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Sample records for ago2 immunoprecipitation identifies

  1. Ago2 immunoprecipitation identifies predicted microRNAs in human embryonic stem cells and neural precursors.

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    Loyal A Goff

    Full Text Available BACKGROUND: MicroRNAs are required for maintenance of pluripotency as well as differentiation, but since more microRNAs have been computationally predicted in genome than have been found, there are likely to be undiscovered microRNAs expressed early in stem cell differentiation. METHODOLOGY/PRINCIPAL FINDINGS: SOLiD ultra-deep sequencing identified >10(7 unique small RNAs from human embryonic stem cells (hESC and neural-restricted precursors that were fit to a model of microRNA biogenesis to computationally predict 818 new microRNA genes. These predicted genomic loci are associated with chromatin patterns of modified histones that are predictive of regulated gene expression. 146 of the predicted microRNAs were enriched in Ago2-containing complexes along with 609 known microRNAs, demonstrating association with a functional RISC complex. This Ago2 IP-selected subset was consistently expressed in four independent hESC lines and exhibited complex patterns of regulation over development similar to previously-known microRNAs, including pluripotency-specific expression in both hESC and iPS cells. More than 30% of the Ago2 IP-enriched predicted microRNAs are new members of existing families since they share seed sequences with known microRNAs. CONCLUSIONS/SIGNIFICANCE: Extending the classic definition of microRNAs, this large number of new microRNA genes, the majority of which are less conserved than their canonical counterparts, likely represent evolutionarily recent regulators of early differentiation. The enrichment in Ago2 containing complexes, the presence of chromatin marks indicative of regulated gene expression, and differential expression over development all support the identification of 146 new microRNAs active during early hESC differentiation.

  2. Direct targets of the tomato-ripening regulator RIN identified by transcriptome and chromatin immunoprecipitation analyses.

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    Fujisawa, Masaki; Shima, Yoko; Higuchi, Naoki; Nakano, Toshitsugu; Koyama, Yoshiyuki; Kasumi, Takafumi; Ito, Yasuhiro

    2012-06-01

    The physiological and biochemical changes in fruit ripening produce key attributes of fruit quality including color, taste, aroma and texture. These changes are driven by the highly regulated and synchronized activation of a huge number of ripening-associated genes. In tomato (Solanum lycopersicum), a typical climacteric fruit, the MADS-box transcription factor RIN is one of the earliest-acting ripening regulators, required for both ethylene-dependent and ethylene-independent pathways. Although we previously identified several direct RIN targets, many additional targets remain unidentified, likely including key ripening-associated genes. Here, we report the identification of novel RIN targets by transcriptome and chromatin immunoprecipitation (ChIP) analyses. Transcriptome comparisons by microarray of wild-type and rin mutant tomatoes identified 342 positively regulated genes and 473 negatively regulated genes by RIN during ripening. Most of the positively regulated genes contained possible RIN-binding (CArG-box) sequences in their promoters. Subsequently, we selected six genes from the positively regulated genes and a ripening regulator gene, CNR, and assayed their promoters by quantitative ChIP-PCR to examine RIN binding. All of the seven genes, which are involved in cell wall modification, aroma and flavor development, pathogen defense and transcriptional regulation during ripening, are targets of RIN, suggesting that RIN may control multiple diverse ripening processes. In particular, RIN directly regulates the expression of the ripening-associated transcription factors, CNR, TDR4 and a GRAS family gene, providing an important clue to elucidate the complicated transcriptional cascade for fruit ripening.

  3. RNA-Seq and RNA Immunoprecipitation Analyses of the Transcriptome of Streptomyces coelicolor Identify Substrates for RNase III

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    Gatewood, Marcha L.; Bralley, Patricia; Weil, M. Ryan

    2012-01-01

    RNase III is a key enzyme in the pathways of RNA degradation and processing in bacteria and has been suggested as a global regulator of antibiotic production in Streptomyces coelicolor. Using RNA-Seq, we have examined the transcriptomes of S. coelicolor M145 and an RNase III (rnc)-null mutant of that strain. RNA preparations with reduced levels of structural RNAs were prepared by subtractive hybridization prior to RNA-Seq analysis. We initially identified 7,800 transcripts of known and putative protein-coding genes in M145 and the null mutant, JSE1880, along with transcripts of 21 rRNA genes and 65 tRNA genes. Approximately 3,100 of the protein-coding transcripts were categorized as low-abundance transcripts. For further analysis, we selected those transcripts of known and putative protein-coding genes whose levels changed by ≥2-fold between the two S. coelicolor strains and organized those transcripts into 16 functional categories. We refined our analysis by performing RNA immunoprecipitation of the mRNA preparation from JSE1880 using a mutant RNase III protein that binds to transcripts but does not cleave them. This analysis identified ca. 800 transcripts that were enriched in the RNA immunoprecipitates, including 28 transcripts whose levels also changed by ≥2-fold in the RNA-Seq analysis. We compare our results with those obtained by microarray analysis of the S. coelicolor transcriptome and with studies describing the characterization of small noncoding RNAs. We have also used the RNA immunoprecipitation results to identify new substrates for RNase III cleavage. PMID:22389483

  4. Novel in vivo targets of ΔNp63 in keratinocytes identified by a modified chromatin immunoprecipitation approach

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    Ortt Kori

    2007-05-01

    Full Text Available Abstract Background p63 is a transcription factor that plays an important role in skin epidermal development and differentiation. The p63 gene encodes for two major protein isoforms, those containing an amino-terminal trans-activation domain (TAp63 and those lacking this domain (ΔNp63. Both the TA and ΔN transcripts are also alternatively spliced at the 3' end producing proteins with unique C-termini that are designated as α, β and γ isoforms. Recent research has suggested that ΔNp63 is the predominant isoform expressed and active in keratinocytes. Results To better elucidate the biological role of p63 in regulating gene expression in keratinocytes we performed chromatin immunoprecipitation (ChIP experiments with ΔNp63-specific antibodies. We included an additional step in the ChIP procedure to enrich for ΔNp63 targets by screening the library of immunoprecipitated DNA for its ability to bind recombinant GST-ΔNp63. Cloning of ΔNp63-ChIP-derived DNA fragments identified more than 60 potential ΔNp63 target loci that were located close to or embedded within known or predicted genes. Identity of these target genes suggests that they may participate in a myriad of cellular processes including transcriptional regulation, signaling and metabolism. Here we confirm the binding of ΔNp63 to several of these genomic loci both by EMSA and replicate ChIP assays. Finally we show that the expression of many of these target genes is altered when ΔNp63 levels in keratinocytes are reduced by siRNA, further confirming that these are bona fide targets. Conclusion This unbiased genomic approach has allowed us to uncover functional targets of ΔNp63 and serves as the initial step in further analysis of the transcriptional regulatory mechanisms that are governed by p63 in keratinocytes.

  5. Genome-wide identification of Ago2 binding sites from mouse embryonic stem cells with and without mature microRNAs

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    Leung, Anthony K L; Young, Amanda G; Bhutkar, Arjun; Zheng, Grace X; Bosson, Andrew D; Nielsen, Cydney B; Sharp, Phillip A

    2010-01-01

    MicroRNAs (miRNAs) are 19-22nt non-coding RNAs that post-transcriptionally regulate mRNA targets. To identify endogenous miRNA binding sites, we performed photo-crosslinking immunoprecipitation using Ago2 antibodies, followed by deep-sequencing of RNAs (CLIP-seq) in mouse embryonic stem cells (mESCs). We also performed CLIP-seq in Dicer−/− mESCs that lack mature miRNAs, allowing us to define whether the association of Ago2 with the identified sites was miRNA-dependent. A significantly enriched motif, GCACUU, was identified only in wild-type mESCs in 3′ untranslated and coding regions. This motif matches the seed of a miRNA family that constitutes ∼68% of the mESC miRNA population. Unexpectedly, a G-rich motif was enriched in sequences crosslinked to Ago2 in the presence and absence of miRNAs. Expression analysis and reporter assays confirmed that the seed-related motif confers miRNA-directed regulation on host mRNAs and that the G-rich motif can modulate this regulation. PMID:21258322

  6. Analysis list: AGO2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available AGO2 Blood,Prostate + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/A...GO2.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/AGO2.5.tsv http://dbarchive.biosciencedbc.j...p/kyushu-u/hg19/target/AGO2.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/AGO2.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/AGO2.Prostate.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Prostate.gml ...

  7. Chromatin immunoprecipitation and multiplex sequencing (ChIP-Seq) to identify global transcription factor binding sites in the nematode Caenorhabditis elegans.

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    Brdlik, Cathleen M; Niu, Wei; Snyder, Michael

    2014-01-01

    The global identification of transcription factor (TF) binding sites is a critical step in the elucidation of the functional elements of the genome. Several methods have been developed that map TF binding in human cells, yeast, and other model organisms. These methods make use of chromatin immunoprecipitation, or ChIP, and take advantage of the fact that formaldehyde fixation of living cells can be used to cross-link DNA sequences to the TFs that bind them in vivo. In ChIP, the cross-linked TF-DNA complexes are sheared by sonication, size fractionated, and incubated with antibody specific to the TF of interest to generate a library of TF-bound DNA sequences. ChIP-chip was the first technology developed to globally identify TF-bound DNA sequences and involves subsequent hybridization of the ChIP DNA to oligonucleotide microarrays. However, ChIP-chip proved to be costly, labor-intensive, and limited by the fixed number of probes available on the microarray chip. ChIP-Seq combines ChIP with massively parallel high-throughput sequencing (see Explanatory Chapter: Next Generation Sequencing) and has demonstrated vast improvement over ChIP-chip with respect to time and cost, signal-to-noise ratio, and resolution. In particular, multiplex sequencing can be used to achieve a higher throughput in ChIP-Seq analyses involving organisms with genomes of lower complexity than that of human (Lefrançois et al., 2009) and thereby reduce the cost and amount of time needed for each result. The multiplex ChIP-Seq method described in this section has been developed for Caenorhabditis elegans, but is easily adaptable for other organisms.

  8. An antiviral defense role of AGO2 in plants.

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    Jagger J W Harvey

    Full Text Available BACKGROUND: Argonaute (AGO proteins bind to small-interfering (siRNAs and micro (miRNAs to target RNA silencing against viruses, transgenes and in regulation of mRNAs. Plants encode multiple AGO proteins but, in Arabidopsis, only AGO1 is known to have an antiviral role. METHODOLOGY/PRINCIPAL FINDINGS: To uncover the roles of specific AGOs in limiting virus accumulation we inoculated turnip crinkle virus (TCV to Arabidopsis plants that were mutant for each of the ten AGO genes. The viral symptoms on most of the plants were the same as on wild type plants although the ago2 mutants were markedly hyper-susceptible to this virus. ago2 plants were also hyper-susceptible to cucumber mosaic virus (CMV, confirming that the antiviral role of AGO2 is not specific to a single virus. For both viruses, this phenotype was associated with transient increase in virus accumulation. In wild type plants the AGO2 protein was induced by TCV and CMV infection. CONCLUSIONS/SIGNIFICANCE: Based on these results we propose that there are multiple layers to RNA-mediated defense and counter-defense in the interactions between plants and their viruses. AGO1 represents a first layer. With some viruses, including TCV and CMV, this layer is overcome by viral suppressors of silencing that can target AGO1 and a second layer involving AGO2 limits virus accumulation. The second layer is activated when the first layer is suppressed because AGO2 is repressed by AGO1 via miR403. The activation of the second layer is therefore a direct consequence of the loss of the first layer of defense.

  9. Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis of the Penicillium chrysogenum Velvet Protein PcVelA Identifies Methyltransferase PcLlmA as a Novel Downstream Regulator of Fungal Development.

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    Becker, Kordula; Ziemons, Sandra; Lentz, Katharina; Freitag, Michael; Kück, Ulrich

    2016-01-01

    Penicillium chrysogenum is the sole industrial producer of the β-lactam antibiotic penicillin, which is the most commonly used drug for treating bacterial infections. In P. chrysogenum and other filamentous fungi, secondary metabolism and morphogenesis are controlled by the highly conserved multisubunit velvet complex. Here we present the first chromatin immunoprecipitation next-generation sequencing (ChIP-seq) analysis of a fungal velvet protein, providing experimental evidence that a velvet homologue in P. chrysogenum (PcVelA) acts as a direct transcriptional regulator at the DNA level in addition to functioning as a regulator at the protein level in P. chrysogenum, which was previously described. We identified many target genes that are related to processes known to be dependent on PcVelA, e.g., secondary metabolism as well as asexual and sexual development. We also identified seven PcVelA target genes that encode putative methyltransferases. Yeast two-hybrid and bimolecular fluorescence complementation analyses showed that one of the putative methyltransferases, PcLlmA, directly interacts with PcVelA. Furthermore, functional characterization of PcLlmA demonstrated that this protein is involved in the regulation of conidiosporogenesis, pellet formation, and hyphal morphology, all traits with major biotechnological relevance. IMPORTANCE Filamentous fungi are of major interest for biotechnological and pharmaceutical applications. This is due mainly to their ability to produce a wide variety of secondary metabolites, many of which are relevant as antibiotics. One of the most prominent examples is penicillin, a β-lactam antibiotic that is produced on the industrial scale by fermentation of P. chrysogenum. In recent years, the multisubunit protein complex velvet has been identified as one of the key regulators of fungal secondary metabolism and development. However, until recently, only a little has been known about how velvet mediates regulation at the

  10. AGO1 and AGO2 act redundantly in miR408-mediated plantacyanin regulation

    OpenAIRE

    Nicolas Maunoury; Hervé Vaucheret

    2011-01-01

    Background : In Arabidopsis, AGO1 and AGO2 associate with small RNAs that exhibit a Uridine and an Adenosine at their 5′ end, respectively. Because most plant miRNAs have a 5′U, AGO1 plays many essential roles in miRNA-mediated regulation of development and stress responses. In contrast, AGO2 has only been implicated in antibacterial defense in association with miR393*, which has a 5′A. AGO2 also participates in antiviral defense in association with viral siRNAs. Principal Findings : This ...

  11. Site occupancy and magnetic properties of pyrochlore-structured AgOs2O6

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    Shu, G. J.; Hsu, S. L.; Chu, M.-W.; Lee, C. C.; Chou, F. C.

    2012-09-01

    AgOs2O6 prepared from ion-exchanged superconducting β-pyrochlore KOs2O6 has been shown to be non-superconducting. Synchrotron x-ray structure refinement suggests that AgOs2O6 has the Ag ion mostly occupying the low-symmetry 32e site in the F d\\bar {3}m space group of proper occupancy, which is different from the original major occupancy at the high-symmetry 8b site for KOs2O6, and similar to non-superconducting Na1.4Os2O6ṡH2O. Magnetic susceptibility measurements found no magnetic ordering down to ˜1.7 K. The trace amount of isolated spins suggests that the Ag could be neutral and lead to a pure Os6+ valence state of zero spin in the newly prepared AgOs2O6.

  12. Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

    DEFF Research Database (Denmark)

    Gao, Min; Wei, Wei; Li, Ming Hua

    2014-01-01

    DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute...... (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian...

  13. eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference

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    Yi, Tingfang; Arthanari, Haribabu; Akabayov, Barak; Song, Huaidong; Papadopoulos, Evangelos; Qi, Hank H.; Jedrychowski, Mark; Güttler, Thomas; Guo, Cuicui; Luna, Rafael E.; Gygi, Steven P.; Huang, Stephen A.; Wagner, Gerhard

    2015-05-01

    MicroRNA (miRNA) biogenesis and miRNA-guided RNA interference (RNAi) are essential for gene expression in eukaryotes. Here we report that translation initiation factor eIF1A directly interacts with Ago2 and promotes Ago2 activities in RNAi and miR-451 biogenesis. Biochemical and NMR analyses demonstrate that eIF1A binds to the MID domain of Ago2 and this interaction does not impair translation initiation. Alanine mutation of the Ago2-facing Lys56 in eIF1A impairs RNAi activities in human cells and zebrafish. The eIF1A-Ago2 assembly facilitates Dicer-independent biogenesis of miR-451, which mediates erythrocyte maturation. Human eIF1A (heIF1A), but not heIF1A(K56A), rescues the erythrocyte maturation delay in eif1axb knockdown zebrafish. Consistently, miR-451 partly compensates erythrocyte maturation defects in zebrafish with eif1axb knockdown and eIF1A(K56A) expression, supporting a role of eIF1A in miRNA-451 biogenesis in this model. Our results suggest that eIF1A is a novel component of the Ago2-centred RNA-induced silencing complexes (RISCs) and augments Ago2-dependent RNAi and miRNA biogenesis.

  14. HuR and Ago2 Bind the Internal Ribosome Entry Site of Enterovirus 71 and Promote Virus Translation and Replication.

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    Jing-Yi Lin

    Full Text Available EV71 (enterovirus 71 RNA contains an internal ribosomal entry site (IRES that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs. We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication. Since its mechanism of action is unknown, we hypothesized that it might control association of ITAFs with the IRES. Here, we identified the mRNA stability factor HuR and the RISC subunit Argonaute 2 (Ago2 as two ITAFs that bind stem-loop II. In contrast to AUF1, HuR and Ago2 promote EV71 IRES activity and virus replication. In vitro RNA-binding assays revealed that vsRNA1 can alter association of Ago2, HuR, and AUF1 with stem-loop II. This presents a possible mechanism by which vsRNA1 could control viral translation and replication.

  15. The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif

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    Grishin Nick V

    2009-01-01

    Full Text Available Abstract Background Argonaute (Ago proteins interact with small regulatory RNAs to mediate gene regulatory pathways. A recent report by Kiriakidou et al. 1 describes an MC sequence region identified in Ago2 that displays similarity to the cap-binding motif in translation initiation factor 4E (eIF4E. In a cap-bound eIF4E structure, two important aromatic residues of the motif stack on either side of a 7-methylguanosine 5'-triphosphate (m7Gppp base. The corresponding Ago2 aromatic residues (F450 and F505 were hypothesized to perform the same cap-binding function. However, the detected similarity between the MC sequence and the eIF4E cap-binding motif was questionable. Results A number of sequence-based and structure-based bioinformatics methods reveal the reported similarity between the Ago2 MC sequence region and the eIF4E cap-binding motif to be spurious. Alternatively, the MC sequence region is confidently assigned to the N-terminus of the Ago piwi module, within the mid domain of experimentally determined prokaryotic Ago structures. Confident mapping of the Ago2 MC sequence region to the piwi mid domain results in a homology-based structure model that positions the identified aromatic residues over 20 Å apart, with one of the aromatic side chains (F450 contributing instead to the hydrophobic core of the domain. Conclusion Correct functional prediction based on weak sequence similarity requires substantial evolutionary and structural support. The evolutionary context of the Ago mid domain suggested by multiple sequence alignment is limited to a conserved hydrophobicity profile required for the fold and a motif following the MC region that binds guide RNA. Mapping of the MC sequence to the mid domain structure reveals Ago2 aromatics that are incompatible with eIF4E-like mRNA cap-binding, yet display some limited local structure similarities that cause the chance sequence match to eIF4E. Reviewers This article was reviewed by Arcady Mushegian

  16. Bioenergetics and gene silencing approaches for unraveling nucleotide recognition by the human EIF2C2/Ago2 PAZ domain.

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    Kandeel, Mahmoud; Al-Taher, Abdullah; Nakashima, Remi; Sakaguchi, Tomoya; Kandeel, Ali; Nagaya, Yuki; Kitamura, Yoshiaki; Kitade, Yukio

    2014-01-01

    Gene silencing and RNA interference are major cellular processes that control gene expression via the cleavage of target mRNA. Eukaryotic translation initiation factor 2C2 (EIF2C2, Argonaute protein 2, Ago2) is considered to be the major player of RNAi as it is the core component of RISC complexes. While a considerable amount of research has focused on RNA interference and its associated mechanisms, the nature and mechanisms of nucleotide recognition by the PAZ domain of EIF2C2/Ago2 have not yet been characterized. Here, we demonstrate that the EIF2C2/Ago2 PAZ domain has an inherent lack of binding to adenine nucleotides, a feature that highlights the poor binding of 3'-adenylated RNAs with the PAZ domain as well as the selective high trimming of the 3'-ends of miRNA containing adenine nucleotides. We further show that the PAZ domain selectively binds all ribonucleotides (except adenosine), whereas it poorly recognizes deoxyribonucleotides. In this context, the modification of dTMP to its ribonucleotide analogue gave a drastic improvement of binding enthalpy and, hence, binding affinity. Additionally, higher in vivo gene silencing efficacy was correlated with the stronger PAZ domain binders. These findings provide new insights into the nature of the interactions of the EIF2C2/Ago2 PAZ domain.

  17. Bioenergetics and gene silencing approaches for unraveling nucleotide recognition by the human EIF2C2/Ago2 PAZ domain.

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    Mahmoud Kandeel

    Full Text Available Gene silencing and RNA interference are major cellular processes that control gene expression via the cleavage of target mRNA. Eukaryotic translation initiation factor 2C2 (EIF2C2, Argonaute protein 2, Ago2 is considered to be the major player of RNAi as it is the core component of RISC complexes. While a considerable amount of research has focused on RNA interference and its associated mechanisms, the nature and mechanisms of nucleotide recognition by the PAZ domain of EIF2C2/Ago2 have not yet been characterized. Here, we demonstrate that the EIF2C2/Ago2 PAZ domain has an inherent lack of binding to adenine nucleotides, a feature that highlights the poor binding of 3'-adenylated RNAs with the PAZ domain as well as the selective high trimming of the 3'-ends of miRNA containing adenine nucleotides. We further show that the PAZ domain selectively binds all ribonucleotides (except adenosine, whereas it poorly recognizes deoxyribonucleotides. In this context, the modification of dTMP to its ribonucleotide analogue gave a drastic improvement of binding enthalpy and, hence, binding affinity. Additionally, higher in vivo gene silencing efficacy was correlated with the stronger PAZ domain binders. These findings provide new insights into the nature of the interactions of the EIF2C2/Ago2 PAZ domain.

  18. Designing Ago2-specific siRNA/shRNA to Avoid Competition with Endogenous miRNAs.

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    Ma, Hongming; Zhang, Junli; Wu, Haoquan

    2014-07-15

    Relatively large amounts of transfected siRNA can compete for Ago proteins and thus compromise endogenous miRNA function, potentially leading to toxicities. Here, we show that shRNA can also perturb endogenous miRNA function similarly. More importantly, we also show that the problem can be solved by designing shRNAs in the context of pre-miR-451 structure with completely complementary stem, which significantly improves the Ago2 specificity. This shRNA was shown to be Ago2-specific, and maintain target-silencing ability while avoiding competition with endogenous miRNAs by not competing for Agos 1, 3, and 4. We conclude that modified pre-miR-451 structure provides a general platform to design shRNAs that significantly reduce perturbation of miRNA function.

  19. Taenia taeniaeformis: immunoprecipitation analysis of the protein antigens of oncospheres and larvae.

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    Bowtell, D D; Mitchell, G F; Anders, R F; Lightowlers, M W; Rickard, M D

    1983-12-01

    Biosynthetically or exogenously labeled proteins and immunoprecipitated protein antigens of established 28-day-old larvae of Taenia taeniaeformis were compared with proteins and antigens of infective oncospheres using single and two-dimensional gel electrophoresis. Immunoprecipitation was carried out using sera from infected mice and mouse antisera raised to larvae or oncospheres, and emphasis was placed on identifying antigens common to both oncospheres and larvae. Two major larval antigens of Mr 40,000 and 200,000, designated Tt40 and Tt200, are common to somatic larval preparations and oncospheres. Additionally, two major oncosphere antigens of Mr 55,000 and 60,000, designated Tt55 and Tt60, are also present in larval excretory and secretory (i.e., ES or exoantigen) products. Information obtained from these immunoprecipitation analyses will facilitate isolation and production of common as well as stage-specific protein antigens in the development of defined-antigen vaccines in this model system of cysticercosis.

  20. Identification of an archaeal mercury regulon by chromatin immunoprecipitation.

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    Rudrappa, Deepak; Yao, Andrew I; White, Derrick; Pavlik, Benjamin J; Singh, Raghuveer; Facciotti, Marc T; Blum, Paul

    2015-12-01

    Mercury is a heavy metal and toxic to all forms of life. Metal exposure can invoke a response to improve survival. In archaea, several components of a mercury response system have been identified, but it is not known whether metal transport is a member of this system. To identify such missing components, a peptide-tagged MerR transcription factor was used to localize enriched chromosome regions by chromosome immunoprecipitation combined with DNA sequence analysis. Such regions could serve as secondary regulatory binding sites to control the expression of additional genes associated with mercury detoxification. Among the 31 highly enriched loci, a subset of five was pursued as potential candidates based on their current annotations. Quantitative reverse transcription-PCR analysis of these regions with and without mercury treatment in WT and mutant strains lacking merR indicated significant regulatory responses under these conditions. Of these, a Family 5 extracellular solute-binding protein and the MarR transcription factor shown previously to control responses to oxidation were most strongly affected. Inactivation of the solute-binding protein by gene disruption increased the resistance of mutant cells to mercury challenge. Inductively coupled plasma-MS analysis of the mutant cell line following metal challenge indicated there was less intracellular mercury compared with the isogenic WT strain. Together, these regulated genes comprise new members of the archaeal MerR regulon and reveal a cascade of transcriptional control not previously demonstrated in this model organism.

  1. Nanodisc-based Co-immunoprecipitation for Mass Spectrometric Identification of Membrane-interacting Proteins

    DEFF Research Database (Denmark)

    Borch-Jensen, Jonas; Roepstorff, Peter; Møller-Jensen, Jakob

    2011-01-01

    enterotoxigenic Escherischia coli, GM1-nanodiscs were employed for co-immunoprecipitation. The B subunit of heat labile enterotoxin was identified as a specific interaction partner by mass spectrometry, thus demonstrating that nanodisc technology is useful for highly specific detection and identification...

  2. Inferring protein-protein interaction complexes from immunoprecipitation data

    NARCIS (Netherlands)

    Kutzera, J.; Hoefsloot, H.C.J.; Malovannaya, A.; Smit, A.B.; Van Mechelen, I.; Smilde, A.K.

    2013-01-01

    BACKGROUND: Protein inverted question markprotein interactions in cells are widely explored using small inverted question markscale experiments. However, the search for protein complexes and their interactions in data from high throughput experiments such as immunoprecipitation is still a challenge.

  3. Whole genome methylation profiling by immunoprecipitation of methylated DNA.

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    Sharp, Andrew J

    2012-01-01

    I provide a protocol for DNA methylation profiling based on immunoprecipitation of methylated DNA using commercially available monoclonal antibodies that specifically recognize 5-methylcytosine. Quantification of the level of enrichment of the resulting DNA enables DNA methylation to be assayed for any genomic locus, including entire chromosomes or genomes if appropriate microarray or high-throughput sequencing platforms are used. In previous studies (1, 2), I have used hybridization to oligonucleotide arrays from Roche Nimblegen Inc, which allow any genomic region of interest to be interrogated, dependent on the array design. For example, using modern tiling arrays comprising millions of oligonucleotide probes, several complete human chromosomes can be assayed at densities of one probe per 100 bp or greater, sufficient to yield high-quality data. However, other methods such as quantitative real-time PCR or high-throughput sequencing can be used, giving either measurement of methylation at a single locus or across the entire genome, respectively. While the data produced by single locus assays is relatively simple to analyze and interpret, global assays such as microarrays or high-throughput sequencing require more complex statistical approaches in order to effectively identify regions of differential methylation, and a brief outline of some approaches is given.

  4. Chromatin immunoprecipitation in microfluidic droplets: towards fast and cheap analyses.

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    Teste, Bruno; Champ, Jerome; Londono-Vallejo, Arturo; Descroix, Stéphanie; Malaquin, Laurent; Viovy, Jean-Louis; Draskovic, Irena; Mottet, Guillaume

    2017-01-31

    Genetic organization is governed by the interaction of DNA with histone proteins, and differential modifications of these proteins is a fundamental mechanism of gene regulation. Histone modifications are primarily studied through chromatin immunoprecipitation (ChIP) assays, however conventional ChIP procedures are time consuming, laborious and require a large number of cells. Here we report for the first time the development of ChIP in droplets based on a microfluidic platform combining nanoliter droplets, magnetic beads (MB) and magnetic tweezers (MT). The droplet approach enabled compartmentalization and improved mixing, while reducing the consumption of samples and reagents in an integrated workflow. Anti-histone antibodies grafted to MB were used as a solid support to capture and transfer the target chromatin from droplets to droplets in order to perform chromatin immunoprecipitation, washing, elution and purification of DNA. We designed a new ChIP protocol to investigate four different types of modified histones with known roles in gene activation or repression. We evaluated the performances of this new ChIP in droplet assay in comparison with conventional methods. The proposed technology dramatically reduces analytical time from a few days to 7 hours, simplifies the ChIP protocol and decreases the number of cells required by 100 fold while maintaining a high degree of sensitivity and specificity. Therefore this droplet-based ChIP assay represents a new, highly advantageous and convenient approach to epigenetic analyses.

  5. Methylation profiling using methylated DNA immunoprecipitation and tiling array hybridization.

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    Cheung, Hoi-Hung; Lee, Tin-Lap; Rennert, Owen M; Chan, Wai-Yee

    2012-01-01

    DNA methylation is an important epigenetic modification that regulates development and plays a role in the pathophysiology of many diseases. It is dynamically changed during germline development. Methylated DNA immunoprecipitation (MeDIP) is an efficient, cost-effective method for locus-specific and genome-wide analysis. Methylated DNA fragments are enriched by a 5-methylcytidine-recognizing antibody, therefore allowing the analysis of both CpG and non-CpG methylation. The enriched DNA fragments can be amplified and hybridized to tiling arrays covering CpG islands, promoters, or the entire genome. Comparison of different methylomes permits the discovery of differentially methylated regions that might be important in disease- or tissue-specific expression. Here, we describe an established MeDIP protocol and tiling array hybridization method for profiling methylation of testicular germ cells.

  6. Chromatin immunoprecipitation: optimization, quantitative analysis and data normalization

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    Peterhansel Christoph

    2007-09-01

    Full Text Available Abstract Background Chromatin remodeling, histone modifications and other chromatin-related processes play a crucial role in gene regulation. A very useful technique to study these processes is chromatin immunoprecipitation (ChIP. ChIP is widely used for a few model systems, including Arabidopsis, but establishment of the technique for other organisms is still remarkably challenging. Furthermore, quantitative analysis of the precipitated material and normalization of the data is often underestimated, negatively affecting data quality. Results We developed a robust ChIP protocol, using maize (Zea mays as a model system, and present a general strategy to systematically optimize this protocol for any type of tissue. We propose endogenous controls for active and for repressed chromatin, and discuss various other controls that are essential for successful ChIP experiments. We experienced that the use of quantitative PCR (QPCR is crucial for obtaining high quality ChIP data and we explain why. The method of data normalization has a major impact on the quality of ChIP analyses. Therefore, we analyzed different normalization strategies, resulting in a thorough discussion of the advantages and drawbacks of the various approaches. Conclusion Here we provide a robust ChIP protocol and strategy to optimize the protocol for any type of tissue; we argue that quantitative real-time PCR (QPCR is the best method to analyze the precipitates, and present comprehensive insights into data normalization.

  7. Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.

    Science.gov (United States)

    Cejas, Paloma; Li, Lewyn; O'Neill, Nicholas K; Duarte, Melissa; Rao, Prakash; Bowden, Michaela; Zhou, Chensheng W; Mendiola, Marta; Burgos, Emilio; Feliu, Jaime; Moreno-Rubio, Juan; Guadalajara, Héctor; Moreno, Víctor; García-Olmo, Damián; Bellmunt, Joaquim; Mullane, Stephanie; Hirsch, Michelle; Sweeney, Christopher J; Richardson, Andrea; Liu, X Shirley; Brown, Myles; Shivdasani, Ramesh A; Long, Henry W

    2016-06-01

    Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits the ability to study the epigenomes of valuable, clinically annotated tissue resources. Here we describe fixed-tissue chromatin immunoprecipitation sequencing (FiT-seq), a method that enables reliable extraction of soluble chromatin from formalin-fixed paraffin-embedded (FFPE) tissue samples for accurate detection of histone marks. We demonstrate that FiT-seq data from FFPE specimens are concordant with ChIP-seq data from fresh-frozen samples of the same tumors. By using multiple histone marks, we generate chromatin-state maps and identify cis-regulatory elements in clinical samples from various tumor types that can readily allow us to distinguish between cancers by the tissue of origin. Tumor-specific enhancers and superenhancers that are elucidated by FiT-seq analysis correlate with known oncogenic drivers in different tissues and can assist in the understanding of how chromatin states affect gene regulation.

  8. A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue.

    Science.gov (United States)

    Haim, Yulia; Tarnovscki, Tanya; Bashari, Dana; Rudich, Assaf

    2013-11-01

    Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.

  9. 白纹伊蚊AGO2和Dcr-2基因片段克隆及各发育期转录水平分析%Cloning of AGO2 and Dcr-2 Gene Fragments and Analysis of Their Transcription Level in Different Developmental Stages of Aedes albopictus

    Institute of Scientific and Technical Information of China (English)

    蔡燕丽; 郑学礼

    2012-01-01

    Objective To perform molecular cloning of the ACO2 and Dcr-2 gene fragments associated with RNA interference pathway of Aedes albopictus and characterize the transcription level of the two genes across all life stages of the mosquito. Methods The degenerate primers were designed based on the conserved regions of AGO2 and Dcr-2 amino acid sequences, and the AGO2 and Dcr-2 cDNA fragments were amplified from total RNA of a female mosquito by RT-PCR. The PCR products were cloned into pMD18-T vector and transformed into E. Coli DH5α strain, and the positive clones were selected and sequenced, with the results for homology analysis by Blastx. The specific primers were designed according to the sequences of ACO2 and Dcr-2 from Ae. Albopictus, which were used to investigate the transcription levels of these two genes from eggs, Ⅰ and Ⅱ instars larvae, Ⅲ and IV instars larvae, pupa, male and female mosquitoes by semi-quantitative RT-PCR. Results The AGO2 and Dcr-2 cDNA fragments obtained were 326 bp and 491 bp in length, with the Accession number of JQ764670 and JQ764671, respectively. The Blastx analysis showed that the AC02 and Dcr-2 amino acid sequences shared 91% similarity to AGO2 of Ae. Aegypti and 98% to Dcr-2 of Ae. Albopictus. The transcription of ACO2 and Dcr-2 genes was detected in all life stages of Ae. Albopictus, with the highest level of mRNA in female mosquitoes, which was 3.1 times and 15.5 times higher for AGO2 and Dcr-2 than in male mosquitoes, respectively, and significantly higher than other developmental stages (P<0.05). Conclusion The AGO2 and Dcr-2 cDNA sequences have been partially obtained and the hightest transcription level found in female Ae. Albopictus, suggesting that AGO2 and Dcr-2 are the key genes of RNA interference in female mosquitoes.%目的 克隆白纹伊蚊(Aedes albopictus )RNA干扰通路相关AGO2和Dcr-2基因片段,并分析该蚊种不同发育阶段这2个基因片段的转录水平.方法

  10. Proteomics Analysis of Cellular Proteins Co-Immunoprecipitated with Nucleoprotein of Influenza A Virus (H7N9)

    Science.gov (United States)

    Sun, Ningning; Sun, Wanchun; Li, Shuiming; Yang, Jingbo; Yang, Longfei; Quan, Guihua; Gao, Xiang; Wang, Zijian; Cheng, Xin; Li, Zehui; Peng, Qisheng; Liu, Ning

    2015-01-01

    Avian influenza A viruses are serious veterinary pathogens that normally circulate among avian populations, causing substantial economic impacts. Some strains of avian influenza A viruses, such as H5N1, H9N2, and recently reported H7N9, have been occasionally found to adapt to humans from other species. In order to replicate efficiently in the new host, influenza viruses have to interact with a variety of host factors. In the present study, H7N9 nucleoprotein was transfected into human HEK293T cells, followed by immunoprecipitated and analyzed by proteomics approaches. A series of host proteins co-immunoprecipitated were identified with high confidence, some of which were found to be acetylated at their lysine residues. Bioinformatics analysis revealed that spliceosome might be the most relevant pathway involved in host response to nucleoprotein expression, increasing our emerging knowledge of host proteins that might be involved in influenza virus replication activities. PMID:26528969

  11. Proteomics Analysis of Cellular Proteins Co-Immunoprecipitated with Nucleoprotein of Influenza A Virus (H7N9

    Directory of Open Access Journals (Sweden)

    Ningning Sun

    2015-10-01

    Full Text Available Avian influenza A viruses are serious veterinary pathogens that normally circulate among avian populations, causing substantial economic impacts. Some strains of avian influenza A viruses, such as H5N1, H9N2, and recently reported H7N9, have been occasionally found to adapt to humans from other species. In order to replicate efficiently in the new host, influenza viruses have to interact with a variety of host factors. In the present study, H7N9 nucleoprotein was transfected into human HEK293T cells, followed by immunoprecipitated and analyzed by proteomics approaches. A series of host proteins co-immunoprecipitated were identified with high confidence, some of which were found to be acetylated at their lysine residues. Bioinformatics analysis revealed that spliceosome might be the most relevant pathway involved in host response to nucleoprotein expression, increasing our emerging knowledge of host proteins that might be involved in influenza virus replication activities.

  12. Genome-Wide Chromatin Immunoprecipitation in Candida albicans and Other Yeasts

    Science.gov (United States)

    Lohse, Matthew B.; Kongsomboonvech, Pisiwat; Madrigal, Maria; Hernday, Aaron D.; Nobile, Clarissa J.

    2016-01-01

    Chromatin immunoprecipitation experiments are critical to investigating the interactions between DNA and a wide range of nuclear proteins within a cell or biological sample. In this chapter we outline an optimized protocol for genome-wide chromatin immunoprecipitation that has been used successfully for several distinct morphological forms of numerous yeast species, and include an optimized method for amplification of chromatin immunoprecipitated DNA samples and hybridization to a high-density oligonucleotide tiling microarray. We also provide detailed suggestions on how to analyze the complex data obtained from these experiments. PMID:26483022

  13. A DNA immunoprecipitation assay used in quantitative detection of in vitro DNA-protein complex binding.

    Science.gov (United States)

    Kim, Min Young; Chae, Ji Hyung; Oh, Chang-Ho; Kim, Chul Geun

    2013-10-15

    To begin gene transcription, several transcription factors must bind to specific DNA sequences to form a complex via DNA-protein interactions. We established an in vitro method for specific and sensitive analyses of DNA-protein interactions based on a DNA immunoprecipitation (DIP) method. We verified the accuracy and efficiency of the DIP assay in quantitatively measuring DNA-protein binding using transcription factor CP2c as a model. With our DIP assay, we could detect specific interactions within a DNA-CP2c complex, with reproducible and quantitative binding values. In addition, we were able to effectively measure the changes in DNA-CP2c binding by the addition of a small molecule, FQI1 (factor quinolinone inhibitor 1), previously identified as a specific inhibitor of this binding. To identify a new regulator of DNA-CP2c binding, we analyzed several CP2c binding peptides and found that only one class of peptide severely inhibits DNA-CP2c binding. These data show that our DIP assay is very useful in quantitatively detecting the binding dynamics of DNA-protein complex. Because DNA-protein interaction is very dynamic in different cellular environments, our assay can be applied to the detection of active transcription factors, including promoter occupancy in normal and disease conditions. Moreover, it may be used to develop a targeted regulator of specific DNA-protein interaction.

  14. Identification of potential target genes for the tomato fruit-ripening regulator RIN by chromatin immunoprecipitation

    Directory of Open Access Journals (Sweden)

    Nakano Toshitsugu

    2011-01-01

    Full Text Available Abstract Background During ripening, climacteric fruits increase their ethylene level and subsequently undergo various physiological changes, such as softening, pigmentation and development of aroma and flavor. These changes occur simultaneously and are caused by the highly synchronized expression of numerous genes at the onset of ripening. In tomatoes, the MADS-box transcription factor RIN has been regarded as a key regulator responsible for the onset of ripening by acting upstream of both ethylene- and non-ethylene-mediated controls. However, except for LeACS2, direct targets of RIN have not been clarified, and little is known about the transcriptional cascade for ripening. Results Using immunoprecipitated (IPed DNA fragments recovered by chromatin immunoprecipitation (ChIP with anti-RIN antibody from ripening tomato fruit, we analyzed potential binding sites for RIN (CArG-box sites in the promoters of representative ripening-induced genes by quantitative PCR. Results revealed nearly a 5- to 20-fold enrichment of CArG boxes in the promoters of LeACS2, LeACS4, PG, TBG4, LeEXP1, and LeMAN4 and of RIN itself, indicating direct interaction of RIN with their promoters in vivo. Moreover, sequence analysis and genome mapping of 51 cloned IPed DNAs revealed potential RIN binding sites. Quantitative PCR revealed that four of the potential binding sites were enriched 4- to 17-fold in the IPed DNA pools compared with the controls, indicating direct interaction of RIN with these sites in vivo. Near one of the four CArG boxes we found a gene encoding a protein similar to thioredoxin y1. An increase in the transcript level of this gene was observed with ripening in normal fruit but not in the rin mutant, suggesting that RIN possibly induces its expression. Conclusions The presented results suggest that RIN controls fruit softening and ethylene production by the direct transcriptional regulation of cell-wall-modifying genes and ethylene biosynthesis genes

  15. Immunoprecipitation techniques and Elisa in the detection of anti-Fonsecaea pedrosoi antibodies in chromoblastomycosis

    Directory of Open Access Journals (Sweden)

    Vidal Mônica Scarpelli Martinelli

    2003-01-01

    Full Text Available Chromoblastomycosis (CBM is a chronic subcutaneous infection caused by several dematiaceous fungi. The most commonly etiological agent found in Brazil is Fonsecaea pedrosoi, which appears as thick walled, brownish colored cells with transverse and longitudinal division in the lesions, called "muriform cells". This disease is found worldwide but countries like Madagascar and Brazil have highest incidence. Diagnosis is made by clinical, direct and histopathologic examination and culture of specimens. Serological tests have been used to identify specific antibodies against Fonsecaea pedrosoi antigens, as well as immunotechniques have been used for CBM serological identification and diagnosis. In the present study double immunodiffusion (DID, counterimmunoelectrophoresis (CIE and immunoenzymatic test (ELISA have been used to evaluate humoral immune response in patients with CBM caused by F. pedrosoi. Metabolic antigen was used for immunoprecipitation tests (DID and CIE while somatic antigen for ELISA. Our results demonstrated 53% sensitivity and 96% specificity for DID, while CIE presented 68% sensitivity and 90.5% specificity. ELISA demonstrated 78% sensibility and 83% specificity. Serological tests can be a useful tool to study different aspects of CBM, such as helping differential diagnosis, when culture of the pathogenic agent is impossible.

  16. Protocol: fine-tuning of a Chromatin Immunoprecipitation (ChIP protocol in tomato

    Directory of Open Access Journals (Sweden)

    Iusem Norberto D

    2010-04-01

    Full Text Available Abstract Background Searching thoroughly for plant cis-elements corresponding to transcription factors is worthwhile to reveal novel gene activation cascades. At the same time, a great deal of research is currently focused on epigenetic events in plants. A widely used method serving both purposes is chromatin immunoprecipitation, which was developed for Arabidopsis and other plants but is not yet operational for tomato (Solanum lycopersicum, a model plant species for a group of economically important crops. Results We developed a chromatin immunoprecipitation protocol suitable for tomato by adjusting the parameters to optimise in vivo crosslinking, purification of nuclei, chromatin extraction, DNA shearing and precipitate analysis using real-time PCR. Results were obtained with two different antibodies, five control loci and two normalisation criteria. Conclusion Here we provide a chromatin immunoprecipitation procedure for tomato leaves that could be combined with high-throughput sequencing to generate a detailed map of epigenetic modifications or genome-wide nucleosome positioning data.

  17. Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein.

    Science.gov (United States)

    Verhelst, Judith; De Vlieger, Dorien; Saelens, Xavier

    2015-04-21

    Studying the interaction between proteins is key in understanding their function(s). A very powerful method that is frequently used to study interactions of proteins with other macromolecules in a complex sample is called co-immunoprecipitation. The described co-immunoprecipitation protocol allows to demonstrate and further investigate the interaction between the antiviral myxovirus resistance protein 1 (Mx1) and one of its viral targets, the influenza A virus nucleoprotein (NP). The protocol starts with transfected mammalian cells, but it is also possible to use influenza A virus infected cells as starting material. After cell lysis, the viral NP protein is pulled-down with a specific antibody and the resulting immune-complexes are precipitated with protein G beads. The successful pull-down of NP and the co-immunoprecipitation of the antiviral Mx1 protein are subsequently revealed by western blotting. A prerequisite for successful co-immunoprecipitation of Mx1 with NP is the presence of N-ethylmaleimide (NEM) in the cell lysis buffer. NEM alkylates free thiol groups. Presumably this reaction stabilizes the weak and/or transient NP-Mx1 interaction by preserving a specific conformation of Mx1, its viral target or an unknown third component. An important limitation of co-immunoprecipitation experiments is the inadvertent pull-down of contaminating proteins, caused by nonspecific binding of proteins to the protein G beads or antibodies. Therefore, it is very important to include control settings to exclude false positive results. The described co-immunoprecipitation protocol can be used to study the interaction of Mx proteins from different vertebrate species with viral proteins, any pair of proteins, or of a protein with other macromolecules. The beneficial role of NEM to stabilize weak and/or transient interactions needs to be tested for each interaction pair individually.

  18. Characterizing RNA-protein interaction using cross-linking and metabolite supplemented nuclear RNA-immunoprecipitation.

    Science.gov (United States)

    Au, Phil Chi Khang; Helliwell, Chris; Wang, Ming-Bo

    2014-05-01

    RNA-immunoprecipitation (RNA-IP) is a method used to isolate and identify RNA molecules specifically associated with an RNA-binding protein. Non-coding RNAs are emerging as key regulators of many biological and developmental pathways and RNA-IP has become an important tool in studying their function(s). While RNA-IP is successfully used to determine protein-RNA interaction, specific details regarding the level of this association and the metabolic requirement of this interaction which can influence the success of RNA-IP remain unclear. Here, we investigate the conditions required for efficient nuclear RNA-IP using Arabidopsis AGO4 (Argonaute 4) and siRNA binding as the study model. We showed that formaldehyde cross-linking, but not UV cross-linking, allowed for efficient pull-down of 24-nt siRNAs, suggesting that AGO4-siRNA interaction involves other protein(s). We also showed that, while formaldehyde cross-linking could also be performed on purified nuclei, ATP supplementation to the nuclei isolation buffer was needed to efficiently pull down 24-nt siRNAs. This result indicates that ATP is required for efficient siRNA loading onto AGO4. As most of the known RNA-mediated regulatory processes occur in the nucleus, our findings on cross-linking conditions and metabolite requirement for successful AGO4 nuclear RNA-IP provide a valuable insight and future consideration when studying the function of protein-RNA interactions in plants.

  19. Genomic response to Wnt signalling is highly context-dependent - Evidence from DNA microarray and chromatin immunoprecipitation screens of Wnt/TCF targets

    Energy Technology Data Exchange (ETDEWEB)

    Railo, Antti [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Pajunen, Antti [Department of Biochemistry, University of Oulu (Finland); Itaeranta, Petri; Naillat, Florence; Vuoristo, Jussi; Kilpelaeinen, Pekka [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland); Vainio, Seppo, E-mail: Seppo.Vainio@oulu.fi [Oulu Centre for Cell Matrix Research, Biocenter Oulu, Laboratory of Developmental Biology and Department of Medical Biochemistry and Molecular Biology, FIN-90014, University of Oulu, P. O. Box 5000 (Finland)

    2009-10-01

    Wnt proteins are important regulators of embryonic development, and dysregulated Wnt signalling is involved in the oncogenesis of several human cancers. Our knowledge of the downstream target genes is limited, however. We used a chromatin immunoprecipitation-based assay to isolate and characterize the actual gene segments through which Wnt-activatable transcription factors, TCFs, regulate transcription and an Affymetrix microarray analysis to study the global transcriptional response to the Wnt3a ligand. The anti-{beta}-catenin immunoprecipitation of DNA-protein complexes from mouse NIH3T3 fibroblasts expressing a fusion protein of {beta}-catenin and TCF7 resulted in the identification of 92 genes as putative TCF targets. GeneChip assays of gene expression performed on NIH3T3 cells and the rat pheochromocytoma cell line PC12 revealed 355 genes in NIH3T3 and 129 genes in the PC12 cells with marked changes in expression after Wnt3a stimulus. Only 2 Wnt-regulated genes were shared by both cell lines. Surprisingly, Disabled-2 was the only gene identified by the chromatin immunoprecipitation approach that displayed a marked change in expression in the GeneChip assay. Taken together, our approaches give an insight into the complex context-dependent nature of Wnt pathway transcriptional responses and identify Disabled-2 as a potential new direct target for Wnt signalling.

  20. Bioorthogonal click chemistry to assay mu-opioid receptor palmitoylation using 15-hexadecynoic acid and immunoprecipitation

    OpenAIRE

    2014-01-01

    We have developed a modification of bioorthogonal click chemistry to assay the palmitoylation of cellular proteins. This assay utilizes 15-hexadecynoic acid (15-HDYA) as a chemical probe in combination with protein immunoprecipitation using magnetic beads in order to detect S-palmitoylation of proteins of interest. Here we demonstrate the utility of this approach for the mu-opioid receptor (MOR), a GPCR responsible for mediating the analgesic and addictive properties of most clinically releva...

  1. A Microfluidic Device with Integrated Sonication and Immunoprecipitation for Sensitive Epigenetic Assays.

    Science.gov (United States)

    Cao, Zhenning; Lu, Chang

    2016-02-01

    Epigenetic studies increasingly require analysis of a small number of cells that are of one specific type and derived from patients or animals. In this report, we demonstrate a simple microfluidic device that integrates sonication and immunoprecipitation (IP) for epigenetic assays, such as chromatin immunoprecipitation (ChIP) and methylated DNA immunoprecipitation (MeDIP). By incorporating an ultrasonic transducer with a microfluidic chamber, we implemented microscale sonication for both shearing chromatin/DNA and mixing/washing of IP beads. Such integration allowed highly sensitive tests starting with 100 cross-linked cells for ChIP or 500 pg of genomic DNA for MeDIP (compared to 10(6)-10(7) cells for ChIP and 1-10 μg of DNA for MeDIP in conventional assays). The entire on-chip process of sonication and IP took only 1 h. Our tool will be useful for highly sensitive epigenetic studies based on a small quantity of sample.

  2. Protocol: methodology for chromatin immunoprecipitation (ChIP in Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Strenkert Daniela

    2011-11-01

    Full Text Available Abstract We report on a detailed chromatin immunoprecipitation (ChIP protocol for the unicellular green alga Chlamydomonas reinhardtii. The protocol is suitable for the analysis of nucleosome occupancy, histone modifications and transcription factor binding sites at the level of mononucleosomes for targeted and genome-wide studies. We describe the optimization of conditions for crosslinking, chromatin fragmentation and antibody titer determination and provide recommendations and an example for the normalization of ChIP results as determined by real-time PCR.

  3. Autoantibodies to IA-2 in insulin-dependent diabetes mellitus. Measurements with a new immunoprecipitation assay.

    Science.gov (United States)

    Masuda, M; Powell, M; Chen, S; Beer, C; Fichna, P; Rees Smith, B; Furmaniak, J

    2000-01-20

    An immunoprecipitation assay for autoantibodies (Abs) to the human islet cell antigen IA-2 has been developed using 125I-labelled recombinant IA-2 expressed in E. coli. With this assay IA-2 Abs were detected in 103/217 (47%) of IDDM patients of different ages and with different disease duration. IA-2 Ab prevalence was higher in younger patients (at the age of 15 years or below) with the recent onset IDDM (64/113; 57%) compared to patients above the age of 15 years (11/25; 44%). One of 40 (2.5%) Graves' disease patients and five of 204 (2.5%) of NIDDM patients were also positive. IA-2 Abs were not detected in sera from patients with Hashimoto's thyroiditis (n=32), myasthenia gravis (n=20) or systemic lupus erythematosus (n=10). IA-2 Ab measurements based on 125I-labelled IA-2 showed a good correlation with the results of an immunoprecipitation assay based on 35S-labelled IA-2 produced in the in vitro transcription/translation system (r=0.78; n=113; pAb testing in IDDM. Overall, the IA-2 Ab assay based on 125I-labelled recombinant IA-2 showed good sensitivity, precision and specificity which, combined with an easy and convenient protocol, makes it attractive for routine use.

  4. Effective identification of Akt interacting proteins by two-step chemical crosslinking, co-immunoprecipitation and mass spectrometry.

    Science.gov (United States)

    Huang, Bill X; Kim, Hee-Yong

    2013-01-01

    Akt is a critical protein for cell survival and known to interact with various proteins. However, Akt binding partners that modulate or regulate Akt activation have not been fully elucidated. Identification of Akt-interacting proteins has been customarily achieved by co-immunoprecipitation combined with western blot and/or MS analysis. An intrinsic problem of the method is loss of interacting proteins during procedures to remove non-specific proteins. Moreover, antibody contamination often interferes with the detection of less abundant proteins. Here, we developed a novel two-step chemical crosslinking strategy to overcome these problems which resulted in a dramatic improvement in identifying Akt interacting partners. Akt antibody was first immobilized on protein A/G beads using disuccinimidyl suberate and allowed to bind to cellular Akt along with its interacting proteins. Subsequently, dithiobis[succinimidylpropionate], a cleavable crosslinker, was introduced to produce stable complexes between Akt and binding partners prior to the SDS-PAGE and nanoLC-MS/MS analysis. This approach enabled identification of ten Akt partners from cell lysates containing as low as 1.5 mg proteins, including two new potential Akt interacting partners. None of these but one protein was detectable without crosslinking procedures. The present method provides a sensitive and effective tool to probe Akt-interacting proteins. This strategy should also prove useful for other protein interactions, particularly those involving less abundant or weakly associating partners.

  5. Probing flagellar promoter occupancy in wild-type and mutant Caulobacter crescentus by chromatin immunoprecipitation.

    Science.gov (United States)

    Davis, Nicole J; Viollier, Patrick H

    2011-06-01

    In the asymmetric predivisional cell of Caulobacter crescentus, TipF and TipN mark the cellular pole for future flagellar development. TipF is essential for motility and contains a cyclic-di-GMP phosphodiesterase-like (EAL) domain that is necessary for proper function. TipN is localized to the flagellar pole before TipF and is essential for the proper placement of the flagellum in C. crescentus. Using β-galactosidase promoter-probe assays and quantitative chromatin immunoprecipitation, we investigated the influence of the C. crescentus flagellar assembly regulator TipF on flagellar gene transcription. We compared the transcriptional activity of class II-fliF-lacZ, class III-flgE-lacZ, and class IV-fljL-lacZ fusions in a ΔtipF mutant with that of other flagellar mutants and the wild-type strain. We subsequently verified the in vivo occupancy of the fliF, flgE, and fljL flagellar promoters by the flagellar regulators CtrA, FlbD, and FliX in addition to RNA polymerase. We deduce that TipF contributes to proper expression of flagellar genes in C. crescentus by acting both within and outside of the canonical flagellar gene expression hierarchy.

  6. Chromatin analyses of Zymoseptoria tritici: Methods for chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq).

    Science.gov (United States)

    Soyer, Jessica L; Möller, Mareike; Schotanus, Klaas; Connolly, Lanelle R; Galazka, Jonathan M; Freitag, Michael; Stukenbrock, Eva H

    2015-06-01

    The presence or absence of specific transcription factors, chromatin remodeling machineries, chromatin modification enzymes, post-translational histone modifications and histone variants all play crucial roles in the regulation of pathogenicity genes. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) provides an important tool to study genome-wide protein-DNA interactions to help understand gene regulation in the context of native chromatin. ChIP-seq is a convenient in vivo technique to identify, map and characterize occupancy of specific DNA fragments with proteins against which specific antibodies exist or which can be epitope-tagged in vivo. We optimized existing ChIP protocols for use in the wheat pathogen Zymoseptoria tritici and closely related sister species. Here, we provide a detailed method, underscoring which aspects of the technique are organism-specific. Library preparation for Illumina sequencing is described, as this is currently the most widely used ChIP-seq method. One approach for the analysis and visualization of representative sequence is described; improved tools for these analyses are constantly being developed. Using ChIP-seq with antibodies against H3K4me2, which is considered a mark for euchromatin or H3K9me3 and H3K27me3, which are considered marks for heterochromatin, the overall distribution of euchromatin and heterochromatin in the genome of Z. tritici can be determined. Our ChIP-seq protocol was also successfully applied to Z. tritici strains with high levels of melanization or aberrant colony morphology, and to different species of the genus (Z. ardabiliae and Z. pseudotritici), suggesting that our technique is robust. The methods described here provide a powerful framework to study new aspects of chromatin biology and gene regulation in this prominent wheat pathogen.

  7. Immunoprecipitation of native botulinum neurotoxin complexes from Clostridium botulinum subtype A strains.

    Science.gov (United States)

    Lin, Guangyun; Tepp, William H; Bradshaw, Marite; Fredrick, Chase M; Johnson, Eric A

    2015-01-01

    Botulinum neurotoxins (BoNTs) naturally exist as components of protein complexes containing nontoxic proteins. The nontoxic proteins impart stability of BoNTs in the gastrointestinal tract and during purification and handling. The two primary neurotoxin complexes (TCs) are (i) TC1, consisting of BoNT, nontoxin-nonhemagglutinin (NTNH), and hemagglutinins (HAs), and (ii) TC2, consisting of BoNT and NTNH (and possibly OrfX proteins). In this study, BoNT/A subtypes A1, A2, A3, and A5 were examined for the compositions of their TCs in culture extracts using immunoprecipitation (IP). IP analyses showed that BoNT/A1 and BoNT/A5 form TC1s, while BoNT/A2 and BoNT/A3 form TC2s. A Clostridium botulinum host strain expressing recombinant BoNT/A4 (normally present as a TC2) from an extrachromosomal plasmid formed a TC1 with complexing proteins from the host strain, indicating that the HAs and NTNH encoded on the chromosome associated with the plasmid-encoded BoNT/A4. Strain NCTC 2916 (A1/silent B1), which carries both an ha silent bont/b cluster and an orfX bont/a1 cluster, was also examined. IP analysis revealed that NCTC 2916 formed only a TC2 containing BoNT/A1 and its associated NTNH. No association between BoNT/A1 and the nontoxic proteins from the silent bont/b cluster was detected, although the HAs were expressed as determined by Western blotting analysis. Additionally, NTNH and HAs from the silent bont/b cluster did not form a complex in NCTC 2916. The stabilities of the two types of TC differed at various pHs and with addition of KCl and NaCl. TC1 complexes were more stable than TC2 complexes. Mouse serum stabilized TC2, while TC1 was unaffected.

  8. Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays

    Directory of Open Access Journals (Sweden)

    Yu Jingjing

    2011-11-01

    Full Text Available Abstract Background The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin structure, which is regulated by DNA methylation and histone modification, is at the center of gene regulation. Immunoprecipitations of chromatin (ChIP and methylated DNA (MeDIP represent a major achievement in this area that allow researchers to probe chromatin modifications as well as specific protein-DNA interactions in vivo and to estimate the density of proteins at specific sites genome-wide. Although a critical component of chromatin structure, DNA methylation has often been studied independently of other chromatin events and transcription. Results To allow simultaneous measurements of DNA methylation with other genomic processes, we developed and validated a simple and easy-to-use high throughput microplate-based platform for analysis of DNA methylation. Compared to the traditional beads-based MeDIP the microplate MeDIP was more sensitive and had lower non-specific binding. We integrated the MeDIP method with a microplate ChIP assay which allows measurements of both DNA methylation and histone marks at the same time, Matrix ChIP-MeDIP platform. We illustrated several applications of this platform to relate DNA methylation, with chromatin and transcription events at selected genes in cultured cells, human cancer and in a model of diabetic kidney disease. Conclusion The high throughput capacity of Matrix ChIP-MeDIP to profile tens and potentially hundreds of different genomic events at the same time as DNA methylation represents a powerful platform to explore complex genomic mechanism at selected genes in cultured cells and in whole tissues. In this regard, Matrix ChIP-MeDIP should be useful to complement genome-wide studies where the rich chromatin and transcription database resources provide fruitful foundation

  9. Genome-wide mapping of protein-DNA interaction by chromatin immunoprecipitation and DNA microarray hybridization (ChIP-chip). Part B: ChIP-chip data analysis.

    Science.gov (United States)

    Göbel, Ulrike; Reimer, Julia; Turck, Franziska

    2010-01-01

    Genome-wide targets of chromatin-associated factors can be identified by a combination of chromatin-immunoprecipitation and oligonucleotide microarray hybridization. Genome-wide mircoarray data analysis represents a major challenge for the experimental biologist. This chapter introduces ChIPR, a package written in the R statistical programming language that facilitates the analysis of two-color microarrays from Roche-Nimblegen. The workflow of ChIPR is illustrated with sample data from Arabidopsis thaliana. However, ChIPR supports ChIP-chip data preprocessing, target identification, and cross-annotation of any species for which genome annotation data is available in GFF format. This chapter describes how to use ChIPR as a software tool without the requirement for programming skills in the R language.

  10. D-Isonucleotide (isoNA) incorporation around cleavage site of passenger strand promotes the vibration of Ago2-PAZ domain and enhances in vitro potency of siRNA.

    Science.gov (United States)

    Huang, Ye; Tian, Miao; Zhang, Yichao; Sheng, Gang; Chen, Zhuo; Ma, Yuan; Chen, Yue; Peng, Yihong; Zhao, Yi-Lei; Wang, Yanli; Zhang, Lihe; Yang, Zhenjun

    2015-11-28

    It has been demonstrated that passenger strand cleavage is important for the activation of RNA-induced silencing complex (RISC), which is a crucial step for siRNA-mediated gene silencing. Herein, we report that isonucleotide (isoNA) modification around the cleavage site of the passenger strand would affect the in vitro potency of modified siRNAs by altering the motion pattern of the Ago2-PAZ domain. According to western blotting, q-PCR and antiviral test results, we proved that D-isonucleotide (isoNA) modification at the position 8 of the passenger strand (siMek1-S08D), which is adjacent to the cleavage site, markedly improved the in vitro potency of the modified siRNA, whereas siRNAs with D-isoNA incorporation at position 9 (siMek1-S09D) or L-isoNA incorporation at positions 8 and 9 (siMek1-S08L, siMek1-S09L) displayed lower activity compared to native siRNA. Kinetics evaluation of passenger strand cleavage induced by T. thermophilus Ago (Tt-Ago) showed that D-isoNA modification at position 8 of the passenger strand had no significant influence on the cleavage rate, but L-isoNA modification at position 8 slowed the cleavage rate markedly. Moreover, the results of molecular dynamics simulations showed that D-isoNA modification at position 8 affected the open-close motion of the PAZ domain in the Ago/siRNA complex, which may promote the loading of RISC and release of a passenger strand cleavage product, and consequently accelerate the activation of RISC and enhance silencing activity. However, D-isoNA modification at position 9 or L-isoNA modification at position 8 or 9 exerted opposite influences on the motion of the Ago-PAZ domain.

  11. Inference of RNA polymerase II transcription dynamics from chromatin immunoprecipitation time course data.

    Directory of Open Access Journals (Sweden)

    Ciira wa Maina

    2014-05-01

    Full Text Available Gene transcription mediated by RNA polymerase II (pol-II is a key step in gene expression. The dynamics of pol-II moving along the transcribed region influence the rate and timing of gene expression. In this work, we present a probabilistic model of transcription dynamics which is fitted to pol-II occupancy time course data measured using ChIP-Seq. The model can be used to estimate transcription speed and to infer the temporal pol-II activity profile at the gene promoter. Model parameters are estimated using either maximum likelihood estimation or via Bayesian inference using Markov chain Monte Carlo sampling. The Bayesian approach provides confidence intervals for parameter estimates and allows the use of priors that capture domain knowledge, e.g. the expected range of transcription speeds, based on previous experiments. The model describes the movement of pol-II down the gene body and can be used to identify the time of induction for transcriptionally engaged genes. By clustering the inferred promoter activity time profiles, we are able to determine which genes respond quickly to stimuli and group genes that share activity profiles and may therefore be co-regulated. We apply our methodology to biological data obtained using ChIP-seq to measure pol-II occupancy genome-wide when MCF-7 human breast cancer cells are treated with estradiol (E2. The transcription speeds we obtain agree with those obtained previously for smaller numbers of genes with the advantage that our approach can be applied genome-wide. We validate the biological significance of the pol-II promoter activity clusters by investigating cluster-specific transcription factor binding patterns and determining canonical pathway enrichment. We find that rapidly induced genes are enriched for both estrogen receptor alpha (ERα and FOXA1 binding in their proximal promoter regions.

  12. DNA immunoprecipitation semiconductor sequencing (DIP-SC-seq) as a rapid method to generate genome wide epigenetic signatures.

    Science.gov (United States)

    Thomson, John P; Fawkes, Angie; Ottaviano, Raffaele; Hunter, Jennifer M; Shukla, Ruchi; Mjoseng, Heidi K; Clark, Richard; Coutts, Audrey; Murphy, Lee; Meehan, Richard R

    2015-05-14

    Modification of DNA resulting in 5-methylcytosine (5 mC) or 5-hydroxymethylcytosine (5hmC) has been shown to influence the local chromatin environment and affect transcription. Although recent advances in next generation sequencing technology allow researchers to map epigenetic modifications across the genome, such experiments are often time-consuming and cost prohibitive. Here we present a rapid and cost effective method of generating genome wide DNA modification maps utilising commercially available semiconductor based technology (DNA immunoprecipitation semiconductor sequencing; "DIP-SC-seq") on the Ion Proton sequencer. Focussing on the 5hmC mark we demonstrate, by directly comparing with alternative sequencing strategies, that this platform can successfully generate genome wide 5hmC patterns from as little as 500 ng of genomic DNA in less than 4 days. Such a method can therefore facilitate the rapid generation of multiple genome wide epigenetic datasets.

  13. Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    Science.gov (United States)

    Breitkopf, Susanne B; Yuan, Min; Pihan, German A; Asara, John M

    2012-10-02

    Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec). BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon to other cancers. Three different IP-MS experiments central to cell signaling pathways were sufficient to discover a BCR-ABL fusion in H929 cells: phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3-kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase activity, p85 IP informs the activating adaptors and receptor tyrosine kinases (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors leading to ERK activation. Integration of the bait-prey data from the three separate experiments identified the BCR-ABL protein complex, which was confirmed by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2 fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein, important for MAPK signaling, were common to all three IP-MS experiments. The comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down-regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest a model for directed proteomics from patient tumor samples for selecting the appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM patients, in addition to CML patients, may benefit from BCR-ABL diagnostic screening.

  14. Specific detection of peste des petits ruminants virus antibodies in sheep and goat sera by the luciferase immunoprecipitation system.

    Science.gov (United States)

    Berguido, Francisco J; Bodjo, Sanne Charles; Loitsch, Angelika; Diallo, Adama

    2016-01-01

    Peste des petits ruminants (PPR) is a contagious and often fatal transboundary animal disease affecting mostly sheep, goats and wild small ruminants. This disease is endemic in most of Africa, the Middle, Near East, and large parts of Asia. The causal agent is peste des petits ruminants virus (PPRV), which belongs to the genus Morbillivirus in the family Paramyxoviridae. This genus also includes measles virus (MV), canine distemper virus (CDV) and rinderpest virus (RPV). All are closely related viruses with serological cross reactivity. In this study, we have developed a Luciferase Immunoprecipitation System (LIPS) for the rapid detection of antibodies against PPRV in serum samples and for specific differentiation from antibodies against RPV. PPR and rinderpest (RP) serum samples were assayed by PPR-LIPS and two commercially available PPR cELISA tests. The PPR-LIPS showed high sensitivity and specificity for the samples tested and showed no cross reactivity with RPV unlike the commercial PPR cELISA tests which did cross react with RPV. Based on the results shown in this study, PPR-LIPS is presented as a good candidate for the specific serosurveillance of PPR.

  15. MOBE-ChIP: a large-scale chromatin immunoprecipitation assay for cell type-specific studies.

    Science.gov (United States)

    Lau, On Sun; Bergmann, Dominique C

    2015-10-01

    Cell type-specific transcriptional regulators play critical roles in the generation and maintenance of multicellularity. As they are often expressed at low levels, in vivo DNA-binding studies of these regulators by standard chromatin immunoprecipitation (ChIP) assays are technically challenging. We describe here an optimized ChIP protocol termed Maximized Objects for Better Enrichment (MOBE)-ChIP, which enhances the sensitivity of ChIP assays for detecting cell type-specific signals. The protocol, which is based on the disproportional increase of target signals over background at higher scales, uses substantially greater volume of starting materials than conventional ChIPs to achieve high signal enrichment. This technique can capture weak binding events that are ambiguous in standard ChIP assays, and is useful both in gene-specific and whole-genome analysis. This protocol has been optimized for Arabidopsis, but should be applicable to other model systems with minor modifications. The full procedure can be completed within 3 days.

  16. Chromatin immunoprecipitation (ChIP) of plant transcription factors followed by sequencing (ChIP-SEQ) or hybridization to whole genome arrays (ChIP-CHIP)

    NARCIS (Netherlands)

    Kaufmann, K.; Muiño, J.M.; Østerås, M.; Farinelli, L.; Krajewski, P.; Angenent, G.C.

    2010-01-01

    Chromatin immunoprecipitation (ChIP) is a powerful technique to study interactions between transcription factors (TFs) and DNA in vivo. For genome-wide de novo discovery of TF-binding sites, the DNA that is obtained in ChIP experiments needs to be processed for sequence identification. The sequences

  17. Analysis of antibody responses to Hymenolepis nana infection in mice by the enzyme-linked immunosorbent assay and immunoprecipitation.

    Science.gov (United States)

    Ito, A; Honey, R D; Scanlon, T; Lightowlers, M W; Rickard, M D

    1988-05-01

    Serum antibody responses in two strains of mice infected with embryonated eggs of Hymenolepis nana were analysed by the enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation (IP) using sodium deoxycholate (DOC)-solubilized antigens prepared from embryonated eggs (eggs), mouse-derived cysticercoids (cysts) and adult tapeworms with immature segments only (adults). Highly susceptible dd mice, which harbour mature tapeworms for a long period (greater than 70 days), produced high levels of antibodies to all three different stages of H. nana. BALB/c mice, almost all of which expel adult tapeworms by 30 days after infection, produced high levels of antibody against egg antigens only. The high antibody titres to cyst and adult antigens in dd mice did not lead to expulsion of the worms. However, worms are rejected early in BALB/c mice when there is little or no detectable serum antibody. The antibody responses to eggs seen in BALB/c mice which had long since shed their adult worms were probably due to ingestion of eggs from faeces of other infected mice. Antibodies to eggs were not detected in BALB/c mice which were initially inoculated with eggs (day 0) and then treated with praziquantel on day 6 after the tissue phase of infection only. The different antibody responses to egg antigens and the other two antigens (cyst and adult) in BALB/c mice suggest a difference in antigen specificity between eggs and both cysts and adults. A major antigen component with Mr 32,000 appears to be specific to the egg (or oncosphere) stage of H. nana. Antibody to this major component of eggs was absorbed only with intact eggs, but not with intact cysts nor adults with immature segments only, so that the antigen appears to be on the surface of the oncosphere.

  18. Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging.

    Science.gov (United States)

    Tatavosian, Roubina; Zhen, Chao Yu; Duc, Huy Nguyen; Balas, Maggie M; Johnson, Aaron M; Ren, Xiaojun

    2015-11-20

    Epigenetic complexes play an essential role in regulating chromatin structure, but information about their assembly stoichiometry on chromatin within cells is poorly understood. The cellular assembly stoichiometry is critical for appreciating the initiation, propagation, and maintenance of epigenetic inheritance during normal development and in cancer. By combining genetic engineering, chromatin biochemistry, and single-molecule fluorescence imaging, we developed a novel and sensitive approach termed single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) to enable investigation of the cellular assembly stoichiometry of epigenetic complexes on chromatin. Sm-ChIPi was validated by using chromatin complexes with known stoichiometry. The stoichiometry of subunits within a polycomb complex and the assembly stoichiometry of polycomb complexes on chromatin have been extensively studied but reached divergent views. Moreover, the cellular assembly stoichiometry of polycomb complexes on chromatin remains unexplored. Using Sm-ChIPi, we demonstrated that within mouse embryonic stem cells, one polycomb repressive complex (PRC) 1 associates with multiple nucleosomes, whereas two PRC2s can bind to a single nucleosome. Furthermore, we obtained direct physical evidence that the nucleoplasmic PRC1 is monomeric, whereas PRC2 can dimerize in the nucleoplasm. We showed that ES cell differentiation induces selective alteration of the assembly stoichiometry of Cbx2 on chromatin but not other PRC1 components. We additionally showed that the PRC2-mediated trimethylation of H3K27 is not required for the assembly stoichiometry of PRC1 on chromatin. Thus, these findings uncover that PRC1 and PRC2 employ distinct mechanisms to assemble on chromatin, and the novel Sm-ChIPi technique could provide single-molecule insight into other epigenetic complexes.

  19. Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

    Directory of Open Access Journals (Sweden)

    Minh T Than

    2013-06-01

    Full Text Available Identifying the physiological functions of microRNAs (miRNAs is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1, an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in

  20. RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors

    DEFF Research Database (Denmark)

    Thompson, Nancy; Gésina, Emilie; Scheinert, Peter;

    2012-01-01

    Pancreas development is initiated by the specification and expansion of a small group of endodermal cells. Several transcription factors are crucial for progenitor maintenance and expansion, but their interactions and the downstream targets mediating their activity are poorly understood. Among...... those factors, PTF1a, a basic helix-loop-helix (bHLH) transcription factor which controls pancreas exocrine cell differentiation, maintenance, and functionality, is also needed for the early specification of pancreas progenitors. We used RNA profiling and chromatin immunoprecipitation (ChIP) sequencing...... to identify a set of targets in pancreas progenitors. We demonstrate that Mnx1, a gene that is absolutely required in pancreas progenitors, is a major direct target of PTF1a and is regulated by a distant enhancer element. Pdx1, Nkx6.1, and Onecut1 are also direct PTF1a targets whose expression is promoted...

  1. Quantitative Assessment of Chromatin Immunoprecipitation Grade Antibodies Directed against Histone Modifications Reveals Patterns of Co-occurring Marks on Histone Protein Molecules*

    OpenAIRE

    Peach, Sally E.; Rudomin, Emily L.; Udeshi, Namrata D.; Carr, Steven A.; Jaffe, Jacob D.

    2012-01-01

    The defining step in most chromatin immunoprecipitation (ChIP) assays is the use of an antibody to enrich for a particular protein or histone modification state associated with segments of chromatin. The specificity of the antibody is critical to the interpretation of the experiment, yet this property is rarely reported. Here, we present a quantitative method using mass spectrometry to characterize the specificity of key histone H3 modification-targeting antibodies that have previously been u...

  2. Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and heterodimerization analysis by fluorescence resonance energy transfer and co-immunoprecipitation.

    Science.gov (United States)

    Operaña, Theresa N; Tukey, Robert H

    2007-02-16

    UDP-glucuronosyltransferases (UGTs) are membrane-bound proteins localized to the endoplasmic reticulum and catalyze the formation of beta-d-glucopyranosiduronic acids (glucuronides) using UDP-glucuronic acid and acceptor substrates such as drugs, steroids, bile acids, xenobiotics, and dietary nutrients. Recent biochemical evidence indicates that the UGT proteins may oligomerize in the membrane, but conclusive evidence is still lacking. In the present study, we have used fluorescence resonance energy transfer (FRET) to study UGT1A oligomerization in live cells. This technique demonstrated that UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 self-oligomerize (homodimerize). Heterodimer interactions were also explored, and it was determined that UGT1A1 was capable of binding with UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. In addition to the in vivo FRET analysis, UGT1A protein-protein interactions were demonstrated through co-immunoprecipitation experiments. Co-expression of hemagglutinin-tagged and cyan fluorescent protein-tagged UGT1A proteins, followed by immunoprecipitation with anti-hemagglutinin beads, illustrated the potential of each UGT1A protein to homodimerize. Co-immunoprecipitation results also confirmed that UGT1A1 was capable of forming heterodimer complexes with all of the UGT1A proteins, corroborating the FRET results in live cells. These preliminary studies suggest that the UGT1A family of proteins form oligomerized complexes in the membrane, a property that may influence function and substrate selectivity.

  3. Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data

    Science.gov (United States)

    Sharov, Alexei A; Masui, Shinji; Sharova, Lioudmila V; Piao, Yulan; Aiba, Kazuhiro; Matoba, Ryo; Xin, Li; Niwa, Hitoshi; Ko, Minoru SH

    2008-01-01

    Background Target genes of a transcription factor (TF) Pou5f1 (Oct3/4 or Oct4), which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES) cells, have previously been identified based on their response to Pou5f1 manipulation and occurrence of Chromatin-immunoprecipitation (ChIP)-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation. Results To reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR) criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR < 0.2) to a compendium of published and new microarray data (3, 6, 12, and 24 hr after Pou5f1 suppression) and published ChIP data, we identified 420 tentative target genes (TTGs) for Pou5f1. The majority of TTGs (372) were down-regulated after Pou5f1 suppression, indicating that the Pou5f1 functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that Sox2 and Nanog also function mostly as transcription activators in cooperation with Pou5f1. Conclusion We have identified the most reliable sets of direct target genes for key pluripotency genes – Pou5f1, Sox2, and Nanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly. PMID:18522731

  4. Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation data

    Directory of Open Access Journals (Sweden)

    Xin Li

    2008-06-01

    Full Text Available Abstract Background Target genes of a transcription factor (TF Pou5f1 (Oct3/4 or Oct4, which is essential for pluripotency maintenance and self-renewal of embryonic stem (ES cells, have previously been identified based on their response to Pou5f1 manipulation and occurrence of Chromatin-immunoprecipitation (ChIP-binding sites in promoters. However, many responding genes with binding sites may not be direct targets because response may be mediated by other genes and ChIP-binding site may not be functional in terms of transcription regulation. Results To reduce the number of false positives, we propose to separate responding genes into groups according to direction, magnitude, and time of response, and to apply the false discovery rate (FDR criterion to each group individually. Using this novel algorithm with stringent statistical criteria (FDR Pou5f1 suppression and published ChIP data, we identified 420 tentative target genes (TTGs for Pou5f1. The majority of TTGs (372 were down-regulated after Pou5f1 suppression, indicating that the Pou5f1 functions as an activator of gene expression when it binds to promoters. Interestingly, many activated genes are potent suppressors of transcription, which include polycomb genes, zinc finger TFs, chromatin remodeling factors, and suppressors of signaling. Similar analysis showed that Sox2 and Nanog also function mostly as transcription activators in cooperation with Pou5f1. Conclusion We have identified the most reliable sets of direct target genes for key pluripotency genes – Pou5f1, Sox2, and Nanog, and found that they predominantly function as activators of downstream gene expression. Thus, most genes related to cell differentiation are suppressed indirectly.

  5. Cross-linking immunoprecipitation-MS (xIP-MS): Topological Analysis of Chromatin-associated Protein Complexes Using Single Affinity Purification.

    Science.gov (United States)

    Makowski, Matthew M; Willems, Esther; Jansen, Pascal W T C; Vermeulen, Michiel

    2016-03-01

    In recent years, cross-linking mass spectrometry has proven to be a robust and effective method of interrogating macromolecular protein complex topologies at peptide resolution. Traditionally, cross-linking mass spectrometry workflows have utilized homogenous complexes obtained through time-limiting reconstitution, tandem affinity purification, and conventional chromatography workflows. Here, we present cross-linking immunoprecipitation-MS (xIP-MS), a simple, rapid, and efficient method for structurally probing chromatin-associated protein complexes using small volumes of mammalian whole cell lysates, single affinity purification, and on-bead cross-linking followed by LC-MS/MS analysis. We first benchmarked xIP-MS using the structurally well-characterized phosphoribosyl pyrophosphate synthetase complex. We then applied xIP-MS to the chromatin-associated cohesin (SMC1A/3), XRCC5/6 (Ku70/86), and MCM complexes, and we provide novel structural and biological insights into their architectures and molecular function. Of note, we use xIP-MS to perform topological studies under cell cycle perturbations, showing that the xIP-MS protocol is sufficiently straightforward and efficient to allow comparative cross-linking experiments. This work, therefore, demonstrates that xIP-MS is a robust, flexible, and widely applicable methodology for interrogating chromatin-associated protein complex architectures.

  6. Identifying Activity

    CERN Document Server

    Lewis, Adrian S

    2009-01-01

    Identification of active constraints in constrained optimization is of interest from both practical and theoretical viewpoints, as it holds the promise of reducing an inequality-constrained problem to an equality-constrained problem, in a neighborhood of a solution. We study this issue in the more general setting of composite nonsmooth minimization, in which the objective is a composition of a smooth vector function c with a lower semicontinuous function h, typically nonsmooth but structured. In this setting, the graph of the generalized gradient of h can often be decomposed into a union (nondisjoint) of simpler subsets. "Identification" amounts to deciding which subsets of the graph are "active" in the criticality conditions at a given solution. We give conditions under which any convergent sequence of approximate critical points finitely identifies the activity. Prominent among these properties is a condition akin to the Mangasarian-Fromovitz constraint qualification, which ensures boundedness of the set of...

  7. Genome-wide mapping of the distribution of CarD, RNAP σA, and RNAP β on the Mycobacterium smegmatis chromosome using chromatin immunoprecipitation sequencing

    Science.gov (United States)

    Landick, Robert; Krek, Azra; Glickman, Michael S.; Socci, Nicholas D.; Stallings, Christina L.

    2014-01-01

    CarD is an essential mycobacterial protein that binds the RNA polymerase (RNAP) and affects the transcriptional profile of Mycobacterium smegmatis and Mycobacterium tuberculosis [6]. We predicted that CarD was directly regulating RNAP function but our prior experiments had not determined at what stage of transcription CarD was functioning and at which genes CarD interacted with the RNAP. To begin to address these open questions, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to survey the distribution of CarD throughout the M. smegmatis chromosome. The distribution of RNAP subunits β and σA were also profiled. We expected that RNAP β would be present throughout transcribed regions and RNAP σA would be predominantly enriched at promoters based on work in Escherichia coli [3], however this had yet to be determined in mycobacteria. The ChIP-seq analyses revealed that CarD was never present on the genome in the absence of RNAP, was primarily associated with promoter regions, and was highly correlated with the distribution of RNAP σA. The colocalization of σA and CarD led us to propose that in vivo, CarD associates with RNAP initiation complexes at most promoters and is therefore a global regulator of transcription initiation. Here we describe in detail the data from the ChIP-seq experiments associated with the study published by Srivastava and colleagues in the Proceedings of the National Academy of Science in 2013 [5] as well as discuss the findings from this dataset in relation to both CarD and mycobacterial transcription as a whole. The ChIP-seq data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE48164). PMID:25089258

  8. Genome-Wide Mapping of the Distribution of CarD, RNAP σ(A), and RNAP β on the Mycobacterium smegmatis Chromosome using Chromatin Immunoprecipitation Sequencing.

    Science.gov (United States)

    Landick, Robert; Krek, Azra; Glickman, Michael S; Socci, Nicholas D; Stallings, Christina L

    2014-12-01

    CarD is an essential mycobacterial protein that binds the RNA polymerase (RNAP) and affects the transcriptional profile of Mycobacterium smegmatis and Mycobacterium tuberculosis (6). We predicted that CarD was directly regulating RNAP function but our prior experiments had not determined at what stage of transcription CarD was functioning and at which genes CarD interacted with the RNAP. To begin to address these open questions, we performed Chromatin Immunoprecipitation sequencing (ChIP-seq) to survey the distribution of CarD throughout the M. smegmatis chromosome. The distribution of RNAP subunits β and σ(A) were also profiled. We expected that RNAP β would be present throughout transcribed regions and RNAP σ(A) would be predominantly enriched at promoters based on work in Escherichia coli (3), however this had yet to be determined in mycobacteria. The ChIP-seq analyses revealed that CarD was never present on the genome in the absence of RNAP, was primarily associated with promoter regions, and was highly correlated with the distribution of RNAP σ(A). The colocalization of σ(A) and CarD led us to propose that in vivo, CarD associates with RNAP initiation complexes at most promoters and is therefore a global regulator of transcription initiation. Here we describe in detail the data from the ChIP-seq experiments associated with the study published by Srivastava and colleagues in the Proceedings of the National Academy of Science in 2013 (5) as well as discuss the findings from this dataset in relation to both CarD and mycobacterial transcription as a whole. The ChIP-seq data have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE48164).

  9. Quantitative assessment of chromatin immunoprecipitation grade antibodies directed against histone modifications reveals patterns of co-occurring marks on histone protein molecules.

    Science.gov (United States)

    Peach, Sally E; Rudomin, Emily L; Udeshi, Namrata D; Carr, Steven A; Jaffe, Jacob D

    2012-05-01

    The defining step in most chromatin immunoprecipitation (ChIP) assays is the use of an antibody to enrich for a particular protein or histone modification state associated with segments of chromatin. The specificity of the antibody is critical to the interpretation of the experiment, yet this property is rarely reported. Here, we present a quantitative method using mass spectrometry to characterize the specificity of key histone H3 modification-targeting antibodies that have previously been used to characterize the "histone code." We further extend the use of these antibody reagents to the observation of long range correlations among disparate histone modifications. Using purified human histones representing the mixture of chromatin states present in living cells, we were able to quantify the degree of target enrichment and the specificity of several commonly used, commercially available ChIP grade antibodies. We found significant differences in enrichment efficiency among various reagents directed against four frequently studied chromatin marks: H3K4me2, H3K4me3, H3K9me3, and H3K27me3. For some antibodies, we also detected significant off target enrichment of alternate modifications at the same site (i.e., enrichment of H3K4me2 by an antibody directed against H3K4me3). Through cluster analysis, we were able to recognize patterns of co-enrichment of marks at different sites on the same histone protein. Surprisingly, these co-enrichments corresponded well to "canonical" chromatin states that are exemplary of activated and repressed regions of chromatin. Altogether, our findings suggest that 1) the results of ChIP experiments need to be evaluated with caution given the potential for cross-reactivity of the commonly used histone modification recognizing antibodies, 2) multiple marks with consistent biological interpretation exist on the same histone protein molecule, and 3) some components of the histone code may be transduced on single proteins in living cells.

  10. Quantitative Assessment of Chromatin Immunoprecipitation Grade Antibodies Directed against Histone Modifications Reveals Patterns of Co-occurring Marks on Histone Protein Molecules*

    Science.gov (United States)

    Peach, Sally E.; Rudomin, Emily L.; Udeshi, Namrata D.; Carr, Steven A.; Jaffe, Jacob D.

    2012-01-01

    The defining step in most chromatin immunoprecipitation (ChIP) assays is the use of an antibody to enrich for a particular protein or histone modification state associated with segments of chromatin. The specificity of the antibody is critical to the interpretation of the experiment, yet this property is rarely reported. Here, we present a quantitative method using mass spectrometry to characterize the specificity of key histone H3 modification-targeting antibodies that have previously been used to characterize the “histone code.” We further extend the use of these antibody reagents to the observation of long range correlations among disparate histone modifications. Using purified human histones representing the mixture of chromatin states present in living cells, we were able to quantify the degree of target enrichment and the specificity of several commonly used, commercially available ChIP grade antibodies. We found significant differences in enrichment efficiency among various reagents directed against four frequently studied chromatin marks: H3K4me2, H3K4me3, H3K9me3, and H3K27me3. For some antibodies, we also detected significant off target enrichment of alternate modifications at the same site (i.e., enrichment of H3K4me2 by an antibody directed against H3K4me3). Through cluster analysis, we were able to recognize patterns of co-enrichment of marks at different sites on the same histone protein. Surprisingly, these co-enrichments corresponded well to “canonical” chromatin states that are exemplary of activated and repressed regions of chromatin. Altogether, our findings suggest that 1) the results of ChIP experiments need to be evaluated with caution given the potential for cross-reactivity of the commonly used histone modification recognizing antibodies, 2) multiple marks with consistent biological interpretation exist on the same histone protein molecule, and 3) some components of the histone code may be transduced on single proteins in living

  11. Dataset of integrin-linked kinase protein: Protein interactions in cardiomyocytes identified by mass spectrometry

    Directory of Open Access Journals (Sweden)

    Alexandra Traister

    2016-06-01

    Full Text Available Using hearts from mice overexpressing integrin linked kinase (ILK behind the cardiac specific promoter αMHC, we have performed immunoprecipitation and mass spectrometry to identify novel ILK protein:protein interactions that regulate cardiomyocyte activity and calcium flux. Integrin linked kinase complexes were captured from mouse heart lysates using a commercial antibody, with subsequent liquid chromatography tandem mass spectral analysis. Interacting partners were identified using the MASCOT server, and important interactions verified using reverse immunoprecipitation and mass spectrometry. All ILK interacting proteins were identified in a non-biased manner, and are stored in the ProteomeXchange Consortium via the PRIDE partner repository (reference ID PRIDE: http://www.ebi.ac.uk/pride/archive/projects/PXD001053. The functional role of identified ILK interactions in cardiomyocyte function and arrhythmia were subsequently confirmed in human iPSC-cardiomyocytes.

  12. Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using co-immunoprecipitation and time-resolved fluorescence resonance energy transfer.

    Science.gov (United States)

    Gazi, Lucien; López-Giménez, Juan F; Rüdiger, Martin P; Strange, Philip G

    2003-10-01

    Human D2Long (D2L) and D2Short (D2S) dopamine receptor isoforms were modified at their N-terminus by the addition of a human immunodeficiency virus (HIV) or a FLAG epitope tag. The receptors were then expressed in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus system, and their oligomerization was investigated by means of co-immunoprecipitation and time-resolved fluorescence resonance energy transfer (FRET). [3H]Spiperone labelled D2 receptors in membranes prepared from Sf9 cells expressing epitope-tagged D2L or D2S receptors, with a pKd value of approximately 10. Co-immunoprecipitation using antibodies specific for the tags showed constitutive homo-oligomerization of D2L and D2S receptors in Sf9 cells. When the FLAG-tagged D2S and HIV-tagged D2L receptors were co-expressed, co-immunoprecipitation showed that the two isoforms can also form hetero-oligomers in Sf9 cells. Time-resolved FRET with europium and XL665-labelled antibodies was applied to whole Sf9 cells and to membranes from Sf9 cells expressing epitope-tagged D2 receptors. In both cases, constitutive homo-oligomers were revealed for D2L and D2S isoforms. Time-resolved FRET also revealed constitutive homo-oligomers in HEK293 cells expressing FLAG-tagged D2S receptors. The D2 receptor ligands dopamine, R-(-)propylnorapomorphine, and raclopride did not affect oligomerization of D2L and D2S in Sf9 and HEK293 cells. Human D2 dopamine receptors can therefore form constitutive oligomers in Sf9 cells and in HEK293 cells that can be detected by different approaches, and D2 oligomerization in these cells is not regulated by ligands.

  13. Identification of oxidised proteins in the matrix of rice leaf mitochondria by immunoprecipitation and two-dimensional liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Kristensen, B.K.; Askerlund, P.; Bykova, N.V.

    2004-01-01

    of peptides was analysed by nano-HPLC coupled online to an ESI-Quad-TOF mass spectrometer. The peptides were separated by stepwise ion exchange chromatography followed by reverse phase chromatography (2D-LC), and analysed by MS/MS. Proteins were identified by un-interpreted fragment ion database searches...

  14. 染色质免疫沉淀技术分析HePG2细胞TCF7L2蛋白与IDE基因转录启动子的结合%Detection of TCF7L2 Binding to IDE Gene Promoters by Chromatin Immunoprecipitation

    Institute of Scientific and Technical Information of China (English)

    许丹; 任伟; 郑晓雅; 毕健琨

    2012-01-01

    TCF7L2 is the key transcriptional factor regulating glucose metabolism through the Wnt signaling pathway. Insulin-degrading enzyme (IDE) plays a key role in insulin degradation in celluar level and is closely related to hyperglycemia, insulin resistance as well as hyperinsulinemia in patients with Type 2 diabetes mellitus (T2DM). To identify the region in IDE gene promoter where the transcriptional factor TCF7L2 can bind in HePG2 cells. Chromatin immunoprecipitation and PCR were performed using the antibody specific for TCF7L2 to verify the binding of TCF7L2 to IDE promoter. Results indicated that IDE gene specific fragments were detected in the DNA fragments immunoprecipitated by antibody specific for TCF7L2. Thus it proved that TCF7L2 protein could bind to the promoter regions of IDE gene in HePG2 cells and may involved in regulation of IDE gene expression.%TCF7L2是一种重要的转录因子,通过Wnt信号途径,调节葡萄糖代谢.胰岛素降解酶(IDE)是细胞水平催化胰岛素降解的最关键的酶,与2型糖尿病(T2DM)高血糖、胰岛素抵抗、高胰岛素血症密切相关.为了检测HePG2细胞内转录因子TCF7L2与IDE基因启动子区的结合情况,采用染色质免疫沉淀技术结合PCR技术检测IDE基因启动子序列.结果表明,在特异性TCF7L2抗体免疫沉淀的DNA片段中扩增出IDE基因启动子序列,因此证实在HePG2细胞内,TCF7L2蛋白可与IDE基因转录启动子的特异区域结合,进而可能参与IDE基因的表达调控.

  15. Isolation of Specific Genomic Regions and Identification of Their Associated Molecules by Engineered DNA-Binding Molecule-Mediated Chromatin Immunoprecipitation (enChIP) Using the CRISPR System and TAL Proteins.

    Science.gov (United States)

    Fujii, Hodaka; Fujita, Toshitsugu

    2015-09-09

    Comprehensive understanding of genome functions requires identification of molecules (proteins, RNAs, genomic regions, etc.) bound to specific genomic regions of interest in vivo. To perform biochemical and molecular biological analysis of specific genomic regions, we developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) to purify genomic regions of interest. In enChIP, specific genomic regions are tagged for biochemical purification using engineered DNA-binding molecules, such as transcription activator-like (TAL) proteins and a catalytically inactive form of the clustered regularly interspaced short palindromic repeats (CRISPR) system. enChIP is a comprehensive approach that emphasizes non-biased search using next-generation sequencing (NGS), microarrays, mass spectrometry (MS), and other methods. Moreover, this approach is not restricted to cultured cell lines and can be easily extended to organisms. In this review, we discuss applications of enChIP to elucidating the molecular mechanisms underlying genome functions.

  16. Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

    Science.gov (United States)

    Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

    2017-01-01

    Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (Pgastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

  17. Quantitative Characterization of E-selectin Interaction with Native CD44 and P-selectin Glycoprotein Ligand-1 (PSGL-1) Using a Real Time Immunoprecipitation-based Binding Assay

    KAUST Repository

    Abu Samra, Dina Bashir Kamil

    2015-06-29

    Selectins (E-, P-, and L-selectins) interact with glycoprotein ligands to mediate the essential tethering/rolling step in cell transport and delivery that captures migrating cells from the circulating flow. In this work, we developed a real time immunoprecipitation assay on a surface plasmon resonance chip that captures native glycoforms of two well known E-selectin ligands (CD44/hematopoietic cell E-/L-selectin ligand and P-selectin glycoprotein ligand-1) from hematopoietic cell extracts. Here we present a comprehensive characterization of their binding to E-selectin. We show that both ligands bind recombinant monomeric E-selectin transiently with fast on- and fast off-rates, whereas they bind dimeric E-selectin with remarkably slow onand off-rates. This binding requires the sialyl Lewis x sugar moiety to be placed on both O- and N-glycans, and its association, but not dissociation, is sensitive to the salt concentration. Our results suggest a mechanism through which monomeric selectins mediate initial fast on and fast off kinetics to help capture cells out of the circulating shear flow; subsequently, tight binding by dimeric/oligomeric selectins is enabled to significantly slow rolling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Analysing Java Identifier Names

    OpenAIRE

    Butler, Simon

    2016-01-01

    Identifier names are the principal means of recording and communicating ideas in source code and are a significant source of information for software developers and maintainers, and the tools that support their work. This research aims to increase understanding of identifier name content types - words, abbreviations, etc. - and phrasal structures - noun phrases, verb phrases, etc. - by improving techniques for the analysis of identifier names. The techniques and knowledge acquired can be appl...

  19. Identifiability in stochastic models

    CERN Document Server

    1992-01-01

    The problem of identifiability is basic to all statistical methods and data analysis, occurring in such diverse areas as Reliability Theory, Survival Analysis, and Econometrics, where stochastic modeling is widely used. Mathematics dealing with identifiability per se is closely related to the so-called branch of ""characterization problems"" in Probability Theory. This book brings together relevant material on identifiability as it occurs in these diverse fields.

  20. Human papillomavirus type 18 E6*, E6, and E7 protein synthesis in cell-free translation systems and comparison of E6 and E7 in vitro translation products to proteins immunoprecipitated from human epithelial cells.

    Science.gov (United States)

    Roggenbuck, B; Larsen, P M; Fey, S J; Bartsch, D; Gissmann, L; Schwarz, E

    1991-09-01

    Expression of the E6 and E7 transforming genes of human papillomavirus type 18 (HPV18) occurs via structurally bicistronic mRNAs in which the downstream open reading frame (ORF) E7 is preceded either by the full-length ORF E6 or by a spliced ORF, E6*. We have used in vitro transcription and translation of HPV18 cDNAs in order to analyze the synthesis of E6*, E6, and E7 proteins and to compare the E6 and E7 in vitro translation products with the authentic proteins immunoprecipitated from cervical cancer cells. In wheat germ extract, in vitro translation resulted in the production of all three proteins, E6*, E6, and E7. In rabbit reticulocyte lysate, however, only the E6 and E7 proteins were produced. The lack of E6* protein was due neither to template RNA degradation nor to an inhibitory influence of the RNA 5' leader sequences, thus indicating the possibility of either inhibition of synthesis or degradation of E6* protein in reticulocyte lysate. The E7 protein was synthesized from both E6*-E7 and E6-E7 RNAs. In vitro-synthesized and authentic HPV18 E7 proteins revealed identical electrophoretic mobilities in two-dimensional gel electrophoresis, thus indicating similar modifications. By using a monoclonal antibody against the N terminus of HPV18 E6* and E6, an 18-kDa protein was detected not only in HPV18-positive but also in HPV18-negative epithelial cells. The 18-kDa proteins and the in vitro-synthesized HPV18 E6 protein exhibited comparable electrophoretic characteristics in two-dimensional gels. These results suggest the possible existence of a cellular protein related to HPV18 E6.

  1. Genome-Wide Chromatin Immunoprecipitation Sequencing Analysis Shows that WhiB Is a Transcription Factor That Cocontrols Its Regulon with WhiA To Initiate Developmental Cell Division in Streptomyces

    Directory of Open Access Journals (Sweden)

    Matthew J. Bush

    2016-04-01

    Full Text Available WhiB is the founding member of a family of proteins (the WhiB-like [Wbl] family that carry a [4Fe-4S] iron-sulfur cluster and play key roles in diverse aspects of the biology of actinomycetes, including pathogenesis, antibiotic resistance, and the control of development. In Streptomyces, WhiB is essential for the process of developmentally controlled cell division that leads to sporulation. The biochemical function of Wbl proteins has been controversial; here, we set out to determine unambiguously if WhiB functions as a transcription factor using chromatin immunoprecipitation sequencing (ChIP-seq in Streptomyces venezuelae. In the first demonstration of in vivo genome-wide Wbl binding, we showed that WhiB regulates the expression of key genes required for sporulation by binding upstream of ~240 transcription units. Strikingly, the WhiB regulon is identical to the previously characterized WhiA regulon, providing an explanation for the identical phenotypes of whiA and whiB mutants. Using ChIP-seq, we demonstrated that in vivo DNA binding by WhiA depends on WhiB and vice versa, showing that WhiA and WhiB function cooperatively to control expression of a common set of WhiAB target genes. Finally, we show that mutation of the cysteine residues that coordinate the [4Fe-4S] cluster in WhiB prevents DNA binding by both WhiB and WhiA in vivo.

  2. Identifying Knowledge and Communication

    Directory of Open Access Journals (Sweden)

    Eduardo Coutinho Lourenço de Lima

    2006-12-01

    Full Text Available In this paper, I discuss how the principle of identifying knowledge which Strawson advances in ‘Singular Terms and Predication’ (1961, and in ‘Identifying Reference and Truth-Values’ (1964 turns out to constrain communication. The principle states that a speaker’s use of a referring expression should invoke identifying knowledge on the part of the hearer, if the hearer is to understand what the speaker is saying, and also that, in so referring, speakers are attentive to hearers’ epistemic states. In contrasting it with Russell’s Principle (Evans 1982, as well as with the principle of identifying descriptions (Donnellan 1970, I try to show that the principle of identifying knowledge, ultimately a condition for understanding, makes sense only in a situation of conversation. This allows me to conclude that the cooperative feature of communication (Grice 1975 and reference (Clark andWilkes-Gibbs 1986 holds also at the understanding level. Finally, I discuss where Strawson’s views seem to be unsatisfactory, and suggest how they might be improved.

  3. Identifying learning styles.

    Science.gov (United States)

    Hughes, Grace

    2016-12-14

    What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article explored different learning styles and outlined some of the models that can be used to identify them. It discussed the limitations of these models, indicating that although they can be helpful in identifying a student's preferred learning style, this is not 'fixed' and might change over time. Learning is also influenced by other factors, such as culture and age.

  4. Identifying Nursing's Future Leaders.

    Science.gov (United States)

    Gunning, Carolyn S.; Hawken, Patty L.

    1990-01-01

    A study determined that encouraging and supporting students in professional activities while they were still in school would lead those students to participate in professional nursing organizations after they graduated. Organized nursing needs to identify the factors that influence nurses to join organizations and concentrate on these factors to…

  5. Identifying and Managing Risk.

    Science.gov (United States)

    Abraham, Janice M.

    1999-01-01

    The role of the college or university chief financial officer in institutional risk management is (1) to identify risk (physical, casualty, fiscal, business, reputational, workplace safety, legal liability, employment practices, general liability), (2) to develop a campus plan to reduce and control risk, (3) to transfer risk, and (4) to track and…

  6. Identifying Instability Pockets

    Science.gov (United States)

    2014-12-04

    TYPE SAMS Monograph 3. DATES COVERED (From - To) FEB 2014 – DEC 2014 4. TITLE AND SUBTITLE IDENTIFYING INSTABILITY POCKETS 5a. CONTRACT...century, and if the first few years of the new century are indicative of the future, Central Asia is surely destined to be a focus of the world...reasons. First, there is a possibility of the collapse and instability of Afghanistan once all the U.S troops vacate .107 This stability will most

  7. Strategies to identify long noncoding RNAs involved in gene regulation

    Directory of Open Access Journals (Sweden)

    Lee Catherine

    2012-11-01

    Full Text Available Abstract Long noncoding RNAs (lncRNAs have been detected in nearly every cell type and found to be fundamentally involved in many biological processes. The characterization of lncRNAs has immense potential to advance our comprehensive understanding of cellular processes and gene regulation, along with implications for the treatment of human disease. The recent ENCODE (Encyclopedia of DNA Elements study reported 9,640 lncRNA loci in the human genome, which corresponds to around half the number of protein-coding genes. Because of this sheer number and their functional diversity, it is crucial to identify a pool of potentially relevant lncRNAs early on in a given study. In this review, we evaluate the methods for isolating lncRNAs by immunoprecipitation and review the advantages, disadvantages, and applications of three widely used approaches – microarray, tiling array, and RNA-seq – for identifying lncRNAs involved in gene regulation. We also look at ways in which data from publicly available databases such as ENCODE can support the study of lncRNAs.

  8. Random Cell Identifiers Assignment

    Directory of Open Access Journals (Sweden)

    Robert Bestak

    2012-01-01

    Full Text Available Despite integration of advanced functions that enable Femto Access Points (FAPs to be deployed in a plug-and-play manner, the femtocell concept still cause several opened issues to be resolved. One of them represents an assignment of Physical Cell Identifiers (PCIs to FAPs. This paper analyses a random based assignment algorithm in LTE systems operating in diverse femtocell scenarios. The performance of the algorithm is evaluated by comparing the number of confusions for various femtocell densities, PCI ranges and knowledge of vicinity. Simulation results show that better knowledge of vicinity can significantly reduce the number of confusions events.

  9. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells

    DEFF Research Database (Denmark)

    Ali, D.; Hamam, R.; Alfayez, M.;

    2016-01-01

    abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell...... proliferation and differentiation that were targeted by abexinostat. Concordantly, ChIP-quantitative polymerase chain reaction revealed marked increase in H3K9Ac epigenetic mark on the promoter region of AdipoQ, FABP4, PPARγ, KLF15, CEBPA, SP7, and ALPL in abexinostat-treated hMSCs. Pharmacological inhibition...

  10. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR/sub 2/), also identifies a 72Kd secreted fragment of CR/sub 2/ that contains the C3d-binding site

    Energy Technology Data Exchange (ETDEWEB)

    Myones, B.L.; Ross, G.D.

    1986-03-05

    CR/sub 2/ is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR/sub 2/, blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR/sub 2/, does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR/sub 2/ because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of /sup 125/I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from /sup 125/I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence /sup 3/H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of /sup 125/I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR/sub 2/ molecule, also identifies a 72Kd shed fragment of CR/sub 2/ isolated from Raji cell media, which contains the C3d-binding site.

  11. Blood pressure loci identified with a gene-centric array.

    Science.gov (United States)

    Johnson, Toby; Gaunt, Tom R; Newhouse, Stephen J; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W; Tzoulaki, Ioanna; O'Brien, Eoin T; Poulter, Neil R; Sever, Peter; Shields, Denis C; Thom, Simon; Wannamethee, Sasiwarang G; Whincup, Peter H; Brown, Morris J; Connell, John M; Dobson, Richard J; Howard, Philip J; Mein, Charles A; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Davey Smith, George; Day, Ian N M; Lawlor, Debbie A; Goodall, Alison H; Fowkes, F Gerald; Abecasis, Gonçalo R; Elliott, Paul; Gateva, Vesela; Braund, Peter S; Burton, Paul R; Nelson, Christopher P; Tobin, Martin D; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-François; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sõber, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S; Hastie, Claire E; Hedner, Thomas; Lee, Wai K; Melander, Olle; Wahlstrand, Björn; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A; Palmen, Jutta; Chen, Li; Stewart, Alexandre F R; Wells, George A; Westra, Harm-Jan; Wolfs, Marcel G M; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Maris; Kuh, Diana; Humphries, Steve E; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V; Dominiczak, Anna F; Farrall, Martin; Hingorani, Aroon D; Samani, Nilesh J; Caulfield, Mark J; Munroe, Patricia B

    2011-12-09

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

  12. 蜱传脑炎病毒prM-E蛋白的真核表达及其在荧光素酶免疫共沉淀技术中的应用∗%EXPRESSION OF TICK-BORNE ENCEPHALITIS VIRUS PRM-E PROTEIN IN EUKARYOTIC SYSTEM AND ITS APPLICATION IN LUCIFERASE IMMUNOPRECIPITATION SYSTEM

    Institute of Scientific and Technical Information of China (English)

    冉鑫; 康晓平; 李裕昌; 吴晓燕; 霍耐凡; 贾佳; 曹雪峰; 杨银辉

    2016-01-01

    In order to establish a novel serologic test—Luciferase immunoprecipitation system ( LIPS) , full⁃length prM⁃E of TBE virus was expressed by eukaryotic expression system and its effect was evaluated by LIPS technology. Firstly, using TBEV′s RNA as template, prM⁃E gene of TBEV was amplified by RT⁃PCR, eukaryotic expression vector pNLF⁃prM⁃E was constructed through inserting prM⁃E gene into pNLF1⁃secN vector. Fusion protein prM⁃E⁃luciferase was expressed by transfecting Cos7 cells. The expression of fusion protein was measured by testing values of luciferase in supernatant of Cos7 cells. Immunofluorescence assay ( IFA) was employed to identify the specificity of the recombinant protein and LIPS was used to detect the serum of TBEV infected patients. High expression level of luciferase was tested in the supernatants of the transfected cells. The specific binding of prM⁃E with TBEV antibody was confirmed by IFA. The LIPS assay detected 19 positive results out of 20 sera of the TBEV infected patients, 7 control sera all showed negative results. The results indicated that the expressed prM⁃E had good sensitivity and specitivity, which could be used as a candidate diagnostic antigen for LIPS assay for TBEV infection.%为了探索一种新型的血清学技术的荧光素酶免疫共沉淀技术(LIPS),本研究利用真核表达系统制备了蜱传脑炎病毒结构蛋白prM⁃E与荧光素酶融合蛋白,并评价了其在LIPS系统中的检测效果。首先以蜱传脑炎病毒RNA为模板,采用RT⁃PCR技术扩增prM⁃E抗原基因,连接到pNLF1⁃secN质粒上构建真核表达载体pNLF⁃prM⁃E,使prM⁃E蛋白与荧光素酶串联融合表达,并将该质粒转染到Cos7细胞中。结果显示,转染重组质粒pNLF⁃prM⁃E的细胞上清中可检测到荧光素酶的高表达;进而用间接免疫荧光试验( IFA)检测到转染的细胞与蜱传脑炎病毒抗体特异性结合;在此基础上,

  13. Machine learning helps identify CHRONO as a circadian clock component.

    Directory of Open Access Journals (Sweden)

    Ron C Anafi

    2014-04-01

    Full Text Available Over the last decades, researchers have characterized a set of "clock genes" that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3. One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator. Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics.

  14. Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells

    DEFF Research Database (Denmark)

    Ali; Hamam; Alfayez;

    2016-01-01

    The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including...... abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell...... or stromal) stem cells (hMSCs). These data provide new insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways controlling adipocyte and osteoblast differentiation of hMSCs. Manipulating...

  15. New criteria to identify spectrum

    DEFF Research Database (Denmark)

    Jensen, Arne; Krishna, M.

    2005-01-01

    In this paper we give some new criteria for identifying the components of a probability measure, in its Lebesgue decomposition. This enables us to give new criteria to identify spectral types of self-adjoint operators on Hilbert spaces, especially those of interest....

  16. New Criteria to Identify Spectrum

    Indian Academy of Sciences (India)

    A Jensen; M Krishna

    2005-05-01

    In this paper we give some new criteria for identifying the components of a probability measure, in its Lebesgue decomposition. This enables us to give new criteria to identify spectral types of self-adjoint operators on Hilbert spaces, especially those of interest.

  17. Author Identifiers in Scholarly Repositories

    CERN Document Server

    Warner, Simeon

    2010-01-01

    Bibliometric and usage-based analyses and tools highlight the value of information about scholarship contained within the network of authors, articles and usage data. Less progress has been made on populating and using the author side of this network than the article side, in part because of the difficulty of unambiguously identifying authors. I briefly review a sample of author identifier schemes, and consider use in scholarly repositories. I then describe preliminary work at arXiv to implement public author identifiers, services based on them, and plans to make this information useful beyond the boundaries of arXiv.

  18. Identifiability, exchangeability and confounding revisited

    OpenAIRE

    Greenland, Sander; Robins, James Matthew

    2009-01-01

    In 1986 the International Journal of Epidemiology published "Identifiability, Exchangeability and Epidemiological Confounding". We review the article from the perspective of a quarter century after it was first drafted and relate it to subsequent developments on confounding, ignorability, and collapsibility.

  19. Identifying discharge practice training needs.

    Science.gov (United States)

    Lees, L; Emmerson, K

    A training needs analysis tool was developed to identify nurses' discharge training needs and to improve discharge practice. The tool includes 49 elements of discharge practice subdivided into four areas: corporate, operational, clinical and nurse-led discharge. The tool was disseminated to 15 wards on two hospital sites with assistance from the practice development team. Analysis of discharge training is important to assess discharge training needs and to identify staff who may assist with training.

  20. Individual Identifiability Predicts Population Identifiability in Forensic Microsatellite Markers.

    Science.gov (United States)

    Algee-Hewitt, Bridget F B; Edge, Michael D; Kim, Jaehee; Li, Jun Z; Rosenberg, Noah A

    2016-04-01

    Highly polymorphic genetic markers with significant potential for distinguishing individual identity are used as a standard tool in forensic testing [1, 2]. At the same time, population-genetic studies have suggested that genetically diverse markers with high individual identifiability also confer information about genetic ancestry [3-6]. The dual influence of polymorphism levels on ancestry inference and forensic desirability suggests that forensically useful marker sets with high levels of individual identifiability might also possess substantial ancestry information. We study a standard forensic marker set-the 13 CODIS loci used in the United States and elsewhere [2, 7-9]-together with 779 additional microsatellites [10], using direct population structure inference to test whether markers with substantial individual identifiability also produce considerable information about ancestry. Despite having been selected for individual identification and not for ancestry inference [11], the CODIS markers generate nontrivial model-based clustering patterns similar to those of other sets of 13 tetranucleotide microsatellites. Although the CODIS markers have relatively low values of the F(ST) divergence statistic, their high heterozygosities produce greater ancestry inference potential than is possessed by less heterozygous marker sets. More generally, we observe that marker sets with greater individual identifiability also tend toward greater population identifiability. We conclude that population identifiability regularly follows as a byproduct of the use of highly polymorphic forensic markers. Our findings have implications for the design of new forensic marker sets and for evaluations of the extent to which individual characteristics beyond identification might be predicted from current and future forensic data.

  1. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  2. Football refereeing: Identifying innovative methods

    Directory of Open Access Journals (Sweden)

    Reza MohammadKazemi

    2014-08-01

    Full Text Available The aim of the present study is to identify the potentials innovation in football industry. Data were collected from 10 national and international referees, assistant referees and referees’ supervisors in Iran. In this study, technological innovations are identified that assist better refereeing performances. The analysis revealed a significant relationship between using new technologies and referees ‘performance. The results indicate that elite referees, assistant referees and supervisors agreed to use new technological innovations during the game. According to their comments, this kind of technology causes the referees’ performance development.

  3. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    Energy Technology Data Exchange (ETDEWEB)

    Fardini, Yann [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Perez-Cervera, Yobana [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Facultad de Odontología, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca (Mexico); Camoin, Luc [INSERM, U1068, CRCM, Marseille Protéomique IBiSA, Marseille, F-13009 (France); Institut Paoli-Calmettes Team, Cell Polarity, Cell Signaling and Cancer, Marseille, F-13009 (France); Aix-Marseille Université, F-13284, Marseille (France); CNRS, UMR7258, CRCM, Marseille, F-13009 (France); Pagesy, Patrick [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France); Lefebvre, Tony [Structural and Functional Glycobiology Unit, Lille 1 University, CNRS (UMR 8576), IFR 117, Villeneuve d' Ascq (France); Issad, Tarik, E-mail: tarik.issad@inserm.fr [INSERM, U1016, Institut Cochin, Paris (France); CNRS, UMR8104, Paris (France); Université Paris Descartes, Sorbonne Paris Cité, Paris (France)

    2015-06-26

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity.

  4. Identifying the Gifted Child Humorist.

    Science.gov (United States)

    Fern, Tami L.

    1991-01-01

    This study attempted to identify gifted child humorists among 1,204 children in grades 3-6. Final identification of 13 gifted child humorists was determined through application of such criteria as funniness, originality, and exemplary performance or product. The influence of intelligence, development, social factors, sex differences, family…

  5. SNP interaction pattern identifier (SIPI)

    DEFF Research Database (Denmark)

    Lin, Hui-Yi; Chen, Dung-Tsa; Huang, Po-Yu

    2016-01-01

    MOTIVATION: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped. RESULTS: We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45...

  6. Studying RNA-protein interactions in vivo by RNA immunoprecipitation

    DEFF Research Database (Denmark)

    Selth, Luke A; Close, Pierre; Svejstrup, Jesper Q

    2011-01-01

    The crucial roles played by RNA-binding proteins in all aspects of RNA metabolism, particularly in the regulation of transcription, have become increasingly evident. Moreover, other factors that do not directly interact with RNA molecules can nevertheless function proximally to RNA polymerases an...

  7. Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia.

    Science.gov (United States)

    Meyer, Urs; Feldon, Joram; Schedlowski, Manfred; Yee, Benjamin K

    2005-01-01

    Epidemiological studies have indicated an association between maternal bacterial and viral infections during pregnancy and the higher incidence of schizophrenia in the resultant offspring post-puberty. One hypothesis asserts that the reported epidemiological link is mediated by prenatal activation of the foetal immune system in response to the elevation of maternal cytokine level due to infection. Here, we report that pregnant mouse dams receiving a single exposure to the cytokine-releasing agent, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 2.5, 5.0, or 10.0 mg/kg) on gestation day 9 produced offspring that subsequently exhibited multiple schizophrenia-related behavioural deficits in adulthood, in comparison to offspring from vehicle injected or non-injected control dams. The efficacy of the PolyI:C challenge to induce cytokine responses in naïve non-pregnant adult female mice and in foetal brain tissue when injected to pregnant mice were further ascertained in separate subjects: (i) a dose-dependent elevation of interleukin-10 was detected in the adult female mice at 1 and 6h post-injection, (ii) 12 h following prenatal PolyI:C challenge, the foetal levels of interleukin-1beta were elevated. The spectrum of abnormalities included impairments in exploratory behaviour, prepulse inhibition, latent inhibition, the US-pre-exposure effect, spatial working memory; and enhancement in the locomotor response to systemic amphetamine (2.5 mg/kg, i.p.) as well as in discrimination reversal learning. The neuropsychological parallels between prenatal PolyI:C treatment in mice and psychosis in humans, demonstrated here, leads us to conclude that prenatal PolyI:C treatment represents one of the most powerful environmental-developmental models of schizophrenia to date. The uniqueness of this model lies in its epidemiological and immunological relevance. It is, sui generis, ideally suited for the investigation of the neuropsychoimmunological mechanisms implicated in the developmental aetiology and disease processes of schizophrenia.

  8. Immunoprecipitation of bisphenol A by antibody–mesoporous silica composites

    Directory of Open Access Journals (Sweden)

    Toru Orita

    2014-09-01

    Full Text Available Bisphenol A (BPA is of global concern because of its disruption of endocrine systems and ubiquity in aquatic environment. In this study, BPA antibody was successfully immobilised on novel mesoporous silica (MPS carriers that display unique properties such as high surface area, highly uniform pore distribution and high adsorption capacity. Mobil Crystalline Material MCM-41 (2.7 nm, Santa Barbara Amorphous SBA-15-1 (12.3 nm and SBA-15-2 (24.0 nm materials were used as supports for these antibodies. On these carriers, the BPA antibody immobilisation reached 40 μg mg−1. For each MPS, 15 ng of BPA antigen was adsorbed on 1 mg of MPS–antibody composite, which resulted in an antibody activity of 30%. The highest recovery rate of BPA antigen was observed for 80% acetonitrile in 10 mM phosphate buffer (pH 7. After six repeated runs, BPA antibodies immobilised on SBA-15-1 and SBA-15-2 retained about 30% of their initial activity. In contrast, these antibodies showed 13% lower residual activity on MCM-41 than on SBA-15-1 and SBA-15-2. This result indicated that entire antibody molecules were adsorbed inside SBA-15-1 and SBA-15-2 pores, stabilising their structural conformation.

  9. Tagging of MADS domain proteins for chromatin immunoprecipitation

    NARCIS (Netherlands)

    Folter, de S.; Urbanus, S.L.; Zuijlen, L.; Kaufmann, K.; Angenent, G.C.

    2007-01-01

    Most transcription factors fulfill their role in complexes and regulate their target genes upon binding to DNA motifs located in upstream regions or introns. To date, knowledge about transcription factor target genes and their corresponding transcription factor binding sites are still very limited.

  10. Sparse Linear Identifiable Multivariate Modeling

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2011-01-01

    In this paper we consider sparse and identifiable linear latent variable (factor) and linear Bayesian network models for parsimonious analysis of multivariate data. We propose a computationally efficient method for joint parameter and model inference, and model comparison. It consists of a fully...... Bayesian hierarchy for sparse models using slab and spike priors (two-component δ-function and continuous mixtures), non-Gaussian latent factors and a stochastic search over the ordering of the variables. The framework, which we call SLIM (Sparse Linear Identifiable Multivariate modeling), is validated...... and bench-marked on artificial and real biological data sets. SLIM is closest in spirit to LiNGAM (Shimizu et al., 2006), but differs substantially in inference, Bayesian network structure learning and model comparison. Experimentally, SLIM performs equally well or better than LiNGAM with comparable...

  11. The coilin interactome identifies hundreds of small noncoding RNAs that traffic through Cajal bodies.

    Science.gov (United States)

    Machyna, Martin; Kehr, Stephanie; Straube, Korinna; Kappei, Dennis; Buchholz, Frank; Butter, Falk; Ule, Jernej; Hertel, Jana; Stadler, Peter F; Neugebauer, Karla M

    2014-11-06

    Coilin protein scaffolds Cajal bodies (CBs)-subnuclear compartments enriched in small nuclear RNAs (snRNAs)-and promotes efficient spliceosomal snRNP assembly. The molecular function of coilin, which is intrinsically disordered with no defined motifs, is poorly understood. We use UV crosslinking and immunoprecipitation (iCLIP) to determine whether mammalian coilin binds RNA in vivo and to identify targets. Robust detection of snRNA transcripts correlated with coilin ChIP-seq peaks on snRNA genes, indicating that coilin binding to nascent snRNAs is a site-specific CB nucleator. Surprisingly, several hundred small nucleolar RNAs (snoRNAs) were identified as coilin interactors, including numerous unannotated mouse and human snoRNAs. We show that all classes of snoRNAs concentrate in CBs. Moreover, snoRNAs lacking specific CB retention signals traffic through CBs en route to nucleoli, consistent with the role of CBs in small RNP assembly. Thus, coilin couples snRNA and snoRNA biogenesis, making CBs the cellular hub of small ncRNA metabolism.

  12. Identifying the health conscious consumer.

    Science.gov (United States)

    Kraft, F B; Goodell, P W

    1993-01-01

    Individuals who lead a "wellness-oriented" lifestyle are concerned with nutrition, fitness, stress, and their environment. They accept responsibility for their health and are excellent customers for health-related products and services. Those who lack a wellness orientation are identified as higher health risks and become candidates for health promotion program intervention. The authors report a new scale by which to measure the wellness-oriented lifestyle. Scale development procedures are detailed, followed by information from five studies that support its validity. The authors suggest ways health care marketers may use the Wellness Scale to segment and target potential customers and position their products and services.

  13. RECOVIR Software for Identifying Viruses

    Science.gov (United States)

    Chakravarty, Sugoto; Fox, George E.; Zhu, Dianhui

    2013-01-01

    Most single-stranded RNA (ssRNA) viruses mutate rapidly to generate a large number of strains with highly divergent capsid sequences. Determining the capsid residues or nucleotides that uniquely characterize these strains is critical in understanding the strain diversity of these viruses. RECOVIR (an acronym for "recognize viruses") software predicts the strains of some ssRNA viruses from their limited sequence data. Novel phylogenetic-tree-based databases of protein or nucleic acid residues that uniquely characterize these virus strains are created. Strains of input virus sequences (partial or complete) are predicted through residue-wise comparisons with the databases. RECOVIR uses unique characterizing residues to identify automatically strains of partial or complete capsid sequences of picorna and caliciviruses, two of the most highly diverse ssRNA virus families. Partition-wise comparisons of the database residues with the corresponding residues of more than 300 complete and partial sequences of these viruses resulted in correct strain identification for all of these sequences. This study shows the feasibility of creating databases of hitherto unknown residues uniquely characterizing the capsid sequences of two of the most highly divergent ssRNA virus families. These databases enable automated strain identification from partial or complete capsid sequences of these human and animal pathogens.

  14. Characterization of Human Macrophage Antigens Identified by Monoclonal Antibodies

    Science.gov (United States)

    1984-01-01

    Total extracts of iodinated glycoproteins or iodinated surface proteins were dis- solved in 50 pLl O’Farrell Buffer A [9,5 M urea. 2% (w,’v) nonidet -P...the c:ll surface labeled by vectorial iodination. p40 skas not immunoprecipitable from an iodinated concanavalin A-glycoprotein fraction of U937...of U937 cells. T cell clone. B cell clone, and peripheral blood granulocytes and monocytes. but not lymphocytes (Table 3). p40 was also detected in

  15. Direct and heterologous approaches to identify the LET-756/FGF interactome

    Directory of Open Access Journals (Sweden)

    Birnbaum Daniel

    2006-05-01

    Full Text Available Abstract Background Fibroblast growth factors (FGFs are multifunctional proteins that play important roles in cell communication, proliferation and differentiation. However, many aspects of their activities are not well defined. LET-756, one of the two C. elegans FGFs, is expressed throughout development and is essential for worm development. It is both expressed in the nucleus and secreted. Results To identify nuclear factors associated with LET-756, we used three approaches. First, we screened a two-hybrid cDNA library derived from mixed stages worms and from a normalized library, using LET-756 as bait. This direct approach allowed the identification of several binding partners that play various roles in the nucleus/nucleolus, such as PAL-1, a transcription regulator, or RPS-16, a component of the small ribosomal subunit. The interactions were validated by co-immunoprecipitation and determination of their site of occurrence in mammalian cells. Second, because patterns of protein interactions may be conserved throughout species, we searched for orthologs of known mammalian interactors and measured binary interaction with these predicted candidates. We found KIN-3 and KIN-10, the orthologs of CK2α and CK2β, as new partners of LET-756. Third, following the assumption that recognition motifs mediating protein interaction may be conserved between species, we screened a two-hybrid cDNA human library using LET-756 as bait. Among the few FGF partners detected was 14-3-3β. In support of this interaction we showed that the two 14-3-3β orthologous proteins, FTT-1 and FTT-2/PAR-5, interacted with LET-756. Conclusion We have conducted the first extensive search for LET-756 interactors using a multi-directional approach and established the first interaction map of LET-756/FGF with other FGF binding proteins from other species. The interactors identified play various roles in developmental process or basic biochemical events such as ribosome biogenesis.

  16. International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents

    Science.gov (United States)

    Parmar, Priyakumari Ganesh; Taal, H. Rob; Timpson, Nicholas J.; Howe, Laura D.; Verwoert, Germaine; Aalto, Ville; Uitterlinden, Andre G.; Briollais, Laurent; Evans, Dave M.; Wright, Margie J.; Newnham, John P.; Whitfield, John B.; Lyytikäinen, Leo-Pekka; Rivadeneira, Fernando; Boomsma, Dorrett I.; Viikari, Jorma; Gillman, Matthew W.; St Pourcain, Beate; Hottenga, Jouke-Jan; Montgomery, Grant W.; Hofman, Albert; Kähönen, Mika; Martin, Nicholas G.; Tobin, Martin D.; Raitakari, Ollie; Vioque, Jesus; Jaddoe, Vincent W.V.; Jarvelin, Marjo-Riita; Beilin, Lawrence J.; Heinrich, Joachim; van Duijn, Cornelia M.; Pennell, Craig E.; Lawlor, Debbie A.; Palmer, Lyle J.

    2017-01-01

    Background Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. Methods and Results Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4–7 years), puberty (8–12 years), and postpuberty (13–20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5′-C-phosphate-G-3′ methylation site) during prepuberty (P=2.86×10–8) and rs872256 during puberty (P=8.67×10–9). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10–3. Using a P value threshold of <5×10–3, we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. Conclusions Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects. PMID:26969751

  17. A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.

    Directory of Open Access Journals (Sweden)

    Li Xie

    Full Text Available Numerous genetic and epigenetic alterations render cancer cells selectively dependent on specific genes and regulatory pathways, and represent potential vulnerabilities that can be therapeutically exploited. Here we describe an RNA interference (RNAi-based synthetic interaction screen to identify genes preferentially required for proliferation of p53-deficient (p53- human cancer cells. We find that compared to p53-competent (p53+ human cancer cell lines, diverse p53- human cancer cell lines are preferentially sensitive to loss of the transcription factor ETV1 and the DNA damage kinase ATR. In p53- cells, RNAi-mediated knockdown of ETV1 or ATR results in decreased expression of the telomerase catalytic subunit TERT leading to growth arrest, which can be reversed by ectopic TERT expression. Chromatin immunoprecipitation analysis reveals that ETV1 binds to a region downstream of the TERT transcriptional start-site in p53- but not p53+ cells. We find that the role of ATR is to phosphorylate and thereby stabilize ETV1. Our collective results identify a regulatory pathway involving ETV1, ATR, and TERT that is preferentially important for proliferation of diverse p53- cancer cells.

  18. Bacterial beta-lactamase fragmentation complementation strategy can be used as a method for identifying interacting protein pairs.

    Science.gov (United States)

    Park, Jong-Hwa; Back, Jung Ho; Hahm, Soo Hyun; Shim, Hye-Young; Park, Min Ju; Ko, Sung Il; Han, Ye Sun

    2007-10-01

    We investigated the applicability of the TEM-1 beta- lactamase fragment complementation (BFC) system to develop a strategy for the screening of protein-protein interactions in bacteria. A BFC system containing a human Fas-associated death domain (hFADD) and human Fas death domain (hFasDD) was generated. The hFADD-hFasDD interaction was verified by cell survivability in ampicillin-containing medium and the colorimetric change of nitrocefin. It was also confirmed by His pull-down assay using cell lysates obtained in selection steps. A coiled-coil helix coiled-coil domain-containing protein 5 (CHCH5) was identified as an interacting protein of human uracil DNA glycosylase (hUNG) from the bacterial BFC cDNA library strategy. The interaction between hUNG and CHCH5 was further confirmed with immunoprecipitation using a mammalian expression system. CHCH5 enhanced the DNA glycosylase activity of hUNG to remove uracil from DNA duplexes containing a U/G mismatch pair. These results suggest that the bacterial BFC cDNA library strategy can be effectively used to identify interacting protein pairs.

  19. Live-cell monitoring of periodic gene expression in synchronous human cells identifies Forkhead genes involved in cell cycle control.

    Science.gov (United States)

    Grant, Gavin D; Gamsby, Joshua; Martyanov, Viktor; Brooks, Lionel; George, Lacy K; Mahoney, J Matthew; Loros, Jennifer J; Dunlap, Jay C; Whitfield, Michael L

    2012-08-01

    We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle-dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant.

  20. 10 Ways to Identify Hearing Loss

    Science.gov (United States)

    ... Current Issue Past Issues 10 Ways to Identify Hearing Loss Past Issues / Spring 2007 Table of Contents For ... exposure and other causes. 10 Ways to Identify Hearing Loss Take the following quiz to help determine if ...

  1. NIH Researchers Identify OCD Risk Gene

    Science.gov (United States)

    ... News From NIH NIH Researchers Identify OCD Risk Gene Past Issues / Summer 2006 Table of Contents For ... and Alcoholism (NIAAA) have identified a previously unknown gene variant that doubles an individual's risk for obsessive- ...

  2. Identifying Causal Effects with Computer Algebra

    CERN Document Server

    García-Puente, Luis David; Sullivant, Seth

    2010-01-01

    The long-standing identification problem for causal effects in graphical models has many partial results but lacks a systematic study. We show how computer algebra can be used to either prove that a causal effect can be identified, generically identified, or show that the effect is not generically identifiable. We report on the results of our computations for linear structural equation models, where we determine precisely which causal effects are generically identifiable for all graphs on three and four vertices.

  3. Ability of Slovakian Pupils to Identify Birds

    Science.gov (United States)

    Prokop, Pavol; Rodak, Rastislav

    2009-01-01

    A pupil's ability to identify common organisms is necessary for acquiring further knowledge of biology. We investigated how pupils were able to identify 25 bird species following their song, growth habits, or both features presented simultaneously. Just about 19% of birds were successfully identified by song, about 39% by growth habit, and 45% of…

  4. 47 CFR 2.926 - FCC identifier.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false FCC identifier. 2.926 Section 2.926... Authorizations § 2.926 FCC identifier. (a) A grant of equipment authorization issued by the Commission will list the validated FCC Identifier consisting of the grantee code assigned by the FCC pursuant to...

  5. 29 CFR 4010.7 - Identifying information.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Identifying information. 4010.7 Section 4010.7 Labor... DISCLOSURE REQUIREMENTS ANNUAL FINANCIAL AND ACTUARIAL INFORMATION REPORTING § 4010.7 Identifying information..., http://www.pbgc.gov, the following identifying information with respect to each member of the...

  6. IVOA Identifiers Version 2.0

    CERN Document Server

    Demleitner, Markus; Linde, Tony; Williams, Roy; Noddle, Keith

    2016-01-01

    An IVOA Identifier is a globally unique name for a resource within the Virtual Observatory. This name can be used to retrieve a unique description of the resource from an IVOA-compliant registry or to identify an entity like a dataset or a protocol without dereferencing the identifier. This document describes the syntax for IVOA Identifiers as well as how they are created. The syntax has been defined to encourage global-uniqueness naturally and to maximize the freedom of resource providers to control the character content of an identifier.

  7. De-identifying an EHR Database

    DEFF Research Database (Denmark)

    Lauesen, Søren; Pantazos, Kostas; Lippert, Søren

    2011-01-01

    Abstract. Electronic health records (EHR) contain a large amount of structured data and free text. Exploring and sharing clinical data can improve healthcare and facilitate the development of medical software. However, revealing confidential information is against ethical principles and laws. We de...... lists of identifiers from the database and external resources, define a replacement for each identifier, and replace identifiers in structured data and free text. Some patient records could not be safely de-identified, so the de-identified database has 323,122 patient records with an acceptable degree...

  8. Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.

    Science.gov (United States)

    Sazonova, Olga; Zhao, Yuqi; Nürnberg, Sylvia; Miller, Clint; Pjanic, Milos; Castano, Victor G; Kim, Juyong B; Salfati, Elias L; Kundaje, Anshul B; Bejerano, Gill; Assimes, Themistocles; Yang, Xia; Quertermous, Thomas

    2015-05-01

    To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.

  9. Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.

    Directory of Open Access Journals (Sweden)

    Olga Sazonova

    2015-05-01

    Full Text Available To functionally link coronary artery disease (CAD causal genes identified by genome wide association studies (GWAS, and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC. Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.

  10. Computational analysis of siRNA recognition by the Ago2 PAZ domain and identification of the determinants of RNA-induced gene silencing.

    Science.gov (United States)

    Kandeel, Mahmoud; Kitade, Yukio

    2013-01-01

    RNA interference (RNAi) is a highly specialized process of protein-siRNA interaction that results in the regulation of gene expression and cleavage of target mRNA. The PAZ domain of the Argonaute proteins binds to the 3' end of siRNA, and during RNAi the attaching end of the siRNA switches between binding and release from its binding pocket. This biphasic interaction of the 3' end of siRNA with the PAZ domain is essential for RNAi activity; however, it remains unclear whether stronger or weaker binding with PAZ domain will facilitate or hinder the overall RNAi process. Here we report the correlation between the binding of modified siRNA 3' overhang analogues and their in vivo RNAi efficacy. We found that higher RNAi efficacy was associated with the parameters of lower Ki value, lower total intermolecular energy, lower free energy, higher hydrogen bonding, smaller total surface of interaction and fewer van der Waals interactions. Electrostatic interaction was a minor contributor to compounds recognition, underscoring the presence of phosphate groups in the modified analogues. Thus, compounds with lower binding affinity are associated with better gene silencing. Lower binding strength along with the smaller interaction surface, higher hydrogen bonding and fewer van der Waals interactions were among the markers for favorable RNAi activity. Within the measured parameters, the interaction surface, van der Waals interactions and inhibition constant showed a statistically significant correlation with measured RNAi efficacy. The considerations provided in this report will be helpful in the design of new compounds with better gene silencing ability.

  11. Identifying Bilingual Semantic Neural Representations across Languages

    Science.gov (United States)

    Buchweitz, Augusto; Shinkareva, Svetlana V.; Mason, Robert A.; Mitchell, Tom M.; Just, Marcel Adam

    2012-01-01

    The goal of the study was to identify the neural representation of a noun's meaning in one language based on the neural representation of that same noun in another language. Machine learning methods were used to train classifiers to identify which individual noun bilingual participants were thinking about in one language based solely on their…

  12. Identifying Information Focuses in Listening Comprehension

    Science.gov (United States)

    Zhang, Hong-yan

    2011-01-01

    The study explains the process of learners' listening comprehension within Halliday's information theory in functional grammar, including the skills of identifying focuses while listening in college English teaching. Identifying information focuses in listening is proved to improve the students' communicative listening ability by the means of a…

  13. Healthcare Identifiers legislation: a whiff of fourberie.

    Science.gov (United States)

    Mendelson, Danuta

    2010-05-01

    The Healthcare Identifiers Bill 2010 (Cth), which will establish "the national e-health Healthcare Identifiers Service to provide that patients, healthcare providers and provider organisations can be consistently identified", is in the process of being enacted by the Australian Federal Parliament. The legislation will enable the government to assign to each "healthcare recipient" a 26-digit electronic "Healthcare Identifier", which will be accessible, with or without the recipient's consent, to a broad range of health care service providers as well as other entities. The individual Healthcare Identifier file will initially contain such identifying information as, where applicable, the Medicare number and/or the Veterans' Affairs number; name; address; gender; date of birth; and "the date of birth accuracy indicator" presumably birth certificate. However, since each "service" provided by a health care provider to a health care recipient will be automatically recorded on each individual's Healthcare Identifier file, in time these electronic files should contain a full record of such services or contacts. Moreover, the Healthcare Identifiers are considered a "key" to, or a "foundation stone" for, the implementation of the shared electronic health records scheme, because they will enable linkage with and retrieval of each patient's clinical records throughout the health care service system. However, there has been virtually no discussion about the legal, ethical and social implications of this legislation.

  14. Drosophila Imp iCLIP identifies an RNA assemblage coordinating F-actin formation

    DEFF Research Database (Denmark)

    Hansen, Heidi Theil; Rasmussen, Simon Horskjær; Adolph, Sidsel Kramshøj;

    2015-01-01

    BACKGROUND: Post-transcriptional RNA regulons ensure co-ordinated expression of monocistronic mRNAs encoding functionally related proteins. In this study, we employ a combination of RIP-seq and short- and long-wave individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP...

  15. Parameter identifiability of linear dynamical systems

    Science.gov (United States)

    Glover, K.; Willems, J. C.

    1974-01-01

    It is assumed that the system matrices of a stationary linear dynamical system were parametrized by a set of unknown parameters. The question considered here is, when can such a set of unknown parameters be identified from the observed data? Conditions for the local identifiability of a parametrization are derived in three situations: (1) when input/output observations are made, (2) when there exists an unknown feedback matrix in the system and (3) when the system is assumed to be driven by white noise and only output observations are made. Also a sufficient condition for global identifiability is derived.

  16. Identifiability of Causal Graphs using Functional Models

    CERN Document Server

    Peters, Jonas; Janzing, Dominik; Schoelkopf, Bernhard

    2012-01-01

    This work addresses the following question: Under what assumptions on the data generating process can one infer the causal graph from the joint distribution? The approach taken by conditional independence-based causal discovery methods is based on two assumptions: the Markov condition and faithfulness. It has been shown that under these assumptions the causal graph can be identified up to Markov equivalence (some arrows remain undirected) using methods like the PC algorithm. In this work we propose an alternative by defining Identifiable Functional Model Classes (IFMOCs). As our main theorem we prove that if the data generating process belongs to an IFMOC, one can identify the complete causal graph. To the best of our knowledge this is the first identifiability result of this kind that is not limited to linear functional relationships. We discuss how the IFMOC assumption and the Markov and faithfulness assumptions relate to each other and explain why we believe that the IFMOC assumption can be tested more eas...

  17. Identifying key odorants from animal feeding operations

    Science.gov (United States)

    Odor emissions from animal agriculutre negatively impact air qualitly in surrounding communities. Current analytical practices are biased against agriculutral odorants and thus inadequate for odor quantification. The purpose of this study was to evaluate two different techniques ability to identify ...

  18. Identifying associations between genomic alterations in tumors.

    Science.gov (United States)

    George, Joshy; Gorringe, Kylie L; Smyth, Gordon K; Bowtell, David D L

    2013-01-01

    Single-nucleotide polymorphism (SNP) mapping arrays are a reliable method for identifying somatic copy number alterations in cancer samples. Though this is immensely useful to identify potential driver genes, it is not sufficient to identify genes acting in a concerted manner. In cancer cells, co-amplified genes have been shown to provide synergistic effects, and genomic alterations targeting a pathway have been shown to occur in a mutually exclusive manner. We therefore developed a bioinformatic method for detecting such gene pairs using an integrated analysis of genomic copy number and gene expression data. This approach allowed us to identify a gene pair that is co-amplified and co-expressed in high-grade serous ovarian cancer. This finding provided information about the interaction of specific genetic events that contribute to the development and progression of this disease.

  19. Regions of constrained maximum likelihood parameter identifiability

    Science.gov (United States)

    Lee, C.-H.; Herget, C. J.

    1975-01-01

    This paper considers the parameter identification problem of general discrete-time, nonlinear, multiple-input/multiple-output dynamic systems with Gaussian-white distributed measurement errors. Knowledge of the system parameterization is assumed to be known. Regions of constrained maximum likelihood (CML) parameter identifiability are established. A computation procedure employing interval arithmetic is proposed for finding explicit regions of parameter identifiability for the case of linear systems. It is shown that if the vector of true parameters is locally CML identifiable, then with probability one, the vector of true parameters is a unique maximal point of the maximum likelihood function in the region of parameter identifiability and the CML estimation sequence will converge to the true parameters.

  20. Identifiable Data Files - Health Outcomes Survey (HOS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Health Outcomes Survey (HOS) identifiable data files are comprised of the entire national sample for a given 2-year cohort (including both respondents...

  1. IDENTIFYING KEY CONTRIBUTIONS TO INFORMATION SCIENCE,

    Science.gov (United States)

    Several alternative approaches were examined to determine how one might identify some of the key (written) contributions to ’ information science ’. The...references. The unclear selective patterns in current bibliographies in the information science field also present problems. It is suggested that in...identifying key contributions we are far from common agreement on the conceptual, methodological or practical contributions to the information science field

  2. ORCID Author Identifiers: A Primer for Librarians.

    Science.gov (United States)

    Akers, Katherine G; Sarkozy, Alexandra; Wu, Wendy; Slyman, Alison

    2016-01-01

    The ORCID (Open Researcher and Contributor ID) registry helps disambiguate authors and streamline research workflows by assigning unique 16-digit author identifiers that enable automatic linkages between researchers and their scholarly activities. This article describes how ORCID works, the benefits of using ORCID, and how librarians can promote ORCID at their institutions by raising awareness of ORCID, helping researchers create and populate ORCID profiles, and integrating ORCID identifiers into institutional repositories and other university research information systems.

  3. Identifying Image Manipulation Software from Image Features

    Science.gov (United States)

    2015-03-26

    an overview of the DCT based encoding process [5]. When an image is processed by lossless compression, a file’s size is reduced while still...IDENTIFYING IMAGE MANIPULATION SOFTWARE FROM IMAGE FEATURES THESIS Devlin T. Boyter, CPT, USA AFIT-ENG-MS-15-M-051 DEPARTMENT OF THE AIR FORCE AIR...to copyright protection in the United States. AFIT-ENG-MS-15-M-051 IDENTIFYING IMAGE MANIPULATION SOFTWARE FROM IMAGE FEATURES THESIS Presented to

  4. Identifying knowledge in decision-making processes

    DEFF Research Database (Denmark)

    Jensen, Anna Rose Vagn; Ahmed-Kristensen, Saeema

    2010-01-01

    Managing knowledge reflects the innovation capability of a company. Mapping decision processes and links to knowledge is a way to learn more in structuring knowledge in innovation processes. Through an empirical study the paper aims to identify knowledge......Managing knowledge reflects the innovation capability of a company. Mapping decision processes and links to knowledge is a way to learn more in structuring knowledge in innovation processes. Through an empirical study the paper aims to identify knowledge...

  5. Identifying Motivational Factors within a Multinational Company

    OpenAIRE

    Daniela Bradutanu

    2011-01-01

    The aim of the study is to identify the main motivational factors within a multinational company. The first objective is to identify work functions, formulated on Abraham Maslow’s pyramid, following the identification of the key characteristics that motivate an employee at the work place and last, but not least, the type of motivation that employees focus, intrinsic or extrinsic. The research method targeted a questionnaire based survey, including various company employees and an interv...

  6. Combined Antibody/Lectin Enrichment Identifies Extensive Changes in the O-GlcNAc Sub-proteome upon Oxidative Stress.

    Science.gov (United States)

    Lee, Albert; Miller, Devin; Henry, Roger; Paruchuri, Venkata D P; O'Meally, Robert N; Boronina, Tatiana; Cole, Robert N; Zachara, Natasha E

    2016-12-02

    O-Linked N-acetyl-β-d-glucosamine (O-GlcNAc) is a dynamic post-translational modification that modifies and regulates over 3000 nuclear, cytoplasmic, and mitochondrial proteins. Upon exposure to stress and injury, cells and tissues increase the O-GlcNAc modification, or O-GlcNAcylation, of numerous proteins promoting the cellular stress response and thus survival. The aim of this study was to identify proteins that are differentially O-GlcNAcylated upon acute oxidative stress (H2O2) to provide insight into the mechanisms by which O-GlcNAc promotes survival. We achieved this goal by employing Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC) and a novel "G5-lectibody" immunoprecipitation strategy that combines four O-GlcNAc-specific antibodies (CTD110.6, RL2, HGAC39, and HGAC85) and the lectin WGA. Using the G5-lectibody column in combination with basic reversed phase chromatography and C18 RPLC-MS/MS, 990 proteins were identified and quantified. Hundreds of proteins that were identified demonstrated increased (>250) or decreased (>110) association with the G5-lectibody column upon oxidative stress, of which we validated the O-GlcNAcylation status of 24 proteins. Analysis of proteins with altered glycosylation suggests that stress-induced changes in O-GlcNAcylation cluster into pathways known to regulate the cell's response to injury and include protein folding, transcriptional regulation, epigenetics, and proteins involved in RNA biogenesis. Together, these data suggest that stress-induced O-GlcNAcylation regulates numerous and diverse cellular pathways to promote cell and tissue survival.

  7. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  8. On the relationship between sloppiness and identifiability.

    Science.gov (United States)

    Chis, Oana-Teodora; Villaverde, Alejandro F; Banga, Julio R; Balsa-Canto, Eva

    2016-12-01

    Dynamic models of biochemical networks are often formulated as sets of non-linear ordinary differential equations, whose states are the concentrations or abundances of the network components. They typically have a large number of kinetic parameters, which must be determined by calibrating the model with experimental data. In recent years it has been suggested that dynamic systems biology models are universally sloppy, meaning that the values of some parameters can be perturbed by several orders of magnitude without causing significant changes in the model output. This observation has prompted calls for focusing on model predictions rather than on parameters. In this work we examine the concept of sloppiness, investigating its links with the long-established notions of structural and practical identifiability. By analysing a set of case studies we show that sloppiness is not equivalent to lack of identifiability, and that sloppy models can be identifiable. Thus, using sloppiness to draw conclusions about the possibility of estimating parameter values can be misleading. Instead, structural and practical identifiability analyses are better tools for assessing the confidence in parameter estimates. Furthermore, we show that, when designing new experiments to decrease parametric uncertainty, designs that optimize practical identifiability criteria are more informative than those that minimize sloppiness.

  9. Identifying glass compositions in fly ash

    Directory of Open Access Journals (Sweden)

    Katherine eAughenbaugh

    2016-01-01

    Full Text Available In this study, four Class F fly ashes were studied with a scanning electron microscope; the glassy phases were identified and their compositions quantified using point compositional analysis with k-means clustering and multispectral image analysis. The results showed that while the bulk oxide contents of the fly ashes were different, the four fly ashes had somewhat similar glassy phase compositions. Aluminosilicate glasses (AS, calcium aluminosilicate glasses (CAS, a mixed glass, and, in one case, a high iron glass were identified in the fly ashes. Quartz and iron crystalline phases were identified in each fly ash as well. The compositions of the three main glasses identified, AS, CAS, and mixed glass, were relatively similar in each ash. The amounts of each glass were varied by fly ash, with the highest calcium fly ash containing the most of calcium-containing glass. Some of the glasses were identified as intermixed in individual particles, particularly the calcium-containing glasses. Finally, the smallest particles in the fly ashes, with the most surface area available to react in alkaline solution, such as when mixed with portland cement or in alkali-activated fly ash, were not different in composition than the large particles, with each of the glasses represented. The method used in the study may be applied to a fly ash of interest for use as a cementing material in order to understand its potential for reactivity.

  10. Identifying Cell Type-Specific Transcription Factors by Integrating ChIP-seq and eQTL Data-Application to Monocyte Gene Regulation.

    Science.gov (United States)

    Choudhury, Mudra; Ramsey, Stephen A

    2016-01-01

    We describe a novel computational approach to identify transcription factors (TFs) that are candidate regulators in a human cell type of interest. Our approach involves integrating cell type-specific expression quantitative trait locus (eQTL) data and TF data from chromatin immunoprecipitation-to-tag-sequencing (ChIP-seq) experiments in cell lines. To test the method, we used eQTL data from human monocytes in order to screen for TFs. Using a list of known monocyte-regulating TFs, we tested the hypothesis that the binding sites of cell type-specific TF regulators would be concentrated in the vicinity of monocyte eQTLs. For each of 397 ChIP-seq data sets, we obtained an enrichment ratio for the number of ChIP-seq peaks that are located within monocyte eQTLs. We ranked ChIP-seq data sets according to their statistical significances for eQTL overlap, and from this ranking, we observed that monocyte-regulating TFs are more highly ranked than would be expected by chance. We identified 27 TFs that had significant monocyte enrichment scores and mapped them into a protein interaction network. Our analysis uncovered two novel candidate monocyte-regulating TFs, BCLAF1 and SIN3A. Our approach is an efficient method to identify candidate TFs that can be used for any cell/tissue type for which eQTL data are available.

  11. Scientometric methods for identifying emerging technologies

    Science.gov (United States)

    Abercrombie, Robert K; Schlicher, Bob G; Sheldon, Frederick T

    2015-11-03

    Provided is a method of generating a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, worldwide patents, news archives, and on-line mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain.

  12. Identifying Turbulent Structures through Topological Segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, Peer-Timo; Gruber, Andrea; Bennett, Janine C.; Gyulassy, Attila; Kolla, Hemanth; Chen, Jacqueline H.; Grout, Ray W.

    2016-01-01

    A new method of extracting vortical structures from a turbulent flow is proposed whereby topological segmentation of an indicator function scalar field is used to identify the regions of influence of the individual vortices. This addresses a long-standing challenge in vector field topological analysis: indicator functions commonly used produce a scalar field based on the local velocity vector field; reconstructing regions of influence for a particular structure requires selecting a threshold to define vortex extent. In practice, the same threshold is rarely meaningful throughout a given flow. By also considering the topology of the indicator field function, the characteristics of vortex strength and extent can be separated and the ambiguity in the choice of the threshold reduced. The proposed approach is able to identify several types of vortices observed in a jet in cross-flow configuration simultaneously where no single threshold value for a selection of common indicator functions appears able to identify all of these vortex types.

  13. Identifying Information Senders of Web Pages

    Science.gov (United States)

    Kato, Yoshikiyo; Kawahara, Daisuke; Inui, Kentaro; Kurohashi, Sadao; Shibata, Tomohide

    The source of information is one of the crucial elements when judging the credibility of the information. On the current Web, however, the information about the source is not readily available to the users. In this paper, we formulate the problem of identifying the information source as the problem of identifying the information sender configuration (ISC) of a Web page. An information sender of a Web page is an entity which is involved in the publication of the information on the page. An information sender configuration of a Web page describes the information senders of the page and the relationship among them. Information sender identification is a sub-problem of identifying ISC, and we present a method for extracting information senders from Web pages, along with its evaluation. ISC provides a basis for deeper analysis of information on the Web.

  14. Identifying Geographic Clusters: A Network Analytic Approach

    CERN Document Server

    Catini, Roberto; Penner, Orion; Riccaboni, Massimo

    2015-01-01

    In recent years there has been a growing interest in the role of networks and clusters in the global economy. Despite being a popular research topic in economics, sociology and urban studies, geographical clustering of human activity has often studied been by means of predetermined geographical units such as administrative divisions and metropolitan areas. This approach is intrinsically time invariant and it does not allow one to differentiate between different activities. Our goal in this paper is to present a new methodology for identifying clusters, that can be applied to different empirical settings. We use a graph approach based on k-shell decomposition to analyze world biomedical research clusters based on PubMed scientific publications. We identify research institutions and locate their activities in geographical clusters. Leading areas of scientific production and their top performing research institutions are consistently identified at different geographic scales.

  15. Photoacoustic tomography to identify inflammatory arthritis

    Science.gov (United States)

    Rajian, Justin Rajesh; Girish, Gandikota; Wang, Xueding

    2012-09-01

    Identifying neovascularity (angiogenesis) as an early feature of inflammatory arthritis can help in early accurate diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT) is a hybrid imaging modality which relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. PAT is used to identify changes in the development of inflammatory arthritis in a rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, on rats revealed that there is a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histology images obtained from both the normal and the arthritis affected rats correlated well with the PAT findings. Results support the fact that the emerging PAT could become a new tool for clinical management of inflammatory arthritis.

  16. Identifying Discourse Markers in Spoken Dialog

    CERN Document Server

    Heeman, P A; Allen, J F; Heeman, Peter A.; Byron, Donna; Allen, James F.

    1998-01-01

    In this paper, we present a method for identifying discourse marker usage in spontaneous speech based on machine learning. Discourse markers are denoted by special POS tags, and thus the process of POS tagging can be used to identify discourse markers. By incorporating POS tagging into language modeling, discourse markers can be identified during speech recognition, in which the timeliness of the information can be used to help predict the following words. We contrast this approach with an alternative machine learning approach proposed by Litman (1996). This paper also argues that discourse markers can be used to help the hearer predict the role that the upcoming utterance plays in the dialog. Thus discourse markers should provide valuable evidence for automatic dialog act prediction.

  17. Identifying motivational factors within a multinational company

    Directory of Open Access Journals (Sweden)

    Daniela Bradutanu

    2011-08-01

    Full Text Available The aim of the study is to identify the main motivational factors within a multinational company. The first objective is to identify work functions, formulated on Abraham Maslow’s pyramid, following the identification of the key characteristics that motivate an employee at the work place and last, but not least, the type of motivation that employees focus, intrinsic or extrinsic. The research method targeted a questionnaire based survey, including various company employees and an interview with the manager. The results confirmed that in Romania, employees put great emphasis on extrinsic motivation, a certain income and job security being primary. These results have implications for managers that in order to effectively motivate staff, first, must know their needs and expectations. To identify the main needs and motivational factors we had as a starting point Maslow's pyramid.

  18. Global identifiability of linear structural equation models

    CERN Document Server

    Drton, Mathias; Sullivant, Seth

    2010-01-01

    Structural equation models are multivariate statistical models that are defined by specifying noisy functional relationships among random variables. We consider the classical case of linear relationships and additive Gaussian noise terms. We give a necessary and sufficient condition for global identifiability of the model in terms of a mixed graph encoding the linear structural equations and the correlation structure of the error terms. Global identifiability is understood to mean injectivity of the parametrization of the model and is fundamental in particular for applicability of standard statistical methodology.

  19. Molecular Fingerprints to Identify Candida Species

    Directory of Open Access Journals (Sweden)

    Claudia Spampinato

    2013-01-01

    Full Text Available A wide range of molecular techniques have been developed for genotyping Candida species. Among them, multilocus sequence typing (MLST and microsatellite length polymorphisms (MLP analysis have recently emerged. MLST relies on DNA sequences of internal regions of various independent housekeeping genes, while MLP identifies microsatellite instability. Both methods generate unambiguous and highly reproducible data. Here, we review the results achieved by using these two techniques and also provide a brief overview of a new method based on high-resolution DNA melting (HRM. This method identifies sequence differences by subtle deviations in sample melting profiles in the presence of saturating fluorescent DNA binding dyes.

  20. Identifying, analysing and solving problems in practice.

    Science.gov (United States)

    Hewitt-Taylor, Jaqui

    When a problem is identified in practice, it is important to clarify exactly what it is and establish the cause before seeking a solution. This solution-seeking process should include input from those directly involved in the problematic situation, to enable individuals to contribute their perspective, appreciate why any change in practice is necessary and what will be achieved by the change. This article describes some approaches to identifying and analysing problems in practice so that effective solutions can be devised. It includes a case study and examples of how the Five Whys analysis, fishbone diagram, problem tree analysis, and Seven-S Model can be used to analyse a problem.

  1. Minimal covariant observables identifying all pure states

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio, E-mail: claudio.carmeli@gmail.com [D.I.M.E., Università di Genova, Via Cadorna 2, I-17100 Savona (Italy); I.N.F.N., Sezione di Genova, Via Dodecaneso 33, I-16146 Genova (Italy); Heinosaari, Teiko, E-mail: teiko.heinosaari@utu.fi [Turku Centre for Quantum Physics, Department of Physics and Astronomy, University of Turku (Finland); Toigo, Alessandro, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy); I.N.F.N., Sezione di Milano, Via Celoria 16, I-20133 Milano (Italy)

    2013-09-02

    It has been recently shown by Heinosaari, Mazzarella and Wolf (2013) [1] that an observable that identifies all pure states of a d-dimensional quantum system has minimally 4d−4 outcomes or slightly less (the exact number depending on d). However, no simple construction of this type of minimal observable is known. We investigate covariant observables that identify all pure states and have minimal number of outcomes. It is shown that the existence of this kind of observables depends on the dimension of the Hilbert space.

  2. Methods of Identifying and Preventing SQL Attacks

    Directory of Open Access Journals (Sweden)

    Bojken Shehu

    2012-11-01

    Full Text Available The paper begins by identifying the organizations which are vulnerable to the SQL attack referred to as an SQL injection attack. The term SQL injection attack is defined and a diagram is used to illustrate the way that attack occurs. In another section, the paper identifies the methods used to detect an attack to SQL, whereby the techniques are discussed extensively using relevant diagrams for illustration. The other sections cover the preventive methods, where the methods are also discussed with an illustration using diagrams.

  3. Diagnostics Tools Identify Faults Prior to Failure

    Science.gov (United States)

    2013-01-01

    Through the SBIR program, Rochester, New York-based Impact Technologies LLC collaborated with Ames Research Center to commercialize the Center s Hybrid Diagnostic Engine, or HyDE, software. The fault detecting program is now incorporated into a software suite that identifies potential faults early in the design phase of systems ranging from printers to vehicles and robots, saving time and money.

  4. Identifying motifs in folktales using topic models

    NARCIS (Netherlands)

    Karsdorp, F.; Bosch, A.P.J. van den

    2013-01-01

    With the undertake of various folktale digitalization initiatives, the need for computational aids to explore these collections is increasing. In this paper we compare Labeled LDA (L-LDA) to a simple retrieval model on the task of identifying motifs in folktales. We show that both methods are well a

  5. Teaching science students to identify entrepreneurial opportunities

    NARCIS (Netherlands)

    Nab, J.

    2015-01-01

    This dissertation describes a research project on teaching science students to identify entrepreneurial opportunities, which is a core competence for entrepreneurs that should be emphasized in education. This research consists of four studies. The first case study aims at finding design strategies f

  6. Professional Development: Identifying Effective Instructional Coaching Activities

    Science.gov (United States)

    Mannino, Gina

    2014-01-01

    The purpose of this study was to identify the instructional coaching activities most used by instructional coaches in southeast Texas school districts and to test if there was a relationship between the use of instructional coaching and perceived improvement in the instructional practices of teachers and student achievement. The participants for…

  7. Identifying Protein-Calorie Malnutrition Workshop.

    Science.gov (United States)

    Walker, Susan S.; Barker, Ellen M.

    Instructional materials are provided for a workshop to enable participants to assist in identifying patients at risk with protein-calorie malnutrition and in corrrecting this nutritional deficiency. Representative topics are nutrients; protein, mineral, and vitamin sources, functions, and deficiency symptoms; malnutrition; nutritional deficiency…

  8. Identifying personal microbiomes using metagenomic codes.

    Science.gov (United States)

    Franzosa, Eric A; Huang, Katherine; Meadow, James F; Gevers, Dirk; Lemon, Katherine P; Bohannan, Brendan J M; Huttenhower, Curtis

    2015-06-02

    Community composition within the human microbiome varies across individuals, but it remains unknown if this variation is sufficient to uniquely identify individuals within large populations or stable enough to identify them over time. We investigated this by developing a hitting set-based coding algorithm and applying it to the Human Microbiome Project population. Our approach defined body site-specific metagenomic codes: sets of microbial taxa or genes prioritized to uniquely and stably identify individuals. Codes capturing strain variation in clade-specific marker genes were able to distinguish among 100s of individuals at an initial sampling time point. In comparisons with follow-up samples collected 30-300 d later, ∼30% of individuals could still be uniquely pinpointed using metagenomic codes from a typical body site; coincidental (false positive) matches were rare. Codes based on the gut microbiome were exceptionally stable and pinpointed >80% of individuals. The failure of a code to match its owner at a later time point was largely explained by the loss of specific microbial strains (at current limits of detection) and was only weakly associated with the length of the sampling interval. In addition to highlighting patterns of temporal variation in the ecology of the human microbiome, this work demonstrates the feasibility of microbiome-based identifiability-a result with important ethical implications for microbiome study design. The datasets and code used in this work are available for download from huttenhower.sph.harvard.edu/idability.

  9. National Board Certification Identifies Strong Teachers

    Science.gov (United States)

    Education Digest: Essential Readings Condensed for Quick Review, 2009

    2009-01-01

    Advanced certification through the National Board for Professional Teaching Standards (NBPTS) is an effective way to identify highly skilled teachers, according to a congressionally mandated report from the National Research Council. Students taught by NBPTS-certified teachers make greater gains on achievement tests than students taught by…

  10. Identifying the Multiple Intelligences of Your Students

    Science.gov (United States)

    McClellan, Joyce A.; Conti, Gary J.

    2008-01-01

    One way of addressing individual differences among adult learners is to identify the Multiple Intelligences of the learner. Multiple Intelligences refers to the concept developed by Howard Gardner that challenges the traditional view of intelligence and explains the presence of nine different Multiple Intelligences. The purpose of this study was…

  11. Identifying Teaching Methods that Engage Entrepreneurship Students

    Science.gov (United States)

    Balan, Peter; Metcalfe, Mike

    2012-01-01

    Purpose: Entrepreneurship education particularly requires student engagement because of the complexity of the entrepreneurship process. The purpose of this paper is to describe how an established measure of engagement can be used to identify relevant teaching methods that could be used to engage any group of entrepreneurship students.…

  12. Identifying Ethical Hypernorms for Accounting Educators

    Science.gov (United States)

    Siegel, Philip H.; Mintz, Steven; Naser-Tavakolian, Mohsen; O'Shaughnessy, John

    2012-01-01

    Accounting educators have a unique role in academe because students learn about codes of ethics that will guide their actions as professionals. We identify hypernorms related to internal auditing educators that reflect unethical behaviors believed to be universally unacceptable by that community. We then compare the results to a prior survey of…

  13. Identifying systematic DFT errors in catalytic reactions

    DEFF Research Database (Denmark)

    Christensen, Rune; Hansen, Heine Anton; Vegge, Tejs

    2015-01-01

    Using CO2 reduction reactions as examples, we present a widely applicable method for identifying the main source of errors in density functional theory (DFT) calculations. The method has broad applications for error correction in DFT calculations in general, as it relies on the dependence...

  14. Automatically identifying periodic social events from Twitter

    NARCIS (Netherlands)

    Kunneman, F.A.; Bosch, A.P.J. van den

    2015-01-01

    Many events referred to on Twitter are of a periodic nature, characterized by roughly constant time intervals in between occurrences. Examples are annual music festivals, weekly television programs, and the full moon cycle. We propose a system that can automatically identify periodic events from Twi

  15. Identifying Benefit Segments among College Students.

    Science.gov (United States)

    Brown, Joseph D.

    1991-01-01

    Using concept of market segmentation (dividing market into distinct groups requiring different product benefits), surveyed 398 college students to determine benefit segments among students selecting a college to attend and factors describing each benefit segment. Identified one major segment of students (classroomers) plus three minor segments…

  16. Identify Your Brand, Before You Market.

    Science.gov (United States)

    Claggett, Laura

    2002-01-01

    Discusses marketing in special libraries and suggests that librarians need to identify library services that set them apart from others. Highlights include the competitive environment and alternatives for the consumer; value that the library offers; targeting consumers; return on investment; and determining why consumers choose your services. (LRW)

  17. The external muon identifier (EMI) for BEBC

    CERN Multimedia

    1977-01-01

    This detector identifies muons produced in neutrino interactions in BEBC. Whereas hadrons are absorbed in the iron shield around BEBC, muons penetrate and are detected in a 150 m2 layer of proportional chambers, each equipped with three sensitive planes, i.e. two anode wire and one cathode plane.

  18. Zebrafish phenotypic screen identifies novel Notch antagonists.

    Science.gov (United States)

    Velaithan, Vithya; Okuda, Kazuhide Shaun; Ng, Mei Fong; Samat, Norazwana; Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Shaari, Khozirah; Cheong, Sok Ching; Tan, Pei Jean; Patel, Vyomesh

    2017-04-01

    Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27(KIP1). Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.

  19. Identifying the Rhetoric of Uncertainty Reduction.

    Science.gov (United States)

    Williams, David E.

    Offering a rhetorical perspective of uncertainty reduction, this paper (1) discusses uncertainty reduction theory and dramatism; (2) identifies rhetorical strategies inherent in C. W. Berger and R. J. Calabrese's theory; (3) extends predicted outcome value to influenced outcome value; and (4) argues that the goal of uncertainty reduction and…

  20. Identifying Mentors for Student Employees on Campus

    Science.gov (United States)

    Frock, David

    2015-01-01

    Purpose: This exploratory research project aims to seek an effective process for identifying supervisors of part-time student employees who also serve in a mentoring capacity. Design/methodology/approach: This paper is based on a review of literature and an evaluation process focused on established traits and functions of mentoring as applied to…

  1. Systematic Determination of Human Cyclin Dependent Kinase (CDK)-9 Interactome Identifies Novel Functions in RNA Splicing Mediated by the DEAD Box (DDX)-5/17 RNA Helicases.

    Science.gov (United States)

    Yang, Jun; Zhao, Yingxin; Kalita, Mridul; Li, Xueling; Jamaluddin, Mohammad; Tian, Bing; Edeh, Chukwudi B; Wiktorowicz, John E; Kudlicki, Andrzej; Brasier, Allan R

    2015-10-01

    Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 complex in unstimulated cells and from cells activated by a synthetic dsRNA, polyinosinic/polycytidylic acid [poly (I:C)]. 245 CDK9 interacting proteins were identified with high confidence in the basal state and 20 proteins in four functional classes were validated by IP-SRM-MS. These data identified that CDK9 interacts with DDX 5/17, a family of ATP-dependent RNA helicases, important in alternative RNA splicing of NFAT5, and mH2A1 mRNA two proteins controlling redox signaling. A direct comparison of the basal versus activated state was performed using stable isotope labeling and validated by IP-SRM-MS. Recruited into the CDK9 interactome in response to poly(I:C) stimulation are HSPB1, DNA dependent kinases, and cytoskeletal myosin proteins that exchange with 60S ribosomal structural proteins. An integrated human CDK9 interactome map was developed containing all known human CDK9- interacting proteins. These data were used to develop a probabilistic global map of CDK9-dependent target genes that predicted two functional states controlling distinct cellular functions, one important in immune and stress responses. The CDK9-DDX5/17 complex was shown to be functionally important by shRNA-mediated knockdown, where differential accumulation of alternatively spliced NFAT5 and mH2A1 transcripts and alterations in downstream redox signaling were seen. The requirement of CDK9 for DDX5 recruitment to NFAT5 and mH2A1

  2. Where to look when identifying roadkilled amphibians?

    Directory of Open Access Journals (Sweden)

    Marc Franch

    2015-12-01

    Full Text Available Roads have multiple effects on wildlife; amphibians are one of the groups more intensely affected by roadkills. Monitoring roadkills is expensive and time consuming. Automated mapping systems for detecting roadkills, based on robotic computer vision techniques, are largely necessary. Amphibians can be recognised by a set of features as shape, size, colouration, habitat and location. This species identification by using multiple features at the same time is known as “jizz”. In a similar way to human vision, computer vision algorithms must incorporate a prioritisation process when analysing the objects in an image. Our main goal here was to give a numerical priority sequence of particular characteristics of roadkilled amphibians to improve the computing and learning process of algorithms. We asked hundred and five amateur and professional herpetologists to answer a simple test of five sets with ten images each of roadkilled amphibians, in order to determine which body parts or characteristics (body form, colour, and other patterns are used to identify correctly the species. Anura was the group most easily identified when it was roadkilled and Caudata was the most difficult. The lower the taxonomic level of amphibian, the higher the difficulty of identifying them, both in Anura and Caudata. Roadkilled amphibians in general and Anura group were mostly identified by the Form, by the combination of Form and Colour, and finally by Colour. Caudata was identified mainly on Form and Colour and on Colour. Computer vision algorithms must incorporate these combinations of features, avoiding to work exclusively in one specific feature.

  3. Data Identifiers and Citations Enable Reproducible Science

    Science.gov (United States)

    Tilmes, C.

    2011-12-01

    Modern science often involves data processing with tremendous volumes of data. Keeping track of that data has been a growing challenge for data center. Researchers who access and use that data don't always reference and cite their data sources adequately for consumers of their research to follow their methodology or reproduce their analyses or experiments. Recent research has led to recommendations for good identifiers and citations that can help address this problem. This paper will describe some of the best practices in data identifiers, reference and citation. Using a simplified example scenario based on a long term remote sensing satellite mission, it will explore issues in identifying dynamic data sets and the importance of good data citations for reproducibility. It will describe the difference between granule and collection level identifiers, using UUIDs and DOIs to illustrate some recommendations for developing identifiers and assigning them during data processing. As data processors create data products, the provenance of the input products and precise steps that led to their creation are recorded and published for users of the data to see. As researchers access the data from an archive, they can use the provenance to help understand the genesis of the data, which could have effects on their usage of the data. By citing the data on publishing their research, others can retrieve the precise data used in their research and reproduce the analyses and experiments to confirm the results. Describing the experiment to a sufficient extent to reproduce the research enforces a formal approach that lends credibility to the results, and ultimately, to the policies of decision makers depending on that research.

  4. Identifying confounders using additive noise models

    CERN Document Server

    Janzing, Dominik; Mooij, Joris; Schoelkopf, Bernhard

    2012-01-01

    We propose a method for inferring the existence of a latent common cause ('confounder') of two observed random variables. The method assumes that the two effects of the confounder are (possibly nonlinear) functions of the confounder plus independent, additive noise. We discuss under which conditions the model is identifiable (up to an arbitrary reparameterization of the confounder) from the joint distribution of the effects. We state and prove a theoretical result that provides evidence for the conjecture that the model is generically identifiable under suitable technical conditions. In addition, we propose a practical method to estimate the confounder from a finite i.i.d. sample of the effects and illustrate that the method works well on both simulated and real-world data.

  5. Wham: Identifying Structural Variants of Biological Consequence.

    Directory of Open Access Journals (Sweden)

    Zev N Kronenberg

    2015-12-01

    Full Text Available Existing methods for identifying structural variants (SVs from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham, with documentation on a wiki (http://zeeev.github.io/wham/. For community support please post questions to https://www.biostars.org/.

  6. Identifiability of linear systems in physical coordinates

    Science.gov (United States)

    Su, Tzu-Jeng; Juang, Jer-Nan

    1992-01-01

    Identifiability of linear, time-invariant systems in physical coordinates is discussed. It is shown that identification of the system matrix in physical coordinates can be accomplished by determining a transformation matrix that relates the physical locations of actuators and sensors to the test-data-derived input and output matrices. For systems with symmetric matrices, the solution of a constrained optimization problem is used to characterize all the possible solutions of the transformation matrix. Conditions for the existence of a unique transformation matrix are established easily from the explicit form of the solutions. For systems with limited inputs and outputs, the question about which part of the system can be uniquely identified is also answered. A simple mass-spring system is used to verify the conclusions of this study.

  7. An Xpert screen to identify carbapenemases

    Directory of Open Access Journals (Sweden)

    Mubin Kazi

    2016-01-01

    Full Text Available To prevent the spread of carbapenemases-producing Enterobacteriaceae (CPE active surveillance, contact isolation and cohorting infected patients should be practiced. Rectal swabs for the Xpert MDRO-assay of 32 patients were included. 71.85% were positive for targets incorporated into the MDRO-assay; whereas 28% were phenotypically not CRE and Xpert negative (9.37% had different mechanism [bla OXA]. The assay identified 59.3%, 9.37% and 3.1% as bla NDM, bla NDM+VIM and bla VIM, respectively. The assay is a screening test that identifies CPE harbouring organism within an hour and can be installed at tertiary-care facilities to screen colonized patients.

  8. Trustworthy persistent identifier systems of the future

    Science.gov (United States)

    Golodoniuc, Pavel; Klump, Jens; Car, Nicholas

    2016-04-01

    Over the last two decades, persistent identifier (PID) systems have seen some significant changes in their governance policies, system capabilities, and technology. The development of most systems was driven by two main application areas, namely archives and libraries. Guidelines and criteria for trustworthy PID systems have been clearly devised (Bütikofer, 2009) and many PID system implementations for the identification of static digital objects have been built (e.g., PURL). However systems delivering persistent identifiers for dynamic datasets are not yet mature. There has been a rapid proliferation of different PID systems caused by the specific technical or organisational requirements of various communities that could not be met by existing systems such as DOI, ISBN, and EAN. Many of these different systems were limited by their inability to provide native means of persistent identifier resolution. This has prompted a decoupling of PID-associated data from the resolution service and this is where the Handle system has played a significant role. The Handle allowed to build a distributed system of independently managed resolver services. A trustworthy PID system must be designed to outlive the objects it provides persistent identifiers for, which may cease to exist or otherwise be deprecated, and the technology used to implement it, which will certainly need to change with time. We propose that such a system should rest on four pillars of agreements - (i) definitions, (ii) policies, (iii) services, and (iv) data services, to ensure longevity. While we believe all four pillars are equally important, we intentionally leave regulating aspects of issuing of identifiers and their registration out of the scope of this paper and focus on the agreements that have to be established between PID resolver services and the data sources indicated by the persistent identifiers. We propose an approach to development of PID systems that combines the use of (a) the Handle system

  9. Identifying the Isomorphism of Kinematic Chains

    Directory of Open Access Journals (Sweden)

    Romaniak Krystyna

    2016-09-01

    Full Text Available Identification of isomorphic kinematic chains is one of the key issues in researching the structure of mechanisms. As a result the structures which duplicate are eliminated and further research is carried out on kinematic chains that do not duplicate. This dilemma has been taken up by many scholars who have come up with a variety of ideas how to solve it. The review of the methods for identifying the isomorphism of kinematic chains suggested by researchers is contained in this study, including Hamming Number Technique, eigenvalues and eigenvectors, perimeter graphs, dividing and matching vertices. The spectrum of methods applied to the issue of identifying the iso-morphism of mechanisms reflects the researchers’ efforts to obtain a precise result in the shortest time possible.

  10. Identifying pelagic ecosystem indicators for management

    DEFF Research Database (Denmark)

    Trenkel, Verena; Hintzen, Niels; Rindorf, Anna

    2013-01-01

    to pelagic fisheries to further explore the setting of management objectives. The objectives were identified through a participatory process including industry, management, scientist and NGO representatives. These objectives were used to identify appropriate driver, pressure and state indicators. The links......When exploiting fish populations under the ecosystem approach, aiming for MSY is not necessarily sufficient to ensure wider ecosystem sustainability. All of the large stocks of pelagic fish are managed through harvest control rules based on an MSY approach. Ensuring good environmental status...... will probably require further constraints to be imposed by management. Most of the current paradigm with regards to GES for fisheries has been based on demersal fish. Pelagic fisheries and fish are operationally and biologically respectively different. We use the example of applying the ecosystem approach...

  11. Wham: Identifying Structural Variants of Biological Consequence.

    Science.gov (United States)

    Kronenberg, Zev N; Osborne, Edward J; Cone, Kelsey R; Kennedy, Brett J; Domyan, Eric T; Shapiro, Michael D; Elde, Nels C; Yandell, Mark

    2015-12-01

    Existing methods for identifying structural variants (SVs) from short read datasets are inaccurate. This complicates disease-gene identification and efforts to understand the consequences of genetic variation. In response, we have created Wham (Whole-genome Alignment Metrics) to provide a single, integrated framework for both structural variant calling and association testing, thereby bypassing many of the difficulties that currently frustrate attempts to employ SVs in association testing. Here we describe Wham, benchmark it against three other widely used SV identification tools-Lumpy, Delly and SoftSearch-and demonstrate Wham's ability to identify and associate SVs with phenotypes using data from humans, domestic pigeons, and vaccinia virus. Wham and all associated software are covered under the MIT License and can be freely downloaded from github (https://github.com/zeeev/wham), with documentation on a wiki (http://zeeev.github.io/wham/). For community support please post questions to https://www.biostars.org/.

  12. Persistent Identifiers for Dutch cultural heritage institutions

    Science.gov (United States)

    Ras, Marcel; Kruithof, Gijsbert

    2016-04-01

    Over the past years, more and more collections belonging to archives, libraries, media, museums, and knowledge institutes are being digitised and made available online. These are exciting times for ALM institutions. They are realising that, in the information society, their collections are goldmines. Unfortunately most heritage institutions in the Netherlands do not yet meet the basic preconditions for long-term availability of their collections. The digital objects often have no long lasting fixed reference yet. URL's and web addresses change. Some digital objects that were referenced in Europeana and other portals can no longer be found. References in scientific articles have a very short life span, which is damaging for scholarly research. In 2015, the Dutch Digital Heritage Network (NDE) has started a two-year work program to co-ordinate existing initiatives in order to improve the (long-term) accessibility of the Dutch digital heritage for a wide range of users, anytime, anyplace. The Digital Heritage Network is a partnership established on the initiative of the Ministry of Education, Culture and Science. The members of the NDE are large, national institutions that strive to professionally preserve and manage digital data, e.g. the National Library, The Netherlands Institute for Sound and Vision, the Netherlands Cultural Heritage Agency, the Royal Netherlands Academy of Arts and Sciences, the National Archive of the Netherlands and the DEN Foundation, and a growing number of associations and individuals both within and outside the heritage sector. By means of three work programmes the goals of the Network should be accomplished and improve the visibility, the usability and the sustainability of digital heritage. Each programme contains of a set of projects. Within the sustainability program a project on creating a model for persistent identifiers is taking place. The main goals of the project are (1) raise awareness among cultural heritage institutions on the

  13. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.

    2012-05-15

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.

  14. Identifying Hearing Loss by Means of Iridology

    OpenAIRE

    Stearn, Natalie; Swanepoel, De Wet

    2006-01-01

    Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without ...

  15. High pt identified particle production in ALICE

    CERN Document Server

    Christiansen, Peter

    2013-01-01

    The ALICE experiment is a dedicated heavy ion physics detector at the LHC with unique capabilities for studying identified particle production. In this proceeding preliminary results for RAA for pi and K+p (sum), are reported, based on measurements in pp at sqrt(s) = 2.76 TeV and Pb-Pb at sqrt(sNN) = 2.76 TeV. The results are compared to theoretical predictions and measurements at RHIC.

  16. The Complexity of Identifying Large Equivalence Classes

    DEFF Research Database (Denmark)

    Skyum, Sven; Frandsen, Gudmund Skovbjerg; Miltersen, Peter Bro

    1999-01-01

    We prove that at least 3k−4/k(2k−3)(n/2) – O(k)equivalence tests and no more than 2/k (n/2) + O(n) equivalence tests are needed in the worst case to identify the equivalence classes with at least k members in set of n elements. The upper bound is an improvement by a factor 2 compared to known res...

  17. Identifying excessive credit growth and leverage

    OpenAIRE

    Alessi, Lucia; Detken, Carsten

    2014-01-01

    This paper aims at providing policymakers with a set of early warning indicators helpful in guiding decisions on when to activate macroprudential tools targeting excessive credit growth and leverage. To robustly select the key indicators we apply the “Random Forest” method, which bootstraps and aggregates a multitude of decision trees. On these identified key indicators we grow a binary classification tree which derives the associated optimal early warning thresholds. By using credit to GDP g...

  18. Identifying the Universal part of TMDs

    CERN Document Server

    Van der Veken, F F

    2016-01-01

    We attempt to identify a path layout in the definition of transverse-momentum-dependent T-odd parton distribution functions (TMD)s which combines features of both, initial- and final-state interactions, so that it remains universal despite the fact that the Wilson lines entering such TMDs change their orientation. The generic structure of the quark correlator for this path layout is calculated.

  19. Identifying Topics in Microblogs Using Wikipedia.

    Science.gov (United States)

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail.

  20. Data Identifiers, Versioning, and Micro-citation

    Science.gov (United States)

    Parsons, M. A.; Duerr, R. E.

    2012-12-01

    Data citation, especially using Digital Object Identifiers (DOIs), is an increasingly accepted scientific practice. For example, the AGU Council asserts that data "publications" should "be credited and cited like the products of any other scientific activity," and Thomson Reuters has recently announced a data citation index built from DOIs assigned to data sets. Correspondingly, formal guidelines for how to cite a data set (using DOIs or similar identifiers/locators) have recently emerged, notably those from the international DataCite consortium, the UK Digital Curation Centre, and the US Federation of Earth Science Information Partners. These different data citation guidelines are largely congruent. They agree on the basic practice and elements of data citation, especially for relatively static, whole data collections. There is less agreement on some of the more subtle nuances of data citation. They define different methods for handling different data set versions, especially for the very dynamic, growing data sets that are common in Earth Sciences. They also differ in how people should cite specific, arbitrarily large elements, "passages," or subsets of a larger data collection, i.e., the precise data records actually used in a study. This detailed "micro-citation", and careful reference to exact versions of data are essential to ensure scientific reproducibility. Identifiers such as DOIs are necessary but not sufficient for the precise, detailed, references necessary. Careful practice must be coupled with the use of curated identifiers. In this paper we review the pros and cons of different approaches to versioning and micro-citation. We suggest a workable solution for most existing Earth science data and suggest a more rigorous path forward for the future.

  1. Identifying familiar strangers in human encounter networks

    Science.gov (United States)

    Liang, Di; Li, Xiang; Zhang, Yi-Qing

    2016-10-01

    Familiar strangers, pairs of individuals who encounter repeatedly but never know each other, have been discovered for four decades yet lack an effective method to identify. Here we propose a novel method called familiar stranger classifier (FSC) to identify familiar strangers from three empirical datasets, and classify human relationships into four types, i.e., familiar stranger (FS), in-role (IR), friend (F) and stranger (S). The analyses of the human encounter networks show that the average number of FS one may encounter is finite but larger than the Dunbar Number, and their encounters are structurally more stable and denser than those of S, indicating the encounters of FS are not limited by the social capacity, and more robust than the random scenario. Moreover, the temporal statistics of encounters between FS over the whole time span show strong periodicity, which are diverse from the bursts of encounters within one day, suggesting the significance of longitudinal patterns of human encounters. The proposed method to identify FS in this paper provides a valid framework to understand human encounter patterns and analyse complex human social behaviors.

  2. Identifying differentially regulated subnetworks from phosphoproteomic data

    Directory of Open Access Journals (Sweden)

    Tebbe Andreas

    2010-06-01

    Full Text Available Abstract Background Various high throughput methods are available for detecting regulations at the level of transcription, translation or posttranslation (e.g. phosphorylation. Integrating these data with protein networks should make it possible to identify subnetworks that are significantly regulated. Furthermore, such integration can support identification of regulated entities from often noisy high throughput data. In particular, processing mass spectrometry-based phosphoproteomic data in this manner may expose signal transduction pathways and, in the case of experiments with drug-treated cells, reveal the drug's mode of action. Results Here, we introduce SubExtractor, an algorithm that combines phosphoproteomic data with protein network information from STRING to identify differentially regulated subnetworks and individual proteins. The method is based on a Bayesian probabilistic model combined with a genetic algorithm and rigorous significance testing. The Bayesian model accounts for information about both differential regulation and network topology. The method was tested with artificial data and subsequently applied to a comprehensive phosphoproteomics study investigating the mode of action of sorafenib, a small molecule kinase inhibitor. Conclusions SubExtractor reliably identifies differentially regulated subnetworks from phosphoproteomic data by integrating protein networks. The method can also be applied to gene or protein expression data.

  3. Identifiability of large phylogenetic mixture models.

    Science.gov (United States)

    Rhodes, John A; Sullivant, Seth

    2012-01-01

    Phylogenetic mixture models are statistical models of character evolution allowing for heterogeneity. Each of the classes in some unknown partition of the characters may evolve by different processes, or even along different trees. Such models are of increasing interest for data analysis, as they can capture the variety of evolutionary processes that may be occurring across long sequences of DNA or proteins. The fundamental question of whether parameters of such a model are identifiable is difficult to address, due to the complexity of the parameterization. Identifiability is, however, essential to their use for statistical inference.We analyze mixture models on large trees, with many mixture components, showing that both numerical and tree parameters are indeed identifiable in these models when all trees are the same. This provides a theoretical justification for some current empirical studies, and indicates that extensions to even more mixture components should be theoretically well behaved. We also extend our results to certain mixtures on different trees, using the same algebraic techniques.

  4. Persistent Identifiers, Discoverability and Open Science (Communication)

    Science.gov (United States)

    Murphy, Fiona; Lehnert, Kerstin; Hanson, Brooks

    2016-04-01

    Early in 2016, the American Geophysical Union announced it was incorporating ORCIDs into its submission workflows. This was accompanied by a strong statement supporting the use of other persistent identifiers - such as IGSNs, and the CrossRef open registry 'funding data'. This was partly in response to funders' desire to track and manage their outputs. However the more compelling argument, and the reason why the AGU has also signed up to the Center for Open Science's Transparency and Openness Promotion (TOP) Guidelines (http://cos.io/top), is that ultimately science and scientists will be the richer for these initiatives due to increased opportunities for interoperability, reproduceability and accreditation. The AGU has appealed to the wider community to engage with these initiatives, recognising that - unlike the introduction of Digital Object Identifiers (DOIs) for articles by CrossRef - full, enriched use of persistent identifiers throughout the scientific process requires buy-in from a range of scholarly communications stakeholders. At the same time, across the general research landscape, initiatives such as Project CRediT (contributor roles taxonomy), Publons (reviewer acknowledgements) and the forthcoming CrossRef DOI Event Tracker are contributing to our understanding and accreditation of contributions and impact. More specifically for earth science and scientists, the cross-functional Coalition for Publishing Data in the Earth and Space Sciences (COPDESS) was formed in October 2014 and is working to 'provide an organizational framework for Earth and space science publishers and data facilities to jointly implement and promote common policies and procedures for the publication and citation of data across Earth Science journals'. Clearly, the judicious integration of standards, registries and persistent identifiers such as ORCIDs and International Geo Sample Numbers (IGSNs) to the research and research output processes is key to the success of this venture

  5. Body linear traits for identifying prolific goats

    Directory of Open Access Journals (Sweden)

    Avijit Haldar

    2014-12-01

    Full Text Available Aim: The present study was conducted on prolific goat breed to identify body linear type traits that might be associated with prolificacy trait in goats. Materials and Methods: Two-stage stratified random sample survey based data were collected from 1427 non-pregnant goats with the history of single, twin and triplet litter sizes (LZ between January 2008 to February 2011 for 3 years in 68 villages located in East and North East India. Data on sixteen body linear traits were analyzed using logistic regression model to do the step-wise selection for identifying the body linear traits that could determine LZ. An average value for each identified body linear trait was determined for classifying the goats into three categories: Goats having the history of single LZ, goats having the history of twin LZ and goats having the history of triplet LZ. Results: The LZ proportions for single, twin and triplet, were 29.50, 59.14 and 11.36%, respectively, with the prolificacy rate of 181.85% in Indian Black Bengal goats. A total of eight body linear traits that could determine LZ in prolific goats were identified. Heart girth (HG measurement (>60.90 cm, paunch girth (PG (>70.22 cm, wither height (WH (>49.75 cm, neck length (>21.45 cm, ear length (>12.80 cm and distance between trochanter major (DTM bones (>12.28 cm, pelvic triangle area (PTA (>572.25 cm2 and clearance at udder (CU (>23.16 cm showed an increase likelihood of multiple LZ when compared to single LZ. Further, HG measurement (>62.29 cm, WH (>50.54 cm, PG (>71.85 cm and ear length (>13.00 cm, neck length (>22.01 cm, PTA (>589.64 cm2, CU (>23.20 cm and DTM bones (>12.47 cm were associated with increased likelihood of triplet LZ, when compared with that of twin LZ. Conclusion: HG measurement was the best discriminating factor, while PG, neck length, DTM bones, CU, PTA, WH and ear length measurements were other important factors that could be used for identifying prolific goats to achieve economic

  6. CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

    Science.gov (United States)

    Hestand, Matthew S; van Galen, Michiel; Villerius, Michel P; van Ommen, Gert-Jan B; den Dunnen, Johan T; 't Hoen, Peter AC

    2008-01-01

    Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites) that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at . It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites. PMID:19036135

  7. Characterization of novel MSX1 mutations identified in Japanese patients with nonsyndromic tooth agenesis.

    Directory of Open Access Journals (Sweden)

    Seishi Yamaguchi

    Full Text Available Since MSX1 and PAX9 are linked to the pathogenesis of nonsyndromic tooth agenesis, we performed detailed mutational analysis of these two genes sampled from Japanese patients. We identified two novel MSX1 variants with an amino acid substitution within the homeodomain; Thr174Ile (T174I from a sporadic hypodontia case and Leu205Arg (L205R from a familial oligodontia case. Both the Thr174 and Leu205 residues in the MSX1 homeodomain are highly conserved among different species. To define possible roles of mutations at these amino acids in the pathogenesis of nonsyndromic tooth agenesis, we performed several functional analyses. It has been demonstrated that MSX1 plays a pivotal role in hard tissue development as a suppressor for mesenchymal cell differentiation. To evaluate the suppression activity of the variants in mesenchymal cells, we used the myoD-promoter, which is one of convenient reporter assay system for MSX1. Although the gene products of these MSX1 variants are stable and capable of normal nuclear localization, they do not suppress myoD-promoter activity in differentiated C2C12 cells. To clarify the molecular mechanisms underlying our results, we performed further analyses including electrophoretic mobility shift assays, and co-immunoprecipitation assays to survey the molecular interactions between the mutant MSX1 proteins and the oligonucleotide DNA with MSX1 consensus binding motif or EZH2 methyltransferase. Since EZH2 is reported to interact with MSX1 and regulate MSX1 mediated gene suppression, we hypothesized that the T174I and L205R substitutions would impair this interaction. We conclude from the results of our experiments that the DNA binding ability of MSX1 is abolished by these two amino acid substitutions. This illustrates a causative role of the T174I and L205R MSX1 homeodomain mutations in tooth agenesis, and suggests that they may influence cell proliferation and differentiation resulting in lesser tooth germ formation in

  8. Identifying and overcoming barriers to technology implementation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, M.; Warren, S.; McCune, M. [Dept. of Energy, Germantown, MD (United States)] [and others

    1996-12-31

    In a recent General Accounting Office report, the Department of Energy`s (DOE) Office of Environmental Management was found to be ineffective in integrating their environmental technology development efforts with the cleanup actions. As a result of these findings, a study of remediation documents was performed by the Technology Applications Team within DOE`s Office of Environmental Restoration (EM-40) to validate this finding and to understand why it was occurring. A second initiative built on the foundation of the remediation document study and evaluated solutions to the ineffective implementation of improved technologies. The Technology Applications Team examined over 50 remediation documents (17 projects) which included nearly 600 proposed remediation technologies. It was determined that very few technologies are reaching the Records of Decision documents. In fact, most are eliminated in the early stages of consideration. These observations stem from regulators` and stakeholders` uncertainties in cost and performance of the technology and the inability of the technology to meet site specific conditions. The Technology Applications Team also set out to identify and evaluate solutions to barriers to implementing innovative technology into the DOE`s environmental management activities. Through the combined efforts of DOE and the Hazardous Waste Action Coalition (HWAC), a full day workshop was conducted at the annual HWAC meeting in June 1995 to solve barriers to innovative technology implementation. Three barriers were identified as widespread throughout the DOE complex and industry. Identified barriers included a lack of verified or certified cost and performance data for innovative technologies; risk of failure to reach cleanup goals using innovative technologies; and communication barriers that are present at virtually every stage of the characterization/remediation process from development through implementation.

  9. Identifying Airborne Pathogens in Time to Respond

    Energy Technology Data Exchange (ETDEWEB)

    Hazi, A

    2006-01-25

    Among the possible terrorist activities that might threaten national security is the release of an airborne pathogen such as anthrax. Because the potential damage to human health could be severe, experts consider 1 minute to be an operationally useful time limit for identifying the pathogen and taking action. Many commercial systems can identify airborne pathogenic microbes, but they take days or, at best, hours to produce results. The Department of Homeland Security (DHS) and other U.S. government agencies are interested in finding a faster approach. To answer this national need, a Livermore team, led by scientist Eric Gard, has developed the bioaerosol mass spectrometry (BAMS) system--the only instrument that can detect and identify spores at low concentrations in less than 1 minute. BAMS can successfully distinguish between two related but different spore species. It can also sort out a single spore from thousands of other particles--biological and nonbiological--with no false positives. The BAMS team won a 2005 R&D 100 Award for developing the system. Livermore's Laboratory Directed Research and Development (LDRD) Program funded the biomedical aspects of the BAMS project, and the Department of Defense's Technical Support Working Group and Defense Advanced Research Project Agency funded the biodefense efforts. Developing a detection system that can analyze small samples so quickly has been challenging. Livermore engineer Vincent Riot, who worked on the BAMS project, explains, ''A typical spore weighs approximately one-trillionth of a gram and is dispersed in the atmosphere, which contains naturally occurring particles that could be present at concentrations thousands of times higher. Previous systems also had difficulty separating benign organisms from those that are pathogenic but very similar, which has resulted in false alarms''.

  10. Identifying single copy orthologs in Metazoa.

    Directory of Open Access Journals (Sweden)

    Christopher J Creevey

    2011-12-01

    Full Text Available The identification of single copy (1-to-1 orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified a robust set of 1,126 orthologous groups that have been retained in single copy since the last common ancestor of Metazoa. We found that the use of the phylogenetic procedure increased the number of single copy orthologs found by over a third more than standard taxon-count approaches. The orthologs represented a wide range of functional categories, expression profiles and levels of divergence.To demonstrate the value of our set of single copy orthologs, we used them to assess the completeness of 24 currently published metazoan genomes and 62 EST datasets. We found that the annotated genes in published genomes vary in coverage from 79% (Ciona intestinalis to 99.8% (human with an average of 92%, suggesting a value for the underlying error rate in genome annotation, and a strategy for identifying single copy orthologs in larger datasets. In contrast, the vast majority of EST datasets with no corresponding genome sequence available are largely under-sampled and probably do not accurately represent the actual genomic complement of the organisms from which they are derived.

  11. Identifying novel drug indications through automated reasoning.

    Directory of Open Access Journals (Sweden)

    Luis Tari

    Full Text Available BACKGROUND: With the large amount of pharmacological and biological knowledge available in literature, finding novel drug indications for existing drugs using in silico approaches has become increasingly feasible. Typical literature-based approaches generate new hypotheses in the form of protein-protein interactions networks by means of linking concepts based on their cooccurrences within abstracts. However, this kind of approaches tends to generate too many hypotheses, and identifying new drug indications from large networks can be a time-consuming process. METHODOLOGY: In this work, we developed a method that acquires the necessary facts from literature and knowledge bases, and identifies new drug indications through automated reasoning. This is achieved by encoding the molecular effects caused by drug-target interactions and links to various diseases and drug mechanism as domain knowledge in AnsProlog, a declarative language that is useful for automated reasoning, including reasoning with incomplete information. Unlike other literature-based approaches, our approach is more fine-grained, especially in identifying indirect relationships for drug indications. CONCLUSION/SIGNIFICANCE: To evaluate the capability of our approach in inferring novel drug indications, we applied our method to 943 drugs from DrugBank and asked if any of these drugs have potential anti-cancer activities based on information on their targets and molecular interaction types alone. A total of 507 drugs were found to have the potential to be used for cancer treatments. Among the potential anti-cancer drugs, 67 out of 81 drugs (a recall of 82.7% are indeed known cancer drugs. In addition, 144 out of 289 drugs (a recall of 49.8% are non-cancer drugs that are currently tested in clinical trials for cancer treatments. These results suggest that our method is able to infer drug indications (original or alternative based on their molecular targets and interactions alone and has

  12. Newly Identified Rydberg Emission Lines in Novae

    Science.gov (United States)

    Lynch, David K.; Rudy, R. J.; Bernstein, L. S.

    2008-09-01

    Newly Identified Rydberg Emission Lines in Novae David K. Lynch, Richard. J. Rudy (The Aerospace Corporation) & Lawrence S. Bernstein (Spectral Sciences, Inc.) Novae spectra in the near infrared frequently show a set of six emission lines that have not been positively identified (Williams, Longmore, & Geballe 1996, MNRAS, 279, 804; Lynch et al. 2001, AJ, 122, 2013; Rudy et al. 2002 ApJ, 573, 794; Lynch et al. 2004 Astron. J. 127, 1089-1097). These lines are at 0.8926, 1.1114, 1.1901, 1.5545, 2.0996 and 2.425 µm ± 0.005 µm. Krautter et al. (1984 A&A 137, 304) suggested that three of the lines were due to rydberg (hydrogenic) transitions in an unspecified atomic species that was in the 4th or 5th ionization stage (core charge = 4 & 5). We believe that Krautter et al.'s explanation is correct based on 4 additional lines that we have identified in the visible and near infrared spectrum of V723 Cassiopeiae. The observed Rydberg lines appear to originate from high angular momentum states with negligible quantum defects. The species cannot be determined with any certainty because in rydberg states, the outer electron sees a nucleus shielded by the inner electrons and together the inner atom appears to have a charge of +1, like hydrogen. As a result, the atom looks hydrogenic and species such as CV, NV, OV, MgV, SiV, etc. have their rydberg transitions at very similar wavelengths. All the lines represent permitted transitions, most likely formed by recombination. Atoms with core charges 4, 5 & 6 are rarely seen in the astrophysical environment because an extremely hot radiation field is necessary to ionize them. Thermonuclear runaways on the surface of a white dwarf can reach millions of degrees K, and thus there are enough X-ray photons available to achieve the necessary high ionization levels.

  13. Melanoma biomolecules: independently identified but functionally intertwined.

    Science.gov (United States)

    Dye, Danielle E; Medic, Sandra; Ziman, Mel; Coombe, Deirdre R

    2013-09-24

    The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (CSPG4), and paired box 3 (PAX3). The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology.

  14. Identifying Codes on Directed De Bruijn Graphs

    Science.gov (United States)

    2015-08-27

    2. 15. SUBJECT TERMS Identifying Code; De Bruijn Network; Graph Theory 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER...our assumption on T and our earlier reasoning . Since x 6= y, this means that ~B(d, n) contains both directed arcs x → y and y → x. This allows us to...G) so that f(s) = g(s) for all s ∈ S, then f(v) = g(v) for all v ∈ V (G). That is, every automorphism is completely determined by its action on a

  15. Identifying PHM market and network opportunities.

    Science.gov (United States)

    Grube, Mark E; Krishnaswamy, Anand; Poziemski, John; York, Robert W

    2015-11-01

    Two key processes for healthcare organizations seeking to assume a financially sustainable role in population health management (PHM), after laying the groundwork for the effort, are to identify potential PHM market opportunities and determine the scope of the PHM network. Key variables organizations should consider with respect to market opportunities include the patient population, the overall insurance/employer market, and available types of insurance products. Regarding the network's scope, organizations should consider both traditional strategic criteria for a viable network and at least five additional criteria: network essentiality and PHM care continuum, network adequacy, service distribution right-sizing, network growth strategy, and organizational agility.

  16. Identifying Phase Space Boundaries with Voronoi Tessellations

    CERN Document Server

    Debnath, Dipsikha; Kilic, Can; Kim, Doojin; Matchev, Konstantin T; Yang, Yuan-Pao

    2016-01-01

    Determining the masses of new physics particles appearing in decay chains is an important and longstanding problem in high energy phenomenology. Recently it has been shown that these mass measurements can be improved by utilizing the boundary of the allowed region in the fully differentiable phase space in its full dimensionality. Here we show that the practical challenge of identifying this boundary can be solved using techniques based on the geometric properties of the cells resulting from Voronoi tessellations of the relevant data. The robust detection of such phase space boundaries in the data could also be used to corroborate a new physics discovery based on a cut-and-count analysis.

  17. Method of identifying defective particle coatings

    Science.gov (United States)

    Cohen, Mark E.; Whiting, Carlton D.

    1986-01-01

    A method for identifying coated particles having defective coatings desig to retain therewithin a build-up of gaseous materials including: (a) Pulling a vacuum on the particles; (b) Backfilling the particles at atmospheric pressure with a liquid capable of wetting the exterior surface of the coated particles, said liquid being a compound which includes an element having an atomic number higher than the highest atomic number of any element in the composition which forms the exterior surface of the particle coating; (c) Drying the particles; and (d) Radiographing the particles. By television monitoring, examination of the radiographs is substantially enhanced.

  18. Cheater identifiable visual secret sharing scheme

    Institute of Scientific and Technical Information of China (English)

    Gan Zhi; Chen Kefei

    2005-01-01

    The visual secret sharing scheme proposed by Naor and Shamir provides a way to encrypt a secret black-white image into shares. A qualified group of participants can recover the secret message without using any cryptographic computation. But the original scheme can easily be corrupted by malicious participant. We propose an extension of VSS(visual secret sharing) to identify cheaters before the secret is recovered. Without the need for any additional information and cryptographic computation, every participant can verify the validity of shares of other participants, thus the security of VSS is enhanced.

  19. Identifying Synonymous Regulatory Elements in Vertebrate Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Ovcharenko, I; Nobrega, M A

    2005-02-07

    Synonymous gene regulation, defined as driving shared temporal and/or spatial expression of groups of genes, is likely predicated on genomic elements that contain similar modules of certain transcription factor binding sites (TFBS). We have developed a method to scan vertebrate genomes for evolutionary conserved modules of TFBS in a predefined configuration, and created a tool, named SynoR that identify synonymous regulatory elements (SREs) in vertebrate genomes. SynoR performs de novo identification of SREs utilizing known patterns of TFBS in active regulatory elements (REs) as seeds for genome scans. Layers of multiple-species conservation allow the use of differential phylogenetic sequence conservation filters in the search of SREs and the results are displayed as to provide an extensive annotation of genes containing detected REs. Gene Ontology categories are utilized to further functionally classify the identified genes, and integrated GNF Expression Atlas 2 data allow the cataloging of tissue-specificities of the predicted SREs. We illustrate how this new tool can be used to establish a linkage between human diseases and noncoding genomic content. SynoR is publicly available at http://synor.dcode.org.

  20. Identifying MMORPG Bots: A Traffic Analysis Approach

    Directory of Open Access Journals (Sweden)

    Wen-Chin Chen

    2008-11-01

    Full Text Available Massively multiplayer online role playing games (MMORPGs have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1 the regularity in the release time of client commands, 2 the trend and magnitude of traffic burstiness in multiple time scales, and 3 the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  1. Examining primacy as an identifier of salience.

    Science.gov (United States)

    Demorest, Amy; Gleckel, Jareb

    2014-08-01

    This article examines whether the first things people report in narrative accounts represent themes of particular importance to them. In two studies, college students recounted autobiographical memories in an interview setting (Study 1: N = 56; Mage = 19.4; 29 male, 27 female; 48.2% Caucasian, 17.9% Asian, 14.3% African American, 10.7% Hispanic/Latino; Study 2: N = 40; Mage = 18.7; 27 female, 13 male; 57.5% Caucasian, 15% Asian, 12.5% Hispanic/Latino, 7.5% African American). Participants reported happy and sad memories (Study 1) or memories of any emotional type (Study 2), and narrative themes were identified from these memories using standard categories of emotion-eliciting events. Study 2 included a follow-up task one month later in which participants rated the importance of these themes. The themes from the first memories recurred in subsequent memories significantly more often than would be expected by chance, and this recurrence was not a function of the order of memories, the participant's gender, or the type of theme. Furthermore, the themes from the first memories were rated as significantly more important than other themes in the follow-up task. These findings provide strong empirical evidence that primacy identifies important material in the context of narrative analysis.

  2. Identifying Bitcoin users by transaction behavior

    Science.gov (United States)

    Monaco, John V.

    2015-05-01

    Digital currencies, such as Bitcoin, offer convenience and security to criminals operating in the black marketplace. Some Bitcoin marketplaces, such as Silk Road, even claim anonymity. This claim contradicts the findings in this work, where long term transactional behavior is used to identify and verify account holders. Transaction timestamps and network properties observed over time contribute to this finding. The timestamp of each transaction is the result of many factors: the desire purchase an item, daily schedule and activities, as well as hardware and network latency. Dynamic network properties of the transaction, such as coin flow and the number of edge outputs and inputs, contribute further to reveal account identity. In this paper, we propose a novel methodology for identifying and verifying Bitcoin users based on the observation of Bitcoin transactions over time. The behavior we attempt to quantify roughly occurs in the social band of Newell's time scale. A subset of the Blockchain 230686 is taken, selecting users that initiated between 100 and 1000 unique transactions per month for at least 6 different months. This dataset shows evidence of being nonrandom and nonlinear, thus a dynamical systems approach is taken. Classification and authentication accuracies are obtained under various representations of the monthly Bitcoin samples: outgoing transactions, as well as both outgoing and incoming transactions are considered, along with the timing and dynamic network properties of transaction sequences. The most appropriate representations of monthly Bitcoin samples are proposed. Results show an inherent lack of anonymity by exploiting patterns in long-term transactional behavior.

  3. Identifying MMORPG Bots: A Traffic Analysis Approach

    Science.gov (United States)

    Chen, Kuan-Ta; Jiang, Jhih-Wei; Huang, Polly; Chu, Hao-Hua; Lei, Chin-Laung; Chen, Wen-Chin

    2008-12-01

    Massively multiplayer online role playing games (MMORPGs) have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1) the regularity in the release time of client commands, 2) the trend and magnitude of traffic burstiness in multiple time scales, and 3) the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  4. Identifying nonlinear biomechanical models by multicriteria analysis

    Science.gov (United States)

    Srdjevic, Zorica; Cveticanin, Livija

    2012-02-01

    In this study, the methodology developed by Srdjevic and Cveticanin (International Journal of Industrial Ergonomics 34 (2004) 307-318) for the nonbiased (objective) parameter identification of the linear biomechanical model exposed to vertical vibrations is extended to the identification of n-degree of freedom (DOF) nonlinear biomechanical models. The dynamic performance of the n-DOF nonlinear model is described in terms of response functions in the frequency domain, such as the driving-point mechanical impedance and seat-to-head transmissibility function. For randomly generated parameters of the model, nonlinear equations of motion are solved using the Runge-Kutta method. The appropriate data transformation from the time-to-frequency domain is performed by a discrete Fourier transformation. Squared deviations of the response functions from the target values are used as the model performance evaluation criteria, thus shifting the problem into the multicriteria framework. The objective weights of criteria are obtained by applying the Shannon entropy concept. The suggested methodology is programmed in Pascal and tested on a 4-DOF nonlinear lumped parameter biomechanical model. The identification process over the 2000 generated sets of parameters lasts less than 20 s. The model response obtained with the imbedded identified parameters correlates well with the target values, therefore, justifying the use of the underlying concept and the mathematical instruments and numerical tools applied. It should be noted that the identified nonlinear model has an improved accuracy of the biomechanical response compared to the accuracy of a linear model.

  5. Factor analysis identifies subgroups of constipation

    Institute of Scientific and Technical Information of China (English)

    Philip G Dinning; Mike Jones; Linda Hunt; Sergio E Fuentealba; Jamshid Kalanter; Denis W King; David Z Lubowski; Nicholas J Talley; Ian J Cook

    2011-01-01

    AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging selfreport questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.

  6. Identifying states of a financial market.

    Science.gov (United States)

    Münnix, Michael C; Shimada, Takashi; Schäfer, Rudi; Leyvraz, Francois; Seligman, Thomas H; Guhr, Thomas; Stanley, H Eugene

    2012-01-01

    The understanding of complex systems has become a central issue because such systems exist in a wide range of scientific disciplines. We here focus on financial markets as an example of a complex system. In particular we analyze financial data from the S&P 500 stocks in the 19-year period 1992-2010. We propose a definition of state for a financial market and use it to identify points of drastic change in the correlation structure. These points are mapped to occurrences of financial crises. We find that a wide variety of characteristic correlation structure patterns exist in the observation time window, and that these characteristic correlation structure patterns can be classified into several typical "market states". Using this classification we recognize transitions between different market states. A similarity measure we develop thus affords means of understanding changes in states and of recognizing developments not previously seen.

  7. Identifying States of a Financial Market

    Science.gov (United States)

    Münnix, Michael C.; Shimada, Takashi; Schäfer, Rudi; Leyvraz, Francois; Seligman, Thomas H.; Guhr, Thomas; Stanley, H. Eugene

    2012-09-01

    The understanding of complex systems has become a central issue because such systems exist in a wide range of scientific disciplines. We here focus on financial markets as an example of a complex system. In particular we analyze financial data from the S&P 500 stocks in the 19-year period 1992-2010. We propose a definition of state for a financial market and use it to identify points of drastic change in the correlation structure. These points are mapped to occurrences of financial crises. We find that a wide variety of characteristic correlation structure patterns exist in the observation time window, and that these characteristic correlation structure patterns can be classified into several typical ``market states''. Using this classification we recognize transitions between different market states. A similarity measure we develop thus affords means of understanding changes in states and of recognizing developments not previously seen.

  8. Identifying modular relations in complex brain networks

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Mørup, Morten; Siebner, Hartwig

    2012-01-01

    We evaluate the infinite relational model (IRM) against two simpler alternative nonparametric Bayesian models for identifying structures in multi subject brain networks. The models are evaluated for their ability to predict new data and infer reproducible structures. Prediction and reproducibility...... are measured within the data driven NPAIRS split-half framework. Using synthetic data drawn from each of the generative models we show that the IRM model outperforms the two competing models when data contain relational structure. For data drawn from the other two simpler models the IRM does not overfit...... and obtains comparable reproducibility and predictability. For resting state functional magnetic resonance imaging data from 30 healthy controls the IRM model is also superior to the two simpler alternatives, suggesting that brain networks indeed exhibit universal complex relational structure...

  9. Identifying Excessively Rounded or Truncated Data

    CERN Document Server

    Knuth, Kevin H; Wheeler, Kevin R

    2016-01-01

    All data are digitized, and hence are essentially integers rather than true real numbers. Ordinarily this causes no difficulties since the truncation or rounding usually occurs below the noise level. However, in some instances, when the instruments or data delivery and storage systems are designed with less than optimal regard for the data or the subsequent data analysis, the effects of digitization may be comparable to important features contained within the data. In these cases, information has been irrevocably lost in the truncation process. While there exist techniques for dealing with truncated data, we propose a straightforward method that will allow us to detect this problem before the data analysis stage. It is based on an optimal histogram binning algorithm that can identify when the statistical structure of the digitization is on the order of the statistical structure of the data set itself.

  10. Identifying links between origami and compliant mechanisms

    Directory of Open Access Journals (Sweden)

    H. C. Greenberg

    2011-12-01

    Full Text Available Origami is the art of folding paper. In the context of engineering, orimimetics is the application of folding to solve problems. Kinetic origami behavior can be modeled with the pseudo-rigid-body model since the origami are compliant mechanisms. These compliant mechanisms, when having a flat initial state and motion emerging out of the fabrication plane, are classified as lamina emergent mechanisms (LEMs. To demonstrate the feasibility of identifying links between origami and compliant mechanism analysis and design methods, four flat folding paper mechanisms are presented with their corresponding kinematic and graph models. Principles from graph theory are used to abstract the mechanisms to show them as coupled, or inter-connected, mechanisms. It is anticipated that this work lays a foundation for exploring methods for LEM synthesis based on the analogy between flat-folding origami models and linkage assembly.

  11. Identifying Functional Modules in Complex Networks

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, we propose a new method that enables us to detect and describe the functional modules in complex networks. Using the proposed method, we can classify the nodes of networks into different modules according to their pattern of intra- and extra-module links. We use our method to analyze the modular structures of the ER random networks. We find that different modules of networks have different structure properties, such as the clustering coefficient. Moreover, at the same time, many nodes of networks participate different modules. Remarkably, we find that in the ER random networks, when the probability p is small, different modules or different roles of nodes can be identified by different regionsin the c-p parameter space.

  12. Identifying driver mutations in sequenced cancer genomes

    DEFF Research Database (Denmark)

    Raphael, Benjamin J; Dobson, Jason R; Oesper, Layla

    2014-01-01

    High-throughput DNA sequencing is revolutionizing the study of cancer and enabling the measurement of the somatic mutations that drive cancer development. However, the resulting sequencing datasets are large and complex, obscuring the clinically important mutations in a background of errors, noise......, and random mutations. Here, we review computational approaches to identify somatic mutations in cancer genome sequences and to distinguish the driver mutations that are responsible for cancer from random, passenger mutations. First, we describe approaches to detect somatic mutations from high-throughput DNA...... sequencing data, particularly for tumor samples that comprise heterogeneous populations of cells. Next, we review computational approaches that aim to predict driver mutations according to their frequency of occurrence in a cohort of samples, or according to their predicted functional impact on protein...

  13. Identifying the structural discontinuities of human interactions

    CERN Document Server

    Grauwin, Sebastian; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabasi, Albert-Laszlo; Ratti, Carlo

    2015-01-01

    The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. In the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls and uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylize the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models, thus increasing our ability to predict social activiti...

  14. Identifying Galactic PeVatrons with Neutrinos

    CERN Document Server

    González-Garciá, M C; Mohapatra, Soumya

    2009-01-01

    We perform a realistic evaluation of the potential of IceCube, a kilometer-scale neutrino detector under construction at the South Pole, to detect neutrinos in the direction of the potential accelerators of the Galactic cosmic rays. We take fully account of the fact that the measurement of the energy of the secondary muons can be used to further discriminate between the signal and the background of atmospheric neutrinos. We conclude that IceCube could identify the sources in the Milagro sky map as the sources of the Galactic cosmic rays at the 3 sigma level in one year and at the 5 sigma level in three years. We discuss the dependence of these expectations on ambiguities, mostly associated with our incomplete knowledge of the astrophysics of the sources.

  15. Identifying multiquark hadrons from heavy ion collisions.

    Science.gov (United States)

    Cho, Sungtae; Furumoto, Takenori; Hyodo, Tetsuo; Jido, Daisuke; Ko, Che Ming; Lee, Su Houng; Nielsen, Marina; Ohnishi, Akira; Sekihara, Takayasu; Yasui, Shigehiro; Yazaki, Koichi

    2011-05-27

    Identifying hadronic molecular states and/or hadrons with multiquark components either with or without exotic quantum numbers is a long-standing challenge in hadronic physics. We suggest that studying the production of these hadrons in relativistic heavy ion collisions offers a promising resolution to this problem as yields of exotic hadrons are expected to be strongly affected by their structures. Using the coalescence model for hadron production, we find that, compared to the case of a nonexotic hadron with normal quark numbers, the yield of an exotic hadron is typically an order of magnitude smaller when it is a compact multiquark state and a factor of 2 or more larger when it is a loosely bound hadronic molecule. We further find that some of the newly proposed heavy exotic states could be produced and realistically measured in these experiments.

  16. Identifying the seasonal origins of human campylobacteriosis.

    Science.gov (United States)

    Strachan, N J C; Rotariu, O; Smith-Palmer, A; Cowden, J; Sheppard, S K; O'Brien, S J; Maiden, M C J; Macrae, M; Bessell, P R; Matthews, L; Reid, S W J; Innocent, G T; Ogden, I D; Forbes, K J

    2013-06-01

    Human campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden.

  17. Advances in identifying beryllium sensitization and disease.

    Science.gov (United States)

    Middleton, Dan; Kowalski, Peter

    2010-01-01

    Beryllium is a lightweight metal with unique qualities related to stiffness, corrosion resistance, and conductivity. While there are many useful applications, researchers in the 1930s and 1940s linked beryllium exposure to a progressive occupational lung disease. Acute beryllium disease is a pulmonary irritant response to high exposure levels, whereas chronic beryllium disease (CBD) typically results from a hypersensitivity response to lower exposure levels. A blood test, the beryllium lymphocyte proliferation test (BeLPT), was an important advance in identifying individuals who are sensitized to beryllium (BeS) and thus at risk for developing CBD. While there is no true "gold standard" for BeS, basic epidemiologic concepts have been used to advance our understanding of the different screening algorithms.

  18. Identifying seasonal stars in Kaurna astronomical traditions

    CERN Document Server

    Hamacher, Duane W

    2015-01-01

    Early ethnographers and missionaries recorded Aboriginal languages and oral traditions across Australia. Their general lack of astronomical training resulted in misidentifications, transcription errors, and omissions in these records. Additionally, many of these early records are fragmented. In western Victoria and southeast South Australia, many astronomical traditions were recorded, but curiously, some of the brightest stars in the sky were omitted. Scholars claimed these stars did not feature in Aboriginal traditions. This under-representation continues to be repeated in the literature, but current research shows that some of these stars may in fact feature in Aboriginal traditions and could be seasonal calendar markers. This paper uses established techniques in cultural astronomy to identify seasonal stars in the traditions of the Kaurna Aboriginal people of the Adelaide Plains, South Australia.

  19. Identifying Community Structures in Dynamic Networks

    CERN Document Server

    Alvari, Hamidreza; Sukthankar, Gita; Lakkaraju, Kiran

    2016-01-01

    Most real-world social networks are inherently dynamic, composed of communities that are constantly changing in membership. To track these evolving communities, we need dynamic community detection techniques. This article evaluates the performance of a set of game theoretic approaches for identifying communities in dynamic networks. Our method, D-GT (Dynamic Game Theoretic community detection), models each network node as a rational agent who periodically plays a community membership game with its neighbors. During game play, nodes seek to maximize their local utility by joining or leaving the communities of network neighbors. The community structure emerges after the game reaches a Nash equilibrium. Compared to the benchmark community detection methods, D-GT more accurately predicts the number of communities and finds community assignments with a higher normalized mutual information, while retaining a good modularity.

  20. Melanoma biomolecules: independently identified but functionally intertwined

    Directory of Open Access Journals (Sweden)

    Danielle Erin Dye

    2013-09-01

    Full Text Available The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (< 1mm thick will have recurrence and die within 10 years, despite no evidence of local or metastatic spread at the time of diagnosis. Thus, there is a need for additional prognostic markers to help identify those patients that may be at risk of recurrent disease. Many studies and several meta-analyses have compared gene and protein expression in melanocytes, naevi, primary and metastatic melanoma in an attempt to find informative prognostic markers for these patients. However, although a large number of putative biomarkers have been described, few of these molecules are informative when used in isolation. The best approach is likely to involve a combination of molecules. We believe one approach could be to analyze the expression of a group of interacting proteins that regulate different aspects of the metastatic pathway. This is because a primary lesion expressing proteins involved in multiple stages of metastasis may be more likely to lead to secondary disease than one that does not. This review focuses on five putative biomarkers - melanoma cell adhesion molecule (MCAM, galectin-3 (gal-3, matrix metalloproteinase 2 (MMP-2, chondroitin sulfate proteoglycan 4 (CSPG4 and paired box 3 (PAX3. The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology.

  1. Identifying sites for elk restoration in Arkansas

    Science.gov (United States)

    Telesco, R.L.; Van Manen, F.T.; Clark, J.D.; Cartwright, Michael E.

    2007-01-01

    We used spatial data to identify potential areas for elk (Cervus elaphus) restoration in Arkansas. To assess habitat, we used locations of 239 elk groups collected from helicopter surveys in the Buffalo National River area of northwestern Arkansas, USA, from 1992 to 2002. We calculated the Mahalanobis distance (D2) statistic based on the relationship between those elk-group locations and a suite of 9 landscape variables to evaluate winter habitat in Arkansas. We tested model performance in the Buffalo National River area by comparing the D2 values of pixels representing areas with and without elk pellets along 19 fixed-width transects surveyed in March 2002. Pixels with elk scat had lower D2 values than pixels in which we found no pellets (logistic regression: Wald χ2 = 24.37, P cover, gently sloping ridge tops and valleys, low human population density, and low road densities. To assess the potential for elk–human conflicts in Arkansas, we used the analytical hierarchy process to rank the importance of 8 criteria based on expert opinion from biologists involved in elk management. The biologists ranked availability of forage on public lands as having the strongest influence on the potential for elk–human conflict (33%), followed by human population growth rate (22%) and the amount of private land in row crops (18%). We then applied those rankings in a weighted linear summation to map the relative potential for elk–human conflict. Finally, we used white-tailed deer (Odocoileus virginianus) densities to identify areas where success of elk restoration may be hampered due to meningeal worm (Parelaphostrongylus tenuis) transmission. By combining results of the 3 spatial data layers (i.e., habitat model, elk–human conflict model, deer density), our model indicated that restoration sites located in west-central and north-central Arkansas were most favorable for reintroduction.

  2. Vulnerability of critical infrastructures : identifying critical nodes.

    Energy Technology Data Exchange (ETDEWEB)

    Cox, Roger Gary; Robinson, David Gerald

    2004-06-01

    The objective of this research was the development of tools and techniques for the identification of critical nodes within critical infrastructures. These are nodes that, if disrupted through natural events or terrorist action, would cause the most widespread, immediate damage. This research focuses on one particular element of the national infrastructure: the bulk power system. Through the identification of critical elements and the quantification of the consequences of their failure, site-specific vulnerability analyses can be focused at those locations where additional security measures could be effectively implemented. In particular, with appropriate sizing and placement within the grid, distributed generation in the form of regional power parks may reduce or even prevent the impact of widespread network power outages. Even without additional security measures, increased awareness of sensitive power grid locations can provide a basis for more effective national, state and local emergency planning. A number of methods for identifying critical nodes were investigated: small-world (or network theory), polyhedral dynamics, and an artificial intelligence-based search method - particle swarm optimization. PSO was found to be the only viable approach and was applied to a variety of industry accepted test networks to validate the ability of the approach to identify sets of critical nodes. The approach was coded in a software package called Buzzard and integrated with a traditional power flow code. A number of industry accepted test networks were employed to validate the approach. The techniques (and software) are not unique to power grid network, but could be applied to a variety of complex, interacting infrastructures.

  3. Identifying crucial parameter correlations maintaining bursting activity.

    Directory of Open Access Journals (Sweden)

    Anca Doloc-Mihu

    2014-06-01

    Full Text Available Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA to each of these four groups. PCA identified a set of three maximal conductances (leak current, [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a persistent Na+ current, [Formula: see text]P that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of [Formula: see text]Leak, [Formula: see text]K2, and [Formula: see text]P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained.

  4. Notch3 interactome analysis identified WWP2 as a negative regulator of Notch3 signaling in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Jin-Gyoung Jung

    2014-10-01

    Full Text Available The Notch3 signaling pathway is thought to play a critical role in cancer development, as evidenced by the Notch3 amplification and rearrangement observed in human cancers. However, the molecular mechanism by which Notch3 signaling contributes to tumorigenesis is largely unknown. In an effort to identify the molecular modulators of the Notch3 signaling pathway, we screened for Notch3-intracellular domain (N3-ICD interacting proteins using a human proteome microarray. Pathway analysis of the Notch3 interactome demonstrated that ubiquitin C was the molecular hub of the top functional network, suggesting the involvement of ubiquitination in modulating Notch3 signaling. Thereby, we focused on functional characterization of an E3 ubiquitin-protein ligase, WWP2, a top candidate in the Notch3 interactome list. Co-immunoprecipitation experiments showed that WWP2 interacted with N3-ICD but not with intracellular domains from other Notch receptors. Wild-type WWP2 but not ligase-deficient mutant WWP2 increases mono-ubiquitination of the membrane-tethered Notch3 fragment, therefore attenuating Notch3 pathway activity in cancer cells and leading to cell cycle arrest. The mono-ubiquitination by WWP2 may target an endosomal/lysosomal degradation fate for Notch3 as suggested by the fact that the process could be suppressed by the endosomal/lysosomal inhibitor. Analysis of The Cancer Genome Atlas dataset showed that the majority of ovarian carcinomas harbored homozygous or heterozygous deletions in WWP2 locus, and there was an inverse correlation in the expression levels between WWP2 and Notch3 in ovarian carcinomas. Furthermore, ectopic expression of WWP2 decreased tumor development in a mouse xenograft model and suppressed the Notch3-induced phenotypes including increase in cancer stem cell-like cell population and platinum resistance. Taken together, our results provide evidence that WWP2 serves as a tumor suppressor by negatively regulating Notch3 signaling

  5. Electrophoretic mobility shift assay identifies vitamin D binding protein (Gc-globulin) in human, rat, and mouse sera.

    Science.gov (United States)

    Tang, W X; Bazaraa, H M; Magiera, H; Cooke, N E; Haddad, J G

    1996-06-01

    Serum vitamin D binding protein (DBP, also known as Gc-globulin) is a multifunctional protein capable of binding both vitamin D metabolites and actin. DBP can be visualized when analyzed by polyacrylamide gel electrophoresis followed by staining. Confirmation of its identity had previously required immunoprecipitation with specific anti-DBP antisera or occupancy of the protein with radioactive vitamin D sterols. We present studies showing that preincubation of G-actin with mammalian sera produced a discernible DBP protein band shift on native gel electrophoresis. Addition of DNaseI, a 33-kDa intracellular protein with an avid actin-binding site, to the incubations resulted in a supershift of DBP-actin complexes to an even more cathodal region of the gels. Following incubations with human, rat, and murine sera the same actin shift occurred as did the actin plus DNaseI supershift. The migrations of each complex were correlated with purified DBP migrations under identical conditions. It was confirmed that the supershifted bands contained DBP by Western blotting and detection of DBP by binding of 25-OH[3H]D3. After intravenous G-actin injections into living mice, a serum DBP-actin complex could be detected on native gels as the uncomplexed DBP band decreased in intensity. This simple, direct-staining technique appears to be suitable for identifying DBP/Gc phenotypes in human populations as well as for semiquantitatively monitoring the plasma actin-scavenger system in vivo in animal models or in human diseases.

  6. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Science.gov (United States)

    Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred

    2013-01-01

    The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  7. Using BAC transgenesis in zebrafish to identify regulatory sequences of the amyloid precursor protein gene in humans

    Directory of Open Access Journals (Sweden)

    Shakes Leighcraft A

    2012-09-01

    Full Text Available Abstract Background Non-coding DNA in and around the human Amyloid Precursor Protein (APP gene that is central to Alzheimer’s disease (AD shares little sequence similarity with that of appb in zebrafish. Identifying DNA domains regulating expression of the gene in such situations becomes a challenge. Taking advantage of the zebrafish system that allows rapid functional analyses of gene regulatory sequences, we previously showed that two discontinuous DNA domains in zebrafish appb are important for expression of the gene in neurons: an enhancer in intron 1 and sequences 28–31 kb upstream of the gene. Here we identify the putative transcription factor binding sites responsible for this distal cis-acting regulation, and use that information to identify a regulatory region of the human APP gene. Results Functional analyses of intron 1 enhancer mutations in enhancer-trap BACs expressed as transgenes in zebrafish identified putative binding sites of two known transcription factor proteins, E4BP4/ NFIL3 and Forkhead, to be required for expression of appb. A cluster of three E4BP4 sites at −31 kb is also shown to be essential for neuron-specific expression, suggesting that the dependence of expression on upstream sequences is mediated by these E4BP4 sites. E4BP4/ NFIL3 and XFD1 sites in the intron enhancer and E4BP4/ NFIL3 sites at −31 kb specifically and efficiently bind the corresponding zebrafish proteins in vitro. These sites are statistically over-represented in both the zebrafish appb and the human APP genes, although their locations are different. Remarkably, a cluster of four E4BP4 sites in intron 4 of human APP exists in actively transcribing chromatin in a human neuroblastoma cell-line, SHSY5Y, expressing APP as shown using chromatin immunoprecipitation (ChIP experiments. Thus although the two genes share little sequence conservation, they appear to share the same regulatory logic and are regulated by a similar set of transcription

  8. Identifying functional decline: a methodological challenge

    Directory of Open Access Journals (Sweden)

    Grimmer K

    2013-08-01

    Full Text Available Karen Grimmer, Kate Beaton, Kevan Hendry International Centre for Allied Health Evidence, University of South Australia, Adelaide, SA, Australia Background: Functional decline (FD in older people has commonly been measured in the hospital setting with instruments which have been validated on decrease over time in capacity to undertake basic activities of daily living (ADL. In a nonhospitalized sample of older people (independently community dwelling, but potentially on the cusp of FD, it is possible that other measures could be used to predict decline. Early, accurate, and efficient identification of older community-dwelling people who are on the cusp of FD can assist in identifying appropriate interventions to slow the rate of decline. Methods: This paper reports on associations between four outcome measures which have been associated with FD (instrumental ADLs [IADLs], quality of life, hospitalizations and falls. The sample was older individuals who were discharged from one large metropolitan emergency department (ED during 2011–2012, without an inpatient admission. Results: Of 597 individuals aged 65+ who provided baseline information, 148 subjects provided four outcome measures at both 1 and 3 months follow up. Overall, approximately 24% demonstrated decreased IADL scores over the 3 months, with domains of home activities, laundry, shopping, and getting places declining the most. Over this time, 18% fell often, and 11% were consistently hospitalized. Between 1 and 3 months follow up, 41% declined in mental component scores, and 50% declined in physical component scores. Low mental and physical component quality of life scores were associated with downstream increased falls and hospitalizations, and decreased quality of life and IADLs. However, change in the four outcome measures was largely independent in factor analysis. Conclusion: Measuring the four outcome measures over 3 months post-discharge from an ED presentation, showed that

  9. Identifying high-redshift GRBs with RATIR

    CERN Document Server

    Littlejohns, O M; Cucchiara, A; Watson, A M; Kutyrev, A S; Lee, W H; Richer, M G; Klein, C R; Fox, O D; Prochaska, J X; Bloom, J S; Troja, E; Ramirez-Ruiz, E; de Diego, J A; Georgiev, L; González, J; Román-Zúñiga, C G; Gehrels, N; Moseley, H

    2013-01-01

    We present a template fitting algorithm for determining photometric redshifts, $z_{\\rm phot}$, of candidate high-redshift gamma-ray bursts (GRBs). Using afterglow photometry, obtained by the Reionization And Transients InfraRed (RATIR) camera, this algorithm accounts for the intrinsic GRB afterglow spectrum, host dust extinction and the effect of neutral hydrogen (local and cosmological) along the line of sight. We present the results obtained by this algorithm and RATIR photometry of GRB 130606A, finding $z_{\\rm phot} = 6.01_{-0.08}^{+0.16}$ for a model with negligible host dust extinction, consistent with spectroscopic measurements of the redshift of this GRB. Using simulated RATIR photometry, we find our algorithm provides precise measures of $z_{\\rm phot}$ in the ranges $4 4$. Further testing highlights the required caution in cases of highly dust extincted host galaxies. These tests also show that our algorithm minimizes false negatives thus allowing us to rapidly identify all potential high-redshift eve...

  10. Asteroid secular dynamics: Ceres' fingerprint identified

    CERN Document Server

    Novaković, Bojan; Tsirvoulis, Georgios; Knezević, Zoran

    2015-01-01

    Here we report on the significant role of a so far overlooked dynamical aspect, namely a secular resonance between the dwarf planet Ceres and other asteroids. We demonstrate that this type of secular resonance can be the dominant dynamical factor in certain regions of the main asteroid belt. Specifically, we performed a dynamical analysis of the asteroids belonging to the (1726) Hoffmeister family. To identify which dynamical mechanisms are actually at work in this part of the main asteroid belt, i.e. to isolate the main perturber(s), we study the evolution of this family in time. The study is accomplished using numerical integrations of test particles performed within different dynamical models. The obtained results reveal that the post-impact evolution of the Hoffmeister asteroid family is a direct consequence of the nodal secular resonance with Ceres. This leads us to the conclusion that similar effects must exist in other parts of the asteroid belt. In this respect, the obtained results shed light on an i...

  11. Identifying and Evaluating of Oil Reservoir

    Institute of Scientific and Technical Information of China (English)

    Yang Haixia

    2002-01-01

    The identification and evaluation of oil reservoir with logging data are one of most important ways in geologic logging services. For the last decades, with the further development of the oil & gas exploration, great advances have been achieved in techniques on the acquisition, processing and interpretative evaluation of logging data. How to identify fluid characteristics and evaluate the productivity in light oil reservoir (the crude density being between 0.74g/cm3 and 0.82g/cm3)has become one of the difficulties.With the establishment of the regional interpretation criterion of the study blocks, the optimized logging parameters that reflect the reservoir characteristics have been used to establish the chart for the interpretation of oil-water reservoir combining with well logging parameters. Then, to begin with geologic reserves of crude in single well, we establish evaluation criterion for productivity in oil reservoir with determining lower limit value of the reservoir and applying the relationship between chart parameters. The techniques are verified in production and get better effect.On the basis of the reservoir characteristics analysis of both basin A and B, We established the evaluation method of static productivity on light oil reservoir with getting quantitative evaluation parameters after quantitatively evaluating the date of core, pyrolysis chromatogram and gas chromatogram. It provides new technique 7 for new well interpretation and old well review, as well as evidence for project.design of well testing.

  12. Identifying electrons and positrons with AMS-02

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Nikolas [RWTH Aachen University (Germany)

    2015-07-01

    The AMS-02 experiment is a multi-purpose detector for cosmic ray particles mounted on the International Space Station. It recorded over 40 billion events since its installation in 2011. The bulk of these events are protons, which are most abundant in cosmic rays. Electrons are 100 times and positrons 1000 times less abundant. Measuring the positrons as function of energy is especially interesting, as an excess over the expected astrophysical background may hint at an additional source of positrons in the galaxy or a new phenomena responsible for the excess, e.g. dark-matter annihilation. In order to measure positrons accurately with a small uncertainty, a large proton rejection of 10{sup 6} is needed. AMS-02 offers a transition radiation detector to separate positrons from protons and an electromagnetic calorimeter allowing a precise measurement of the kinetic energy of an incoming lepton. This talk covers the general strategy of identifying electrons/positrons with AMS-02 and presents the so-obtained electron/positron fluxes that were recently published.

  13. Identifying hearing loss by means of iridology.

    Science.gov (United States)

    Stearn, Natalie; Swanepoel, De Wet

    2006-11-13

    Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without hearing loss. Fifty hearing impaired and fifty normal hearing subjects, between the ages of 15 and 19 years, controlled for gender, participated in the study. An experienced iridologist analyzed the randomised set of participants' irises. A 70% correct identification of hearing status was obtained by iridological analyses with a false negative rate of 41% compared to a 19% false positive rate. The respective sensitivity and specificity rates therefore came to 59% and 81%. Iridological analysis of hearing status indicated a statistically significant relationship to actual hearing status (P iridology were not comparable to those of traditional audiological screening procedures.

  14. Identifying murder victims with endodontic radiographs

    Science.gov (United States)

    Silva, Rhonan Ferreira; Franco, Ademir; Mendes, Solon Diego Santos Carvalho; Picoli, Fernando Fortes; Nunes, Fernando Gomes; Estrela, Carlos

    2016-01-01

    Endodontics is a special branch of dentistry constantly guided by imaging examinations. From a forensic scope, endodontics plays a valuable role providing solid antemortem (AM) radiographic evidence for comparison with postmortem findings in human identifications. This study illustrates the interface between endodontics and forensic odontology describing three cases of human identification based on radiographic endodontic records. From 2009 to 2012, three unknown male victims of murder were examined in a local Brazilian medico-legal institute to retrieve identity and potential cause of death. Specifically, when asked for AM data, a relative of the three victims provided periapical radiographs of endodontic treatments. Based on that, forensic dentists reproduced the same imaging acquisition techniques obtaining similar periapical radiographs, enabling a comparative dental identification. All the victims were positively identified based on patterns of dental morphology and treatment intervention. This study draws the attention of general and forensic dentists highlight the importance of properly recording dental treatments and searching for evidence in AM endodontic data, respectively. PMID:28123272

  15. Indexing molecules with chemical graph identifiers.

    Science.gov (United States)

    Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

    2011-09-01

    Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used.

  16. Can we identify source lithology of basalt?

    Science.gov (United States)

    Yang, Zong-Feng; Zhou, Jun-Hong

    2013-01-01

    The nature of source rocks of basaltic magmas plays a fundamental role in understanding the composition, structure and evolution of the solid earth. However, identification of source lithology of basalts remains uncertainty. Using a parameterization of multi-decadal melting experiments on a variety of peridotite and pyroxenite, we show here that a parameter called FC3MS value (FeO/CaO-3*MgO/SiO2, all in wt%) can identify most pyroxenite-derived basalts. The continental oceanic island basalt-like volcanic rocks (MgO>7.5%) (C-OIB) in eastern China and Mongolia are too high in the FC3MS value to be derived from peridotite source. The majority of the C-OIB in phase diagrams are equilibrium with garnet and clinopyroxene, indicating that garnet pyroxenite is the dominant source lithology. Our results demonstrate that many reputed evolved low magnesian C-OIBs in fact represent primary pyroxenite melts, suggesting that many previous geological and petrological interpretations of basalts based on the single peridotite model need to be reconsidered.

  17. Utilizing Surface Sensors to Identify Wake Regimes

    Science.gov (United States)

    Wang, Mengying; Hemati, Maziar S.

    2016-11-01

    Marine swimmers often exploit external flow structures to reduce locomotive effort. To achieve this advantage, these swimmers utilize mechanosensory organs on the surface of their bodies to detect hydrodynamic signals from the surrounding fluid, which can then be used to inform the control task. Recently, there has been a growing interest in developing similar flow sensing systems to achieve enhanced propulsive efficiency and maneuverability in human-engineered underwater vehicles. In particular, much attention has been given to the problem of wake sensing; however, these investigations have concentrated on a restricted class of wakes-i.e., Kármán-type vortex streets-whereas more complicated wake structures can arise in practice. In this talk, we will explore the possibility of identifying wake regimes through the use of surface sensors. Potential flow theory is adopted to simulate the interactions of various wakes with a fish-like body. Wakes in different dynamical regimes impart distinct hydrodynamic signatures on the body, which permits these regimes to be distinguished from one another in an automated fashion. Our results can provide guidance for improving flow sensing capabilities in human-engineered systems and hint at how marine swimmers may sense their hydrodynamic surroundings.

  18. From Slovene into English: Identifying Definiteness

    Directory of Open Access Journals (Sweden)

    Frančiška Lipovšek

    2008-06-01

    Full Text Available The paper addresses some typical instances of the translator’s failure to recognize definite reference in Slovene, which, in turn, results in an inappropriate determiner selection in English. It is argued that errors of this kind are ascribable not solely to the fact that the Slovene determiner system lacks an overt non-selective determiner parallel to the definite article, but to the relatively scarce use of overt determiners in general. Since definiteness is typically signalled by an anaphoric relation, some factors are explored that may help identify textual co-reference despite the absence of explicit anaphoric markers. Besides the translator’s inability to recognize the given phrase as anaphoric, two other major causes of inappropriate determiner selection are discussed: the misconception that the absence of an anaphoric relation entails indefiniteness and the translator’s misinterpreting an anaphoric expression as an ascriptive, non-referential entity. The second part of the paper focuses on the difference in use between the selective demonstrative pronoun and the non-selective definite article.

  19. The Ku-band Polarization Identifier

    CERN Document Server

    Gundersen, J O

    2003-01-01

    The Ku-band Polarization Identifier (KUPID) will integrate a very low noise 12-18 GHz, correlation polarimeter onto the Crawford Hill seven meter, millimeter-wave antenna. The primary components of the polarimeter will be built at the University of Miami and other key components, including the microwave horn and data acquisition system will be built at the University of Chicago and Princeton University. This project will measure the Q and U Stokes parameters in regions near the north celestial pole, in regions of low galactic contamination, and in regions near the galactic plane. The KUPID survey experiment makes use of many of the techniques employed in the Princeton IQU Experiment (PIQUE) that was developed by the members of this collaboration to detect CMB polarization at shorter wavelengths. The KUPID experiment will be constructed in parallel and on the same timescale as the CAPMAP experiment (see Barkats, this volume) which is the follow-on experiment to PIQUE. KUPID will observe on the Crawford Hill an...

  20. A New Observable for Identifying Dijet Resonances

    CERN Document Server

    Izaguirre, Eder; Yavin, Itay

    2014-01-01

    The development of techniques for identifying hadronic signals from the overwhelming multi-jet backgrounds is an important part of the Large Hadron Collider (LHC) program. Of prime importance are resonances decaying into a pair of partons, such as the Higgs and $\\rm W$/$\\rm Z$ bosons, as well as hypothetical new particles. We present a simple observable to help discriminate a dijet resonance from background that is effective even when the decaying resonance is not strongly boosted. We find consistent performance of the observable over a variety of processes and degree of boosts, and show that it leads to a reduction of the background by a factor of $3-5$ relative to signal at the price of $10-20\\%$ signal efficiency. This approach represents a significant increase in sensitivity for Standard Model (SM) measurements and searches for new physics that are dominated by systematic uncertainties, which is true of many analyses involving jets - particularly in the high-luminosity running of the LHC.

  1. The Protein Identifier Cross-Referencing (PICR service: reconciling protein identifiers across multiple source databases

    Directory of Open Access Journals (Sweden)

    Leinonen Rasko

    2007-10-01

    Full Text Available Abstract Background Each major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs. Results We have created the Protein Identifier Cross-Reference (PICR service, a web application that provides interactive and programmatic (SOAP and REST access to a mapping algorithm that uses the UniProt Archive (UniParc as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV or Microsoft Excel (XLS files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface. Conclusion We offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR

  2. Identifying enabling management practices for employee engagement

    Directory of Open Access Journals (Sweden)

    Marius Joubert

    2011-12-01

    Full Text Available Orientation: A currently emerging viewpoint is that today's management practices no longer add value to organisations. The focus of this article is to conduct a systematic review of the scholarly literature on management practices that could be related to employee engagement. Research purpose: This study searched for evidence in support of the notion of a management value chain, and enabling management practices within each value chain component that could relate to employee engagement. Motivation for the study: An alternative management value chain model could contribute towards a better understanding of which management practices may potentially impact employee engagement. Research design, approach, and method: This is a non-empirical (theoretical study, based on a systematic, in-depth literature review to identify the key management components and enabling practices within this proposed management value chain. Scholarly research databases were sourced for relevant peer reviewed research conducted since 1990, not excluding important contributions prior to 1990. The literature was systematically searched, selected, studied, and contextualized within this study. Main findings: Support was found for the notion of a management value chain, for enabling management practices within each proposed management value chain component, and it was also established these management practices indeed have an impact on employee engagement. Practical/managerial/implications: The possibility that management work can be presented as a generic management value chain allows managers to approach engaging management practices more systematically. Contribution/value-add: This study highlights the importance of some management practices that have never been seen as part of management work.

  3. Identifying the causes of contact dermatitis.

    Science.gov (United States)

    Jones, Ruth; Horn, Helen M

    2014-06-01

    Contact dermatitis results from skin contact with an exogenous substance. It can be caused by direct contact, airborne particles, vapours or light. Individuals of any age can be affected. The two most common variants are irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). ICD is more common and has a worse prognosis. Other less common forms of contact dermatitis include photocontact allergy and, in food handlers, protein contact dermatitis. ICD is a form of eczema and is induced by direct inflammatory pathways without prior sensitisation. Classical ACD is mediated by type 4 cell-mediated immunity. Sensitisation occurs within 5 to 16 days of skin contact with a potential allergen but at this first exposure there is no inflammation. Frequent exposure and high concentrations of potential allergens increase the risk of sensitisation. If eczema is recurrent/persistent, or occurs in an individual with no previous history of eczema, contact dermatitis should be considered. Dorsal aspects of the hands are most often affected by ICD, usually with involvement of the finger webs. Cumulative effects of water, soaps and detergents are the most common cause of ICD which affects the hands more often than any other site. Nickel, fragrances, rubber accelerators and biocides are the most common sensitisers in ACD. Patients with leg ulcers and stasis eczema are at especially high risk of developing allergies to ingredients of their topical treatments, dressings and bandages. If ACD is suspected the patient should be referred to secondary care for patch testing. Age should not be a deterrent to patch testing. Accurate diagnosis, avoidance of identified allergens and protection from irritants are the key to successful treatment.

  4. An approach to identify urban groundwater recharge

    Directory of Open Access Journals (Sweden)

    E. Vázquez-Suñé

    2010-10-01

    Full Text Available Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, .... The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i Identification of potential recharge sources, (ii Selection of tracers, (iii Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%, the sewage network losses (30%, rainfall, concentrated in the non-urbanized areas (17%, from runoff infiltration (20%, and the Besòs River (11%. Regarding species, halogens (chloride, fluoride and bromide, sulfate, total nitrogen, and stable isotopes (18O, 2H, and 34S behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations.

  5. An approach to identify urban groundwater recharge

    Directory of Open Access Journals (Sweden)

    E. Vázquez-Suñé

    2010-04-01

    Full Text Available Evaluating the proportion in which waters from different origins are mixed in a given water sample is relevant for many hydrogeological problems, such as quantifying total recharge, assessing groundwater pollution risks, or managing water resources. Our work is motivated by urban hydrogeology, where waters with different chemical signature can be identified (losses from water supply and sewage networks, infiltration from surface runoff and other water bodies, lateral aquifers inflows, .... The relative contribution of different sources to total recharge can be quantified by means of solute mass balances, but application is hindered by the large number of potential origins. Hence, the need to incorporate data from a large number of conservative species, the uncertainty in sources concentrations and measurement errors. We present a methodology to compute mixing ratios and end-members composition, which consists of (i Identification of potential recharge sources, (ii Selection of tracers, (iii Characterization of the hydrochemical composition of potential recharge sources and mixed water samples, and (iv Computation of mixing ratios and reevaluation of end-members. The analysis performed in a data set from samples of the Barcelona city aquifers suggests that the main contributors to total recharge are the water supply network losses (22%, the sewage network losses (30%, rainfall, concentrated in the non-urbanized areas (17%, from runoff infiltration (20%, and the Besòs River (11%. Regarding species, halogens (chloride, fluoride and bromide, sulfate, total nitrogen, and stable isotopes (18O2H, and 34S behaved quite conservatively. Boron, residual alkalinity, EDTA and Zn did not. Yet, including these species in the computations did not affect significantly the proportion estimations.

  6. Identifying human influences on atmospheric temperature.

    Science.gov (United States)

    Santer, Benjamin D; Painter, Jeffrey F; Mears, Carl A; Doutriaux, Charles; Caldwell, Peter; Arblaster, Julie M; Cameron-Smith, Philip J; Gillett, Nathan P; Gleckler, Peter J; Lanzante, John; Perlwitz, Judith; Solomon, Susan; Stott, Peter A; Taylor, Karl E; Terray, Laurent; Thorne, Peter W; Wehner, Michael F; Wentz, Frank J; Wigley, Tom M L; Wilcox, Laura J; Zou, Cheng-Zhi

    2013-01-02

    We perform a multimodel detection and attribution study with climate model simulation output and satellite-based measurements of tropospheric and stratospheric temperature change. We use simulation output from 20 climate models participating in phase 5 of the Coupled Model Intercomparison Project. This multimodel archive provides estimates of the signal pattern in response to combined anthropogenic and natural external forcing (the fingerprint) and the noise of internally generated variability. Using these estimates, we calculate signal-to-noise (S/N) ratios to quantify the strength of the fingerprint in the observations relative to fingerprint strength in natural climate noise. For changes in lower stratospheric temperature between 1979 and 2011, S/N ratios vary from 26 to 36, depending on the choice of observational dataset. In the lower troposphere, the fingerprint strength in observations is smaller, but S/N ratios are still significant at the 1% level or better, and range from three to eight. We find no evidence that these ratios are spuriously inflated by model variability errors. After removing all global mean signals, model fingerprints remain identifiable in 70% of the tests involving tropospheric temperature changes. Despite such agreement in the large-scale features of model and observed geographical patterns of atmospheric temperature change, most models do not replicate the size of the observed changes. On average, the models analyzed underestimate the observed cooling of the lower stratosphere and overestimate the warming of the troposphere. Although the precise causes of such differences are unclear, model biases in lower stratospheric temperature trends are likely to be reduced by more realistic treatment of stratospheric ozone depletion and volcanic aerosol forcing.

  7. Identifying Hendra virus diversity in pteropid bats.

    Directory of Open Access Journals (Sweden)

    Ina Smith

    Full Text Available Hendra virus (HeV causes a zoonotic disease with high mortality that is transmitted to humans from bats of the genus Pteropus (flying foxes via an intermediary equine host. Factors promoting spillover from bats to horses are uncertain at this time, but plausibly encompass host and/or agent and/or environmental factors. There is a lack of HeV sequence information derived from the natural bat host, as previously sequences have only been obtained from horses or humans following spillover events. In order to obtain an insight into possible variants of HeV circulating in flying foxes, collection of urine was undertaken in multiple flying fox roosts in Queensland, Australia. HeV was found to be geographically widespread in flying foxes with a number of HeV variants circulating at the one time at multiple locations, while at times the same variant was found circulating at disparate locations. Sequence diversity within variants allowed differentiation on the basis of nucleotide changes, and hypervariable regions in the genome were identified that could be used to differentiate circulating variants. Further, during the study, HeV was isolated from the urine of flying foxes on four occasions from three different locations. The data indicates that spillover events do not correlate with particular HeV isolates, suggesting that host and/or environmental factors are the primary determinants of bat-horse spillover. Thus future spillover events are likely to occur, and there is an on-going need for effective risk management strategies for both human and animal health.

  8. Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis.

    Science.gov (United States)

    Wang, Qi; Drouin, Elise E; Yao, Chunxiang; Zhang, Jiyang; Huang, Yu; Leon, Deborah R; Steere, Allen C; Costello, Catherine E

    2017-01-06

    Human leukocyte antigen-antigen D related (HLA-DR) molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins. A total of 67% of the peptides identified in SFMC and 55% of those found in PBMC were found in ST, but analysis of SFMC/PBMC also revealed new antigen-presented peptides. Peptides were synthesized and examined for reactivity with the patients' PBMC. To date, three autoantigens in RA and four novel autoantigens in LA, presented in ST and/or PBMC, were shown to be targets of T- and B-cell responses in these diseases; ongoing analyses may add to this list. Thus, immunoprecipitation and LC-MS/MS can now identify hundreds of HLA-DR-presented self-peptides from individual patients' tissues or fluids with mixed cell populations. Importantly, identification of HLA-DR-presented peptides from SFMC or PBMC allows testing of more patients, including those early in the disease. Direct analysis of clinical samples facilitates identification of novel immunogenic T-cell epitopes.

  9. Stathmin, a new target of PRL-3 identified by proteomic methods, plays a key role in progression and metastasis of colorectal cancer.

    Science.gov (United States)

    Zheng, Ping; Liu, Yong-Xia; Chen, Lin; Liu, Xun-Hua; Xiao, Zheng-Quan; Zhao, Liang; Li, Guang-Qiu; Zhou, Jun; Ding, Yan-Qing; Li, Jian-Ming

    2010-10-01

    To better understand the role of PRL-3 in progression and metastasis of colorectal cancer (CRC), we searched for PRL-3 associated proteins using proteomic methods. We identified 39 PRL-3 associated proteins based on proteomic strategy. Stathmin, a key oncoprotein, was proved to be a new PRL-3 associated protein. Notably, co-immunoprecipitation assays in both endogenous CRC cell lines and CRC tissues indicated that PRL-3 could interact with stathmin. And, both stathmin and PRL-3 contributed to microtubule (MT) destabilization of CRC cells. Moreover, gain-of-function and loss-of-function analyses revealed that stathmin promoted proliferation, cell adhesion, and migration of human CRC cells. Immunohistochemical analysis of 149 colorectal tumor samples showed that overexpression of stathmin was strongly correlated with tumor differentiation (P = 0.035), tumor invasion (P = 0.024), lymph node status (P PRL-3 associated proteins for the first time. The oncoprotein stathmin plays a key role in CRC as a new target of PRL-3. Interaction between PRL-3 and stathmin leads to MT destabilization of CRC cells, which contributes to progression and metastasis of CRC.

  10. Identifying the important HIV-1 recombination breakpoints.

    Directory of Open Access Journals (Sweden)

    John Archer

    Full Text Available Recombinant HIV-1 genomes contribute significantly to the diversity of variants within the HIV/AIDS pandemic. It is assumed that some of these mosaic genomes may have novel properties that have led to their prevalence, particularly in the case of the circulating recombinant forms (CRFs. In regions of the HIV-1 genome where recombination has a tendency to convey a selective advantage to the virus, we predict that the distribution of breakpoints--the identifiable boundaries that delimit the mosaic structure--will deviate from the underlying null distribution. To test this hypothesis, we generate a probabilistic model of HIV-1 copy-choice recombination and compare the predicted breakpoint distribution to the distribution from the HIV/AIDS pandemic. Across much of the HIV-1 genome, we find that the observed frequencies of inter-subtype recombination are predicted accurately by our model. This observation strongly indicates that in these regions a probabilistic model, dependent on local sequence identity, is sufficient to explain breakpoint locations. In regions where there is a significant over- (either side of the env gene or under- (short regions within gag, pol, and most of env representation of breakpoints, we infer natural selection to be influencing the recombination pattern. The paucity of recombination breakpoints within most of the envelope gene indicates that recombinants generated in this region are less likely to be successful. The breakpoints at a higher frequency than predicted by our model are approximately at either side of env, indicating increased selection for these recombinants as a consequence of this region, or at least part of it, having a tendency to be recombined as an entire unit. Our findings thus provide the first clear indication of the existence of a specific portion of the genome that deviates from a probabilistic null model for recombination. This suggests that, despite the wide diversity of recombinant forms seen in

  11. Identifying the Important HIV-1 Recombination Breakpoints

    Science.gov (United States)

    Fan, Jun; Simon-Loriere, Etienne; Arts, Eric J.; Negroni, Matteo; Robertson, David L.

    2008-01-01

    Recombinant HIV-1 genomes contribute significantly to the diversity of variants within the HIV/AIDS pandemic. It is assumed that some of these mosaic genomes may have novel properties that have led to their prevalence, particularly in the case of the circulating recombinant forms (CRFs). In regions of the HIV-1 genome where recombination has a tendency to convey a selective advantage to the virus, we predict that the distribution of breakpoints—the identifiable boundaries that delimit the mosaic structure—will deviate from the underlying null distribution. To test this hypothesis, we generate a probabilistic model of HIV-1 copy-choice recombination and compare the predicted breakpoint distribution to the distribution from the HIV/AIDS pandemic. Across much of the HIV-1 genome, we find that the observed frequencies of inter-subtype recombination are predicted accurately by our model. This observation strongly indicates that in these regions a probabilistic model, dependent on local sequence identity, is sufficient to explain breakpoint locations. In regions where there is a significant over- (either side of the env gene) or under- (short regions within gag, pol, and most of env) representation of breakpoints, we infer natural selection to be influencing the recombination pattern. The paucity of recombination breakpoints within most of the envelope gene indicates that recombinants generated in this region are less likely to be successful. The breakpoints at a higher frequency than predicted by our model are approximately at either side of env, indicating increased selection for these recombinants as a consequence of this region, or at least part of it, having a tendency to be recombined as an entire unit. Our findings thus provide the first clear indication of the existence of a specific portion of the genome that deviates from a probabilistic null model for recombination. This suggests that, despite the wide diversity of recombinant forms seen in the viral

  12. Identifying Canadian freshwater fishes through DNA barcodes.

    Directory of Open Access Journals (Sweden)

    Nicolas Hubert

    species can be efficiently identified through the use of DNA barcoding, especially the species complex of small-sized species, and that the present COI library can be used for subsequent applications in ecology and systematics.

  13. Identifying hidden sexual bridging communities in Chicago.

    Science.gov (United States)

    Youm, Yoosik; Mackesy-Amiti, Mary Ellen; Williams, Chyvette T; Ouellet, Lawrence J

    2009-07-01

    Bridge populations can play a central role in the spread of human immunodeficiency virus (HIV) by providing transmission links between higher and lower prevalence populations. While social network methods are well suited to the study of bridge populations, analyses tend to focus on dyads (i.e., risk between drug and/or sex partners) and ignore bridges between distinct subpopulations. This study takes initial steps toward moving the analysis of sexual network linkages beyond individual and risk group levels to a community level in which Chicago's 77 community areas are examined as subpopulations for the purpose of identifying potential bridging communities. Of particular interest are "hidden" bridging communities; that is, areas with above-average levels of sexual ties with other areas but whose below-average AIDS prevalence may hide their potential importance for HIV prevention. Data for this analysis came from the first wave of recruiting at the Chicago Sexual Acquisition and Transmission of HIV Cooperative Agreement Program site. Between August 2005 through October 2006, respondent-driven sampling was used to recruit users of heroin, cocaine, or methamphetamine, men who have sex with men regardless of drug use, the sex partners of these two groups, and sex partners of the sex partners. In this cross-sectional study of the sexual transmission of HIV, participants completed a network-focused computer-assisted self-administered interview, which included questions about the geographic locations of sexual contacts with up to six recent partners. Bridging scores for each area were determined using a matrix representing Chicago's 77 community areas and were assessed using two measures: non-redundant ties and flow betweenness. Bridging measures and acquired immunodeficiency syndrome (AIDS) case prevalence rates were plotted for each community area on charts representing four conditions: below-average bridging and AIDS prevalence, below-average bridging and above

  14. Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus.

    Directory of Open Access Journals (Sweden)

    Evelyn N Kouwenhoven

    2010-08-01

    Full Text Available Heterozygous mutations in p63 are associated with split hand/foot malformations (SHFM, orofacial clefting, and ectodermal abnormalities. Elucidation of the p63 gene network that includes target genes and regulatory elements may reveal new genes for other malformation disorders. We performed genome-wide DNA-binding profiling by chromatin immunoprecipitation (ChIP, followed by deep sequencing (ChIP-seq in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63. We show that p63 binds to an enhancer element in the SHFM1 locus on chromosome 7q and that this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development. A unique micro-deletion including this enhancer element, but not the DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly indicates disruption of a non-coding cis-regulatory element located more than 250 kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes.

  15. Roles and programming of Arabidopsis ARGONAUTE proteins during Turnip mosaic virus infection.

    Science.gov (United States)

    Garcia-Ruiz, Hernan; Carbonell, Alberto; Hoyer, J Steen; Fahlgren, Noah; Gilbert, Kerrigan B; Takeda, Atsushi; Giampetruzzi, Annalisa; Garcia Ruiz, Mayra T; McGinn, Michaela G; Lowery, Nicholas; Martinez Baladejo, Maria T; Carrington, James C

    2015-03-01

    In eukaryotes, ARGONAUTE proteins (AGOs) associate with microRNAs (miRNAs), short interfering RNAs (siRNAs), and other classes of small RNAs to regulate target RNA or target loci. Viral infection in plants induces a potent and highly specific antiviral RNA silencing response characterized by the formation of virus-derived siRNAs. Arabidopsis thaliana has ten AGO genes of which AGO1, AGO2, and AGO7 have been shown to play roles in antiviral defense. A genetic analysis was used to identify and characterize the roles of AGO proteins in antiviral defense against Turnip mosaic virus (TuMV) in Arabidopsis. AGO1, AGO2 and AGO10 promoted anti-TuMV defense in a modular way in various organs, with AGO2 providing a prominent antiviral role in leaves. AGO5, AGO7 and AGO10 had minor effects in leaves. AGO1 and AGO10 had overlapping antiviral functions in inflorescence tissues after systemic movement of the virus, although the roles of AGO1 and AGO10 accounted for only a minor amount of the overall antiviral activity. By combining AGO protein immunoprecipitation with high-throughput sequencing of associated small RNAs, AGO2, AGO10, and to a lesser extent AGO1 were shown to associate with siRNAs derived from silencing suppressor (HC-Pro)-deficient TuMV-AS9, but not with siRNAs derived from wild-type TuMV. Co-immunoprecipitation and small RNA sequencing revealed that viral siRNAs broadly associated with wild-type HC-Pro during TuMV infection. These results support the hypothesis that suppression of antiviral silencing during TuMV infection, at least in part, occurs through sequestration of virus-derived siRNAs away from antiviral AGO proteins by HC-Pro. These findings indicate that distinct AGO proteins function as antiviral modules, and provide a molecular explanation for the silencing suppressor activity of HC-Pro.

  16. Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells.

    Directory of Open Access Journals (Sweden)

    Lyne Khair

    2015-08-01

    Full Text Available Activation-induced cytidine deaminase (AID is required for initiation of Ig class switch recombination (CSR and somatic hypermutation (SHM of antibody genes during immune responses. AID has also been shown to induce chromosomal translocations, mutations, and DNA double-strand breaks (DSBs involving non-Ig genes in activated B cells. To determine what makes a DNA site a target for AID-induced DSBs, we identify off-target DSBs induced by AID by performing chromatin immunoprecipitation (ChIP for Nbs1, a protein that binds DSBs, followed by deep sequencing (ChIP-Seq. We detect and characterize hundreds of off-target AID-dependent DSBs. Two types of tandem repeats are highly enriched within the Nbs1-binding sites: long CA repeats, which can form Z-DNA, and tandem pentamers containing the AID target hotspot WGCW. These tandem repeats are not nearly as enriched at AID-independent DSBs, which we also identified. Msh2, a component of the mismatch repair pathway and important for genome stability, increases off-target DSBs, similar to its effect on Ig switch region DSBs, which are required intermediates during CSR. Most of the off-target DSBs are two-ended, consistent with generation during G1 phase, similar to DSBs in Ig switch regions. However, a minority are one-ended, presumably due to conversion of single-strand breaks to DSBs during replication. One-ended DSBs are repaired by processes involving homologous recombination, including break-induced replication repair, which can lead to genome instability. Off-target DSBs, especially those present during S phase, can lead to chromosomal translocations, deletions and gene amplifications, resulting in the high frequency of B cell lymphomas derived from cells that express or have expressed AID.

  17. CORE_TF: a user-friendly interface to identify evolutionary conserved transcription factor binding sites in sets of co-regulated genes

    Directory of Open Access Journals (Sweden)

    den Dunnen Johan T

    2008-11-01

    Full Text Available Abstract Background The identification of transcription factor binding sites is difficult since they are only a small number of nucleotides in size, resulting in large numbers of false positives and false negatives in current approaches. Computational methods to reduce false positives are to look for over-representation of transcription factor binding sites in a set of similarly regulated promoters or to look for conservation in orthologous promoter alignments. Results We have developed a novel tool, "CORE_TF" (Conserved and Over-REpresented Transcription Factor binding sites that identifies common transcription factor binding sites in promoters of co-regulated genes. To improve upon existing binding site predictions, the tool searches for position weight matrices from the TRANSFACR database that are over-represented in an experimental set compared to a random set of promoters and identifies cross-species conservation of the predicted transcription factor binding sites. The algorithm has been evaluated with expression and chromatin-immunoprecipitation on microarray data. We also implement and demonstrate the importance of matching the random set of promoters to the experimental promoters by GC content, which is a unique feature of our tool. Conclusion The program CORE_TF is accessible in a user friendly web interface at http://www.LGTC.nl/CORE_TF. It provides a table of over-represented transcription factor binding sites in the users input genes' promoters and a graphical view of evolutionary conserved transcription factor binding sites. In our test data sets it successfully predicts target transcription factors and their binding sites.

  18. A practical guideline for identifying research intent with projects that collect private, identifiable health information.

    Science.gov (United States)

    Amdur, Robert J; Speers, Marjorie A

    2003-06-01

    Radiation oncologists frequently engage in activities that involve the collection and analysis of data from medical records. Access to health information is an ethical issue because, if not done according to appropriate guidelines, it constitutes an invasion of privacy or breach in confidentiality. To protect patients for the social harm that may result from medical record review, our society has established laws and regulations that apply to projects that require medical record review. A major branch point in the guidelines for such projects is whether private information will be collected for research or nonresearch purposes. However, a problem with discussing privacy protection in terms of a research versus nonresearch model is that it is difficult to make this distinction for many kinds of projects. The purpose of this paper is to establish a practical guideline that can be used to decide if a project that involves analysis of private, identifiable medical information should be considered research from the regulatory standpoint.

  19. Teacher Effectiveness in Identifying High-Risk Kindergarten Children.

    Science.gov (United States)

    Colarusso, Ronald P.; And Others

    1979-01-01

    Teacher effectiveness in identifying children "at risk" for learning problems was studied with five Head Start teachers. Results showed that, after training in classroom observation techniques, paraprofessional teachers are capable of identifying developmental delays in children. (PHR)

  20. Can a structured questionnaire identify patients with reduced renal function?

    DEFF Research Database (Denmark)

    Azzouz, Manal; Rømsing, Janne; Thomsen, Henrik

    2014-01-01

    To evaluate a structured questionnaire in identifying outpatients with renal dysfunction before MRI or CT in various age groups.......To evaluate a structured questionnaire in identifying outpatients with renal dysfunction before MRI or CT in various age groups....

  1. 3 Drugs Identified to Potentially Fight Zika Virus

    Science.gov (United States)

    ... html 3 Drugs Identified to Potentially Fight Zika Virus But only one is already approved in the ... fetuses protection against the damaging effects of Zika virus, a new multicenter study reports. Researchers identified these ...

  2. 26 CFR 1.6109-1 - Identifying numbers.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Identifying numbers. 1.6109-1 Section 1.6109-1...) INCOME TAXES Miscellaneous Provisions § 1.6109-1 Identifying numbers. (a) Information to be furnished after April 15, 1974. For provisions concerning the requesting and furnishing of identifying...

  3. 26 CFR 41.6109-1 - Identifying numbers.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Identifying numbers. 41.6109-1 Section 41.6109-1... Application to Tax On Use of Certain Highway Motor Vehicles § 41.6109-1 Identifying numbers. Every person required under § 41.6011(a)-1 to make a return must provide the identifying number required by...

  4. Decision Level Fusion of Fingerprint Minutiae Based Pseudonymous Identifiers

    NARCIS (Netherlands)

    Yang, Bian; Busch, Christoph; Groot, de Koen; Xu, Haiyun; Veldhuis, Raymond N.J.

    2011-01-01

    In a biometric template protected authentication system, a pseudonymous identifier is the part of a protected biometric template that can be compared directly against other pseudonymous identifiers. Each compared pair of pseudonymous identifiers results in a verification decision testing whether bot

  5. 40 CFR 174.529 - Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Bacillus thuringiensis modified Cry1Ab... Tolerance Exemptions § 174.529 Bacillus thuringiensis modified Cry1Ab protein as identified under OECD... Bacillus thuringiensis modified Cry1Ab protein as identified under OECD Unique Identifier SYN-IR67B-1...

  6. HIV-1 RNAs are Not Part of the Argonaute 2 Associated RNA Interference Pathway in Macrophages.

    Directory of Open Access Journals (Sweden)

    Valentina Vongrad

    Full Text Available MiRNAs and other small noncoding RNAs (sncRNAs are key players in post-transcriptional gene regulation. HIV-1 derived small noncoding RNAs (sncRNAs have been described in HIV-1 infected cells, but their biological functions still remain to be elucidated. Here, we approached the question whether viral sncRNAs may play a role in the RNA interference (RNAi pathway or whether viral mRNAs are targeted by cellular miRNAs in human monocyte derived macrophages (MDM.The incorporation of viral sncRNAs and/or their target RNAs into RNA-induced silencing complex was investigated using photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP as well as high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP, which capture Argonaute2-bound miRNAs and their target RNAs. HIV-1 infected monocyte-derived macrophages (MDM were chosen as target cells, as they have previously been shown to express HIV-1 sncRNAs. In addition, we applied small RNA deep sequencing to study differential cellular miRNA expression in HIV-1 infected versus non-infected MDMs.PAR-CLIP and HITS-CLIP data demonstrated the absence of HIV-1 RNAs in Ago2-RISC, although the presence of a multitude of HIV-1 sncRNAs in HIV-1 infected MDMs was confirmed by small RNA sequencing. Small RNA sequencing revealed that 1.4% of all sncRNAs were of HIV-1 origin. However, neither HIV-1 derived sncRNAs nor putative HIV-1 target sequences incorporated into Ago2-RISC were identified suggesting that HIV-1 sncRNAs are not involved in the canonical RNAi pathway nor is HIV-1 targeted by this pathway in HIV-1 infected macrophages.

  7. [3H]Azidodantrolene photoaffinity labeling, synthetic domain peptides and monoclonal antibody reactivity identify the dantrolene binding sequence on RyR1

    Energy Technology Data Exchange (ETDEWEB)

    Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Bhat, Manju B.; Ma, Jianjie; Ikemoto, Noriaki; Jimenez, Leslie S.; Morimoto, Hiromi; Williams, Philip G.; Parness, Jerome

    2002-06-14

    Dantrolene is a drug that suppresses intracellular Ca2+ release from sarcoplasmic reticulum in normal skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Though its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum, as a molecular target for dantrolene using the photoaffinity analog [3H]azidodantrolene(1). Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [3H]azidodantrolene,indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1, previously shown to affect RyR1 function in vitro and in vivo, were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2, peptide s containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [3H]azidodantrolene. A monoclonal anti-RyR1 antibody which recognizes RyR1 and its 1400 amino acid N-terminal fragment, recognizes DP1 and DP1-2 in both Western blots and immunoprecipitation assays, and specifically inhibits [3H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in sarcoplasmic reticulum. Our results indicate that synthetic domain peptides can mimic a native, ligand binding conformation in vitro, and that the dantrolene binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino-acids 590-609.

  8. ChIP-on-chip analysis identifies IL-22 as direct target gene of ectopically expressed FOXP3 transcription factor in human T cells

    Directory of Open Access Journals (Sweden)

    Jeron Andreas

    2012-12-01

    Full Text Available Abstract Background The transcription factor (TF forkhead box P3 (FOXP3 is constitutively expressed at high levels in naturally occurring CD4+CD25+ regulatory T cells (nTregs. It is not only the most accepted marker for that cell population but is also considered lineage determinative. Chromatin immunoprecipitation (ChIP of TFs in combination with genomic tiling microarray analysis (ChIP-on-chip has been shown to be an appropriate tool for identifying FOXP3 transcription factor binding sites (TFBSs on a genome-wide scale. In combination with microarray expression analysis, the ChIP-on-chip technique allows identification of direct FOXP3 target genes. Results ChIP-on-chip analysis of the human FOXP3 expressed in resting and PMA/ionomycin–stimulated Jurkat T cells revealed several thousand putative FOXP3 binding sites and demonstrated the importance of intronic regions for FOXP3 binding. The analysis of expression data showed that the stimulation-dependent down-regulation of IL-22 was correlated with direct FOXP3 binding in the IL-22 promoter region. This association was confirmed by real-time PCR analysis of ChIP-DNA. The corresponding ChIP-region also contained a matching FOXP3 consensus sequence. Conclusions Knowledge of the general distribution patterns of FOXP3 TFBSs in the human genome under resting and activated conditions will contribute to a better understanding of this TF and its influence on direct target genes, as well as its importance for the phenotype and function of Tregs. Moreover, FOXP3-dependent repression of Th17-related IL-22 may be relevant to an understanding of the phenomenon of Treg/Th17 cell plasticity.

  9. Global sensitivity and identifiability implications in systems biology

    OpenAIRE

    Dobre, Simona; Bastogne, Thierry; Richard, Alain

    2010-01-01

    International audience; In systems biology, a common approach to model biological processes is to use large systems of differential equations.The associated parameter estimation problem requires to prior handle identifiability and sensitivity issues in a practical biological framework. The lack of method to assess global practical identifiability has leaded us to analyze and establish bridges between global sensitivity and identifiability measures. Specifically, we are interested in deriving ...

  10. Accuracy of ultrasound to identify chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Richard; Allan; Kerry; Thoirs; Maureen; Phillips

    2010-01-01

    AIM:To identify and assess studies reporting the diagnostic performance of ultrasound imaging for identifying chronic liver disease(CLD)in a high risk population. METHODS:A search was performed to identify studies investigating the diagnostic accuracy of ultrasound imaging for CLD.Two authors independently used the quality assessment of diagnostic accuracy studies(QUADAS)checklist to assess the methodological quality of the selected studies.Inter-observer reliability of the QUADAS tool was assessed by measu...

  11. 44 CFR 5.27 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Deletion of identifying details. 5.27 Section 5.27 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY..., FEMA may delete identifying details when making available or publishing an opinion, statement of...

  12. A Note of the Investigation of Local and Global Identifiability.

    Science.gov (United States)

    McDonald, Roderick P.

    1982-01-01

    Typically, nonlinear models such as those used in the analysis of covariance structures, are not globally identifiable. Investigations of local identifiability must either yield a mapping onto the entire parameter space, or be confined to points of special interest such as the maximum likelihood point. (Author/JKS)

  13. Genomic Regions Affecting Cheese Making Properties Identified in Danish Holsteins

    DEFF Research Database (Denmark)

    Gregersen, Vivi Raundahl; Bertelsen, Henriette Pasgaard; Poulsen, Nina Aagaard

    The cheese renneting process is affected by a number of factors associated to milk composition and a number of Danish Holsteins has previously been identified to have poor milk coagulation ability. Therefore, the aim of this study was to identify genomic regions affecting the technological...

  14. Identifying a K-10 Developmental Framework for Teaching Philosophy

    Science.gov (United States)

    Poulton, Janette

    2014-01-01

    The intention of the study was to identify predictable opportunities for teachers to scaffold middle year students' philosophical learning. Such opportunities were identified in terms of students' readiness to learn certain behaviours in the context of a "community of inquiry". Thus it was hoped that the project would provide a useful…

  15. Contact endoscopy for identifying the parathyroid glands during thyroidectomy.

    Science.gov (United States)

    Guimarães, A V; Brandão, L G; Dedivitis, R A

    2010-02-01

    Aim of this study was to analyse contact endoscopy as an auxiliary method for identifying parathyroid glands during thyroid surgery and to identify other variables that may interfere with this correlation. Overall, 125 patients underwent thyroid surgery between January 2004 and February 2006. The variables analysed were: the total duration of surgery; time taken to locate and identify parathyroid glands; improvement in identifying these; numbers of parathyroid glands located by the surgeon and confirmed by contact endoscopy; histopathological diagnosis; presence of thyroiditis; thyroid weight; number of parathyroid glands left in thyroid specimens; and number of parathyroid gland autotransplantations. A total of 331 parathyroid glands were observed by the surgeon. However, 282 glands were identified by contact endoscopy. Nine parathyroid glands (7.2%) were observed together with thyroid specimens (Kappa = 0.534). The longer the total duration of surgery (p = 0.03) and time taken to locate and identify (p = 0.00) the parathyroid glands by contact endoscopy, the lower the observed agreement. The second year of performing contact endoscopy led to better agreement between the results (p = 0.02). In conclusion, contact endoscopy is an efficient auxiliary method for identifying parathyroid glands during thyroid surgery. During the period studied, association between total duration of surgery and time taken to locate and identify parathyroid glands was statistically significant.

  16. 36 CFR 1223.16 - How are vital records identified?

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false How are vital records identified? 1223.16 Section 1223.16 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS... identify vital records in the context of the emergency management function. Vital records are those...

  17. Identifying Interbank Loans, Rates, and Claims Networks from Transactional Data

    NARCIS (Netherlands)

    Leon Rincon, C.E.; Cely, Jorge; Cadena, Carlos

    2015-01-01

    We identify interbank (i.e. non-collateralized) loans from the Colombian large-value payment system by implementing Furfine’s method. After identifying interbank loans from transactional data we obtain the interbank rates and claims without relying on financial institutions’ reported data. Contrasti

  18. Identifiability of causal effect for a simple causal model

    Institute of Scientific and Technical Information of China (English)

    郑忠国; 张艳艳; 童行伟

    2002-01-01

    Counterfactual model is put forward to discuss the causal inference in the directed acyclic graph and its corresponding identifiability is thus studied with the ancillary information based on conditional independence. It is shown that the assumption of ignorability can be expanded to the assumption of replaceability,under which the causal efiects are identifiable.

  19. Evolving a NASA Digital Object Identifiers System with Community Engagement

    Science.gov (United States)

    Wanchoo, Lalit; James, Nathan

    2016-01-01

    To demonstrate how the ESDIS (Earth Science Data and Information System) DOI (Digital Object Identifier) system and its processes have evolved over these years based on the recommendations provided by the user community (whether the community members create and manage DOI information or use DOIs in the data citations). The user community is comprised of people with common interests and needs for data identifiers who are actively involved in the creation and usage process. Engagement describes the interactive context wherein the community provides information, evaluates the proposed processes, and provides guidance in the area of identifiers.

  20. Identifying Super-Spreader Nodes in Complex Networks

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Fu

    2015-01-01

    Full Text Available Identifying the most influential individuals spreading information or infectious diseases can assist or hinder information dissemination, product exposure, and contagious disease detection. Hub nodes, high betweenness nodes, high closeness nodes, and high k-shell nodes have been identified as good initial spreaders, but efforts to use node diversity within network structures to measure spreading ability are few. Here we describe a two-step framework that combines global diversity and local features to identify the most influential network nodes. Results from susceptible-infected-recovered epidemic simulations indicate that our proposed method performs well and stably in single initial spreader scenarios associated with various complex network datasets.

  1. Field potential soil variability index to identify precision agriculture opportunity

    Science.gov (United States)

    Precision agriculture (PA) technologies used for identifying and managing within-field variability are not widely used despite decades of advancement. Technological innovations in agronomic tools, such as canopy reflectance or electrical conductivity sensors, have created opportunities to achieve a ...

  2. A novel stroke locus identified in a northern Sweden pedigree

    DEFF Research Database (Denmark)

    Janunger, T.; Nilsson-Ardnor, S.; Wiklund, P.-G.

    2009-01-01

    to identify novel stroke susceptibility loci. METHODS: Through genealogy, 7 nuclear families with a common ancestor, connected over 8 generations, were identified. A genome-wide scan using 449 microsatellite markers was performed with subsequent haplotype analyses. RESULTS: A maximum allele-sharing lod score......OBJECTIVES: The population of northern Sweden is characterized by reduced genetic diversity and a high incidence of stroke. We sought to reduce genetic variation further, using genealogic analysis in a set of nuclear families affected by stroke, and we subsequently performed a genome-wide scan...... of 4.81 on chromosome 9q31-q33 was detected. Haplotype analysis identified a common 2.2-megabase interval in the chromosomal region in 4 of the nuclear families, where an overrepresentation of intracerebral hemorrhage was observed. CONCLUSIONS: We have identified a novel susceptibility locus for stroke...

  3. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

    2015-01-01

    , this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  4. 42 CFR 401.118 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... Deletion of identifying details. When CMS publishes or otherwise makes available an opinion or order, statement of policy, or other record which relates to a private party or parties, the name or names or...

  5. Can Zebrafish be used to Identify Developmentally Neurotoxic Chemicals

    Science.gov (United States)

    Can Zebrafish be Used to Identify Developmentally Neurotoxic Chemicals? The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental neurotoxicity. We are exploring behavioral methods using zebrafish by desig...

  6. Structure-based drug design identifies novel LPA3 antagonists.

    Science.gov (United States)

    Fells, James I; Tsukahara, Ryoko; Liu, Jianxiong; Tigyi, Gabor; Parrill, Abby L

    2009-11-01

    Compound 5 ([5-(3-nitrophenoxy)-1,3-dioxo-1,3-dihydro-2-isoindol-2-yl]acetic acid) was identified as a weak selective LPA(3) antagonist (IC(50)=4504 nM) in a virtual screening effort to optimize a dual LPA(2 and 3) antagonist. Structure-based drug design techniques were used to prioritize similarity search matches of compound 5. This strategy rapidly identified 10 novel antagonists. The two most efficacious compounds identified inhibit activation of the LPA(3) receptor by 200 nM LPA with IC(50) values of 752 nM and 2992 nM. These compounds additionally define changes to our previously reported pharmacophore that will improve its ability to identify more potent and selective LPA(3) receptor antagonists. The results of the combined computational and experimental screening are reported.

  7. Time delay and partial coherence analyses to identify cortical connectivities

    CERN Document Server

    Govindan, R B; Deuschl, G; Kopper, F; Raethjen, J

    2005-01-01

    Recently it has been demonstrated by Albo that partial coherence analysis is sensitive to signal to noise ratio (SNR) and that it will always identify the signal with the highest SNR among the three signals as the main (driving) influence. We propose to use time delay analysis in parallel to partial coherence analysis to identify the connectivities between the multivariate time series. Both are applied to a theoretical model (used by Albo) to analyse the connections introduced in the model. Time delay analysis identifies the connections correctly. We also apply these analyses to the electroencephalogram (EEG) and electromyogram (EMG) of essential tremor patients and EEG of normal subjects while bimanually tapping their index fingers. Biologically plausible cortico-muscular and cortico-cortical connections are identified by these methods.

  8. Novel lipid constituents identified in seeds of Nigella sativa (Linn)

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, B.K.; Verma, Manjul; Gupta, Meenal [Vikram University (India). School of Studies in Chemistry and Biochemistry]. E-mail: bkmehta11@yahoo.com

    2008-07-01

    Novel lipids were isolated from the unsaponifiable matter extracted from seeds of Nigella sativa Linn by using n-hexane. The new dienoate and two monoesters were the new lipids identified by spectral (IR, {sup 1}H- and {sup 13}C-NMR spectra, mass spectrum, elemental analysis) and chemical analysis. The dienoate (1) was identified as methylnonadeca-15,17-dienoate and two monoesters were identified as pentyl hexadec-12-enoate (2) and pentyl pentadec-11-enoate (3). Linoleic acid, oleic acid, {beta}-sitosterol and stigmasterol were identified as part of the lipid structures. All compounds exhibited moderate activity against Staphylococcus aureus and poor activity against shigella spp, and Klebsiella pneumoniae. (author)

  9. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

  10. Procedures for Identifying and Selecting a Minimum Competency Test.

    Science.gov (United States)

    Wildemuth, Barbara

    1979-01-01

    Describes the steps that a school district should follow in the first stages of implementing a minimum competency testing program: preparatory activities, defining the project, identifying existing tests, evaluating tests, developing a local test, and sharing knowledge. (Author)

  11. Identifying victims of violence using register-based data

    DEFF Research Database (Denmark)

    Kruse, Marie; Sørensen, Jan; Brønnum-Hansen, Henrik

    2010-01-01

    . We found significant differences between victims and non-victims according to socio-economic status, education, marital status, and ethnic origin, and also between victims by source of identification. CONCLUSIONS: We have identified a study population consisting of individual victims of violence......AIMS: The aim of this study was twofold. Firstly we identified victims of violence in national registers and discussed strengths and weaknesses of this approach. Secondly we assessed the magnitude of violence and the characteristics of the victims using register-based data. METHODS: We used three...... nationwide registers to identify victims of violence: The National Patient Register, the Victim Statistics, and the Causes of Death Register. We merged these data and assessed the degree of overlap between data sources. We identified a reference population by selecting all individuals in Denmark over 15...

  12. Using the National Provider Identifier for Health Care...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The establishment in recent years of a National Provider Identifier (NPI) offers a new method for counting and categorizing physicians and other health care...

  13. Identifying refuge resources of concern and management priorities : A handbook

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This handbook provides a strategy for anyone who must identify priorities (refuge resources of concern) that will guide future refuge wildlife and habitat...

  14. Comparing complete and partial classification for identifying customers at risk

    NARCIS (Netherlands)

    Bloemer, J.M.M.; Brijs, T.; Vanhoof, K.; Swinnen, S.P.

    2003-01-01

    This paper evaluates complete versus partial classification for the problem of identifying customers at risk. We define customers at risk as customers reporting overall satisfaction, but these customers also possess characteristics that are strongly associated with dissatisfied customers. This defin

  15. Identifying clinical course patterns in SMS data using cluster analysis

    DEFF Research Database (Denmark)

    Kent, Peter; Kongsted, Alice

    2012-01-01

    ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically importa...... of cluster analysis. More research is needed, especially head-to-head studies, to identify which technique is best to use under what circumstances.......ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically important...... by spline analysis. However, cluster analysis of SMS data in its original untransformed form may be simpler and offer other advantages. Therefore, the aim of this study was to determine whether cluster analysis could be used for identifying clinical course patterns distinct from the pattern of the whole...

  16. Covert Flow Graph Approach to Identifying Covert Channels

    OpenAIRE

    XiangMei Song; ShiGuang Ju

    2011-01-01

    In this paper, the approach for identifying covert channels using a graph structure called Covert Flow Graph is introduced. Firstly, the construction of Covert Flow Graph which can offer information flows of the system for covert channel detection is proposed, and the search and judge algorithm used to identify covert channels in Covert Flow Graph is given. Secondly, an example file system analysis using Covert Flow Graph approach is provided, and the analysis result is compared with that of ...

  17. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    Science.gov (United States)

    2015-04-01

    AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR: Dr. Purnima...SUBTITLE Sa. CONTRACT NUMBER W81XWH-1 3-1-0429 Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium 5b. GRANT NUMBER 5c. PROGRAM...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Sporozo ite infection of the liver is the first obl igate step of the Plasmodium

  18. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    Science.gov (United States)

    2016-06-01

    AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry " to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR...29Mar2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0429 Using click chemistry to identify potential drug targets in Plasmodium 5b...Al-Tsp derivatives begins. Two classes of Tsp derivatives (Al-Tsp) are appropriate for click chemistry (Fig. 1). Class I derivatives carry a

  19. An Advanced Threshold Secret Sharing Scheme for Identifying Cheaters

    Institute of Scientific and Technical Information of China (English)

    XIE Shu-cui; ZHANG Jian-zhong

    2003-01-01

    In this paper an advanced threshold secret sharing scheme for identifying cheaters is proposed by using authentication codes. The performance of the scheme is discussed. The results show that in the scheme the valid shareholders can not only identify the impersonation of an adversary, but also detect cheating of some valid shareholders. In particular one honest shareholder is able to detect cheating of other participants forming a collection, and the information rate of the scheme is higher than that of others.

  20. Identifying Epigenetic Modulators of Resistance to ERK Signaling Inhibitors

    Science.gov (United States)

    2015-08-01

    AWARD NUMBER: WSlXWH-14-1-0230 TITLE: Identifying Epigenetic Modulators of Resistance to ERK Signaling Inhibitors PRINCIPAL INVESTIGATOR: Emily...5a. CONTRACT NUMBER Identifying Epigenetic Modulators of Resistance to ERK Signaling Inhibitors 5b. GRANT NUMBER W8 1XWH- 1 4 - 1 - 0230 5c...response to targeted therapies in cancer. However, a global and unbiased approach to decipher the epigenetic mechanisms underlying melanoma drug

  1. Identifying People with Soft-Biometrics at Fleet Week

    Science.gov (United States)

    2013-03-01

    Forensics , Security and Intelligence, Firenze, Italy, 2010, pp. 25-30. [7] U. Park and A. Jain, "Face matching and retrieval using soft biometrics ...Identifying People with Soft- Biometrics at Fleet Week Eric Martinson NRC Post-Doctoral Fellow US Naval Research Laboratory Washington, DC...number of different features by which people can be identified. This work describes three alternative, soft biometrics (clothing, complexion, and

  2. Identifying risks in the realm of enterprise risk management.

    Science.gov (United States)

    Carroll, Roberta

    2016-01-01

    An enterprise risk management (ERM) discipline is comprehensive and organization-wide. The effectiveness of ERM is governed in part by the strength and breadth of its practices and processes. An essential element in decision making is a thorough process by which organizational risks and value opportunities can be identified. This article will offer identification techniques that go beyond those used in traditional risk management programs and demonstrate how these techniques can be used to identify risks and opportunity in the ERM environment.

  3. Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

    Directory of Open Access Journals (Sweden)

    Victor M. Bii

    2016-10-01

    Full Text Available Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types.

  4. Identifying and retargeting transcriptional hot spots in the human genome.

    Science.gov (United States)

    Cheng, Joseph K; Lewis, Amanda M; Kim, Do Soon; Dyess, Timothy; Alper, Hal S

    2016-08-01

    Mammalian cell line development requires streamlined methodologies that will reduce both the cost and time to identify candidate cell lines. Improvements in site-specific genomic editing techniques can result in flexible, predictable, and robust cell line engineering. However, an outstanding question in the field is the specific site of integration. Here, we seek to identify productive loci within the human genome that will result in stable, high expression of heterologous DNA. Using an unbiased, random integration approach and a green fluorescent reporter construct, we identify ten single-integrant, recombinant human cell lines that exhibit stable, high-level expression. From these cell lines, eight unique corresponding integration loci were identified. These loci are concentrated in non-protein coding regions or intronic regions of protein coding genes. Expression mapping of the surrounding genes reveals minimal disruption of endogenous gene expression. Finally, we demonstrate that targeted de novo integration at one of the identified loci, the 12(th) exon-intron region of the GRIK1 gene on chromosome 21, results in superior expression and stability compared to the standard, illegitimate integration approach at levels approaching 4-fold. The information identified here along with recent advances in site-specific genomic editing techniques can lead to expedited cell line development.

  5. Two statistics for evaluating parameter identifiability and error reduction

    Science.gov (United States)

    Doherty, John; Hunt, Randall J.

    2009-01-01

    Two statistics are presented that can be used to rank input parameters utilized by a model in terms of their relative identifiability based on a given or possible future calibration dataset. Identifiability is defined here as the capability of model calibration to constrain parameters used by a model. Both statistics require that the sensitivity of each model parameter be calculated for each model output for which there are actual or presumed field measurements. Singular value decomposition (SVD) of the weighted sensitivity matrix is then undertaken to quantify the relation between the parameters and observations that, in turn, allows selection of calibration solution and null spaces spanned by unit orthogonal vectors. The first statistic presented, "parameter identifiability", is quantitatively defined as the direction cosine between a parameter and its projection onto the calibration solution space. This varies between zero and one, with zero indicating complete non-identifiability and one indicating complete identifiability. The second statistic, "relative error reduction", indicates the extent to which the calibration process reduces error in estimation of a parameter from its pre-calibration level where its value must be assigned purely on the basis of prior expert knowledge. This is more sophisticated than identifiability, in that it takes greater account of the noise associated with the calibration dataset. Like identifiability, it has a maximum value of one (which can only be achieved if there is no measurement noise). Conceptually it can fall to zero; and even below zero if a calibration problem is poorly posed. An example, based on a coupled groundwater/surface-water model, is included that demonstrates the utility of the statistics. ?? 2009 Elsevier B.V.

  6. SitesIdentify: a protein functional site prediction tool

    Directory of Open Access Journals (Sweden)

    Doig Andrew J

    2009-11-01

    Full Text Available Abstract Background The rate of protein structures being deposited in the Protein Data Bank surpasses the capacity to experimentally characterise them and therefore computational methods to analyse these structures have become increasingly important. Identifying the region of the protein most likely to be involved in function is useful in order to gain information about its potential role. There are many available approaches to predict functional site, but many are not made available via a publicly-accessible application. Results Here we present a functional site prediction tool (SitesIdentify, based on combining sequence conservation information with geometry-based cleft identification, that is freely available via a web-server. We have shown that SitesIdentify compares favourably to other functional site prediction tools in a comparison of seven methods on a non-redundant set of 237 enzymes with annotated active sites. Conclusion SitesIdentify is able to produce comparable accuracy in predicting functional sites to its closest available counterpart, but in addition achieves improved accuracy for proteins with few characterised homologues. SitesIdentify is available via a webserver at http://www.manchester.ac.uk/bioinformatics/sitesidentify/

  7. On the Identifiability of the Post-Nonlinear Causal Model

    CERN Document Server

    Zhang, Kun

    2012-01-01

    By taking into account the nonlinear effect of the cause, the inner noise effect, and the measurement distortion effect in the observed variables, the post-nonlinear (PNL) causal model has demonstrated its excellent performance in distinguishing the cause from effect. However, its identifiability has not been properly addressed, and how to apply it in the case of more than two variables is also a problem. In this paper, we conduct a systematic investigation on its identifiability in the two-variable case. We show that this model is identifiable in most cases; by enumerating all possible situations in which the model is not identifiable, we provide sufficient conditions for its identifiability. Simulations are given to support the theoretical results. Moreover, in the case of more than two variables, we show that the whole causal structure can be found by applying the PNL causal model to each structure in the Markov equivalent class and testing if the disturbance is independent of the direct causes for each va...

  8. On linear models and parameter identifiability in experimental biological systems.

    Science.gov (United States)

    Lamberton, Timothy O; Condon, Nicholas D; Stow, Jennifer L; Hamilton, Nicholas A

    2014-10-07

    A key problem in the biological sciences is to be able to reliably estimate model parameters from experimental data. This is the well-known problem of parameter identifiability. Here, methods are developed for biologists and other modelers to design optimal experiments to ensure parameter identifiability at a structural level. The main results of the paper are to provide a general methodology for extracting parameters of linear models from an experimentally measured scalar function - the transfer function - and a framework for the identifiability analysis of complex model structures using linked models. Linked models are composed by letting the output of one model become the input to another model which is then experimentally measured. The linked model framework is shown to be applicable to designing experiments to identify the measured sub-model and recover the input from the unmeasured sub-model, even in cases that the unmeasured sub-model is not identifiable. Applications for a set of common model features are demonstrated, and the results combined in an example application to a real-world experimental system. These applications emphasize the insight into answering "where to measure" and "which experimental scheme" questions provided by both the parameter extraction methodology and the linked model framework. The aim is to demonstrate the tools' usefulness in guiding experimental design to maximize parameter information obtained, based on the model structure.

  9. Identifying gene networks underlying the neurobiology of ethanol and alcoholism.

    Science.gov (United States)

    Wolen, Aaron R; Miles, Michael F

    2012-01-01

    For complex disorders such as alcoholism, identifying the genes linked to these diseases and their specific roles is difficult. Traditional genetic approaches, such as genetic association studies (including genome-wide association studies) and analyses of quantitative trait loci (QTLs) in both humans and laboratory animals already have helped identify some candidate genes. However, because of technical obstacles, such as the small impact of any individual gene, these approaches only have limited effectiveness in identifying specific genes that contribute to complex diseases. The emerging field of systems biology, which allows for analyses of entire gene networks, may help researchers better elucidate the genetic basis of alcoholism, both in humans and in animal models. Such networks can be identified using approaches such as high-throughput molecular profiling (e.g., through microarray-based gene expression analyses) or strategies referred to as genetical genomics, such as the mapping of expression QTLs (eQTLs). Characterization of gene networks can shed light on the biological pathways underlying complex traits and provide the functional context for identifying those genes that contribute to disease development.

  10. Identifying glioblastoma gene networks based on hypergeometric test analysis.

    Directory of Open Access Journals (Sweden)

    Vasileios Stathias

    Full Text Available Patient specific therapy is emerging as an important possibility for many cancer patients. However, to identify such therapies it is essential to determine the genomic and transcriptional alterations present in one tumor relative to control samples. This presents a challenge since use of a single sample precludes many standard statistical analysis techniques. We reasoned that one means of addressing this issue is by comparing transcriptional changes in one tumor with those observed in a large cohort of patients analyzed by The Cancer Genome Atlas (TCGA. To test this directly, we devised a bioinformatics pipeline to identify differentially expressed genes in tumors resected from patients suffering from the most common malignant adult brain tumor, glioblastoma (GBM. We performed RNA sequencing on tumors from individual GBM patients and filtered the results through the TCGA database in order to identify possible gene networks that are overrepresented in GBM samples relative to controls. Importantly, we demonstrate that hypergeometric-based analysis of gene pairs identifies gene networks that validate experimentally. These studies identify a putative workflow for uncovering differentially expressed patient specific genes and gene networks for GBM and other cancers.

  11. Fungi identify the geographic origin of dust samples.

    Directory of Open Access Journals (Sweden)

    Neal S Grantham

    Full Text Available There is a long history of archaeologists and forensic scientists using pollen found in a dust sample to identify its geographic origin or history. Such palynological approaches have important limitations as they require time-consuming identification of pollen grains, a priori knowledge of plant species distributions, and a sufficient diversity of pollen types to permit spatial or temporal identification. We demonstrate an alternative approach based on DNA sequencing analyses of the fungal diversity found in dust samples. Using nearly 1,000 dust samples collected from across the continental U.S., our analyses identify up to 40,000 fungal taxa from these samples, many of which exhibit a high degree of geographic endemism. We develop a statistical learning algorithm via discriminant analysis that exploits this geographic endemicity in the fungal diversity to correctly identify samples to within a few hundred kilometers of their geographic origin with high probability. In addition, our statistical approach provides a measure of certainty for each prediction, in contrast with current palynology methods that are almost always based on expert opinion and devoid of statistical inference. Fungal taxa found in dust samples can therefore be used to identify the origin of that dust and, more importantly, we can quantify our degree of certainty that a sample originated in a particular place. This work opens up a new approach to forensic biology that could be used by scientists to identify the origin of dust or soil samples found on objects, clothing, or archaeological artifacts.

  12. Identifying influential spreaders in complex networks based on gravity formula

    Science.gov (United States)

    Ma, Ling-ling; Ma, Chuang; Zhang, Hai-Feng; Wang, Bing-Hong

    2016-06-01

    How to identify the influential spreaders in social networks is crucial for accelerating/hindering information diffusion, increasing product exposure, controlling diseases and rumors, and so on. In this paper, by viewing the k-shell value of each node as its mass and the shortest path distance between two nodes as their distance, then inspired by the idea of the gravity formula, we propose a gravity centrality index to identify the influential spreaders in complex networks. The comparison between the gravity centrality index and some well-known centralities, such as degree centrality, betweenness centrality, closeness centrality, and k-shell centrality, and so forth, indicates that our method can effectively identify the influential spreaders in real networks as well as synthetic networks. We also use the classical Susceptible-Infected-Recovered (SIR) epidemic model to verify the good performance of our method.

  13. A Study of Scientometric Methods to Identify Emerging Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Abercrombie, Robert K [ORNL; Udoeyop, Akaninyene W [ORNL

    2011-01-01

    This work examines a scientometric model that tracks the emergence of an identified technology from initial discovery (via original scientific and conference literature), through critical discoveries (via original scientific, conference literature and patents), transitioning through Technology Readiness Levels (TRLs) and ultimately on to commercial application. During the period of innovation and technology transfer, the impact of scholarly works, patents and on-line web news sources are identified. As trends develop, currency of citations, collaboration indicators, and on-line news patterns are identified. The combinations of four distinct and separate searchable on-line networked sources (i.e., scholarly publications and citation, worldwide patents, news archives, and on-line mapping networks) are assembled to become one collective network (a dataset for analysis of relations). This established network becomes the basis from which to quickly analyze the temporal flow of activity (searchable events) for the example subject domain we investigated.

  14. A predictive approach to identify genes differentially expressed

    Science.gov (United States)

    Saraiva, Erlandson F.; Louzada, Francisco; Milan, Luís A.; Meira, Silvana; Cobre, Juliana

    2012-10-01

    The main objective of gene expression data analysis is to identify genes that present significant changes in expression levels between a treatment and a control biological condition. In this paper, we propose a Bayesian approach to identify genes differentially expressed calculating credibility intervals from predictive densities which are constructed using sampled mean treatment effect from all genes in study excluding the treatment effect of genes previously identified with statistical evidence for difference. We compare our Bayesian approach with the standard ones based on the use of the t-test and modified t-tests via a simulation study, using small sample sizes which are common in gene expression data analysis. Results obtained indicate that the proposed approach performs better than standard ones, especially for cases with mean differences and increases in treatment variance in relation to control variance. We also apply the methodologies to a publicly available data set on Escherichia coli bacteria.

  15. Identifying Differentially Abundant Metabolic Pathways in Metagenomic Datasets

    Science.gov (United States)

    Liu, Bo; Pop, Mihai

    Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of such studies is to identify specific functional adaptations of microbial communities to their habitats. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic data-sets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. We show that MetaPath outperforms other common approaches when evaluated on simulated datasets. We also demonstrate the power of our methods in analyzing two, publicly available, metagenomic datasets: a comparison of the gut microbiome of obese and lean twins; and a comparison of the gut microbiome of infant and adult subjects. We demonstrate that the subpathways identified by our method provide valuable insights into the biological activities of the microbiome.

  16. Benchmarking in Identifying Priority Directions of Development of Telecommunication Operators

    Directory of Open Access Journals (Sweden)

    Zaharchenko Lolita A.

    2013-12-01

    Full Text Available The article analyses evolution of development and possibilities of application of benchmarking in the telecommunication sphere. It studies essence of benchmarking on the basis of generalisation of approaches of different scientists to definition of this notion. In order to improve activity of telecommunication operators, the article identifies the benchmarking technology and main factors, that determine success of the operator in the modern market economy, and the mechanism of benchmarking and component stages of carrying out benchmarking by a telecommunication operator. It analyses the telecommunication market and identifies dynamics of its development and tendencies of change of the composition of telecommunication operators and providers. Having generalised the existing experience of benchmarking application, the article identifies main types of benchmarking of telecommunication operators by the following features: by the level of conduct of (branch, inter-branch and international benchmarking; by relation to participation in the conduct (competitive and joint; and with respect to the enterprise environment (internal and external.

  17. Family and academic performance: identifying high school student profiles

    Directory of Open Access Journals (Sweden)

    Alicia Aleli Chaparro Caso López

    2016-01-01

    Full Text Available The objective of this study was to identify profiles of high school students, based on variables related to academic performance, socioeconomic status, cultural capital and family organization. A total of 21,724 high school students, from the five municipalities of the state of Baja California, took part. A K-means cluster analysis was performed to identify the profiles. The analyses identified two clearly-defined clusters: Cluster 1 grouped together students with high academic performance and who achieved higher scores for socioeconomic status, cultural capital and family involvement, whereas Cluster 2 brought together students with low academic achievement, and who also obtained lower scores for socioeconomic status and cultural capital, and had less family involvement. It is concluded that the family variables analyzed form student profiles that can be related to academic achievement.

  18. Identifying genetics and genomics nursing competencies common among published recommendations.

    Science.gov (United States)

    Greco, Karen E; Salveson, Catherine

    2009-10-01

    The purpose of this article is to identify published recommendations for genetics and genomics competencies or curriculum for nurses in the United States and to summarize genetic and genomic nursing competencies based on common themes among these documents. A review of the literature between January 1998 and June 2008 was conducted. Efforts were also made to access the gray literature. Five consensus documents describing recommendations for genetics and genomics competencies for nurses meeting inclusion criteria were analyzed. Twelve genetics and genomics competencies were created based on common themes among the recommendations. These competencies include: demonstrate an understanding of basic genetic and genomic concepts, provide and explain genetic and genomic information, refer to appropriate genetics professionals and services, and identify the limits of one's own genetics and genomics expertise. The competencies represent fundamental genetics and genomics competencies for nurses on the basis of common themes among several consensus recommendations identified in the literature.

  19. Identifying attributes of GPU programs for difficulty evaluation

    Directory of Open Access Journals (Sweden)

    Dale Tristram

    2014-08-01

    Full Text Available General-purpose computation on graphics processing units (GPGPU has great potential to accelerate many scientific models and algorithms. However, some problems are considerably more difficult to accelerate than others, and it may be challenging for those new to GPGPU to ascertain the difficulty of accelerating a particular problem. Through what was learned in the acceleration of three problems, problem attributes have been identified that can assist in the evaluation of the difficulty of accelerating a problem on a GPU. The identified attributes are a problem's available parallelism, inherent parallelism, synchronisation requirements, and data transfer requirements. We envisage that with further development, these attributes could form the foundation of a difficulty classification system that could be used to determine whether GPU acceleration is practical for a candidate GPU acceleration problem, aid in identifying appropriate techniques and optimisations, and outline the required GPGPU knowledge.

  20. The Patent Literature As A Shortcut To Identify Knowledge Suppliers

    DEFF Research Database (Denmark)

    Søberg, Peder Veng

    The present paper explores characteristics of valuable patents that have been subject to litigation which resulted in some of the largest fines to patent infringers reported in history. The valuable patents are compared with less valuable patents in order to identify new methods of evaluating pat...... patents which decreases the time span between a patent is filed and its value can be evaluated when searching the patent literature. A potential benefit thereof could be that the patent literature could become relevant in order to identify potential knowledge suppliers.......The present paper explores characteristics of valuable patents that have been subject to litigation which resulted in some of the largest fines to patent infringers reported in history. The valuable patents are compared with less valuable patents in order to identify new methods of evaluating...

  1. Nursing diagnoses identified in children with acute respiration infection

    Directory of Open Access Journals (Sweden)

    Flávia Paula Magalhães Monteiro

    2006-08-01

    Full Text Available A cross-sectional study developed with 78 children with until five years old, bearers of acute respiration infection interned in pediatric hospital of the periphery of a great city, with the purpose to identify the nursing diagnoses presented by these children. The number of nursing diagnoses, defining characteristics, related factors and risk factors identified and other numerical variables were analyzed based in theirs central tendency and dispersion measures. It was identified a total of 26 nursing diagnoses, 43 related factors, 14 risk factors e 67 defining characteristics. In average, It was found 5,32 nursing diagnoses; 4,10 related factors; 2,03 risk factors and 7,33 defining characteristics. The nursing diagnoses with the biggest proportion were: Ineffective Breathing Pattern, Risk for delayed growth, Ineffective protection and Altered oral mucous membrane. We concluded that children with acute respiration infection present a complex diagnostic frame including human responses of multiples domains.

  2. A Community-Based Approach to Identifying Influential Spreaders

    Directory of Open Access Journals (Sweden)

    Zhiying Zhao

    2015-04-01

    Full Text Available Identifying influential spreaders in complex networks has a significant impact on understanding and control of spreading process in networks. In this paper, we introduce a new centrality index to identify influential spreaders in a network based on the community structure of the network. The community-based centrality (CbC considers both the number and sizes of communities that are directly linked by a node. We discuss correlations between CbC and other classical centrality indices. Based on simulations of the single source of infection with the Susceptible-Infected-Recovered (SIR model, we find that CbC can help to identify some critical influential nodes that other indices cannot find. We also investigate the stability of CbC.

  3. Rapid identifying high-influence nodes in complex networks

    Institute of Scientific and Technical Information of China (English)

    宋波; 蒋国平; 宋玉蓉; 夏玲玲

    2015-01-01

    A tiny fraction of infl uential individuals play a critical role in the dynamics on complex systems. Identifying the infl uential nodes in complex networks has theoretical and practical significance. Considering the uncertainties of network scale and topology, and the timeliness of dynamic behaviors in real networks, we propose a rapid identifying method (RIM) to find the fraction of high-infl uential nodes. Instead of ranking all nodes, our method only aims at ranking a small number of nodes in network. We set the high-infl uential nodes as initial spreaders, and evaluate the performance of RIM by the susceptible–infected–recovered (SIR) model. The simulations show that in different networks, RIM performs well on rapid identifying high-infl uential nodes, which is verified by typical ranking methods, such as degree, closeness, betweenness, and eigenvector centrality methods.

  4. A Note on the Identifiability of Generalized Linear Mixed Models

    DEFF Research Database (Denmark)

    Labouriau, Rodrigo

    2014-01-01

    I present here a simple proof that, under general regularity conditions, the standard parametrization of generalized linear mixed model is identifiable. The proof is based on the assumptions of generalized linear mixed models on the first and second order moments and some general mild regularity ...... conditions, and, therefore, is extensible to quasi-likelihood based generalized linear models. In particular, binomial and Poisson mixed models with dispersion parameter are identifiable when equipped with the standard parametrization......I present here a simple proof that, under general regularity conditions, the standard parametrization of generalized linear mixed model is identifiable. The proof is based on the assumptions of generalized linear mixed models on the first and second order moments and some general mild regularity...

  5. A New Method for Identifying the Life Parameters via Radar

    Directory of Open Access Journals (Sweden)

    Lu Guohua

    2007-01-01

    Full Text Available It has been proved that the vital signs can be detected via radar. To better identify the life parameters such as respiration and heartbeat, a novel method combined with several signal processing techniques is presented. Firstly, to improve the signal-to-noise ratio (SNR of the life signals, the signal accumulation technique by FFT is used. Then, to restrain the interferences produced by moving objects, a dual filtering algorithm (DFA which is able to remove the interferences by tracing the interfering spectral peaks is proposed. Finally, the wavelet transform is applied to separate the heartbeat from the respiration signal. The method cannot only help to automatically detect the existence of human beings effectively, but also identifying the parameters like respiration, heartbeat, and body-moving signals significantly. Experimental results demonstrated that the method is very promising in identifying the life parameters via radar.

  6. Identifying information technology competencies needed in Singapore nursing education.

    Science.gov (United States)

    Yee, Chia Choon

    2002-01-01

    The purpose of the study was to identify Singapore's healthcare industry's minimum information technology (IT) performance standard expectations for nurses' competencies. A needs assessment was conducted with a panel representing nursing education, nursing management and nursing practice. The findings in this study would provide suggestions to improve the current diploma and advanced diploma nursing programs curricula to meet the present workforce demands. The experts agreed that information technology is necessary and there were two main categories of IT skills identified, basic IT skills and work-related IT skills.

  7. Identifying different learning styles to enhance the learning experience.

    Science.gov (United States)

    Anderson, Irene

    2016-10-12

    Identifying your preferred learning style can be a useful way to optimise learning opportunities, and can help learners to recognise their strengths and areas for development in the way that learning takes place. It can also help teachers (educators) to recognise where additional activities are required to ensure the learning experience is robust and effective. There are several models available that may be used to identify learning styles. This article discusses these models and considers their usefulness in healthcare education. Models of teaching styles are also considered.

  8. Recent Developments in Methods for Identifying Reaction Coordinates

    CERN Document Server

    Li, Wenjin

    2015-01-01

    In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the reaction coordinates based on limited information from molecular dynamics simulations. In this review, we provide a brief survey over a number of major methods developed in the past decade, some of which are discussed in greater detail, to provide an overview of the problems that are partially solved and challenges that still remain. A particular emphasis has been placed on methods for identifying reaction coordinates that are related to the committor.

  9. Recent developments in methods for identifying reaction coordinates.

    Science.gov (United States)

    Li, Wenjin; Ma, Ao

    2014-01-01

    In the study of rare events in complex systems with many degrees of freedom, a key element is to identify the reaction coordinates of a given process. Over recent years, a number of methods and protocols have been developed to extract the reaction coordinates based on limited information from molecular dynamics simulations. In this review, we provide a brief survey over a number of major methods developed in the past decade, some of which are discussed in greater detail, to provide an overview of the problems that are partially solved and challenges that still remain. A particular emphasis has been placed on methods for identifying reaction coordinates that are related to the committor.

  10. PlateRunner: A Search Engine to Identify EMR Boilerplates.

    Science.gov (United States)

    Divita, Guy; Workman, T Elizabeth; Carter, Marjorie E; Redd, Andrew; Samore, Matthew H; Gundlapalli, Adi V

    2016-01-01

    Medical text contains boilerplated content, an artifact of pull-down forms from EMRs. Boilerplated content is the source of challenges for concept extraction on clinical text. This paper introduces PlateRunner, a search engine on boilerplates from the US Department of Veterans Affairs (VA) EMR. Boilerplates containing concepts should be identified and reviewed to recognize challenging formats, identify high yield document titles, and fine tune section zoning. This search engine has the capability to filter negated and asserted concepts, save and search query results. This tool can save queries, search results, and documents found for later analysis.

  11. Identifying the interactions in a colored dynamical network

    Institute of Scientific and Technical Information of China (English)

    吴召艳; 弓晓利

    2015-01-01

    The interactions of a colored dynamical network play a great role in its dynamical behaviour and are denoted by outer and inner coupling matrices. In this paper, the outer and inner coupling matrices are assumed to be unknown and need to be identified. A corresponding network estimator is designed for identifying the unknown interactions by adopting proper adaptive laws. Based on the Lyapunov function method and Barbalat’s lemma, the obtained result is analytically proved. A colored network coupled with chaotic Lorenz, Chen, and L ¨u systems is considered as a numerical example to illustrate the effectiveness of the proposed method.

  12. On Identifying which Intermediate Nodes Should Code in Multicast Networks

    DEFF Research Database (Denmark)

    Pinto, Tiago; Roetter, Daniel Enrique Lucani; Médard, Muriel

    2013-01-01

    the data packets. Previous work has shown that in lossless wireline networks, the performance of tree-packing mechanisms is comparable to network coding, albeit with added complexity at the time of computing the trees. This means that most nodes in the network need not code. Thus, mechanisms that identify...... intermediate nodes that do require coding is instrumental for the efficient operation of coded networks and can have a significant impact in overall energy consumption. We present a distributed, low complexity algorithm that allows every node to identify if it should code and, if so, through what output link...

  13. Pitfalls of mapping high throughput sequencing data to repetitive sequences: Piwi’s genomic targets still not identified

    Science.gov (United States)

    Marinov, Georgi K.; Wang, Jie; Handler, Dominik; Wold, Barbara J.; Weng, Zhiping; Hannon, Gregory J.; Aravin, Alexei A.; Zamore, Phillip D.; Brennecke, Julius; Toth, Katalin Fejes

    2015-01-01

    Huang et al. (2013) recently reported that chromatin immuno-precipitation followed by sequencing (ChIP-seq) reveals the genome-wide sites of occupancy by Piwi - a piRNA-guided Argonaute protein central to transposon silencing in Drosophila. Their study also reported that loss of Piwi causes widespread rewiring of transcriptional patterns as evidenced by changes in RNA polymerase II occupancy across the genome. Here we reanalyze their underlying deep sequencing data and report that the data do not support the author’s central conclusions. PMID:25805138

  14. Peer Promotions as a Method to Identify Quality Content

    Science.gov (United States)

    Gunnarsson, Bjorn Levi; Alterman, Richard

    2014-01-01

    Promoting blog content is a social activity--a means of communicating one student's appreciation of another student's work. This article explores the feasibility of using student promotions of content, in a blogosphere, to identify quality content, and implications for students and instructors. We show that students actively and voluntarily…

  15. An Analytical Method of Identifying Biased Test Items.

    Science.gov (United States)

    Plake, Barbara S.; Hoover, H. D.

    1979-01-01

    A follow-up technique is needed to identify items contributing to items-by-groups interaction when using an ANOVA procedure to examine a test for biased items. The method described includes distribution theory for assessing level of significance and is sensitive to items at all difficulty levels. (Author/GSK)

  16. Using mixed methods to identify factors influencing patient flow.

    Science.gov (United States)

    Van Vaerenbergh, Cindy

    2009-11-01

    An effective method of identifying operational factors that influence patient flow can potentially lead to improvements and thus have huge benefits on the efficiency of hospital departments. This paper presents a new inductive mixed-method approach to identify operational factors that influence patient flow through an accident and emergency (A&E) department. Preliminary explorative observations were conducted, followed by semi-structured interviews with key stakeholders. A questionnaire survey of all medical, nursing, porter and clerical staff was then conducted. The observations provided factors for further exploration: skill-mix, long working hours, equipment availability, lack of orientation programmes, inefficient IT use and issues regarding communication structures. Interviewees highlighted several factors, including availability of medical supervision and senior nursing staff, nursing documentation issues, lack of morale due to overcrowding, personality differences and factors relating to the department layout. The questionnaire respondents strongly supported the importance of the previously identified factors. This paper demonstrates an effective mixed-method approach that can be replicated by other health-care managers to identify factors influencing patient flow. Further benefits include increased volume and quality of data, increased staff awareness for the influence of internal factors on patient flow and enhancing the evidence base for future decision making when prioritizing A&E projects.

  17. Systems constellations : A better way to identify branding opportunities?

    NARCIS (Netherlands)

    Jurg, W.; Bloemer, J.; Doorewaard, H.; Peelen, E.

    2008-01-01

    Building strong brands has become one of the main marketing priorities for brand-supportive companies. The leading positivist paradigm in marketing may not be, however, the most-effective perspective in identifying branding opportunities. This paper offers an alternative phenomenological point of vi

  18. Identifying and Mitigating Sources of School Revenue Erosion

    Science.gov (United States)

    Prombo, Michael; Dalianis, Ares G.; Metcalf, Scott R.

    2009-01-01

    Preserving existing revenues is an essential component of the work of school business officials. The broad ranges of activities that can affect school district revenues make identifying potential threats difficult. By understanding the issues that affect school district revenue, school business officials are better able to diminish its erosion--a…

  19. Identifying the "Truly Disadvantaged": A Comprehensive Biosocial Approach

    Science.gov (United States)

    Barnes, J. C.; Beaver, Kevin M.; Connolly, Eric J.; Schwartz, Joseph A.

    2016-01-01

    There has been significant interest in examining the developmental factors that predispose individuals to chronic criminal offending. This body of research has identified some social-environmental risk factors as potentially important. At the same time, the research producing these results has generally failed to employ genetically sensitive…

  20. Identifying Balanced Action Learning: Cases of South Korean Practices

    Science.gov (United States)

    Cho, Yonjoo; Bong, Hyeon-Cheol

    2010-01-01

    Despite considerable commitment to the application of action learning as leadership and organization development by a large number of Korean organizations, few identified empirical studies of action learning practices have been reported. The purpose of this study was to conduct case studies of South Korean action learning practices to examine…

  1. How to Identify and Forecast Bull and Bear Markets?

    NARCIS (Netherlands)

    H.J.W.G. Kole (Erik); D.J.C. van Dijk (Dick)

    2013-01-01

    textabstractThe state of the equity market, often referred to as a bull or a bear market, is of key importance for financial decisions and economic analyses. Its latent nature has led to several methods to identify past and current states of the market and forecast future states. These methods encom

  2. BIOELECTRICAL IMPEDANCE VECTOR ANALYSIS IDENTIFIES SARCOPENIA IN NURSING HOME RESIDENTS

    Science.gov (United States)

    Loss of muscle mass and water shifts between body compartments are contributing factors to frailty in the elderly. The body composition changes are especially pronounced in institutionalized elderly. We investigated the ability of single-frequency bioelectrical impedance analysis (BIA) to identify b...

  3. Identifying subgroups of patients using latent class analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Mølgaard; Kent, Peter; Hestbæk, Lise

    2017-01-01

    BACKGROUND: Heterogeneity in patients with low back pain (LBP) is well recognised and different approaches to subgrouping have been proposed. Latent Class Analysis (LCA) is a statistical technique that is increasingly being used to identify subgroups based on patient characteristics. However, as ...

  4. Identifying Subgroups among Hardcore Smokers: a Latent Profile Approach

    NARCIS (Netherlands)

    Bommelé, J.; Kleinjan, M.; Schoenmakers, T.M.; Eijnden, R. van den; Mheen, D. van de

    2015-01-01

    Introduction: Hardcore smokers are smokers who have little to no intention to quit. Previous research suggests that there are distinct subgroups among hardcore smokers and that these subgroups vary in the perceived pros and cons of smoking and quitting. Identifying these subgroups could help to deve

  5. Use of Photogrammetry and Biomechanical Gait analysis to Identify Individuals

    DEFF Research Database (Denmark)

    Larsen, Peter Kastmand; Simonsen, Erik Bruun; Lynnerup, Niels

    Photogrammetry and recognition of gait patterns are valuable tools to help identify perpetrators based on surveillance recordings. We have found that stature but only few other measures have a satisfying reproducibility for use in forensics. Several gait variables with high recognition rates were...

  6. Researchers Develop Method to Identify Sparticles in Big Bang Conditions

    CERN Multimedia

    2008-01-01

    Three Northeastern University researchers have proposed a new approach for the highly anticipated discovery of supersymmetric particles, often called sparticles. The methodology, which was published in the December 21 issue of the Physical Review Letters, is based on identifying the hierarchical mass patterns of sparticles, which are assumed to exist in a new class of particle physics theories beyond the Standard Model.

  7. Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

    Energy Technology Data Exchange (ETDEWEB)

    Cook, Melloni N. [University of Memphis; Dunning, Jonathan P [University of Memphis; Wiley, Ronald G [Vanderbilt University and Veterans Administration, Nashville, TN; Chesler, Elissa J [ORNL; Johnson, Dabney K [ORNL; Goldowitz, Daniel [University of Tennessee Health Science Center, Memphis

    2007-01-01

    We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsiveness to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.

  8. Identifying targets for quality improvement in hospital antibiotic prescribing

    NARCIS (Netherlands)

    Spreuwel, P.C. van; Blok, H.; Langelaar, M.F.; Kullberg, B.J.; Mouton, J.W.; Natsch, S.S.

    2015-01-01

    OBJECTIVES: To audit antibiotic use in a university hospital and to identify targets for quality improvement in a setting with low antibiotic use and resistance rates. METHODOLOGY: A point-prevalence survey (PPS), using a patient-based audit tool for antibiotic use, was executed in the Radboud Unive

  9. Using Impact Modulation to Identify Loose Bolts on a Satellite

    Science.gov (United States)

    2011-10-21

    damping parameters can be extracted. Bowden and Dugundji [33] and Esteben and Rogers [34] also identified stiffness and damping parameters in a beam...M. Bowden and J. Dugundji . Joint damping and nonlinearity in dynamics of space structures. AIAA Journal, 28(4):740–749, 1988. [34] J.Esteban and C. A

  10. 75 FR 14539 - Furnishing Identifying Number of Tax Return Preparer

    Science.gov (United States)

    2010-03-26

    ..., will increase tax compliance and allow taxpayers to be confident that the tax return preparers to whom... required to obtain and use a PTIN as the exclusive preparer identifying number and undergo a tax-compliance... testing, continuing education, and tax compliance checks. The Report contemplates that only...

  11. New technique for identifying varieties resistance to rice blast

    Institute of Scientific and Technical Information of China (English)

    ZHUPeiliang

    1994-01-01

    After 8 yrs lab experiments and field tests, an advanced technique for identifying varieties resistance to rice blast was developed by a research group in Plant Protection Institute, Zhejiang Academy of AgricuLltural Sciences. With this technique, the inoculum was prepared on a maizc-rice-straw-agar media which was suitable for sporulation of most rice blast pathogen isolates.

  12. Research to Identify Effective Antifungal Agents, 1992 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Carl

    1993-03-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990 and Schreck et al. 1991). The objectives of the present study were to select and evaluate up to 10 candidate fungicides.

  13. Adaptive Neural Network Nonparametric Identifier With Normalized Learning Laws.

    Science.gov (United States)

    Chairez, Isaac

    2016-04-05

    This paper addresses the design of a normalized convergent learning law for neural networks (NNs) with continuous dynamics. The NN is used here to obtain a nonparametric model for uncertain systems described by a set of ordinary differential equations. The source of uncertainties is the presence of some external perturbations and poor knowledge of the nonlinear function describing the system dynamics. A new adaptive algorithm based on normalized algorithms was used to adjust the weights of the NN. The adaptive algorithm was derived by means of a nonstandard logarithmic Lyapunov function (LLF). Two identifiers were designed using two variations of LLFs leading to a normalized learning law for the first identifier and a variable gain normalized learning law. In the case of the second identifier, the inclusion of normalized learning laws yields to reduce the size of the convergence region obtained as solution of the practical stability analysis. On the other hand, the velocity of convergence for the learning laws depends on the norm of errors in inverse form. This fact avoids the peaking transient behavior in the time evolution of weights that accelerates the convergence of identification error. A numerical example demonstrates the improvements achieved by the algorithm introduced in this paper compared with classical schemes with no-normalized continuous learning methods. A comparison of the identification performance achieved by the no-normalized identifier and the ones developed in this paper shows the benefits of the learning law proposed in this paper.

  14. Identifying Heterogeneities in Subsurface Environment using the Level Set Method

    Energy Technology Data Exchange (ETDEWEB)

    Lei, Hongzhuan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lu, Zhiming [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vesselinov, Velimir Valentinov [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-25

    These are slides from a presentation on identifying heterogeneities in subsurface environment using the level set method. The slides start with the motivation, then explain Level Set Method (LSM), the algorithms, some examples are given, and finally future work is explained.

  15. Examination of Leadership Practices of Principals Identified as Servant Leaders

    Science.gov (United States)

    Taylor, Tim; Martin, Barbara N.; Hutchinson, Sandy; Jinks, Michael

    2007-01-01

    The purpose of this study was to examine the leadership practices of principals identified as servant leaders. The conceptual framework used to access the leadership behaviours was the leadership practices advocated by Kouzes and Posner. Statistical analysis included a multivariate test to determine if the demographic variables were significantly…

  16. Identifying Different Registers of Digital Literacy in Virtual Learning Environments

    Science.gov (United States)

    Knutsson, Ola; Blasjo, Mona.; Hallsten, Stina; Karlstrom, Petter

    2012-01-01

    In this paper social semiotics, and systemic functional linguistics in particular, are used in order to identify registers of digital literacy in the use of virtual learning environments. The framework of social semiotics provides means to systemize and discuss digital literacy as a linguistic and semiotic issue. The following research question…

  17. Identifying cognitive predictors of reactive and proactive aggression

    NARCIS (Netherlands)

    Brugman, S.; Lobbestael, J.; Arntz, A.; Cima, M.; Schuhmann, T.; Dambacher, F.; Sack, A.T.

    2015-01-01

    The aim of this study was to identify implicit cognitive predictors of aggressive behavior. Specifically, the predictive value of an attentional bias for aggressive stimuli and automatic association of the self and aggression was examined for reactive and proactive aggressive behavior in a non-clini

  18. X-factor for innovation: identifying future excellent professionals

    NARCIS (Netherlands)

    Banis-den Hertog, Jaantje Hazina

    2016-01-01

    In this study we wanted to identify which type of individual is capable of achieving professional excellence. Our main question therefore read: which individual antecedents predict professional excellence? We chose to focus on personality traits and specifically on proactive personality - the entrep

  19. Part-Time Faculty: Identifying the Trends and Challenges.

    Science.gov (United States)

    German, Kathleen M.

    1996-01-01

    Considers the scope of the problem of the trend toward part-time faculty. Identifies the characteristics of part-time instructors. Assesses the effects of part-time appointments on the profession. Notes that women are most often found in the lower ranks of part-time faculty. (PA)

  20. Supernumerary ring chromosome 17 identified by fluorescent in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Fagan, K. [Hunter Area Pathology Service, New South Wales (Australia); Edwards, M. [Western Suburbs Hospital, New South Wales (Australia)

    1997-04-14

    We present a patient with multiple anomalies and severe developmental delay. A small supernumerary ring chromosome was found in 40% of her lymphocyte cells at birth. The origin of the marker chromosome could not be determined by GTG banding, but fluorescent in situ hybridization (FISH) later identified the marker as deriving from chromosome 17. 20 refs., 2 figs., 1 tab.

  1. Similarity transformation approach to identifiability analysis of nonlinear compartmental models.

    Science.gov (United States)

    Vajda, S; Godfrey, K R; Rabitz, H

    1989-04-01

    Through use of the local state isomorphism theorem instead of the algebraic equivalence theorem of linear systems theory, the similarity transformation approach is extended to nonlinear models, resulting in finitely verifiable sufficient and necessary conditions for global and local identifiability. The approach requires testing of certain controllability and observability conditions, but in many practical examples these conditions prove very easy to verify. In principle the method also involves nonlinear state variable transformations, but in all of the examples presented in the paper the transformations turn out to be linear. The method is applied to an unidentifiable nonlinear model and a locally identifiable nonlinear model, and these are the first nonlinear models other than bilinear models where the reason for lack of global identifiability is nontrivial. The method is also applied to two models with Michaelis-Menten elimination kinetics, both of considerable importance in pharmacokinetics, and for both of which the complicated nature of the algebraic equations arising from the Taylor series approach has hitherto defeated attempts to establish identifiability results for specific input functions.

  2. The Development of Procedures for Identifying Competitive Behavior in Children

    Science.gov (United States)

    Mithaug, Dennis E.

    1973-01-01

    Identifies events in the competitive process that could be employed to discriminate between competition and individual, nonsocial behaviors. If a subject is working for the competitive contingency and checks his progress against another's, his behavior may be classified as competitive rather than individual, nonsocial behavior. (DP)

  3. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    were linked to MMR status based on immunostaining and BRAF mutation status.MMR defects were identified in 22.7% of the tumors, with 46 classified as sporadic. When the clinical parameters of age, sex, and proximal tumor location were combined with the morphologic features with the highest relative...

  4. Identifying workers at risk of sickness absence by questionnaire

    NARCIS (Netherlands)

    Roelen, Corne A. M.; van der Pol, Tjepke R.; Koopmans, Petra C.; Groothoff, Johan W.

    2006-01-01

    Background Sickness absence is an important economic problem, because of high costs and lost productivity. Determining factors associated with increased risk of sickness absence may lead to the development of preventive measures. Aims To determine whether self-report questionnaires can identify thos

  5. Identifying populations at risk from environmental contamination from point sources

    OpenAIRE

    Williams, F; Ogston, S

    2002-01-01

    Objectives: To compare methods for defining the population at risk from a point source of air pollution. A major challenge for environmental epidemiology lies in correctly identifying populations at risk from exposure to environmental pollutants. The complexity of today's environment makes it essential that the methods chosen are accurate and sensitive.

  6. A Framework for Identifying and Understanding Enterprise Systems Benefits

    DEFF Research Database (Denmark)

    Schubert, Petra; Williams, Susan P.

    2011-01-01

    Purpose – Identifying the benefits arising from implementations of enterprise systems and realizing business value remains a significant challenge for both research and industry. This paper aims to consolidate previous work. It presents a framework for investigating enterprise systems benefits an...

  7. Identifying and prioritising services in European terrestrial and freshwater ecosystems

    NARCIS (Netherlands)

    Harrison, P.A.; Vandewalle, M.; Sykes, M.T.; Berry, P.M.; Bugter, R.J.F.; Bello, de F.; Feld, C.K.; Grandin, U.; Harrington, R.; Haslett, J.R.; Jongman, R.H.G.; Luck, G.W.; Martins da Silva, P.; Moora, M.; Settele, J.; Sousa, J.P.; Zobel, M.

    2010-01-01

    Ecosystems are multifunctional and provide humanity with a broad array of vital services. Effective management of services requires an improved evidence base, identifying the role of ecosystems in delivering multiple services, which can assist policy-makers in maintaining them. Here, information fro

  8. Identifying a Small Molecule Blocking Antigen Presentation in Autoimmune Thyroiditis.

    Science.gov (United States)

    Li, Cheuk Wun; Menconi, Francesca; Osman, Roman; Mezei, Mihaly; Jacobson, Eric M; Concepcion, Erlinda; David, Chella S; Kastrinsky, David B; Ohlmeyer, Michael; Tomer, Yaron

    2016-02-19

    We previously showed that an HLA-DR variant containing arginine at position 74 of the DRβ1 chain (DRβ1-Arg74) is the specific HLA class II variant conferring risk for autoimmune thyroid diseases (AITD). We also identified 5 thyroglobulin (Tg) peptides that bound to DRβ1-Arg74. We hypothesized that blocking the binding of these peptides to DRβ1-Arg74 could block the continuous T-cell activation in thyroiditis needed to maintain the autoimmune response to the thyroid. The aim of the current study was to identify small molecules that can block T-cell activation by Tg peptides presented within DRβ1-Arg74 pockets. We screened a large and diverse library of compounds and identified one compound, cepharanthine that was able to block peptide binding to DRβ1-Arg74. We then showed that Tg.2098 is the dominant peptide when inducing experimental autoimmune thyroiditis (EAT) in NOD mice expressing human DRβ1-Arg74. Furthermore, cepharanthine blocked T-cell activation by thyroglobulin peptides, in particular Tg.2098 in mice that were induced with EAT. For the first time we identified a small molecule that can block Tg peptide binding and presentation to T-cells in autoimmune thyroiditis. If confirmed cepharanthine could potentially have a role in treating human AITD.

  9. Beyond basic citation—What to identify, when, and why

    Science.gov (United States)

    Parsons, M. A.

    2015-12-01

    Persistent identifiers (and locators) have emerged as a critical component in designing and implementing information systems and networks. This is especially evident in the use of the Digital Object Identifier in association with formal bibliographic citation of literature and increasingly of data sets. Indeed, the principles and methods of data citation have been a hot topic in the informatics community over the last decade or so. To date the focus has typically been on closely linking data sets to associated literature and generally emulating bibliographic-style citation. To design a sustainable, trusted data infrastructure, however, requires us to unambiguously reference many things in many ways, be they data, software, instruments, methods, or people. Design of this infrastructure also requires us to consider the entire data lifecycle and when important elements come into play and need to be identified. This paper will advocate an "ecological" model of data sharing that takes a more holistic perspective than many traditional data publication approaches. It will explore a variety of use cases around what elements of an information ecosystem need to be unambiguously identified and located, at what point in the data production process, and to what explicit purpose.

  10. Opportunistic Beacon Networks: Information Dissemination via Wireless Network Identifiers

    NARCIS (Netherlands)

    Türkes, Okan; Scholten, Hans; Havinga, Paul J.M.

    2016-01-01

    This paper presents OBN, a universal opportunistic ad hoc networking model particularly intended for smart mobile devices. It enables fast and lightweight data dissemination in wireless community networks through the utilization of universally-available wireless network identifiers. As a ubiquitous

  11. Identifying core domains to assess flare in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bartlett, Susan J; Hewlett, Sarah; Bingham, Clifton O;

    2012-01-01

    For rheumatoid arthritis (RA), there is no consensus on how to define and assess flare. Variability in flare definitions impairs understanding of findings across studies and limits ability to pool results. The OMERACT RA Flare Group sought to identify domains to define RA flares from patient...

  12. Fetal alcohol-spectrum disorders: identifying at-risk mothers.

    Science.gov (United States)

    Montag, Annika C

    2016-01-01

    Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children.

  13. Text mining electronic health records to identify hospital adverse events

    DEFF Research Database (Denmark)

    Gerdes, Lars Ulrik; Hardahl, Christian

    2013-01-01

    Manual reviews of health records to identify possible adverse events are time consuming. We are developing a method based on natural language processing to quickly search electronic health records for common triggers and adverse events. Our results agree fairly well with those obtained using manual...... reviews, and we therefore believe that it is possible to develop automatic tools for monitoring aspects of patient safety....

  14. Identifying Emotions through Language Means in Early Childhood

    Directory of Open Access Journals (Sweden)

    Malanov S.V.

    2015-08-01

    Full Text Available The paper focuses on the development of higher mental functions responsible for emotional regulation and describes a study revealing the stages in which young children acquire certain language means that help them to identify emotional states and understand emotional relationships. The sample of the study consisted of 94 children aged from 1.8 to 7.5 years. The outcomes suggest that at the age of 1.8 the children begin to acquire skills necessary for recognizing emotions basing on what the adults tell them. The revealed general tendency in the development of object reference of words is as follows: at first the children are able to identify emotional states and relationships according to the context of intersubjective interactions; later, basing on facial expressions; and finally, basing on pictograms of facial expressions. At the age of 2.4 years the children begin to employ language tools for identifying and naming emotions in others by themselves. Basing on their experience of analyzing emotions in others, the children then gradually develop the skills for identifying and partly recognizing their own emotions. Such skills may actually be found in some children at the age of 3.5 years, but usually it is not until the age of 7.5 that they can be observed in most preschoolers

  15. Identifying Hearing Loss in Young Children: Technology Replaces the Bell

    Science.gov (United States)

    Eiserman, William; Shisler, Lenore

    2010-01-01

    Hearing loss can too easily be misdiagnosed or overlooked by providers serving young children. Parents and professionals may observe a language delay--an "invisible" condition--while failing to identify the underlying cause. Otoacoustic emissions (OAE) hearing screening technology, used extensively with newborns, is becoming an essential tool,…

  16. Modelling intelligence-led policing to identify its potential

    NARCIS (Netherlands)

    Hengst-Bruggeling, M. den; Graaf, H.A.L.M. de; Scheepstal, P.G.M. van

    2014-01-01

    lntelligence-led policing is a concept of policing that has been applied throughout the world. Despite some encouraging reports, the effect of intelligence-led policing is largely unknown. This paper presents a method with which it is possible to identify intelligence-led policing's potential to inc

  17. Identifying Genes Responsible for Tamoxifen Resistance in Breast Cancer

    NARCIS (Netherlands)

    D. Meijer (Daniëlle)

    2008-01-01

    textabstractBreast cancer is one of the leading causes of death of women in western countries. It affects one out of eight females in the USA (1) and one out of nine females in The Netherlands (www.kankerregistratie.nl) during their lifetime. Many risk factors for breast cancer have been identified

  18. Identifying Outpatients with Entrenched Suicidal Ideation Following Hospitalization

    Science.gov (United States)

    O'Connor, Stephen S.; Jobes, David A.; Comtois, Katherine Anne; Atkins, David C.; Janis, Karin; Chessen, Chloe E.; Landes, Sara J.

    2012-01-01

    The purpose of this study was to identify outpatients who experience entrenched suicidal ideation following inpatient psychiatric hospitalization. Our findings suggest that the use of a suicidal ambivalence index score was helpful at discriminating those who reported significantly greater ratings of suicidal ideation across a 1-year period of…

  19. 26 CFR 301.6109-1 - Identifying numbers.

    Science.gov (United States)

    2010-04-01

    ... effectively connected with the conduct of a U.S. trade or business at any time during the taxable year; (ii) A... during the taxable year; (iii) A nonresident alien treated as a resident under section 6013(g) or (h... number means a taxpayer identifying number issued to an alien individual by the Internal Revenue...

  20. Identifying the methodological characteristics of European green city rankings

    NARCIS (Netherlands)

    Meijering, J.V.; Kern, K.; Tobi, H.

    2014-01-01

    City rankings that aim to measure the environmental sustainability of European cities may contribute to the evaluation and development of environmental policy of European cities. The objective of this study is to identify and evaluate the methodological characteristics of these city rankings. First,

  1. Identifying failure mechanisms in LDMOS transistors by analytical stability analysis

    NARCIS (Netherlands)

    Ferrara, A.; Steeneken, P.G.; Boksteen, B.K.; Heringa, A.; Scholten, A.J.; Schmitz, J.; Hueting, R.J.E.

    2014-01-01

    In this work, analytical stability equations are derived and combined with a physics-based model of an LDMOS transistor in order to identify the primary cause of failure in different operating and bias conditions. It is found that there is a gradual boundary between an electrical failure region at h

  2. Identifying Molecular Targets for PTSD Treatment Using Single Prolonged Stress

    Science.gov (United States)

    2015-10-01

    extinction memory involves a number of different psychological processes, and in this aim, we set out to determine the psychological mechanism by...project is: using structural and functional longitudinal MRI studies, to identify neuroimaging profiles that predict specific disease trajectories in

  3. On the Identifiability of Transmission Dynamic Models for Infectious Diseases.

    Science.gov (United States)

    Lintusaari, Jarno; Gutmann, Michael U; Kaski, Samuel; Corander, Jukka

    2016-03-01

    Understanding the transmission dynamics of infectious diseases is important for both biological research and public health applications. It has been widely demonstrated that statistical modeling provides a firm basis for inferring relevant epidemiological quantities from incidence and molecular data. However, the complexity of transmission dynamic models presents two challenges: (1) the likelihood function of the models is generally not computable, and computationally intensive simulation-based inference methods need to be employed, and (2) the model may not be fully identifiable from the available data. While the first difficulty can be tackled by computational and algorithmic advances, the second obstacle is more fundamental. Identifiability issues may lead to inferences that are driven more by prior assumptions than by the data themselves. We consider a popular and relatively simple yet analytically intractable model for the spread of tuberculosis based on classical IS6110 fingerprinting data. We report on the identifiability of the model, also presenting some methodological advances regarding the inference. Using likelihood approximations, we show that the reproductive value cannot be identified from the data available and that the posterior distributions obtained in previous work have likely been substantially dominated by the assumed prior distribution. Further, we show that the inferences are influenced by the assumed infectious population size, which generally has been kept fixed in previous work. We demonstrate that the infectious population size can be inferred if the remaining epidemiological parameters are already known with sufficient precision.

  4. Identifying Food Safety Concerns when Communication Barriers Exist

    Science.gov (United States)

    Neal, Jack A.; Dawson, Mary; Madera, Juan M.

    2011-01-01

    Abstract: Students must be prepared to lead a diverse workforce. The objective of this study was to establish a teaching method that helps students identify barriers to food safety while working in a simulated environment with communication barriers. This study employed a perspective taking exercise based upon the principles of social learning…

  5. Challenges of Identifying Communities with Shared Semantics in Enterprise Modeling

    NARCIS (Netherlands)

    Hoppenbrouwers, Stijn; Linden, D. van der

    2012-01-01

    In this paper we discuss the use and challenges of identifying communities with shared semantics in Enterprise Modeling. People tend to understand modeling meta-concepts (i.e., a modeling language’s constructs or types) in a certain way and can be grouped by this understanding. Having an insight int

  6. Identifying intrinsic and reflexive contributions to low-back stabilization

    NARCIS (Netherlands)

    Van Drunen, P.; Maaswinkel, E.; Van der Helm, F.C.T.; Van Dieën, J.H.; Happee, R.

    2013-01-01

    Motor control deficits have been suggested as potential cause and/or effect of a-specific chronic low-back pain and its recurrent behavior. Therefore, the goal of this study is to identify motor control in low-back stabilization by simultaneously quantifying the intrinsic and reflexive contributions

  7. From Unresolved Anger to Sadness: Identifying Physiological Correlates

    Science.gov (United States)

    Rochman, Daniel; Diamond, Gary M.

    2008-01-01

    This study was designed to identify physiological correlates of unresolved anger and sadness, and the shift between these emotions, in a context similar to that of emotion-focused, experiential psychotherapy. Twenty-seven university students reporting unresolved anger toward an attachment figure were induced to experience and express unresolved…

  8. Fetal alcohol-spectrum disorders: identifying at-risk mothers

    Science.gov (United States)

    Montag, Annika C

    2016-01-01

    Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. PMID:27499649

  9. Easy Long-Term Identifiers and the "Data Paper"

    Science.gov (United States)

    Kunze, John

    2011-05-01

    A new publishing paradigm is needed to cope with the deluge of data artifacts produced by data-intensive science, many of which are vital to data re-use and verification of published scientific conclusions. Due to the limitations of traditional publishing, most of these artifacts are not usually disseminated, cited, or preserved. At the California Digital Library (CDL), one promising approach to the problem is to wrap these artifacts in the metaphor of a "data paper", assigning and managing data citations with our EZID (easy-eye-dee) identifier service. A data paper is a somewhat unfamiliar bundle of scholarly output with a familiar facade: minimally, a set of links to archived artifacts and a cover sheet containing familiar elements such as title, authors, date, abstract, and persistent identifier _ just enough to create basic citations, build "overlay journals", and enable discovery of data by internet search engines. Over time, we expect to add elements that permit deeper domain-specific discovery and re-use, such as variable names, methods, etc. At the same time, for data and identifiers that we manage, we will leverage as much domain-agnosticism data and identifier as possible.

  10. A Triangulation Method for Identifying Hydrostratigraphic Locations of Well Screens

    Energy Technology Data Exchange (ETDEWEB)

    Whiteside, T. S. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL). Radiological Performance Assessment

    2015-01-31

    A method to identify the hydrostratigraphic location of well screens was developed using triangulation with known locations. This method was applied to all of the monitor wells being used to develop the new GSA groundwater model. Results from this method are closely aligned with those from an alternate method which uses a mesh surface.

  11. Improvements in the Protein Identifier Cross-Reference service.

    Science.gov (United States)

    Wein, Samuel P; Côté, Richard G; Dumousseau, Marine; Reisinger, Florian; Hermjakob, Henning; Vizcaíno, Juan A

    2012-07-01

    The Protein Identifier Cross-Reference (PICR) service is a tool that allows users to map protein identifiers, protein sequences and gene identifiers across over 100 different source databases. PICR takes input through an interactive website as well as Representational State Transfer (REST) and Simple Object Access Protocol (SOAP) services. It returns the results as HTML pages, XLS and CSV files. It has been in production since 2007 and has been recently enhanced to add new functionality and increase the number of databases it covers. Protein subsequences can be Basic Local Alignment Search Tool (BLAST) against the UniProt Knowledgebase (UniProtKB) to provide an entry point to the standard PICR mapping algorithm. In addition, gene identifiers from UniProtKB and Ensembl can now be submitted as input or mapped to as output from PICR. We have also implemented a 'best-guess' mapping algorithm for UniProt. In this article, we describe the usefulness of PICR, how these changes have been implemented, and the corresponding additions to the web services. Finally, we explain that the number of source databases covered by PICR has increased from the initial 73 to the current 102. New resources include several new species-specific Ensembl databases as well as the Ensembl Genome ones. PICR can be accessed at http://www.ebi.ac.uk/Tools/picr/.

  12. Gifted Students: How to Identify Them and Meet Their Needs

    Science.gov (United States)

    Genco, Susan L.

    2010-01-01

    The federal government has been making strides to make the term "appropriate" an inclusive term that recognizes and addresses the special learning needs of all students. In an effort to appropriately educate students who have been identified as "gifted," the New Jersey State Board of Education readopted Standards and Assessment…

  13. Identifying the Clumsy Child in School: An Exploratory Study.

    Science.gov (United States)

    Dussart, Georges

    1994-01-01

    This article reports on the development of a screening checklist for identifying children who might have developmental coordination disorder (DCD), use of the checklist to determine incidence rates in East Kent (United Kingdom), and possible relationships between DCD and left-handedness and between DCD and self-concept. (DB)

  14. Identifying Children at High Risk for a Child Maltreatment Report

    Science.gov (United States)

    Dubowitz, Howard; Kim, Jeongeun; Black, Maureen M.; Weisbart, Cindy; Semiatin, Joshua; Magder, Laurence S.

    2011-01-01

    Objective: To help professionals identify factors that place families at risk for future child maltreatment, to facilitate necessary services and to potentially help prevent abuse and neglect. Method: The data are from a prospective, longitudinal study of 332 low-income families recruited from urban pediatric primary care clinics, followed for…

  15. Developing Communities of Innovation by Identifying Innovation Champions

    Science.gov (United States)

    Coakes, Elayne; Smith, Peter

    2007-01-01

    Purpose: The purpose of this paper is to propose that a form of communities of practice (CoP), a community of innovation (CoInv), is the best support for sustainable innovation. It aims to outline a method for identifying champions of innovation in organisation. Design/methodology/approach: The paper draws on extant research to argue that…

  16. Beyond the Folklore: A Strategy for Identifying Quality Undergraduate Colleges

    Science.gov (United States)

    Conrad, Clinton F.

    2012-01-01

    College and university quality--what it is and how to identify it--is a preoccupation of many prospective college students and their parents, high school counselors, and college admission personnel. Regardless of class, race, and gender, it is no longer enough for a growing number of individuals simply to attend college: matriculating at an…

  17. Identifying the Key Weaknesses in Network Security at Colleges.

    Science.gov (United States)

    Olsen, Florence

    2000-01-01

    A new study identifies and ranks the 10 security gaps responsible for most outsider attacks on college computer networks. The list is intended to help campus system administrators establish priorities as they work to increase security. One network security expert urges that institutions utilize multiple security layers. (DB)

  18. Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes

    NARCIS (Netherlands)

    J. Molenaar (Jan); J. Koster (Jan); D. Zwijnenburg (Danny); P. van Sluis (Peter); L.J. Valentijn (Linda); I. van der Ploeg (Ida); M. Hamdi (Mohamed); J. van Nes (Johan); B.A. Westerman (Bart); J. van Arkel (Jennemiek); M.E. Ebus; F. Haneveld (Franciska); A. Lakeman (Arjan); L. Schild (Linda); P. Molenaar (Piet); P. Stroeken (Peter); M.M. van Noesel (Max); I. Øra (Ingrid); J.P. di Santo (James); H.N. Caron (Huib); E.M. Westerhout (Ellen); R. Versteeg (Rogier)

    2012-01-01

    textabstractNeuroblastoma is a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour. Frequently detected gene alterations are limited to MYCN amplification (

  19. Blood Pressure Loci Identified with a Gene-Centric Array

    NARCIS (Netherlands)

    Johnson, Toby; Gaunt, Tom R.; Newhouse, Stephen J.; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W.; Tzoulaki, Ioanna; O'Brien, Eoin T.; Poulter, Neil R.; Sever, Peter; Shields, Denis C.; Thom, Simon; Wannamethee, Sasiwarang G.; Whincup, Peter H.; Brown, Morris J.; Connell, John M.; Dobson, Richard J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Smith, George Davey; Day, Ian N. M.; Lawlor, Debbie A.; Goodall, Alison H.; Fowkes, F. Gerald; Abecasis, Goncalo R.; Elliott, Paul; Gateva, Vesela; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Tobin, Martin D.; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A.; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-Francois; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sober, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S.; Hastie, Claire E.; Hedner, Thomas; Lee, Wai K.; Melander, Olle; Wahlstrand, Bjoern; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A.; Palmen, Jutta; Chen, Li; Stewart, Alexandre F. R.; Wells, George A.; Westra, Harm-Jan; Wolfs, Marcel G. M.; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F.; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H.; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V.; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J.; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Mans; Kuh, Diana; Humphries, Steve E.; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V.; Dominiczak, Anna F.; Farrall, Martin; Hingorani, Aroon D.; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2011-01-01

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a besp

  20. Identifying and Researching Market Opportunities for New High Technology Products.

    Science.gov (United States)

    Dunstan, Peter

    Using a product called the synchro-pulse welder as a case study example, this paper discusses the activities of CSIRO (Commonwealth Scientific and Industrial Research Organisation) in identifying and marketing new high-technology products. A general discussion of CSIRO's market research plans includes two goals to be attained within the next 5…

  1. Identifying the needs of brain tumor patients and their caregivers.

    Science.gov (United States)

    Parvataneni, Rupa; Polley, Mei-Yin; Freeman, Teresa; Lamborn, Kathleen; Prados, Michael; Butowski, Nicholas; Liu, Raymond; Clarke, Jennifer; Page, Margaretta; Rabbitt, Jane; Fedoroff, Anne; Clow, Emelia; Hsieh, Emily; Kivett, Valerie; Deboer, Rebecca; Chang, Susan

    2011-09-01

    The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers' questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were "very important" but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients' lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients' treatment process.

  2. Training Guide for Identifying, Meeting, and Evaluating Training Needs.

    Science.gov (United States)

    Federal Highway Administration (DOT), Washington, DC. National Highway Inst.

    This manual is a guide for the training supervisor, specialist, or other official who has to plan, develop, and carry through a training program for improving the effectiveness of the employee development program, particularly in a governmental department of highways. The content is in three chapters: (1) Identifying Training Needs briefly…

  3. Leadership Developmental Needs--A System for Identifying Them

    Science.gov (United States)

    Takala, Marjatta; Winegar, David; Kuusela, Jorma

    2009-01-01

    This study is an evaluation of the developmental needs of business leaders. Altogether, 190 leaders, representing 22 nationalities, participated in 12 four-day training sessions. The first aim of this study was to identify the key developmental concerns of leaders; the second was to determine what kinds of training methods the leaders preferred;…

  4. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  5. Identifying acute coronary syndrome patients approaching end-of-life.

    Directory of Open Access Journals (Sweden)

    Stephen Fenning

    Full Text Available BACKGROUND: Acute coronary syndrome (ACS is common in patients approaching the end-of-life (EoL, but these patients rarely receive palliative care. We compared the utility of a palliative care prognostic tool (Gold Standards Framework (GSF and the Global Registry of Acute Coronary Events (GRACE score, to help identify patients approaching EoL. METHODS AND FINDINGS: 172 unselected consecutive patients with confirmed ACS admitted over an eight-week period were assessed using prognostic tools and followed up for 12 months. GSF criteria identified 40 (23% patients suitable for EoL care while GRACE identified 32 (19% patients with ≥ 10% risk of death within 6 months. Patients meeting GSF criteria were older (p = 0.006, had more comorbidities (1.6 ± 0.7 vs. 1.2 ± 0.9, p = 0.007, more frequent hospitalisations before (p = 0.001 and after (0.0001 their index admission, and were more likely to die during follow-up (GSF+ 20% vs GSF- 7%, p = 0.03. GRACE score was predictive of 12-month mortality (C-statistic 0.75 and this was improved by the addition of previous hospital admissions and previous history of stroke (C-statistic 0.88. CONCLUSIONS: This study has highlighted a potentially large number of ACS patients eligible for EoL care. GSF or GRACE could be used in the hospital setting to help identify these patients. GSF identifies ACS patients with more comorbidity and at increased risk of hospital readmission.

  6. Identifying dysregulated pathways in cancers from pathway interaction networks

    Directory of Open Access Journals (Sweden)

    Liu Ke-Qin

    2012-06-01

    Full Text Available Abstract Background Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. Results In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. Conclusions Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used

  7. Postural control deficits identify lingering post-concussion neurological deficits

    Institute of Scientific and Technical Information of China (English)

    Thomas A. Buckley; Jessie R. Oldham; Jaclyn B. Caccese

    2016-01-01

    Concussion, or mild traumatic brain injury, incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom. The purpose of this review is to provide an overview of the linear and non-linear assessments of post-concussion postural control. The current acute evaluation for concussion utilizes the subjective balance error scoring system (BESS) to assess postural control. While the sensitivity of the overall test battery is high, the sensitivity of the BESS is unacceptably low and, with repeat administration, is unable to accurately identify recovery. Sophisticated measures of postural control, utilizing traditional linear assessments, have identified impairments in postural control well beyond BESS recovery. Both assessments of quiet stance and gait have identified lingering impairments for at least 1 month post-concussion. Recently, the application of non-linear metrics to concussion recovery have begun to receive limited attention with the most commonly utilized metric being approximate entropy (ApEn). ApEn, most commonly in the medial-lateral plane, has successfully identified impaired postural control in the acute post-concussion timeframe even when linear assessments of instrumented measures are equivalent to healthy pre-injury values;unfortunately these studies have not gone beyond the acute phase of recovery. One study has identified lingering deficits in postural control, utilizing Shannon and Renyi entropy metrics, which persist at least through clinical recovery and return to participation. Finally, limited evidence from two studies suggest that individuals with a previous history of a single concussion, even months or years prior, may display altered ApEn metrics. Overall, non-linear metrics provide a fertile area for future study to further the understanding of postural control impairments acutely post-concussion and address the current challenge of sensitive identification of recovery.

  8. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    Directory of Open Access Journals (Sweden)

    Julia Breger

    2007-02-01

    Full Text Available There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2% that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.

  9. Identifying and relating biological concepts in the Catalogue of Life

    Directory of Open Access Journals (Sweden)

    Jones Andrew C

    2011-10-01

    Full Text Available Abstract Background In this paper we describe our experience of adding globally unique identifiers to the Species 2000 and ITIS Catalogue of Life, an on-line index of organisms which is intended, ultimately, to cover all the world's known species. The scientific species names held in the Catalogue are names that already play an extensive role as terms in the organisation of information about living organisms in bioinformatics and other domains, but the effectiveness of their use is hindered by variation in individuals' opinions and understanding of these terms; indeed, in some cases more than one name will have been used to refer to the same organism. This means that it is desirable to be able to give unique labels to each of these differing concepts within the catalogue and to be able to determine which concepts are being used in other systems, in order that they can be associated with the concepts in the catalogue. Not only is this needed, but it is also necessary to know the relationships between alternative concepts that scientists might have employed, as these determine what can be inferred when data associated with related concepts is being processed. A further complication is that the catalogue itself is evolving as scientific opinion changes due to an increasing understanding of life. Results We describe how we are using Life Science Identifiers (LSIDs as globally unique identifiers in the Catalogue of Life, explaining how the mapping to species concepts is performed, how concepts are associated with specific editions of the catalogue, and how the Taxon Concept Schema has been adopted in order to express information about concepts and their relationships. We explore the implications of using globally unique identifiers in order to refer to abstract concepts such as species, which incorporate at least a measure of subjectivity in their definition, in contrast with the more traditional use of such identifiers to refer to more tangible

  10. The Invisible Hunger: Is Famine Identifiable from the Archaeological Record?

    Directory of Open Access Journals (Sweden)

    Johanna Morgan

    2013-06-01

    Full Text Available Famine, as defined by an acute (short-term or chronic (long-term or cyclical period of starvation, is identifiable in the historical period from written records and potentially with archaeological corroboration, but in prehistory other approaches must be employed. Several of these are discussed including studies of diet and nutrition, paleodemography, environmental catalysts, and funerary ritual. Despite a multifactorial analysis integrating palynology, dendrochronology, stable isotope analyses, osteoarchaeology, and social archaeology, difficulties in contemporizing paleodemographic events them with osteological assemblages are substantial enough that the detection of a famine is not possible solely from the archaeological record. More significant is the conclusion that all apparent indicators for acute or chronic starvation are also representative of epidemic disease. Because of this uncertainty, it is not possible to identify famine in prehistory.

  11. Pharmacy students' ability to identify plagiarism after an educational intervention.

    Science.gov (United States)

    Degeeter, Michelle; Harris, Kira; Kehr, Heather; Ford, Carolyn; Lane, Daniel C; Nuzum, Donald S; Compton, Cynthia; Gibson, Whitney

    2014-03-12

    Objective. To determine if an educational intervention in a doctor of pharmacy (PharmD) degree program increases pharmacy students' ability to identify plagiarism. Methods. First-year (P1), second-year (P2), and third-year (P3) pharmacy students attended an education session during which types of plagiarism and methods for avoiding plagiarism were reviewed. Students completed a preintervention assessment immediately prior to the session and a postintervention assessment the following semester to measure their ability. Results. Two hundred fifty-two students completed both preintervention and postintervention assessments. There was a 4% increase from preintervention to postintervention in assessment scores for the overall student sample (pstudents (5% and 4.8%, respectively). Conclusion. An educational intervention about plagiarism can significantly improve students' ability to identify plagiarism.

  12. Quantitative proteomics identifies unanticipated regulators of nitrogen- and glucose starvation

    DEFF Research Database (Denmark)

    Rødkær, Steven V; Pultz, Dennis; Brusch, Michelle;

    2014-01-01

    starvation. We identify nearly 1400 phosphorylation sites of which more than 500 are regulated in a temporal manner in response to glucose- or nitrogen starvation. By bioinformatics and network analyses, we have identified the cyclin-dependent kinase (CDK) inhibitor Sic1, the Hsp90 co-chaperone Cdc37......, and the Hsp90 isoform Hsp82 to putatively mediate some of the starvation responses. Consistently, quantitative expression analyses showed that Sic1, Cdc37, and Hsp82 are required for normal expression of nutrient-responsive genes. Collectively, we therefore propose that Sic1, Cdc37, and Hsp82 may orchestrate...... parts of the cellular starvation response by regulating transcription factor- and kinase activities....

  13. Comparison of Algorithms for an Electronic Nose in Identifying Liquors

    Institute of Scientific and Technical Information of China (English)

    Zhi-biao Shi; Tao Yu; Qun Zhao; Yang Li; Yu-bin Lan

    2008-01-01

    When the electronic nose is used to identify different varieties of distilled liquors, the pattern recognition algorithm is chosen on the basis of the experience, which lacks the guiding principle. In this research, the different brands of distilled spirits were identified using the pattern recognition algorithms (principal component analysis and the artificial neural network). The recognition rates of different algorithms were compared. The recognition rate of the Back Propagation Neural Network (BPNN) is the highest. Owing to the slow convergence speed of the BPNN, it tends easily to get into a local minimum. A chaotic BPNN was tried in order to overcome the disadvantage of the BPNN. The convergence speed of the chaotic BPNN is 75.5 times faster than that of the BPNN.

  14. Identifying and Ranking the Determinants of Tourism Performance

    DEFF Research Database (Denmark)

    Assaf, A.George; Josiassen, Alexander

    2012-01-01

    , their tourism industries, and tourism businesses seek to improve the performance of the tourism industry and its constituents by vigorously promoting themselves to international tourists, cutting costs, and identifying synergies in their tourism endeavors. In seeking to improve the tourism industry......, the determinants that affect tourism performance are of key interest to the stakeholders. A key obstacle toward improving performance is the multitude of determinants that can affect tourism performance. The literature has yet to provide concrete insights into the determinants of tourism performance...... and their relative importance. The present study addresses this important gap. We identify and rank the determinants of tourism performance. We also provide performance measures of international tourism destinations. The results are derived using the Data Envelopment Analysis (DEA) and bootstrap truncated regression...

  15. Adaptive algorithms for identifying large flows in IP traffic

    CERN Document Server

    Chabchoub, Yousra; Guillemin, Fabrice; Robert, Philippe

    2009-01-01

    We develop in this paper an adaptive algorithm based on Bloom filters in order to identify large flows. While most algorithms proposed so far in the technical literature rely on a periodic erasure of the Bloom filter, we propose in this paper to progressively decrement the various counters of the filter according to some overload criteria. When tested against real traffic traces, the proposed algorithm performs well in the sense that a high percentage of large flows in traffic are detected by the algorithm. In order to improve the accuracy of the algorithm, we introduce a shadow Bloom filter, which is less frequently decremented so that elephants have more chance of being identified. Since elephant detection issue is very close to flood attack detection, we adapt the proposed algorithm in order to detect SYN and volume flood attack in Internet traffic. The attack detection algorithm is tested against traffic traces from France Telecom collect and transit networks. Some performance issues are finally discussed...

  16. Covert Flow Graph Approach to Identifying Covert Channels

    Directory of Open Access Journals (Sweden)

    XiangMei Song

    2011-12-01

    Full Text Available In this paper, the approach for identifying covert channels using a graph structure called Covert Flow Graph is introduced. Firstly, the construction of Covert Flow Graph which can offer information flows of the system for covert channel detection is proposed, and the search and judge algorithm used to identify covert channels in Covert Flow Graph is given. Secondly, an example file system analysis using Covert Flow Graph approach is provided, and the analysis result is compared with that of Shared Resource Matrix and Covert Flow Tree method. Finally, the comparison between Covert Flow Graph approach and other two methods is discussed. Different from previous methods, Covert Flow Graph approach provides a deep insight for system’s information flows, and gives an effective algorithm for covert channel identification.

  17. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH

    Directory of Open Access Journals (Sweden)

    Coze Carole

    2006-01-01

    Full Text Available Abstract Background Pleuropulmonary blastoma (PPB is a rare childhood dysontogenetic intrathoracic neoplasm associated with an unfavourable clinical behaviour. Cases presentation We report pathological and cytogenetic findings in two cases of PPB at initial diagnosis and recurrence. Both tumors were classified as type III pneumoblastoma and histological findings were similar at diagnosis and relapse. In both cases, conventional cytogenetic techniques revealed complex numerical and structural chromosomal abnormalities. Molecular cytogenetic analysis (interphase/metaphase FISH and multicolor FISH identified accurately chromosomal aberrations. In one case, TP53 gene deletion was detected on metaphase FISH. To date, only few cytogenetic data have been published about PPB. Conclusion The PPB genetic profile remains to be established and compared to others embryonal neoplasia. Our cytogenetic data are discussed reviewing cytogenetics PPBs published cases, illustrating the contribution of multicolor FISH in order to identify pathogenetically important recurrent aberrations in PPB.

  18. Identifying communities by influence dynamics in social networks

    CERN Document Server

    Stanoev, Angel; Kocarev, Ljupco

    2011-01-01

    Communities are not static; they evolve, split and merge, appear and disappear, i.e. they are product of dynamical processes that govern the evolution of the network. A good algorithm for community detection should not only quantify the topology of the network, but incorporate the dynamical processes that take place on the network. We present a novel algorithm for community detection that combines network structure with processes that support creation and/or evolution of communities. The algorithm does not embrace the universal approach but instead tries to focus on social networks and model dynamic social interactions that occur on those networks. It identifies leaders, and communities that form around those leaders. It naturally supports overlapping communities by associating each node with a membership vector that describes node's involvement in each community. This way, in addition to overlapping communities, we can identify nodes that are good followers to their leader, and also nodes with no clear commu...

  19. Identifying new persistent and bioaccumulative organics among chemicals in commerce.

    Science.gov (United States)

    Howard, Philip H; Muir, Derek C G

    2010-04-01

    The goal of this study was to identify commercial chemicals that might be persistent and bioaccumulative (P&B) and that were not being considered in current Great Lakes, North American, and Arctic contaminant measurement programs. We combined the Canadian Domestic Substance List (DSL), a list of 3059 substances of "unknown or variable composition complex reaction products and biological materials" (UVCBs), and the U.S. Environmental Protection Agency (U.S. EPA) Toxic Substances Control Act (TSCA) Inventory Update Rule (IUR) database for years 1986, 1990, 1994, 1998, 2002, and 2006 yielding a database of 22263 commercial chemicals. From that list, 610 chemicals were identified by estimates from U.S EPA EPISuite software and using expert judgment. This study has yielded some interesting and probable P&B chemicals that should be considered for further study. Recent studies, following up our initial reports and presentations on this work, have confirmed the presence of many of these chemicals in the environment.

  20. Identifying critical factors for implementing good agricultural practice

    Directory of Open Access Journals (Sweden)

    Nelson Gutiérrez Guzmán

    2010-05-01

    Full Text Available This paper deals with identifying the critical factors (CFs involved in implementing a good agricultural practice (GAP programme for coffee and fruit farmers in the Huila department of Colombia. An exploratory factor analysis using principal component analy- sis (PCA factorisation was used. Data matrixes were constructed from the results of applying two defined-structure assessment tools to the populations being studied: Starbucks’ coffee and farmer equity (CAFE practices for small-scale coffee growers and coffee-producers and the EUREPGAP V2.1 Oct.2004 / checklist for fruit and vegetables, as applied to fruit-producers. This inves- tigation led to identifying 6 CFs which must be considered when implementing a GAP programme: infrastructure, established production activities, preparing and maintaining records, environmental awareness, workers’ welfare and safety and quality con- trol.

  1. Short period eclipsing binary candidates identified using SuperWASP

    CERN Document Server

    Norton, A J; Evans, T; West, R G; Wheatley, P J; Anderson, D R; Barros, S C C; Butters, O W; Cameron, A Collier; Christian, D J; Enoch, B; Faedi, F; Haswell, C A; Hellier, C; Holmes, S; Horne, K D; Lister, T A; Maxted, P F L; Parley, N; Pollacco, D; Simpson, E K; Skillen, I; Smalley, B; Southworth, J; Street, R A

    2011-01-01

    We present light curves and periods of 53 candidates for short period eclipsing binary stars identified by SuperWASP. These include 48 newly identified objects with periods <2x10^4 seconds (~0.23d), as well as the shortest period binary known with main sequence components (GSC2314-0530 = 1SWASP J022050.85+332047.6) and four other previously known W UMa stars (although the previously reported periods for two of these four are shown to be incorrect). The period distribution of main sequence contact binaries shows a sharp cut-off at a lower limit of around 0.22d, but until now, very few systems were known close to this limit. These new candidates will therefore be important for understanding the evolution of low mass stars and to allow investigation of the cause of the period cut-off.

  2. Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine

    Directory of Open Access Journals (Sweden)

    Tonia C. Carter

    2016-01-01

    Full Text Available Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug-associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.

  3. Vulnerable Earthworm Species Identified from Nilgiri Biosphere Reserve

    Directory of Open Access Journals (Sweden)

    E.V. Ramasamy

    2011-01-01

    Full Text Available Diversity of earthworms at Nilgiri Biosphere Reserve is less known even though it is one among the biodiversity hot spots. Unless an authentic record of available earthworm species is made, the consequences of human alternation or climate change on the earthworm species diversity cannot be assessed. In this regard, the present study is relevant. Earthworms were collected from twenty three sites of NBR. The findings of this study showed that out of the total earthworm species identified from selected areas of NBR, 83.4% are native species and 16.6% are exotic. This indicates the predominance of native species in the study area possibly due to low level of disturbance in the area. Among the species identified from Mukurthi, Priodichaeta pellucida (Bourne which is listed as vulnerable and has not been encountered since its discovery about 100 years ago.

  4. Identifying Lead Markets in the European Automotive Industry

    DEFF Research Database (Denmark)

    Cleff, Thomas; Grimpe, Christoph; Rammer, Christian

    2015-01-01

    of excellence in technology and interaction among users and producers, the lead market approach focuses on the role of demand characteristics. Based on the concept of innovation design, a lead market is defined as a country where customers prefer that design which subsequently becomes the globally dominant......This paper presents an indicator-based methodology to identify lead markets in the European automotive industry. The lead market approach tries to explain why certain countries are better positioned than others for developing and launching new products. While much research stresses the role...... design. We use an indicator-based approach which has been successfully employed for individual products as well as for various industries in order to identify lead markets in the European automotive industry. Employing five lead market factors, our results show that the EU is by far no homogeneous market...

  5. Identifying 21st century STEM competencies using workplace data

    CERN Document Server

    Jang, Hyewon

    2015-01-01

    Gaps between Science, Technology, Engineering, and Mathematics (STEM) education and required workplace skills have been identified in industry, academia, and government. Educators acknowledge the need to reform STEM education to better prepare students for their future careers. We pursue this growing interest in the skills needed for STEM disciplines and ask whether frameworks for 21st century skills and engineering education cover all of important STEM competencies. In this study, we identify important STEM competencies and evaluate the relevance of current frameworks applied in education using the standardized job-specific database operated and maintained by the United States Department of Labor. Our analysis of the importance of 109 skills, types of knowledge and work activities, revealed 18 skills, seven categories of knowledge, and 27 work activities important for STEM workers. We investigate the perspectives of STEM and non-STEM job incumbents, comparing the importance of each skill, knowledge, and work...

  6. Identifying the ejected population from disintegrating multiple systems

    CERN Document Server

    Yip, A K P; Kurtev, R; Gromadzki, M; Marocco, F

    2016-01-01

    Kinematic studies of the Hipparcos catalogue have revealed associations that are best explained as disintegrating multiple systems, presumably resulting from a dynamical encounter between single/multiple systems in the field (Li et al. 2009). In this work we explore the possibility that known ultra-cool dwarfs may be components of disintegrating multiple systems, and consider the implications for the properties of these objects. We will present here the methods/techniques that can be used to search for and identify disintegrating benchmark systems in three database/catalogues: Dwarf Archive, the Hipparcos Main Catalogue, and the Gliese-Jahrei{\\ss} Catalogue. Placing distance constraints on objects with parallax or colour-magnitude information from spectrophotometry allowed us to identify common distance associations. Proper motion measurements allowed us to separate common proper motion multiples from our sample of disintegrating candidates. Moreover, proper motion and positional information allowed us to sel...

  7. On Codes with w-identifiable Parent Property

    Institute of Scientific and Technical Information of China (English)

    MA Jun; XIONG Yu

    2008-01-01

    A code is said to be a w-identifiable parent property code (or w-IPP code for short) if whenever d is a descendant of w (or fewer) codewords, and one can always identify at least one of the parents of d. Let C be an (N, w + 1, q)-code and C* an (w + 1)-color graph for C. If a graph G is a subgraph of C* and consists of w + 1 edges with different colors, then G is called a (w + 1)-pattern of C*. In this paper, we proved that C is a w-IPP code if and only if there exists at most one vertex with color degree more than 1 in any (w + 1)-pattern of C*.

  8. Identifying Influential Spreaders of Epidemics on Community Networks

    CERN Document Server

    Luo, Shi-Long; Kang, Li

    2016-01-01

    An efficient strategy for the identification of influential spreaders that could be used to control epidemics within populations would be of considerable importance. Generally, populations are characterized by its community structures and by the heterogeneous distributions of weak ties among nodes bridging over communities. A strategy for community networks capable of identifying influential spreaders that accelerate the spread of disease is here proposed. In this strategy, influential spreaders serve as target nodes. This is based on the idea that, in k-shell decomposition, weak ties and strong ties are processed separately. The strategy was used on empirical networks constructed from online social networks, and results indicated that this strategy is more accurate than other strategies. Its effectiveness stems from the patterns of connectivity among neighbors, and it successfully identified the important nodes. In addition, the performance of the strategy remained robust even when there were errors in the s...

  9. Identifiability and identification of a Synthesis Load Model

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A Synthesis Load Model (SLM) including both the power load and the distribution network has been proposed in the references. The identifiability of SLM is analyzed at first, it is concluded that the model parameters are identifiable if one of the resistance, reactance and the ratio of them is known. The conclusion is validated through a simulation example. A strategy for parameter identification of SLM is proposed with the combination of the component based approach and the measurement based approach. During parameter identification, only the key parameters playing very important roles in the dynamics of the load and the system are estimated, while the other parameters playing limited role are set as the default values. The proposed strategy is verified by the field measurements.

  10. Identifying decision strategies in a consumer choice situation

    Directory of Open Access Journals (Sweden)

    Nils Reisen

    2008-12-01

    Full Text Available In two studies on mobile phone purchase decisions, we investigated consumers' decision strategies with a newly developed process tracing tool called extit{InterActive Process Tracing} (IAPT. This tool is a combination of several process tracing techniques (Active Information Search, Mouselab, and retrospective verbal protocol. After repeatedly choosing one of four mobile phones, participants formalized their strategy so that it could be used to make choices for them. The choices made by the identified strategies correctly predicted the observed choices in 73\\% (Experiment 1 and 67\\% (Experiment 2 of the cases. Moreover, in Experiment 2 we directly compared Mouselab and eye tracking with respect to their impact on information search and strategy description. We found only minor differences between these two methods. We conclude that IAPT is a useful research tool to identify choice strategies, and that using eye tracking technology did not increase its validity beyond that gained with Mouselab.

  11. To identify morbidity and mortality predictors in acute organophosphate poisoning

    Directory of Open Access Journals (Sweden)

    Arti Muley

    2014-01-01

    Full Text Available Background: Organophosphorus poisoning remains an important cause of morbidity and mortality, but no definite parameters have been identified as predictors of outcome. Prediction of morbidity at presentation might help in decision making in places of limited resources like rural settings in developing countries. Materials and Methods: A total of 76 cases were included in this retrospective cohort study. Logged relative risk of requirement of mechanical ventilation and hospital stay >7 days was measured in patients with serum acetylcholinesterase (s. acetylcholinesterase 1000, presenting in 12 and in patients with SpO 2 7 days. Conclusion: S. acetylcholinesterase, SpO 2 at room air, GCS, and duration of exposure at presentation can be used to identify the requirement of special care in acute organophosphorus poisoning. This can aid in decision making regarding admission to intensive care unit and referral in the places with limited resources.

  12. Identifying Unbiased Items for Screening Preschoolers for Disruptive Behavior Problems.

    Science.gov (United States)

    Studts, Christina R; Polaha, Jodi; van Zyl, Michiel A

    2016-10-25

    OBJECTIVE : Efficient identification and referral to behavioral services are crucial in addressing early-onset disruptive behavior problems. Existing screening instruments for preschoolers are not ideal for pediatric primary care settings serving diverse populations. Eighteen candidate items for a new brief screening instrument were examined to identify those exhibiting measurement bias (i.e., differential item functioning, DIF) by child characteristics. METHOD : Parents/guardians of preschool-aged children (N = 900) from four primary care settings completed two full-length behavioral rating scales. Items measuring disruptive behavior problems were tested for DIF by child race, sex, and socioeconomic status using two approaches: item response theory-based likelihood ratio tests and ordinal logistic regression. RESULTS : Of 18 items, eight were identified with statistically significant DIF by at least one method. CONCLUSIONS : The bias observed in 8 of 18 items made them undesirable for screening diverse populations of children. These items were excluded from the new brief screening tool.

  13. How do we identify and foster talent in medical schools?

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh; Cristiancho, Sayra; Jensen, Rune Dall

    2016-01-01

    Background: Talent is highly regarded in high performance sports as a key feature for athletes to succeed. In medicine, talent is not a commonly held conversation, even though, medical students are usually identified as high achieving, internally motivated individuals. We suggest that bringing...... talent into the conversation of medical education research, will help us enrich how medical schools design selection processes. In this workshop we will bring awareness into the notion of talent from sports science research and invite discussion around how to embrace talent identification and development...... in medicine. The participants in this workshop will gain a better understanding of the notion of talent across different professional contexts. Furthermore, the workshop will encourage participants to share their personal experiences and practices in identifying and selecting talented medical students...

  14. Identifying Emotions on the Basis of Neural Activation.

    Directory of Open Access Journals (Sweden)

    Karim S Kassam

    Full Text Available We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1 neural activation of the same individual in other trials, 2 neural activation of other individuals who experienced similar trials, and 3 neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

  15. Identifying Parents Who Are Amenable to Pro-Vaccination Conversations

    Directory of Open Access Journals (Sweden)

    Emily K. Brunson MPH, PhD

    2015-11-01

    Full Text Available While health care providers are often cited as parents’ most trusted source for information and advice about vaccination, parents differ in their level of receptiveness to pro-vaccination conversations. The purpose of this research was to identify points in individual parents’ decision-making processes when parents are particularly open to receiving information and advice from their children’s health care providers. Interview data were collected from 20 mothers and 5 couples. Analysis of these data suggested 3 primary circumstances when parents were particularly open to receiving information and advice: during parents’ initial decision-making, as parents continued to assess vaccination options, and during particular circumstances that prompted parents to reconsider previously made vaccination choices. These results provide a mechanism for providers to identify parents who may be particularly receptive to pro-vaccination conversations. By prioritizing conversations with parents at one of these points, health care providers’ efforts at promoting vaccination may be more effective.

  16. A whole genome RNAi screen identifies replication stress response genes.

    Science.gov (United States)

    Kavanaugh, Gina; Ye, Fei; Mohni, Kareem N; Luzwick, Jessica W; Glick, Gloria; Cortez, David

    2015-11-01

    Proper DNA replication is critical to maintain genome stability. When the DNA replication machinery encounters obstacles to replication, replication forks stall and the replication stress response is activated. This response includes activation of cell cycle checkpoints, stabilization of the replication fork, and DNA damage repair and tolerance mechanisms. Defects in the replication stress response can result in alterations to the DNA sequence causing changes in protein function and expression, ultimately leading to disease states such as cancer. To identify additional genes that control the replication stress response, we performed a three-parameter, high content, whole genome siRNA screen measuring DNA replication before and after a challenge with replication stress as well as a marker of checkpoint kinase signalling. We identified over 200 replication stress response genes and subsequently analyzed how they influence cellular viability in response to replication stress. These data will serve as a useful resource for understanding the replication stress response.

  17. An Efficient Approach for Identifying Stable Lobes with Discretization Method

    Directory of Open Access Journals (Sweden)

    Baohai Wu

    2013-01-01

    Full Text Available This paper presents a new approach for quick identification of chatter stability lobes with discretization method. Firstly, three different kinds of stability regions are defined: absolute stable region, valid region, and invalid region. Secondly, while identifying the chatter stability lobes, three different regions within the chatter stability lobes are identified with relatively large time intervals. Thirdly, stability boundary within the valid regions is finely calculated to get exact chatter stability lobes. The proposed method only needs to test a small portion of spindle speed and cutting depth set; about 89% computation time is savedcompared with full discretization method. It spends only about10 minutes to get exact chatter stability lobes. Since, based on discretization method, the proposed method can be used for different immersion cutting including low immersion cutting process, the proposed method can be directly implemented in the workshop to promote machining parameters selection efficiency.

  18. Identifying Sources of Difference in Reliability in Content Analysis

    Directory of Open Access Journals (Sweden)

    Elizabeth Murphy

    2005-07-01

    Full Text Available This paper reports on a case study which identifies and illustrates sources of difference in agreement in relation to reliability in a context of quantitative content analysis of a transcript of an online asynchronous discussion (OAD. Transcripts of 10 students in a month-long online asynchronous discussion were coded by two coders using an instrument with two categories, five processes, and 19 indicators of Problem Formulation and Resolution (PFR. Sources of difference were identified in relation to: coders; tasks; and students. Reliability values were calculated at the levels of categories, processes, and indicators. At the most detailed level of coding on the basis of the indicator, findings revealed that the overall level of reliability between coders was .591 when measured with Cohen’s kappa. The difference between tasks at the same level ranged from .349 to .664, and the difference between participants ranged from .390 to .907. Implications for training and research are discussed.

  19. Identifying Semantic Relations for DiseaseTreatment in Medline

    Directory of Open Access Journals (Sweden)

    P. Menaka

    2012-03-01

    Full Text Available The Machine Learning (ML is almost used in any domain of research and now it has become a reliable tool in the medical domain.ML is a tool by which medical field is integrated with the computer based systems to provide more efficient medical care. The main objective of this work is to show what Natural Language Processing (NLP and Machine Learning (ML techniques used for representation of information and what classification algorithms are suitable for identifying and classifying relevant medical information in short texts. It acknowledges the fact that tools capable of identifying reliable information in the medical domain stand as building blocks for a healthcare system that is up-to-date with the latest discoveries. In this research, it focuses on diseases and treatment information, and the relation that exists between these two entities.

  20. Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

    Directory of Open Access Journals (Sweden)

    Fahad Benthani

    2015-05-01

    Full Text Available Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.

  1. Identifying influential factors of business process performance using dependency analysis

    Science.gov (United States)

    Wetzstein, Branimir; Leitner, Philipp; Rosenberg, Florian; Dustdar, Schahram; Leymann, Frank

    2011-02-01

    We present a comprehensive framework for identifying influential factors of business process performance. In particular, our approach combines monitoring of process events and Quality of Service (QoS) measurements with dependency analysis to effectively identify influential factors. The framework uses data mining techniques to construct tree structures to represent dependencies of a key performance indicator (KPI) on process and QoS metrics. These dependency trees allow business analysts to determine how process KPIs depend on lower-level process metrics and QoS characteristics of the IT infrastructure. The structure of the dependencies enables a drill-down analysis of single factors of influence to gain a deeper knowledge why certain KPI targets are not met.

  2. A quantitative telomeric chromatin isolation protocol identifies different telomeric states

    Science.gov (United States)

    Grolimund, Larissa; Aeby, Eric; Hamelin, Romain; Armand, Florence; Chiappe, Diego; Moniatte, Marc; Lingner, Joachim

    2013-11-01

    Telomere composition changes during tumourigenesis, aging and in telomere syndromes in a poorly defined manner. Here we develop a quantitative telomeric chromatin isolation protocol (QTIP) for human cells, in which chromatin is cross-linked, immunopurified and analysed by mass spectrometry. QTIP involves stable isotope labelling by amino acids in cell culture (SILAC) to compare and identify quantitative differences in telomere protein composition of cells from various states. With QTIP, we specifically enrich telomeric DNA and all shelterin components. We validate the method characterizing changes at dysfunctional telomeres, and identify and validate known, as well as novel telomere-associated polypeptides including all THO subunits, SMCHD1 and LRIF1. We apply QTIP to long and short telomeres and detect increased density of SMCHD1 and LRIF1 and increased association of the shelterins TRF1, TIN2, TPP1 and POT1 with long telomeres. Our results validate QTIP to study telomeric states during normal development and in disease.

  3. Outpatient Preoperative Education Needs Identified by Nurses and Patients.

    Science.gov (United States)

    2007-11-02

    PREOPERATIVE EDUCATION NEEDS IDENTIFIED BY NURSES AND PATIENTS Cheryl Anne Reilly APPROVED: Supervising Prdessor Date APPROVED: / "Sanfor• Miller , P... anesthesiologist will visit them before 5 4 3 2 1 surgery to discuss what anesthesia would be used. 27. Their incision may pull, bum, or itch while it is 5 4...such as, giving me an injection & asking me to empty my bladder. 26. An anesthesiologist would visit me before Yes No 5 4 3 2 1 surgery to discuss

  4. Identifying Differences in Cultural Behavior in Online Groups

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, Michelle L.; Engel, David W.; Bell, Eric B.; Mcgrath, Liam R.

    2012-07-23

    We have developed methods to identify online communities, or groups, using a combination of structural information variables and content information variables from weblog posts and their comments to build a characteristic footprint for groups. We have worked with both explicitly connected groups and 'abstract' groups, in which the connection between individuals is in interest (as determined by content based features) and behavior (metadata based features) as opposed to explicit links. We find that these variables do a good job at identifying groups, placing members within a group, and helping determine the appropriate granularity for group boundaries. The group footprint can then be used to identify differences between the online groups. In the work described here we are interested in determining how an individual's online behavior is influenced by their membership in more than one group. For example, individuals belong to a certain culture; they may belong as well to a demographic group, and other 'chosen' groups such as churches or clubs. There is a plethora of evidence surrounding the culturally sensitive adoption, use, and behavior on the Internet. In this work we begin to investigate how culturally defined internet behaviors may influence behaviors of subgroups. We do this through a series of experiments in which we analyze the interaction between culturally defined behaviors and the behaviors of the subgroups. Our goal is to (a) identify if our features can capture cultural distinctions in internet use, and (b) determine what kinds of interaction there are between levels and types of groups.

  5. Lung cancer screening: identifying the high risk cohort

    OpenAIRE

    Marcus, Michael W.; Raji, Olaide Y; John K. Field

    2015-01-01

    Low dose computed tomography (LDCT) is a viable screening tool for early lung cancer detection and mortality reduction. In practice, the success of any lung cancer screening programme will depend on successful identification of individuals at high risk in order to maximise the benefit-harm ratio. Risk prediction models incorporating multiple risk factors have been recognised as a method of identifying individuals at high risk of developing lung cancer. Identification of individuals at high ri...

  6. cgaTOH: extended approach for identifying tracts of homozygosity.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available Identification of disease variants via homozygosity mapping and investigation of the effects of genome-wide homozygosity regions on traits of biomedical importance have been widely applied recently. Nonetheless, the existing methods and algorithms to identify long tracts of homozygosity (TOH are not able to provide efficient and rigorous regions for further downstream association investigation. We expanded current methods to identify TOHs by defining "surrogate-TOH", a region covering a cluster of TOHs with specific characteristics. Our defined surrogate-TOH includes cTOH, viz a common TOH region where at least ten TOHs present; gTOH, whereby a group of highly overlapping TOHs share proximal boundaries; and aTOH, which are allelically-matched TOHs. Searching for gTOH and aTOH was based on a repeated binary spectral clustering algorithm, where a hierarchy of clusters is created and represented by a TOH cluster tree. Based on the proposed method of identifying different species of surrogate-TOH, our cgaTOH software was developed. The software provides an intuitive and interactive visualization tool for better investigation of the high-throughput output with special interactive navigation rings, which will find its applicability in both conventional association studies and more sophisticated downstream analyses. NCBI genome map viewer is incorporated into the system. Moreover, we discuss the choice of implementing appropriate empirical ranges of critical parameters by applying to disease models. This method identifies various patterned clusters of SNPs demonstrating extended homozygosity, thus one can observe different aspects of the multi-faceted characteristics of TOHs.

  7. Using statistical design experiment methodologies to identify customers' needs

    OpenAIRE

    Huertas Garcia, Rubén; Consolación Segura, Carolina María

    2009-01-01

    Customer satisfaction has become one of the main objectives in all areas of business, especially the tourist trade. One of the most difficult problems is to know how to obtain this satisfaction, which involves identifying customers' needs and desires, and transferring them to our product or service specifications. In order to ascertain the consumer voice, we can ask consumers directly, or thy to deduce their requirements by indirect methods. Statistical design of experiments (SDE) is consider...

  8. Benchmarking in Identifying Priority Directions of Development of Telecommunication Operators

    OpenAIRE

    Zaharchenko Lolita A.; Kolesnyk Oksana A.

    2013-01-01

    The article analyses evolution of development and possibilities of application of benchmarking in the telecommunication sphere. It studies essence of benchmarking on the basis of generalisation of approaches of different scientists to definition of this notion. In order to improve activity of telecommunication operators, the article identifies the benchmarking technology and main factors, that determine success of the operator in the modern market economy, and the mechanism of benchmarking an...

  9. From mythology to psychology: Identifying archetypal symbols in movies

    OpenAIRE

    Díaz Boladeras, Marta; Català Mallofré, Andreu; Chen, Wei; Rauterberg, Mattias; Ivonin, Leonid; Huang-Ming, Chang

    2013-01-01

    In this article, we introduce the theory of archetype, which explains the connection between ancient myths and the human mind. Based on the assumption that archetypes are in the deepest level of human mind, we propose that archetypal symbolism is a kind of knowledge that supports the cognitive process for creating subjective world-view towards the physical world we live in. According to archetypal symbolism, we conducted an empirical study to identify archetypal symbols in modern movies. A ne...

  10. Identifying Innovators for the Cross-Selling of New Products

    OpenAIRE

    Wagner A. Kamakura; Bruce S. Kossar; Michel Wedel

    2004-01-01

    With recent advances in information technology, most companies are amassing extensive customer databases. The wealth of information in these databases can be useful in identifying those customers most likely to purchase a new product and in predicting when this adoption may take place. This can assist database marketers in determining when individuals should be targeted for the promotion of a new product, which may increase the efficiency of manufacturing and distribution, and assure a faster...

  11. Expression profiling identifies microRNA signature in pancreatic cancer

    OpenAIRE

    Lee, Eun Joo; Gusev, Yuriy; Jiang, Jinmai; Gerard J Nuovo; Lerner, Megan R; Frankel, Wendy L.; Morgan, Daniel L.; Postier, Russell G.; Brackett, Daniel J; Schmittgen, Thomas D.

    2007-01-01

    microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pan...

  12. Evidential method to identify influential nodes in complex networks

    Institute of Scientific and Technical Information of China (English)

    Hongming Mo; Cai Gao; Yong Deng

    2015-01-01

    Identifying influential nodes in complex networks is stil an open issue. In this paper, a new comprehensive centrality mea-sure is proposed based on the Dempster-Shafer evidence theory. The existing measures of degree centrality, betweenness centra-lity and closeness centrality are taken into consideration in the proposed method. Numerical examples are used to il ustrate the effectiveness of the proposed method.

  13. Identifying factors affecting optimal management of agricultural water

    Directory of Open Access Journals (Sweden)

    Masoud Samian

    2015-01-01

    In addition to quantitative methodology such as descriptive statistics and factor analysis a qualitative methodology was employed for dynamic simulation among variables through Vensim software. In this study, the factor analysis technique was used through the Kaiser-Meyer-Olkin (KMO and Bartlett tests. From the results, four key elements were identified as factors affecting the optimal management of agricultural water in Hamedan area. These factors were institutional and legal factors, technical and knowledge factors, economic factors and social factors.

  14. Community and law: identifying the locus of law in community

    OpenAIRE

    Yaylali, Mustafa

    2012-01-01

    "Community and law approach" provides an illuminating insight into alternative legal orderings within a social unit. The comprehensiveness of legal systems within a community or a social unit, provides a suitable basis for a structural framework of alternative legal systems or Legal Pluralism, which is missing in the discourse on Legal Pluralism. "Identifying the locus of law within a community", provides us with an indication on how autopoetic a legal system can be within a social unit, taki...

  15. An Alternative Method for Identifying Interplanetary Magnetic Cloud Regions

    Science.gov (United States)

    Ojeda-Gonzalez, A.; Mendes, O.; Calzadilla, A.; Domingues, M. O.; Prestes, A.; Klausner, V.

    2017-03-01

    Spatio-temporal entropy (STE) analysis is used as an alternative mathematical tool to identify possible magnetic cloud (MC) candidates. We analyze Interplanetary Magnetic Field (IMF) data using a time interval of only 10 days. We select a convenient data interval of 2500 records moving forward by 200 record steps until the end of the time series. For every data segment, the STE is calculated at each step. During an MC event, the STE reaches values close to zero. This extremely low value of STE is due to MC structure features. However, not all of the magnetic components in MCs have STE values close to zero at the same time. For this reason, we create a standardization index (the so-called Interplanetary Entropy, IE, index). This index is a worthwhile effort to develop new tools to help diagnose ICME structures. The IE was calculated using a time window of one year (1999), and it has a success rate of 70% over other identifiers of MCs. The unsuccessful cases (30%) are caused by small and weak MCs. The results show that the IE methodology identified 9 of 13 MCs, and emitted nine false alarm cases. In 1999, a total of 788 windows of 2500 values existed, meaning that the percentage of false alarms was 1.14%, which can be considered a good result. In addition, four time windows, each of 10 days, are studied, where the IE method was effective in finding MC candidates. As a novel result, two new MCs are identified in these time windows.

  16. Data Mining and Pattern Recognition Models for Identifying Inherited Diseases

    DEFF Research Database (Denmark)

    Iddamalgoda, Lahiru; Das, Partha S; Aponso, Achala;

    2016-01-01

    Data mining and pattern recognition methods reveal interesting findings in genetic studies, especially on how the genetic makeup is associated with inherited diseases. Although researchers have proposed various data mining models for biomedical approaches, there remains a challenge in accurately...... prioritizing the single nucleotide polymorphisms (SNP) associated with the disease. In this commentary, we review the state-of-art data mining and pattern recognition models for identifying inherited diseases and deliberate the need of binary classification- and scoring-based prioritization methods...

  17. Identifying interacting pairs of sites in infinite range Ising models

    CERN Document Server

    Galves, Antonio; Takahashi, Daniel Yasumasa

    2010-01-01

    We consider Ising models (pairwise interaction Gibbs probability measures) in $\\Z^d$ with an infinite range potential. We address the problem of identifying pairs of interacting sites from a finite sample of independent realisations of the Ising model. The sample contains only the values assigned by the Ising model to a finite set of sites in $\\Z^d$. Our main result is an upperbound for the probability with our estimator to misidentify the pairs of interacting sites in this finite set.

  18. Identifying microRNAs that Regulate Neuroblastoma Cell Differentiation

    Science.gov (United States)

    2015-10-01

    supplemented with 10% fetal bovine serum. Detection and quantification of neurite outgrowth Cells were plated and treated in 96-well plates. For measuring...inhibits the stemness of glioma stem cells by target- ing RTVP-1. Oncotarget 2013; 4(5):665-76; PMID:23714687 14. Trang P, Wiggins JF, Daige CL, Cho C...Award Number: W81XWH-13-1-0241 TITLE: Identifying that Regulate Neuroblastoma Cell Differentiation PRINCIPAL INVESTIGATOR: Dr. Liqin Du

  19. Identifying Competitive Positioning Strategies of Universities: Evidence from Turkey

    Directory of Open Access Journals (Sweden)

    Burçak Cagla Garipagaoglu

    2015-06-01

    Full Text Available This research aims to identify the factors affecting the students’ and parents’ choice of university in Turkey and strives to understand how they classify or position the universities in their minds. Since the focus of this research is to explore the main factors leading to the students’ and parents’ choice of university and to identify the dimensions for segmentation within the universities in Turkey, this research is qualitative in nature. Data was collected with a series of in-depth interviews with prospective university students and two focus group discussions with parents. Based on the findings, three dimensions, which were used to segment universities by the Turkish higher education market, were identified: 1 the diploma value of the program in a university, in terms of graduate employment, 2 the student social-life that the students expect to experience throughout their undergraduate years, and 3 the constraints limiting the students’ choice of university. Using these dimensions as a basis for segmentation, a simplified conceptual framework of competitive positioning strategies for universities was generated and four university types were identified: goal-oriented, exclusive, commodity and honeymoon. Turkish universities were then advised to consider their competitive positioning styles in the marketplace that is already perceived by the market and to develop appropriate marketing strategies, accordingly. By doing so, this research both aims to assist university leaders in developing their offerings with a unique and strong brand promise with the help of marketing orientation and make a significant contribution to a little researched, but increasingly topical, issue in the literature.

  20. Psychological impact of identifying character strengths in people with psychosis.

    Science.gov (United States)

    Sims, Anna; Barker, Chris; Price, Claire; Fornells-Ambrojo, Miriam

    2015-04-03

    A one group pre-post test design investigated the impact of identifying character strengths using the Values In Action Inventory of Strengths (VIA-IS) with individuals with early psychosis (N = 29). Post-test improvements in positive affect and cognitive performance were observed. Neither self-esteem nor self-efficacy improved. The technique appears feasible for use within early intervention services. Adverse consequences should be monitored and additional components considered to enhance benefits.

  1. Identifying Innovation Strategies: Insights from the Greek Food Industry

    OpenAIRE

    Matopoulos, Aristides; Vlachopoulou, Maro

    2008-01-01

    This paper emphasizes on the concept of innovation which is more and more nowadays recognized as of significant importance for all companies across different business sectors. The paper initially provides a review of the innovation literature in terms of types, classifications, and sources of innovation that have been proposed over time. Then, innovation in the context of the food industry is examined and it is attempted to identify innovation strategies followed by Greek food companies based...

  2. A comparison of computational methods for identifying virulence factors.

    Directory of Open Access Journals (Sweden)

    Lu-Lu Zheng

    Full Text Available Bacterial pathogens continue to threaten public health worldwide today. Identification of bacterial virulence factors can help to find novel drug/vaccine targets against pathogenicity. It can also help to reveal the mechanisms of the related diseases at the molecular level. With the explosive growth in protein sequences generated in the postgenomic age, it is highly desired to develop computational methods for rapidly and effectively identifying virulence factors according to their sequence information alone. In this study, based on the protein-protein interaction networks from the STRING database, a novel network-based method was proposed for identifying the virulence factors in the proteomes of UPEC 536, UPEC CFT073, P. aeruginosa PAO1, L. pneumophila Philadelphia 1, C. jejuni NCTC 11168 and M. tuberculosis H37Rv. Evaluated on the same benchmark datasets derived from the aforementioned species, the identification accuracies achieved by the network-based method were around 0.9, significantly higher than those by the sequence-based methods such as BLAST, feature selection and VirulentPred. Further analysis showed that the functional associations such as the gene neighborhood and co-occurrence were the primary associations between these virulence factors in the STRING database. The high success rates indicate that the network-based method is quite promising. The novel approach holds high potential for identifying virulence factors in many other various organisms as well because it can be easily extended to identify the virulence factors in many other bacterial species, as long as the relevant significant statistical data are available for them.

  3. A multiway analysis for identifying high integrity bovine BACs

    OpenAIRE

    McEwan John C; Brauning Rudiger; McWilliam Sean; Barris Wesley; Ratnakumar Abhirami; Snelling Warren M; Dalrymple Brian P

    2009-01-01

    Abstract Background In large genomics projects involving many different types of analyses of bacterial artificial chromosomes (BACs), such as fingerprinting, end sequencing (BES) and full BAC sequencing there are many opportunities for the identities of BACs to become confused. However, by comparing the results from the different analyses, inconsistencies can be identified and a set of high integrity BACs preferred for future research can be defined. Results The location of each bovine BAC in...

  4. Fetal alcohol-spectrum disorders: identifying at-risk mothers

    Directory of Open Access Journals (Sweden)

    Montag AC

    2016-07-01

    Full Text Available Annika C Montag Department of Pediatrics, Division of Dysmorphology and Teratology, University of California San Diego, San Diego, CA, USA Abstract: Fetal alcohol-spectrum disorders (FASDs are a collection of physical and neuro­behavioral disabilities caused by prenatal exposure to alcohol. To prevent or mitigate the costly effects of FASD, we must identify mothers at risk for having a child with FASD, so that we may reach them with interventions. Identifying mothers at risk is beneficial at all time points, whether prior to pregnancy, during pregnancy, or following the birth of the child. In this review, three approaches to identifying mothers at risk are explored: using characteristics of the mother and her pregnancy, using laboratory biomarkers, and using self-report assessment of alcohol-consumption risk. At present, all approaches have serious limitations. Research is needed to improve the sensitivity and specificity of biomarkers and screening instruments, and to link them to outcomes as opposed to exposure. Universal self-report screening of all women of childbearing potential should ideally be incorporated into routine obstetric and gynecologic care, followed by brief interventions, including education and personalized feedback for all who consume alcohol, and referral to treatment as indicated. Effective biomarkers or combinations of biomarkers may be used during pregnancy and at birth to determine maternal and fetal alcohol exposure. The combination of self-report and biomarker screening may help identify a greater proportion of women at risk for having a child with FASD, allowing them to access information and treatment, and empowering them to make decisions that benefit their children. Keywords: fetal alcohol-spectrum disorder (FASD, alcohol, pregnancy, screening, biomarkers, SBIRT

  5. Asthma trajectories in early childhood: identifying modifiable factors.

    Directory of Open Access Journals (Sweden)

    Lidia Panico

    Full Text Available BACKGROUND: There are conflicting views as to whether childhood wheezing represents several discreet entities or a single but variable disease. Classification has centered on phenotypes often derived using subjective criteria, small samples, and/or with little data for young children. This is particularly problematic as asthmatic features appear to be entrenched by age 6/7. In this paper we aim to: identify longitudinal trajectories of wheeze and other atopic symptoms in early childhood; characterize the resulting trajectories by the socio-economic background of children; and identify potentially modifiable processes in infancy correlated with these trajectories. DATA AND METHODS: The Millennium Cohort Study is a large, representative birth cohort of British children born in 2000-2002. Our analytical sample includes 11,632 children with data on key variables (wheeze in the last year; ever hay-fever and/or eczema reported by the main carers at age 3, 5 and 7 using a validated tool, the International Study of Asthma and Allergies in Childhood module. We employ longitudinal Latent Class Analysis, a clustering methodology which identifies classes underlying the observed population heterogeneity. RESULTS: Our model distinguished four latent trajectories: a trajectory with both low levels of wheeze and other atopic symptoms (54% of the sample; a trajectory with low levels of wheeze but high prevalence of other atopic symptoms (29%; a trajectory with high prevalence of both wheeze and other atopic symptoms (9%; and a trajectory with high levels of wheeze but low levels of other atopic symptoms (8%. These groups differed in terms of socio-economic markers and potential intervenable factors, including household damp and breastfeeding initiation. CONCLUSION: Using data-driven techniques, we derived four trajectories of asthmatic symptoms in early childhood in a large, population based sample. These groups differ in terms of their socio-economic profiles

  6. A parameter identifiability study of two chalk tracer tests

    Directory of Open Access Journals (Sweden)

    S. A. Mathias

    2006-08-01

    Full Text Available As with most fractured rock formations, Chalk is highly heterogeneous. Therefore, meaningful estimates of model parameters must be obtained at a scale comparable with the process of concern. These are frequently obtained by calibrating an appropriate model to observed concentration-time data from radially convergent tracer tests (RCTT. Arguably, an appropriate model should consider radially convergent dispersion (RCD and Fickian matrix diffusion. Such a model requires the estimation of at least four parameters. A question arises as to whether or not this level of model complexity is supported by the information contained within the calibration data. Generally modellers have not answered this question due to the calibration techniques employed. A dual-porosity model with RCD was calibrated to two tracer test datasets from different UK Chalk aquifers. A multivariate sensitivity analysis, which assumed only a priori upper and lower bounds for each model parameter, was undertaken. Rather than looking at measures of uncertainty, the shape of the multivariate objective function surface was used to determine whether a parameter was identifiable. Non-identifiable parameters were then removed and the procedure was repeated until all remaining parameters were identifiable.

    It was found that the single fracture model (SFM (which ignores mechanical dispersion obtained the best mass recovery, excellent model performance and best parameter identifiability in both the tests studied. However, there was no objective evidence suggesting that mechanical dispersion was negligible. Moreover, the SFM (with just two parameters was found to be good at approximating the Single Fracture Dispersion Model SFDM (with three parameters when different, and potentially erroneous parameters, were used. Overall, this study emphasises the importance of adequate temporal sampling of breakthrough curve data prior to peak concentrations, to ensure adequate characterisation of

  7. Engaging basic scientists in translational research: identifying opportunities, overcoming obstacles

    Directory of Open Access Journals (Sweden)

    Hobin Jennifer A

    2012-04-01

    Full Text Available Abstract This report is based on the Federation of American Societies for Experimental Biology’s symposium, “Engaging basic Scientists in Translational Research: Identifying Opportunities, Overcoming Obstacles,” held in Chevy Chase, MD, March 24–25, 2011. Meeting participants examined the benefits of engaging basic scientists in translational research, the challenges to their participation in translational research, and the roles that research institutions, funding organizations, professional societies, and scientific publishers can play to address these challenges.

  8. Identifying and transferring offenders with mental health needs.

    Science.gov (United States)

    Mullins, James; Paler, Helen

    This article provides an overview of the challenges encountered by mental health staff involved in the transfer of offenders with mental health problems between prisons and secure hospital settings. The article presents a case study demonstrating the importance of identifying offenders with mental health needs to provide appropriate care and support, prevent further mental deterioration and reduce the risk of offenders harming themselves or others.

  9. IDDTL: A Novel Identified Internet Data Transport Layer Mechanism

    Directory of Open Access Journals (Sweden)

    Yangyang Gao

    2014-01-01

    Full Text Available This paper proposes an identified data transport layer (IDDTL mechanism, which is implemented based on our present concepts of connection identifier (CID and CID additional information (CID-info. Since the fast evolved Internet scale and largely emerging various applications, especially with the new Internet architectures developed such as information centric network (ICN, the traditional end-to-end transport model has been exposed many defects in sorts of aspects, such as network management, flexibility and security. The novelty of the mechanism consists of two points: 1 it always conceals part of the communication information during the specific data transport process; 2 it splits the whole end-to-end communication process into two segments and forms a three-party and two-segment communication process model. Performance analysis shows that the mechanism could easily mitigate the problems such as distributed denial of service (D/DOS attacks and greatly improve the network management, flexibility and mobility. Furthermore, our simulation and test results demonstrate that IDDTL can be implemented with unique identifiers within an acceptable extra time cost of about 3.6 useconds compared with the traditional end-to-end model.

  10. Using hyperspectral imaging technology to identify diseased tomato leaves

    Science.gov (United States)

    Li, Cuiling; Wang, Xiu; Zhao, Xueguan; Meng, Zhijun; Zou, Wei

    2016-11-01

    In the process of tomato plants growth, due to the effect of plants genetic factors, poor environment factors, or disoperation of parasites, there will generate a series of unusual symptoms on tomato plants from physiology, organization structure and external form, as a result, they cannot grow normally, and further to influence the tomato yield and economic benefits. Hyperspectral image usually has high spectral resolution, not only contains spectral information, but also contains the image information, so this study adopted hyperspectral imaging technology to identify diseased tomato leaves, and developed a simple hyperspectral imaging system, including a halogen lamp light source unit, a hyperspectral image acquisition unit and a data processing unit. Spectrometer detection wavelength ranged from 400nm to 1000nm. After hyperspectral images of tomato leaves being captured, it was needed to calibrate hyperspectral images. This research used spectrum angle matching method and spectral red edge parameters discriminant method respectively to identify diseased tomato leaves. Using spectral red edge parameters discriminant method produced higher recognition accuracy, the accuracy was higher than 90%. Research results have shown that using hyperspectral imaging technology to identify diseased tomato leaves is feasible, and provides the discriminant basis for subsequent disease control of tomato plants.

  11. Identifying best practice through benchmarking and outcome measurement.

    Science.gov (United States)

    Lanier, Lynne

    2004-01-01

    Collecting and analyzing various types of data are essential to identifying areas for improvement. Data collection and analysis are routinely performed in hospitals and are even required by some regulatory agencies. Realization of the full benefits, which may be achieved through collection and analysis of data, should be actively pursued to prevent a meaningless exercise in paperwork. Internal historical comparison of data may be helpful but does not achieve the ultimate goal of identifying external benchmarks in order to determine best practice. External benchmarks provide a means of comparison with similar facilities, allowing the identification of processes needing improvement. The specialty of ophthalmology presents unique practice situations that are not comparable with other specialties, making it imperative to benchmark against other facilities where quick surgical case time, efficient surgical turnover times, low infection rates, and cost containment are essential and standard operations. Important data to benchmark include efficiency data, financial data, and quality or patient outcome data. After identifying facilities that excel in certain aspects of performance, it is necessary to analyze how their procedures help them achieve these favorable results. Careful data collection and analysis lead to improved practice and patient care.

  12. Identifiability of Gaussian Structural Equation Models with Same Error Variances

    CERN Document Server

    Peters, Jonas

    2012-01-01

    We consider structural equation models (SEMs) in which variables can be written as a function of their parents and noise terms (the latter are assumed to be jointly independent). Corresponding to each SEM, there is a directed acyclic graph (DAG) G_0 describing the relationships between the variables. In Gaussian SEMs with linear functions, the graph can be identified from the joint distribution only up to Markov equivalence classes (assuming faithfulness). It has been shown, however, that this constitutes an exceptional case. In the case of linear functions and non-Gaussian noise, the DAG becomes identifiable. Apart from few exceptions the same is true for non-linear functions and arbitrarily distributed additive noise. In this work, we prove identifiability for a third modification: if we require all noise variables to have the same variances, again, the DAG can be recovered from the joint Gaussian distribution. Our result can be applied to the problem of causal inference. If the data follow a Gaussian SEM w...

  13. Urinary peptidomics identifies potential biomarkers for major depressive disorder.

    Science.gov (United States)

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng

    2014-06-30

    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD.

  14. Rapid identifying high-influence nodes in complex networks

    Science.gov (United States)

    Song, Bo; Jiang, Guo-Ping; Song, Yu-Rong; Xia, Ling-Ling

    2015-10-01

    A tiny fraction of influential individuals play a critical role in the dynamics on complex systems. Identifying the influential nodes in complex networks has theoretical and practical significance. Considering the uncertainties of network scale and topology, and the timeliness of dynamic behaviors in real networks, we propose a rapid identifying method (RIM) to find the fraction of high-influential nodes. Instead of ranking all nodes, our method only aims at ranking a small number of nodes in network. We set the high-influential nodes as initial spreaders, and evaluate the performance of RIM by the susceptible-infected-recovered (SIR) model. The simulations show that in different networks, RIM performs well on rapid identifying high-influential nodes, which is verified by typical ranking methods, such as degree, closeness, betweenness, and eigenvector centrality methods. Project supported by the National Natural Science Foundation of China (Grant Nos. 61374180 and 61373136), the Ministry of Education Research in the Humanities and Social Sciences Planning Fund Project, China (Grant No. 12YJAZH120), and the Six Projects Sponsoring Talent Summits of Jiangsu Province, China (Grant No. RLD201212).

  15. Identifying, studying and making good use of macromolecular crystals

    Energy Technology Data Exchange (ETDEWEB)

    Calero, Guillermo [University of Pittsburgh Medical School, Pittsburgh, PA 15261 (United States); Cohen, Aina E. [SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025 (United States); Luft, Joseph R. [Hauptman–Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203 (United States); State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States); Newman, Janet [CSIRO Collaborative Crystallisation Centre, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Snell, Edward H., E-mail: esnell@hwi.buffalo.edu [Hauptman–Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203 (United States); State University of New York at Buffalo, 700 Ellicott Street, Buffalo, NY 14203 (United States); University of Pittsburgh Medical School, Pittsburgh, PA 15261 (United States)

    2014-07-25

    As technology advances, the crystal volume that can be used to collect useful X-ray diffraction data decreases. The technologies available to detect and study growing crystals beyond the optical resolution limit and methods to successfully place the crystal into the X-ray beam are discussed. Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed.

  16. Stimulators of translation identified during a small molecule screening campaign.

    Science.gov (United States)

    Shin, Unkyung; Williams, David E; Kozakov, Dima; Hall, David R; Beglov, Dmitri; Vajda, Sandor; Andersen, Raymond J; Pelletier, Jerry

    2014-02-15

    In screening a library of natural and synthetic products for eukaryotic translation modulators, we identified two natural products, isohymenialdisine and hymenialdisine, that exhibit stimulatory effects on translation. The characterization of these compounds led to the insight that mRNA used to program the translation extracts during high-throughput assay setup was leading to phosphorylation of eIF2α, a potent negative regulatory event that is mediated by one of four kinases. We identified double-stranded RNA-dependent protein kinase (PKR) as the eIF2α kinase that was being activated by exogenously added mRNA template. Characterization of the mode of action of isohymenialdisine revealed that it directly acts on PKR by inhibiting autophosphorylation, perturbs the PKR-eIF2α phosphorylation axis, and can be modeled into the PKR ATP binding site. Our results identify a source of "false positives" for high-throughput screen campaigns using translation extracts, raising a cautionary note for this type of screen.

  17. An Automated Summarization Assessment Algorithm for Identifying Summarizing Strategies

    Science.gov (United States)

    Abdi, Asad; Idris, Norisma; Alguliyev, Rasim M.; Aliguliyev, Ramiz M.

    2016-01-01

    Background Summarization is a process to select important information from a source text. Summarizing strategies are the core cognitive processes in summarization activity. Since summarization can be important as a tool to improve comprehension, it has attracted interest of teachers for teaching summary writing through direct instruction. To do this, they need to review and assess the students' summaries and these tasks are very time-consuming. Thus, a computer-assisted assessment can be used to help teachers to conduct this task more effectively. Design/Results This paper aims to propose an algorithm based on the combination of semantic relations between words and their syntactic composition to identify summarizing strategies employed by students in summary writing. An innovative aspect of our algorithm lies in its ability to identify summarizing strategies at the syntactic and semantic levels. The efficiency of the algorithm is measured in terms of Precision, Recall and F-measure. We then implemented the algorithm for the automated summarization assessment system that can be used to identify the summarizing strategies used by students in summary writing. PMID:26735139

  18. Identifying and aligning expectations in a mentoring relationship.

    Science.gov (United States)

    Huskins, W Charles; Silet, Karin; Weber-Main, Anne Marie; Begg, Melissa D; Fowler, Vance G; Hamilton, John; Fleming, Michael

    2011-12-01

    The mentoring relationship between a scholar and their primary mentor is a core feature of research training. Anecdotal evidence suggests this relationship is adversely affected when scholar and mentor expectations are not aligned. We examined three questions: (1) What is the value in assuring that the expectations of scholars and mentors are mutually identified and aligned? (2) What types of programmatic interventions facilitate this process? (3) What types of expectations are important to identify and align? We addressed these questions through a systematic literature review, focus group interviews of mentors and scholars, a survey of Clinical and Translational Science Award (CTSA) KL2 program directors, and review of formal programmatic mechanisms used by KL2 programs. We found broad support for the importance of identifying and aligning the expectations of scholars and mentors and evidence that mentoring contracts, agreements, and training programs facilitate this process. These tools focus on aligning expectations with respect to the scholar's research, education, professional development and career advancement as well as support, communication, and personal conduct and interpersonal relations. Research is needed to assess test the efficacy of formal alignment activities.

  19. Identifying problematic drugs based on the characteristics of their targets

    Directory of Open Access Journals (Sweden)

    Tiago Jose eDa Silva Lopes

    2015-09-01

    Full Text Available Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60%¬–70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

  20. Identifying coevolutionary patterns in human leukocyte antigen (HLA) molecules.

    Science.gov (United States)

    Jiang, Xiaowei; Fares, Mario A

    2010-05-01

    The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor (TCR) function as a complex to initiate effectors' mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host-pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen-binding pockets (P1-P9) and among these and TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host-pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII.