01-01

    PEX genes encode proteins, termed peroxins, that are required for the biogenesis and proliferation of microbodies (peroxisomes). We have screened the available protein and DNA databases to identify putative peroxin orthologs in 17 fungal species (yeast and filamentous fungi) and in humans. This

  20. NCCOS Assessment: Groundfish biodiversity hotspots off the Pacific Coast of Oregon from 1971-09-05 to 2010-09-20 (NCEI Accession 0156467)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set comprises maps of predicted long-term groundfish biodiversity hotspot probabilities off the Pacific Coast of Oregon. Predicted hotspot probabilities...

  1. A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

    DEFF Research Database (Denmark)

    Thorgeirsson, T E; Steinberg, S; Reginsson, G. W.

    2016-01-01

    Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution,...

  2. Rare kaon decays

    Energy Technology Data Exchange (ETDEWEB)

    Bryman, D.A.

    1989-01-01

    Major advances spanning several orders of magnitude in sensitivity are anticipated in the current round of experiments with rare kaon decays. Observations of allowed processes, like /Kappa//sup +/ /yields/ /pi//sup +/ /nu//nu/-bar and /Kappa//sup 0//sub L/ /yields/ /mu//sup +//mu//sup -/, shed light on detailed aspects of the standard model. New sources of T or CP violation could be manifested by measurements of muon polarization in /Kappa/ /yields/ /delta//mu//nu//sub /mu// and /Kappa//sup 0//sub L/ /yields/ /mu//sup +//mu//sup -/ decays and by studies of reactions like /Kappa//sup 0//sub L/ /yields/ /pi//sup 0/e/sup +/e/sup -/. Evidence for new particlews and new interactions could appear in advanced efforts to observe /Kappa/ /yields/ /pi/chichi' and /Kappa/ /yields/ /pi/chi decays, where chi and chi' represent hypothethetical neutral particles, and in searches for lepton flavor violating processes /Kappa//sup 0//sub L/ /yields/ /mu/e and /Kappa//sup +/ /yields/ /pi//sup +/ /mu/e. The experiments are reviewed and their theoretical context is discussed.

  3. Recent genomic heritage in Scotland.

    Science.gov (United States)

    Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Wilson, James F; Hastie, Nick; Vitart, Veronique; Hayward, Caroline; Navarro, Pau; Haley, Chris S

    2015-06-06

    The Generation Scotland Scottish Family Health Study (GS:SFHS) includes 23,960 participants from across Scotland with records for many health-related traits and environmental covariates. Genotypes at ~700 K SNPs are currently available for 10,000 participants. The cohort was designed as a resource for genetic and health related research and the study of complex traits. In this study we developed a suite of analyses to disentangle the genomic differentiation within GS:SFHS individuals to describe and optimise the sample and methods for future analyses. We combined the genotypic information of GS:SFHS with 1092 individuals from the 1000 Genomes project and estimated their genomic relationships. Then, we performed Principal Component Analyses of the resulting relationships to investigate the genomic origin of different groups. We characterised two groups of individuals: those with a few sparse rare markers in the genome, and those with several large rare haplotypes which might represent relatively recent exogenous ancestors. We identified some individuals with likely Italian ancestry and a group with some potential African/Asian ancestry. An analysis of homozygosity in the GS:SFHS sample revealed a very similar pattern to other European populations. We also identified an individual carrying a chromosome 1 uniparental disomy. We found evidence of local geographic stratification within the population having impact on the genomic structure. These findings illuminate the history of the Scottish population and have implications for further analyses such as the study of the contributions of common and rare variants to trait heritabilities and the evaluation of genomic and phenotypic prediction of disease.

  4. Complete genomes of Hairstreak butterflies, their speciation, and nucleo-mitochondrial incongruence.

    Science.gov (United States)

    Cong, Qian; Shen, Jinhui; Borek, Dominika; Robbins, Robert K; Otwinowski, Zbyszek; Grishin, Nick V

    2016-04-28

    Comparison of complete genomes of closely related species enables research on speciation and how phenotype is determined by genotype. Lepidoptera, an insect order of 150,000 species with diverse phenotypes, is well-suited for such comparative genomics studies if new genomes, which cover additional Lepidoptera families are acquired. We report a 729 Mbp genome assembly of the Calycopis cecrops, the first genome from the family Lycaenidae and the largest available Lepidoptera genome. As detritivore, Calycopis shows expansion in detoxification and digestion enzymes. We further obtained complete genomes of 8 Calycopis specimens: 3 C. cecrops and 5 C. isobeon, including a dry specimen stored in the museum for 30 years. The two species differ subtly in phenotype and cannot be differentiated by mitochondrial DNA. However, nuclear genomes revealed a deep split between them. Genes that can clearly separate the two species (speciation hotspots) mostly pertain to circadian clock, mating behavior, transcription regulation, development and cytoskeleton. The speciation hotspots and their function significantly overlap with those we previously found in Pterourus, suggesting common speciation mechanisms in these butterflies.

  5. Mutations of the Spliceosome Complex Genes Occur In Adult Patients but Are Very Rare In Children with Myeloid Neoplasia

    DEFF Research Database (Denmark)

    Hirabayashi, Shinsuke; Moetter, Jessica; Yoshida, Kenichi

    patient was diagnosed at age of 17 years with systemic mastocytosis positive for c-kit D816V mutation, and with associated clonal hematological non-mast cell lineage disease: refractory cytopenia with normal cytogenetics. SCT was also performed with success on this patient. To ensure that the low rate...... in methylation and chromatin regulation (TET2, DNMT3A, ASXL1). Although mutations of these genes are present at high frequency in adult cohorts, they are very rare events in children with myeloid disease. Based on the results from a large-scale whole exome sequencing study of adult patients with myeloid....... In summary, re-sequencing of 3 spliceosome gene hotspots revealed the presence of heterozygous mutations in 2/339 children and 4/19 adults with myeloid disease. The analysis of another gene-hotspot implicated in the MDS whole exome study, SF3B1 K700 is ongoing, but all pediatric cases analyzed to date were...

  6. Ocean-wide tracking of pelagic sharks reveals extent of overlap with longline fishing hotspots.

    Science.gov (United States)

    Queiroz, Nuno; Humphries, Nicolas E; Mucientes, Gonzalo; Hammerschlag, Neil; Lima, Fernando P; Scales, Kylie L; Miller, Peter I; Sousa, Lara L; Seabra, Rui; Sims, David W

    2016-02-09

    Overfishing is arguably the greatest ecological threat facing the oceans, yet catches of many highly migratory fishes including oceanic sharks remain largely unregulated with poor monitoring and data reporting. Oceanic shark conservation is hampered by basic knowledge gaps about where sharks aggregate across population ranges and precisely where they overlap with fishers. Using satellite tracking data from six shark species across the North Atlantic, we show that pelagic sharks occupy predictable habitat hotspots of high space use. Movement modeling showed sharks preferred habitats characterized by strong sea surface-temperature gradients (fronts) over other available habitats. However, simultaneous Global Positioning System (GPS) tracking of the entire Spanish and Portuguese longline-vessel fishing fleets show an 80% overlap of fished areas with hotspots, potentially increasing shark susceptibility to fishing exploitation. Regions of high overlap between oceanic tagged sharks and longliners included the North Atlantic Current/Labrador Current convergence zone and the Mid-Atlantic Ridge southwest of the Azores. In these main regions, and subareas within them, shark/vessel co-occurrence was spatially and temporally persistent between years, highlighting how broadly the fishing exploitation efficiently "tracks" oceanic sharks within their space-use hotspots year-round. Given this intense focus of longliners on shark hotspots, our study argues the need for international catch limits for pelagic sharks and identifies a future role of combining fine-scale fish and vessel telemetry to inform the ocean-scale management of fisheries.

  7. Hot-Spot Engineering in 3D Multi-Branched Nanostructures

    DEFF Research Database (Denmark)

    Chirumamilla, Manohar; Chirumamilla, Anisha; Roberts, Alexander

    2017-01-01

    The detection of probe molecules at ultralow concentrations, even at the single-molecule level, can be addressed with the breakthrough concept of plasmonic hot-spot engineering. In view of that, the fabrication of nanostructures endowed with sub-10 nm gaps and extremely large near-field enhanceme...

  8. Subglacial discharges create fluctuating foraging hotspots for sea birds in tidewater glacier bays

    Science.gov (United States)

    Urbanski, Jacek Andrzej; Stempniewicz, Lech; Węsławski, Jan Marcin; Dragańska-Deja, Katarzyna; Wochna, Agnieszka; Goc, Michał; Iliszko, Lech

    2017-01-01

    Although the processes occurring at the front of an ice face in tidewater glacier bays still await thorough investigation, their importance to the rapidly changing polar environment is spurring a considerable research effort. Glacier melting, sediment delivery and the formation of seabird foraging hotspots are governed by subglacial discharges of meltwater. We have combined the results of tracking black-legged kittiwakes Rissa tridactyla equipped with GPS loggers, analyses of satellite images and in situ measurements of water temperature, salinity and turbidity in order to examine the magnitude and variability of such hotspots in the context of glacier bay hydrology. Small though these hotspots are in size, foraging in them appears to be highly intensive. They come into existence only if the subglacial discharge reaches the surface, if the entrainment velocity at a conduit is high and if there is sufficient macroplankton in the entrainment layer. The position and type of subglacial discharges may fluctuate in time and space, thereby influencing glacier bay hydrology and the occurrence of foraging hotspots. PMID:28266602

  9. Submesoscale hotspots of productivity and respiration: Insights from high-resolution oxygen and fluorescence sections

    Science.gov (United States)

    Stanley, Rachel H. R.; McGillicuddy, Dennis J.; Sandwith, Zoe O.; Pleskow, Haley M.

    2017-12-01

    Modeling studies have shown that mesoscale and submesoscale processes can stimulate phytoplankton productivity and export production. Here, we present observations from an undulating, towed Video Plankton Recorder (VPR-II) in the tropical Atlantic. The VPR-II collected profiles of oxygen, fluorescence, temperature and salinity in the upper 140 m of the water column at a spatial resolution of 1 m in the vertical and temperature and salinity surfaces, hotspots are more often areas of net respiration than areas of net production - although the inferred changes in oxygen are subject to uncertainty in the determination of the source of the upwelled waters since the true source water may not have been sampled. We discuss the spatial distribution of these hotspots and present a conceptual model outlining their possible generation and decline. Simultaneous measurements of O2/Ar in the mixed layer from a shipboard mass spectrometer provide estimates of rates of surface net community production. We find that the subsurface biological hotspots are often expressed as an increase in mixed layer rates of net community production. Overall, the large number of these hotspots support the growing evidence that submesoscale processes are important drivers in upper ocean biological production.

  10. Galileo SSI and Cassini ISS Observations of Io's Pele Hotspot: Temperatures, Areas, and Variation with Time

    Science.gov (United States)

    Radebaugh, J.; McEwen, A. S.; Milazzo, M.; Davies, A. G.; Keszthelyi, L. P.; Geissler, P.

    2002-01-01

    Temperatures of Io's Pele hotspot were found using dual-filter observations from Galileo and Cassini. Temperatures average 1375 K, but vary widely over tens of minutes. Dropoff in emission with rotation consistent with lava fountaining at a lava lake. Additional information is contained in the original extended abstract.

  11. A rapid burst in hotspot motion through the interaction of tectonics and deep mantle flow.

    Science.gov (United States)

    Hassan, Rakib; Müller, R Dietmar; Gurnis, Michael; Williams, Simon E; Flament, Nicolas

    2016-05-12

    Volcanic hotspot tracks featuring linear progressions in the age of volcanism are typical surface expressions of plate tectonic movement on top of narrow plumes of hot material within Earth's mantle. Seismic imaging reveals that these plumes can be of deep origin--probably rooted on thermochemical structures in the lower mantle. Although palaeomagnetic and radiometric age data suggest that mantle flow can advect plume conduits laterally, the flow dynamics underlying the formation of the sharp bend occurring only in the Hawaiian-Emperor hotspot track in the Pacific Ocean remains enigmatic. Here we present palaeogeographically constrained numerical models of thermochemical convection and demonstrate that flow in the deep lower mantle under the north Pacific was anomalously vigorous between 100 million years ago and 50 million years ago as a consequence of long-lasting subduction systems, unlike those in the south Pacific. These models show a sharp bend in the Hawaiian-Emperor hotspot track arising from the interplay of plume tilt and the lateral advection of plume sources. The different trajectories of the Hawaiian and Louisville hotspot tracks arise from asymmetric deformation of thermochemical structures under the Pacific between 100 million years ago and 50 million years ago. This asymmetric deformation waned just before the Hawaiian-Emperor bend developed, owing to flow in the deepest lower mantle associated with slab descent in the north and south Pacific.

  12. General Practice Clinical Data Help Identify Dementia Hotspots: A Novel Geospatial Analysis Approach.

    Science.gov (United States)

    Bagheri, Nasser; Wangdi, Kinley; Cherbuin, Nicolas; Anstey, Kaarin J

    2018-01-01

    We have a poor understanding of whether dementia clusters geographically, how this occurs, and how dementia may relate to socio-demographic factors. To shed light on these important questions, this study aimed to compute a dementia risk score for individuals to assess spatial variation of dementia risk, identify significant clusters (hotspots), and explore their association with socioeconomic status. We used clinical records from 16 general practices (468 Statistical Area level 1 s, N = 14,746) from the city of west Adelaide, Australia for the duration of 1 January 2012 to 31 December 2014. Dementia risk was estimated using The Australian National University-Alzheimer's Disease Risk Index. Hotspot analyses were applied to examine potential clusters in dementia risk at small area level. Significant hotspots were observed in eastern and southern areas while coldspots were observed in the western area within the study perimeter. Additionally, significant hotspots were observed in low socio-economic communities. We found dementia risk scores increased with age, sex (female), high cholesterol, no physical activity, living alone (widow, divorced, separated, or never married), and co-morbidities such as diabetes and depression. Similarly, smoking was associated with a lower dementia risk score. The identification of dementia risk clusters may provide insight into possible geographical variations in risk factors for dementia and quantify these risks at the community level. As such, this research may enable policy makers to tailor early prevention strategies to the correct individuals within their precise locations.

  13. An investigation of scalable anomaly detection techniques for a large network of Wi-Fi hotspots

    CSIR Research Space (South Africa)

    Machaka, P

    2015-01-01

    Full Text Available . The Neural Networks, Bayesian Networks and Artificial Immune Systems were used for this experiment. Using a set of data extracted from a live network of Wi-Fi hotspots managed by an ISP; we integrated algorithms into a data collection system to detect...

  14. Landscape-scale analyses suggest both nutrient and antipredator advantages to Serengeti herbivore hotspots

    NARCIS (Netherlands)

    Anderson, T. Michael; Hopcraft, J. Grant C.; Eby, Stephanie; Ritchie, Mark; Grace, James B.; Olff, Han; Young, T.P.

    Mechanistic explanations of herbivore spatial distribution have focused largely on either resource-related (bottom-up) or predation-related (top-down) factors. We studied direct and indirect influences on the spatial distributions of Serengeti herbivore hotspots, defined as temporally stable areas

  15. Hotspots of soil N2O emission enhanced through water absorption by plant residue

    Science.gov (United States)

    Kravchenko, A. N.; Toosi, E. R.; Guber, A. K.; Ostrom, N. E.; Yu, J.; Azeem, K.; Rivers, M. L.; Robertson, G. P.

    2017-07-01

    N2O is a highly potent greenhouse gas and arable soils represent its major anthropogenic source. Field-scale assessments and predictions of soil N2O emission remain uncertain and imprecise due to the episodic and microscale nature of microbial N2O production, most of which occurs within very small discrete soil volumes. Such hotspots of N2O production are often associated with decomposing plant residue. Here we quantify physical and hydrological soil characteristics that lead to strikingly accelerated N2O emissions in plant residue-induced hotspots. Results reveal a mechanism for microscale N2O emissions: water absorption by plant residue that creates unique micro-environmental conditions, markedly different from those of the bulk soil. Moisture levels within plant residue exceeded those of bulk soil by 4-10-fold and led to accelerated N2O production via microbial denitrification. The presence of large (∅ >35 μm) pores was a prerequisite for maximized hotspot N2O production and for subsequent diffusion to the atmosphere. Understanding and modelling hotspot microscale physical and hydrologic characteristics is a promising route to predict N2O emissions and thus to develop effective mitigation strategies and estimate global fluxes in a changing environment.

  16. Suicides on the Austrian railway network: hotspot analysis and effect of proximity to psychiatric institutions.

    Science.gov (United States)

    Strauss, Markus J; Klimek, Peter; Sonneck, Gernot; Niederkrotenthaler, Thomas

    2017-03-01

    Railway suicide is a significant public health problem. In addition to the loss of lives, these suicides occur in public space, causing traumatization among train drivers and passengers, and significant public transport delays. Prevention efforts depend upon accurate knowledge of clustering phenomena across the railway network, and spatial risk factors. Factors such as proximity to psychiatric institutions have been discussed to impact on railway suicides, but analytic evaluations are scarce and limited. We identify 15 hotspots on the Austrian railway system while taking case location uncertainties into account. These hotspots represent 0.9% of the total track length (5916 km/3676 miles) that account for up to 17% of all railway suicides (N=1130). We model suicide locations on the network using a smoothed inhomogeneous Poisson process and validate it using randomization tests. We find that the density of psychiatric beds is a significant predictor of railway suicide. Further predictors are population density, multitrack structure and-less consistently-spatial socio-economic factors including total suicide rates. We evaluate the model for the identified hotspots and show that the actual influence of these variables differs across individual hotspots. This analysis provides important information for suicide prevention research and practice. We recommend structural separation of railway tracks from nearby psychiatric institutions to prevent railway suicide.

  17. A rapid burst in hotspot motion through the interaction of tectonics and deep mantle flow

    Science.gov (United States)

    Hassan, Rakib; Müller, R. Dietmar; Gurnis, Michael; Williams, Simon E.; Flament, Nicolas

    2016-05-01

    Volcanic hotspot tracks featuring linear progressions in the age of volcanism are typical surface expressions of plate tectonic movement on top of narrow plumes of hot material within Earth’s mantle. Seismic imaging reveals that these plumes can be of deep origin—probably rooted on thermochemical structures in the lower mantle. Although palaeomagnetic and radiometric age data suggest that mantle flow can advect plume conduits laterally, the flow dynamics underlying the formation of the sharp bend occurring only in the Hawaiian-Emperor hotspot track in the Pacific Ocean remains enigmatic. Here we present palaeogeographically constrained numerical models of thermochemical convection and demonstrate that flow in the deep lower mantle under the north Pacific was anomalously vigorous between 100 million years ago and 50 million years ago as a consequence of long-lasting subduction systems, unlike those in the south Pacific. These models show a sharp bend in the Hawaiian-Emperor hotspot track arising from the interplay of plume tilt and the lateral advection of plume sources. The different trajectories of the Hawaiian and Louisville hotspot tracks arise from asymmetric deformation of thermochemical structures under the Pacific between 100 million years ago and 50 million years ago. This asymmetric deformation waned just before the Hawaiian-Emperor bend developed, owing to flow in the deepest lower mantle associated with slab descent in the north and south Pacific.

  18. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces

    NARCIS (Netherlands)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D G; Cordeiro, Maria Natália D S; Gümüş, Zeynep H; Costa, Joaquim; Bonvin, Alexandre M J J; de Sousa Moreira, Irina

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model

  19. Subglacial discharges create fluctuating foraging hotspots for sea birds in tidewater glacier bays

    Science.gov (United States)

    Urbanski, Jacek Andrzej; Stempniewicz, Lech; Węsławski, Jan Marcin; Dragańska-Deja, Katarzyna; Wochna, Agnieszka; Goc, Michał; Iliszko, Lech

    2017-03-01

    Although the processes occurring at the front of an ice face in tidewater glacier bays still await thorough investigation, their importance to the rapidly changing polar environment is spurring a considerable research effort. Glacier melting, sediment delivery and the formation of seabird foraging hotspots are governed by subglacial discharges of meltwater. We have combined the results of tracking black-legged kittiwakes Rissa tridactyla equipped with GPS loggers, analyses of satellite images and in situ measurements of water temperature, salinity and turbidity in order to examine the magnitude and variability of such hotspots in the context of glacier bay hydrology. Small though these hotspots are in size, foraging in them appears to be highly intensive. They come into existence only if the subglacial discharge reaches the surface, if the entrainment velocity at a conduit is high and if there is sufficient macroplankton in the entrainment layer. The position and type of subglacial discharges may fluctuate in time and space, thereby influencing glacier bay hydrology and the occurrence of foraging hotspots.

  20. Hotspots of soil N2O emission enhanced through water absorption by plant residue

    Energy Technology Data Exchange (ETDEWEB)

    Kravchenko, A.N.; Toosi, E.R.; Guber, A.K.; Ostrom, N.E.; Yu, J.; Azeem, K.; Rivers, M.L.; Robertson , G.P. (UAF Pakistan); (UC); (Hubei); (MSU)

    2017-06-05

    N2O is a highly potent greenhouse gas and arable soils represent its major anthropogenic source. Field-scale assessments and predictions of soil N2O emission remain uncertain and imprecise due to the episodic and microscale nature of microbial N2O production, most of which occurs within very small discrete soil volumes. Such hotspots of N2O production are often associated with decomposing plant residue. Here we quantify physical and hydrological soil characteristics that lead to strikingly accelerated N2O emissions in plant residue-induced hotspots. Results reveal a mechanism for microscale N2O emissions: water absorption by plant residue that creates unique micro-environmental conditions, markedly different from those of the bulk soil. Moisture levels within plant residue exceeded those of bulk soil by 4–10-fold and led to accelerated N2O production via microbial denitrification. The presence of large (Ø >35 μm) pores was a prerequisite for maximized hotspot N2O production and for subsequent diffusion to the atmosphere. Understanding and modelling hotspot microscale physical and hydrologic characteristics is a promising route to predict N2O emissions and thus to develop effective mitigation strategies and estimate global fluxes in a changing environment.

  1. Impact of metric and sample size on determining malaria hotspot boundaries

    NARCIS (Netherlands)

    Stresman, G.H.; Giorgi, E.; Baidjoe, A.Y.; Knight, P.; Odongo, W.; Owaga, C.; Shagari, S.; Makori, E.; Stevenson, J.; Drakeley, C.; Cox, J.; Bousema, T.; Diggle, P.J.

    2017-01-01

    The spatial heterogeneity of malaria suggests that interventions may be targeted for maximum impact. It is unclear to what extent different metrics lead to consistent delineation of hotspot boundaries. Using data from a large community-based malaria survey in the western Kenyan highlands, we

  2. Spatial Patterns in Discordant Diagnostic Test Results for Chagas Disease: Links to Transmission Hotspots

    Science.gov (United States)

    Levy, Michael Z.; Bowman, Natalie M.; Kawai, Vivian; Plotkin, Joshua B.; Waller, Lance A.; Cabrera, Lilia; Steurer, Frank; Seitz, Amy E.; Pinedo-Cancino, Viviana V.; Carpio, Juan Geny Cornejo del; Benzaquen, Eleazar Cordova; McKenzie, F. Ellis; Maguire, James H.; Gilman, Robert H.; Bern, Caryn

    2009-01-01

    Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting. PMID:19278335

  3. LOFAR imaging of Cygnus A - direct detection of a turnover in the hotspot radio spectra

    NARCIS (Netherlands)

    McKean, J.P.; Godfrey, L.E.H.; Vegetti, S.; Wise, M.W.; Morganti, R.; Bentum, Marinus Jan; Hardcastle, M.J.; Rafferty, D.; Anderson, J.; Avruch, I.M.; Beck, R.; Bell, M.E.; van Bemmel, I.; Bernardi, G.

    2016-01-01

    The low-frequency radio spectra of the hotspots within powerful radio galaxies can provide valuable information about the physical processes operating at the site of the jet termination. These processes are responsible for the dissipation of jet kinetic energy, particle acceleration, and

  4. Dependence of hotspot criticality on molecular structure: amorphous vs. crystalline RDX

    Science.gov (United States)

    Sakano, Michael; Hamilton, Brenden; Islam, Md Mahbubul; Strachan, Alejandro

    2017-06-01

    Recent large-scale molecular dynamics (MD) simulations showed that hotspots resulting from the dynamical collapse of a void are significantly more reactive that nominally identical ones (in terms of size and thermodynamic conditions) but created under equilibrium conditions. In this work we assess whether the molecular disorder caused by the pore collapse is the main culprit for the increased reactivity of the dynamical hot spot. We use MD with the reactive force field ReaxFF to characterize the kinetics of decomposition of crystalline and amorphous RDX and to characterize the criticality of cylindrical hotspots in both materials. The simulations indicate negligible differences in the reactivity between the two structures when subjected to homogeneous heating. We also studied the chemical decomposition and reaction of cylindrical hotspots of various sizes and temperatures in the two structures. Our preliminary results indicate that hotspots in amorphous RDX are more reactive and, for a given size, transition to a deflagration wave at lower temperatures. We will discuss the possible origin of these surprising observation, including differences in thermal conductivity, temperature-induced structural transformations and the difference in exothermicity between the two systems..

  5. Projected loss of a salamander diversity hotspot as a consequence of projected global climate change

    Science.gov (United States)

    Joseph R. Milanovich; William E. Peterman; Nathan P. Nibbelink; John C. Maerz

    2010-01-01

    Background: Significant shifts in climate are considered a threat to plants and animals with significant physiological limitations and limited dispersal abilities. The southern Appalachian Mountains are a global hotspot for plethodontid salamander diversity. Plethodontids are lungless ectotherms, so their ecology is strongly governed by temperature and precipitation....

  6. Sistem Autentikasi Hotspot Menggunakan LDAP dan Radius pada Jaringan Internet Wireless Prodi Teknik Sistem Komputer

    National Research Council Canada - National Science Library

    Ahmad Herdinal Muttaqin; Adian Fatchur Rochim; Eko Didik Widianto

    2016-01-01

    ... it’s need creating a security system with LDAP and RADIUS.The results of this study is a network authentication server using OpenLDAP and FreeRadius Hotspot that will be integrated with an account of Academic Information System, which is implemented on Prodi Computer Systems Engineering Department of the University of Diponegoro.

  7. Using a distribution and conservation status weighted hotspot approach to identify areas in need of conservation action to benefit Idaho bird species

    Science.gov (United States)

    Haines, Aaron M.; Leu, Matthias; Svancara, Leona K.; Wilson, Gina; Scott, J. Michael

    2010-01-01

    Identification of biodiversity hotspots (hereafter, hotspots) has become a common strategy to delineate important areas for wildlife conservation. However, the use of hotspots has not often incorporated important habitat types, ecosystem services, anthropogenic activity, or consistency in identifying important conservation areas. The purpose of this study was to identify hotspots to improve avian conservation efforts for Species of Greatest Conservation Need (SGCN) in the state of Idaho, United States. We evaluated multiple approaches to define hotspots and used a unique approach based on weighting species by their distribution size and conservation status to identify hotspot areas. All hotspot approaches identified bodies of water (Bear Lake, Grays Lake, and American Falls Reservoir) as important hotspots for Idaho avian SGCN, but we found that the weighted approach produced more congruent hotspot areas when compared to other hotspot approaches. To incorporate anthropogenic activity into hotspot analysis, we grouped species based on their sensitivity to specific human threats (i.e., urban development, agriculture, fire suppression, grazing, roads, and logging) and identified ecological sections within Idaho that may require specific conservation actions to address these human threats using the weighted approach. The Snake River Basalts and Overthrust Mountains ecological sections were important areas for potential implementation of conservation actions to conserve biodiversity. Our approach to identifying hotspots may be useful as part of a larger conservation strategy to aid land managers or local governments in applying conservation actions on the ground.

  8. Rare B decays at LHCb

    CERN Document Server

    Puig Navarro, Albert

    2017-01-01

    Rare decays are flavour changing neutral current processes that allow sensitive searches for phenomena beyond the Standard Model (SM). In the SM, rare decays are loop-suppressed and new particles in SM extensions can give significant contributions. The very rare decay $B^0_s\\to\\mu^+\\mu^-$ in addition helicity suppressed and constitutes a powerful probe for new (pseudo) scalar particles. Of particular interest are furthermore tests of lepton universality in rare $b\\to s\\ell^+\\ell^-$ decays. The LHCb experiment is designed for the study of b-hadron decays and ideally suited for the analysis of rare decays due to its high trigger efficiency, as well as excellent tracking and particle identification performance. Recent results from the LHCb experiment in the area of rare decays are presented, including tests of lepton universality and searches for lepton flavour violation.

  9. IMPLEMENTASI SISTEM AUTENTIKASI JARINGAN HOTSPOT UNIVERSITAS UDAYANA DENGAN MENGGUNAKAN OPEN SOURCE FREERADIUS

    Directory of Open Access Journals (Sweden)

    Pande sudiarta

    2010-07-01

    Full Text Available Universitas Udayana sudah menyediakan layanan akses hotspot di beberapa Fakultasnya baik yang berada diKampus Denpasar, Kampus Nias, maupun di Kampus Bukit Jimbaran. Untuk dapat memanfaatkan layanan hotspot,user harus login terlebih dahulu dan melewati proses autentikasi username dan password. Saat ini user account digeneratedari ticket printer yang terpasang ke masing-masing akses poin yang ada di Universitas Udayana. Melihatbanyaknya layanan hotspot yang ada di Universitas Udayana, tentunya akan menyulitkan user karena masingmasinghotspot mempunyai account yang berbeda-beda. Sehingga dilakukan penelitian bagaimanamengimplementasikan sistem autentikasi terpusat menggunakan open source freeradius dan mysql sebagai databaseuser serta mengimplementasikan manajemen sistem yang berbasis web interface untuk memudahkan administratoratau operator dalam mengelola user.Hasil penelitian ini akan dipakai sebagai sistem yang akan menangani autentikasi user jaringan hotspot secaraterpusat di Universitas Udayana. Metode analisis yang digunakan pada penelitian ini yaitu dengan metode analisisdeskriftif yaitu menganalisis data-data hasil pengujian yang dilakukan dan menarik kesimpulan dari hasil analisistersebut. Pengujian dilakukan dengan menguji kestabilan sistem dalam menangani permintaan autentikasi dalamjumlah yang banyak yang login dalam waktu yang bersamaan, menerapkan secondary server, melakukan pengujianseberapa signifikan pengaruh jarak terhadap time latency autentikasi user dengan account radius, pengujian timelatency autentikasi user yang akses ke extended akses poin baik yang menggunakan gelombang radio dan fiber optikdengan account radius. Dalam mengimplementasikan sistem autentikasi radius diperlukan server radius yang akanmenangani proses autentikasi, autorisasi dan accounting user. Semua hotspot yang terintegrasi dengan server radiusakan melakukan autentikasi ke sebuah server radius.Dengan menerapkan web based administration interface, maka

  10. SLR-induced temporal and spatial changes in hotspots to storms along the Catalan coast

    Science.gov (United States)

    Jiménez, Jose A.; Sanuy, Marc; Valdemoro, Herminia

    2017-04-01

    Coastal hotspots to storms can be simply defined as locations where the magnitude of the storm-induced risk is significantly higher than neighbouring areas for a given probability of occurrence. Their distribution along the coast depends on the magnitude of storm-induced hazards and on the coastal resilient capacity. Increasing damages observed in our coasts during the last decades have driven the need to include specific chapters on risk management in ICZM plans. In this context, the identification of hotspots is one of the first points to be considered. This permits to better allocate resources for risk management by concentrating efforts in specific locations. Within this context, we have identified hotspots along the Catalan coast (Spanish Mediterranean) to storm-induced erosion and inundation hazards. This has been done by using the methodology developed within the RISCKIT EU project where storm-induced hazards (erosion and inundation) are characterised in probabilistic terms by using simple inundation and erosion models as a function of water level and wave climates and local coastal morphology. The final result was a set of inundation and erosion hotspots along the coast under current conditions for selected probabilities of occurrences, P. For low return periods, Tr, few hotspots appear and they represent coastal locations frequently affected by the corresponding hazard. On the other, for high Tr, a larger number (and of larger extension) of hotspots appear, that although less frequently affected, they are subjected to a larger impact. Although this is valuable information for coastal managers, it is only valid for making decisions for a short time horizon or under steady conditions. However, since the proper time scale for coastal planning is in the order of several decades, it is not likely that conditions will remain steady. Thus, although most of existing predictions of climate-induce changes in storminess in the Mediterranean indicate the absence of

  11. Rare-earth elements

    Science.gov (United States)

    Van Gosen, Bradley S.; Verplanck, Philip L.; Seal, Robert R.; Long, Keith R.; Gambogi, Joseph; Schulz, Klaus J.; DeYoung, John H.; Seal, Robert R.; Bradley, Dwight C.

    2017-12-19

    The rare-earth elements (REEs) are 15 elements that range in atomic number from 57 (lanthanum) to 71 (lutetium); they are commonly referred to as the “lanthanides.” Yttrium (atomic number 39) is also commonly regarded as an REE because it shares chemical and physical similarities and has affinities with the lanthanides. Although REEs are not rare in terms of average crustal abundance, the concentrated deposits of REEs are limited in number.Because of their unusual physical and chemical properties, the REEs have diverse defense, energy, industrial, and military technology applications. The glass industry is the leading consumer of REE raw materials, which are used for glass polishing and as additives that provide color and special optical properties to the glass. Lanthanum-based catalysts are used in petroleum refining, and cerium-based catalysts are used in automotive catalytic converters. The use of REEs in magnets is a rapidly increasing application. Neodymium-iron-boron magnets, which are the strongest known type of magnets, are used when space and weight are restrictions. Nickel-metal hydride batteries use anodes made of a lanthanum-based alloys.China, which has led the world production of REEs for decades, accounted for more than 90 percent of global production and supply, on average, during the past decade. Citing a need to retain its limited REE resources to meet domestic requirements as well as concerns about the environmental effects of mining, China began placing restrictions on the supply of REEs in 2010 through the imposition of quotas, licenses, and taxes. As a result, the global rare-earth industry has increased its stockpiling of REEs; explored for deposits outside of China; and promoted new efforts to conserve, recycle, and substitute for REEs. New mine production began at Mount Weld in Western Australia, and numerous other exploration and development projects noted in this chapter are ongoing throughout the world.The REE-bearing minerals are

  12. Genomics for environmental microbiology

    Energy Technology Data Exchange (ETDEWEB)

    Deutschbauer, Adam M.; Chivian, Dylan; Arkin, Adam P.

    2006-03-16

    The utilization of natural microbial diversity inbiotechnology is hindered by both our inability to culture the vastmajority of microorganisms and the observation that lab engineeredbacteria rarely function in the wild. It is now clear that anunderstanding of the community structure, function, and evolution ofbacteria in their natural environments is required to meet the promise ofmicrobial biotechnology. To meet these new challenges, microbiologistsare applying the tools of genomics and related high-throughputtechnologies to both cultured microbes and environmental samples. The newviews on ecosystems and biological function together with thebiotechnology that are enabled by this science are discussed as are thenew technologies and the challenges therein.

  13. Overlooked mountain rock pools in deserts are critical local hotspots of biodiversity.

    Science.gov (United States)

    Vale, Cândida Gomes; Pimm, Stuart L; Brito, José Carlos

    2015-01-01

    The world is undergoing exceptional biodiversity loss. Most conservation efforts target biodiversity hotspots at large scales. Such approach overlooks small-sized local hotspots, which may be rich in endemic and highly threatened species. We explore the importance of mountain rock pools (gueltas) as local biodiversity hotspots in the Sahara-Sahel. Specifically, we considered how many vertebrates (total and endemics) use gueltas, what factors predict species richness, and which gueltas are of most priority for conservation. We expected to provide management recommendations, improve local biodiversity conservation, and simultaneously contribute with a framework for future enhancement of local communities' economy. The identification of local hotspots of biodiversity is important for revaluating global conservation priorities. We quantified the number of vertebrate species from each taxonomic group and endemics present in 69 gueltas in Mauritania, then compared these with species present in a surrounding area and recorded in the country. We evaluated the predictors of species number's present in each guelta through a multiple regression model. We ranked gueltas by their priority for conservation taking into account the percentage of endemics and threats to each guelta. Within a mere aggregate extent of 43 ha, gueltas hold about 32% and 78% of the total taxa analysed and endemics of Mauritania, respectively. The number of species present in each guelta increased with the primary productivity and area of gueltas and occurrence of permanent water. Droughts and human activities threaten gueltas, while 64% of them are currently unprotected. Gueltas are crucial for local biodiversity conservation and human activities. They require urgent management plans in Mauritania's mountains. They could provide refugia under climate change being important for long-term conservation of Sahara-Sahel biodiversity. Given their disproportional importance in relation to their size, they are

  14. Overlooked mountain rock pools in deserts are critical local hotspots of biodiversity.

    Directory of Open Access Journals (Sweden)

    Cândida Gomes Vale

    Full Text Available The world is undergoing exceptional biodiversity loss. Most conservation efforts target biodiversity hotspots at large scales. Such approach overlooks small-sized local hotspots, which may be rich in endemic and highly threatened species. We explore the importance of mountain rock pools (gueltas as local biodiversity hotspots in the Sahara-Sahel. Specifically, we considered how many vertebrates (total and endemics use gueltas, what factors predict species richness, and which gueltas are of most priority for conservation. We expected to provide management recommendations, improve local biodiversity conservation, and simultaneously contribute with a framework for future enhancement of local communities' economy. The identification of local hotspots of biodiversity is important for revaluating global conservation priorities.We quantified the number of vertebrate species from each taxonomic group and endemics present in 69 gueltas in Mauritania, then compared these with species present in a surrounding area and recorded in the country. We evaluated the predictors of species number's present in each guelta through a multiple regression model. We ranked gueltas by their priority for conservation taking into account the percentage of endemics and threats to each guelta. Within a mere aggregate extent of 43 ha, gueltas hold about 32% and 78% of the total taxa analysed and endemics of Mauritania, respectively. The number of species present in each guelta increased with the primary productivity and area of gueltas and occurrence of permanent water. Droughts and human activities threaten gueltas, while 64% of them are currently unprotected.Gueltas are crucial for local biodiversity conservation and human activities. They require urgent management plans in Mauritania's mountains. They could provide refugia under climate change being important for long-term conservation of Sahara-Sahel biodiversity. Given their disproportional importance in relation to their

  15. The California Hotspots Project: identifying regions of rapid diversification of mammals.

    Science.gov (United States)

    Davis, Edward Byrd; Koo, Michelle S; Conroy, Chris; Patton, James L; Moritz, Craig

    2008-01-01

    The high rate of anthropogenic impact on natural systems mandates protection of the evolutionary processes that generate and sustain biological diversity. Environmental drivers of diversification include spatial heterogeneity of abiotic and biotic agents of divergent selection, features that suppress gene flow, and climatic or geological processes that open new niche space. To explore how well such proxies perform as surrogates for conservation planning, we need first to map areas with rapid diversification -'evolutionary hotspots'. Here we combine estimates of range size and divergence time to map spatial patterns of neo-endemism for mammals of California, a global biodiversity hotspot. Neo-endemism is explored at two scales: (i) endemic species, weighted by the inverse of range size and mtDNA sequence divergence from sisters; and (ii) as a surrogate for spatial patterns of phenotypic divergence, endemic subspecies, again using inverse-weighting of range size. The species-level analysis revealed foci of narrowly endemic, young taxa in the central Sierra Nevada, northern and central coast, and Tehachapi and Peninsular Ranges. The subspecies endemism-richness analysis supported the last four areas as hotspots for diversification, but also highlighted additional coastal areas (Monterey to north of San Francisco Bay) and the Inyo Valley to the east. We suggest these hotspots reflect the major processes shaping mammal neo-endemism: steep environmental gradients, biotic admixture areas, and areas with recent geological/climate change. Anthropogenic changes to both environment and land use will have direct impacts on regions of rapid divergence. However, despite widespread changes to land cover in California, the majority of the hotspots identified here occur in areas with relatively intact ecological landscapes. The geographical scope of conserving evolutionary process is beyond the scale of any single agency or nongovernmental organization. Choosing which land to

  16. Identification of burden hotspots and risk factors for cholera in India: An observational study.

    Science.gov (United States)

    Ali, Mohammad; Sen Gupta, Sanjukta; Arora, Nisha; Khasnobis, Pradeep; Venkatesh, Srinivas; Sur, Dipika; Nair, Gopinath B; Sack, David A; Ganguly, Nirmal K

    2017-01-01

    Even though cholera has existed for centuries and many parts of the country have sporadic, endemic and epidemic cholera, it is still an under-recognized health problem in India. A Cholera Expert Group in the country was established to gather evidence and to prepare a road map for control of cholera in India. This paper identifies cholera burden hotspots and factors associated with an increased risk of the disease. We acquired district level data on cholera case reports of 2010-2015 from the Integrated Disease Surveillance Program. Socioeconomic characteristics and coverage of water and sanitation was obtained from the 2011 census. Spatial analysis was performed to identify cholera hotspots, and a zero-inflated Poisson regression was employed to identify the factors associated with cholera and predicted case count in the district. 27,615 cholera cases were reported during the 6-year period. Twenty-four of 36 states of India reported cholera during these years, and 13 states were classified as endemic. Of 641 districts, 78 districts in 15 states were identified as "hotspots" based on the reported cases. On the other hand, 111 districts in nine states were identified as "hotspots" from model-based predicted number of cases. The risk for cholera in a district was negatively associated with the coverage of literate persons, households using treated water source and owning mobile telephone, and positively associated with the coverage of poor sanitation and drainage conditions and urbanization level in the district. The study reaffirms that cholera continues to occur throughout a large part of India and identifies the burden hotspots and risk factors. Policymakers may use the findings of the article to develop a roadmap for prevention and control of cholera in India.

  17. Next-Generation Invaders? Hotspots for Naturalised Sleeper Weeds in Australia under Future Climates

    Science.gov (United States)

    Roger, Erin; Hughes, Lesley; Downey, Paul O.; Leishman, Michelle R.

    2013-01-01

    Naturalised, but not yet invasive plants, pose a nascent threat to biodiversity. As climate regimes continue to change, it is likely that a new suite of invaders will emerge from the established pool of naturalised plants. Pre-emptive management of locations that may be most suitable for a large number of potentially invasive plants will help to target monitoring, and is vital for effective control. We used species distribution models (SDM) and invasion-hotspot analysis to determine where in Australia suitable habitat may occur for 292 naturalised plants. SDMs were built in MaxEnt using both climate and soil variables for current baseline conditions. Modelled relationships were projected onto two Representative Concentration Pathways for future climates (RCP 4.5 and 8.5), based on seven global climate models, for two time periods (2035, 2065). Model outputs for each of the 292 species were then aggregated into single ‘hotspot’ maps at two scales: continental, and for each of Australia’s 37 ecoregions. Across Australia, areas in the south-east and south-west corners of the continent were identified as potential hotspots for naturalised plants under current and future climates. These regions provided suitable habitat for 288 and 239 species respectively under baseline climates. The areal extent of the continental hotspot was projected to decrease by 8.8% under climates for 2035, and by a further 5.2% by 2065. A similar pattern of hotspot contraction under future climates was seen for the majority of ecoregions examined. However, two ecoregions - Tasmanian temperate forests and Australian Alps montane grasslands - showed increases in the areal extent of hotspots of >45% under climate scenarios for 2065. The alpine ecoregion also had an increase in the number of naturalised plant species with abiotically suitable habitat under future climate scenarios, indicating that this area may be particularly vulnerable to future incursions by naturalised plants. PMID

  18. Climate change hotspots in the CMIP5 global climate model ensemble.

    Science.gov (United States)

    Diffenbaugh, Noah S; Giorgi, Filippo

    2012-01-10

    We use a statistical metric of multi-dimensional climate change to quantify the emergence of global climate change hotspots in the CMIP5 climate model ensemble. Our hotspot metric extends previous work through the inclusion of extreme seasonal temperature and precipitation, which exert critical influence on climate change impacts. The results identify areas of the Amazon, the Sahel and tropical West Africa, Indonesia, and the Tibetan Plateau as persistent regional climate change hotspots throughout the 21 st century of the RCP8.5 and RCP4.5 forcing pathways. In addition, areas of southern Africa, the Mediterranean, the Arctic, and Central America/western North America also emerge as prominent regional climate change hotspots in response to intermediate and high levels of forcing. Comparisons of different periods of the two forcing pathways suggest that the pattern of aggregate change is fairly robust to the level of global warming below approximately 2°C of global warming (relative to the late-20 th -century baseline), but not at the higher levels of global warming that occur in the late-21 st -century period of the RCP8.5 pathway, with areas of southern Africa, the Mediterranean, and the Arctic exhibiting particular intensification of relative aggregate climate change in response to high levels of forcing. Although specific impacts will clearly be shaped by the interaction of climate change with human and biological vulnerabilities, our identification of climate change hotspots can help to inform mitigation and adaptation decisions by quantifying the rate, magnitude and causes of the aggregate climate response in different parts of the world.

  19. Ostracod (Ostracoda, Crustacea) genomics - Promises and challenges.

    Science.gov (United States)

    Schön, Isa; Martens, Koen

    2016-10-01

    Ostracods are well-suited model organisms for evolutionary research. Classic genetic techniques have mostly been used for phylogenetic studies on Ostracoda and were somewhat affected by the lack of large numbers of suitable markers. Genomic methods with their huge potential have so far rarely been applied to this group of crustaceans. We provide relevant examples of genomic studies on other organisms to propose future avenues of genomic ostracod research. At the same time, we suggest solutions to the potential problems in ostracods that the application of genomic techniques might present. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Genomic networks of hybrid sterility.

    Directory of Open Access Journals (Sweden)

    Leslie M Turner

    2014-02-01

    Full Text Available Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities". The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL. Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is

  1. Genomic networks of hybrid sterility.

    Science.gov (United States)

    Turner, Leslie M; White, Michael A; Tautz, Diethard; Payseur, Bret A

    2014-02-01

    Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad

  2. Genomic Networks of Hybrid Sterility

    Science.gov (United States)

    Turner, Leslie M.; White, Michael A.; Tautz, Diethard; Payseur, Bret A.

    2014-01-01

    Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci (“Dobzhansky-Muller incompatibilities”). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL—but not cis eQTL—were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is

  3. Use of local Moran's I and GIS to identify pollution hotspots of Pb in urban soils of Galway, Ireland.

    Science.gov (United States)

    Zhang, Chaosheng; Luo, Lin; Xu, Weilin; Ledwith, Valerie

    2008-07-15

    Pollution hotspots in urban soils need to be identified for better environmental management. It is important to know if there are hotspots and if the hotspots are statistically significant. In this study identification of pollution hotspots was investigated using Pb concentrations in urban soils of Galway City in Ireland as an example, and the influencing factors on results of hotspot identification were investigated. The index of local Moran's I is a useful tool for identifying pollution hotspots of Pb pollution in urban soils, and for classifying them into spatial clusters and spatial outliers. The results were affected by the definition of weight function, data transformation and existence of extreme values. Compared with the results for the positively skewed raw data, the transformed data and data with extreme values excluded revealed a larger area for the high value spatial clusters in the city centre. While it is hard to decide the best way of using this index, it is suggested that all these influencing factors should be considered until reasonable and reliable results are obtained. GIS mapping can be applied to help evaluate the results via visualization of the spatial patterns. Meanwhile, selected pollution hotspots (extreme values) in this study were confirmed by re-analyses and re-sampling.

  4. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images

    Science.gov (United States)

    Kather, Jakob Nikolas; Marx, Alexander; Reyes-Aldasoro, Constantino Carlos; Schad, Lothar R.; Zöllner, Frank Gerrit; Weis, Cleo-Aron

    2015-01-01

    Blood vessels in solid tumors are not randomly distributed, but are clustered in angiogenic hotspots. Tumor microvessel density (MVD) within these hotspots correlates with patient survival and is widely used both in diagnostic routine and in clinical trials. Still, these hotspots are usually subjectively defined. There is no unbiased, continuous and explicit representation of tumor vessel distribution in histological whole slide images. This shortcoming distorts angiogenesis measurements and may account for ambiguous results in the literature. In the present study, we describe and evaluate a new method that eliminates this bias and makes angiogenesis quantification more objective and more efficient. Our approach involves automatic slide scanning, automatic image analysis and spatial statistical analysis. By comparing a continuous MVD function of the actual sample to random point patterns, we introduce an objective criterion for hotspot detection: An angiogenic hotspot is defined as a clustering of blood vessels that is very unlikely to occur randomly. We evaluate the proposed method in N=11 images of human colorectal carcinoma samples and compare the results to a blinded human observer. For the first time, we demonstrate the existence of statistically significant hotspots in tumor images and provide a tool to accurately detect these hotspots. PMID:26061817

  5. Genome Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genome Imprinting - The Silencing of Genes and Genomes. H A Ranganath M T Tanuja. General Article Volume 5 Issue 9 September 2000 pp 49-57. Fulltext. Click here to view fulltext PDF. Permanent link:

  6. Baculovirus Genomics

    NARCIS (Netherlands)

    Oers, van M.M.; Vlak, J.M.

    2007-01-01

    Baculovirus genomes are covalently closed circles of double stranded-DNA varying in size between 80 and 180 kilobase-pair. The genomes of more than fourty-one baculoviruses have been sequenced to date. The majority of these (37) are pathogenic to lepidopteran hosts; three infect sawflies

  7. Status of rare decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Littenberg, L.S.

    1984-01-01

    Some results are given for rare muon decay experiments currently running. Also, plans are discussed for rare kaon decay experiments. Some of the events sought come from processes which violate lepton flavor conservation. Several apparatuses used in the search are described. 35 references. (LEW)

  8. The impact of hotspot-targeted interventions on malaria transmission: study protocol for a cluster-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bousema Teun

    2013-02-01

    Full Text Available Abstract Background Malaria transmission is highly heterogeneous in most settings, resulting in the formation of recognizable malaria hotspots. Targeting these hotspots might represent a highly efficacious way of controlling or eliminating malaria if the hotspots fuel malaria transmission to the wider community. Methods/design Hotspots of malaria will be determined based on spatial patterns in age-adjusted prevalence and density of antibodies against malaria antigens apical membrane antigen-1 and merozoite surface protein-1. The community effect of interventions targeted at these hotspots will be determined. The intervention will comprise larviciding, focal screening and treatment of the human population, distribution of long-lasting insecticide-treated nets and indoor residual spraying. The impact of the intervention will be determined inside and up to 500 m outside the targeted hotspots by PCR-based parasite prevalence in cross-sectional surveys, malaria morbidity by passive case detection in selected facilities and entomological monitoring of larval and adult Anopheles populations. Discussion This study aims to provide direct evidence for a community effect of hotspot-targeted interventions. The trial is powered to detect large effects on malaria transmission in the context of ongoing malaria interventions. Follow-up studies will be needed to determine the effect of individual components of the interventions and the cost-effectiveness of a hotspot-targeted approach, where savings made by reducing the number of compounds that need to receive interventions should outweigh the costs of hotspot-detection. Trial registration NCT01575613. The protocol was registered online on 20 March 2012; the first community was randomized on 26 March 2012.

  9. Genomic footprinting.

    Science.gov (United States)

    Vierstra, Jeff; Stamatoyannopoulos, John A

    2016-03-01

    The advent of DNA footprinting with DNase I more than 35 years ago enabled the systematic analysis of protein-DNA interactions, and the technique has been instrumental in the decoding of cis-regulatory elements and the identification and characterization of transcription factors and other DNA-binding proteins. The ability to analyze millions of individual genomic cleavage events via massively parallel sequencing has enabled in vivo DNase I footprinting on a genomic scale, offering the potential for global analysis of transcription factor occupancy in a single experiment. Genomic footprinting has opened unique vistas on the organization, function and evolution of regulatory DNA; however, the technology is still nascent. Here we discuss both prospects and challenges of genomic footprinting, as well as considerations for its application to complex genomes.

  10. Reconciling Observations of the Yellowstone Hotspot with the Standard Plume Model

    Science.gov (United States)

    Ihinger, P. D.; Watkins, J. M.; Johnson, B. R.

    2004-12-01

    The Yellowstone hotspot represents the type example of plume magmatism in the continental setting. The propagation of large silicic magmatic centers along the Snake River Plain independently tracks the southwestward trajectory of North American plate motion over the last 13 My. Structural deformation associated with the hotspot track is consistent with thermal upwelling, and tomographic studies image a well-defined cylindrical conduit at least down to the mantle transition zone. Furthermore, the high 3He/4He signatures suggest a deep mantle origin for Yellowstone magmas. Yet, there are several observations of the Yellowstone region that do not fit the standard plume model for hotspot magmatism. These include: 1) prevalent coeval magmatism in and around the hotspot track that continued well after passage of the underlying plume, 2) significant bimodal magmatism that occurred throughout the Great Basin during this time, and 3) the outpouring of the Miocene Columbia River flood basalts (CRFB) well north of the hotspot track. These features have led a number of researchers to favor a shallow upper mantle origin for Yellowstone hotspot activity controlled by structural weaknesses in the continental lithosphere. Here, we propose that the observations listed above conform to the standard plume model by considering interaction of the Yellowstone plume with the descending Farallon Plate beginning at 80 Ma. Anomalous geologic activity occurred throughout the Cenozoic Era in the North American Cordillera (NAC) and must be addressed in any model for the origin of magmatism in the western US, including the Yellowstone hotspot. In particular, extensive field and geochemical studies document a pronounced eastward migration of deformation and magmatism throughout the NAC from 80 to 40 Ma. Most researchers attribute this activity to shallowing of the Farallon slab beneath NA at this time. In addition, geochemical studies in the NAC document a transition in magmatism from

  11. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming

    2013-07-26

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  12. Jumbled genomes: missing Apicomplexan synteny.

    Science.gov (United States)

    DeBarry, Jeremy D; Kissinger, Jessica C

    2011-10-01

    Whole-genome comparisons provide insight into genome evolution by informing on gene repertoires, gene gains/losses, and genome organization. Most of our knowledge about eukaryotic genome evolution is derived from studies of multicellular model organisms. The eukaryotic phylum Apicomplexa contains obligate intracellular protist parasites responsible for a wide range of human and veterinary diseases (e.g., malaria, toxoplasmosis, and theileriosis). We have developed an in silico protein-encoding gene based pipeline to investigate synteny across 12 apicomplexan species from six genera. Genome rearrangement between lineages is extensive. Syntenic regions (conserved gene content and order) are rare between lineages and appear to be totally absent across the phylum, with no group of three genes found on the same chromosome and in the same order within 25 kb up- and downstream of any orthologous genes. Conserved synteny between major lineages is limited to small regions in Plasmodium and Theileria/Babesia species, and within these conserved regions, there are a number of proteins putatively targeted to organelles. The observed overall lack of synteny is surprising considering the divergence times and the apparent absence of transposable elements (TEs) within any of the species examined. TEs are ubiquitous in all other groups of eukaryotes studied to date and have been shown to be involved in genomic rearrangements. It appears that there are different criteria governing genome evolution within the Apicomplexa relative to other well-studied unicellular and multicellular eukaryotes.

  13. Climatic and topographical correlates of plant palaeo- and neoendemism in a Mediterranean biodiversity hotspot.

    Science.gov (United States)

    Molina-Venegas, Rafael; Aparicio, Abelardo; Lavergne, Sébastien; Arroyo, Juan

    2017-01-01

    Understanding the evolutionary and ecological forces contributing to the emergence of biodiversity hotspots is of outstanding importance to elucidate how they may withstand current climate changes. Here we explored patterns of phylogenetic and non-phylogenetic plant endemism in a Mediterranean biodiversity hotspot. We hypothesized that areas with wet and equable climatic conditions would be prone to long-term persistence of endemic lineages (palaeoendemism), whilst areas of recent local speciation (neoendemism) would be more related to harsher environmental conditions and to high topographical relief promoting speciation. We focused on the Baetic-Rifan biodiversity hotspot (southern Iberian Peninsula and northern Morocco) in combination with molecular phylogenetic information and relative phylogenetic endemism (RPE), a recent phylogenetic measure of endemism, allowing us to discern centres of palaeo- from those of neoendemism. Using eco-geographical regions as study units, we explored correlations between both RPE and endemic species richness with precipitation- and temperature-related variables and with elevation range. Centres of neoendemism were concentrated towards the easternmost part of the hotspot, while centres of palaeoendemism were clustered in the vicinity of the Strait of Gibraltar. The RPE index, indicating more palaeoendemism, was positively correlated with total annual precipitation, while endemic species richness showed a poor correlation. In contrast, elevation range and mean annual temperature were poor predictors of RPE, despite elevation range showing a strong correlation with endemic species richness. The Baetic-Rifan biodiversity hotspot shows clearly differentiated centres of neo- and palaeoendemism. Topographical relief may have driven evolutionary diversification of newly evolved species, while water availability seems more critical for the long-term persistence of ancient lineages in refuge areas of smoother topography. Given climatic

  14. Current Global Absolute Plate Velocities Inferred from the Trends of Hotspot Tracks: Implications for Motion between Groups of Hotspots and Comparison and Combination with Absolute Velocities Inferred from the Orientation of Seismic Anisotropy

    Science.gov (United States)

    Wang, C.; Gordon, R. G.; Zheng, L.

    2016-12-01

    Hotspot tracks are widely used to estimate the absolute velocities of plates, i.e., relative to the lower mantle. Knowledge of current motion between hotspots is important for both plate kinematics and mantle dynamics and informs the discussion on the origin of the Hawaiian-Emperor Bend. Following Morgan & Morgan (2007), we focus only on the trends of young hotspot tracks and omit volcanic propagation rates. The dispersion of the trends can be partitioned into between-plate and within-plate dispersion. Applying the method of Gripp & Gordon (2002) to the hotspot trend data set of Morgan & Morgan (2007) constrained to the MORVEL relative plate angular velocities (DeMets et al., 2010) results in a standard deviation of the 56 hotspot trends of 22°. The largest angular misfits tend to occur on the slowest moving plates. Alternatively, estimation of best-fitting poles to hotspot tracks on the nine individual plates, results in a standard deviation of trends of only 13°, a statistically significant reduction from the introduction of 15 additional adjustable parameters. If all of the between-plate misfit is due to motion of groups of hotspots (beneath different plates), nominal velocities relative to the mean hotspot reference frame range from 1 to 4 mm/yr with the lower bounds ranging from 1 to 3 mm/yr and the greatest upper bound being 8 mm/yr. These are consistent with bounds on motion between Pacific and Indo-Atlantic hotspots over the past ≈50 Ma, which range from zero (lower bound) to 8 to 13 mm/yr (upper bounds) (Koivisto et al., 2014). We also determine HS4-MORVEL, a new global set of plate angular velocities relative to the hotspots constrained to consistency with the MORVEL relative plate angular velocities, using a two-tier analysis similar to that used by Zheng et al. (2014) to estimate the SKS-MORVEL global set of absolute plate velocities fit to the orientation of seismic anisotropy. We find that the 95% confidence limits of HS4-MORVEL and SKS

  15. Antarctic Genomics

    Directory of Open Access Journals (Sweden)

    Alex D. Rogers

    2006-03-01

    Full Text Available With the development of genomic science and its battery of technologies, polar biology stands on the threshold of a revolution, one that will enable the investigation of important questions of unprecedented scope and with extraordinary depth and precision. The exotic organisms of polar ecosystems are ideal candidates for genomic analysis. Through such analyses, it will be possible to learn not only the novel features that enable polar organisms to survive, and indeed thrive, in their extreme environments, but also fundamental biological principles that are common to most, if not all, organisms. This article aims to review recent developments in Antarctic genomics and to demonstrate the global context of such studies.

  16. A Rare Nasopharyngeal Foreign Body

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar Singh

    2008-04-01

    Full Text Available Nasopharynx is an exceptionally rare anatomical location for foreign body impaction. We present a rare case of nasopharyngeal foreign body (NFB in a 7 years old child. The diagnosis was confirmed by nasal endoscopy. Immediate removal of foreign body (FB in the nasopharynx was performed under general anesthesia. This rare situation is potentially dangerous, since its dislodgment may cause fatal airway obstruction. Therefore, in all cases with missing foreign bodies in the aerodigestive system, nasopharyngeal impaction should be kept in mind and endoscopic examination of the region should be considered.

  17. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili

    2011-11-01

    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  18. Routine use of the Ion Torrent AmpliSeq™ Cancer Hotspot Panel for identification of clinically actionable somatic mutations.

    Science.gov (United States)

    Tsongalis, Gregory J; Peterson, Jason D; de Abreu, Francine B; Tunkey, Christopher D; Gallagher, Torrey L; Strausbaugh, Linda D; Wells, Wendy A; Amos, Christopher I

    2014-05-01

    Somatic mutation analysis is standard of practice for solid tumors in order to identify therapeutic sensitizing and resistance mutations. Our laboratory routinely performed standalone PCR-based methods for mutations in several genes. Rapid discovery and introduction of new therapeutics has demanded additional genomic information for adequate management of the cancer patient. We evaluated a next generation sequencing assay, the Ion Torrent AmpliSeq Cancer Hotspot Panelv2 (CHPv2), capable of identifying multiple somatic mutations in 50 genes in a single assay. Accuracy, precision, limit of detection, and specificity were evaluated using DNA from well-characterized cell lines, genetically engineered cell lines fixed and embedded in paraffin, and previously tested mutation positive or negative, formalin-fixed, paraffin-embedded (FFPE) tissues. Normal kidney, tonsil and colon FFPE tissues were used as controls. Accuracy studies showed 100% concordance in each patient sample between previous PCR results and the corresponding variants identified using the Ion Torrent panel. Precision studies gave consistent results when libraries were prepared from the same original DNA and were run on multiple 316 chips. The limit of detection was determined to be 5% for single nucleotide variants (SNVs) and 20% for insertions and deletions (indels). Specificity studies using normal FFPE tissue previously tested by PCR methods were also 100%. We have evaluated the performance of the AmpliSeq Cancer Panel Hotspotv2 and show that it is suitable for clinical testing. This next generation sequencing panel has allowed the laboratory to consolidate a broader range of molecular oncology testing to a single platform and single assay.

  19. Hotspot electron temperature from x-ray continuum measurements on the NIF.

    Science.gov (United States)

    Jarrott, L C; Benedetti, L R; Chen, H; Izumi, N; Khan, S F; Ma, T; Nagel, S R; Landen, O L; Pak, A; Patel, P K; Schneider, M; Scott, H A

    2016-11-01

    We report on measurements of the electron temperature in the hotspot of inertially confined, layered, spherical implosions on the National Ignition Facility using a differential filtering diagnostic. Measurements of the DT and DD ion temperatures using neutron time-of-flight detectors are complicated by the contribution of hot spot motion to the peak width, which produce an apparent temperature higher than the thermal temperature. The electron temperature is not sensitive to this non-thermal velocity and is thus a valuable input to interpreting the stagnated hot spot conditions. Here we show that the current differential filtering diagnostic provides insufficient temperature resolution for the hot spot temperatures of interest. We then propose a new differential filter configuration utilizing larger pinhole size to increase spectral fluence, as well as thicker filtration. This new configuration will improve measurement uncertainty by more than a factor of three, allowing for a more accurate hotspot temperature.

  20. Nutrient supply, surface currents, and plankton dynamics predict zooplankton hotspots in coastal upwelling systems

    Science.gov (United States)

    Messié, Monique; Chavez, Francisco P.

    2017-09-01

    A simple combination of wind-driven nutrient upwelling, surface currents, and plankton growth/grazing equations generates zooplankton patchiness and hotspots in coastal upwelling regions. Starting with an initial input of nitrate from coastal upwelling, growth and grazing equations evolve phytoplankton and zooplankton over time and space following surface currents. The model simulates the transition from coastal (large phytoplankton, e.g., diatoms) to offshore (picophytoplankton and microzooplankton) communities, and in between generates a large zooplankton maximum. The method was applied to four major upwelling systems (California, Peru, Northwest Africa, and Benguela) using latitudinal estimates of wind-driven nitrate supply and satellite-based surface currents. The resulting zooplankton simulations are patchy in nature; areas of high concentrations coincide with previously documented copepod and krill hotspots. The exercise highlights the importance of the upwelling process and surface currents in shaping plankton communities.

  1. The Magellan seamount trail: implications for Cretaceous hotspot volcanism and absolute Pacific plate motion

    Science.gov (United States)

    Koppers, Anthony A. P.; Staudigel, Hubert; Wijbrans, Jan R.; Pringle, Malcolm S.

    1998-11-01

    The Magellan Seamount Trail (MST) delineates a northwest trending chain of four Cretaceous guyots in the West Pacific Seamount Province (WPSP). Seamount morphology, 40Ar/ 39Ar geochronology and Sr-Nd-Pb geochemistry of the MST provides evidence for a hotspot origin between the Samoa, Rarotonga and Society hotspots of the South Pacific Isotopic and Thermal Anomaly (SOPITA). The MST yields an excellent linear age progression of 47.6±1.6 mm/yr ( r2=1.000; MSWD = 0.23; 1 σ SE) including Vlinder guyot (95.1±0.5 Ma, n=5; 2 σ SD), Pako guyot (91.3±0.3 Ma, n=3) and Ioah guyot (87.1±0.3 Ma, n=2). The MST also exhibits a small range in Sr-Nd-Pb isotopic compositions indicating enriched mantle sources with an affinity of EMI. Nevertheless, three volcanic events are found out of sequence with linear MST hotspot volcanism: (1) an independent volcanic pedestal was formed 4-7 Myr before shield-volcanism started at Vlinder guyot, (2) a post-erosional volcanic cone was formed at least 20-30 Myr after drowning of Vlinder guyot, and (3) Ita Mai Tai guyot (118.1±0.5 Ma, n=3) was formed 34-36 Myr before the MST hotspot arrived at the predicted location of this guyot. By identifying and ruling out discordant volcanic events, we can use the age progression in MST to test the fixity of its hotspot. When presuming the fixed hotspot hypothesis, the local age progressions of the MST (47.6±1.6 mm/yr) and the copolar Musicians seamount trail (55.8±6.4 mm/yr) are not compatible with their 100-80 Ma Euler pole. We investigate two options: (1) acceptance of a `forced' Euler pole obeying the hotspot hypothesis by using both the age progressions and the azimuths of the studied seamount trails, or (2) acceptance of a `best-fit' Euler pole by using the azimuths of the studied seamount trail exclusively. In the first option, the angular speed of the Pacific plate during the 100-80 Ma stage pole is calculated at 0.502±0.017°/Myr. In the second option, the `best-fit' Euler pole is found

  2. Trace metal accumulation in marine macrophytes: Hotspots of coastal contamination worldwide.

    Science.gov (United States)

    Sánchez-Quiles, David; Marbà, Núria; Tovar-Sánchez, Antonio

    2017-01-15

    This study quantifies the concentration of trace metals in coastal marine macrophytes (seagrasses, Chlorophytae, Phaeophytae and Rhodophytae). We do so by compiling, from 155 peer review research articles, almost 23,000 estimates of trace metals (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn) contents in natural populations of marine macroalgae and seagrasses distributed worldwide. The objective was to explore the global distribution of concentrations of these metals in marine macrophytes, provide an estimate of their average and range in its tissues and to identify hotspots of coastal pollution. Our results reveal Phaeophytae as the group with the largest accumulation capacity and tolerance to elevated concentrations of metals regardless the species and the location. The mapping of geographic distribution of metal accumulation in marine macrophytes identifies some coastal areas as hotspots of trace metal contamination, where concentrations could reach levels up to 600 times higher than the mean. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Material Proximities and Hotspots: Toward an Anthropology of Viral Hemorrhagic Fevers

    Science.gov (United States)

    Brown, Hannah; Kelly, Ann H

    2014-01-01

    This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human–animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities—between animals, humans, and objects—that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. PMID:24752909

  4. Identifying Victims of Human Trafficking at Hotspots by Focusing on People Smuggled to Europe

    Directory of Open Access Journals (Sweden)

    Matilde Ventrella

    2017-06-01

    Full Text Available Research has shown that smuggling of migrants is associated with human trafficking. Hence, victims of human trafficking amongst smuggled migrants should be identified by EU Member States at hotspots established by the European Commission, to overcome the migrant and refugee crisis. Identified victims should be given a visa and a programme of protection to escape their traffickers. In order to achieve these objectives, research suggests that EU law on migrant smuggling should be amended and the Temporary Protection Directive should be applied to smuggled persons when there is an indication that they may be victims of human trafficking. This approach should be adopted by the EASO in cooperation with police forces investigating smuggling and trafficking at hotspots.

  5. A model to identify urban traffic congestion hotspots in complex networks

    CERN Document Server

    Solé-Ribalta, Albert; Arenas, Alex

    2016-01-01

    The rapid growth of population in urban areas is jeopardizing the mobility and air quality worldwide. One of the most notable problems arising is that of traffic congestion. With the advent of technologies able to sense real-time data about cities, and its public distribution for analysis, we are in place to forecast scenarios valuable for improvement and control. Here, we propose an idealized model, based on the critical phenomena arising in complex networks, that allows to analytically predict congestion hotspots in urban environments. Results on real cities' road networks, considering, in some experiments, real-traffic data, show that the proposed model is capable of identifying susceptible junctions that might becomes hotspots if mobility demand increases.

  6. Hotspot electron temperature from x-ray continuum measurements on the NIF

    Science.gov (United States)

    Jarrott, L. C.; Benedetti, L. R.; Chen, H.; Izumi, N.; Khan, S. F.; Ma, T.; Nagel, S. R.; Landen, O. L.; Pak, A.; Patel, P. K.; Schneider, M.; Scott, H. A.

    2016-11-01

    We report on measurements of the electron temperature in the hotspot of inertially confined, layered, spherical implosions on the National Ignition Facility using a differential filtering diagnostic. Measurements of the DT and DD ion temperatures using neutron time-of-flight detectors are complicated by the contribution of hot spot motion to the peak width, which produce an apparent temperature higher than the thermal temperature. The electron temperature is not sensitive to this non-thermal velocity and is thus a valuable input to interpreting the stagnated hot spot conditions. Here we show that the current differential filtering diagnostic provides insufficient temperature resolution for the hot spot temperatures of interest. We then propose a new differential filter configuration utilizing larger pinhole size to increase spectral fluence, as well as thicker filtration. This new configuration will improve measurement uncertainty by more than a factor of three, allowing for a more accurate hotspot temperature.

  7. Material proximities and hotspots: toward an anthropology of viral hemorrhagic fevers.

    Science.gov (United States)

    Brown, Hannah; Kelly, Ann H

    2014-06-01

    This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human-animal entanglements with an ethnographic interest in the social production of space, we seek to enrich conceptualizations of viral movement by elaborating the circumstances through which viruses, humans, objects, and animals come into contact. We suggest that attention to the material proximities-between animals, humans, and objects-that constitute the hotspot opens a frontier site for critical and methodological development in medical anthropology and for future collaborations in VHF management and control. © 2014 by the American Anthropological Association.

  8. Multidimensional Analysis and Location Intelligence Application for Spatial Data Warehouse Hotspot in Indonesia using SpagoBI

    Science.gov (United States)

    Uswatun Hasanah, Gamma; Trisminingsih, Rina

    2016-01-01

    Spatial data warehouse refers to data warehouse which has a spatial component that represents the geographic location of the position or an object on the Earth's surface. Spatial data warehouse can be visualized in the form of a crosstab tables, graphs, and maps. Spatial data warehouse of hotspot in Indonesia has been constructed by researchers from FIRM NASA 2006-2015. This research develops multidimensional analysis module and location intelligence module using SpagoBI. The multidimensional analysis module is able to visualize online analytical processing (OLAP). The location intelligence module creates dynamic map visualization in map zone and map point. Map zone can display the different colors based on the number of hotspot in each region and map point can display different sizes of the point to represent the number of hotspots in each region. This research is expected to facilitate users in the presentation of hotspot data as needed.

  9. ANALISIS HUBUNGAN KODE-KODE SPBK (SISTEM PERINGKAT BAHAYA KEBAKARAN DAN HOTSPOT DENGAN KEBAKARAN HUTAN DAN LAHAN DI KALIMANTAN TENGAH

    Directory of Open Access Journals (Sweden)

    Indah Prasasti

    2012-12-01

    Full Text Available Land and forest fire is one of causes ofland degradation in Central Kalimantan. Remote sensing dataapplications, especially READY-ARL NOAA and CMORPH data, are benefit forthe available climate observation data. The objectives of this research are: (1 to analyzis relationship between hotspots, FDRS and occurences of land and forest fire, and (2 to develop the estimation model of burned area from hotspot and FDRS codes. The result of this research showed that burned area can not be estimated by using number of hotspots. The drought code (DC wich is one of FDRS codes has correlation with burned area. So, burned area can be estimated using drought code (DC (R-sq = 58% by using the following formula: Burned Area (Ha = -62.9 + 5.14 (DC – 500.Keywords: land and forest fire, NOAA, CMORPH, hotspot

  10. The distribution of large herbivore hotspots in relation to environmental and anthropogenic correlates in the Mara region of Kenya

    National Research Council Canada - National Science Library

    Bhola, Nina; Ogutu, Joseph O; Said, Mohamed Y; Piepho, Hans-Peter; Olff, Han; Fryxell, John

    2012-01-01

    .... We analyse changes in distributions of herbivore hotspots to understand their environmental and anthropogenic correlates using 50 aerial surveys conducted at a spatial resolution of 5 x 5 km(2) (n = 289 cells...

  11. HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering

    National Research Council Canada - National Science Library

    Bendl, Jaroslav; Stourac, Jan; Sebestova, Eva; Vavra, Ondrej; Musil, Milos; Brezovsky, Jan; Damborsky, Jiri

    2016-01-01

    HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins' stability, catalytic activity, substrate specificity and enantioselectivity...

  12. A Fully Automatic Instantaneous Fire Hotspot Detection Processor Based on AVHRR Imagery—A TIMELINE Thematic Processor

    Directory of Open Access Journals (Sweden)

    Simon Plank

    2017-01-01

    Full Text Available The German Aerospace Center’s (DLR TIMELINE project aims to develop an operational processing and data management environment to process 30 years of National Oceanic and Atmospheric Administration (NOAA—Advanced Very High Resolution Radiometer (AVHRR raw data into L1b, L2 and L3 products. This article presents the current status of the fully automated L2 active fire hotspot detection processor, which is based on single-temporal datasets in orbit geometry. Three different probability levels of fire detection are provided. The results of the hotspot processor were tested with simulated fire data. Moreover, the processing results of real AVHRR imagery were validated with five different datasets: MODIS hotspots, visually confirmed MODIS hotspots, fire-news data from the European Forest Fire Information System (EFFIS, burnt area mapping of the Copernicus Emergency Management Service (EMS and data of the Piedmont fire database.

  13. Population connectivity and the effectiveness of marine protected areas to protect vulnerable, exploited and endemic coral reef fishes at an endemic hotspot

    KAUST Repository

    Van Der Meer, Martin H.

    2014-12-23

    Marine protected areas (MPAs) aim to mitigate anthropogenic impacts by conserving biodiversity and preventing overfishing. The effectiveness of MPAs depends on population connectivity patterns between protected and non-protected areas. Remote islands are endemism hotspots for coral reef fishes and provide rare examples of coral reefs with limited fishing pressure. This study explored population genetic connectivity across a network of protected and non-protected areas for the endemic wrasse, Coris bulbifrons, which is listed as “vulnerable” by the IUCN due to its small, decreasing geographic range and declining abundance. Mitochondrial DNA (mtDNA) and microsatellite DNA (msatDNA) markers were used to estimate historic and contemporary gene flow to determine the level of population self-replenishment and to measure genetic and genotypic diversity among all four locations in the species range (south-west Pacific Ocean)—Middleton Reef (MR), Elizabeth Reef (ER), Lord Howe Island (LHI) and Norfolk Island (NI). MPAs exist at MR and LHI and are limited or non-existent at ER and NI, respectively. There was no obvious differentiation in mtDNA among locations, however, msatDNA revealed differentiation between the most peripheral (NI) and all remaining locations (MR, ER and LHI). Despite high mtDNA connectivity (M = 259–1,144), msatDNA connectivity was limited (M = 3–9) with high self-replenishment (68–93 %) at all locations. NI is the least connected and heavily reliant on self-replenishment, and the absence of MPAs at NI needs to be rectified to ensure the persistence of endemic species at this location. Other endemic fishes exhibit similar patterns of high self-replenishment across the four locations, indicating that a single spatial management approach consisting of a MPA network protecting part of each location could provide reasonable protection for these species. Thus, the existing network of MPAs at this endemic hotspot appears adequate at some locations

  14. Relations between species rarity, vulnerability, and range contraction for a beetle group in a densely populated region in the Mediterranean biodiversity hotspot.

    Science.gov (United States)

    Fattorini, Simone

    2014-02-01

    Rarity is often considered an indication of species extinction risk, and it is frequently used to obtain measures of species vulnerability. However, there is no strong evidence of a correlation between species vulnerability and threat. Moreover, there is no consensus about how rarity should be measured. I used a multidimensional characterization of species rarity to calculate a vulnerability index for tenebrionid beetles inhabiting an Italian region in the Mediterranean biodiversity hotspot. I used different metrics to examine 3 dimensions of rarity: species range, ecology, and population. Species with rarity values below the median were scored as rare for each dimension. I combined rarity scores into a vulnerability index. I then correlated species vulnerability with range trends (expanded vs. contracted). Different measures of the same rarity dimension were strongly correlated and produced similar vulnerability scores. This result indicates rarity-based vulnerability estimates are slightly affected by the way a certain rarity dimension is measured. Vulnerability was correlated with range trends; species with the highest vulnerability had the strongest range contraction. However, a large number of common species also underwent range contraction in the last 50 years, and there was no clear relation between range contraction and their ecology. This indicates that in general human-induced environmental changes affected species irrespective of their assumed vulnerability and that focusing only on rare species may severely bias perceptions of the extent of species decline. © 2013 Society for Conservation Biology.

  15. A pathway-centric approach to rare variant association analysis

    Science.gov (United States)

    Richardson, Tom G; Timpson, Nicholas J; Campbell, Colin; Gaunt, Tom R

    2017-01-01

    Current endeavours in rare variant analysis are typically underpowered when investigating association signals from individual genes. We undertook an approach to rare variant analysis which utilises biological pathway information to analyse functionally relevant genes together. Conventional filtering approaches for rare variant analysis are based on variant consequence and are therefore confined to coding regions of the genome. Therefore, we undertook a novel approach to this process by obtaining functional annotations from the Combined Annotation Dependent Depletion (CADD) tool, which allowed potentially deleterious variants from intronic regions of genes to be incorporated into analyses. This work was undertaken using whole-genome sequencing data from the UK10K project. Rare variants from the KEGG pathway for arginine and proline metabolism were collectively associated with systolic blood pressure (P=3.32x10−5) based on analyses using the optimal sequence kernel association test. Variants along this pathway also showed evidence of replication using imputed data from the Avon Longitudinal Study of Parents and Children cohort (P=0.02). Subsequent analyses found that the strength of evidence diminished when analysing genes in this pathway individually, suggesting that they would have been overlooked in a conventional gene-based analysis. Future studies that adopt similar approaches to investigate polygenic effects should yield value in better understanding the genetic architecture of complex disease. PMID:27577545

  16. Genomic Imprinting

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 5; Issue 9. Genomic Imprinting - Some Interesting Implications for the Evolution of Social Behaviour. Raghavendra Gadagkar. General Article Volume 5 Issue 9 September 2000 pp 58-68 ...

  17. Herbarium genomics

    DEFF Research Database (Denmark)

    Bakker, Freek T.; Lei, Di; Yu, Jiaying

    2016-01-01

    Herbarium genomics is proving promising as next-generation sequencing approaches are well suited to deal with the usually fragmented nature of archival DNA. We show that routine assembly of partial plastome sequences from herbarium specimens is feasible, from total DNA extracts and with specimens...... up to 146 years old. We use genome skimming and an automated assembly pipeline, Iterative Organelle Genome Assembly, that assembles paired-end reads into a series of candidate assemblies, the best one of which is selected based on likelihood estimation. We used 93 specimens from 12 different...... correlation between plastome coverage and nuclear genome size (C value) in our samples, but the range of C values included is limited. Finally, we conclude that routine plastome sequencing from herbarium specimens is feasible and cost-effective (compared with Sanger sequencing or plastome...

  18. Identification of water quality degradation hotspots in developing countries by applying large scale water quality modelling

    Science.gov (United States)

    Malsy, Marcus; Reder, Klara; Flörke, Martina

    2014-05-01

    Decreasing water quality is one of the main global issues which poses risks to food security, economy, and public health and is consequently crucial for ensuring environmental sustainability. During the last decades access to clean drinking water increased, but 2.5 billion people still do not have access to basic sanitation, especially in Africa and parts of Asia. In this context not only connection to sewage system is of high importance, but also treatment, as an increasing connection rate will lead to higher loadings and therefore higher pressure on water resources. Furthermore, poor people in developing countries use local surface waters for daily activities, e.g. bathing and washing. It is thus clear that water utilization and water sewerage are indispensable connected. In this study, large scale water quality modelling is used to point out hotspots of water pollution to get an insight on potential environmental impacts, in particular, in regions with a low observation density and data gaps in measured water quality parameters. We applied the global water quality model WorldQual to calculate biological oxygen demand (BOD) loadings from point and diffuse sources, as well as in-stream concentrations. Regional focus in this study is on developing countries i.e. Africa, Asia, and South America, as they are most affected by water pollution. Hereby, model runs were conducted for the year 2010 to draw a picture of recent status of surface waters quality and to figure out hotspots and main causes of pollution. First results show that hotspots mainly occur in highly agglomerated regions where population density is high. Large urban areas are initially loading hotspots and pollution prevention and control become increasingly important as point sources are subject to connection rates and treatment levels. Furthermore, river discharge plays a crucial role due to dilution potential, especially in terms of seasonal variability. Highly varying shares of BOD sources across

  19. Hotspot analysis: a first prototype Python plugin enabling exploratory spatial data analysis into QGIS

    OpenAIRE

    Oxoli, Daniele; Zurbarán, Mayra A.; Shaji, Stanly; Muthusamy, Arun K.

    2016-01-01

    The growing popularity of Free and Open Source (FOSS) GIS software is without doubts due to the possibility to build and customize geospatial applications to meet specific requirements for any users. From this point of view, QGIS is one of the most flexible as well as fashionable GIS software environment which enables users to develop powerful geospatial applications using Python. Exploiting this feature, we present here a first prototype plugin for QGIS dedicated to Hotspot analysis, one of ...

  20. Deforestation and Forest Fragmentation in South Ecuador since the 1970s - Losing a Hotspot of Biodiversity.

    OpenAIRE

    María Fernanda Tapia-Armijos; Jürgen Homeier; Carlos Iván Espinosa; Christoph Leuschner; Marcelino de la Cruz

    2015-01-01

    Deforestation and fragmentation are major components of global change; both are contributing to the rapid loss of tropical forest area with important implications for ecosystem functioning and biodiversity conservation. The forests of South Ecuador are a biological 'hotspot' due to their high diversity and endemism levels. We examined the deforestation and fragmentation patterns in this area of high conservation value using aerial photographs and Aster satellite scenes. The registered annual ...

  1. A study on clinical nursing research trends and hotspots based on bibliometric analysis

    OpenAIRE

    Shi-Fan Han; Rui-Fang Zhu; Ting-Ting Qin

    2017-01-01

    Objective: This study was conducted to understand the trends and research hotspots of clinical nursing in China and abroad, thereby to provide guidance for nursing practice and studies. Methods: We retrieved clinical nursing literature (excluding literature related to psychological nursing and traditional Chinese medicine nursing) cited in Wanfang Data (www.wanfangdata.com.cn) and PubMed between 2007 and 2015 and subsequently performed bibliometric analyses on article volume, journal, cluster...

  2. Localized Hotspots Drive Continental Geography of Abnormal Amphibians on U.S. Wildlife Refuges

    Science.gov (United States)

    Reeves, Mari K.; Medley, Kimberly A.; Pinkney, Alfred E.; Holyoak, Marcel; Johnson, Pieter T. J.; Lannoo, Michael J.

    2013-01-01

    Amphibians with missing, misshapen, and extra limbs have garnered public and scientific attention for two decades, yet the extent of the phenomenon remains poorly understood. Despite progress in identifying the causes of abnormalities in some regions, a lack of knowledge about their broader spatial distribution and temporal dynamics has hindered efforts to understand their implications for amphibian population declines and environmental quality. To address this data gap, we conducted a nationwide, 10-year assessment of 62,947 amphibians on U.S. National Wildlife Refuges. Analysis of a core dataset of 48,081 individuals revealed that consistent with expected background frequencies, an average of 2% were abnormal, but abnormalities exhibited marked spatial variation with a maximum prevalence of 40%. Variance partitioning analysis demonstrated that factors associated with space (rather than species or year sampled) captured 97% of the variation in abnormalities, and the amount of partitioned variance decreased with increasing spatial scale (from site to refuge to region). Consistent with this, abnormalities occurred in local to regional hotspots, clustering at scales of tens to hundreds of kilometers. We detected such hotspot clusters of high-abnormality sites in the Mississippi River Valley, California, and Alaska. Abnormality frequency was more variable within than outside of hotspot clusters. This is consistent with dynamic phenomena such as disturbance or natural enemies (pathogens or predators), whereas similarity of abnormality frequencies at scales of tens to hundreds of kilometers suggests involvement of factors that are spatially consistent at a regional scale. Our characterization of the spatial and temporal variation inherent in continent-wide amphibian abnormalities demonstrates the disproportionate contribution of local factors in predicting hotspots, and the episodic nature of their occurrence. PMID:24260103

  3. Marine Caves of the Mediterranean Sea: A Sponge Biodiversity Reservoir within a Biodiversity Hotspot

    OpenAIRE

    Vasilis Gerovasileiou; Eleni Voultsiadou

    2012-01-01

    Marine caves are widely acknowledged for their unique biodiversity and constitute a typical feature of the Mediterranean coastline. Herein an attempt was made to evaluate the ecological significance of this particular ecosystem in the Mediterranean Sea, which is considered a biodiversity hotspot. This was accomplished by using Porifera, which dominate the rocky sublittoral substrata, as a reference group in a meta-analytical approach, combining primary research data from the Aegean Sea (easte...

  4. Exploring spatial patterns and hotspots of diarrhea in Chiang Mai, Thailand

    Directory of Open Access Journals (Sweden)

    Tripathi Nitin K

    2009-06-01

    Full Text Available Abstract Background Diarrhea is a major public health problem in Thailand. The Ministry of Public Health, Thailand, has been trying to monitor and control this disease for many years. The methodology and the results from this study could be useful for public health officers to develop a system to monitor and prevent diarrhea outbreaks. Methods The objective of this study was to analyse the epidemic outbreak patterns of diarrhea in Chiang Mai province, Northern Thailand, in terms of their geographical distributions and hotspot identification. The data of patients with diarrhea at village level and the 2001–2006 population censuses were collected to achieve the objective. Spatial analysis, using geographic information systems (GIS and other methods, was used to uncover the hidden phenomena from the data. In the data analysis section, spatial statistics such as quadrant analysis (QA, nearest neighbour analysis (NNA, and spatial autocorrelation analysis (SAA, were used to identify the spatial patterns of diarrhea in Chiang Mai province. In addition, local indicators of spatial association (LISA and kernel density (KD estimation were used to detect diarrhea hotspots using data at village level. Results The hotspot maps produced by the LISA and KD techniques showed spatial trend patterns of diarrhea diffusion. Villages in the middle and northern regions revealed higher incidences. Also, the spatial patterns of diarrhea during the years 2001 and 2006 were found to represent spatially clustered patterns, both at global and local scales. Conclusion Spatial analysis methods in GIS revealed the spatial patterns and hotspots of diarrhea in Chiang Mai province from the year 2001 to 2006. To implement specific and geographically appropriate public health risk-reduction programs, the use of such spatial analysis tools may become an integral component in the epidemiologic description, analysis, and risk assessment of diarrhea.

  5. Identifying Social Impacts in Product Supply Chains:Overview and Application of the Social Hotspot Database

    OpenAIRE

    Gregory Norris; Deana Aulisio Cavan; Catherine Benoit-Norris

    2012-01-01

    One emerging tool to measure the social-related impacts in supply chains is Social Life Cycle Assessment (S-LCA), a derivative of the well-established environmental LCA technique. LCA has recently started to gain popularity among large corporations and initiatives, such as The Sustainability Consortium or the Sustainable Apparel Coalition. Both have made the technique a cornerstone of their applied-research program. The Social Hotspots Database (SHDB) is an overarching, global database that e...

  6. Disentangling environmental correlates of vascular plant biodiversity in a Mediterranean hotspot.

    Science.gov (United States)

    Molina-Venegas, Rafael; Aparicio, Abelardo; Pina, Francisco José; Valdés, Benito; Arroyo, Juan

    2013-10-01

    We determined the environmental correlates of vascular plant biodiversity in the Baetic-Rifan region, a plant biodiversity hotspot in the western Mediterranean. A catalog of the whole flora of Andalusia and northern Morocco, the region that includes most of the Baetic-Rifan complex, was compiled using recent comprehensive floristic catalogs. Hierarchical cluster analysis (HCA) and detrended correspondence analysis (DCA) of the different ecoregions of Andalusia and northern Morocco were conducted to determine their floristic affinities. Diversity patterns were studied further by focusing on regional endemic taxa. Endemic and nonendemic alpha diversities were regressed to several environmental variables. Finally, semi-partial regressions on distance matrices were conducted to extract the respective contributions of climatic, altitudinal, lithological, and geographical distance matrices to beta diversity in endemic and nonendemic taxa. We found that West Rifan plant assemblages had more similarities with Andalusian ecoregions than with other nearby northern Morocco ecoregions. The endemic alpha diversity was explained relatively well by the environmental variables related to summer drought and extreme temperature values. Of all the variables, geographical distance contributed by far the most to spatial turnover in species diversity in the Baetic-Rifan hotspot. In the Baetic range, elevation was the most significant driver of nonendemic species beta diversity, while lithology and elevation were the main drivers of endemic beta diversity. Despite the fact that Andalusia and northern Morocco are presently separated by the Atlantic Ocean and the Mediterranean Sea, the Baetic and Rifan mountain ranges have many floristic similarities - especially in their western ranges - due to past migration of species across the Strait of Gibraltar. Climatic variables could be shaping the spatial distribution of endemic species richness throughout the Baetic-Rifan hotspot. Determinants

  7. Disentangling environmental correlates of vascular plant biodiversity in a Mediterranean hotspot

    OpenAIRE

    Molina-Venegas, Rafael; Aparicio, Abelardo; Pina, Francisco Jos?; Vald?s, Benito; Arroyo, Juan

    2013-01-01

    We determined the environmental correlates of vascular plant biodiversity in the Baetic-Rifan region, a plant biodiversity hotspot in the western Mediterranean. A catalog of the whole flora of Andalusia and northern Morocco, the region that includes most of the Baetic-Rifan complex, was compiled using recent comprehensive floristic catalogs. Hierarchical cluster analysis (HCA) and detrended correspondence analysis (DCA) of the different ecoregions of Andalusia and northern Morocco were conduc...

  8. Hotspot Patterns: The Formal Definition and Automatic Detection of Architecture Smells

    Science.gov (United States)

    2015-01-15

    Hotspot Patterns: The Formal Definition and Automatic Detection of Architecture Smells Ran Mo∗, Yuanfang Cai∗, Rick Kazman†, Lu Xiao∗ ∗ Drexel...they are associated with extremely high error-proneness and/or change-proneness, cannot be characterized by existing notions such as code smells [7...software system. Code Smell Detection: Fowler [7] describes the concept of a “bad smell ” as a heuristic for identifying refactoring opportunities. Code

  9. Leg 197 synthesis: Southward motion and geochemical variability of the Hawaiian hotspot

    Science.gov (United States)

    Duncan, Robert A.; Tarduno, John A.; Scholl, David W.

    2006-01-01

    The bend in the Hawaiian-Emperor volcanic chain is an often-cited example of a change in plate motion with respect to a stationary hotspot. Growing evidence, however, suggests that the bend might instead record variable drift of the Hawaiian hotspot within a convecting mantle. Paleomagnetic and radiometric age data from samples recovered during Ocean Drilling Program (ODP) Leg 197 define an age-progressive paleolatitude history, indicating that the Emperor Seamounts volcanic trend was formed principally by rapid (4–5 cm/yr) southward motion of the Hawaiian hotspot during Late Cretaceous to early Tertiary time (81–47 Ma). Paleointensity data derived from Leg 197 suggest an inverse relationship between field strength and reversal frequency, consistent with an active lower mantle that controls the efficiency of the geodynamo. Petrochemical data and observations of volcanic products (lava flows and volcaniclastic sediments) from Detroit, Nintoku, and Koko Seamounts provide records of the evolution of these volcanic systems for comparison with recent activity in the Hawaiian Islands. We find that the Emperor Seamounts formed from similar mantle sources for melting (plume components and lithosphere) and in much the same stages of volcanic activity and time span as the Hawaiian volcanoes. Changes in major and trace element and Sr isotopic compositions of shield lavas along the lineament can be related to variations in thickness of the lithosphere overlying the hotspot that control the depth and extent of partial melting. Other geochemical tracers, such as He, Pb, and Hf isotopic compositions, indicate persistent contributions to melting from the plume throughout the volcanic chain.

  10. Material Proximities and Hotspots: Toward an Anthropology of Viral Hemorrhagic Fevers

    OpenAIRE

    Brown, Hannah; Kelly, Ann H

    2014-01-01

    This article outlines a research program for an anthropology of viral hemorrhagic fevers (collectively known as VHFs). It begins by reviewing the social science literature on Ebola, Marburg, and Lassa fevers and charting areas for future ethnographic attention. We theoretically elaborate the hotspot as a way of integrating analysis of the two routes of VHF infection: from animal reservoirs to humans and between humans. Drawing together recent anthropological investigations of human–animal ent...

  11. ANALISIS HUBUNGAN KODE-KODE SPBK (SISTEM PERINGKAT BAHAYA KEBAKARAN) DAN HOTSPOT DENGAN KEBAKARAN HUTAN DAN LAHAN DI KALIMANTAN TENGAH

    OpenAIRE

    Indah Prasasti; Rizaldi Boer; Muhammad Ardiansyah; Agus Buono; Lailan Syaufina; Yenni Vetrita

    2012-01-01

    Land and forest fire is one of causes ofland degradation in Central Kalimantan. Remote sensing dataapplications, especially READY-ARL NOAA and CMORPH data, are benefit forthe available climate observation data. The objectives of this research are: (1) to analyzis relationship between hotspots, FDRS and occurences of land and forest fire, and (2) to develop the estimation model of burned area from hotspot and FDRS codes. The result of this research showed that burned area can not be estimated ...

  12. Analisis Hubungan Kode-kode Spbk (Sistem Peringkat Bahaya Kebakaran) Dan Hotspot Dengan Kebakaran Hutan Dan Lahan Di Kalimantan Tengah

    OpenAIRE

    Prasasti, Indah; Boer, Rizaldi; Ardiansyah, Muhammad; Buono, Agus; Syaufina, Lailan; Vetrita, Yenni

    2012-01-01

    Land and forest fire is one of causes ofland degradation in Central Kalimantan. Remote sensing dataapplications, especially READY-ARL NOAA and CMORPH data, are benefit forthe available climate observation data. The objectives of this research are: (1) to analyzis relationship between hotspots, FDRS and occurences of land and forest fire, and (2) to develop the estimation model of burned area from hotspot and FDRS codes. The result of this research showed that burned area can not be estimated ...

  13. Rare beauty and charm decays

    Science.gov (United States)

    Blake, T.; LHCb Collaboration

    2017-07-01

    Rare beauty and charm decays can provide powerful probes of physics beyond the Standard Model. These proceedings summarise the latest measurements of rare beauty and charm decays from the LHCb experiment at the end of Run 1 of the LHC. Whilst the majority of the measurements are consistent with SM predictions, small differences are seen in the rate and angular distribution of ℓ- decay processes.

  14. [A rare cause of talalgia].

    Science.gov (United States)

    Bousbaa, Hicham; Ouahidi, Mohammed; Bennani, Mourad; Cherrad, Tawfik; Zejjari, Hassan; Kasmaoui, El Houssine; Louaste, Jamal; Rachid, Khalid; Amhajji, Laarbi

    2017-01-01

    Talalgie is one of the most common symptoms involving the foot. Intra-bone lipoma is one of the most rare bone tumors of the calcaneus. We report the case of a patient presenting with intermittent and spontaneous chronic heel pain. Clinical and radiological examinations confirmed the diagnosis of lipoma of the calcaneus. This study aimed to educate clinicians about the existence of this rare lesion.

  15. Rare Earth Optical Temperature Sensor

    Science.gov (United States)

    Chubb, Donald L. (Inventor); Jenkins, Phillip (Inventor)

    2004-01-01

    A rare earth optical temperature sensor is disclosed for measuring high temperatures. Optical temperature sensors exist that channel emissions from a sensor to a detector using a light pipe. The invention uses a rare earth emitter to transform the sensed thermal energy into a narrow band width optical signal that travels to a detector using a light pipe. An optical bandpass filter at the detector removes any noise signal outside of the band width of the signal from the emitter.

  16. Evaluating Global Biodiversity Hotspots – Very Rich and Even More Endangered

    Directory of Open Access Journals (Sweden)

    Hrdina Aleš

    2017-01-01

    Full Text Available Species on the Earth are under increasing human pressure, according to some authors, the current rate of extinction occurred only a few times in the past, for the last time in the Cretaceous Period in the Mesozoic Era. The main goal of current nature conservation is to maintain the highest native biological diversity and to preserve and enhance life-supporting ecosystem processes, functions and services with the best possible use of financial resources. The areas where can be found the highest concentrations of endemic species and that also face the highest loss of natural habitats are called biodiversity hotspots. Globally, now there are 36 hotspots, covering 2.4 % of the Earth’s land area and harbouring about 50 % of endemic plant species and 42 % of endemic terrestrial vertebrate species in the world. The areas can be compared in terms of species richness, endemism, natural habitat loss or territorial protection and nature conservation can be carried out in the most efficient way. The most important hotspots are Madagascar and the Indian Ocean Islands and Sundaland.

  17. A novel approach to detect hot-spots in large-scale multivariate data

    Directory of Open Access Journals (Sweden)

    Kendrick Keith M

    2007-09-01

    Full Text Available Abstract Background Progressive advances in the measurement of complex multifactorial components of biological processes involving both spatial and temporal domains have made it difficult to identify the variables (genes, proteins, neurons etc. significantly changed activities in response to a stimulus within large data sets using conventional statistical approaches. The set of all changed variables is termed hot-spots. The detection of such hot spots is considered to be an NP hard problem, but by first establishing its theoretical foundation we have been able to develop an algorithm that provides a solution. Results Our results show that a first-order phase transition is observable whose critical point separates the hot-spot set from the remaining variables. Its application is also found to be more successful than existing approaches in identifying statistically significant hot-spots both with simulated data sets and in real large-scale multivariate data sets from gene arrays, electrophysiological recording and functional magnetic resonance imaging experiments. Conclusion In summary, this new statistical algorithm should provide a powerful new analytical tool to extract the maximum information from complex biological multivariate data.

  18. Metazoan parasite species richness in Neotropical fishes: hotspots and the geography of biodiversity.

    Science.gov (United States)

    Luque, J L; Poulin, R

    2007-06-01

    Although research on parasite biodiversity has intensified recently, there are signs that parasites remain an underestimated component of total biodiversity in many regions of the planet. To identify geographical hotspots of parasite diversity, we performed qualitative and quantitative analyses of the parasite-host associations in fishes from Latin America and the Caribbean, a region that includes known hotspots of plant and animal biodiversity. The database included 10,904 metazoan parasite-host associations involving 1660 fish species. The number of host species with at least 1 parasite record was less than 10% of the total known fish species in the majority of countries. Associations involving adult endoparasites in actinopterygian fish hosts dominated the database. Across the whole region, no significant difference in parasite species richness was detected between marine and freshwater fishes. As a rule, host body size and study effort (number of studies per fish species) were good predictors of parasite species richness. Some interesting patterns emerged when we included only the regions with highest fish species biodiversity and study effort (Brazil, Mexico and the Caribbean Islands). Independently of differences in study effort or host body sizes, Mexico stands out as a hotspot of parasite diversity for freshwater fishes, as does Brasil for marine fishes. However, among 57 marine fish species common to all 3 regions, populations from the Caribbean consistently harboured more parasite species. These differences may reflect true biological patterns, or regional discrepancies in study effort and local priorities for fish parasitology research.

  19. Invasive fishes generate biogeochemical hotspots in a nutrient-limited system.

    Directory of Open Access Journals (Sweden)

    Krista A Capps

    Full Text Available Fishes can play important functional roles in the nutrient dynamics of freshwater systems. Aggregating fishes have the potential to generate areas of increased biogeochemical activity, or hotspots, in streams and rivers. Many of the studies documenting the functional role of fishes in nutrient dynamics have focused on native fish species; however, introduced fishes may restructure nutrient storage and cycling freshwater systems as they can attain high population densities in novel environments. The purpose of this study was to examine the impact of a non-native catfish (Loricariidae: Pterygoplichthys on nitrogen and phosphorus remineralization and estimate whether large aggregations of these fish generate measurable biogeochemical hotspots within nutrient-limited ecosystems. Loricariids formed large aggregations during daylight hours and dispersed throughout the stream during evening hours to graze benthic habitats. Excretion rates of phosphorus were twice as great during nighttime hours when fishes were actively feeding; however, there was no diel pattern in nitrogen excretion rates. Our results indicate that spatially heterogeneous aggregations of loricariids can significantly elevate dissolved nutrient concentrations via excretion relative to ambient nitrogen and phosphorus concentrations during daylight hours, creating biogeochemical hotspots and potentially altering nutrient dynamics in invaded systems.

  20. ATM modulates the loading of recombination proteins onto a chromosomal translocation breakpoint hotspot.

    Directory of Open Access Journals (Sweden)

    Jiying Sun

    Full Text Available Chromosome translocations induced by DNA damaging agents, such as ionizing radiation and certain chemotherapies, alter genetic information resulting in malignant transformation. Abrogation or loss of the ataxia-telangiectasia mutated (ATM protein, a DNA damage signaling regulator, increases the incidence of chromosome translocations. However, how ATM protects cells from chromosome translocations is still unclear. Chromosome translocations involving the MLL gene on 11q23 are the most frequent chromosome abnormalities in secondary leukemias associated with chemotherapy employing etoposide, a topoisomerase II poison. Here we show that ATM deficiency results in the excessive binding of the DNA recombination protein RAD51 at the translocation breakpoint hotspot of 11q23 chromosome translocation after etoposide exposure. Binding of Replication protein A (RPA and the chromatin remodeler INO80, which facilitate RAD51 loading on damaged DNA, to the hotspot were also increased by ATM deficiency. Thus, in addition to activating DNA damage signaling, ATM may avert chromosome translocations by preventing excessive loading of recombinational repair proteins onto translocation breakpoint hotspots.

  1. The building of a biodiversity hotspot across a land-bridge in the Mediterranean.

    Science.gov (United States)

    Molina-Venegas, Rafael; Aparicio, Abelardo; Lavergne, Sébastien; Arroyo, Juan

    2015-08-22

    Many of the macroevolutionary processes that have shaped present-day phylogenetic patterns were caused by geological events such as plate tectonics and temporary land-bridges. The study of spatial patterns of phylogenetic diversity can provide insights into these past events. Here we focus on a western Mediterranean biodiversity hotspot located in the southern Iberian Peninsula and northwest Africa, two regions that are separated by the Strait of Gibraltar. We explore the spatial structure of the phylogenetic relationships within and across large-scale plant assemblages. Significant turnover in terminal lineages tends to occur between landmasses, whereas turnover in deep lineages tends to occur within landmasses. Plant assemblages in the western ecoregions of this hotspot tend to be phylogenetically overdispersed but are phylogenetically clustered on its eastern margins. We discuss our results in the light of potential scenarios of niche evolution (or conservatism) and lineage diversification. The significant turnover between landmasses suggests a common scenario of allopatric speciation that could have been facilitated by the intermittent joining of the two continents. This may have constituted an important stimulus for diversification and the emergence of this western Mediterranean biodiversity hotspot. © 2015 The Author(s).

  2. Foraging and recruitment hotspot dynamics for the largest Atlantic loggerhead turtle rookery.

    Science.gov (United States)

    Ceriani, Simona A; Weishampel, John F; Ehrhart, Llewellyn M; Mansfield, Katherine L; Wunder, Michael B

    2017-12-04

    Determining patterns of migratory connectivity for highly-mobile, wide-ranging species, such as sea turtles, is challenging. Here, we combined satellite telemetry and stable isotope analysis to estimate foraging locations for 749 individual loggerheads nesting along the east central Florida (USA) coast, the largest rookery for the Northwest Atlantic population. We aggregated individual results by year, identified seven foraging hotspots and tracked these summaries to describe the dynamics of inter-annual contributions of these geographic areas to this rookery over a nine-year period. Using reproductive information for a subset of turtles (n = 513), we estimated hatchling yields associated with each hotspots. We found considerable inter-annual variability in the relative contribution of foraging areas to the nesting adults. Also reproductive success differed among foraging hotspots; females using southern foraging areas laid nests that produced more offspring in all but one year of the study. These analyses identified two high priority areas for future research and conservation efforts: the continental shelf adjacent to east central Florida and the Great Bahama Bank, which support higher numbers of foraging females that provide higher rates of hatchling production. The implementation of the continuous-surface approach to determine geographic origins of unknown migrants is applicable to other migratory species.

  3. Spatio-Temporal Distribution and Hotspots of Hand, Foot and Mouth Disease (HFMD in Northern Thailand

    Directory of Open Access Journals (Sweden)

    Ratchaphon Samphutthanon

    2013-12-01

    Full Text Available Hand, Foot and Mouth Disease (HFMD is an emerging viral disease, and at present, there are no antiviral drugs or vaccines available to control it. Outbreaks have persisted for the past 10 years, particularly in northern Thailand. This study aimed to elucidate the phenomenon of HFMD outbreaks from 2003 to 2012 using general statistics and spatial-temporal analysis employing a GIS-based method. The spatial analysis examined data at the village level to create a map representing the distribution pattern, mean center, standard deviation ellipse and hotspots for each outbreak. A temporal analysis was used to analyze the correlation between monthly case data and meteorological factors. The results indicate that the disease can occur at any time of the year, but appears to peak in the rainy and cold seasons. The distribution of outbreaks exhibited a clustered pattern. Most mean centers and standard deviation ellipses occurred in similar areas. The linear directional mean values of the outbreaks were oriented toward the south. When separated by season, it was found that there was a significant correlation with the direction of the southwest monsoon at the same time. An autocorrelation analysis revealed that hotspots tended to increase even when patient cases subsided. In particular, a new hotspot was found in the recent year in Mae Hong Son province.

  4. Crack initiation and potential hot-spot formation around a cylindrical defect under dynamic compression

    Science.gov (United States)

    Ma, Xiao; Li, Xinguo; Zheng, Xianxu; Li, Kewu; Hu, Qiushi; Li, Jianling

    2017-11-01

    In recent decades, the hot-spot theory of condensed-phase explosives has been a compelling focus of scientific investigation attracting many researchers. The defect in the polymeric binder of the polymer-bonded explosive is called the intergranular defect. In this study, the real polymeric binder was substituted by poly(methyl methacrylate) (PMMA) as it is transparent and has similar thermodynamic properties to some binders. A set of modified split Hopkinson pressure bars equipped with a time-resolved shadowgraph was used to study the process of crack initiation and potential hot-spot formation around a cylindrical defect in PMMA. The new and significant phenomenon that the opening-mode crack emerged earlier than the shearing-mode crack from the cylindrical defect has been published for the first time in this paper. Furthermore, a two-dimensional numerical simulation was performed to show the evolution of both the stress field and the temperature field. The simulation results were in good agreement with the experiment. Finally, the law of potential hot-spot formation is discussed in detail.

  5. Carbon footprint hotspots of prefabricated sandwich panels for hostel construction in Perlis

    Science.gov (United States)

    Razali, Norashikin; Ayob, Afizah; Chandra, Muhammad Erwan Shah; Zaki, Mohd Faiz Mohammad; Ahmad, Abdul Ghapar

    2017-10-01

    Sustainable design and construction have gained increasing research interest, and reduction of carbon from building construction has become the main focus of environmental strategies in Malaysia. This study uses life cycle assessment and life cycle inventory analysis frameworks to estimate the amount of carbon footprint expressed in carbon dioxide equivalent tons (CO2e) produced by manufacturing prefabricated Industrialized Building System sandwich panels and its installation for a five-story hostel in Perlis, Malaysia. Results show that the carbon footprint hotspots were centered on boiler machine operation and cement with 4.52 and 369.04 tons CO2e, respectively. This finding is due to the extensive energy used for steam heating and high engine rating for the boiler. However, for cement, the carbon footprint hotspots are caused by the large quantity of cement applied in shotcrete mixture and its high extraction and production CO2 emission values. The overall onsite materials generated 96.36% of the total carbon footprint. These carbon footprint hotspot results constitute a necessary base for the Malaysian government in accomplishing an adequate dimensioning of carbon emissions in the building sector.

  6. Identifying multidrug resistant tuberculosis transmission hotspots using routinely collected data12

    Science.gov (United States)

    Manjourides, Justin; Lin, Hsien-Ho; Shin, Sonya; Jeffery, Caroline; Contreras, Carmen; Cruz, Janeth Santa; Jave, Oswaldo; Yagui, Martin; Asencios, Luis; Pagano, Marcello; Cohen, Ted

    2012-01-01

    SUMMARY In most countries with large drug resistant tuberculosis epidemics, only those cases that are at highest risk of having MDRTB receive a drug sensitivity test (DST) at the time of diagnosis. Because of this prioritized testing, identification of MDRTB transmission hotspots in communities where TB cases do not receive DST is challenging, as any observed aggregation of MDRTB may reflect systematic differences in how testing is distributed in communities. We introduce a new disease mapping method, which estimates this missing information through probability–weighted locations, to identify geographic areas of increased risk of MDRTB transmission. We apply this method to routinely collected data from two districts in Lima, Peru over three consecutive years. This method identifies an area in the eastern part of Lima where previously untreated cases have increased risk of MDRTB. This may indicate an area of increased transmission of drug resistant disease, a finding that may otherwise have been missed by routine analysis of programmatic data. The risk of MDR among retreatment cases is also highest in these probable transmission hotspots, though a high level of MDR among retreatment cases is present throughout the study area. Identifying potential multidrug resistant tuberculosis (MDRTB) transmission hotspots may allow for targeted investigation and deployment of resources. PMID:22401962

  7. Episodic swell growth inferred from variable uplift of the Cape Verde hotspot islands

    Science.gov (United States)

    Ramalho, R.; Helffrich, G.; Cosca, M.; Vance, D.; Hoffmann, D.; Schmidt, D.N.

    2010-01-01

    On the Beagle voyage, Charles Darwin first noted the creation and subsidence of ocean islands, establishing in geology's infancy that island freeboard changes with time. Hotspot ocean islands have an obvious mechanism for freeboard change through the growth of the bathymetric anomaly, or swell, on which the islands rest. Models for swell development indicate that flexural, thermal or dynamic pressure contributions, as well as spreading of melt residue from the hotspot, can all contribute to island uplift. Here we test various models for swell development using the uplift histories for the islands of the Cape Verde hotspot, derived from isotopic dating of marine terraces and subaerial to submarine lava-flow morphologies. The island uplift histories, in conjunction with inter-island spacing, uplift rate and timing differences, rule out flexural, thermal or dynamic pressure contributions. We also find that uplift cannot be reconciled with models that advocate the spreading of melt residue in swell development unless swell growth is episodic. Instead, we infer from the uplift histories that two processes have acted to raise the islands during the past 6 Myr. During an initial phase, mantle processes acted to build the swell. Subsequently, magmatic intrusions at the island edifice caused 350 m of local uplift at the scale of individual islands. Finally, swell-wide uplift contributed a further 100 m of surface rise.

  8. Effect of hotspot position fluctuation to writing capability in heated-dot magnetic recording

    Science.gov (United States)

    Tipcharoen, Warunee; Warisarn, Chanon; Kaewrawang, Arkom; Kovintavewat, Piya

    2016-07-01

    This work presents the effect of hotspot position fluctuation to writing capability in heated-dot magnetic recording systems at an areal density (AD) beyond 2 Tbpsi via a micromagnetic modeling. At high ADs, the hotspot and the write field gradient may not be correctly focused on the target island because the bit islands are closely positioned to one another. This may lead to the overwriting/erasing of the previously written islands, which can severely affect the recording performance. Therefore, this work studies the 3-by-3 data patterns that easily cause an error when the hotspot and write head positions are fluctuated by various island pitches. Simulation results indicate that the data pattern that leads to the highest/lowest error occurrence frequency is the one with the first, second and fourth islands having the opposite/same magnetization direction to/as the write field, regardless of the magnetization direction of the third island. This result can, for example, be utilized to design a two-dimensional modulation code to prevent such destructive data patterns, thus helping enhance the overall system performance.

  9. Invasive Fishes Generate Biogeochemical Hotspots in a Nutrient-Limited System

    Science.gov (United States)

    Capps, Krista A.; Flecker, Alexander S.

    2013-01-01

    Fishes can play important functional roles in the nutrient dynamics of freshwater systems. Aggregating fishes have the potential to generate areas of increased biogeochemical activity, or hotspots, in streams and rivers. Many of the studies documenting the functional role of fishes in nutrient dynamics have focused on native fish species; however, introduced fishes may restructure nutrient storage and cycling freshwater systems as they can attain high population densities in novel environments. The purpose of this study was to examine the impact of a non-native catfish (Loricariidae: Pterygoplichthys) on nitrogen and phosphorus remineralization and estimate whether large aggregations of these fish generate measurable biogeochemical hotspots within nutrient-limited ecosystems. Loricariids formed large aggregations during daylight hours and dispersed throughout the stream during evening hours to graze benthic habitats. Excretion rates of phosphorus were twice as great during nighttime hours when fishes were actively feeding; however, there was no diel pattern in nitrogen excretion rates. Our results indicate that spatially heterogeneous aggregations of loricariids can significantly elevate dissolved nutrient concentrations via excretion relative to ambient nitrogen and phosphorus concentrations during daylight hours, creating biogeochemical hotspots and potentially altering nutrient dynamics in invaded systems. PMID:23342083

  10. CRAF Phase 1, a framework to identify coastal hotspots to storm impacts

    Directory of Open Access Journals (Sweden)

    Ferreira Oscar

    2016-01-01

    Full Text Available Low-frequency high-impact storms can cause flood and erosion over large coastal areas, which in turn can lead to a significant risk to coastal occupation, producing devastation and immobilising cities and even countries. It is therefore paramount to evaluate risk along the coast at a regional scale through the identification of storm impact hotspots. The Coastal Risk Assessment Framework Phase 1 (CRAF1 is a screening process based on a coastal-index approach that assesses the potential exposure of every kilometre along the coast to previously identified hazards. CRAF1 integrates both hazard (e.g. overwash, erosion and exposure indicators to create a final Coastal Index (CI. The application of CRAF1 at two contrasting case studies (Ria Formosa, Portugal and the Belgian coast, validated against existing information, demonstrates the utility and reliability of this framework on the identification of hotspots. CRAF1 represents a powerful and useful instrument for coastal managers and/or end-users to identify and rank potential hotspot areas in order to define priorities and support disaster reduction plans.

  11. RD-Connect: An Integrated Platform Connecting Databases, Registries, Biobanks and Clinical Bioinformatics for Rare Disease Research

    National Research Council Canada - National Science Library

    Thompson, Rachel; Johnston, Louise; Taruscio, Domenica; Monaco, Lucia; Beroud, Christophe; Gut, Ivo G; Hansson, Mats G; 't Hoen, Peter-Bram A; Patrinos, George P; Dawkins, Hugh; Ensini, Monica; Zatloukal, Kurt; Koubi, David; Heslop, Emma; Paschall, Justin E; Posada, Manuel; Robinson, Peter N; Bushby, Kate; Lochmueller, Hanns

    2014-01-01

    ...), RD-Connect is a global infrastructure project initiated in November 2012 that links genomic data with registries, biobanks, and clinical bioinformatics tools to produce a central research resource for rare diseases.

  12. The Promise and Payoff of Rare Diseases Research, From NIH Director Dr. Francis S. Collins | NIH MedlinePlus the ...

    Science.gov (United States)

    ... version of this page please turn Javascript on. The Promise and Payoff of Rare Diseases Research, From ... them at the present time. How much does the mapping of the human genome help? The Human ...

  13. Improvement of sampling strategies for randomly distributed hotspots in soil applying a computerized simulation considering the concept of uncertainty.

    Science.gov (United States)

    Hildebrandt, Thomas; Pick, Denis; Einax, Jürgen W

    2012-02-01

    The pollution of soil and environment as a result of human activity is a major problem. Nowadays, the determination of local contaminations is of interest for environmental remediation. These hotspots can have various toxic effects on plants, animals, humans, and the whole ecological system. However, economical and juridical consequences are also possible, e.g., high costs for remediation measures. In this study three sampling strategies (simple random sampling, stratified sampling, and systematic sampling) were applied on randomly distributed hotspot contaminations to prove their efficiency in term of finding hotspots. The results were used for the validation of a computerized simulation. This application can simulate the contamination on a field, the sampling pattern, and a virtual sampling. A constant hit rate showed that none of the sampling patterns could reach better results than others. Furthermore, the uncertainty associated with the results is described by confidence intervals. It is to be considered that the uncertainty during sampling is enormous and will decrease slightly, even the number of samples applied was increased to an unreasonable amount. It is hardly possible to identify the exact number of randomly distributed hotspot contaminations by statistical sampling. But a range of possible results could be calculated. Depending on various parameters such as shape and size of the area, number of hotspots, and sample quantity, optimal sampling strategies could be derived. Furthermore, an estimation of bias arising from sampling methodology is possible. The developed computerized simulation is an innovative tool for optimizing sampling strategies in terrestrial compartments for hotspot distributions.

  14. Unique properties of multiple tandem copies of the M26 recombination hotspot in mitosis and meiosis in Schizosaccharomyces pombe.

    Science.gov (United States)

    Steiner, Walter W; Recor, Chelsea L; Zakrzewski, Bethany M

    2016-11-15

    The M26 hotspot of the fission yeast Schizosaccharomyces pombe is one of the best-characterized eukaryotic hotspots of recombination. The hotspot requires a seven bp sequence, ATGACGT, that serves as a binding site for the Atf1-Pcr1 transcription factor, which is also required for activity. The M26 hotspot is active in meiosis but not mitosis and is active in some but not all chromosomal contexts and not on a plasmid. A longer palindromic version of M26, ATGACGTCAT, shows significantly greater activity than the seven bp sequence. Here, we tested whether the properties of the seven bp sequence were also true of the longer sequence by placing one, two, or three copies of the sequence into the ade6 gene, where M26 was originally discovered. These constructs were tested for activity when located on a plasmid or on a chromosome in mitosis and meiosis. We found that two copies of the 10bp M26 motif on a chromosome were significantly more active for meiotic recombination than one, but no further increase was observed with three copies. However, three copies of M26 on a chromosome created an Atf1-dependent mitotic recombination hotspot. When located on a plasmid, M26 also appears to behave as a mitotic recombination hotspot; however, this behavior most likely results from Atf1-dependent inter-allelic complementation between the plasmid and chromosomal ade6 alleles. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. How and when plume zonation appeared during the 132 Myr evolution of the Tristan Hotspot.

    Science.gov (United States)

    Hoernle, Kaj; Rohde, Joana; Hauff, Folkmar; Garbe-Schönberg, Dieter; Homrighausen, Stephan; Werner, Reinhard; Morgan, Jason P

    2015-07-27

    Increasingly, spatial geochemical zonation, present as geographically distinct, subparallel trends, is observed along hotspot tracks, such as Hawaii and the Galapagos. The origin of this zonation is currently unclear. Recently zonation was found along the last ∼70 Myr of the Tristan-Gough hotspot track. Here we present new Sr-Nd-Pb-Hf isotope data from the older parts of this hotspot track (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the Etendeka and Parana flood basalts erupted at the initiation of the hotspot track. We show that only the enriched Gough, but not the less-enriched Tristan, component is present in the earlier (70-132 Ma) history of the hotspot. Here we present a model that can explain the temporal evolution and origin of plume zonation for both the Tristan-Gough and Hawaiian hotspots, two end member types of zoned plumes, through processes taking place in the plume sources at the base of the lower mantle.

  16. Genome-wide association study of multiplex schizophrenia pedigrees

    DEFF Research Database (Denmark)

    Levinson, Douglas F; Shi, Jianxin; Wang, Kai

    2012-01-01

    The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs).......The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs)....

  17. Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016.

    Science.gov (United States)

    Bwire, Godfrey; Ali, Mohammad; Sack, David A; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K; Ngwa, Moise C; Brooks, W Abdullah; Garimoi Orach, Christopher

    2017-12-01

    Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. We obtained district level confirmed cholera outbreak data from 2011 to 2016 from the Ministry of Health, Uganda. Population and rainfall data were obtained from the Uganda Bureau of Statistics, and water, sanitation and hygiene data from the Ministry of Water and Environment. A spatial scan test was performed to identify the significantly high risk clusters. Cholera hotspots were defined as districts whose center fell within a significantly high risk cluster or where a significantly high risk cluster was completely superimposed onto a district. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. In total 11,030 cases of cholera were reported during the 6-year period. 37(33%) of 112 districts reported cholera outbreaks in one of the six years, and 20 (18%) districts experienced cholera at least twice in those years. We identified 22 districts as high risk for cholera, of which 13 were near a border of Democratic Republic of Congo (DRC), while 9 districts were near a border of Kenya. The relative risk of having cholera inside the high-risk districts (hotspots) were 2 to 22 times higher than elsewhere in the country. In total, 7 million people were within cholera hotspots. The negative binomial component of the ZINB model shows people living near a lake or the Nile river were at increased risk for cholera (incidence rate ratio, IRR = 0.98, 95% CI: 0.97 to 0.99, p cholera in a district (IRR = 0.99, 95% CI: 0.98 to 1.00, p = .02 and IRR = 1.02, 95% CI: 1.01 to 1.03, p cholera in the district. The study identified cholera

  18. A Rare Presentation of a Rare Disease: Pulmonary Lymphomatoid Granulomatosis

    Directory of Open Access Journals (Sweden)

    Ghulam Rehman Mohyuddin

    2012-01-01

    Full Text Available A 70-year-old female presented with a 4-week history of dry cough and wheezing. Chest radiograph showed a 10.5 cm mass-like density in the anterior mediastinum which had not been previously visualized. Computed tomography scan (CT of the chest showed a right hilar mass encasing and narrowing right upper lobe bronchus and right mainstem bronchus and secondary atelectatic changes. Biopsy was consistent with a diagnosis of lymphomatoid granulomatosis Grade 3. She responded well clinically and radiologically to therapy. Lymphomatoid granulomatosis is a rare EBV-associated disorder which is considered a lymphoproliferative disease. The most common radiographic feature is multiple lung nodules. An isolated hilar mass is an exceptionally rare presentation of this rare disease.

  19. Bayesian analysis of rare events

    Science.gov (United States)

    Straub, Daniel; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

  20. Global distribution and conservation of rare and threatened vertebrates.

    Science.gov (United States)

    Grenyer, Richard; Orme, C David L; Jackson, Sarah F; Thomas, Gavin H; Davies, Richard G; Davies, T Jonathan; Jones, Kate E; Olson, Valerie A; Ridgely, Robert S; Rasmussen, Pamela C; Ding, Tzung-Su; Bennett, Peter M; Blackburn, Tim M; Gaston, Kevin J; Gittleman, John L; Owens, Ian P F

    2006-11-02

    Global conservation strategies commonly assume that different taxonomic groups show congruent geographical patterns of diversity, and that the distribution of extinction-prone species in one group can therefore act as a surrogate for vulnerable species in other groups when conservation decisions are being made. The validity of these assumptions remains unclear, however, because previous tests have been limited in both geographical and taxonomic extent. Here we use a database on the global distribution of 19,349 living bird, mammal and amphibian species to show that, although the distribution of overall species richness is very similar among these groups, congruence in the distribution of rare and threatened species is markedly lower. Congruence is especially low among the very rarest species. Cross-taxon congruence is also highly scale dependent, being particularly low at the finer spatial resolutions relevant to real protected areas. 'Hotspots' of rarity and threat are therefore largely non-overlapping across groups, as are areas chosen to maximize species complementarity. Overall, our results indicate that 'silver-bullet' conservation strategies alone will not deliver efficient conservation solutions. Instead, priority areas for biodiversity conservation must be based on high-resolution data from multiple taxa.

  1. A new conceptual model for whole mantle convection and the origin of hotspot plumes

    Science.gov (United States)

    Yoshida, Masaki

    2014-08-01

    A new conceptual model of mantle convection is constructed for consideration of the origin of hotspot plumes, using recent evidence from seismology, high-pressure experiments, geodynamic modeling, geoid inversion studies, and post-glacial rebound analyses. This conceptual model delivers several key points. Firstly, some of the small-scale mantle upwellings observed as hotspots on the Earth's surface originate at the base of the mantle transition zone (MTZ), in which the Archean granitic continental material crust (TTG; tonalite-trondhjemite-granodiorite) with abundant radiogenic elements is accumulated. Secondly, the TTG crust and the subducted oceanic crust that have accumulated at the base of MTZ could act as thermal or mechanical insulators, leading to the formation of a hot and less viscous layer just beneath the MTZ; which may enhance the instability of plume generation at the base of the MTZ. Thirdly, the origin of some hotspot plumes is isolated from the large low shear-wave velocity provinces (LLSVPs) under Africa and the South Pacific. I consider that the conceptual model explains why almost all the hotspots around Africa are located above the margins of the African LLSVP. Because a planetary-scale trench system surrounding a “Pangean cell” has been spatially stable throughout the Phanerozoic, a large amount of the oceanic crustal layer is likely to be trapped in the MTZ under the Pangean cell. Therefore, under Africa, almost all of the hotspot plumes originate from the base of the MTZ, where a large amount of TTG and/or oceanic crusts has accumulated. This conceptual model may explain the fact that almost all the hotspots around Africa are located on margins above the African LLSVP. It is also considered that some of the hotspot plumes under the South Pacific thread through the TTG/oceanic crusts accumulated around the bottom of the MTZ, and some have their roots in the South Pacific LLSVP while others originate from the MTZ. The numerical simulations

  2. Correlates of injecting in an HIV incidence hotspot among substance users in Tijuana, Mexico.

    Science.gov (United States)

    Kori, Nana; Roth, Alexis M; Lozada, Remedios; Vera, Alicia; Brouwer, Kimberly C

    2014-05-01

    Substance use and HIV are growing problems in the Mexico-U.S. border city of Tijuana, a sex tourism destination situated on a northbound drug trafficking route. In a previous longitudinal study of injection drug users (IDUs), we found that >90% of incident HIV cases occurred within an 'HIV incidence hotspot,' consisting of 2.5-blocks. This study examines behavioral, social, and environmental correlates associated with injecting in this HIV hotspot. From 4/06 to 6/07, IDUs aged ≥18 years were recruited using respondent-driven sampling. Participants underwent antibody testing for HIV and syphilis and interviewer-administered surveys eliciting information on demographics, drug use, sexual behaviors, and socio-environmental influences. Participants were defined as injecting in the hotspot if they most frequently injected within a 3 standard deviational ellipse of the cohort's incident HIV cases. Logistic regression was used to identify individual and structural factors associated with the HIV 'hotspot'. Of 1031 IDUs, the median age was 36 years; 85% were male; HIV prevalence was 4%. As bivariate analysis indicated different correlates for males and females, models were stratified by sex. Factors independently associated with injecting in the HIV hotspot for male IDUs included homelessness (AOR 1.72; 95%CI 1.14-2.6), greater intra-urban mobility (AOR 3.26; 95%CI 1.67-6.38), deportation (AOR 1.58; 95%CI 1.18-2.12), active syphilis (AOR 3.03; 95%CI 1.63-5.62), needle sharing (AOR 0.57; 95%CI 0.42-0.78), various police interactions, perceived HIV infection risk (AOR 1.52; 95%CI 1.13-2.03), and health insurance status (AOR 0.53; 95%CI 0.33-0.87). For female IDUs, significant factors included sex work (AOR 8.2; 95%CI 2.2-30.59), lifetime syphilis exposure (AOR 2.73; 95%CI 1.08-6.93), injecting inside (AOR 5.26; 95%CI 1.54-17.92), arrests for sterile syringe possession (AOR 4.87; 95%I 1.56-15.15), prior HIV testing (AOR 2.45; 95%CI 1.04-5.81), and health insurance status

  3. Current Plate Motion Relative to the Hotspots and to the Mantle

    Science.gov (United States)

    Zheng, L.; Gordon, R. G.; Argus, D.; Demets, C.; Kreemer, C. W.

    2010-12-01

    We present several new global sets of angular velocities of the plates relative to the deeper mantle. A starting point for our estimate of plate motion relative to the hotspots is HS3, a hotspot data set developed by Gripp & Gordon [2002], which consists of two volcanic propagation rates and eleven segment trends from the Pacific, Nazca, South America, and North America plates. Due to the bias (argon loss) inherent in K-Ar measurements, the volcanic ages in HS3 are probably systematically too young and the volcanic propagation rates are thus probably biased (i.e., they are too high) [Morgan & Phipps Morgan, 2007]. Here we use the difference between an astrogeochronologic-based geomagnetic reversal time scale [Gradstein et al. 2004] and a K-Ar-based geomagnetic reversal time scale [Harland et al. 1982] as a proxy to estimate the recalibration required for K-Ar measurements. This recalibration of K-Ar ages reduces the volcanic propagation rates of the Hawaii hotspot track and the Society hotspot track by 8% and 6% respectively. We incorporate these revised volcanic propagation rates into the HS3B data set, which is merely HS3 corrected for this bias. We combine the HS3B data set with the MORVEL global set of plate relative angular velocities [DeMets et al., 2010] to determine HS3B-MORVEL, a new global set of plate angular velocities relative to the hotspots. Unsurprisingly, the motion of the Pacific plate relative to the hotspots is slower in HS3B-MORVEL than in HS3-NUVEL1A. Because the orientations of seismic anisotropy inferred from shear-wave splitting may in many places indicate the direction of motion of lithosphere relative to the deeper mantle, Kreemer [2009] compiled a data set of 474 shear-wave splitting data, which we refer to as the SKS data set. When we invert these data in a manner similar to his, but using the MORVEL relative angular velocities, we find that the azimuth residuals of SKS-MORVEL are strongly correlated within each plate and do not have

  4. A rare metastasis from a rare brain tumour

    DEFF Research Database (Denmark)

    Aabenhus, Kristine; Hahn, Christoffer Holst

    2014-01-01

    This case report presents the story of a patient with an oligodendroglioma metastasizing to the bone marrow and to lymph nodes of the neck. The patient had undergone primary brain surgery 13 years prior to the discovery of metastases and radiotherapy directed at the brain tumour two months prior........ Oligodendroglioma are rare primary brain tumours of which extraneural metastasis is even more rare. The incidence of cases like this may be increasing because of better treatment and thus longer survival of patients with oligodendroglioma....

  5. Imaging genomics.

    Science.gov (United States)

    Thompson, Paul M; Martin, Nicholas G; Wright, Margaret J

    2010-08-01

    Imaging genomics is an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease. Worldwide, thousands of individuals are being scanned with high-throughput genotyping (genome-wide scans), and new imaging techniques [high angular resolution diffusion imaging and resting state functional magnetic resonance imaging (MRI)] that provide fine-grained measures of the brain's structural and functional connectivity. Along with clinical diagnosis and cognitive testing, brain imaging offers highly reproducible measures that can be subjected to genetic analysis. Recent studies of twin, pedigree, and population-based datasets have discovered several candidate genes that consistently show small to moderate effects on brain measures. Many studies measure single phenotypes from the images, such as hippocampal volume, but voxel-wise genomic methods can plot the profile of genetic association at each 3D point in the brain. This exploits the full arsenal of imaging statistics to discover and replicate gene effects. Imaging genomics efforts worldwide are now working together to discover and replicate many promising leads. By studying brain phenotypes closer to causative gene action, larger gene effects are detectable with realistic sample sizes obtainable from meta-analysis of smaller studies. Imaging genomics has broad applications to dementia, mental illness, and public health.

  6. Marine genomics

    DEFF Research Database (Denmark)

    Oliveira Ribeiro, Ângela Maria; Foote, Andrew David; Kupczok, Anne

    2017-01-01

    evolutionary biology of non-model organisms to species of commercial relevance for fishing, aquaculture and biomedicine. Instead of providing an exhaustive list of available genomic data, we rather set to present contextualized examples that best represent the current status of the field of marine genomics.......Marine ecosystems occupy 71% of the surface of our planet, yet we know little about their diversity. Although the inventory of species is continually increasing, as registered by the Census of Marine Life program, only about 10% of the estimated two million marine species are known. This lag......-throughput sequencing approaches have been helping to improve our knowledge of marine biodiversity, from the rich microbial biota that forms the base of the tree of life to a wealth of plant and animal species. In this review, we present an overview of the applications of genomics to the study of marine life, from...

  7. Listeria Genomics

    Science.gov (United States)

    Cabanes, Didier; Sousa, Sandra; Cossart, Pascale

    The opportunistic intracellular foodborne pathogen Listeria monocytogenes has become a paradigm for the study of host-pathogen interactions and bacterial adaptation to mammalian hosts. Analysis of L. monocytogenes infection has provided considerable insight into how bacteria invade cells, move intracellularly, and disseminate in tissues, as well as tools to address fundamental processes in cell biology. Moreover, the vast amount of knowledge that has been gathered through in-depth comparative genomic analyses and in vivo studies makes L. monocytogenes one of the most well-studied bacterial pathogens. This chapter provides an overview of progress in the exploration of genomic, transcriptomic, and proteomic data in Listeria spp. to understand genome evolution and diversity, as well as physiological aspects of metabolism used by bacteria when growing in diverse environments, in particular in infected hosts.

  8. Ancient genomics

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Allentoft, Morten Erik; Avila Arcos, Maria del Carmen

    2015-01-01

    The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence...... by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans......, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when...

  9. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  10. Organizational Learning in Rare Events

    DEFF Research Database (Denmark)

    Vaarst Andersen, Kristina; Beukel, Karin; Tyler, Beverly B.

    their intellectual property to court. We propose, that organizations can learn to litigate, although it is a rare event, by applying mechanisms in a current litigation case that have been successful in previous litigation cases. However, we also posit, that the usefulness of these learning mechanisms for a current......When organizations encounter rare events they often find it challenging to extract learning from the experience. We analyze opportunities for organizational learning in one such rare event, namely Intellectual Property (IP) litigation, i.e., when organizations take disputes regarding...... litigation case is contingent on the type of litigation, contract versus infringement cases. If the organization is involved in litigation based on a contract breach, we suggest that learning will be less useful because the contract preceding the litigation defines the modus operandi and leaves...

  11. Organizational learning in rare events

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst; Beukel, Karin; Tyler, Beverly

    In this paper we build a theoretical framework for understanding whether and how firms learn from the rare event of litigating intellectual property cases. We draw on literature on organizational learning from rare events and examine the conditions under which firms can learn from rare events. We...... find that, when plaintiffs in IP litigation receive quick and clear positive feedback, this helps focus their attention on litigation feedback and motivates them to allocate resources that enhance learning. We explore the moderating effect of case type, finding that organizational learning is most...... applicable in cases without contractual constraints. In the setting studied, the learning effect of previous successes is contingent on case type, being less useful when firms litigate based on breach of contract....

  12. Building treasures for rare disorders.

    Science.gov (United States)

    Baas, Melanie; Huisman, Sylvia; van Heukelingen, John; Koekkoek, Gerritjan; Laan, Henk-Willem; Hennekam, Raoul C

    2015-01-01

    The internet pre-eminently marks an era with unprecedented chances for patient care. Especially individuals with rare disorders and their families can benefit. Their handicap of low numbers vanishes and can become a strength, as small, motivated and well-organized international support groups allow easily fruitful collaborations with physicians and researchers. Jointly setting research agendas and building wikipedias has eventually led to building of multi-lingual databases of longitudinal data on physical and behavioural characteristics of individuals with several rare disorders which we call waihonapedias (waihona meaning treasure in Hawaiian). There are hurdles to take, like online security and reliability of diagnoses, but sharing experiences and true collaborations will allow better research and patient care for fewer costs to patients with rare disorders. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Drug discovery and development for rare genetic disorders.

    Science.gov (United States)

    Sun, Wei; Zheng, Wei; Simeonov, Anton

    2017-09-01

    Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.

  14. The Matchmaker Exchange: a platform for rare disease gene discovery.

    Science.gov (United States)

    Philippakis, Anthony A; Azzariti, Danielle R; Beltran, Sergi; Brookes, Anthony J; Brownstein, Catherine A; Brudno, Michael; Brunner, Han G; Buske, Orion J; Carey, Knox; Doll, Cassie; Dumitriu, Sergiu; Dyke, Stephanie O M; den Dunnen, Johan T; Firth, Helen V; Gibbs, Richard A; Girdea, Marta; Gonzalez, Michael; Haendel, Melissa A; Hamosh, Ada; Holm, Ingrid A; Huang, Lijia; Hurles, Matthew E; Hutton, Ben; Krier, Joel B; Misyura, Andriy; Mungall, Christopher J; Paschall, Justin; Paten, Benedict; Robinson, Peter N; Schiettecatte, François; Sobreira, Nara L; Swaminathan, Ganesh J; Taschner, Peter E; Terry, Sharon F; Washington, Nicole L; Züchner, Stephan; Boycott, Kym M; Rehm, Heidi L

    2015-10-01

    There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow. © 2015 WILEY PERIODICALS, INC.

  15. Zebra: searching for rare diseases

    DEFF Research Database (Denmark)

    Dragusin, Radu; Petcu, Paula; Lioma, Christina

    2012-01-01

    disease diagnostic hypotheses in the domain of medical IR. In this work, we build upon an existing vertical medical search engine, Zebra, that is focused on rare disease diagnosis. In previous work, Zebra has been evaluated using real-life medical cases of rare and difficult diseases, and has been found...... to be a useful and competitive tool for clinicians. In this work, we extend Zebra’s functionalities to optimise the task of medical diagnosis through search as follows: we add the option of grouping retrieved documents into clusters based on disease name occurrence, and we offer a ‘disease-ranking’ option...

  16. Genomic imbalances in pediatric patients with chronic kidney disease

    OpenAIRE

    Verbitsky, Miguel; Sanna-Cherchi, Simone; Fasel, David A.; Levy, Brynn; Kiryluk, Krzysztof; Wuttke, Matthias; Abraham, Alison G.; Kaskel, Frederick; Köttgen, Anna; Warady, Bradley A.; Furth, Susan L; Wong, Craig S.; Gharavi, Ali G.

    2015-01-01

    BACKGROUND. There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown.

  17. Mitochondrial genome evolution in Alismatales: Size reduction and extensive loss of ribosomal protein genes

    DEFF Research Database (Denmark)

    Petersen, Gitte; Cuenca, Argelia; Zervas, Athanasios

    2017-01-01

    The order Alismatales is a hotspot for evolution of plant mitochondrial genomes characterized by remarkable differences in genome size, substitution rates, RNA editing, retrotranscription, gene loss and intron loss. Here we have sequenced the complete mitogenomes of Zostera marina and Stratiotes ...... mitogenome from a non-parasitic plant. Using a broad sample of the Alismatales, the evolutionary history of ribosomal protein gene loss is analyzed. In Zostera almost all ribosomal protein genes are lost from the mitogenome, but only some can be found in the nucleus....

  18. Demographic history and rare allele sharing among human populations

    Science.gov (United States)

    Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott;