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Sample records for multiple cis-regulatory elements

  1. Multiple cis-regulatory elements are involved in the complex regulation of the sieve element-specific MtSEO-F1 promoter from Medicago truncatula.

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    Bucsenez, M; Rüping, B; Behrens, S; Twyman, R M; Noll, G A; Prüfer, D

    2012-09-01

    The sieve element occlusion (SEO) gene family includes several members that are expressed specifically in immature sieve elements (SEs) in the developing phloem of dicotyledonous plants. To determine how this restricted expression profile is achieved, we analysed the SE-specific Medicago truncatula SEO-F1 promoter (PMtSEO-F1) by constructing deletion, substitution and hybrid constructs and testing them in transgenic tobacco plants using green fluorescent protein as a reporter. This revealed four promoter regions, each containing cis-regulatory elements that activate transcription in SEs. One of these segments also contained sufficient information to suppress PMtSEO-F1 transcription in the phloem companion cells (CCs). Subsequent in silico analysis revealed several candidate cis-regulatory elements that PMtSEO-F1 shares with other SEO promoters. These putative sieve element boxes (PSE boxes) are promising candidates for cis-regulatory elements controlling the SE-specific expression of PMtSEO-F1. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  2. Changes in Cis-regulatory Elements during Morphological Evolution

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    Yu-Lee Paul

    2012-10-01

    Full Text Available How have animals evolved new body designs (morphological evolution? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the forelimbs of mice and bats, and the necks of amphibians and reptiles. The genetic changes and pathways involved in these evolutionary steps require identification. Many, though not all, of these events occur by changes in cis-regulatory (enhancer elements within developmental genes. Enhancers are modular, each affecting expression in only one or a few tissues. Therefore it is possible to add, remove or alter an enhancer without producing changes in multiple tissues, and thereby avoid widespread (pleiotropic deleterious effects. Ideally, for a given step in morphological evolution it is necessary to identify (i the change in phenotype, (ii the changes in gene expression, (iii the DNA region, enhancer or otherwise, affected, (iv the mutation involved, (v the nature of the transcription or other factors that bind to this site. In practice these data are incomplete for most of the published studies upon morphological evolution. Here, the investigations are categorized according to how far these analyses have proceeded.

  3. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

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    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  4. BLSSpeller: exhaustive comparative discovery of conserved cis-regulatory elements.

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    De Witte, Dieter; Van de Velde, Jan; Decap, Dries; Van Bel, Michiel; Audenaert, Pieter; Demeester, Piet; Dhoedt, Bart; Vandepoele, Klaas; Fostier, Jan

    2015-12-01

    The accurate discovery and annotation of regulatory elements remains a challenging problem. The growing number of sequenced genomes creates new opportunities for comparative approaches to motif discovery. Putative binding sites are then considered to be functional if they are conserved in orthologous promoter sequences of multiple related species. Existing methods for comparative motif discovery usually rely on pregenerated multiple sequence alignments, which are difficult to obtain for more diverged species such as plants. As a consequence, misaligned regulatory elements often remain undetected. We present a novel algorithm that supports both alignment-free and alignment-based motif discovery in the promoter sequences of related species. Putative motifs are exhaustively enumerated as words over the IUPAC alphabet and screened for conservation using the branch length score. Additionally, a confidence score is established in a genome-wide fashion. In order to take advantage of a cloud computing infrastructure, the MapReduce programming model is adopted. The method is applied to four monocotyledon plant species and it is shown that high-scoring motifs are significantly enriched for open chromatin regions in Oryza sativa and for transcription factor binding sites inferred through protein-binding microarrays in O.sativa and Zea mays. Furthermore, the method is shown to recover experimentally profiled ga2ox1-like KN1 binding sites in Z.mays. BLSSpeller was written in Java. Source code and manual are available at http://bioinformatics.intec.ugent.be/blsspeller Klaas.Vandepoele@psb.vib-ugent.be or jan.fostier@intec.ugent.be. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  5. Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

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    Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

    2015-12-01

    Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

  6. Cis-regulatory RNA elements that regulate specialized ribosome activity.

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    Xue, Shifeng; Barna, Maria

    2015-01-01

    Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

  7. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

    International Nuclear Information System (INIS)

    Mao, Grace; Brody, James P.

    2007-01-01

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s -1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase

  8. Bounded search for de novo identification of degenerate cis-regulatory elements

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    Khetani Radhika S

    2006-05-01

    Full Text Available Abstract Background The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach. Results In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally. Conclusion The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error

  9. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

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    Arindam Deb

    Full Text Available Combinations of cis-regulatory elements (CREs present at the promoters facilitate the binding of several transcription factors (TFs, thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic

  10. Identification of putative cis-regulatory elements in Cryptosporidium parvum by de novo pattern finding

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    Kissinger Jessica C

    2007-01-01

    Full Text Available Abstract Background Cryptosporidium parvum is a unicellular eukaryote in the phylum Apicomplexa. It is an obligate intracellular parasite that causes diarrhea and is a significant AIDS-related pathogen. Cryptosporidium parvum is not amenable to long-term laboratory cultivation or classical molecular genetic analysis. The parasite exhibits a complex life cycle, a broad host range, and fundamental mechanisms of gene regulation remain unknown. We have used data from the recently sequenced genome of this organism to uncover clues about gene regulation in C. parvum. We have applied two pattern finding algorithms MEME and AlignACE to identify conserved, over-represented motifs in the 5' upstream regions of genes in C. parvum. To support our findings, we have established comparative real-time -PCR expression profiles for the groups of genes examined computationally. Results We find that groups of genes that share a function or belong to a common pathway share upstream motifs. Different motifs are conserved upstream of different groups of genes. Comparative real-time PCR studies show co-expression of genes within each group (in sub-sets during the life cycle of the parasite, suggesting co-regulation of these genes may be driven by the use of conserved upstream motifs. Conclusion This is one of the first attempts to characterize cis-regulatory elements in the absence of any previously characterized elements and with very limited expression data (seven genes only. Using de novo pattern finding algorithms, we have identified specific DNA motifs that are conserved upstream of genes belonging to the same metabolic pathway or gene family. We have demonstrated the co-expression of these genes (often in subsets using comparative real-time-PCR experiments thus establishing evidence for these conserved motifs as putative cis-regulatory elements. Given the lack of prior information concerning expression patterns and organization of promoters in C. parvum we

  11. In silico modeling of epigenetic-induced changes in photoreceptor cis-regulatory elements.

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    Hossain, Reafa A; Dunham, Nicholas R; Enke, Raymond A; Berndsen, Christopher E

    2018-01-01

    DNA methylation is a well-characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of transcription is controlled by proteins that regulate recruitment and activity of RNA polymerase by binding to specific cis-regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell-specific gene expression. Although much is known about the functions and DNA binding specificity of CRX, little is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements. We used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions of RHO , PDE6B, PAX6 , and LINE1 retrotransposon repeats. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on human RHO regulatory sequences. In this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the human RHO and PDE6B genes and their subsequent transcription in human ocular tissues. Docking of CRX to the DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of the RHO promoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate changes in the local dynamics of CRX binding sites within RHO regulatory sequences which may account for the repression of CRX-dependent transcription. Collectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.

  12. A HLA class I cis-regulatory element whose activity can be modulated by hormones.

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    Sim, B C; Hui, K M

    1994-12-01

    To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

  13. [Analysis of cis-regulatory element distribution in gene promoters of Gossypium raimondii and Arabidopsis thaliana].

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    Sun, Gao-Fei; He, Shou-Pu; Du, Xiong-Ming

    2013-10-01

    Cotton genomic studies have boomed since the release of Gossypium raimondii draft genome. In this study, cis-regulatory element (CRE) in 1 kb length sequence upstream 5' UTR of annotated genes were selected and scanned in the Arabidopsis thaliana (At) and Gossypium raimondii (Gr) genomes, based on the database of PLACE (Plant cis-acting Regulatory DNA Elements). According to the definition of this study, 44 (12.3%) and 57 (15.5%) CREs presented "peak-like" distribution in the 1 kb selected sequences of both genomes, respectively. Thirty-four of them were peak-like distributed in both genomes, which could be further categorized into 4 types based on their core sequences. The coincidence of TATABOX peak position and their actual position ((-) -30 bp) indicated that the position of a common CRE was conservative in different genes, which suggested that the peak position of these CREs was their possible actual position of transcription factors. The position of a common CRE was also different between the two genomes due to stronger length variation of 5' UTR in Gr than At. Furthermore, most of the peak-like CREs were located in the region of -110 bp-0 bp, which suggested that concentrated distribution might be conductive to the interaction of transcription factors, and then regulate the gene expression in downstream.

  14. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

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    Junhua Li

    2014-01-01

    Full Text Available Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

  15. BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.

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    Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R

    2016-04-19

    The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

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    Neuman, Sarah D.; Bashirullah, Arash; Kumar, Justin P.

    2016-01-01

    The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so) mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis. PMID:27930646

  17. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

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    Kusters, Elske; Della Pina, Serena; Castel, Rob; Souer, Erik; Koes, Ronald

    2015-08-15

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of leafy (LFY) and the petunia homolog aberrant leaf and flower (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double top (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan. © 2015. Published by The Company of Biologists Ltd.

  18. Implications of duplicated cis-regulatory elements in the evolution of metazoans: the DDI model or how simplicity begets novelty.

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    Jiménez-Delgado, Senda; Pascual-Anaya, Juan; Garcia-Fernàndez, Jordi

    2009-07-01

    The discovery that most regulatory genes were conserved among animals from distant phyla challenged the ideas that gene duplication and divergence of homologous coding sequences were the basis for major morphological changes in metazoan evolution. In recent years, however, the interest for the roles, conservation and changes of non-coding sequences grew-up in parallel with genome sequencing projects. Presently, many independent studies are highlighting the importance that subtle changes in cis-regulatory regions had in the evolution of morphology trough the Animal Kingdom. Here we will show and discuss some of these studies, and underscore the future of cis-Evo-Devo research. Nevertheless, we would also explore how gene duplication, which includes duplication of regulatory regions, may have been critical for spatial or temporal co-option of new regulatory networks, causing the deployment of new transcriptome scenarios, and how these induced morphological changes were critical for the evolution of new forms. Forty years after Susumu Ohno famous sentence 'natural selection merely modifies, while redundancy creates', we suggest the alternative: 'natural selection modifies, while redundancy of cis-regulatory elements innovates', and propose the Duplication-Degeneration-Innovation model to explain the increased evolvability of duplicated cis-regulatory regions. Paradoxically, making regulation simpler by subfunctionalization paved the path for future complexity or, in other words, 'to make it simple to make it complex'.

  19. Characterization of a putative cis-regulatory element that controls transcriptional activity of the pig uroplakin II gene promoter

    International Nuclear Information System (INIS)

    Kwon, Deug-Nam; Park, Mi-Ryung; Park, Jong-Yi; Cho, Ssang-Goo; Park, Chankyu; Oh, Jae-Wook; Song, Hyuk; Kim, Jae-Hwan; Kim, Jin-Hoi

    2011-01-01

    Highlights: → The sequences of -604 to -84 bp of the pUPII promoter contained the region of a putative negative cis-regulatory element. → The core promoter was located in the 5F-1. → Transcription factor HNF4 can directly bind in the pUPII core promoter region, which plays a critical role in controlling promoter activity. → These features of the pUPII promoter are fundamental to development of a target-specific vector. -- Abstract: Uroplakin II (UPII) is a one of the integral membrane proteins synthesized as a major differentiation product of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but little is known about its transcription response elements and molecular mechanism. To identify the cis-regulatory elements in the pig UPII (pUPII) gene promoter region, we constructed pUPII 5' upstream region deletion mutants and demonstrated that each of the deletion mutants participates in controlling the expression of the pUPII gene in human bladder carcinoma RT4 cells. We also identified a new core promoter region and putative negative cis-regulatory element within a minimal promoter region. In addition, we showed that hepatocyte nuclear factor 4 (HNF4) can directly bind in the pUPII core promoter (5F-1) region, which plays a critical role in controlling promoter activity. Transient cotransfection experiments showed that HNF4 positively regulates pUPII gene promoter activity. Thus, the binding element and its binding protein, HNF4 transcription factor, may be involved in the mechanism that specifically regulates pUPII gene transcription.

  20. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

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    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  1. Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element

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    Grewal Savraj S

    2010-01-01

    Full Text Available Abstract Background Nutrient availability is a key determinant of eukaryotic cell growth. In unicellular organisms many signaling and transcriptional networks link nutrient availability to the expression of metabolic genes required for growth. However, less is known about the corresponding mechanisms that operate in metazoans. We used gene expression profiling to explore this issue in developing Drosophila larvae. Results We found that starvation for dietary amino acids (AA's leads to dynamic changes in transcript levels of many metabolic genes. The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals. We found that many AA starvation-responsive transcripts were also altered in TOR mutants. In contrast, although PI3K overexpression induced robust changes in the expression of many metabolic genes, these changes showed limited overlap with the AA starvation expression profile. We did however identify a strong overlap between genes regulated by the transcription factor, Myc, and AA starvation-responsive genes, particularly those involved in ribosome biogenesis, protein synthesis and mitochondrial function. The consensus Myc DNA binding site is enriched in promoters of these AA starvation genes, and we found that Myc overexpression could bypass dietary AA to induce expression of these genes. We also identified another sequence motif (Motif 1 enriched in the promoters of AA starvation-responsive genes. We showed that Motif 1 was both necessary and sufficient to mediate transcriptional responses to dietary AA in larvae. Conclusions Our data suggest that many of the transcriptional effects of amino acids are mediated via signaling through the TOR pathway in Drosophila larvae. We also find that these transcriptional effects are mediated through at least two mechanisms: via the transcription factor Myc, and via the Motif 1 cis-regulatory element. These studies begin to elucidate a nutrient

  2. Identification of choriogenin cis-regulatory elements and production of estrogen-inducible, liver-specific transgenic Medaka.

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    Ueno, Tetsuro; Yasumasu, Shigeki; Hayashi, Shinji; Iuchi, Ichiro

    2004-07-01

    Choriogenins (chg-H, chg-L) are precursor proteins of egg envelope of medaka and synthesized in the spawning female liver in response to estrogen. We linked a gene construct chg-L1.5 kb/GFP (a 1.5 kb 5'-upstream region of the chg-L gene fused with a green fluorescence protein (GFP) gene) to another construct emgb/RFP (a cis-regulatory region of embryonic globin gene fused with an RFP gene), injected the double fusion gene construct into 1- or 2-cell-stage embryos, and selected embryos expressing the RFP in erythroid cells. From the embryos, we established two lines of chg-L1.5 kb/GFP-emgb/RFP-transgenic medaka. The 3-month-old spawning females and estradiol-17beta (E2)-exposed males displayed the liver-specific GFP expression. The E2-dependent GFP expression was detected in the differentiating liver of the stage 37-38 embryos. In addition, RT-PCR and whole-mount in situ hybridization showed that the E2-dependent chg expression was found in the liver of the stage 34 embryos of wild medaka, suggesting that such E2-dependency is achieved shortly after differentiation of the liver. Analysis using serial deletion mutants fused with GFP showed that the region -426 to -284 of the chg-L gene or the region -364 to -265 of the chg-H gene had the ability to promote the E2-dependent liver-specific GFP expression of its downstream gene. Further analyses suggested that an estrogen response element (ERE) at -309, an ERE half-site at -330 and a binding site for C/EBP at -363 of the chg-L gene played important roles in its downstream chg-L gene expression. In addition, this transgenic medaka may be useful as one of the test animals for detecting environmental estrogenic steroids.

  3. Nomadic enhancers: tissue-specific cis-regulatory elements of yellow have divergent genomic positions among Drosophila species.

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    Gizem Kalay

    2010-11-01

    Full Text Available cis-regulatory DNA sequences known as enhancers control gene expression in space and time. They are central to metazoan development and are often responsible for changes in gene regulation that contribute to phenotypic evolution. Here, we examine the sequence, function, and genomic location of enhancers controlling tissue- and cell-type specific expression of the yellow gene in six Drosophila species. yellow is required for the production of dark pigment, and its expression has evolved largely in concert with divergent pigment patterns. Using Drosophila melanogaster as a transgenic host, we examined the expression of reporter genes in which either 5' intergenic or intronic sequences of yellow from each species controlled the expression of Green Fluorescent Protein. Surprisingly, we found that sequences controlling expression in the wing veins, as well as sequences controlling expression in epidermal cells of the abdomen, thorax, and wing, were located in different genomic regions in different species. By contrast, sequences controlling expression in bristle-associated cells were located in the intron of all species. Differences in the precise pattern of spatial expression within the developing epidermis of D. melanogaster transformants usually correlated with adult pigmentation in the species from which the cis-regulatory sequences were derived, which is consistent with cis-regulatory evolution affecting yellow expression playing a central role in Drosophila pigmentation divergence. Sequence comparisons among species favored a model in which sequential nucleotide substitutions were responsible for the observed changes in cis-regulatory architecture. Taken together, these data demonstrate frequent changes in yellow cis-regulatory architecture among Drosophila species. Similar analyses of other genes, combining in vivo functional tests of enhancer activity with in silico comparative genomics, are needed to determine whether the pattern of

  4. Cis-regulatory element based targeted gene finding: genome-wide identification of abscisic acid- and abiotic stress-responsive genes in Arabidopsis thaliana.

    Science.gov (United States)

    Zhang, Weixiong; Ruan, Jianhua; Ho, Tuan-Hua David; You, Youngsook; Yu, Taotao; Quatrano, Ralph S

    2005-07-15

    A fundamental problem of computational genomics is identifying the genes that respond to certain endogenous cues and environmental stimuli. This problem can be referred to as targeted gene finding. Since gene regulation is mainly determined by the binding of transcription factors and cis-regulatory DNA sequences, most existing gene annotation methods, which exploit the conservation of open reading frames, are not effective in finding target genes. A viable approach to targeted gene finding is to exploit the cis-regulatory elements that are known to be responsible for the transcription of target genes. Given such cis-elements, putative target genes whose promoters contain the elements can be identified. As a case study, we apply the above approach to predict the genes in model plant Arabidopsis thaliana which are inducible by a phytohormone, abscisic acid (ABA), and abiotic stress, such as drought, cold and salinity. We first construct and analyze two ABA specific cis-elements, ABA-responsive element (ABRE) and its coupling element (CE), in A.thaliana, based on their conservation in rice and other cereal plants. We then use the ABRE-CE module to identify putative ABA-responsive genes in A.thaliana. Based on RT-PCR verification and the results from literature, this method has an accuracy rate of 67.5% for the top 40 predictions. The cis-element based targeted gene finding approach is expected to be widely applicable since a large number of cis-elements in many species are available.

  5. Microevolution of cis-regulatory elements: an example from the pair-rule segmentation gene fushi tarazu in the Drosophila melanogaster subgroup.

    Directory of Open Access Journals (Sweden)

    Mohammed Bakkali

    Full Text Available The importance of non-coding DNAs that control transcription is ever noticeable, but the characterization and analysis of the evolution of such DNAs presents challenges not found in the analysis of coding sequences. In this study of the cis-regulatory elements of the pair rule segmentation gene fushi tarazu (ftz I report the DNA sequences of ftz's zebra element (promoter and a region containing the proximal enhancer from a total of 45 fly lines belonging to several populations of the species Drosophila melanogaster, D. simulans, D. sechellia, D. mauritiana, D. yakuba, D. teissieri, D. orena and D. erecta. Both elements evolve at slower rate than ftz synonymous sites, thus reflecting their functional importance. The promoter evolves more slowly than the average for ftz's coding sequence while, on average, the enhancer evolves more rapidly, suggesting more functional constraint and effective purifying selection on the former. Comparative analysis of the number and nature of base substitutions failed to detect significant evidence for positive/adaptive selection in transcription-factor-binding sites. These seem to evolve at similar rates to regions not known to bind transcription factors. Although this result reflects the evolutionary flexibility of the transcription factor binding sites, it also suggests a complex and still not completely understood nature of even the characterized cis-regulatory sequences. The latter seem to contain more functional parts than those currently identified, some of which probably transcription factor binding. This study illustrates ways in which functional assignments of sequences within cis-acting sequences can be used in the search for adaptive evolution, but also highlights difficulties in how such functional assignment and analysis can be carried out.

  6. Functional dissection of the promoter of the pollen-specific gene NTP303 reveals a novel pollen-specific, and conserved cis-regulatory element.

    Science.gov (United States)

    Weterings, K; Schrauwen, J; Wullems, G; Twell, D

    1995-07-01

    Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.

  7. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  8. Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes

    OpenAIRE

    Kreiman, Gabriel

    2004-01-01

    Sequence information and high‐throughput methods to measure gene expression levels open the door to explore transcriptional regulation using computational tools. Combinatorial regulation and sparseness of regulatory elements throughout the genome allow organisms to control the spatial and temporal patterns of gene expression. Here we study the organization of cis‐regulatory elements in sets of co‐regulated genes. We build an algorithm to search for combinations of transcription factor binding...

  9. Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.

    Directory of Open Access Journals (Sweden)

    Yoav Hadas

    Full Text Available Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1 and Neurofascin (Nfasc are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.

  10. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  11. Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva

    Directory of Open Access Journals (Sweden)

    Guo Xiang

    2008-12-01

    Full Text Available Abstract Background Parasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species. Results Intergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know

  12. PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups

    Directory of Open Access Journals (Sweden)

    Huang Hsien-Da

    2008-11-01

    Full Text Available Abstract Background The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required. Results This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator, for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0, AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs within a defined distance (20 bp to 200 bp to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented. Conclusion In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.

  13. Identification of Predictive Cis-Regulatory Elements Using a Discriminative Objective Function and a Dynamic Search Space.

    Directory of Open Access Journals (Sweden)

    Rahul Karnik

    Full Text Available The generation of genomic binding or accessibility data from massively parallel sequencing technologies such as ChIP-seq and DNase-seq continues to accelerate. Yet state-of-the-art computational approaches for the identification of DNA binding motifs often yield motifs of weak predictive power. Here we present a novel computational algorithm called MotifSpec, designed to find predictive motifs, in contrast to over-represented sequence elements. The key distinguishing feature of this algorithm is that it uses a dynamic search space and a learned threshold to find discriminative motifs in combination with the modeling of motifs using a full PWM (position weight matrix rather than k-mer words or regular expressions. We demonstrate that our approach finds motifs corresponding to known binding specificities in several mammalian ChIP-seq datasets, and that our PWMs classify the ChIP-seq signals with accuracy comparable to, or marginally better than motifs from the best existing algorithms. In other datasets, our algorithm identifies novel motifs where other methods fail. Finally, we apply this algorithm to detect motifs from expression datasets in C. elegans using a dynamic expression similarity metric rather than fixed expression clusters, and find novel predictive motifs.

  14. Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.

    Science.gov (United States)

    Gao, Xin; Goggin, Kevin; Dowling, Camille; Qian, Jason; Hawdon, John M

    2015-01-08

    Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection. Genomic Fragment 2.23 containing a DAF-16 binding element (DBE) was used to identify overlapping complementary expressed sequence tags (ESTs). These sequences were used to search a draft assembly of the Ancylostoma caninum genome, and identified two neighboring genes, snr-3 and lpp-1, in a tail-to-tail orientation. Expression patterns of both genes during parasitic development were determined by qRT-PCR. DAF-16 dependent cis-regulatory activity of fragment 2.23 was investigated using an in vitro reporter system. The snr-3 gene spans approximately 5.6 kb in the genome and contains 3 exons and 2 introns, and contains the DBE in its 3' untranslated region. Downstream from snr-3 in a tail-to-tail arrangement is the gene lpp-1. The lpp-1 gene spans more than 6 kb and contains 10 exons and 9 introns. The A. caninum genome contains 2 apparent splice variants, but there are 7 splice variants in the A. ceylanicum genome. While the gene order is similar, the gene structures of the hookworm genes differ from their C. elegans orthologs. Both genes show peak expression in the late L4 stage. Using a cell culture based expression system, fragment 2.23 was found to have both DAF-16-dependent promoter and enhancer activity that required an intact DBE. Two putative DAF-16 targets were identified by genome wide screening for DAF-16 binding

  15. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

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    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  16. Dissection of cis-regulatory element architecture of the rice oleosin gene promoters to assess abscisic acid responsiveness in suspension-cultured rice cells.

    Science.gov (United States)

    Kim, Sol; Lee, Soo-Bin; Han, Chae-Seong; Lim, Mi-Na; Lee, Sung-Eun; Yoon, In Sun; Hwang, Yong-Sic

    2017-08-01

    Oleosins are the most abundant proteins in the monolipid layer surrounding neutral storage lipids that form oil bodies in plants. Several lines of evidence indicate that they are physiologically important for the maintenance of oil body structure and for mobilization of the lipids stored inside. Rice has six oleosin genes in its genome, the expression of all of which was found to be responsive to abscisic acid (ABA) in our examination of mature embryo and aleurone tissues. The 5'-flanking region of OsOle5 was initially characterized for its responsiveness to ABA through a transient expression assay system using the protoplasts from suspension-cultured rice cells. A series of successive deletions and site-directed mutations identified five regions critical for the hormonal induction of its promoter activity. A search for cis-acting elements in these regions deposited in a public database revealed that they contain various promoter elements previously reported to be involved in the ABA response of various genes. A gain-of-function experiment indicated that multiple copies of all five regions were sufficient to provide the minimal promoter with a distinct ABA responsiveness. Comparative sequence analysis of the short, but still ABA-responsive, promoters of OsOle genes revealed no common modular architecture shared by them, indicating that various distinct promoter elements and independent trans-acting factors are involved in the ABA responsiveness of rice oleosin multigenes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  17. Statistical significance of cis-regulatory modules

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    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  18. Identification and characterization of promoters and cis-regulatory elements of genes involved in secondary metabolites production in hop (Humulus lupulus. L)

    Czech Academy of Sciences Publication Activity Database

    Duraisamy, Ganesh Selvaraj; Mishra, Ajay Kumar; Kocábek, Tomáš; Matoušek, Jaroslav

    2016-01-01

    Roč. 84, October (2016), s. 346-352 ISSN 1476-9271 R&D Projects: GA ČR GA13-03037S Institutional support: RVO:60077344 Keywords : Cis-acting elements * Gene regulation * Humulus lupulus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.331, year: 2016

  19. The cis-regulatory element CCACGTGG is involved in ABA and water-stress responses of the maize gene rab28.

    Science.gov (United States)

    Pla, M; Vilardell, J; Guiltinan, M J; Marcotte, W R; Niogret, M F; Quatrano, R S; Pagès, M

    1993-01-01

    The maize gene rab28 has been identified as ABA-inducible in embryos and vegetative tissues. It is also induced by water stress in young leaves. The proximal promoter region contains the conserved cis-acting element CCACGTGG (ABRE) reported for ABA induction in other plant genes. Transient expression assays in rice protoplasts indicate that a 134 bp fragment (-194 to -60 containing the ABRE) fused to a truncated cauliflower mosaic virus promoter (35S) is sufficient to confer ABA-responsiveness upon the GUS reporter gene. Gel retardation experiments indicate that nuclear proteins from tissues in which the rab28 gene is expressed can interact specifically with this 134 bp DNA fragment. Nuclear protein extracts from embryo and water-stressed leaves generate specific complexes of different electrophoretic mobility which are stable in the presence of detergent and high salt. However, by DMS footprinting the same guanine-specific contacts with the ABRE in both the embryo and leaf binding activities were detected. These results indicate that the rab28 promoter sequence CCACGTGG is a functional ABA-responsive element, and suggest that distinct regulatory factors with apparent similar affinity for the ABRE sequence may be involved in the hormone action during embryo development and in vegetative tissues subjected to osmotic stress.

  20. ChIP-Seq-Annotated Heliconius erato Genome Highlights Patterns of cis-Regulatory Evolution in Lepidoptera

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    James J. Lewis

    2016-09-01

    Full Text Available Uncovering phylogenetic patterns of cis-regulatory evolution remains a fundamental goal for evolutionary and developmental biology. Here, we characterize the evolution of regulatory loci in butterflies and moths using chromatin immunoprecipitation sequencing (ChIP-seq annotation of regulatory elements across three stages of head development. In the process we provide a high-quality, functionally annotated genome assembly for the butterfly, Heliconius erato. Comparing cis-regulatory element conservation across six lepidopteran genomes, we find that regulatory sequences evolve at a pace similar to that of protein-coding regions. We also observe that elements active at multiple developmental stages are markedly more conserved than elements with stage-specific activity. Surprisingly, we also find that stage-specific proximal and distal regulatory elements evolve at nearly identical rates. Our study provides a benchmark for genome-wide patterns of regulatory element evolution in insects, and it shows that developmental timing of activity strongly predicts patterns of regulatory sequence evolution.

  1. Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS

    DEFF Research Database (Denmark)

    Farooq, Muhammad; Troelsen, Jesper T; Boyd, Mette

    2010-01-01

    A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects...... demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells. This finding supports a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more...

  2. Cis-regulatory somatic mutations and gene-expression alteration in B-cell lymphomas.

    Science.gov (United States)

    Mathelier, Anthony; Lefebvre, Calvin; Zhang, Allen W; Arenillas, David J; Ding, Jiarui; Wasserman, Wyeth W; Shah, Sohrab P

    2015-04-23

    With the rapid increase of whole-genome sequencing of human cancers, an important opportunity to analyze and characterize somatic mutations lying within cis-regulatory regions has emerged. A focus on protein-coding regions to identify nonsense or missense mutations disruptive to protein structure and/or function has led to important insights; however, the impact on gene expression of mutations lying within cis-regulatory regions remains under-explored. We analyzed somatic mutations from 84 matched tumor-normal whole genomes from B-cell lymphomas with accompanying gene expression measurements to elucidate the extent to which these cancers are disrupted by cis-regulatory mutations. We characterize mutations overlapping a high quality set of well-annotated transcription factor binding sites (TFBSs), covering a similar portion of the genome as protein-coding exons. Our results indicate that cis-regulatory mutations overlapping predicted TFBSs are enriched in promoter regions of genes involved in apoptosis or growth/proliferation. By integrating gene expression data with mutation data, our computational approach culminates with identification of cis-regulatory mutations most likely to participate in dysregulation of the gene expression program. The impact can be measured along with protein-coding mutations to highlight key mutations disrupting gene expression and pathways in cancer. Our study yields specific genes with disrupted expression triggered by genomic mutations in either the coding or the regulatory space. It implies that mutated regulatory components of the genome contribute substantially to cancer pathways. Our analyses demonstrate that identifying genomically altered cis-regulatory elements coupled with analysis of gene expression data will augment biological interpretation of mutational landscapes of cancers.

  3. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors

    NARCIS (Netherlands)

    J.C. Corbo (Joseph); K.A. Lawrence (Karen); M. Karlstetter (Marcus); C.A. Myers (Connie); M. Abdelaziz (Musa); W. Dirkes (William); K. Weigelt (Karin); M. Seifert (Martin); V. Benes (Vladimir); L.G. Fritsche (Lars); B.H.F. Weber (Bernhard); T. Langmann (Thomas)

    2010-01-01

    textabstractApproximately 98% of mammalian DNA is noncoding, yet we understand relatively little about the function of this enigmatic portion of the genome. The cis-regulatory elements that control gene expression reside in noncoding regions and can be identified by mapping the binding sites of

  4. Genome-wide prediction of cis-regulatory regions using supervised deep learning methods.

    Science.gov (United States)

    Li, Yifeng; Shi, Wenqiang; Wasserman, Wyeth W

    2018-05-31

    In the human genome, 98% of DNA sequences are non-protein-coding regions that were previously disregarded as junk DNA. In fact, non-coding regions host a variety of cis-regulatory regions which precisely control the expression of genes. Thus, Identifying active cis-regulatory regions in the human genome is critical for understanding gene regulation and assessing the impact of genetic variation on phenotype. The developments of high-throughput sequencing and machine learning technologies make it possible to predict cis-regulatory regions genome wide. Based on rich data resources such as the Encyclopedia of DNA Elements (ENCODE) and the Functional Annotation of the Mammalian Genome (FANTOM) projects, we introduce DECRES based on supervised deep learning approaches for the identification of enhancer and promoter regions in the human genome. Due to their ability to discover patterns in large and complex data, the introduction of deep learning methods enables a significant advance in our knowledge of the genomic locations of cis-regulatory regions. Using models for well-characterized cell lines, we identify key experimental features that contribute to the predictive performance. Applying DECRES, we delineate locations of 300,000 candidate enhancers genome wide (6.8% of the genome, of which 40,000 are supported by bidirectional transcription data), and 26,000 candidate promoters (0.6% of the genome). The predicted annotations of cis-regulatory regions will provide broad utility for genome interpretation from functional genomics to clinical applications. The DECRES model demonstrates potentials of deep learning technologies when combined with high-throughput sequencing data, and inspires the development of other advanced neural network models for further improvement of genome annotations.

  5. Using hexamers to predict cis-regulatory motifs in Drosophila

    Directory of Open Access Journals (Sweden)

    Kibler Dennis

    2005-10-01

    Full Text Available Abstract Background Cis-regulatory modules (CRMs are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered. Results We present a simple, efficient method (HexDiff based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements. Conclusion HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.

  6. Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

    Science.gov (United States)

    O'Connor, Timothy R.; Bailey, Timothy L.

    2014-01-01

    Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

  7. On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

    Science.gov (United States)

    Tarpine, Ryan; Istrail, Sorin

    The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

  8. Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis.

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    Michalis Barkoulas

    2016-09-01

    Full Text Available Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression.

  9. Genetic mapping uncovers cis-regulatory landscape of RNA editing.

    Science.gov (United States)

    Ramaswami, Gokul; Deng, Patricia; Zhang, Rui; Anna Carbone, Mary; Mackay, Trudy F C; Li, Jin Billy

    2015-09-16

    Adenosine-to-inosine (A-to-I) RNA editing, catalysed by ADAR enzymes conserved in metazoans, plays an important role in neurological functions. Although the fine-tuning mechanism provided by A-to-I RNA editing is important, the underlying rules governing ADAR substrate recognition are not well understood. We apply a quantitative trait loci (QTL) mapping approach to identify genetic variants associated with variability in RNA editing. With very accurate measurement of RNA editing levels at 789 sites in 131 Drosophila melanogaster strains, here we identify 545 editing QTLs (edQTLs) associated with differences in RNA editing. We demonstrate that many edQTLs can act through changes in the local secondary structure for edited dsRNAs. Furthermore, we find that edQTLs located outside of the edited dsRNA duplex are enriched in secondary structure, suggesting that distal dsRNA structure beyond the editing site duplex affects RNA editing efficiency. Our work will facilitate the understanding of the cis-regulatory code of RNA editing.

  10. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

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    Diana S José-Edwards

    2015-12-01

    Full Text Available A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs, and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

  11. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

    Science.gov (United States)

    José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

    2015-12-01

    A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

  12. Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.

    Science.gov (United States)

    Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav

    2007-08-01

    Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.

  13. Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA.

    Science.gov (United States)

    Pierstorff, Nora; Bergman, Casey M; Wiehe, Thomas

    2006-12-01

    Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a challenging computational task. Commonly used methods to predict CRMs based on the signal of transcription factor binding sites (TFBS) are limited by prior information about transcription factor specificity. More general methods that bypass the reliance on TFBS models are needed for comprehensive CRM prediction. We have developed a method to predict CRMs called CisPlusFinder that identifies high density regions of perfect local ungapped sequences (PLUSs) based on multiple species conservation. By assuming that PLUSs contain core TFBS motifs that are locally overrepresented, the method attempts to capture the expected features of CRM structure and evolution. Applied to a benchmark dataset of CRMs involved in early Drosophila development, CisPlusFinder predicts more annotated CRMs than all other methods tested. Using the REDfly database, we find that some 'false positive' predictions in the benchmark dataset correspond to recently annotated CRMs. Our work demonstrates that CRM prediction methods that combine comparative genomic data with statistical properties of DNA may achieve reasonable performance when applied genome-wide in the absence of an a priori set of known TFBS motifs. The program CisPlusFinder can be downloaded at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All software is licensed under the Lesser GNU Public License (LGPL).

  14. A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: functional characterisation and signatures of selection.

    Science.gov (United States)

    Wilding, Craig S; Smith, Ian; Lynd, Amy; Yawson, Alexander Egyir; Weetman, David; Paine, Mark J I; Donnelly, Martin J

    2012-09-01

    Although cytochrome P450 (CYP450) enzymes are frequently up-regulated in mosquitoes resistant to insecticides, no regulatory motifs driving these expression differences with relevance to wild populations have been identified. Transposable elements (TEs) are often enriched upstream of those CYP450s involved in insecticide resistance, leading to the assumption that they contribute regulatory motifs that directly underlie the resistance phenotype. A partial CuRE1 (Culex Repetitive Element 1) transposable element is found directly upstream of CYP9M10, a cytochrome P450 implicated previously in larval resistance to permethrin in the ISOP450 strain of Culex quinquefasciatus, but is absent from the equivalent genomic region of a susceptible strain. Via expression of CYP9M10 in Escherichia coli we have now demonstrated time- and NADPH-dependant permethrin metabolism, prerequisites for confirmation of a role in metabolic resistance, and through qPCR shown that CYP9M10 is >20-fold over-expressed in ISOP450 compared to a susceptible strain. In a fluorescent reporter assay the region upstream of CYP9M10 from ISOP450 drove 10× expression compared to the equivalent region (lacking CuRE1) from the susceptible strain. Close correspondence with the gene expression fold-change implicates the upstream region including CuRE1 as a cis-regulatory element involved in resistance. Only a single CuRE1 bearing allele, identical to the CuRE1 bearing allele in the resistant strain, is found throughout Sub-Saharan Africa, in contrast to the diversity encountered in non-CuRE1 alleles. This suggests a single origin and subsequent spread due to selective advantage. CuRE1 is detectable using a simple diagnostic. When applied to C. quinquefasciatus larvae from Ghana we have demonstrated a significant association with permethrin resistance in multiple field sites (mean Odds Ratio = 3.86) suggesting this marker has relevance to natural populations of vector mosquitoes. However, when CuRE1 was excised

  15. Barcoded DNA-tag reporters for multiplex cis-regulatory analysis.

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    Jongmin Nam

    Full Text Available Cis-regulatory DNA sequences causally mediate patterns of gene expression, but efficient experimental analysis of these control systems has remained challenging. Here we develop a new version of "barcoded" DNA-tag reporters, "Nanotags" that permit simultaneous quantitative analysis of up to 130 distinct cis-regulatory modules (CRMs. The activities of these reporters are measured in single experiments by the NanoString RNA counting method and other quantitative procedures. We demonstrate the efficiency of the Nanotag method by simultaneously measuring hourly temporal activities of 126 CRMs from 46 genes in the developing sea urchin embryo, otherwise a virtually impossible task. Nanotags are also used in gene perturbation experiments to reveal cis-regulatory responses of many CRMs at once. Nanotag methodology can be applied to many research areas, ranging from gene regulatory networks to functional and evolutionary genomics.

  16. An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

    Science.gov (United States)

    Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

    2016-08-09

    Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance

  17. Cis-regulatory timers for developmental gene expression.

    Directory of Open Access Journals (Sweden)

    Lionel Christiaen

    2013-10-01

    Full Text Available How does a fertilized egg decode its own genome to eventually develop into a mature animal? Each developing cell must activate a battery of genes in a timely manner and according to the function it will ultimately perform, but how? During development of the notochord--a structure akin to the vertebrate spine--in a simple marine invertebrate, an essential protein called Brachyury binds to specific sites in its target genes. A study just published in PLOS Biology reports that if the target gene contains multiple Brachyury-binding sites it will be activated early in development but if it contains only one site it will be activated later. Genes that contain no binding site can still be activated by Brachyury, but only indirectly by an earlier Brachyury-dependent gene product, so later than the directly activated genes. Thus, this study shows how several genes can interpret the presence of a single factor differently to become active at distinct times in development.

  18. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

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    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  19. Computational and molecular dissection of an X-box cis-Regulatory module

    OpenAIRE

    Warrington, Timothy Burton

    2015-01-01

    Ciliopathies are a class of human diseases marked by dysfunction of the cellular organelle, cilia. While many of the molecular components that make up cilia have been identified and studied, comparatively little is understood about the transcriptional regulation of genes encoding these components. The conserved transcription factor Regulatory Factor X (RFX)/DAF-19, which acts through binding to the cis-regulatory motif known as X-box, has been shown to regulate ciliary genes in many animals f...

  20. Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

    Science.gov (United States)

    Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

    2009-03-10

    The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

  1. Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

    Science.gov (United States)

    Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

    2018-01-01

    Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

  2. Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

    Science.gov (United States)

    Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

    2013-09-02

    In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome

  3. Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds

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    Zuniga Aimée

    2012-08-01

    Full Text Available Abstract Background Mouse limb bud is a prime model to study the regulatory interactions that control vertebrate organogenesis. Major aspects of limb bud development are controlled by feedback loops that define a self-regulatory signalling system. The SHH/GREM1/AER-FGF feedback loop forms the core of this signalling system that operates between the posterior mesenchymal organiser and the ectodermal signalling centre. The BMP antagonist Gremlin1 (GREM1 is a critical node in this system, whose dynamic expression is controlled by BMP, SHH, and FGF signalling and key to normal progression of limb bud development. Previous analysis identified a distant cis-regulatory landscape within the neighbouring Formin1 (Fmn1 locus that is required for Grem1 expression, reminiscent of the genomic landscapes controlling HoxD and Shh expression in limb buds. Results Three highly conserved regions (HMCO1-3 were identified within the previously defined critical genomic region and tested for their ability to regulate Grem1 expression in mouse limb buds. Using a combination of BAC and conventional transgenic approaches, a 9 kb region located ~70 kb downstream of the Grem1 transcription unit was identified. This region, termed Grem1 Regulatory Sequence 1 (GRS1, is able to recapitulate major aspects of Grem1 expression, as it drives expression of a LacZ reporter into the posterior and, to a lesser extent, in the distal-anterior mesenchyme. Crossing the GRS1 transgene into embryos with alterations in the SHH and BMP pathways established that GRS1 depends on SHH and is modulated by BMP signalling, i.e. integrates inputs from these pathways. Chromatin immunoprecipitation revealed interaction of endogenous GLI3 proteins with the core cis-regulatory elements in the GRS1 region. As GLI3 is a mediator of SHH signal transduction, these results indicated that SHH directly controls Grem1 expression through the GRS1 region. Finally, all cis-regulatory regions within the Grem1

  4. Plasticity of the cis-regulatory input function of a gene.

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    Avraham E Mayo

    2006-04-01

    Full Text Available The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each with different point mutations in the regulator binding sites, by means of accurate expression measurements from living cells. We find that even a few mutations can significantly change the input function, resulting in functions that resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs.

  5. A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs and their role in transcriptional activation in cells in culture and in transgenic mice.

    Science.gov (United States)

    Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R

    1997-09-05

    To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient

  6. Mapping of cis-regulatory sites in the promoter of testis-specific stellate genes of Drosophila melanogaster.

    Science.gov (United States)

    Olenkina, O M; Egorova, K S; Aravin, A A; Naumova, N M; Gvozdev, V A; Olenina, L V

    2012-11-01

    Tandem Stellate genes organized into two clusters in heterochromatin and euchromatin of the X-chromosome are part of the Ste-Su(Ste) genetic system required for maintenance of male fertility and reproduction of Drosophila melanogaster. Stellate genes encode a regulatory subunit of protein kinase CK2 and are the main targets of germline-specific piRNA-silencing; their derepression leads to appearance of protein crystals in spermatocytes, meiotic disturbances, and male sterility. A short promoter region of 134 bp appears to be sufficient for testis-specific transcription of Stellate, and it contains three closely located cis-regulatory elements called E-boxes. By using reporter analysis, we confirmed a strong functionality of the E-boxes in the Stellate promoter for in vivo transcription. Using selective mutagenesis, we have shown that the presence of the central E-box 2 is preferable to maintain a high-level testis-specific transcription of the reporter gene under the Stellate promoter. The Stellate promoter provides transcription even in heterochromatin, and corresponding mRNAs are translated with the generation of full-size protein products in case of disturbances in the piRNA-silencing process. We have also shown for the first time that the activity of the Stellate promoter is determined by chromatin context of the X-chromosome in male germinal cells, and it increases at about twofold when relocating in autosomes.

  7. Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.

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    Bin Z He

    2011-04-01

    Full Text Available Transcription factor binding site(s (TFBS gain and loss (i.e., turnover is a well-documented feature of cis-regulatory module (CRM evolution, yet little attention has been paid to the evolutionary force(s driving this turnover process. The predominant view, motivated by its widespread occurrence, emphasizes the importance of compensatory mutation and genetic drift. Positive selection, in contrast, although it has been invoked in specific instances of adaptive gene expression evolution, has not been considered as a general alternative to neutral compensatory evolution. In this study we evaluate the two hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS of well-characterized CRM in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans. An important feature of the analysis is classification of TFBS mutations according to the direction of their predicted effect on binding affinity, which allows gains and losses to be evaluated independently along the two phylogenetic lineages. The observed patterns of polymorphism and divergence are not compatible with neutral evolution for either class of mutations. Instead, multiple lines of evidence are consistent with contributions of positive selection to TFBS gain and loss as well as purifying selection in its maintenance. In discussion, we propose a model to reconcile the finding of selection driving TFBS turnover with constrained CRM function over long evolutionary time.

  8. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

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    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  9. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Science.gov (United States)

    2017-01-01

    The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

  10. Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution.

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    Xin He

    2009-03-01

    Full Text Available Cross-species comparison has emerged as a powerful paradigm for predicting cis-regulatory modules (CRMs and understanding their evolution. The comparison requires reliable sequence alignment, which remains a challenging task for less conserved noncoding sequences. Furthermore, the existing models of DNA sequence evolution generally do not explicitly treat the special properties of CRM sequences. To address these limitations, we propose a model of CRM evolution that captures different modes of evolution of functional transcription factor binding sites (TFBSs and the background sequences. A particularly novel aspect of our work is a probabilistic model of gains and losses of TFBSs, a process being recognized as an important part of regulatory sequence evolution. We present a computational framework that uses this model to solve the problems of CRM alignment and prediction. Our alignment method is similar to existing methods of statistical alignment but uses the conserved binding sites to improve alignment. Our CRM prediction method deals with the inherent uncertainties of binding site annotations and sequence alignment in a probabilistic framework. In simulated as well as real data, we demonstrate that our program is able to improve both alignment and prediction of CRM sequences over several state-of-the-art methods. Finally, we used alignments produced by our program to study binding site conservation in genome-wide binding data of key transcription factors in the Drosophila blastoderm, with two intriguing results: (i the factor-bound sequences are under strong evolutionary constraints even if their neighboring genes are not expressed in the blastoderm and (ii binding sites in distal bound sequences (relative to transcription start sites tend to be more conserved than those in proximal regions. Our approach is implemented as software, EMMA (Evolutionary Model-based cis-regulatory Module Analysis, ready to be applied in a broad biological context.

  11. Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

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    Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

    2005-09-01

    We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

  12. Duration judgements over multiple elements

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    Inci eAyhan

    2012-11-01

    Full Text Available We investigated the limits of the number of events observers can simultaneously time. For single targets occurring in one of eight positions sensitivity to duration was improved for spatially pre-cued items as compared to post-cued items indicating that exogenous driven attention can improve duration discrimination. Sensitivity to duration for pre-cued items was also marginally better for single items as compared to eight items indicating that even after the allocation of focal attention, distracter items can interfere with the encoding of duration. For an eight item array discrimination was worse for post-cued locations as compared to pre-cued locations indicating both that attention can improve duration discrimination performance and that it was not possible to access a perfect memory trace of the duration of eight elements. The interference from the distracters in the pre-cued eight item array may reflect some mandatory averaging of target and distracter events. To further explore duration averaging we asked subjects to explicitly compare average durations of multiple item arrays against a single item standard duration. Duration discrimination thresholds were significantly lower for single elements as compared to multiple elements, showing that averaging, either automatically or intentionally, impairs duration discrimination. There was no set size effect. Performance was the same for averages of two and eight items, but performance with even an average of two items was worse than for one item. This was also true for sequential presentation indicating poor performance was not due to limits on the division of attention across items. Rather performance appears to be limited by an inability to remember or aggregate duration information from two or more items. Although it is possible to manipulate perceived duration locally, there appears to be no perceptual mechanisms for aggregating local durations across space.

  13. Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

    Science.gov (United States)

    Kwon, Andrew T.; Chou, Alice Yi; Arenillas, David J.; Wasserman, Wyeth W.

    2011-01-01

    We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions. PMID:22144875

  14. Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.

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    Andrew T Kwon

    2011-12-01

    Full Text Available We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions.

  15. Characterization of Cer-1 cis-regulatory region during early Xenopus development.

    Science.gov (United States)

    Silva, Ana Cristina; Filipe, Mário; Steinbeisser, Herbert; Belo, José António

    2011-05-01

    Cerberus-related molecules are well-known Wnt, Nodal, and BMP inhibitors that have been implicated in different processes including anterior–posterior patterning and left–right asymmetry. In both mouse and frog, two Cerberus-related genes have been isolated, mCer-1 and mCer-2, and Xcer and Xcoco, respectively. Until now, little is known about the mechanisms involved in their transcriptional regulation. Here, we report a heterologous analysis of the mouse Cerberus-1 gene upstream regulatory regions, responsible for its expression in the visceral endodermal cells. Our analysis showed that the consensus sequences for a TATA, CAAT, or GC boxes were absent but a TGTGG sequence was present at position -172 to -168 bp, relative to the ATG. Using a series of deletion constructs and transient expression in Xenopus embryos, we found that a fragment of 1.4 kb of Cer-1 promoter sequence could reproduce the endogenous expression pattern of Xenopus cerberus. A 0.7-kb mcer-1 upstream region was able to drive reporter expression to the involuting mesendodermal cells, while further deletions abolished reporter gene expression. Our results suggest that although no sequence similarity was found between mouse and Xenopus cerberus cis-regulatory regions, the signaling cascades regulating cerberus expression, during gastrulation, is conserved.

  16. PReMod: a database of genome-wide mammalian cis-regulatory module predictions.

    Science.gov (United States)

    Ferretti, Vincent; Poitras, Christian; Bergeron, Dominique; Coulombe, Benoit; Robert, François; Blanchette, Mathieu

    2007-01-01

    We describe PReMod, a new database of genome-wide cis-regulatory module (CRM) predictions for both the human and the mouse genomes. The prediction algorithm, described previously in Blanchette et al. (2006) Genome Res., 16, 656-668, exploits the fact that many known CRMs are made of clusters of phylogenetically conserved and repeated transcription factors (TF) binding sites. Contrary to other existing databases, PReMod is not restricted to modules located proximal to genes, but in fact mostly contains distal predicted CRMs (pCRMs). Through its web interface, PReMod allows users to (i) identify pCRMs around a gene of interest; (ii) identify pCRMs that have binding sites for a given TF (or a set of TFs) or (iii) download the entire dataset for local analyses. Queries can also be refined by filtering for specific chromosomal regions, for specific regions relative to genes or for the presence of CpG islands. The output includes information about the binding sites predicted within the selected pCRMs, and a graphical display of their distribution within the pCRMs. It also provides a visual depiction of the chromosomal context of the selected pCRMs in terms of neighboring pCRMs and genes, all of which are linked to the UCSC Genome Browser and the NCBI. PReMod: http://genomequebec.mcgill.ca/PReMod.

  17. Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.

    Science.gov (United States)

    Haro, Endika; Watson, Billy A; Feenstra, Jennifer M; Tegeler, Luke; Pira, Charmaine U; Mohan, Subburaman; Oberg, Kerby C

    2017-06-01

    Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed by next-generation sequencing (ChIP-seq). Nearly 84% ( n =617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis -regulatory modules (PCRMs). In addition, 73 LBIs mapped to CRMs that are known to be active during limb development. We compared Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization. © 2017. Published by The Company of Biologists Ltd.

  18. Identifying Cis-Regulatory Changes Involved in the Evolution of Aerobic Fermentation in Yeasts

    Science.gov (United States)

    Lin, Zhenguo; Wang, Tzi-Yuan; Tsai, Bing-Shi; Wu, Fang-Ting; Yu, Fu-Jung; Tseng, Yu-Jung; Sung, Huang-Mo; Li, Wen-Hsiung

    2013-01-01

    Gene regulation change has long been recognized as an important mechanism for phenotypic evolution. We used the evolution of yeast aerobic fermentation as a model to explore how gene regulation has evolved and how this process has contributed to phenotypic evolution and adaptation. Most eukaryotes fully oxidize glucose to CO2 and H2O in mitochondria to maximize energy yield, whereas some yeasts, such as Saccharomyces cerevisiae and its relatives, predominantly ferment glucose into ethanol even in the presence of oxygen, a phenomenon known as aerobic fermentation. We examined the genome-wide gene expression levels among 12 different yeasts and found that a group of genes involved in the mitochondrial respiration process showed the largest reduction in gene expression level during the evolution of aerobic fermentation. Our analysis revealed that the downregulation of these genes was significantly associated with massive loss of binding motifs of Cbf1p in the fermentative yeasts. Our experimental assays confirmed the binding of Cbf1p to the predicted motif and the activator role of Cbf1p. In summary, our study laid a foundation to unravel the long-time mystery about the genetic basis of evolution of aerobic fermentation, providing new insights into understanding the role of cis-regulatory changes in phenotypic evolution. PMID:23650209

  19. Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer

    Directory of Open Access Journals (Sweden)

    Matloob Khushi

    2014-11-01

    Full Text Available Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα and progesterone receptor (PR in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS, Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.

  20. Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila.

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    Margaret C W Ho

    2009-11-01

    Full Text Available It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs. How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules.

  1. LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms.

    Science.gov (United States)

    Yang, Peng; Wu, Min; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

    2014-02-17

    As a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs. Recently, an algorithm called "LDsplit" has been designed to detect the association between single nucleotide polymorphisms (SNPs) and proximal meiotic recombination hotspots. The association is measured by the difference of population recombination rates at a hotspot between two alleles of a candidate SNP. Here we present an open source software tool of LDsplit, with integrative data visualization for recombination hotspots and their proximal SNPs. Applying LDsplit on SNPs inside an established 7-mer motif bound by PRDM9 we observed that SNP alleles preserving the original motif tend to have higher recombination rates than the opposite alleles that disrupt the motif. Running on SNP windows around hotspots each containing an occurrence of the 7-mer motif, LDsplit is able to guide the established motif finding algorithm of MEME to recover the 7-mer motif. In contrast, without LDsplit the 7-mer motif could not be identified. LDsplit is a software tool for the discovery of cis-regulatory DNA sequence motifs stimulating meiotic recombination hotspots by screening and narrowing down to hotspot associated SNPs. It is the first computational method that utilizes the genetic variation of

  2. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

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    Girgis Hani Z

    2012-02-01

    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  3. Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis; Rubin, EdwardM.; Couronne, Olivier

    2005-06-13

    Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.

  4. Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

    Science.gov (United States)

    Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

    2009-11-01

    The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

  5. Identification of a cis-regulatory region of a gene in Arabidopsis thaliana whose induction by dehydration is mediated by abscisic acid and requires protein synthesis.

    Science.gov (United States)

    Iwasaki, T; Yamaguchi-Shinozaki, K; Shinozaki, K

    1995-05-20

    In Arabidopsis thaliana, the induction of a dehydration-responsive gene, rd22, is mediated by abscisic acid (ABA) but the gene does not include any sequence corresponding to the consensus ABA-responsive element (ABRE), RYACGTGGYR, in its promoter region. The cis-regulatory region of the rd22 promoter was identified by monitoring the expression of beta-glucuronidase (GUS) activity in leaves of transgenic tobacco plants transformed with chimeric gene fusions constructed between 5'-deleted promoters of rd22 and the coding region of the GUS reporter gene. A 67-bp nucleotide fragment corresponding to positions -207 to -141 of the rd22 promoter conferred responsiveness to dehydration and ABA on a non-responsive promoter. The 67-bp fragment contains the sequences of the recognition sites for some transcription factors, such as MYC, MYB, and GT-1. The fact that accumulation of rd22 mRNA requires protein synthesis raises the possibility that the expression of rd22 might be regulated by one of these trans-acting protein factors whose de novo synthesis is induced by dehydration or ABA. Although the structure of the RD22 protein is very similar to that of a non-storage seed protein, USP, of Vicia faba, the expression of the GUS gene driven by the rd22 promoter in non-stressed transgenic Arabidopsis plants was found mainly in flowers and bolted stems rather than in seeds.

  6. cisMEP: an integrated repository of genomic epigenetic profiles and cis-regulatory modules in Drosophila.

    Science.gov (United States)

    Yang, Tzu-Hsien; Wang, Chung-Ching; Hung, Po-Cheng; Wu, Wei-Sheng

    2014-01-01

    Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms

  7. Redox flow batteries having multiple electroactive elements

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Li, Liyu; Yang, Zhenguo; Nie, Zimin

    2018-05-01

    Introducing multiple redox reactions with a suitable voltage range can improve the energy density of redox flow battery (RFB) systems. One example includes RFB systems utilizing multiple redox pairs in the positive half cell, the negative half cell, or in both. Such RFB systems can have a negative electrolyte, a positive electrolyte, and a membrane between the negative electrolyte and the positive electrolyte, in which at least two electrochemically active elements exist in the negative electrolyte, the positive electrolyte, or both.

  8. Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann–Mangold organizer

    Science.gov (United States)

    Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

    2012-01-01

    How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann–Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer. PMID:22492356

  9. Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.

    Science.gov (United States)

    Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

    2012-05-01

    How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann-Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer.

  10. Unveiling combinatorial regulation through the combination of ChIP information and in silico cis-regulatory module detection

    Science.gov (United States)

    Sun, Hong; Guns, Tias; Fierro, Ana Carolina; Thorrez, Lieven; Nijssen, Siegfried; Marchal, Kathleen

    2012-01-01

    Computationally retrieving biologically relevant cis-regulatory modules (CRMs) is not straightforward. Because of the large number of candidates and the imperfection of the screening methods, many spurious CRMs are detected that are as high scoring as the biologically true ones. Using ChIP-information allows not only to reduce the regions in which the binding sites of the assayed transcription factor (TF) should be located, but also allows restricting the valid CRMs to those that contain the assayed TF (here referred to as applying CRM detection in a query-based mode). In this study, we show that exploiting ChIP-information in a query-based way makes in silico CRM detection a much more feasible endeavor. To be able to handle the large datasets, the query-based setting and other specificities proper to CRM detection on ChIP-Seq based data, we developed a novel powerful CRM detection method ‘CPModule’. By applying it on a well-studied ChIP-Seq data set involved in self-renewal of mouse embryonic stem cells, we demonstrate how our tool can recover combinatorial regulation of five known TFs that are key in the self-renewal of mouse embryonic stem cells. Additionally, we make a number of new predictions on combinatorial regulation of these five key TFs with other TFs documented in TRANSFAC. PMID:22422841

  11. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Directory of Open Access Journals (Sweden)

    Amanda Malvessi Cattani

    Full Text Available Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  12. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Science.gov (United States)

    Cattani, Amanda Malvessi; Siqueira, Franciele Maboni; Guedes, Rafael Lucas Muniz; Schrank, Irene Silveira

    2016-01-01

    Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  13. Piecing together cis-regulatory networks: insights from epigenomics studies in plants.

    Science.gov (United States)

    Huang, Shao-Shan C; Ecker, Joseph R

    2018-05-01

    5-Methylcytosine, a chemical modification of DNA, is a covalent modification found in the genomes of both plants and animals. Epigenetic inheritance of phenotypes mediated by DNA methylation is well established in plants. Most of the known mechanisms of establishing, maintaining and modifying DNA methylation have been worked out in the reference plant Arabidopsis thaliana. Major functions of DNA methylation in plants include regulation of gene expression and silencing of transposable elements (TEs) and repetitive sequences, both of which have parallels in mammalian biology, involve interaction with the transcriptional machinery, and may have profound effects on the regulatory networks in the cell. Methylome and transcriptome dynamics have been investigated in development and environmental responses in Arabidopsis and agriculturally and ecologically important plants, revealing the interdependent relationship among genomic context, methylation patterns, and expression of TE and protein coding genes. Analyses of methylome variation among plant natural populations and species have begun to quantify the extent of genetic control of methylome variation vs. true epimutation, and model the evolutionary forces driving methylome evolution in both short and long time scales. The ability of DNA methylation to positively or negatively modulate binding affinity of transcription factors (TFs) provides a natural link from genome sequence and methylation changes to transcription. Technologies that allow systematic determination of methylation sensitivities of TFs, in native genomic and methylation context without confounding factors such as histone modifications, will provide baseline datasets for building cell-type- and individual-specific regulatory networks that underlie the establishment and inheritance of complex traits. This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods Biological Mechanisms > Regulatory Biology. © 2017 Wiley

  14. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures

    NARCIS (Netherlands)

    Kusters, E.; Della Pina, S.; Castel, R.; Souer, E.; Koes, R.

    2015-01-01

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than

  15. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

    NARCIS (Netherlands)

    Kusters, E.; Della Pina, S.; Castel, R.; Souer, E.J.; Koes, R.E.

    2015-01-01

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than

  16. Cis-regulatory PLETHORA promoter elements directing root and nodule expression are conserved between Arabidopsis thaliana and Medicago truncatula

    NARCIS (Netherlands)

    Franssen, H.G.J.M.; Kulikova, O.; Willemsen, V.A.; Heidstra, R.

    2017-01-01

    Nodules are unique organs formed on roots of legumes by soil-borne bacteria, collectively known as rhizobium. Recently, we have shown that orthologs of the AINTEGUMENTA-like (AIL) AP2 transcription factors PLETHORA (PLT) 1 to 4, that redundantly regulate Arabidopsis thaliana root development are

  17. A novel method for predicting activity of cis-regulatory modules, based on a diverse training set.

    Science.gov (United States)

    Yang, Wei; Sinha, Saurabh

    2017-01-01

    With the rapid emergence of technologies for locating cis-regulatory modules (CRMs) genome-wide, the next pressing challenge is to assign precise functions to each CRM, i.e. to determine the spatiotemporal domains or cell-types where it drives expression. A popular approach to this task is to model the typical k-mer composition of a set of CRMs known to drive a common expression pattern, and assign that pattern to other CRMs exhibiting a similar k-mer composition. This approach does not rely on prior knowledge of transcription factors relevant to the CRM or their binding motifs, and is thus more widely applicable than motif-based methods for predicting CRM activity, but is also prone to false positive predictions. We present a novel strategy to improve the above-mentioned approach: to predict if a CRM drives a specific gene expression pattern, assess not only how similar the CRM is to other CRMs with similar activity but also to CRMs with distinct activities. We use a state-of-the-art statistical method to quantify a CRM's sequence similarity to many different training sets of CRMs, and employ a classification algorithm to integrate these similarity scores into a single prediction of the CRM's activity. This strategy is shown to significantly improve CRM activity prediction over current approaches. Our implementation of the new method, called IMMBoost, is freely available as source code, at https://github.com/weiyangedward/IMMBoost CONTACT: sinhas@illinois.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. RNA-ID, a highly sensitive and robust method to identify cis-regulatory sequences using superfolder GFP and a fluorescence-based assay.

    Science.gov (United States)

    Dean, Kimberly M; Grayhack, Elizabeth J

    2012-12-01

    We have developed a robust and sensitive method, called RNA-ID, to screen for cis-regulatory sequences in RNA using fluorescence-activated cell sorting (FACS) of yeast cells bearing a reporter in which expression of both superfolder green fluorescent protein (GFP) and yeast codon-optimized mCherry red fluorescent protein (RFP) is driven by the bidirectional GAL1,10 promoter. This method recapitulates previously reported progressive inhibition of translation mediated by increasing numbers of CGA codon pairs, and restoration of expression by introduction of a tRNA with an anticodon that base pairs exactly with the CGA codon. This method also reproduces effects of paromomycin and context on stop codon read-through. Five key features of this method contribute to its effectiveness as a selection for regulatory sequences: The system exhibits greater than a 250-fold dynamic range, a quantitative and dose-dependent response to known inhibitory sequences, exquisite resolution that allows nearly complete physical separation of distinct populations, and a reproducible signal between different cells transformed with the identical reporter, all of which are coupled with simple methods involving ligation-independent cloning, to create large libraries. Moreover, we provide evidence that there are sequences within a 9-nt library that cause reduced GFP fluorescence, suggesting that there are novel cis-regulatory sequences to be found even in this short sequence space. This method is widely applicable to the study of both RNA-mediated and codon-mediated effects on expression.

  19. Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints

    Directory of Open Access Journals (Sweden)

    Xu Fuyu

    2012-09-01

    Full Text Available Abstract Background The potential contribution of upstream sequence variation to the unique features of orthologous genes is just beginning to be unraveled. A core subset of stress-associated bZIP transcription factors from rice (Oryza sativa formed ten clusters of orthologous groups (COG with genes from the monocot sorghum (Sorghum bicolor and dicot Arabidopsis (Arabidopsis thaliana. The total cis-regulatory information content of each stress-associated COG was examined by phylogenetic footprinting to reveal ortholog-specific, lineage-specific and species-specific conservation patterns. Results The most apparent pattern observed was the occurrence of spatially conserved ‘core modules’ among the COGs but not among paralogs. These core modules are comprised of various combinations of two to four putative transcription factor binding site (TFBS classes associated with either developmental or stress-related functions. Outside the core modules are specific stress (ABA, oxidative, abiotic, biotic or organ-associated signals, which may be functioning as ‘regulatory fine-tuners’ and further define lineage-specific and species-specific cis-regulatory signatures. Orthologous monocot and dicot promoters have distinct TFBS classes involved in disease and oxidative-regulated expression, while the orthologous rice and sorghum promoters have distinct combinations of root-specific signals, a pattern that is not particularly conserved in Arabidopsis. Conclusions Patterns of cis-regulatory conservation imply that each ortholog has distinct signatures, further suggesting that they are potentially unique in a regulatory context despite the presumed conservation of broad biological function during speciation. Based on the observed patterns of conservation, we postulate that core modules are likely primary determinants of basal developmental programming, which may be integrated with and further elaborated by additional intrinsic or extrinsic signals in

  20. Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus.

    Directory of Open Access Journals (Sweden)

    Alison P Lee

    Full Text Available The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG, recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers.

  1. Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

    Science.gov (United States)

    Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

    2009-01-01

    A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

  2. Quantification of multiple elements in dried blood spot samples

    DEFF Research Database (Denmark)

    Pedersen, Lise; Andersen-Ranberg, Karen; Hollergaard, Mads

    2017-01-01

    BACKGROUND: Dried blood spots (DBS) is a unique matrix that offers advantages compared to conventional blood collection making it increasingly popular in large population studies. We here describe development and validation of a method to determine multiple elements in DBS. METHODS: Elements were...... in venous blood. Samples with different hematocrit were spotted onto filter paper to assess hematocrit effect. RESULTS: The established method was precise and accurate for measurement of most elements in DBS. There was a significant but relatively weak correlation between measurement of the elements Mg, K...

  3. Cis-regulatory control of the nuclear receptor Coup-TF gene in the sea urchin Paracentrotus lividus embryo.

    Directory of Open Access Journals (Sweden)

    Lamprini G Kalampoki

    Full Text Available Coup-TF, an orphan member of the nuclear receptor super family, has a fundamental role in the development of metazoan embryos. The study of the gene's regulatory circuit in the sea urchin embryo will facilitate the placement of this transcription factor in the well-studied embryonic Gene Regulatory Network (GRN. The Paracentrotus lividus Coup-TF gene (PlCoup-TF is expressed throughout embryonic development preferentially in the oral ectoderm of the gastrula and the ciliary band of the pluteus stage. Two overlapping λ genomic clones, containing three exons and upstream sequences of PlCoup-TF, were isolated from a genomic library. The transcription initiation site was determined and 5' deletions and individual segments of a 1930 bp upstream region were placed ahead of a GFP reporter cassette and injected into fertilized P.lividus eggs. Module a (-532 to -232, was necessary and sufficient to confer ciliary band expression to the reporter. Comparison of P.lividus and Strongylocentrotus purpuratus upstream Coup-TF sequences, revealed considerable conservation, but none within module a. 5' and internal deletions into module a, defined a smaller region that confers ciliary band specific expression. Putative regulatory cis-acting elements (RE1, RE2 and RE3 within module a, were specifically bound by proteins in sea urchin embryonic nuclear extracts. Site-specific mutagenesis of these elements resulted in loss of reporter activity (RE1 or ectopic expression (RE2, RE3. It is proposed that sea urchin transcription factors, which bind these three regulatory sites, are necessary for spatial and quantitative regulation of the PlCoup-TF gene at pluteus stage sea urchin embryos. These findings lead to the future identification of these factors and to the hierarchical positioning of PlCoup-TF within the embryonic GRN.

  4. The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the Adult

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    2012-07-01

    Full Text Available Genome-wide studies have identified thousands of long noncoding RNAs (lncRNAs lacking protein-coding capacity. However, most lncRNAs are expressed at a very low level, and in most cases there is no genetic evidence to support their in vivo function. Malat1 (metastasis associated lung adenocarcinoma transcript 1 is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3′-end processing mechanism. In addition, its specific nuclear localization, developmental regulation, and dysregulation in cancer are suggestive of it having a critical biological function. We have characterized a Malat1 loss-of-function genetic model that indicates that Malat1 is not essential for mouse pre- and postnatal development. Furthermore, depletion of Malat1 does not affect global gene expression, splicing factor level and phosphorylation status, or alternative pre-mRNA splicing. However, among a small number of genes that were dysregulated in adult Malat1 knockout mice, many were Malat1 neighboring genes, thus indicating a potential cis-regulatory role of Malat1 gene transcription.

  5. A Survey of 6,300 Genomic Fragments for cis-Regulatory Activity in the Imaginal Discs of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Aurélie Jory

    2012-10-01

    Full Text Available Over 6,000 fragments from the genome of Drosophila melanogaster were analyzed for their ability to drive expression of GAL4 reporter genes in the third-instar larval imaginal discs. About 1,200 reporter genes drove expression in the eye, antenna, leg, wing, haltere, or genital imaginal discs. The patterns ranged from large regions to individual cells. About 75% of the active fragments drove expression in multiple discs; 20% were expressed in ventral, but not dorsal, discs (legs, genital, and antenna, whereas ∼23% were expressed in dorsal but not ventral discs (wing, haltere, and eye. Several patterns, for example, within the leg chordotonal organ, appeared a surprisingly large number of times. Unbiased searches for DNA sequence motifs suggest candidate transcription factors that may regulate enhancers with shared activities. Together, these expression patterns provide a valuable resource to the community and offer a broad overview of how transcriptional regulatory information is distributed in the Drosophila genome.

  6. Expression of the central growth regulator BIG BROTHER is regulated by multiple cis-elements

    Directory of Open Access Journals (Sweden)

    Breuninger Holger

    2012-03-01

    Full Text Available Abstract Background Much of the organismal variation we observe in nature is due to differences in organ size. The observation that even closely related species can show large, stably inherited differences in organ size indicates a strong genetic component to the control of organ size. Despite recent progress in identifying factors controlling organ growth in plants, our overall understanding of this process remains limited, partly because the individual factors have not yet been connected into larger regulatory pathways or networks. To begin addressing this aim, we have studied the upstream regulation of expression of BIG BROTHER (BB, a central growth-control gene in Arabidopsis thaliana that prevents overgrowth of organs. Final organ size and BB expression levels are tightly correlated, implying the need for precise control of its expression. BB expression mirrors proliferative activity, yet the gene functions to limit proliferation, suggesting that it acts in an incoherent feedforward loop downstream of growth activators to prevent over-proliferation. Results To investigate the upstream regulation of BB we combined a promoter deletion analysis with a phylogenetic footprinting approach. We were able to narrow down important, highly conserved, cis-regulatory elements within the BB promoter. Promoter sequences of other Brassicaceae species were able to partially complement the A. thaliana bb-1 mutant, suggesting that at least within the Brassicaceae family the regulatory pathways are conserved. Conclusions This work underlines the complexity involved in precise quantitative control of gene expression and lays the foundation for identifying important upstream regulators that determine BB expression levels and thus final organ size.

  7. Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT genomic binding patterns discerns cell-specific cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Kang Keunsoo

    2013-01-01

    Full Text Available Abstract Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM, which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.

  8. A variant in a Cis-regulatory element enhances claudin-14 expression and is associated with pediatric-onset hypercalciuria and kidney stones

    DEFF Research Database (Denmark)

    Ure, Megan E; Heydari, Emma; Pan, Wanling

    2017-01-01

    The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated....... Recently, renal CLDN14 expression was found to increase in response to increased plasma calcium, thereby inducing calciuria. We hypothesized therefore that some children with hypercalciuria and kidney stones harbor a CLDN14 variant that inappropriately increases gene expression. To test this hypothesis, we...... sequenced the CLDN14 risk haplotype in a cohort of children with idiopathic hypercalciuria and kidney stones. An intronic single nucleotide polymorphism (SNP) was more frequent in affected children. Dual luciferase and cell based assays demonstrated increased reporter or CLDN14 expression when...

  9. A de novo 1.58 Mb deletion, including MAP2K6 and mapping 1.28 Mb upstream to SOX9, identified in a patient with Pierre Robin sequence and osteopenia with multiple fractures.

    Science.gov (United States)

    Smyk, Marta; Roeder, Elizabeth; Cheung, Sau Wai; Szafranski, Przemyslaw; Stankiewicz, Paweł

    2015-08-01

    Defects of long-range regulatory elements of dosage-sensitive genes represent an under-recognized mechanism underlying genetic diseases. Haploinsufficiency of SOX9, the gene essential for development of testes and differentiation of chondrocytes, results in campomelic dysplasia, a skeletal malformation syndrome often associated with sex reversal. Chromosomal rearrangements with breakpoints mapping up to 1.6 Mb up- and downstream to SOX9, and disrupting its distant cis-regulatory elements, have been described in patients with milder forms of campomelic dysplasia, Pierre Robin sequence, and sex reversal. We present an ∼1.58 Mb deletion mapping ∼1.28 Mb upstream to SOX9 that encompasses its putative long-range cis-regulatory element(s) and MAP2K6 in a patient with Pierre Robin sequence and osteopenia with multiple fractures. Low bone mass panel testing using massively parallel sequencing of 23 nuclear genes, including COL1A1 and COL1A2 was negative. Based on the previous mouse model of Map2k6, suggesting that Sox9 is likely a downstream target of the p38 MAPK pathway, and our previous chromosome conformation capture-on-chip (4C) data showing potential interactions between SOX9 promoter and MAP2K6, we hypothesize that deletion of MAP2K6 might have affected SOX9 expression and contributed to our patient's phenotype. © 2015 Wiley Periodicals, Inc.

  10. Multiple-Zone Diffractive Optic Element for Laser Ranging Applications

    Science.gov (United States)

    Ramos-Izquierdo, Luis A.

    2011-01-01

    A diffractive optic element (DOE) can be used as a beam splitter to generate multiple laser beams from a single input laser beam. This technology has been recently used in LRO s Lunar Orbiter Laser Altimeter (LOLA) instrument to generate five laser beams that measure the lunar topography from a 50-km nominal mapping orbit (see figure). An extension of this approach is to use a multiple-zone DOE to allow a laser altimeter instrument to operate over a wider range of distances. In particular, a multiple-zone DOE could be used for applications that require both mapping and landing on a planetary body. In this case, the laser altimeter operating range would need to extend from several hundred kilometers down to a few meters. The innovator was recently involved in an investigation how to modify the LOLA instrument for the OSIRIS asteroid mapping and sample return mission. One approach is to replace the DOE in the LOLA laser beam expander assembly with a multiple-zone DOE that would allow for the simultaneous illumination of the asteroid with mapping and landing laser beams. The proposed OSIRIS multiple-zone DOE would generate the same LOLA five-beam output pattern for high-altitude topographic mapping, but would simultaneously generate a wide divergence angle beam using a small portion of the total laser energy for the approach and landing portion of the mission. Only a few percent of the total laser energy is required for approach and landing operations as the return signal increases as the inverse square of the ranging height. A wide divergence beam could be implemented by making the center of the DOE a diffractive or refractive negative lens. The beam energy and beam divergence characteristics of a multiple-zone DOE could be easily tailored to meet the requirements of other missions that require laser ranging data. Current single-zone DOE lithographic manufacturing techniques could also be used to fabricate a multiple-zone DOE by masking the different DOE zones during

  11. Global multiplicity of dietary standards for trace elements.

    Science.gov (United States)

    Freeland-Graves, Jeanne H; Lee, Jane J

    2012-06-01

    Consistent guidelines across the world for dietary standards of trace elements remain elusive. Harmonization of dietary standards has been suggested by international agencies to facilitate consistency in food and nutrition policies and international trade. Yet significant barriers exist to standardize recommendations on a global basis, such as vast differences in geography, food availability and transport; cultural, social and economic constraints, and biological diversity. Simple commonality is precluded further by the variety of terminologies among countries and regions related to diet. Certain unions have created numerous nutritional descriptive categories for standards, while other large countries are limited to only a few. This paper will explore the global multiplicity of dietary standards and efforts for harmonization. Copyright © 2012 Elsevier GmbH. All rights reserved.

  12. Multiple single-element transducer photoacoustic computed tomography system

    Science.gov (United States)

    Kalva, Sandeep Kumar; Hui, Zhe Zhi; Pramanik, Manojit

    2018-02-01

    Light absorption by the chromophores (hemoglobin, melanin, water etc.) present in any biological tissue results in local temperature rise. This rise in temperature results in generation of pressure waves due to the thermoelastic expansion of the tissue. In a circular scanning photoacoustic computed tomography (PACT) system, these pressure waves can be detected using a single-element ultrasound transducer (SUST) (while rotating in full 360° around the sample) or using a circular array transducer. SUST takes several minutes to acquire the PA data around the sample whereas the circular array transducer takes only a fraction of seconds. Hence, for real time imaging circular array transducers are preferred. However, these circular array transducers are custom made, expensive and not easily available in the market whereas SUSTs are cheap and readily available in the market. Using SUST for PACT systems is still cost effective. In order to reduce the scanning time to few seconds instead of using single SUST (rotating 360° ), multiple SUSTs can be used at the same time to acquire the PA data. This will reduce the scanning time by two-fold in case of two SUSTs (rotating 180° ) or by four-fold and eight-fold in case of four SUSTs (rotating 90° ) and eight SUSTs (rotating 45° ) respectively. Here we show that with multiple SUSTs, similar PA images (numerical and experimental phantom data) can be obtained as that of PA images obtained using single SUST.

  13. Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

    DEFF Research Database (Denmark)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.

    2005-01-01

    years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences......We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each...... between the species-but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence...

  14. Development of Multiple-Element Flame Emission Spectrometer Using CCD Detection

    Science.gov (United States)

    Seney, Caryn S.; Sinclair, Karen V.; Bright, Robin M.; Momoh, Paul O.; Bozeman, Amelia D.

    2005-01-01

    The full wavelength coverage of charge coupled device (CCD) detector when coupled with an echelle spectrography, the system allows for simultaneously multiple element spectroscopy to be performed. The multiple-element flame spectrometer was built and characterized through the analysis of environmentally significant elements such as Ca, K, Na, Cu,…

  15. Location analysis for the estrogen receptor-? reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements

    OpenAIRE

    Mason, Christopher E.; Shu, Feng-Jue; Wang, Cheng; Session, Ryan M.; Kallen, Roland G.; Sidell, Neil; Yu, Tianwei; Liu, Mei Hui; Cheung, Edwin; Kallen, Caleb B.

    2010-01-01

    Location analysis for estrogen receptor-? (ER?)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ER?-bound loci and quantify the incidence of ERE sequences under two stringencies of detection:

  16. Multiple orbital angular momentum generated by dielectric hybrid phase element

    Science.gov (United States)

    Wang, Xuewen; Kuchmizhak, Aleksandr; Hu, Dejiao; Li, Xiangping

    2017-09-01

    Vortex beam carrying multiple orbital angular momentum provides a new degree of freedom to manipulate light leading to the various exciting applications as trapping, quantum optics, information multiplexing, etc. Helical wavefront can be generated either via the geometric or the dynamic phase arising from a space-variant birefringence (q-plate) or from phase accumulation through propagation (spiral-phase-plate), respectively. Using fast direct laser writing technique we fabricate and characterize novel hybrid q-plate generating vortex beam simultaneously carrying two different high-order topological charges, which arise from the spin-orbital conversion and the azimuthal height variation of the recorded structures. We approve the versatile concept to generate multiple-OAM vortex beams combining the spin-orbital interaction and the phase accumulation in a single micro-scale device, a hybrid dielectric phase plate.

  17. Automatic treatment of multiple wound coils in 3D finite element problems including multiply connected regions

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, P.J.; Lai, H.C.; Eastham, J.F.; Al-Akayshee, Q.H. [Univ. of Bath (United Kingdom)

    1996-05-01

    This paper describes an efficient scheme for incorporating multiple wire wound coils into 3D finite element models. The scheme is based on the magnetic scalar representation with an additional basis for each coil. There are no restrictions on the topology of coils with respect to ferromagnetic and conductor regions. Reduced scalar regions and cuts are automatically generated.

  18. Prediction of transcriptional regulatory elements for plant hormone responses based on microarray data

    Directory of Open Access Journals (Sweden)

    Yamaguchi-Shinozaki Kazuko

    2011-02-01

    Full Text Available Abstract Background Phytohormones organize plant development and environmental adaptation through cell-to-cell signal transduction, and their action involves transcriptional activation. Recent international efforts to establish and maintain public databases of Arabidopsis microarray data have enabled the utilization of this data in the analysis of various phytohormone responses, providing genome-wide identification of promoters targeted by phytohormones. Results We utilized such microarray data for prediction of cis-regulatory elements with an octamer-based approach. Our test prediction of a drought-responsive RD29A promoter with the aid of microarray data for response to drought, ABA and overexpression of DREB1A, a key regulator of cold and drought response, provided reasonable results that fit with the experimentally identified regulatory elements. With this succession, we expanded the prediction to various phytohormone responses, including those for abscisic acid, auxin, cytokinin, ethylene, brassinosteroid, jasmonic acid, and salicylic acid, as well as for hydrogen peroxide, drought and DREB1A overexpression. Totally 622 promoters that are activated by phytohormones were subjected to the prediction. In addition, we have assigned putative functions to 53 octamers of the Regulatory Element Group (REG that have been extracted as position-dependent cis-regulatory elements with the aid of their feature of preferential appearance in the promoter region. Conclusions Our prediction of Arabidopsis cis-regulatory elements for phytohormone responses provides guidance for experimental analysis of promoters to reveal the basis of the transcriptional network of phytohormone responses.

  19. Adaptive evolution of conserved noncoding elements in mammals.

    Directory of Open Access Journals (Sweden)

    Su Yeon Kim

    2007-09-01

    Full Text Available Conserved noncoding elements (CNCs are an abundant feature of vertebrate genomes. Some CNCs have been shown to act as cis-regulatory modules, but the function of most CNCs remains unclear. To study the evolution of CNCs, we have developed a statistical method called the "shared rates test" to identify CNCs that show significant variation in substitution rates across branches of a phylogenetic tree. We report an application of this method to alignments of 98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that approximately 68% of CNCs evolve according to a null model where, for each CNC, a single parameter models the level of constraint acting throughout the phylogeny linking these five species. The remaining approximately 32% of CNCs show departures from the basic model including speed-ups and slow-downs on particular branches and occasionally multiple rate changes on different branches. We find that a subset of the significant CNCs have evolved significantly faster than the local neutral rate on a particular branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses suggest a large set of promising targets for future functional studies of adaptation.

  20. Visual processing of multiple elements in the dyslexic brain: evidence for a superior parietal dysfunction

    Directory of Open Access Journals (Sweden)

    Muriel Anne Lobier

    2014-07-01

    Full Text Available The visual attention (VA span deficit hypothesis of developmental dyslexia posits that impaired multiple element processing can be responsible for poor reading outcomes. In VA span impaired dyslexic children, poor performance on letter report tasks is associated with reduced parietal activations for multiple letter processing. While this hints towards a non-specific, attention-based dysfunction, it is still unclear whether reduced parietal activity generalizes to other types of stimuli. Furthermore, putative links between reduced parietal activity and reduced ventral occipito-temporal (vOT in dyslexia have yet to be explored. Using fMRI, we measured brain activity in 12 VA span impaired dyslexic adults and 12 adult skilled readers while they carried out a categorization task on single or multiple alphanumeric or non-alphanumeric characters. While healthy readers activated parietal areas more strongly for multiple than single element processing (right-sided for alphanumeric and bilateral for non-alphanumeric, similar stronger multiple element right parietal activations were absent for dyslexic participants. Contrasts between skilled and dyslexic readers revealed significantly reduced right superior parietal lobule (SPL activity for dyslexic readers regardless of stimuli type. Using a priori anatomically defined ROI, we showed that neural activity was reduced for dyslexic participants in both SPL and vOT bilaterally. Finally, we used multiple regressions to test whether SPL activity could predict vOT activity in each group. In the left hemisphere, SPL activity modulated vOT activity for both normal and dyslexic readers. In contrast, in the right hemisphere, SPL activity modulated vOT activity only for dyslexic readers. These results bring critical support to the visual attention interpretation of the VA Span deficit. In addition, they offer a new insight on how deficits in automatic vOT based word recognition could arise in developmental dyslexia.

  1. Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold

    Science.gov (United States)

    Li, Yizhou; De Luca, Roberto; Cazzamalli, Samuele; Pretto, Francesca; Bajic, Davor; Scheuermann, Jörg; Neri, Dario

    2018-03-01

    In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody-antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor. Similar to antibodies, the encoded display of multiple chemical elements on a constant scaffold enabled practical applications, such as fluorescence microscopy procedures or the selective in vivo delivery of payloads to tumours. Furthermore, the versatile structure of the scaffold facilitated the generation of protein-specific chemical probes, as illustrated by photo-crosslinking.

  2. Comparative genome sequencing of drosophila pseudoobscura: Chromosomal, gene and cis-element evolution

    Energy Technology Data Exchange (ETDEWEB)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Todd, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catherine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenee; Verduzco, Daniel; Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

    2004-04-01

    The genome sequence of a second fruit fly, D. pseudoobscura, presents an opportunity for comparative analysis of a primary model organism D. melanogaster. The vast majority of Drosophila genes have remained on the same arm, but within each arm gene order has been extensively reshuffled leading to the identification of approximately 1300 syntenic blocks. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 35 My since divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome wide average consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than control sequences between the species but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a picture of repeat mediated chromosomal rearrangement, and high co-adaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.

  3. In silico discovery of transcription regulatory elements in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Le Roch Karine G

    2008-02-01

    Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

  4. HiCoDG: A Hierarchical Data-Gathering Scheme Using Cooperative Multiple Mobile Elements

    Science.gov (United States)

    Van Le, Duc; Oh, Hoon; Yoon, Seokhoon

    2014-01-01

    In this paper, we study mobile element (ME)-based data-gathering schemes in wireless sensor networks. Due to the physical speed limits of mobile elements, the existing data-gathering schemes that use mobile elements can suffer from high data-gathering latency. In order to address this problem, this paper proposes a new hierarchical and cooperative data-gathering (HiCoDG) scheme that enables multiple mobile elements to cooperate with each other to collect and relay data. In HiCoDG, two types of mobile elements are used: the mobile collector (MC) and the mobile relay (MR). MCs collect data from sensors and forward them to the MR, which will deliver them to the sink. In this work, we also formulated an integer linear programming (ILP) optimization problem to find the optimal trajectories for MCs and the MR, such that the traveling distance of MEs is minimized. Two variants of HiCoDG, intermediate station (IS)-based and cooperative movement scheduling (CMS)-based, are proposed to facilitate cooperative data forwarding from MCs to the MR. An analytical model for estimating the average data-gathering latency in HiCoDG was also designed. Simulations were performed to compare the performance of the IS and CMS variants, as well as a multiple traveling salesman problem (mTSP)-based approach. The simulation results show that HiCoDG outperforms mTSP in terms of latency. The results also show that CMS can achieve the lowest latency with low energy consumption. PMID:25526356

  5. HiCoDG: a hierarchical data-gathering scheme using cooperative multiple mobile elements.

    Science.gov (United States)

    Van Le, Duc; Oh, Hoon; Yoon, Seokhoon

    2014-12-17

    In this paper, we study mobile element (ME)-based data-gathering schemes in wireless sensor networks. Due to the physical speed limits of mobile elements, the existing data-gathering schemes that use mobile elements can suffer from high data-gathering latency. In order to address this problem, this paper proposes a new hierarchical and cooperative data-gathering (HiCoDG) scheme that enables multiple mobile elements to cooperate with each other to collect and relay data. In HiCoDG, two types of mobile elements are used: the mobile collector (MC) and the mobile relay (MR). MCs collect data from sensors and forward them to the MR, which will deliver them to the sink. In this work, we also formulated an integer linear programming (ILP) optimization problem to find the optimal trajectories for MCs and the MR, such that the traveling distance of MEs is minimized. Two variants of HiCoDG, intermediate station (IS)-based and cooperative movement scheduling (CMS)-based, are proposed to facilitate cooperative data forwarding from MCs to the MR. An analytical model for estimating the average data-gathering latency in HiCoDG was also designed. Simulations were performed to compare the performance of the IS and CMS variants, as well as a multiple traveling salesman problem (mTSP)-based approach. The simulation results show that HiCoDG outperforms mTSP in terms of latency. The results also show that CMS can achieve the lowest latency with low energy consumption.

  6. HiCoDG: A Hierarchical Data-Gathering Scheme Using Cooperative Multiple Mobile Elements

    Directory of Open Access Journals (Sweden)

    Duc Van Le

    2014-12-01

    Full Text Available In this paper, we study mobile element (ME-based data-gathering schemes in wireless sensor networks. Due to the physical speed limits of mobile elements, the existing data-gathering schemes that usemobile elements can suffer from high data-gathering latency. In order to address this problem, this paper proposes a new hierarchical and cooperative data-gathering (HiCoDG scheme that enables multiple mobile elements to cooperate with each other to collect and relay data. In HiCoDG, two types of mobile elements are used: the mobile collector (MC and the mobile relay (MR. MCs collect data from sensors and forward them to the MR, which will deliver them to the sink. In this work, we also formulated an integer linear programming (ILP optimization problem to find the optimal trajectories for MCs and the MR, such that the traveling distance of MEs is minimized. Two variants of HiCoDG, intermediate station (IS-based and cooperative movement scheduling (CMS-based, are proposed to facilitate cooperative data forwarding from MCs to theMR. An analytical model for estimating the average data-gathering latency in HiCoDG was also designed. Simulations were performed to compare the performance of the IS and CMS variants, as well as a multiple traveling salesman problem (mTSP-based approach. The simulation results show that HiCoDG outperformsmTSP in terms of latency. The results also show that CMS can achieve the lowest latency with low energy consumption.

  7. Regulatory elements of the floral homeotic gene AGAMOUS identified by phylogenetic footprinting and shadowing.

    Energy Technology Data Exchange (ETDEWEB)

    Hong, R. L., Hamaguchi, L., Busch, M. A., and Weigel, D.

    2003-06-01

    OAK-B135 In Arabidopsis thaliana, cis-regulatory sequences of the floral homeotic gene AGAMOUS (AG) are located in the second intron. This 3 kb intron contains binding sites for two direct activators of AG, LEAFY (LFY) and WUSCHEL (WUS), along with other putative regulatory elements. We have used phylogenetic footprinting and the related technique of phylogenetic shadowing to identify putative cis-regulatory elements in this intron. Among 29 Brassicaceae, several other motifs, but not the LFY and WUS binding sites previously identified, are largely invariant. Using reporter gene analyses, we tested six of these motifs and found that they are all functionally important for activity of AG regulatory sequences in A. thaliana. Although there is little obvious sequence similarity outside the Brassicaceae, the intron from cucumber AG has at least partial activity in A. thaliana. Our studies underscore the value of the comparative approach as a tool that complements gene-by-gene promoter dissection, but also highlight that sequence-based studies alone are insufficient for a complete identification of cis-regulatory sites.

  8. Activity of genes with functions in human Williams-Beuren Syndrome are impacted by mobile element insertions in the gray wolf genome.

    Science.gov (United States)

    vonHoldt, Bridgett M; Ji, Sarah S; Aardema, Matthew L; Stahler, Daniel; Udell, Monique A R; Sinsheimer, Janet S

    2018-06-01

    In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions in dogs and Yellowstone wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of mobile element insertions (MEIs), suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that mobile element insertions impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.

  9. Quantification of chemical elements in blood of patients affected by multiple sclerosis.

    Science.gov (United States)

    Forte, Giovanni; Visconti, Andrea; Santucci, Simone; Ghazaryan, Anna; Figà-Talamanca, Lorenzo; Cannoni, Stefania; Bocca, Beatrice; Pino, Anna; Violante, Nicola; Alimonti, Alessandro; Salvetti, Marco; Ristori, Giovanni

    2005-01-01

    Although some studies suggested a link between exposure to trace elements and development of multiple sclerosis (MS), clear information on their role in the aetiology of MS is still lacking. In this study the concentrations of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, Tl, V, W, Zn and Zr were determined in the blood of 60 patients with MS and 60 controls. Quantifications were performed by inductively coupled plasma (ICP) atomic emission spectrometry and sector field ICP mass spectrometry. When the two groups were compared, an increased level of Co, Cu and Ni and a decrement of Be, Fe, Hg, Mg, Mo, Pb and Zn in blood of patients were observed. In addition, the discriminant analysis pointed out that Cu, Be, Hg, Co and Mo were able to discriminate between MS patients and controls (92.5% of cases correctly classified).

  10. Study on validation method for femur finite element model under multiple loading conditions

    Science.gov (United States)

    Guan, Fengjiao; Zhang, Guanjun; Liu, Jie; Wang, Shujing; Luo, Xu

    2018-03-01

    Acquisition of accurate and reliable constitutive parameters related to bio-tissue materials was beneficial to improve biological fidelity of a Finite Element (FE) model and predict impact damages more effectively. In this paper, a femur FE model was established under multiple loading conditions with diverse impact positions. Then, based on sequential response surface method and genetic algorithms, the material parameters identification was transformed to a multi-response optimization problem. Finally, the simulation results successfully coincided with force-displacement curves obtained by numerous experiments. Thus, computational accuracy and efficiency of the entire inverse calculation process were enhanced. This method was able to effectively reduce the computation time in the inverse process of material parameters. Meanwhile, the material parameters obtained by the proposed method achieved higher accuracy.

  11. Three-dimensional multiple reciprocity boundary element method for one-group neutron diffusion eigenvalue computations

    International Nuclear Information System (INIS)

    Itagaki, Masafumi; Sahashi, Naoki.

    1996-01-01

    The multiple reciprocity method (MRM) in conjunction with the boundary element method has been employed to solve one-group eigenvalue problems described by the three-dimensional (3-D) neutron diffusion equation. The domain integral related to the fission source is transformed into a series of boundary-only integrals, with the aid of the higher order fundamental solutions based on the spherical and the modified spherical Bessel functions. Since each degree of the higher order fundamental solutions in the 3-D cases has a singularity of order (1/r), the above series of boundary integrals requires additional terms which do not appear in the 2-D MRM formulation. The critical eigenvalue itself can be also described using only boundary integrals. Test calculations show that Wielandt's spectral shift technique guarantees rapid and stable convergence of 3-D MRM computations. (author)

  12. Multiple nano elements of SCC--transition from phenomenology to predictive mechanistics

    International Nuclear Information System (INIS)

    Staehle, R.W.

    2009-01-01

    Full text of publication follows: Predicting the occurrence and rate of stress corrosion cracking in materials of construction is one of the most critical pathways for assuring the reliability of light water nuclear reactor plants. It is the general intention of operators of nuclear plants that they continue performing satisfactorily for times of 60 to 80 years at least. Such times are beyond existing experience, and there are no bases for choosing credible predictions. Present bases for predicting SCC rely on anecdotal experience for predicting what materials sustain SCC in specified environments and on phenomenological correlations using such parameters as K (stress intensity), 1/T (temperature), E(corr) (corrosion potential), pH, [x] a (concentration), other established quantities, and statistical correlations. While these phenomenological correlations have served the industry well in the past, they have also allowed grievous mistakes. Further, such correlations are flawed in their fundamental credibility. Predicting SCC in aqueous solutions means to predict its dependence upon the seven primary variables: potential, pH, species, alloy composition, alloy structure, stress and temperature. A serious prediction of SCC upon these seven primary variables can only be achieved by moving to fundamental nano elements. Unfortunately, useful predictability from the nano approach cannot be achieved quickly or easily; thus, it will continue to be necessary to rely on existing phenomenology. However, as the nano approach evolves, it can contribute increasingly to the quantitative capacity of the phenomenological approach. The nano approach will require quite different talents and thinking than are now applied to the prediction of SCC; while some of the boundary conditions of phenomenology must continue to be applied, elements of the nano approach will include accounting for at least, typically, the following multiple elements as they apply at the sites of initiation and at

  13. Element-specific spectral imaging of multiple contrast agents: a phantom study

    Science.gov (United States)

    Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

    2018-02-01

    This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

  14. On the distribution of trace element concentrations in multiple bone elements in 10 Danish medieval and post-medieval individuals.

    Science.gov (United States)

    Lund Rasmussen, Kaare; Skytte, Lilian; D'imporzano, Paolo; Orla Thomsen, Per; Søvsø, Morten; Lier Boldsen, Jesper

    2017-01-01

    The differences in trace element concentrations among 19 different bone elements procured from 10 archaeologically derived human skeletons have been investigated. The 10 individuals are dated archaeologically and some by radiocarbon dating to the medieval and post-medieval period, an interval from ca. AD 1150 to ca. AD 1810. This study is relevant for two reasons. First, most archaeometric studies analyze only one bone sample from each individual; so to what degree are the bones in the human body equal in trace element chemistry? Second, differences in turnover time of the bone elements makes the cortical tissues record the trace element concentrations in equilibrium with the blood stream over a longer time earlier in life than the trabecular. Therefore, any differences in trace element concentrations between the bone elements can yield what can be termed a chemical life history of the individual, revealing changes in diet, provenance, or medication throughout life. Thorough decontamination and strict exclusion of non-viable data has secured a dataset of high quality. The measurements were carried out using Inductively Coupled Plasma Mass Spectrometry (for Fe, Mn, Al, Ca, Mg, Na, Ba, Sr, Zn, Pb and As) and Cold Vapor Atomic Absorption Spectroscopy (for Hg) on ca. 20 mg samples. Twelve major and trace elements have been measured on 19 bone elements from 10 different individuals interred at five cemeteries widely distributed in medieval and renaissance Denmark. The ranges of the concentrations of elements were: Na (2240-5660 µg g -1 ), Mg (440-2490 µg g -1 ), Al (9-2030 µg g -1 ), Ca (22-36 wt. %), Mn (5-11450 µg g -1 ), Fe (32-41850 µg g -1 ), Zn (69-2610 µg g -1 ), As (0.4-120 µg g -1 ), Sr (101-815 µg g -1 ), Ba (8-880 µg g -1 ), Hg (7-78730 ng g -1 ), and Pb (0.8-426 µg g -1 ). It is found that excess As is mainly of diagenetic origin. The results support that Ba and Sr concentrations are effective provenance or dietary indicators. Migrating

  15. Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO Radar Based on the Elements of the Covariance Matrix

    Directory of Open Access Journals (Sweden)

    Zhengyan Zhang

    2018-03-01

    Full Text Available In this paper, we consider the problem of tracking the direction of arrivals (DOA and the direction of departure (DOD of multiple targets for bistatic multiple-input multiple-output (MIMO radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

  16. Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO) Radar Based on the Elements of the Covariance Matrix.

    Science.gov (United States)

    Zhang, Zhengyan; Zhang, Jianyun; Zhou, Qingsong; Li, Xiaobo

    2018-03-07

    In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

  17. Detailed assessment of gene activation levels by multiple hypoxia-responsive elements under various hypoxic conditions.

    Science.gov (United States)

    Takeuchi, Yasuto; Inubushi, Masayuki; Jin, Yong-Nan; Murai, Chika; Tsuji, Atsushi B; Hata, Hironobu; Kitagawa, Yoshimasa; Saga, Tsuneo

    2014-12-01

    HIF-1/HRE pathway is a promising target for the imaging and the treatment of intractable malignancy (HIF-1; hypoxia-inducible factor 1, HRE; hypoxia-responsive element). The purposes of our study are: (1) to assess the gene activation levels resulting from various numbers of HREs under various hypoxic conditions, (2) to evaluate the bidirectional activity of multiple HREs, and (3) to confirm whether multiple HREs can induce gene expression in vivo. Human colon carcinoma HCT116 cells were transiently transfected by the constructs containing a firefly luciferase reporter gene and various numbers (2, 4, 6, 8, 10, and 12) of HREs (nHRE+, nHRE-). The relative luciferase activities were measured under various durations of hypoxia (6, 12, 18, and 24 h), O2 concentrations (1, 2, 4, 8, and 16 %), and various concentrations of deferoxamine mesylate (20, 40, 80, 160, and 320 µg/mL growth medium). The bidirectional gene activation levels by HREs were examined in the constructs (dual-luc-nHREs) containing firefly and Renilla luciferase reporter genes at each side of nHREs. Finally, to test whether the construct containing 12HRE and the NIS reporter gene (12HRE-NIS) can induce gene expression in vivo, SPECT imaging was performed in a mouse xenograft model. (1) gene activation levels by HREs tended to increase with increasing HRE copy number, but a saturation effect was observed in constructs with more than 6 or 8 copies of an HRE, (2) gene activation levels by HREs increased remarkably during 6-12 h of hypoxia, but not beyond 12 h, (3) gene activation levels by HREs decreased with increasing O2 concentrations, but could be detected even under mild hypoxia at 16 % O2, (4) the bidirectionally proportional activity of the HRE was confirmed regardless of the hypoxic severity, and (5) NIS expression driven by 12 tandem copies of an HRE in response to hypoxia could be visualized on in vivo SPECT imaging. The results of this study will help in the understanding and assessment of

  18. A numerical comparison between the multiple-scales and finite-element solution for sound propagation in lined flow ducts

    NARCIS (Netherlands)

    Rienstra, S.W.; Eversman, W.

    2001-01-01

    An explicit, analytical, multiple-scales solution for modal sound transmission through slowly varying ducts with mean flow and acoustic lining is tested against a numerical finite-element solution solving the same potential flow equations. The test geometry taken is representative of a high-bypass

  19. Close Sequence Comparisons are Sufficient to Identify Humancis-Regulatory Elements

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakar, Shyam; Poulin, Francis; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Couronne, Olivier; Pennacchio, Len A.

    2005-12-01

    Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons, due to the lack of a universal metric for sequence conservation, and also the paucity of empirically defined benchmark sets of cis-regulatory elements. To address this problem, we developed a general-purpose algorithm (Gumby) that detects slowly-evolving regions in primate, mammalian and more distant comparisons without requiring adjustment of parameters, and ranks conserved elements by P-value using Karlin-Altschul statistics. We benchmarked Gumby predictions against previously identified cis-regulatory elements at diverse genomic loci, and also tested numerous extremely conserved human-rodent sequences for transcriptional enhancer activity using reporter-gene assays in transgenic mice. Human regulatory elements were identified with acceptable sensitivity and specificity by comparison with 1-5 other eutherian mammals or 6 other simian primates. More distant comparisons (marsupial, avian, amphibian and fish) failed to identify many of the empirically defined functional noncoding elements. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole genome comparative analysis, which explains some of these findings. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for testing at embryonic time points.

  20. Finite element simulations of interactions between multiple hydraulic fractures in a poroelastic rock

    DEFF Research Database (Denmark)

    Salimzadeh, Saeed; Usui, Tomoya; Paluszny, Adriana

    2017-01-01

    A fully coupled three-dimensional finite-element model for hydraulic fractures in permeable rocks is presented, and used to investigate the ranges of applicability of the classical analytical solutions that are known to be valid in limiting cases. This model simultaneously accounts for fluid flow...

  1. Accuracy of finite-element models for the stress analysis of multiple-holed moderator blocks

    International Nuclear Information System (INIS)

    Smith, P.D.; Sullivan, R.M.; Lewis, A.C.; Yu, H.J.

    1981-01-01

    Two steps have been taken to quantify and improve the accuracy in the analysis. First, the limitations of various approximation techniques have been studied with the aid of smaller benchmark problems containing fewer holes. Second, a new family of computer programs has been developed for handling such large problems. This paper describes the accuracy studies and the benchmark problems. A review is given of some proposed modeling techniques including local mesh refinement, homogenization, a special-purpose finite element, and substructuring. Some limitations of these approaches are discussed. The new finite element programs and the features that contribute to their efficiency are discussed. These include a standard architecture for out-of-core data processing and an equation solver that operates on a peripheral array processor. The central conclusions of the paper are: (1) modeling approximation methods such as local mesh refinement and homogenization tend to be unreliable, and they should be justified by a fine mesh benchmark analysis; and (2) finite element codes are now available that can achieve accurate solutions at a reasonable cost, and there is no longer a need to employ modeling approximations in the two-dimensional analysis of HTGR fuel elements. 10 figures

  2. Trace element analysis of environmental samples by multiple prompt gamma-ray analysis method

    International Nuclear Information System (INIS)

    Oshima, Masumi; Matsuo, Motoyuki; Shozugawa, Katsumi

    2011-01-01

    The multiple γ-ray detection method has been proved to be a high-resolution and high-sensitivity method in application to nuclide quantification. The neutron prompt γ-ray analysis method is successfully extended by combining it with the γ-ray detection method, which is called Multiple prompt γ-ray analysis, MPGA. In this review we show the principle of this method and its characteristics. Several examples of its application to environmental samples, especially river sediments in the urban area and sea sediment samples are also described. (author)

  3. On the multiplicative order of elements in Wiedemann's towers of finite fields

    Directory of Open Access Journals (Sweden)

    R. Popovych

    2016-01-01

    Full Text Available We consider recursive binary finite field extensions $E_{i+1} =E_{i} (x_{i+1} $, $i\\ge -1$, defined by D. Wiedemann. The main object of the paper is to give some proper divisors of the Fermat numbers $N_{i} $ that are not equal to the multiplicative order $O(x_{i} $.

  4. Role of NAA in characterizations of sampling behaviors of multiple elements in CRMs

    International Nuclear Information System (INIS)

    Tian Weizhi; Ni Bangfa; Wang Pingsheng; Nie Huiling

    1997-01-01

    Taking the advantage of high precision and accuracy of neutron activation analysis (NAA), sampling constants have been determined for multielements in several international and Chinese reference materials. The suggested technique may be used for finding elements in existing CRMs qualified for quality control (QC) of small size samples (several mg or less), and characterizing sampling behaviors of multielements in new CRMs specifically made for QC of microanalysis

  5. Role of NAA in determination and characterisation of sampling behaviours of multiple elements in CRMs

    International Nuclear Information System (INIS)

    Tian Weizhi; Ni Bangfa; Wang Pingsheng; Nie Huiling

    2002-01-01

    Taking the advantage of high precision and accuracy of neutron activation analysis (NAA), sampling constants have been determined for multielements in several international and Chinese reference materials. The suggested technique may be used for finding elements in existing CRMs qualified for quality control (QC) of small size samples (several mg or less), and characterizing sampling behaviors of multielements in new CRMs specifically made for QC of microanalysis. (author)

  6. The protist Trichomonas vaginalis harbors multiple lineages of transcriptionally active Mutator-like elements

    Directory of Open Access Journals (Sweden)

    Pereira Gonçalo AG

    2009-07-01

    Full Text Available Abstract Background For three decades the Mutator system was thought to be exclusive of plants, until the first homolog representatives were characterized in fungi and in early-diverging amoebas earlier in this decade. Results Here, we describe and characterize four families of Mutator-like elements in a new eukaryotic group, the Parabasalids. These Trichomonas vaginalis Mutator- like elements, or TvMULEs, are active in T. vaginalis and patchily distributed among 12 trichomonad species and isolates. Despite their relatively distinctive amino acid composition, the inclusion of the repeats TvMULE1, TvMULE2, TvMULE3 and TvMULE4 into the Mutator superfamily is justified by sequence, structural and phylogenetic analyses. In addition, we identified three new TvMULE-related sequences in the genome sequence of Candida albicans. While TvMULE1 is a member of the MuDR clade, predominantly from plants, the other three TvMULEs, together with the C. albicans elements, represent a new and quite distinct Mutator lineage, which we named TvCaMULEs. The finding of TvMULE1 sequence inserted into other putative repeat suggests the occurrence a novel TE family not yet described. Conclusion These findings expand the taxonomic distribution and the range of functional motif of MULEs among eukaryotes. The characterization of the dynamics of TvMULEs and other transposons in this organism is of particular interest because it is atypical for an asexual species to have such an extreme level of TE activity; this genetic landscape makes an interesting case study for causes and consequences of such activity. Finally, the extreme repetitiveness of the T. vaginalis genome and the remarkable degree of sequence identity within its repeat families highlights this species as an ideal system to characterize new transposable elements.

  7. Determine Multiple Elements Simultaneously in the Sera of Umbilical Cord Blood Samples-a Very Simple Method.

    Science.gov (United States)

    Liang, Chunmei; Li, Zhijuan; Xia, Xun; Wang, Qunan; Tao, Ruiwen; Tao, Yiran; Xiang, Haiyun; Tong, Shilu; Tao, Fangbiao

    2017-05-01

    Analyzing the concentrations of heavy metals in the sera of umbilical cord blood samples can provide useful information about prenatal exposure to environmental agents. An analytical method based on ICP-MS to simultaneously determine multiple elements in umbilical cord blood samples was developed for assessing the in utero exposure to metallic and metalloid elements. The method only required as little as 100 μL of serum diluted 1:25 for direct analysis. Matrix-matched protocol was used to eliminate mass matrix interference and kinetic energy discrimination mode was used to eliminate the polyatomic ion interference. The assay was completed on average within 4 min with the detection limits ranging from 0.0002 to 44.4 μg/L for all the targeted elements. The detection rates for most of elements were 100 % other than cadmium (Cd), lead (Pb), and mercury (Hg). The testing results of the certified reference materials were ideal. The method is simple and sensitive, so it is suitable for the monitoring of large quantities of samples.

  8. Three-dimensional finite elements for the analysis of soil contamination using a multiple-porosity approach

    Science.gov (United States)

    El-Zein, Abbas; Carter, John P.; Airey, David W.

    2006-06-01

    A three-dimensional finite-element model of contaminant migration in fissured clays or contaminated sand which includes multiple sources of non-equilibrium processes is proposed. The conceptual framework can accommodate a regular network of fissures in 1D, 2D or 3D and immobile solutions in the macro-pores of aggregated topsoils, as well as non-equilibrium sorption. A Galerkin weighted-residual statement for the three-dimensional form of the equations in the Laplace domain is formulated. Equations are discretized using linear and quadratic prism elements. The system of algebraic equations is solved in the Laplace domain and solution is inverted to the time domain numerically. The model is validated and its scope is illustrated through the analysis of three problems: a waste repository deeply buried in fissured clay, a storage tank leaking into sand and a sanitary landfill leaching into fissured clay over a sand aquifer.

  9. [Simultaneous determination of multiple elements in airborne particulate samples by X-ray fluorescence spectrometry].

    Science.gov (United States)

    Takada, T; Hitosugi, M; Kadowaki, T; Kudo, M

    1983-07-01

    An energy dispersive X-ray fluorescence spectrometer (EDX) has been applied to determine multielements in the workplace air. The standards for X-ray fluorescence analysis were prepared by the chelate precipitation method on polyvinyl chloride (PVC) membrane filter. And, the specimens were prepared to deposit various metal compounds of different chemical forms by the suspension method on PVC membrane filter, and they were determined with EDX and atomic absorption spectrometer (AAS). The results obtained were as follows. Though there is a difference by each element, an amount less than 3 microgram/cm2 per unit area makes it possible to undergo multielement analysis, that is, is has no influence on fine particle effect (particle size; under 5 microns). Then, effects of the X-ray intensity by different chemical forms are negligible. At the presence the neighboring element and other elements this technique showed greater precision by carrying out on corrective treatment, etc. The coefficient of variation of this technique was in the range of 2.5-6.5% at DDTC-Cu of 0.5-5.0 micrograms/cm2, with the limit of detection for As : 0.002 microgram/cm2, Zn : 0.003 microgram/cm2, Pb : 0.003 microgram/cm2, Cu : 0.004 microgram/cm2, Ni : 0.003 microgram/cm2, Fe : 0.005 microgram/cm2, Mn : 0.008 microgram/cm2, Cr : 0.013 microgram/cm2, respectively. Aerosols collected at the workplace were analyzed with EDX and AAS, and the obtained results showed good agreement with such regression line as y = 1.04 chi + 0.04, the coefficient of correlation being r = 0.995. From these results, this technique was found to be a very excellent method for monitoring of multielements in the workplace air.

  10. Investigations of multiple backscattering and albedos of 1.12 MeV gamma photons in elements and alloys

    International Nuclear Information System (INIS)

    Sabharwal, Arvind D.; Singh, Bhajan; Sandhu, B.S.

    2009-01-01

    The energy and intensity distributions of multiple backscattering of 1.12 MeV gamma photons emerging from targets of elements and alloys are observed as a function of thickness and atomic number (Z) of the target. The numbers of these multiply backscattered events show an increase with increase in target thickness, and then saturate for a particular thickness of the target called saturation thickness (depth). The saturation thickness decreases with increasing atomic number and varies as e -Z . The multiple backscattering, an interfering background noise in Compton profile, has been successfully used to assign the 'effective atomic number' to alloys. Monte Carlo calculations also support the present experimental results. The number, energy and dose albedos are also found to be saturating for the same thickness where the numbers of multiply backscattered events saturate.

  11. Experimental investigations of multiple scattering of 662 keV gamma photons in elements and binary alloys

    International Nuclear Information System (INIS)

    Singh, Gurvinderjit; Singh, Manpreet; Sandhu, B.S.; Singh, Bhajan

    2008-01-01

    The energy, intensity and angular distributions of multiple scattering of 662 keV gamma photons, emerging from targets of pure elements and binary alloys, are observed as a function of target thickness in reflection and transmission geometries. The observed spectra recorded by a properly shielded NaI (Tl) scintillation detector, in addition to singly scattered events, consist of photons scattered more than once for thick targets. To extract the contribution of multiply scattered photons from the measured spectra, a singly scattered distribution is reconstructed analytically. We observe that the numbers of multiply scattered events increase with increase in target thickness, and saturate for a particular thickness called saturation thickness. The saturation thickness decreases with increasing atomic number. The multiple scattering, an interfering background noise in Compton profiles and Compton cross-section measurements, has been successfully used as a new technique to assign the 'effective atomic number' to binary alloys. Monte Carlo calculations support the present experimental results

  12. Matrix-type multiple reciprocity boundary element method for solving three-dimensional two-group neutron diffusion equations

    International Nuclear Information System (INIS)

    Itagaki, Masafumi; Sahashi, Naoki.

    1997-01-01

    The multiple reciprocity boundary element method has been applied to three-dimensional two-group neutron diffusion problems. A matrix-type boundary integral equation has been derived to solve the first and the second group neutron diffusion equations simultaneously. The matrix-type fundamental solutions used here satisfy the equation which has a point source term and is adjoint to the neutron diffusion equations. A multiple reciprocity method has been employed to transform the matrix-type domain integral related to the fission source into an equivalent boundary one. The higher order fundamental solutions required for this formulation are composed of a series of two types of analytic functions. The eigenvalue itself is also calculated using only boundary integrals. Three-dimensional test calculations indicate that the present method provides stable and accurate solutions for criticality problems. (author)

  13. Transcriptomic analysis of rice aleurone cells identified a novel abscisic acid response element.

    Science.gov (United States)

    Watanabe, Kenneth A; Homayouni, Arielle; Gu, Lingkun; Huang, Kuan-Ying; Ho, Tuan-Hua David; Shen, Qingxi J

    2017-09-01

    Seeds serve as a great model to study plant responses to drought stress, which is largely mediated by abscisic acid (ABA). The ABA responsive element (ABRE) is a key cis-regulatory element in ABA signalling. However, its consensus sequence (ACGTG(G/T)C) is present in the promoters of only about 40% of ABA-induced genes in rice aleurone cells, suggesting other ABREs may exist. To identify novel ABREs, RNA sequencing was performed on aleurone cells of rice seeds treated with 20 μM ABA. Gibbs sampling was used to identify enriched elements, and particle bombardment-mediated transient expression studies were performed to verify the function. Gene ontology analysis was performed to predict the roles of genes containing the novel ABREs. This study revealed 2443 ABA-inducible genes and a novel ABRE, designated as ABREN, which was experimentally verified to mediate ABA signalling in rice aleurone cells. Many of the ABREN-containing genes are predicted to be involved in stress responses and transcription. Analysis of other species suggests that the ABREN may be monocot specific. This study also revealed interesting expression patterns of genes involved in ABA metabolism and signalling. Collectively, this study advanced our understanding of diverse cis-regulatory sequences and the transcriptomes underlying ABA responses in rice aleurone cells. © 2017 John Wiley & Sons Ltd.

  14. Analytical and experimental investigation on a multiple-mass-element pendulum impact damper for vibration mitigation

    Science.gov (United States)

    Egger, Philipp; Caracoglia, Luca

    2015-09-01

    Impact dampers are often used in the field of civil, mechanical and aerospace engineering for reducing structural vibrations. The behavior of this type of passive control device has been investigated for several decades. In this research a distributed-mass impact damper, similar to the "chain damper" used in wind engineering, has been examined and applied to the vibration reduction on a slender line-like structural element (stay-cable). This study is motivated by a practical problem and describes the derivation of a reduced-order model for explaining the behavior, observed during a field experiment on a prototype system. In its simplest form, the dynamics of the apparatus is modeled as a "resilient damper", composed of mass-spring-dashpot secondary elements, attached to the primary structure. Various sources of excitation are analyzed: free vibration, external harmonic force and random excitation. The proposed model is general and potentially applicable to the analysis of several structural systems. The study also shows that the model can adequately describe and explain the experimentally observed behavior.

  15. Piezoelectric materials selection for sensor applications using finite element and multiple attribute decision-making approaches

    Directory of Open Access Journals (Sweden)

    Anuruddh Kumar

    2015-03-01

    Full Text Available This paper examines the selection and performance evaluation of a variety of piezoelectric materials for cantilever-based sensor applications. The finite element analysis method is implemented to evaluate the relative importance of materials properties such as Young's Modulus (E, piezoelectric stress constants (e31, dielectric constant (ε and Poisson's ratio (υ for cantilever-based sensor applications. An analytic hierarchy process (AHP is used to assign weights to the properties that are studied for the sensor structure under study. A technique for order preference by similarity to ideal solution (TOPSIS is used to rank the performance of the piezoelectric materials in the context of sensor voltage outputs. The ranking achieved by the TOPSIS analysis is in good agreement with the results obtained from finite element method simulation. The numerical simulations show that K0.5Na0.5NbO3–LiSbO3 (KNN–LS materials family is important for sensor application. Young's modulus (E is most influencing material's property followed by piezoelectric constant (e31, dielectric constant (ε and Poisson's ratio (υ for cantilever-based piezoelectric sensor applications.

  16. Detecting the limits of regulatory element conservation anddivergence estimation using pairwise and multiple alignments

    Energy Technology Data Exchange (ETDEWEB)

    Pollard, Daniel A.; Moses, Alan M.; Iyer, Venky N.; Eisen,Michael B.

    2006-08-14

    Background: Molecular evolutionary studies of noncodingsequences rely on multiple alignments. Yet how multiple alignmentaccuracy varies across sequence types, tree topologies, divergences andtools, and further how this variation impacts specific inferences,remains unclear. Results: Here we develop a molecular evolutionsimulation platform, CisEvolver, with models of background noncoding andtranscription factor binding site evolution, and use simulated alignmentsto systematically examine multiple alignment accuracy and its impact ontwo key molecular evolutionary inferences: transcription factor bindingsite conservation and divergence estimation. We find that the accuracy ofmultiple alignments is determined almost exclusively by the pairwisedivergence distance of the two most diverged species and that additionalspecies have a negligible influence on alignment accuracy. Conservedtranscription factor binding sites align better than surroundingnoncoding DNA yet are often found to be misaligned at relatively shortdivergence distances, such that studies of binding site gain and losscould easily be confounded by alignment error. Divergence estimates frommultiple alignments tend to be overestimated at short divergencedistances but reach a tool specific divergence at which they cease toincrease, leading to underestimation at long divergences. Our moststriking finding was that overall alignment accuracy, binding sitealignment accuracy and divergence estimation accuracy vary greatly acrossbranches in a tree and are most accurate for terminal branches connectingsister taxa and least accurate for internal branches connectingsub-alignments. Conclusions: Our results suggest that variation inalignment accuracy can lead to errors in molecular evolutionaryinferences that could be construed as biological variation. Thesefindings have implications for which species to choose for analyses, whatkind of errors would be expected for a given set of species and howmultiple alignment tools and

  17. Phylogenetic consistencies among chondrichthyan and teleost fishes in their bioaccumulation of multiple trace elements from seawater

    Energy Technology Data Exchange (ETDEWEB)

    Jeffree, Ross A., E-mail: R.Jeffree@iaea.org [IAEA Marine Environment Laboratories, 4, Quai Antoine 1er, MC 98000 (Monaco); Oberhansli, Francois; Teyssie, Jean-Louis [IAEA Marine Environment Laboratories, 4, Quai Antoine 1er, MC 98000 (Monaco)

    2010-07-15

    Multi-tracer experiments determined the accumulation from seawater of selected radioactive trace elements (Mn-54, Co-60, Zn-65, Cs-134, Am-241, Cd-109, Ag-110m, Se-75 and Cr-51) by three teleost and three chondrichthyan fish species to test the hypothesis that these phylogenetic groups have different bioaccumulation characteristics, based on previously established contrasts between the carcharhiniform chondrichthyan Scyliorhinus canicula (dogfish) and the pleuronectiform teleost Psetta maxima (turbot). Discriminant function analysis on whole body: water concentration factors (CFs) separated dogfish and turbot in two independent experiments. Classification functions grouped the perciform teleosts, seabream (Sparus aurata) and seabass (Dicentrarchus labrax), with turbot and grouped the chondrichthyans, undulate ray (Raja undulata; Rajiformes) and spotted torpedo (Torpedo marmorata; Torpediniformes), with dogfish, thus supporting our hypothesis. Hierarchical classificatory, multi-dimensional scaling and similarity analyses based on the CFs for the nine radiotracers, also separated all three teleosts (that aggregated lower in the hierarchy) from the three chondrichthyan species. The three chondrichthyans were also more diverse amongst themselves compared to the three teleosts. Particular trace elements that were more important in separating teleosts and chondrichthyans were Cs-134 that was elevated in teleosts and Zn-65 that was elevated in chondrichthyans, these differences being due to their differential rates of uptake rather than loss. Chondrichthyans were also higher in Cr-51, Co-60, Ag-110m and Am-241, whereas teleosts were higher only in Mn-54. These contrasts in bioaccumulation patterns between teleosts and chondrichthyans are interpreted in the context of both proximate causes of underlying differences in physiology and anatomy, as well as the ultimate cause of their evolutionary divergence over more than 500 million years before present (MyBP). Our results

  18. Phylogenetic consistencies among chondrichthyan and teleost fishes in their bioaccumulation of multiple trace elements from seawater

    International Nuclear Information System (INIS)

    Jeffree, Ross A.; Oberhansli, Francois; Teyssie, Jean-Louis

    2010-01-01

    Multi-tracer experiments determined the accumulation from seawater of selected radioactive trace elements (Mn-54, Co-60, Zn-65, Cs-134, Am-241, Cd-109, Ag-110m, Se-75 and Cr-51) by three teleost and three chondrichthyan fish species to test the hypothesis that these phylogenetic groups have different bioaccumulation characteristics, based on previously established contrasts between the carcharhiniform chondrichthyan Scyliorhinus canicula (dogfish) and the pleuronectiform teleost Psetta maxima (turbot). Discriminant function analysis on whole body: water concentration factors (CFs) separated dogfish and turbot in two independent experiments. Classification functions grouped the perciform teleosts, seabream (Sparus aurata) and seabass (Dicentrarchus labrax), with turbot and grouped the chondrichthyans, undulate ray (Raja undulata; Rajiformes) and spotted torpedo (Torpedo marmorata; Torpediniformes), with dogfish, thus supporting our hypothesis. Hierarchical classificatory, multi-dimensional scaling and similarity analyses based on the CFs for the nine radiotracers, also separated all three teleosts (that aggregated lower in the hierarchy) from the three chondrichthyan species. The three chondrichthyans were also more diverse amongst themselves compared to the three teleosts. Particular trace elements that were more important in separating teleosts and chondrichthyans were Cs-134 that was elevated in teleosts and Zn-65 that was elevated in chondrichthyans, these differences being due to their differential rates of uptake rather than loss. Chondrichthyans were also higher in Cr-51, Co-60, Ag-110m and Am-241, whereas teleosts were higher only in Mn-54. These contrasts in bioaccumulation patterns between teleosts and chondrichthyans are interpreted in the context of both proximate causes of underlying differences in physiology and anatomy, as well as the ultimate cause of their evolutionary divergence over more than 500 million years before present (MyBP). Our results

  19. Computational methods to dissect cis-regulatory transcriptional ...

    Indian Academy of Sciences (India)

    The formation of diverse cell types from an invariant set of genes is governed by biochemical and molecular processes that regulate gene activity. A complete understanding of the regulatory mechanisms of gene expression is the major function of genomics. Computational genomics is a rapidly emerging area for ...

  20. Patterns of cis regulatory variation in diverse human populations.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for the transferability of complex trait variants across populations.

  1. Sensitive targeted multiple protein quantification based on elemental detection of Quantum Dots

    Energy Technology Data Exchange (ETDEWEB)

    Montoro Bustos, Antonio R.; Garcia-Cortes, Marta [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); González-Iglesias, Hector [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Ruiz Encinar, Jorge, E-mail: ruizjorge@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Costa-Fernández, José M. [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Coca-Prados, Miguel [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510 (United States); Sanz-Medel, Alfredo, E-mail: asm@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain)

    2015-06-16

    Highlights: • Novel generic platform for multiparametric quantification of proteins. • QDs labeling and ICP-MS detection allow significant analytical signal amplification. • ICP-MS mass balances information provided an internal validation of the immunoassay. • Multiparametric determination of 5 proteins in human serum samples. • ICP-MS reduced matrix effects as compared to other conventional detection techniques. - Abstract: A generic strategy based on the use of CdSe/ZnS Quantum Dots (QDs) as elemental labels for protein quantification, using immunoassays with elemental mass spectrometry (ICP-MS), detection is presented. In this strategy, streptavidin modified QDs (QDs-SA) are bioconjugated to a biotinylated secondary antibody (b-Ab{sub 2}). After a multi-technique characterization of the synthesized generic platform (QDs-SA-b-Ab{sub 2}) it was applied to the sequential quantification of five proteins (transferrin, complement C3, apolipoprotein A1, transthyretin and apolipoprotein A4) at different concentration levels in human serum samples. It is shown how this generic strategy does only require the appropriate unlabeled primary antibody for each protein to be detected. Therefore, it introduces a way out to the need for the cumbersome and specific bioconjugation of the QDs to the corresponding specific recognition antibody for every target analyte (protein). Results obtained were validated with those obtained using UV–vis spectrophotometry and commercial ELISA Kits. As expected, ICP-MS offered one order of magnitude lower DL (0.23 fmol absolute for transferrin) than the classical spectrophotometric detection (3.2 fmol absolute). ICP-MS precision and detection limits, however turned out to be compromised by procedural blanks. The full analytical performance of the ICP-MS-based immunoassay proposed was assessed for detection of transferrin (Tf), present at the low ng mL{sup −1} range in a complex “model” synthetic matrix, where the total protein

  2. Optical frequency-domain reflectometry using multiple wavelength-swept elements of a DFB laser array

    Science.gov (United States)

    DiLazaro, Tom; Nehmetallah, Georges

    2017-02-01

    Coherent optical frequency-domain reflectometry (C-OFDR) is a distance measurement technique with significant sensitivity and detector bandwidth advantages over normal time-of-flight methods. Although several swept-wavelength laser sources exist, many exhibit short coherence lengths, or require precision mechanical tuning components. Semiconductor distributed feedback lasers (DFBs) are advantageous as a mid-to-long range OFDR source because they exhibit a narrow linewidth and can be rapidly tuned simply via injection current. However, the sweep range of an individual DFB is thermally limited. Here, we present a novel high-resolution OFDR system that uses a compact, monolithic 12-element DFB array to create a continuous, gap-free sweep over a wide wavelength range. Wavelength registration is provided by the incorporation of a HCN gas cell and reference interferometer. The wavelength-swept spectra of the 12 DFBs are combined in post-processing to achieve a continuous total wavelength sweep of more than 40 nm (5.4 THz) in the telecommunications C-Band range.

  3. Acceptance of spent nuclear fuel in multiple element sealed canisters by the Federal Waste Management System

    International Nuclear Information System (INIS)

    1990-03-01

    This report is one of a series of eight prepared by E.R. Johnson Associates, Inc. (JAI) under ORNL's contract with DOE's OCRWM Systems Integration Program and in support of the Annual Capacity Report (ACR) Issue Resolution Process. The report topics relate specifically to the list of high priority technical waste acceptance issues developed jointly by DOE and a utility-working group. JAI performed various analyses and studies on each topic to serve as starting points for further discussion and analysis leading eventually to finalizing the process by which DOE will accept spent fuel and waste into its waste management system. The eight reports are concerned with the conditions under which spent fuel and high level waste will be accepted in the following categories: (1) failed fuel; (2) consolidated fuel and associated structural parts; (3) non-fuel-assembly hardware; (4) fuel in metal storage casks; (5) fuel in multi-element sealed canisters; (6) inspection and testing requirements for wastes; (7) canister criteria; (8) spent fuel selection for delivery; and (9) defense and commercial high-level waste packages. 14 refs., 27 figs

  4. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

    Science.gov (United States)

    Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

    2012-08-07

    The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

  5. A geometric buckling expression for regular polygons: II. Analyses based on the multiple reciprocity boundary element method

    International Nuclear Information System (INIS)

    Itagaki, Masafumi; Miyoshi, Yoshinori; Hirose, Hideyuki

    1993-01-01

    A procedure is presented for the determination of geometric buckling for regular polygons. A new computation technique, the multiple reciprocity boundary element method (MRBEM), has been applied to solve the one-group neutron diffusion equation. The main difficulty in applying the ordinary boundary element method (BEM) to neutron diffusion problems has been the need to compute a domain integral, resulting from the fission source. The MRBEM has been developed for transforming this type of domain integral into an equivalent boundary integral. The basic idea of the MRBEM is to apply repeatedly the reciprocity theorem (Green's second formula) using a sequence of higher order fundamental solutions. The MRBEM requires discretization of the boundary only rather than of the domain. This advantage is useful for extensive survey analyses of buckling for complex geometries. The results of survey analyses have indicated that the general form of geometric buckling is B g 2 = (a n /R c ) 2 , where R c represents the radius of the circumscribed circle of the regular polygon under consideration. The geometric constant A n depends on the type of regular polygon and takes the value of π for a square and 2.405 for a circle, an extreme case that has an infinite number of sides. Values of a n for a triangle, pentagon, hexagon, and octagon have been calculated as 4.190, 2.281, 2.675, and 2.547, respectively

  6. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

    Science.gov (United States)

    Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

    2017-04-01

    Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

  7. An ABA-responsive element in the AtSUC1 promoter is involved in the regulation of AtSUC1 expression.

    Science.gov (United States)

    Hoth, Stefan; Niedermeier, Matthias; Feuerstein, Andrea; Hornig, Julia; Sauer, Norbert

    2010-09-01

    Abscisic acid (ABA) and sugars regulate many aspects of plant growth and development, and we are only just beginning to understand the complex interactions between ABA and sugar signaling networks. Here, we show that ABA-dependent transcription factors bind to the promoter of the Arabidopsis thaliana AtSUC1 (At1g71880) sucrose transporter gene in vitro. We present the characterization of a cis-regulatory element by truncation of the AtSUC1 promoter and by electrophoretic mobility shift assays that is identical to a previously characterized ABA-responsive element (ABRE). In yeast 1-hybrid analyses we identified ABI5 (AtbZIP39; At2g36270) and AREB3 (AtbZIP66; At3g56850) as potential interactors. Analyses of plants expressing the beta-glucuronidase reporter gene under the control of ABI5 or AREB3 promoter sequences demonstrated that both transcription factor genes are co-expressed with AtSUC1 in pollen and seedlings, the primary sites of AtSUC1 action. Mutational analyses of the identified cis-regulatory element verified its importance for AtSUC1 expression in young seedlings. In abi5-4 seedlings, we observed an increase of sucrose-dependent anthocyanin accumulation and AtSUC1 mRNA levels. This suggests that ABI5 prevents an overshoot of sucrose-induced AtSUC1 expression and confirmed a novel cross-link between sugar and ABA signaling.

  8. Non-LTR R2 element evolutionary patterns: phylogenetic incongruences, rapid radiation and the maintenance of multiple lineages.

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    Full Text Available Retrotransposons of the R2 superclade specifically insert within the 28S ribosomal gene. They have been isolated from a variety of metazoan genomes and were found vertically inherited even if their phylogeny does not always agree with that of the host species. This was explained with the diversification/extinction of paralogous lineages, being proved the absence of horizontal transfer. We here analyze the widest available collection of R2 sequences, either newly isolated from recently sequenced genomes or drawn from public databases, in a phylogenetic framework. Results are congruent with previous analyses, but new important issues emerge. First, the N-terminal end of the R2-B clade protein, so far unknown, presents a new zinc fingers configuration. Second, the phylogenetic pattern is consistent with an ancient, rapid radiation of R2 lineages: being the estimated time of R2 origin (850-600 Million years ago placed just before the metazoan Cambrian explosion, the wide element diversity and the incongruence with the host phylogeny could be attributable to the sudden expansion of available niches represented by host's 28S ribosomal genes. Finally, we detect instances of coexisting multiple R2 lineages showing a non-random phylogenetic pattern, strongly similar to that of the "library" model known for tandem repeats: a collection of R2s were present in the ancestral genome and then differentially activated/repressed in the derived species. Models for activation/repression as well as mechanisms for sequence maintenance are also discussed within this framework.

  9. Phylogeny based discovery of regulatory elements

    Directory of Open Access Journals (Sweden)

    Cohen Barak A

    2006-05-01

    Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

  10. Contributions to multiple element speciation in vegetable plants: Studies on the type of bonding of numerous elements, particularly zinc and cadmium

    International Nuclear Information System (INIS)

    Guenther, K.

    1997-03-01

    In the first part of the study, the total contents and the solubility characteristics of Zn, Cd, Fe, Mn, Cu, Ca, Sr, K and Rb in 26 different vegetable plants, the majority of them commercially available, are reported, obtained by post-decomposition analyses. The data are given for avocados, bananas, cauliflower, chicory, Chinese cabbage, dill, ice lettuce (two specimens), endive, field salad, cucumbers, kohlrabi, lettuce, chard beet, carrots, peppers, leek, radish, red cabbage, loose leaved lettuce, celery (two specimens), spinach, topinambur, white cabbage, and parsley. Cell decomposition was done by treatment of the plant material with an electric dispersing apparatus (Ultra-Turrax) in buffer solution (liquid shearing). The homogenates were separated into supernatants (cytosoles)and pellets by means of centrifugation. Cell decomposition of the plants by crushing with quartz sand after lyophilization (solid shearing) required much more technical effort and for some elements created problems with the blind values. At least 50% on the average of the elements Zn, Cd, Rb, and K could be transferred to the solutions by the dispersing treatment with Ultra-Turrax. In many cases, the cytosole-borne detectable contents of these 5 elements were above 70%. The solubility of Zn and Cd was more strongly dependent on the plant species than that of Cu, Rb, and K. All five elements thus can be analysed by conventional methods for further enhanced speciation. Mn, Ca, and especially Fe and Sr for the most part were found to be bonded to solid cell constituents. However, the solubility characteristics of Ca and Mn and Sr in particular was very homogeneous. In some plants, the contents of Mn and Sr in the cytosoles was approx. 90%, so that comprehensive speciation of these elements is possible. (orig./AJ) [de

  11. Overcoming Matrix Effects in a Complex Sample: Analysis of Multiple Elements in Multivitamins by Atomic Absorption Spectroscopy

    Science.gov (United States)

    Arnold, Randy J.; Arndt, Brett; Blaser, Emilia; Blosser, Chris; Caulton, Dana; Chung, Won Sog; Fiorenza, Garrett; Heath, Wyatt; Jacobs, Alex; Kahng, Eunice; Koh, Eun; Le, Thao; Mandla, Kyle; McCory, Chelsey; Newman, Laura; Pithadia, Amit; Reckelhoff, Anna; Rheinhardt, Joseph; Skljarevski, Sonja; Stuart, Jordyn; Taylor, Cassie; Thomas, Scott; Tse, Kyle; Wall, Rachel; Warkentien, Chad

    2011-01-01

    A multivitamin tablet and liquid are analyzed for the elements calcium, magnesium, iron, zinc, copper, and manganese using atomic absorption spectrometry. Linear calibration and standard addition are used for all elements except calcium, allowing for an estimate of the matrix effects encountered for this complex sample. Sample preparation using…

  12. POTENTIALLY TOXIC ELEMENT CYCLES AND CHARACTERIZATION OF MULTIPLE SOURCES IN THE IRRIGATION DITCHES FROM THE RAVENNA COASTAL PLAIN THROUGH TRACE ELEMENTS AND ISOTOPE GEOCHEMISTRY

    Directory of Open Access Journals (Sweden)

    Livia Vittori Antisari

    2010-04-01

    Full Text Available While monitoring the physico-chemical characteristics, trace elements and O-H-Sr-B isotopic data were obtained in superficial waters from a number of irrigations canals and ditches in the Ravenna coastal plain, in order to highlight the cycling of potentially toxic elements and the different sources of the solutes. Surveys were conducted during March and July 2008, and considered as representative of the waters in winter and summer, respectively. In summer, the water mass balance in the network is mostly controlled by the ingression of freshwaters from the Canale Emiliano Romagnolo (CER. The O-H isotopic data indicated that, in winter, waters are primarily recharged from Apennine catchments and undergo evaporation to different extents.The boron isotopic signature indicates the important role played by the marine component. A major seawater contribution was evidenced in canals close to the coastline; however, the process controlling the origin of dissolved boron is not solely related to direct mixing with sea water but comprises an additional source probably related to water-soil exchanges and boron of marine origin leaching, owing to the prolonged exposure of alluvial sediments to sea water. An additional boron contribution from the agricultural practice was is also evidenced. Calculation based on the conservative behaviour of chloride ions indicated that in canals and ditches not directly connected with the sea up to the 80% of the Sr budget did not originate from seawater, indicating a source from Al-silicate minerals and supporting the hypothesis of significant soil-water interactions and chemical exchanges.The positive correlation between pH and dissolved oxygen in winter waters is likely to reflect CO2 consumption during algal photosynthesis, favouring the in-situ generation of colloidal particles due to the oxidative precipitation of ferric iron oxy-hydroxides and probably small carbonate particles able to adsorb trace metals on their

  13. The mitochondrial genomes of sponges provide evidence for multiple invasions by Repetitive Hairpin-forming Elements (RHE

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    Lavrov Dennis V

    2009-12-01

    Full Text Available Abstract Background The mitochondrial (mt genomes of sponges possess a variety of features, which appear to be intermediate between those of Eumetazoa and non-metazoan opisthokonts. Among these features is the presence of long intergenic regions, which are common in other eukaryotes, but generally absent in Eumetazoa. Here we analyse poriferan mitochondrial intergenic regions, paying particular attention to repetitive sequences within them. In this context we introduce the mitochondrial genome of Ircinia strobilina (Lamarck, 1816; Demospongiae: Dictyoceratida and compare it with mtDNA of other sponges. Results Mt genomes of dictyoceratid sponges are identical in gene order and content but display major differences in size and organization of intergenic regions. An even higher degree of diversity in the structure of intergenic regions was found among different orders of demosponges. One interesting observation made from such comparisons was of what appears to be recurrent invasions of sponge mitochondrial genomes by repetitive hairpin-forming elements, which cause large genome size differences even among closely related taxa. These repetitive hairpin-forming elements are structurally and compositionally divergent and display a scattered distribution throughout various groups of demosponges. Conclusion Large intergenic regions of poriferan mt genomes are targets for insertions of repetitive hairpin- forming elements, similar to the ones found in non-metazoan opisthokonts. Such elements were likely present in some lineages early in animal mitochondrial genome evolution but were subsequently lost during the reduction of intergenic regions, which occurred in the Eumetazoa lineage after the split of Porifera. Porifera acquired their elements in several independent events. Patterns of their intra-genomic dispersal can be seen in the mt genome of Vaceletia sp.

  14. Matrix elements of the electric multiple transition and relativistic correction operators in the case of complex configurations

    International Nuclear Information System (INIS)

    Kanyauskas, Yu.M.; Rudzikas, Z.B.

    1976-01-01

    Operators and their submatrix elements are studied in the framework of the electric multipole transitions of complex atoms with account of relativistic corrections of the order of the square of the fine structure constant. The analysis is performed by means of irreducible tensor operators and genealogical coefficients. It has been assumed that angular momenta of individual shells are coupled with each other according to ls, lk, jk and jj coupling. Formulas are given for the operator which causes the relativistic corrections for the single-electron multipole transition and for its submatrix element in the case of configurations with two unfilled shells. A possibility is discussed of using the formulas suggested for calculation. As follows from analysis, the relativistic correction operators even with the pure ls coupling allow intercombination transitions with ΔS equals +-1. The expressions obtained may turn out to be useful for performing calculations in the case of the intermediate type of coupling

  15. Resveratrol stimulates c-Fos gene transcription via activation of ERK1/2 involving multiple genetic elements.

    Science.gov (United States)

    Thiel, Gerald; Rössler, Oliver G

    2018-06-05

    The polyphenol resveratrol is found in many plant and fruits and is a constituent of our diet. Resveratrol has been proposed to have chemopreventive and anti-inflammatory activities. On the cellular level, resveratrol activates stimulus-regulated transcription factors. To identify resveratrol-responsive elements within a natural gene promoter, the molecular pathway leading to c-Fos gene expression by resveratrol was dissected. The c-Fos gene encodes a basic region leucine zipper transcription factor and is a prototype of an immediate-early gene that is regulated by a wide range of signaling molecules. We analyzed chromatin-integrated c-Fos promoter-luciferase reporter genes where transcription factor binding sites were destroyed by point mutations or deletion mutagenesis. The results show that mutation of the binding sites for serum response factor (SRF), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) significantly reduced reporter gene transcription following stimulation of the cells with resveratrol. Inactivation of the binding sites for signal transducer and activator of transcription (STAT) or ternary complex factors did not influence resveratrol-regulated c-Fos promoter activity. Thus, the c-Fos promoter contains three resveratrol-responsive elements, the cAMP response element (CRE), and the binding sites for SRF and AP-1. Moreover, we show that the transcriptional activation potential of the c-Fos protein is increased in resveratrol-stimulated cells, indicating that the biological activity of c-Fos is elevated by resveratrol stimulation. Pharmacological and genetic experiments revealed that the protein kinase ERK1/2 is the signal transducer that connects resveratrol treatment with the c-Fos gene. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. 3D Space Shift from CityGML LoD3-Based Multiple Building Elements to a 3D Volumetric Object

    Directory of Open Access Journals (Sweden)

    Shen Ying

    2017-01-01

    Full Text Available In contrast with photorealistic visualizations, urban landscape applications, and building information system (BIM, 3D volumetric presentations highlight specific calculations and applications of 3D building elements for 3D city planning and 3D cadastres. Knowing the precise volumetric quantities and the 3D boundary locations of 3D building spaces is a vital index which must remain constant during data processing because the values are related to space occupation, tenure, taxes, and valuation. To meet these requirements, this paper presents a five-step algorithm for performing a 3D building space shift. This algorithm is used to convert multiple building elements into a single 3D volumetric building object while maintaining the precise volume of the 3D space and without changing the 3D locations or displacing the building boundaries. As examples, this study used input data and building elements based on City Geography Markup Language (CityGML LoD3 models. This paper presents a method for 3D urban space and 3D property management with the goal of constructing a 3D volumetric object for an integral building using CityGML objects, by fusing the geometries of various building elements. The resulting objects possess true 3D geometry that can be represented by solid geometry and saved to a CityGML file for effective use in 3D urban planning and 3D cadastres.

  17. Optimized computational method for determining the beta dose distribution using a multiple-element thermoluminescent dosimeter system

    International Nuclear Information System (INIS)

    Shen, L.; Levine, S.H.; Catchen, G.L.

    1987-01-01

    This paper describes an optimization method for determining the beta dose distribution in tissue, and it describes the associated testing and verification. The method uses electron transport theory and optimization techniques to analyze the responses of a three-element thermoluminescent dosimeter (TLD) system. Specifically, the method determines the effective beta energy distribution incident on the dosimeter system, and thus the system performs as a beta spectrometer. Electron transport theory provides the mathematical model for performing the optimization calculation. In this calculation, parameters are determined that produce calculated doses for each of the chip/absorber components in the three-element TLD system. The resulting optimized parameters describe an effective incident beta distribution. This method can be used to determine the beta dose specifically at 7 mg X cm-2 or at any depth of interest. The doses at 7 mg X cm-2 in tissue determined by this method are compared to those experimentally determined using an extrapolation chamber. For a great variety of pure beta sources having different incident beta energy distributions, good agreement is found. The results are also compared to those produced by a commonly used empirical algorithm. Although the optimization method produces somewhat better results, the advantage of the optimization method is that its performance is not sensitive to the specific method of calibration

  18. Multiple enrichment of the Carpathian-Pannonian mantle: Pb-Sr-Nd isotope and trace element constraints

    Science.gov (United States)

    Rosenbaum, Jeffrey M.; Wilson, Marjorie; Downes, Hilary

    1997-07-01

    Pb isotope compositions of acid-leached clinopyroxene and amphibole mineral separates from spinel peridotite mantle xenoliths entrained in Tertiary-Quaternary alkali basalts from the Carpathian-Pannonian Region of eastern Europe provide important constraints on the processes of metasomatic enrichment of the mantle lithosphere in an extensional tectonic setting associated with recent subduction. Principal component analysis of Pb-Sr-Nd isotope and rare earth element compositions of the pyroxenes is used to identify the geochemical characteristics of the original lithospheric mantle protolith and a spectrum of infiltrating metasomatic agents including subduction-related aqueous fluids and silicate melts derived from a subduction-modified mantle wedge which contains a St. Helena-type (HIMU) plume component. The mantle protolith is highly depleted relative to mid-ocean ridge basalt-source mantle with Pb-Nd-Sr isotope compositions consistent with an ancient depletion event. Silicate melt infiltration into the protolith accounts for the primary variance in the Pb-Sr-Nd isotope compositions of the xenoliths and has locally generated metasomatic amphibole. Infiltration of aqueous fluids has introduced radiogenic Pb and Sr without significantly perturbing the rare earth element signature of the protolith. The Pb isotope compositions of the fluid-modified xenoliths suggest that they reacted with aqueous fluids released from a subduction zone which had equilibrated with sediment derived from an ancient basement terrain. We propose a model for mantle lithosphere evolution consistent with available textural and geochemical data for the xenolith population. The Pb-Sr-Nd isotope compositions of both alkaline mafic magmas and rare, subduction-related, calc-alkaline basaltic andesites from the region provide important constraints for the nature of the asthenospheric mantle wedge and confirm the presence of a HIMU plume component. These silicate melts contribute to the metasomatism

  19. New Insights into Trace Element Partitioning in Amphibole from Multiple Regression Analysis, with Application to the Magma Plumbing System of Mt. Lamington (Papua New Guinea)

    Science.gov (United States)

    Zhang, J.; Humphreys, M.; Cooper, G.; Davidson, J.; Macpherson, C.

    2015-12-01

    We present a new multiple regression (MR) analysis of published amphibole-melt trace element partitioning data, with the aim of retrieving robust relationships between amphibole crystal-chemical compositions and trace element partition coefficients (D). We examined experimental data for calcic amphiboles of kaersutite, pargasite, tschermakite (Tsch), magnesiohornblende (MgHbl) and magnesiohastingsite (MgHst) compositions crystallized from basanitic-rhyolitic melts (n = 150). The MR analysis demonstrates the varying significance of amphibole major element components assigned to different crystallographic sites (T, M1-3, M4, A) as independent variables in controlling D, and it allows us to retrieve statistically significant relationships for REE, Y, Rb, Sr, Pb, Ti, Zr, Nb (n > 25, R2 > 0.6, p-value Ridolfi & Renzulli 2012) with lower Rb and Sr and higher Pb, relative to a hot, andesitic-dacitic melt (950-1,000±50 ºC; 60-70±5 wt % SiO2) where MgHst are crystallized. REE and Nb contents are similar in both types of melts despite higher REE and Nb in MgHbl-Tsch. Therefore, the REE compositional disparity between MgHst and MgHbl-Tsch is driven by the difference in the DREE, rather than the melt REE concentrations.

  20. Cooperative action of multiple cis-acting elements is required for N-myc expression in branchial arches: specific contribution of GATA3.

    Science.gov (United States)

    Potvin, Eric; Beuret, Laurent; Cadrin-Girard, Jean-François; Carter, Marcelle; Roy, Sophie; Tremblay, Michel; Charron, Jean

    2010-11-01

    The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb -8.7 to kb +7.2 are sufficient to reproduce the N-myc embryonic expression profile in developing branchial arches and limb buds. These sequences encompass several regulatory elements dispersed throughout the N-myc locus, including an upstream limb bud enhancer, a downstream somite enhancer, a branchial arch enhancer in the second intron, and a negative regulatory element in the first intron. N-myc expression in the limb buds is under the dominant control of the limb bud enhancer. The expression in the branchial arches necessitates the interplay of three regulatory domains. The branchial arch enhancer cooperates with the somite enhancer region to prevent an inhibitory activity contained in the first intron. The characterization of the branchial arch enhancer has revealed a specific role of the transcription factor GATA3 in the regulation of N-myc expression. Together, these data demonstrate that correct N-myc developmental expression is achieved via cooperation of multiple positive and negative regulatory elements.

  1. Exchange pattern of gaseous elemental mercury in landfill: mercury deposition under vegetation coverage and interactive effects of multiple meteorological conditions.

    Science.gov (United States)

    Tao, Zhengkai; Liu, Yang; Zhou, Meng; Chai, Xiaoli

    2017-12-01

    Landfill is known as a potential source of atmospheric Hg and an important component of the local or regional atmospheric Hg budget. This study investigated the gaseous elemental Hg surface-air fluxes under differing conditions at a typical municipal solid waste landfill site, highlighting the interactive effects of plant coverage and meteorological conditions. The results indicated that Hg fluxes exhibited a feature represented by diel variation. In particular, Hg deposition was observed under a condition of Kochia sieversiana coverage, whereas emission that occurred after K. sieversiana was removed. Hg emission was the dominant mode under conditions of Setaria viridis coverage and its removal; however, the average Hg emission flux with the S. viridis coverage was nearly four times lower than after its removal. These findings verified that the plant coverage should be a key factor influencing the Hg emission from landfills. In addition, Hg fluxes were correlated positively with solar radiation and air/soil temperature and correlated inversely with relative humidity under all conditions, except K. sieversiana coverage. This suggested that the interactive effects of meteorological conditions and plant coverage played a jointly significant role in the Hg emission from landfills. It was established that K. sieversiana can inhibit Hg emission efficiently, and therefore, it could potentially be suitable for use as a plant-based method to control Hg pollution from landfills.

  2. Towards the prediction of multiple necking during dynamic extension of round bar: linear stability approach versus finite element calculations

    International Nuclear Information System (INIS)

    Maï, S El; Petit, J; Mercier, S; Molinari, A

    2014-01-01

    The fragmentation of structures subject to dynamic conditions is a matter of interest for civil industries as well as for Defence institutions. Dynamic expansions of structures, such as cylinders or rings, have been performed to obtain crucial information on fragment distributions. Many authors have proposed to capture by FEA the experimental distribution of fragment size by introducing in the FE model a perturbation. Stability and bifurcation analyses have also been proposed to describe the evolution of the perturbation growth rate. In the proposed contribution, the multiple necking of a round bar in dynamic tensile loading is analysed by the FE method. A perturbation on the initial flow stress is introduced in the numerical model to trigger instabilities. The onset time and the dominant mode of necking have been characterized precisely and showed power law evolutions, with the loading velocities and moderately with the amplitudes and the cell sizes of the perturbations. In the second part of the paper, the development of linear stability analysis and the use of salient criteria in terms of the growth rate of perturbations enabled comparisons with the numerical results. A good correlation in terms of onset time of instabilities and of number of necks is shown.

  3. A 20 bp cis-acting element is both necessary and sufficient to mediate elicitor response of a maize PRms gene.

    Science.gov (United States)

    Raventós, D; Jensen, A B; Rask, M B; Casacuberta, J M; Mundy, J; San Segundo, B

    1995-01-01

    Transient gene expression assays in barley aleurone protoplasts were used to identify a cis-regulatory element involved in the elicitor-responsive expression of the maize PRms gene. Analysis of transcriptional fusions between PRms 5' upstream sequences and a chloramphenicol acetyltransferase reporter gene, as well as chimeric promoters containing PRms promoter fragments or repeated oligonucleotides fused to a minimal promoter, delineated a 20 bp sequence which functioned as an elicitor-response element (ERE). This sequence contains a motif (-246 AATTGACC) similar to sequences found in promoters of other pathogen-responsive genes. The analysis also indicated that an enhancing sequence(s) between -397 and -296 is required for full PRms activation by elicitors. The protein kinase inhibitor staurosporine was found to completely block the transcriptional activation induced by elicitors. These data indicate that protein phosphorylation is involved in the signal transduction pathway leading to PRms expression.

  4. Identification of Smad Response Elements in the Promoter of Goldfish FSHβ Gene and Evidence for Their Mediation of Activin and GnRH Stimulation of FSHβ Expression

    Directory of Open Access Journals (Sweden)

    Man-Tat eLau

    2012-03-01

    Full Text Available As an essential hormone regulating gonads in vertebrates, the biosynthesis and secretion of follicle-stimulating hormone (FSH is controlled by a variety of endocrine and paracrine factors in both mammalian and non-mammalian vertebrates. Activin was initially discovered in the ovary for its specific stimulation of FSH secretion by the pituitary cells. Our earlier studies in fish have shown that activin stimulates FSHβ but suppresses LHβ expression in both the goldfish and zebrafish. Further experiments showed that the regulation of FSHβ in fish occurred at the promoter level involving Smads, in particular Smad3. To further understand the mechanisms by which activin/Smad regulates FSHβ transcription, the present study was undertaken to analyze the promoter of goldfish FSHβ gene (fshb with the aim to identify potential cis-regulatory elements responsible for activin/Smad stimulation. Both serial deletion and site-directed mutagenesis were used, and the promoter activity was tested in the LβT2 cells, a murine gonadotroph cell line. The reporter constructs of goldfish FSHβ promoter-SEAP (secreted alkaline phosphatase were co-transfected with an expression plasmid for Smads (2 or 3 followed by measurement of SEAP activity in the medium. Two putative Smad responsive elements (SRE were identified in the promoter at distal and proximal regions, respectively. The distal site contained a consensus Smad binding element (SBE; AGAC, -1675/-1672 whereas the proximal site (GACCTTGA, -212/-205 was identical to an SF-1 binding site reported in humans, which was preceded by a sequence (AACACTGA highly conserved between fish and mammals. The proximal site also seemed to be involved in mediating stimulation of FSHβ expression by gonadotropin-releasing hormone (GnRH and its potential interaction with activin. In conclusion, we have identified two potential cis-regulatory elements in the promoter of goldfish FSHβ that are responsible for activin

  5. ABFs, a family of ABA-responsive element binding factors.

    Science.gov (United States)

    Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

    2000-01-21

    Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

  6. Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice.

    Science.gov (United States)

    Sumoy, L; Wang, C K; Lichtler, A C; Pierro, L J; Kosher, R A; Upholt, W B

    1995-07-01

    Msx-2 is a member of the Msx family of homeobox-containing genes expressed in a variety of embryonic tissues involved in epithelial-mesenchymal interactions and pattern formation. In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm. In addition, Msx-2 is expressed in the anterior nonskeletal-forming mesoderm of the limb bud, in the posterior necrotic zone, and in the interdigital mesenchyme. Studies of the altered expression patterns of Msx-2 in amelic and polydactylous mutant chick limbs have suggested that the apical ectodermal ridge and mesodermal domains of Msx-2 expression are independently regulated and that there might be separate cis-regulatory elements in the Msx-2 gene controlling its spatially distinct domains of expression. To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice. A variety of these constructs are consistently expressed only in the apical ectodermal ridge and the ectoderm of the genital tubercle and are not expressed in the mesoderm of the limb bud or in other regions of the embryo where the endogenous Msx-2 gene is expressed. These results suggest the presence of spatially specific cis-regulatory elements in the Msx-2 gene. We identified a 348-bp region in the 5' flanking region of the Msx-2 gene which can act as an apical ectodermal ridge enhancer element when placed in reverse orientation in front of the reporter gene with transcription initiation directed by the minimal hsp68 promoter.

  7. Discovery of cis-elements between sorghum and rice using co-expression and evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Haberer Georg

    2009-06-01

    Full Text Available Abstract Background The spatiotemporal regulation of gene expression largely depends on the presence and absence of cis-regulatory sites in the promoter. In the economically highly important grass family, our knowledge of transcription factor binding sites and transcriptional networks is still very limited. With the completion of the sorghum genome and the available rice genome sequence, comparative promoter analyses now allow genome-scale detection of conserved cis-elements. Results In this study, we identified thousands of phylogenetic footprints conserved between orthologous rice and sorghum upstream regions that are supported by co-expression information derived from three different rice expression data sets. In a complementary approach, cis-motifs were discovered by their highly conserved co-occurrence in syntenic promoter pairs. Sequence conservation and matches to known plant motifs support our findings. Expression similarities of gene pairs positively correlate with the number of motifs that are shared by gene pairs and corroborate the importance of similar promoter architectures for concerted regulation. This strongly suggests that these motifs function in the regulation of transcript levels in rice and, presumably also in sorghum. Conclusion Our work provides the first large-scale collection of cis-elements for rice and sorghum and can serve as a paradigm for cis-element analysis through comparative genomics in grasses in general.

  8. Ancient Transposable Elements Transformed the Uterine Regulatory Landscape and Transcriptome during the Evolution of Mammalian Pregnancy

    Directory of Open Access Journals (Sweden)

    Vincent J. Lynch

    2015-02-01

    Full Text Available A major challenge in biology is determining how evolutionarily novel characters originate; however, mechanistic explanations for the origin of new characters are almost completely unknown. The evolution of pregnancy is an excellent system in which to study the origin of novelties because mammals preserve stages in the transition from egg laying to live birth. To determine the molecular bases of this transition, we characterized the pregnant/gravid uterine transcriptome from tetrapods to trace the evolutionary history of uterine gene expression. We show that thousands of genes evolved endometrial expression during the origins of mammalian pregnancy, including genes that mediate maternal-fetal communication and immunotolerance. Furthermore, thousands of cis-regulatory elements that mediate decidualization and cell-type identity in decidualized stromal cells are derived from ancient mammalian transposable elements (TEs. Our results indicate that one of the defining mammalian novelties evolved from DNA sequences derived from ancient mammalian TEs co-opted into hormone-responsive regulatory elements distributed throughout the genome.

  9. Finding cis-regulatory modules in Drosophila using phylogenetic hidden Markov models

    DEFF Research Database (Denmark)

    Wong, Wendy S W; Nielsen, Rasmus

    2007-01-01

    MOTIVATION: Finding the regulatory modules for transcription factors binding is an important step in elucidating the complex molecular mechanisms underlying regulation of gene expression. There are numerous methods available for solving this problem, however, very few of them take advantage of th...

  10. Confocal quantification of cis-regulatory reporter gene expression in living sea urchin.

    Science.gov (United States)

    Damle, Sagar; Hanser, Bridget; Davidson, Eric H; Fraser, Scott E

    2006-11-15

    Quantification of GFP reporter gene expression at single cell level in living sea urchin embryos can now be accomplished by a new method of confocal laser scanning microscopy (CLSM). Eggs injected with a tissue-specific GFP reporter DNA construct were grown to gastrula stage and their fluorescence recorded as a series of contiguous Z-section slices that spanned the entire embryo. To measure the depth-dependent signal decay seen in the successive slices of an image stack, the eggs were coinjected with a freely diffusible internal fluorescent standard, rhodamine dextran. The measured rhodamine fluorescence was used to generate a computational correction for the depth-dependent loss of GFP fluorescence per slice. The intensity of GFP fluorescence was converted to the number of GFP molecules using a conversion constant derived from CLSM imaging of eggs injected with a measured quantity of GFP protein. The outcome is a validated method for accurately counting GFP molecules in given cells in reporter gene transfer experiments, as we demonstrate by use of an expression construct expressed exclusively in skeletogenic cells.

  11. Identification of cis-regulatory sequences that activate transcription in the suspensor of plant embryos.

    Science.gov (United States)

    Kawashima, Tomokazu; Wang, Xingjun; Henry, Kelli F; Bi, Yuping; Weterings, Koen; Goldberg, Robert B

    2009-03-03

    Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the scarlet runner bean (Phaseolus coccineus) G564 gene to understand how genes are activated specifically within the suspensor during early embryo development. Previously, we showed that the G564 upstream region has a block of tandem repeats, which contain a conserved 10-bp motif (GAAAAG(C)/(T)GAA), and that deletion of these repeats results in a loss of suspensor transcription. Here, we use gain-of-function (GOF) experiments with transgenic globular-stage tobacco embryos to show that only 1 of the 5 tandem repeats is required to drive suspensor-specific transcription. Fine-scale deletion and scanning mutagenesis experiments with 1 tandem repeat uncovered a 54-bp region that contains all of the sequences required to activate transcription in the suspensor, including the 10-bp motif (GAAAAGCGAA) and a similar 10-bp-like motif (GAAAAACGAA). Site-directed mutagenesis and GOF experiments indicated that both the 10-bp and 10-bp-like motifs are necessary, but not sufficient to activate transcription in the suspensor, and that a sequence (TTGGT) between the 10-bp and the 10-bp-like motifs is also necessary for suspensor transcription. Together, these data identify sequences that are required to activate transcription in the suspensor of a plant embryo after fertilization.

  12. Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Marica Grskovic

    2007-08-01

    Full Text Available Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and identified genes upregulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle, and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved overrepresented motifs in genes upregulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and embryonic germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation, and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.

  13. A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.

    Directory of Open Access Journals (Sweden)

    Akiko Nakanishi

    Full Text Available Transposable elements, including short interspersed repetitive elements (SINEs, comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs, which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8. Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.

  14. Basic Finite Element Method

    International Nuclear Information System (INIS)

    Lee, Byeong Hae

    1992-02-01

    This book gives descriptions of basic finite element method, which includes basic finite element method and data, black box, writing of data, definition of VECTOR, definition of matrix, matrix and multiplication of matrix, addition of matrix, and unit matrix, conception of hardness matrix like spring power and displacement, governed equation of an elastic body, finite element method, Fortran method and programming such as composition of computer, order of programming and data card and Fortran card, finite element program and application of nonelastic problem.

  15. Evolutionary origin of Rosaceae-specific active non-autonomous hAT elements and their contribution to gene regulation and genomic structural variation.

    Science.gov (United States)

    Wang, Lu; Peng, Qian; Zhao, Jianbo; Ren, Fei; Zhou, Hui; Wang, Wei; Liao, Liao; Owiti, Albert; Jiang, Quan; Han, Yuepeng

    2016-05-01

    Transposable elements account for approximately 30 % of the Prunus genome; however, their evolutionary origin and functionality remain largely unclear. In this study, we identified a hAT transposon family, termed Moshan, in Prunus. The Moshan elements consist of three types, aMoshan, tMoshan, and mMoshan. The aMoshan and tMoshan types contain intact or truncated transposase genes, respectively, while the mMoshan type is miniature inverted-repeat transposable element (MITE). The Moshan transposons are unique to Rosaceae, and the copy numbers of different Moshan types are significantly correlated. Sequence homology analysis reveals that the mMoshan MITEs are direct deletion derivatives of the tMoshan progenitors, and one kind of mMoshan containing a MuDR-derived fragment were amplified predominately in the peach genome. The mMoshan sequences contain cis-regulatory elements that can enhance gene expression up to 100-fold. The mMoshan MITEs can serve as potential sources of micro and long noncoding RNAs. Whole-genome re-sequencing analysis indicates that mMoshan elements are highly active, and an insertion into S-haplotype-specific F-box gene was reported to cause the breakdown of self-incompatibility in sour cherry. Taken together, all these results suggest that the mMoshan elements play important roles in regulating gene expression and driving genomic structural variation in Prunus.

  16. Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs.

    Science.gov (United States)

    Singh, Narendra P; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2012-11-01

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions.

  17. Multiple uses and regulation: elements for the sustain of the water resource systems; Usos multiplos e regulacao: elementos para a sustentabilidade dos sistemas de recursos hidricos

    Energy Technology Data Exchange (ETDEWEB)

    Salles, Lauriberto S. [Secretaria de Estado de Meio Ambiente, Sao Paulo, SP (Brazil). Dept. de Uso do Solo Metropolitano; Bermann, Celio [Sao Paulo Univ., SP (Brazil). Programa Interunidades de Pos-Graduacao em Energia

    1998-12-31

    National and State water resource management plans demand new patterns of relationships between water users and the society. Regarding water resources sustainability, this work appraises some aspects of the water Committee Basins policies related to multiple water uses, within the frame of the regulatory agencies proposed. (author) 4 refs.

  18. Lentiviral vectors containing mouse Csf1r control elements direct macrophage-restricted expression in multiple species of birds and mammals

    Directory of Open Access Journals (Sweden)

    Clare Pridans

    2014-01-01

    Full Text Available The development of macrophages requires signaling through the lineage-restricted receptor Csf1r. Macrophage-restricted expression of transgenic reporters based upon Csf1r requires the highly conserved Fms-intronic regulatory element (FIRE. We have created a lentiviral construct containing mouse FIRE and promoter. The lentivirus is capable of directing macrophage-restricted reporter gene expression in mouse, rat, human, pig, cow, sheep, and even chicken. Rat bone marrow cells transduced with the lentivirus were capable of differentiating into macrophages expressing the reporter gene in vitro. Macrophage-restricted expression may be desirable for immunization or immune response modulation, and for gene therapy for lysosomal storage diseases and some immunodeficiencies. The small size of the Csf1r transcription control elements will allow the insertion of large “cargo” for applications in gene therapy and vaccine delivery.

  19. Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

    KAUST Repository

    Guturu, H.

    2013-11-11

    Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and \\'through-DNA\\' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.

  20. Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

    KAUST Repository

    Guturu, H.; Doxey, A. C.; Wenger, A. M.; Bejerano, G.

    2013-01-01

    Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and 'through-DNA' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.

  1. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.

    Science.gov (United States)

    Chuan, Yap P; Rivera-Hernandez, Tania; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Lua, Linda H L; Middelberg, Anton P J

    2013-09-01

    Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity. Copyright © 2013 Wiley Periodicals, Inc.

  2. Estrogen-dependent downregulation of hairy and enhancer of split homolog-1 gene expression in breast cancer cells is mediated via a 3' distal element.

    Science.gov (United States)

    Müller, Patrick; Merrell, Kenneth W; Crofts, Justin D; Rönnlund, Caroline; Lin, Chin-Yo; Gustafsson, Jan-Ake; Ström, Anders

    2009-03-01

    Regulation of hairy and enhancer of split homologue-1 (HES-1) by estradiol and all-trans retinoic acid affects proliferation of human breast cancer cells. Here, we identify and characterize cis-regulatory elements involved in HES-1 regulation. In the distal 5' promoter of the HES-1 gene, we found a retinoic acid response element and in the distal 3' region, an estrogen receptor alpha(ER)alpha binding site. The ERalpha binding site, composed of an estrogen response element (ERE) and an ERE half-site, is important for both ERalpha binding and transcriptional regulation. Chromatin immunoprecipitation assays revealed that ERalpha is recruited to the ERE and associates with the HES-1 promoter. We also show recruitment of nuclear receptor co-regulators to the ERE in response to estradiol, followed by a decrease in histone acetylation and RNA polymerase II docking in the HES-1 promoter region. Our findings are consistent with a novel type of repressive estrogen response element in the distal 3' region of the HES-1 gene.

  3. Degradation of YRA1 Pre-mRNA in the cytoplasm requires translational repression, multiple modular intronic elements, Edc3p, and Mex67p.

    Directory of Open Access Journals (Sweden)

    Shuyun Dong

    2010-04-01

    Full Text Available Intron-containing pre-mRNAs are normally retained and processed in the nucleus but are sometimes exported to the cytoplasm and degraded by the nonsense-mediated mRNA decay (NMD pathway as a consequence of their inclusion of intronic in-frame termination codons. When shunted to the cytoplasm by autoregulated nuclear export, the intron-containing yeast YRA1 pre-mRNA evades NMD and is targeted by a cytoplasmic decay pathway mediated by the decapping activator Edc3p. Here, we have elucidated this transcript-specific decay mechanism, showing that Edc3p-mediated YRA1 pre-mRNA degradation occurs independently of translation and is controlled through five structurally distinct but functionally interdependent modular elements in the YRA1 intron. Two of these elements target the pre-mRNA as an Edc3p substrate and the other three mediate transcript-specific translational repression. Translational repression of YRA1 pre-mRNA also requires the heterodimeric Mex67p/Mtr2p general mRNA export receptor, but not Edc3p, and serves to enhance Edc3p substrate specificity by inhibiting the susceptibility of this pre-mRNA to NMD. Collectively, our data indicate that YRA1 pre-mRNA degradation is a highly regulated process that proceeds through translational repression, substrate recognition by Edc3p, recruitment of the Dcp1p/Dcp2p decapping enzyme, and activation of decapping.

  4. Standard elements; Elements standards

    Energy Technology Data Exchange (ETDEWEB)

    Blanc, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1958-07-01

    Following his own experience the author recalls the various advantages, especially in the laboratory, of having pre-fabricated vacuum-line components at his disposal. (author) [French] A la suite de sa propre experience, l'auteur veut rappeler les divers avantages que presente, tout particulierement en laboratoire, le fait d'avoir a sa disposition des elements pre-fabriques de canalisations a vide. (auteur)

  5. CONDOR: a database resource of developmentally associated conserved non-coding elements

    Directory of Open Access Journals (Sweden)

    Smith Sarah

    2007-08-01

    Full Text Available Abstract Background Comparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators that control the expression of genes involved in the regulation of early development. The scientific community is showing increasing interest in characterizing the function, evolution and language of these sequences. Despite this, there remains little in the way of user-friendly access to a large dataset of such elements in conjunction with the analysis and the visualization tools needed to study them. Description Here we present CONDOR (COnserved Non-coDing Orthologous Regions available at: http://condor.fugu.biology.qmul.ac.uk. In an interactive and intuitive way the website displays data on > 6800 non-coding elements associated with over 120 early developmental genes and conserved across vertebrates. The database regularly incorporates results of ongoing in vivo zebrafish enhancer assays of the CNEs carried out in-house, which currently number ~100. Included and highlighted within this set are elements derived from duplication events both at the origin of vertebrates and more recently in the teleost lineage, thus providing valuable data for studying the divergence of regulatory roles between paralogs. CONDOR therefore provides a number of tools and facilities to allow scientists to progress in their own studies on the function and evolution of developmental cis-regulation. Conclusion By providing access to data with an approachable graphics interface, the CONDOR database presents a rich resource for further studies into the regulation and evolution of genes involved in early development.

  6. Location analysis for the estrogen receptor-α reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements

    Science.gov (United States)

    Mason, Christopher E.; Shu, Feng-Jue; Wang, Cheng; Session, Ryan M.; Kallen, Roland G.; Sidell, Neil; Yu, Tianwei; Liu, Mei Hui; Cheung, Edwin; Kallen, Caleb B.

    2010-01-01

    Location analysis for estrogen receptor-α (ERα)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERα-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: ERE sequence. We demonstrate that ∼50% of all ERα-bound loci do not have a discernable ERE and show that most ERα-bound EREs are not perfect consensus EREs. Approximately one-third of all ERα-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERα-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERα binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers. PMID:20047966

  7. Location analysis for the estrogen receptor-alpha reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements.

    Science.gov (United States)

    Mason, Christopher E; Shu, Feng-Jue; Wang, Cheng; Session, Ryan M; Kallen, Roland G; Sidell, Neil; Yu, Tianwei; Liu, Mei Hui; Cheung, Edwin; Kallen, Caleb B

    2010-04-01

    Location analysis for estrogen receptor-alpha (ERalpha)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERalpha-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: ERE sequence. We demonstrate that approximately 50% of all ERalpha-bound loci do not have a discernable ERE and show that most ERalpha-bound EREs are not perfect consensus EREs. Approximately one-third of all ERalpha-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERalpha-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERalpha binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers.

  8. Multiple element isotope probes, NanoSIMS, and the functional genomics of microbial carbon cycling in soils in response to chronic climatic change

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, Bruce; Pett-Ridge, Jennifer; Blazewicz, Steven; Blazewicz, Steven; Schwartz, Egbert; Dijkstra, Paul

    2018-03-24

    In this project, we developed an innovative and ground-breaking technique, quantitative stable isotope probing, a technique that uses density separation of nucleic acids as a quantitative measurement technique. This work is substantial because it advances SIP beyond the qualitative technique that has dominate the field for years. The first methods paper was published in Applied and Environmental Microbiology (Hungate et al. 2015), and this paper describes the mathematical model underlying the quantitative interpretation. A second methods paper (Schwartz et al. 2015) provides a conceptual overview of the method and its application to research problems. A third methods paper was just published (Koch et al. 2018), in which we develop the quantitative model combining sequencing and isotope data to estimate actual rates of microbial growth and death in natural populations. This work has met much enthusiasm in scientific presentations around the world. It has met with equally enthusiastic resistance in the peer-review process, though our record of publication to date argues that people are accepting the merits of the approach. The skepticism and resistance are also potentially signs that this technique is pushing the field forward, albeit with some of the discomfort that accompanies extrapolation. Part of this is a cultural element in the field – the field of microbiology is not accustomed to the assumptions of ecosystem science. Research conducted in this project has pushed the philosophical perspective that major advances can occur when we advocate a sound merger between the traditions of strong inference in microbiology with those of grounded scaling in ecosystem science.

  9. Galvanic element. Galvanisches Element

    Energy Technology Data Exchange (ETDEWEB)

    Sprengel, D.; Haelbig, H.

    1980-01-03

    The invention concerns a gas-tight sealed accumulator with positive and negative electrode plates and an auxillary electrode electroconductively bound to the latter for suppressing oxygen pressure. The auxillary electrode is an intermediate film electrode. The film catalysing oxygen reduction is hydrophilic in character and the other film is hydrophobic. A double coated foil has proved to be advantageous, the hydrophilic film being formed from polymer-bound activated carbon and the hydrophrobic film from porous polytetrafluoroethylene. A metallic network of silver or nickel is rolled into the outer side of the activated carbon film. This auxillary electrode can be used to advantage in all galvanic elements. Even primary cells fall within the scope of application for auxillary electrodes because many of these contain a highly oxidized electrodic material which tends to give off oxygen.

  10. Quantification of elemental area densities in multiple metal layers (Au/Ni/Cu) on a Cr-coated quartz glass substrate for certification of NMIJ CRM 5208-a.

    Science.gov (United States)

    Ariga, Tomoko; Zhu, Yanbei; Ito, Mika; Takatsuka, Toshiko; Terauchi, Shinya; Kurokawa, Akira; Inagaki, Kazumi

    2018-04-01

    Area densities of Au/Ni/Cu layers on a Cr-coated quartz substrate were characterized to certify a multiple-metal-layer certified reference material (NMIJ CRM5208-a) that is intended for use in the analysis of the layer area density and the thickness by an X-ray fluorescence spectrometer. The area densities of Au/Ni/Cu layers were calculated from layer mass amounts and area. The layer mass amounts were determined by using wet chemical analyses, namely inductively coupled plasma mass spectrometry (ICP-MS), isotope-dilution (ID-) ICP-MS, and inductively coupled plasma optical emission spectrometry (ICP-OES) after dissolving the layers with diluted mixture of HCl and HNO 3 (1:1, v/v). Analytical results of the layer mass amounts obtained by the methods agreed well with each another within their uncertainty ranges. The area of the layer was determined by using a high-resolution optical scanner calibrated by Japan Calibration Service System (JCSS) standard scales. The property values of area density were 1.84 ± 0.05 μg/mm 2 for Au, 8.69 ± 0.17 μg/mm 2 for Ni, and 8.80 ± 0.14 μg/mm 2 for Cu (mean ± expanded uncertainty, coverage factor k = 2). In order to assess the reliability of these values, the density of each metal layer calculated from the property values of the area density and layer thickness measured by using a scanning electron microscope were compared with available literature values and good agreement between the observed values and values obtained in previous studies.

  11. Molecular characterization of a rice mutator-phenotype derived from an incompatible cross-pollination reveals transgenerational mobilization of multiple transposable elements and extensive epigenetic instability

    Directory of Open Access Journals (Sweden)

    Xu Chunming

    2009-05-01

    Full Text Available Abstract Background Inter-specific hybridization occurs frequently in plants, which may induce genetic and epigenetic instabilities in the resultant hybrids, allopolyploids and introgressants. It remains unclear however whether pollination by alien pollens of an incompatible species may impose a "biological stress" even in the absence of genome-merger or genetic introgression, whereby genetic and/or epigenetic instability of the maternal recipient genome might be provoked. Results We report here the identification of a rice mutator-phenotype from a set of rice plants derived from a crossing experiment involving two remote and apparently incompatible species, Oryza sativa L. and Oenothera biennis L. The mutator-phenotype (named Tong211-LP showed distinct alteration in several traits, with the most striking being substantially enlarged panicles. Expectably, gel-blotting by total genomic DNA of the pollen-donor showed no evidence for introgression. Characterization of Tong211-LP (S0 and its selfed progenies (S1 ruled out contamination (via seed or pollen or polyploidy as a cause for its dramatic phenotypic changes, but revealed transgenerational mobilization of several previously characterized transposable elements (TEs, including a MITE (mPing, and three LTR retrotransposons (Osr7, Osr23 and Tos17. AFLP and MSAP fingerprinting revealed extensive, transgenerational alterations in cytosine methylation and to a less extent also genetic variation in Tong211-LP and its immediate progenies. mPing mobility was found to correlate with cytosine methylation alteration detected by MSAP but not with genetic variation detected by AFLP. Assay by q-RT-PCR of the steady-state transcript abundance of a set of genes encoding for the various putative DNA methyltransferases, 5-methylcytosine DNA glycosylases, and small interference RNA (siRNA pathway-related proteins showed that, relative to the rice parental line, heritable perturbation in expression of 12 out of

  12. Characterization of a hypoxia-response element in the Epo locus of the pufferfish, Takifugu rubripes.

    Science.gov (United States)

    Kulkarni, Rashmi P; Tohari, Sumanty; Ho, Adrian; Brenner, Sydney; Venkatesh, Byrappa

    2010-06-01

    Animals respond to hypoxia by increasing synthesis of the glycoprotein hormone erythropoietin (Epo) which in turn stimulates the production of red blood cells. The gene encoding Epo has been recently cloned in teleost fishes such as the pufferfish Takifugu rubripes (fugu) and zebrafish (Danio rerio). It has been shown that the transcription levels of Epo in teleost fishes increase in response to anemia or hypoxia in a manner similar to its human ortholog. However, the cis-regulatory element(s) mediating the hypoxia response of Epo gene in fishes has not been identified. In the present study, using the human hepatoma cell line (Hep3B), we have identified and characterized a hypoxia response element (HRE) in the fugu Epo locus. The sequence of the fugu HRE (ACGTGCTG) is identical to that of the HRE in the human EPO locus. However, unlike the HRE in the mammalian Epo locus, which is located in the 3' region of the gene, the fugu HRE is located in the 5' flanking region and on the opposite strand of DNA. This HRE is conserved in other teleosts such as Tetraodon and zebrafish in a similar location. A 365-bp fragment containing the fugu HRE was able to drive GFP expression in the liver of transgenic zebrafish. However, we could not ascertain if the expression of transgene is induced by hypoxia in vivo due to the low and variable levels of GFP expression in transgenic zebrafish. Our investigations also revealed that the Epo locus has experienced extensive rearrangements during vertebrate evolution. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

    Science.gov (United States)

    Benko, Sabina; Fantes, Judy A; Amiel, Jeanne; Kleinjan, Dirk-Jan; Thomas, Sophie; Ramsay, Jacqueline; Jamshidi, Negar; Essafi, Abdelkader; Heaney, Simon; Gordon, Christopher T; McBride, David; Golzio, Christelle; Fisher, Malcolm; Perry, Paul; Abadie, Véronique; Ayuso, Carmen; Holder-Espinasse, Muriel; Kilpatrick, Nicky; Lees, Melissa M; Picard, Arnaud; Temple, I Karen; Thomas, Paul; Vazquez, Marie-Paule; Vekemans, Michel; Roest Crollius, Hugues; Hastie, Nicholas D; Munnich, Arnold; Etchevers, Heather C; Pelet, Anna; Farlie, Peter G; Fitzpatrick, David R; Lyonnet, Stanislas

    2009-03-01

    Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

  14. A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements

    Directory of Open Access Journals (Sweden)

    Hicks Chindo

    2010-01-01

    Full Text Available Abstract Background Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We have developed a new tool (SpliceScan II for predicting the effects of genetic variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5'GC splice site (SS sensor used in our tool allows inference on non-canonical exons. Results Our tool performed favorably when compared with the existing methods in the context of genes linked to the Autism Spectrum Disorder (ASD. SpliceScan II was able to predict more aberrant splicing isoforms triggered by the mutations, as documented in DBASS5 and DBASS3 aberrant splicing databases, than other existing methods. Detrimental effects behind some of the polymorphic variations previously associated with Alzheimer's and breast cancer could be explained by changes in predicted splicing patterns. Conclusions We have developed SpliceScan II, an effective and sensitive tool for predicting the detrimental effects of genomic variants on splicing leading to Mendelian and complex hereditary disorders. The method could potentially be used to screen resequenced patient DNA to identify de novo mutations and polymorphic variants that could contribute to a genetic disorder.

  15. Characterization of a Suppressive Cis-acting Element in the Epstein–Barr Virus LMP1 Promoter

    Directory of Open Access Journals (Sweden)

    Masahiro Yoshida

    2017-11-01

    Full Text Available Latent membrane protein 1 (LMP1 is a major oncogene encoded by Epstein–Barr virus (EBV and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited increased LMP1 expression and EBV-mediated immortalization of B cells. However, single mutations of either the E-box or Ikaros sites had limited effects on LMP1 expression and transformation. Our results suggest that this region contains a suppressive cis-regulatory element, but other transcriptional repressors (apart from the E-box and Ikaros transcription factors may remain to be discovered.

  16. Multiple cis-acting elements involved in up-regulation of a cytochrome P450 gene conferring resistance to deltamethrin in smal brown planthopper, Laodelphax striatellus (Fallén).

    Science.gov (United States)

    Pu, Jian; Sun, Haina; Wang, Jinda; Wu, Min; Wang, Kangxu; Denholm, Ian; Han, Zhaojun

    2016-11-01

    As well as arising from single point mutations in binding sites or detoxifying enzymes, it is likely that insecticide resistance mechanisms are frequently controlled by multiple genetic factors, resulting in resistance being inherited as a quantitative trait. However, empirical evidence for this is still rare. Here we analyse the causes of up-regulation of CYP6FU1, a monoxygenase implicated in resistance to deltamethrin in the rice pest Laodelphax striatellus. The 5'-flanking region of this gene was cloned and sequenced from individuals of a susceptible and a resistant strain. A luminescent reporter assay was used to evaluate different 5'-flanking regions and their fragments for promoter activity. Mutations enhancing promoter activity in various fragments were characterized, singly and in combination, by site mutation recovery. Nucleotide diversity in flanking sequences was greatly reduced in deltamethrin-resistant insects compared to susceptible ones. Phylogenetic sequence analysis found that CYP6FU1 had five different types of 5'-flanking region. All five types were present in a susceptible strain but only a single type showing the highest promoter activity was present in a resistant strain. Four cis-acting elements were identified whose influence on up-regulation was much more pronounced in combination than when present singly. Of these, two were new transcription factor (TF) binding sites produced by mutations, another one was also a new TF binding site alternated from an existing one, and the fourth was a unique transcription start site. These results demonstrate that multiple cis-acting elements are involved in up-regulating CYP6FU1 to generate a resistance phenotype. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Quantitative analysis of polycomb response elements (PREs at identical genomic locations distinguishes contributions of PRE sequence and genomic environment

    Directory of Open Access Journals (Sweden)

    Okulski Helena

    2011-03-01

    Full Text Available Abstract Background Polycomb/Trithorax response elements (PREs are cis-regulatory elements essential for the regulation of several hundred developmentally important genes. However, the precise sequence requirements for PRE function are not fully understood, and it is also unclear whether these elements all function in a similar manner. Drosophila PRE reporter assays typically rely on random integration by P-element insertion, but PREs are extremely sensitive to genomic position. Results We adapted the ΦC31 site-specific integration tool to enable systematic quantitative comparison of PREs and sequence variants at identical genomic locations. In this adaptation, a miniwhite (mw reporter in combination with eye-pigment analysis gives a quantitative readout of PRE function. We compared the Hox PRE Frontabdominal-7 (Fab-7 with a PRE from the vestigial (vg gene at four landing sites. The analysis revealed that the Fab-7 and vg PREs have fundamentally different properties, both in terms of their interaction with the genomic environment at each site and their inherent silencing abilities. Furthermore, we used the ΦC31 tool to examine the effect of deletions and mutations in the vg PRE, identifying a 106 bp region containing a previously predicted motif (GTGT that is essential for silencing. Conclusions This analysis showed that different PREs have quantifiably different properties, and that changes in as few as four base pairs have profound effects on PRE function, thus illustrating the power and sensitivity of ΦC31 site-specific integration as a tool for the rapid and quantitative dissection of elements of PRE design.

  18. Efeito do tipo de elemento de rosca na degradação de polipropileno durante múltiplas extrusões Effect of screw element on the polypropylene degradation during multiple extrusions

    Directory of Open Access Journals (Sweden)

    Ana Clélia Babetto

    2000-06-01

    Full Text Available A configuração da rosca de uma extrusora de dupla rosca modular pode ser projetada com vários tipos de elementos de condução e mistura, produzindo diferentes níveis de degradação no polímero fundido. Neste trabalho determinou-se o nível de degradação do polipropileno durante múltiplas extrusões em várias configurações de rosca, através de cromatografia por exclusão de tamanho e espectroscopia de infravermelho. Houve decréscimo do peso molecular e estreitamento da sua distribuição em função do número de extrusões e do aumento da agressividade da rosca, assim como, aumento da concentração de carbonilas e insaturações na cadeia polimérica. O elemento de mistura EM90 causou o maior nível de degradação e a adição de elementos de condução esquerdos ECE reduziram o nível de degradação.The screw configuration of a double screw extruder can be designed to contain kneading and conveying elements inducing different levels of degradation in the polymer melt. In this work the level of degradation in polypropylene have been measured after multiple extrusions for various screw configurations using Size Exclusion Chromatography and Infra-Red Spectroscopy. The average molecular weight and the polydispersity are reduced and the carbonyl and unsaturation indices increase as the number of extrusions and the agressiveness of the screw increase. The kneading element with 90 degrees caused the greater level of degradation and the addition of left hand elements have reduced the level of degradation.

  19. The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes.

    Science.gov (United States)

    Koh, Kyunghee; Bernstein, Yelena; Sundaram, Meera V

    2004-03-01

    egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors essential for viability, seam cell development, and vulval development in Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1 vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1 breakpoint on LGIV is located within approximately 800 bp upstream of a potential transcriptional start site of egl-18. In addition, we have identified a approximately 350-bp cis-regulatory region sufficient for vulval expression just upstream of the nT1 breakpoint. By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development.

  20. Nuclear fuel element

    International Nuclear Information System (INIS)

    Grossman, L.N.; Levin, H.A.

    1975-01-01

    A nuclear fuel element has disposed therein an alloy having the essential components of nickel, titanium and zirconium, and the alloy reacts with water, water vapor and reactive gases at reactor ambient temperatures. The alloy is disposed in the plenum of the fuel element in the form of particles in a hollow gas permeable container having a multiplicity of openings of size smallr than the size of the particles. The container is preferably held in the spring in the plenum of the fuel element. (E.C.B.)

  1. REDfly: a Regulatory Element Database for Drosophila.

    Science.gov (United States)

    Gallo, Steven M; Li, Long; Hu, Zihua; Halfon, Marc S

    2006-02-01

    Bioinformatics studies of transcriptional regulation in the metazoa are significantly hindered by the absence of readily available data on large numbers of transcriptional cis-regulatory modules (CRMs). Even the richly annotated Drosophila melanogaster genome lacks extensive CRM information. We therefore present here a database of Drosophila CRMs curated from the literature complete with both DNA sequence and a searchable description of the gene expression pattern regulated by each CRM. This resource should greatly facilitate the development of computational approaches to CRM discovery as well as bioinformatics analyses of regulatory sequence properties and evolution.

  2. Element Distribution and Multiplicity of Heavy Fragments

    CERN Multimedia

    2002-01-01

    This experiment will measure the energy and angular distribution of heavy fragments produced in the reactions of |1|2C on several targets between |2|7Al and |2|3|8U at 86~MeV/u. The systematic investigation of a highly excited interaction region (fireball) by means of a clean N and Z identification of heavy tar fragments, may result in a better understanding of temperature concept and of the degree of equilibration of the local interaction region with respect to the total system. For this investigation a large-area position sensitive ionization chamber of 50~msr solid angle in conjunction with a time-of-flight telescope consisting of parallel-plate detectors will be used. \\\\ \\\\ In order to get information on the transverse momentum transfer and the inelasticity of the collision, the energy of the PROJECTILE-FRAGMENTS will be measured at forward angles with a plastic scintillator hodoscope. In addition to this inclusive measurement correlations between heavy fragments will be investigated by means of three pos...

  3. Transplutonium elements

    Energy Technology Data Exchange (ETDEWEB)

    Sivaramakrishnan, C. K.; Jadhav, A. V.; Reghuraman, K.; Mathew, K. A.; Nair, P. S.; Ramaniah, M. V.

    1973-07-01

    Research progress is reported on studies of the transplutonium elements including recovery and purification of americium, preparation of /sup 238/Pu, extraction studies using diethylhexyl phosphate. (DHM)

  4. Contributions to multiple element speciation in vegetable plants: Studies on the type of bonding of numerous elements, particularly zinc and cadmium; Beitraege zur Multielement-Speziation in pflanzlichen Lebensmitteln: Studien zur Bindungsform zahlreicher Elemente unter besonderer Beruecksichtigung von Zink und Cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, K.

    1997-03-01

    In the first part of the study, the total contents and the solubility characteristics of Zn, Cd, Fe, Mn, Cu, Ca, Sr, K and Rb in 26 different vegetable plants, the majority of them commercially available, are reported, obtained by post-decomposition analyses. The data are given for avocados, bananas, cauliflower, chicory, Chinese cabbage, dill, ice lettuce (two specimens), endive, field salad, cucumbers, kohlrabi, lettuce, chard beet, carrots, peppers, leek, radish, red cabbage, loose leaved lettuce, celery (two specimens), spinach, topinambur, white cabbage, and parsley. Cell decomposition was done by treatment of the plant material with an electric dispersing apparatus (Ultra-Turrax) in buffer solution (liquid shearing). The homogenates were separated into supernatants (cytosoles)and pellets by means of centrifugation. Cell decomposition of the plants by crushing with quartz sand after lyophilization (solid shearing) required much more technical effort and for some elements created problems with the blind values. At least 50% on the average of the elements Zn, Cd, Rb, and K could be transferred to the solutions by the dispersing treatment with Ultra-Turrax. In many cases, the cytosole-borne detectable contents of these 5 elements were above 70%. The solubility of Zn and Cd was more strongly dependent on the plant species than that of Cu, Rb, and K. All five elements thus can be analysed by conventional methods for further enhanced speciation. Mn, Ca, and especially Fe and Sr for the most part were found to be bonded to solid cell constituents. However, the solubility characteristics of Ca and Mn and Sr in particular was very homogeneous. In some plants, the contents of Mn and Sr in the cytosoles was approx. 90%, so that comprehensive speciation of these elements is possible. (orig./AJ) [Deutsch] Im ersten Teil dieser Studie wurden die Gesamtgehalte und das Loeslichkeitsverhalten von Zn, Cd, Fe, Mn, Cu, Ca, Sr, K und Rb in 26 verschiedenen - ueberwiegend

  5. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors to h...

  6. Two estrogen response element sequences near the PCNA gene are not responsible for its estrogen-enhanced expression in MCF7 cells.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available The proliferating cell nuclear antigen (PCNA is an essential component of DNA replication, cell cycle regulation, and epigenetic inheritance. High expression of PCNA is associated with poor prognosis in patients with breast cancer. The 5'-region of the PCNA gene contains two computationally-detected estrogen response element (ERE sequences, one of which is evolutionarily conserved. Both of these sequences are of undocumented cis-regulatory function. We recently demonstrated that estradiol (E2 enhances PCNA mRNA expression in MCF7 breast cancer cells. MCF7 cells proliferate in response to E2.Here, we demonstrate that E2 rapidly enhanced PCNA mRNA and protein expression in a process that requires ERalpha as well as de novo protein synthesis. One of the two upstream ERE sequences was specifically bound by ERalpha-containing protein complexes, in vitro, in gel shift analysis. Yet, each ERE sequence, when cloned as a single copy, or when engineered as two tandem copies of the ERE-containing sequence, was not capable of activating a luciferase reporter construct in response to E2. In MCF7 cells, neither ERE-containing genomic region demonstrated E2-dependent recruitment of ERalpha by sensitive ChIP-PCR assays.We conclude that E2 enhances PCNA gene expression by an indirect process and that computational detection of EREs, even when evolutionarily conserved and when near E2-responsive genes, requires biochemical validation.

  7. Two estrogen response element sequences near the PCNA gene are not responsible for its estrogen-enhanced expression in MCF7 cells.

    Science.gov (United States)

    Wang, Cheng; Yu, Jie; Kallen, Caleb B

    2008-01-01

    The proliferating cell nuclear antigen (PCNA) is an essential component of DNA replication, cell cycle regulation, and epigenetic inheritance. High expression of PCNA is associated with poor prognosis in patients with breast cancer. The 5'-region of the PCNA gene contains two computationally-detected estrogen response element (ERE) sequences, one of which is evolutionarily conserved. Both of these sequences are of undocumented cis-regulatory function. We recently demonstrated that estradiol (E2) enhances PCNA mRNA expression in MCF7 breast cancer cells. MCF7 cells proliferate in response to E2. Here, we demonstrate that E2 rapidly enhanced PCNA mRNA and protein expression in a process that requires ERalpha as well as de novo protein synthesis. One of the two upstream ERE sequences was specifically bound by ERalpha-containing protein complexes, in vitro, in gel shift analysis. Yet, each ERE sequence, when cloned as a single copy, or when engineered as two tandem copies of the ERE-containing sequence, was not capable of activating a luciferase reporter construct in response to E2. In MCF7 cells, neither ERE-containing genomic region demonstrated E2-dependent recruitment of ERalpha by sensitive ChIP-PCR assays. We conclude that E2 enhances PCNA gene expression by an indirect process and that computational detection of EREs, even when evolutionarily conserved and when near E2-responsive genes, requires biochemical validation.

  8. Estrogen receptor β (ERβ1) transactivation is differentially modulated by the transcriptional coregulator Tip60 in a cis-acting element-dependent manner.

    Science.gov (United States)

    Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

    2013-08-30

    Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1.

  9. Elements of linear space

    CERN Document Server

    Amir-Moez, A R; Sneddon, I N

    1962-01-01

    Elements of Linear Space is a detailed treatment of the elements of linear spaces, including real spaces with no more than three dimensions and complex n-dimensional spaces. The geometry of conic sections and quadric surfaces is considered, along with algebraic structures, especially vector spaces and transformations. Problems drawn from various branches of geometry are given.Comprised of 12 chapters, this volume begins with an introduction to real Euclidean space, followed by a discussion on linear transformations and matrices. The addition and multiplication of transformations and matrices a

  10. Fuel element

    International Nuclear Information System (INIS)

    Armijo, J.S.

    1976-01-01

    A fuel element for nuclear reactors is proposed which has a higher corrosion resisting quality in reactor operations. The zirconium alloy coating around the fuel element (uranium or plutonium compound) has on its inside a protection layer of metal which is metallurgically bound to the substance of the coating. As materials are namned: Alluminium, copper, niobium, stainless steel, and iron. This protective metallic layer has another inner layer, also metallurgically bound to its surface, which consists usually of a zirconium alloy. (UWI) [de

  11. Spread of ISCR1 Elements Containing blaDHA-1 and Multiple Antimicrobial Resistance Genes Leading to Increase of Flomoxef Resistance in Extended-Spectrum-β-Lactamase-Producing Klebsiella pneumoniae▿

    Science.gov (United States)

    Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

    2011-01-01

    Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6′)-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6′)-Ib-cr, armA, and blaDHA-1 were all identified on these self-transferable blaCTX-M-carrying plasmids. The genetic environments of ISCR1 associated with armA, blaDHA-1, and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study. PMID:21746945

  12. Spread of ISCR1 elements containing blaDHA-₁ and multiple antimicrobial resistance genes leading to increase of flomoxef resistance in extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae.

    Science.gov (United States)

    Lee, Chen-Hsiang; Liu, Jien-Wei; Li, Chia-Chin; Chien, Chun-Chih; Tang, Ya-Fen; Su, Lin-Hui

    2011-09-01

    Increasing resistance to quinolones, aminoglycosides, and/or cephamycins in extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae exacerbates the already limited antibiotic treatment options for infections due to these microbes. In this study, the presence of resistance determinants for these antimicrobial agents was examined by PCR among ESBL-producing Klebsiella pneumoniae (ESBL-KP) isolates that caused bacteremia. Pulsed-field gel electrophoresis was used to differentiate the clonal relationship among the isolates studied. Transferability and the location of the resistance genes were analyzed by conjugation experiments, followed by DNA-DNA hybridization. Among the 94 ESBL-KP isolates studied, 20 isolates of flomoxef-resistant ESBL-KP were identified. They all carried a DHA-1 gene and were genetically diverse. CTX-M genes were found in 18 of the isolates. Among these DHA-1/CTX-M-producing K. pneumoniae isolates, ISCR1 was detected in 13 (72%) isolates, qnr genes (1 qnrA and 17 qnrB genes) were detected in 18 (100%), aac(6')-Ib-cr was detected in 11 (61%), and 16S rRNA methylase (all armA genes) was detected in 14 (78%). Four transconjugants were available for further analysis, and qnrB4, aac(6')-Ib-cr, armA, and bla(DHA-1) were all identified on these self-transferable bla(CTX-M)-carrying plasmids. The genetic environments of ISCR1 associated with armA, bla(DHA-1), and qnrB4 genes in the four transconjugants were identical. Replicon-type analysis revealed a FIIA plasmid among the four self-transferable plasmids, although the other three were nontypeable. The cotransfer of multiple resistance genes with the ISCR1 element-carrying plasmids has a clinical impact and warrants close monitoring and further study.

  13. Nuclear fuel element

    International Nuclear Information System (INIS)

    Penrose, R.T.; Thompson, J.R.

    1976-01-01

    A method of protecting the cladding of a nuclear fuel element from internal attack and a nuclear fuel element for use in the core of a nuclear reactor are disclosed. The nuclear fuel element has disposed therein an additive of a barium-containing material and the barium-containing material collects reactive gases through chemical reaction or adsorption at temperatures ranging from room temperature up to fuel element plenum temperatures. The additive is located in the plenum of the fuel element and preferably in the form of particles in a hollow container having a multiplicity of gas permeable openings in one portion of the container with the openings being of a size smaller than the size of the particles. The openings permit gases and liquids entering the plenum to contact the particles. The additive is comprised of elemental barium or a barium alloy containing one or more metals in addition to barium such as aluminum, zirconium, nickel, titanium and combinations thereof. 6 claims, 3 drawing figures

  14. Transplutonium elements - a literature survey

    International Nuclear Information System (INIS)

    Sivaramakrishnan, C.K.; Jadhav, A.V.

    1974-01-01

    The report surveys reported work on the discovery of transplutonium elements and their production through various methods like bombardment of heavy elements with charged ions, successive neutron captures on heavy elements in reactors and multiple neutron captures by heavy elements during nuclear explosions. Estimated yields of transplutonium elements in special targets irradiated in reactors, and also as byproducts from spent power reactor fuels are quoted. Various chemical procedures adopted for recovery of these elements from irradiated target and also from power reactor fuel reprocessing streams are described. A brief survey of shielded facilities available at various centres for transplutonium programmes is also included. Major uses of some of these heavy elements are described. (author)

  15. PELTIER ELEMENTS

    CERN Document Server

    Tani, Laurits

    2015-01-01

    To control Peltier elements, temperature controller was used. I used TEC-1091 that was manufactured my Meerstetter Engineering. To gain control with the temperature controller, software had to be intalled on a controlling PC. There were different modes to control the Peltier: Tempererature controller to control temperature, Static current/voltage to control voltage and current and LIVE ON/OFF to auto-tune the controller respectively to the system. Also, since near the collision pipe there is much radiation, radiation-proof Peltier elements have to be used. To gain the best results, I had to find the most efficient Peltier elements and try to get their cold side to -40 degrees Celsius.

  16. Multiple Functional Variants in cis Modulate PDYN Expression.

    Science.gov (United States)

    Babbitt, Courtney C; Silverman, Jesse S; Haygood, Ralph; Reininga, Jennifer M; Rockman, Matthew V; Wray, Gregory A

    2010-02-01

    Understanding genetic variation and its functional consequences within cis-regulatory regions remains an important challenge in human genetics and evolution. Here, we present a fine-scale functional analysis of segregating variation within the cis-regulatory region of prodynorphin, a gene that encodes an endogenous opioid precursor with roles in cognition and disease. In order to characterize the functional consequences of segregating variation in cis in a region under balancing selection in different human populations, we examined associations between specific polymorphisms and gene expression in vivo and in vitro. We identified five polymorphisms within the 5' flanking region that affect transcript abundance: a 68-bp repeat recognized in prior studies, as well as two microsatellites and two single nucleotide polymorphisms not previously implicated as functional variants. The impact of these variants on transcription differs by brain region, sex, and cell type, implying interactions between cis genotype and the differentiated state of cells. The effects of individual variants on expression level are not additive in some combinations, implying epistatic interactions between nearby variants. These data reveal an unexpectedly complex relationship between segregating genetic variation and its expression-trait consequences and highlights the importance of close functional scrutiny of natural genetic variation within even relatively well-studied cis-regulatory regions.

  17. Fuel element

    International Nuclear Information System (INIS)

    Kennedy, S.T.

    1982-01-01

    A nuclear reactor fuel element wherein a stack of nuclear fuel is prevented from displacement within its sheath by a retainer comprising a tube member which is radially expanded into frictional contact with the sheath by means of a captive ball within a tapered bore. (author)

  18. Transactinide elements

    International Nuclear Information System (INIS)

    Hemingway, J.D.

    1975-01-01

    The review is covered in sections, entitled: predicted nuclear properties - including closed shells, decay characteristics; predicted chemical properties - including electronic structure and calculated properties, X-radiation, extrapolated chemical properties, separation chemistry; methods of synthesis; the natural occurrence of superheavy elements. (U.K.)

  19. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.

    Directory of Open Access Journals (Sweden)

    Alexandra C Nica

    2011-02-01

    Full Text Available While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL, skin, and fat. The samples (156 LCL, 160 skin, 166 fat were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes. In addition, we apply factor analysis (FA to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes. The unique study design (Matched Co-Twin Analysis--MCTA permits immediate replication of eQTLs using co-twins (93%-98% and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20% have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.

  20. Multiple Perspectives / Multiple Readings

    Directory of Open Access Journals (Sweden)

    Simon Biggs

    2005-01-01

    Full Text Available People experience things from their own physical point of view. What they see is usually a function of where they are and what physical attitude they adopt relative to the subject. With augmented vision (periscopes, mirrors, remote cameras, etc we are able to see things from places where we are not present. With time-shifting technologies, such as the video recorder, we can also see things from the past; a time and a place we may never have visited.In recent artistic work I have been exploring the implications of digital technology, interactivity and internet connectivity that allow people to not so much space/time-shift their visual experience of things but rather see what happens when everybody is simultaneously able to see what everybody else can see. This is extrapolated through the remote networking of sites that are actual installation spaces; where the physical movements of viewers in the space generate multiple perspectives, linked to other similar sites at remote locations or to other viewers entering the shared data-space through a web based version of the work.This text explores the processes involved in such a practice and reflects on related questions regarding the non-singularity of being and the sense of self as linked to time and place.

  1. New elements

    International Nuclear Information System (INIS)

    Flerov, G.

    1976-01-01

    The history is briefly described of the investigation of superheavy elements at the Joint Institute for Nuclear Research at Dubna. The significance of the investigation is assessed from the point of view of the nuclear structure study and major problems encountered in experimental efforts are indicated. Current experimental methods aiming at the discovery or the production of superheavy nuclei with Z approximately 114 are listed. (I.W.)

  2. Murine homeobox-containing gene, Msx-1: analysis of genomic organization, promoter structure, and potential autoregulatory cis-acting elements.

    Science.gov (United States)

    Kuzuoka, M; Takahashi, T; Guron, C; Raghow, R

    1994-05-01

    Detailed molecular organization of the coding and upstream regulatory regions of the murine homeodomain-containing gene, Msx-1, is reported. The protein-encoding portion of the gene is contained in two exons, 590 and 1214 bp in length, separated by a 2107-bp intron; the homeodomain is located in the second exon. The two-exon organization of the murine Msx-1 gene resembles a number of other homeodomain-containing genes. The 5'-(GTAAGT) and 3'-(CCCTAG) splicing junctions and the mRNA polyadenylation signal (UAUAA) of the murine Msx-1 gene are also characteristic of other vertebrate genes. By nuclease protection and primer extension assays, the start of transcription of the Msx-1 gene was located 256 bp upstream of the first AUG. Computer analysis of the promoter proximal 1280-bp sequence revealed a number of potentially important cis-regulatory sequences; these include the recognition elements for Ap-1, Ap-2, Ap-3, Sp-1, a possible binding site for RAR:RXR, and a number of TCF-1 consensus motifs. Importantly, a perfect reverse complement of (C/G)TTAATTG, which was recently shown to be an optimal binding sequence for the homeodomain of Msx-1 protein (K.M. Catron, N. Iler, and C. Abate (1993) Mol. Cell. Biol. 13:2354-2365), was also located in the murine Msx-1 promoter. Binding of bacterially expressed Msx-1 homeodomain polypeptide to Msx-1-specific oligonucleotide was experimentally demonstrated, raising a distinct possibility of autoregulation of this developmentally regulated gene.

  3. Chromatin Heterogeneity and Distribution of Regulatory Elements in the Late-Replicating Intercalary Heterochromatin Domains of Drosophila melanogaster Chromosomes.

    Directory of Open Access Journals (Sweden)

    Varvara A Khoroshko

    Full Text Available Late-replicating domains (intercalary heterochromatin in the Drosophila genome display a number of features suggesting their organization is quite unique. Typically, they are quite large and encompass clusters of functionally unrelated tissue-specific genes. They correspond to the topologically associating domains and conserved microsynteny blocks. Our study aims at exploring further details of molecular organization of intercalary heterochromatin and has uncovered surprising heterogeneity of chromatin composition in these regions. Using the 4HMM model developed in our group earlier, intercalary heterochromatin regions were found to host chromatin fragments with a particular epigenetic profile. Aquamarine chromatin fragments (spanning 0.67% of late-replicating regions are characterized as a class of sequences that appear heterogeneous in terms of their decompactization. These fragments are enriched with enhancer sequences and binding sites for insulator proteins. They likely mark the chromatin state that is related to the binding of cis-regulatory proteins. Malachite chromatin fragments (11% of late-replicating regions appear to function as universal transitional regions between two contrasting chromatin states. Namely, they invariably delimit intercalary heterochromatin regions from the adjacent active chromatin of interbands. Malachite fragments also flank aquamarine fragments embedded in the repressed chromatin of late-replicating regions. Significant enrichment of insulator proteins CP190, SU(HW, and MOD2.2 was observed in malachite chromatin. Neither aquamarine nor malachite chromatin types appear to correlate with the positions of highly conserved non-coding elements (HCNE that are typically replete in intercalary heterochromatin. Malachite chromatin found on the flanks of intercalary heterochromatin regions tends to replicate earlier than the malachite chromatin embedded in intercalary heterochromatin. In other words, there exists a

  4. Radiographic element

    International Nuclear Information System (INIS)

    Abbott, T.I.; Jones, C.G.

    1984-01-01

    Radiographic elements are disclosed comprised of first and second silver halide emulsion layers separated by an interposed support capable of transmitting radiation to which the second image portion is responsive. At least the first imaging portion contains a silver halide emulsion in which thin tubular silver halide grains of intermediate aspect ratios (from 5:1 to 8:1) are present. Spectral sensitizing dye is adsorbed to the surface of the tubular grains. Increased photographic speeds can be realized at comparable levels of crossover. (author)

  5. Superheavy elements

    CERN Document Server

    Hofmann, S

    1999-01-01

    The outstanding aim of experimental investigations of heavy nuclei is the exploration of spherical 'SuperHeavy Elements' (SHEs). On the basis of the nuclear shell model, the next double magic shell-closure beyond sup 2 sup 0 sup 8 Pb is predicted at proton numbers between Z=114 and 126 and at neutron number N=184. All experimental efforts aiming at identifying SHEs (Z>=114) were negative so far. A highly sensitive search experiment was performed in November-December 1995 at SHIP. The isotope sup 2 sup 9 sup 0 116 produced by 'radiative capture' was searched for in the course of a 33 days irradiation of a sup 2 sup 0 sup 8 Pb target with sup 8 sup 2 Se projectiles, however, only cross-section limits were measured. Positive results were obtained in experiments searching for elements from 110 to 112 using cold fusion and the 1n evaporation channel. The produced isotopes were unambiguously identified by means of alpha-alpha correlations. Not fission, but alpha emission is the dominant decay mode. The measurement ...

  6. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  7. Nuclear fuel element

    International Nuclear Information System (INIS)

    1974-01-01

    A nuclear fuel element for use in the core of a nuclear reactor is disclosed. A heat conducting fission product retaining metal liner of a refractory metal is incorporated in the fuel element between the cladding and the nuclear fuel to inhibit mechanical interaction between the nuclear fuel and the cladding, to isolate fission products and nuclear fuel impurities from contacting the cladding, and to improve the axial thermal peaking gradient along the length of the fuel rod. The metal liner can be in the form of a tube or hollow cylindrical column, a foil of single or multiple layers in the shape of a hollow cylindrical column, or a coating on the internal surface of the cladding. Preferred refractory metal materials are molybdenum, tungsten, rhenium, niobium and alloys of the foregoing metals

  8. Nuclear fuel element

    International Nuclear Information System (INIS)

    Thompson, J.R.; Rowland, T.C.

    1976-01-01

    A nuclear fuel element for use in the core of a nuclear reactor is disclosed. A heat conducting, fission product retaining metal liner of a refractory metal is incorporated in the fuel element between the cladding and the nuclear fuel to inhibit mechanical interaction between the nuclear fuel and the cladding, to isolate fission products and nuclear fuel impurities from contacting the cladding and to improve the axial thermal peaking gradient along the length of the fuel rod. The metal liner can be in the form of a tube or hollow cylindrical column, a foil of single or multiple layers in the shape of a hollow cylindrical column, or a coating on the internal surface of the cladding. Preferred refractory metal materials are molybdenum, tungsten, rhenium, niobium and alloys of the foregoing metals

  9. Fuel element

    International Nuclear Information System (INIS)

    Hirose, Yasuo.

    1982-01-01

    Purpose: To increase the plenum space in a fuel element used for a liquid metal cooled reactor. Constitution: A fuel pellet is secured at one end with an end plug and at the other with a coil spring in a tubular container. A mechanism for fixing the coil spring composed of a tubular unit is mounted by friction with the inner surface of the tubular container. Accordingly, the recoiling force of the coil spring can be retained by fixing mechanism with a small volume, and since a large amount of plenum space can be obtained, the internal pressure rise in the cladding tube can be suppressed even if large quantities of fission products are discharged. (Kamimura, M.)

  10. MULTIPLE OBJECTS

    Directory of Open Access Journals (Sweden)

    A. A. Bosov

    2015-04-01

    Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

  11. Genome-wide analysis of ABA-responsive elements ABRE and CE3 reveals divergent patterns in Arabidopsis and rice

    Directory of Open Access Journals (Sweden)

    Riaño-Pachón Diego

    2007-08-01

    Full Text Available Abstract Background In plants, complex regulatory mechanisms are at the core of physiological and developmental processes. The phytohormone abscisic acid (ABA is involved in the regulation of various such processes, including stomatal closure, seed and bud dormancy, and physiological responses to cold, drought and salinity stress. The underlying tissue or plant-wide control circuits often include combinatorial gene regulatory mechanisms and networks that we are only beginning to unravel with the help of new molecular tools. The increasing availability of genomic sequences and gene expression data enables us to dissect ABA regulatory mechanisms at the individual gene expression level. In this paper we used an in-silico-based approach directed towards genome-wide prediction and identification of specific features of ABA-responsive elements. In particular we analysed the genome-wide occurrence and positional arrangements of two well-described ABA-responsive cis-regulatory elements (CREs, ABRE and CE3, in thale cress (Arabidopsis thaliana and rice (Oryza sativa. Results Our results show that Arabidopsis and rice use the ABA-responsive elements ABRE and CE3 distinctively. Earlier reports for various monocots have identified CE3 as a coupling element (CE associated with ABRE. Surprisingly, we found that while ABRE is equally abundant in both species, CE3 is practically absent in Arabidopsis. ABRE-ABRE pairs are common in both genomes, suggesting that these can form functional ABA-responsive complexes (ABRCs in Arabidopsis and rice. Furthermore, we detected distinct combinations, orientation patterns and DNA strand preferences of ABRE and CE3 motifs in rice gene promoters. Conclusion Our computational analyses revealed distinct recruitment patterns of ABA-responsive CREs in upstream sequences of Arabidopsis and rice. The apparent absence of CE3s in Arabidopsis suggests that another CE pairs with ABRE to establish a functional ABRC capable of

  12. Genome-wide analysis of ABA-responsive elements ABRE and CE3 reveals divergent patterns in Arabidopsis and rice.

    Science.gov (United States)

    Gómez-Porras, Judith L; Riaño-Pachón, Diego Mauricio; Dreyer, Ingo; Mayer, Jorge E; Mueller-Roeber, Bernd

    2007-08-01

    In plants, complex regulatory mechanisms are at the core of physiological and developmental processes. The phytohormone abscisic acid (ABA) is involved in the regulation of various such processes, including stomatal closure, seed and bud dormancy, and physiological responses to cold, drought and salinity stress. The underlying tissue or plant-wide control circuits often include combinatorial gene regulatory mechanisms and networks that we are only beginning to unravel with the help of new molecular tools. The increasing availability of genomic sequences and gene expression data enables us to dissect ABA regulatory mechanisms at the individual gene expression level. In this paper we used an in-silico-based approach directed towards genome-wide prediction and identification of specific features of ABA-responsive elements. In particular we analysed the genome-wide occurrence and positional arrangements of two well-described ABA-responsive cis-regulatory elements (CREs), ABRE and CE3, in thale cress (Arabidopsis thaliana) and rice (Oryza sativa). Our results show that Arabidopsis and rice use the ABA-responsive elements ABRE and CE3 distinctively. Earlier reports for various monocots have identified CE3 as a coupling element (CE) associated with ABRE. Surprisingly, we found that while ABRE is equally abundant in both species, CE3 is practically absent in Arabidopsis. ABRE-ABRE pairs are common in both genomes, suggesting that these can form functional ABA-responsive complexes (ABRCs) in Arabidopsis and rice. Furthermore, we detected distinct combinations, orientation patterns and DNA strand preferences of ABRE and CE3 motifs in rice gene promoters. Our computational analyses revealed distinct recruitment patterns of ABA-responsive CREs in upstream sequences of Arabidopsis and rice. The apparent absence of CE3s in Arabidopsis suggests that another CE pairs with ABRE to establish a functional ABRC capable of interacting with transcription factors. Further studies will be

  13. Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

    NARCIS (Netherlands)

    C. Nepal (Chirag); Y. Hadzhiev (Yavor); C. Previti (Christopher); V. Haberle (Vanja); N. Li (Nan); H. Takahashi (Hiroyuki); A.M. Suzuki (Ana Maria); Y. Sheng (Ying); R.F. Abdelhamid (Rehab); S. Anand (Santosh); P.A. Gehrig (Paola A.); A. Akalin (Altuna); C. Kockx (Christel); A. Van Der Sloot (Antoine); W.F.J. van IJcken (Wilfred); O. Armant (Olivier); S. Rastegar (Sepand); C. Watson (Craig); U. Strähle (Uwe); E. Stupka (Elia); P. Carninci (Piero); B. Lenhard (Boris); F. Müller (Ferenc)

    2013-01-01

    textabstractSpatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we

  14. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  15. Multiple homicides.

    Science.gov (United States)

    Copeland, A R

    1989-09-01

    A study of multiple homicides or multiple deaths involving a solitary incident of violence by another individual was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during 1983-1987. A total of 107 multiple homicides were studied: 88 double, 17 triple, one quadruple, and one quintuple. The 236 victims were analyzed regarding age, race, sex, cause of death, toxicologic data, perpetrator, locale of the incident, and reason for the incident. This article compares this type of slaying with other types of homicide including those perpetrated by serial killers. Suggestions for future research in this field are offered.

  16. Estrogen Receptor β (ERβ1) Transactivation Is Differentially Modulated by the Transcriptional Coregulator Tip60 in a cis-Acting Element-dependent Manner*

    Science.gov (United States)

    Lee, Ming-Tsung; Leung, Yuet-Kin; Chung, Irving; Tarapore, Pheruza; Ho, Shuk-Mei

    2013-01-01

    Estrogen receptor (ER) β1 and ERα have overlapping and distinct functions despite their common use of estradiol as the physiological ligand. These attributes are explained in part by their differential utilization of coregulators and ligands. Although Tip60 has been shown to interact with both receptors, its regulatory role in ERβ1 transactivation has not been defined. In this study, we found that Tip60 enhances transactivation of ERβ1 at the AP-1 site but suppresses its transcriptional activity at the estrogen-response element (ERE) site in an estradiol-independent manner. However, different estrogenic compounds can modify the Tip60 action. The corepressor activity of Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and bisphenol A, whereas its coactivation at the AP-1 site is augmented by fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at the AP-1 site. We found that coexpression of GRIP1 synergizes the action of Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate ERβ1, and its coregulatory functions are independent of its acetylation activity. In addition, we showed the co-occupancy of ERβ1 and Tip60 at ERE and AP-1 sites of ERβ1 target genes. Tip60 differentially regulates the endogenous expression of the target genes by modulating the binding of ERβ1 to the cis-regulatory regions. Thus, we have identified Tip60 as the first dual-function coregulator of ERβ1. PMID:23857583

  17. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  18. Multiple myeloma.

    LENUS (Irish Health Repository)

    Collins, Conor D

    2012-02-01

    Advances in the imaging and treatment of multiple myeloma have occurred over the past decade. This article summarises the current status and highlights how an understanding of both is necessary for optimum management.

  19. Multiple mononeuropathy

    Science.gov (United States)

    ... with multiple mononeuropathy are prone to new nerve injuries at pressure points such as the knees and elbows. They should avoid putting pressure on these areas, for example, by not leaning on the elbows, crossing the knees, ...

  20. Identification of two evolutionarily conserved 5' cis-elements involved in regulating spatiotemporal expression of Nolz-1 during mouse embryogenesis.

    Directory of Open Access Journals (Sweden)

    Sunny Li-Yun Chang

    Full Text Available Proper development of vertebrate embryos depends not only on the crucial funtions of key evolutionarily conserved transcriptional regulators, but also on the precisely spatiotemporal expression of these transcriptional regulators. The mouse Nolz-1/Znf503/Zfp503 gene is a mammalian member of the conserved zinc-finger containing NET family. The expression pattern of Nolz-1 in mouse embryos is highly correlated with that of its homologues in different species. To study the spatiotemporal regulation of Nolz-1, we first identified two evolutionarily conserved cis-elements, UREA and UREB, in 5' upstream regions of mouse Nolz-1 locus. We then generated UREA-LacZ and UREB-LacZ transgenic reporter mice to characterize the putative enhancer activity of UREA and UREB. The results indicated that both UREA and UREB contained tissue-specific enhancer activity for directing LacZ expression in selective tissue organs during mouse embryogensis. UREA directed LacZ expression preferentially in selective regions of developing central nervous system, including the forebrain, hindbrain and spinal cord, whereas UREB directed LacZ expression mainly in other developing tissue organs such as the Nolz-1 expressing branchial arches and its derivatives, the apical ectodermal ridge of limb buds and the urogenital tissues. Both UREA and UREB directed strong LacZ expression in the lateral plate mesoderm where endogenous Nolz-1 was also expressed. Despite that the LacZ expression pattern did not full recapitulated the endogenous Nolz-1 expression and some mismatched expression patterns were observed, co-expression of LacZ and Nolz-1 did occur in many cells of selective tissue organs, such as in the ventrolateral cortex and ventral spinal cord of UREA-LacZ embryos, and the urogenital tubes of UREB-LacZ embryos. Taken together, our study suggests that UREA and UREB may function as evolutionarily conserved cis-regulatory elements that coordinate with other cis-elements to regulate

  1. [Multiple meningiomas].

    Science.gov (United States)

    Terrier, L-M; François, P

    2016-06-01

    Multiple meningiomas (MMs) or meningiomatosis are defined by the presence of at least 2 lesions that appear simultaneously or not, at different intracranial locations, without the association of neurofibromatosis. They present 1-9 % of meningiomas with a female predominance. The occurrence of multiple meningiomas is not clear. There are 2 main hypotheses for their development, one that supports the independent evolution of these tumors and the other, completely opposite, that suggests the propagation of tumor cells of a unique clone transformation, through cerebrospinal fluid. NF2 gene mutation is an important intrinsic risk factor in the etiology of multiple meningiomas and some exogenous risk factors have been suspected but only ionizing radiation exposure has been proven. These tumors can grow anywhere in the skull but they are more frequently observed in supratentorial locations. Their histologic types are similar to unique meningiomas of psammomatous, fibroblastic, meningothelial or transitional type and in most cases are benign tumors. The prognosis of these tumors is eventually good and does not differ from the unique tumors except for the cases of radiation-induced multiple meningiomas, in the context of NF2 or when diagnosed in children where the outcome is less favorable. Each meningioma lesion should be dealt with individually and their multiple character should not justify their resection at all costs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. K-shell x-ray production cross sections of selected elements Al to Ni for 4. 0 to 38. 0 MeV /sup 10/B ions. [Cross sections, 4. 0 to 38 MeV, binding energy, electron capture decay, PWBA, energy shifts, multiple ionization

    Energy Technology Data Exchange (ETDEWEB)

    Monigold, G.; McDaniel, F.D.; Duggan, J.L.; Mehta, R.; Rice, R.; Miller, P.D.

    1976-01-01

    K-Shell x-ray production cross sections for the target elements Sc, Ti, V, Mn, Fe, Co, and Ni were measured for incident /sup 10/B ions over the energy range 4.0 to 38.0 MeV. The cross section data were compared to the theoretical predictions of the binary encounter approximation (BEA); the plane wave born approximation (PWBA); and the PWBA modified to include corrections for increased binding energy (B), Coulomb deflection of the incident ion (C), orbital perturbation due to polarization (P), and relativistic effects (R). In addition, fluorescence yield variations (W/sub K/) and contributions to the cross sections from electron capture (EC) were included. It was found that the predictions of the fully modified PWBA with contributions from electron capture and fluorescence yield variations included provided the best fit to the experimental data over the entire energy range for each target element. The K..beta../K..cap alpha.. x-ray intensity ratios were compared to theoretical values that assume single hole ionization, and the x-ray energy shifts presented as a function of the energy of the incident ion. These two measurements provided confirmation of the occurrence of multiple ionization for /sup 10/B bombardment of target elements in the range 21 less than or equal to Z/sub 2/ less than or equal to 28.

  3. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  4. Multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Jeong Ick; Ha, Choon Ho; Choi, Karp Shik

    1994-01-01

    Multiple myeloma is a malignant plasma cell tumor that is thought to originate proliferation of a single clone of abnormal plasma cell resulting production of a whole monoclonal paraprotein. The authors experienced a case of multiple myeloma with severe mandibular osteolytic lesions in 46-year-old female. As a result of careful analysis of clinical, radiological, histopathological features, and laboratory findings, we diagnosed it as multiple myeloma, and the following results were obtained. 1. Main clinical symptoms were intermittent dull pain on the mandibular body area, abnormal sensation of lip and pain due to the fracture on the right clavicle. 2. Laboratory findings revealed M-spike, reversed serum albumin-globulin ratio, markedly elevated ESR and hypercalcemia. 3. Radiographically, multiple osteolytic punched-out radiolucencies were evident on the skull, zygoma, jaw bones, ribs, clavicle and upper extremities. Enlarged liver and increased uptakes on the lesional sites in RN scan were also observed. 4. Histopathologically, markedly hypercellular marrow with sheets of plasmoblasts and megakaryocytes were also observed.

  5. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  6. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  7. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  8. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  9. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  10. Parenting Multiples

    Science.gov (United States)

    ... when your babies do. Though it can be hard to let go of the thousand other things you need to do, remember that your well-being is key to your ability to take care of your babies. What Problems Can Happen? It may be hard to tell multiple babies apart when they first ...

  11. Treatment of Cognitive Impairment in Multiple Sclerosis

    OpenAIRE

    Pierson, Susan H.; Griffith, Nathan

    2006-01-01

    Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the co...

  12. System and method for image registration of multiple video streams

    Science.gov (United States)

    Dillavou, Marcus W.; Shum, Phillip Corey; Guthrie, Baron L.; Shenai, Mahesh B.; Deaton, Drew Steven; May, Matthew Benton

    2018-02-06

    Provided herein are methods and systems for image registration from multiple sources. A method for image registration includes rendering a common field of interest that reflects a presence of a plurality of elements, wherein at least one of the elements is a remote element located remotely from another of the elements and updating the common field of interest such that the presence of the at least one of the elements is registered relative to another of the elements.

  13. Multiple photon resonances

    International Nuclear Information System (INIS)

    Elliott, C.J.; Feldman, B.J.

    1979-02-01

    A detailed theoretical analysis is presented of the interaction of intense near-resonant monochromatic radiation with an N-level anharmonic oscillator. In particular, the phenomenon of multiple photon resonance, the process by which an N-level system resonantly absorbs two or more photons simultaneously, is investigated. Starting from the Schroedinger equation, diagrammatic techniques are developed that allow the resonant process to be analyzed quantitatively, in analogy with well-known two-level coherent phenomena. In addition, multiple photon Stark shifts of the resonances, shifts absent in two-level theory, are obtained from the diagrams. Insights into the nature of multiple photon resonances are gained by comparing the quantum mechanical system with classical coupled pendulums whose equations of motion possess identical eigenvalues and eigenvectors. In certain limiting cases, including that of the resonantly excited N-level harmonic oscillator and that of the equally spaced N-level system with equal matrix elements, analytic results are derived. The influence of population relaxation and phase-disrupting collisions on the multiple photon process are also analyzed, the latter by extension of the diagrammatic technique to the density matrix equations of motion. 11 figures

  14. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  15. Discrete Element Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Morris, J; Johnson, S

    2007-12-03

    The Distinct Element Method (also frequently referred to as the Discrete Element Method) (DEM) is a Lagrangian numerical technique where the computational domain consists of discrete solid elements which interact via compliant contacts. This can be contrasted with Finite Element Methods where the computational domain is assumed to represent a continuum (although many modern implementations of the FEM can accommodate some Distinct Element capabilities). Often the terms Discrete Element Method and Distinct Element Method are used interchangeably in the literature, although Cundall and Hart (1992) suggested that Discrete Element Methods should be a more inclusive term covering Distinct Element Methods, Displacement Discontinuity Analysis and Modal Methods. In this work, DEM specifically refers to the Distinct Element Method, where the discrete elements interact via compliant contacts, in contrast with Displacement Discontinuity Analysis where the contacts are rigid and all compliance is taken up by the adjacent intact material.

  16. Chemistry of the elements

    International Nuclear Information System (INIS)

    Greenwood, N.N.; Earnshaw, A.

    1984-01-01

    This textbook presents an account of the chemistry of the elements for both undergraduate and postgraduate students. It covers not only the 'inorganic' chemistry of the elements, but also analytical, theoretical, industrial, organometallic;, bio-inorganic and other areas of chemistry which apply. The following elements of special nuclear interest are included: Rb, Cs, Fr, Sr, Ba, Ra, Po, At, Rn, Sc, Y, Zr, Hf, V, Nb, Ta, Mo, Tc, Ru, the Lanthanide Elements, the Actinide Elements. (U.K.)

  17. Multiple inflation

    International Nuclear Information System (INIS)

    Murphy, P.J.

    1987-01-01

    The Theory of Inflation, namely, that at some point the entropy content of the universe was greatly increased, has much promise. It may solve the puzzles of homogeneity and the creation of structure. However, no particle physics model has yet been found that can successfully drive inflation. The difficulty in satisfying the constraint that the isotropy of the microwave background places on the effective potential of prospective models is immense. In this work we have codified the requirements of such models in a most general form. We have carefully calculated the amounts of inflation the various problems of the Standard Model need for their solution. We have derived a completely model independent upper bond on the inflationary Hubble parameter. We have developed a general notation with which to probe the possibilities of Multiple Inflation. We have shown that only in very unlikely circumstances will any evidence of an earlier inflation, survive the de Sitter period of its successor. In particular, it is demonstrated that it is most unlikely that two bouts of inflation will yield high amplitudes of density perturbations on small scales and low amplitudes on large. We conclude that, while multiple inflation will be of great theoretical interest, it is unlikely to have any observational impact

  18. Treatment of Cognitive Impairment in Multiple Sclerosis

    Science.gov (United States)

    Pierson, Susan H.; Griffith, Nathan

    2006-01-01

    Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

  19. Data Element Registry Services

    Data.gov (United States)

    U.S. Environmental Protection Agency — Data Element Registry Services (DERS) is a resource for information about value lists (aka code sets / pick lists), data dictionaries, data elements, and EPA data...

  20. A Code Division Technique for Multiple Element Synthetic Aperture Transmission

    DEFF Research Database (Denmark)

    Gran, Fredrik; Jensen, Jørgen Arendt; Jakobsson, Andreas

    2004-01-01

    a method in which all transmitting centers can be excited at the same time and separated at the receiver. Hereby the benefits from traditional STA can be utilized and a high fframe rate can be maintained and the images are not influenced by motion artifacts. The different centers are excited using mutually...

  1. Radiolabelled cellular blood elements

    International Nuclear Information System (INIS)

    Sinzinger, H.

    1990-01-01

    This book reports on radiolabelled cellular blood elements, covering new advances made during the past several years, in particular the use of Tc-99 as a tracer for blood elements. Coverage extends to several radiolabelled monoclonal antibodies that are specific for blood components and may label blood elements in vivo

  2. Concentration of stable elements in food products

    International Nuclear Information System (INIS)

    Montford, M.A.; Shank, K.E.; Hendricks, C.; Oakes, T.W.

    1980-01-01

    Food samples were taken from commercial markets and analyzed for stable element content. The concentrations of most stable elements (Ag, Al, As, Au, Ba, Br, Ca, Ce, Cl, Co, Cr, Cs, Cu, Fe, Hf, I, K, La, Mg, Mn, Mo, Na, Rb, Sb, Sc, Se, Sr, Ta, Th, Ti, V, Zn, Zr) were determined using multiple-element neutron activation analysis, while the concentrations of other elements (Cd, Hg, Ni, Pb) were determined using atomic absorption. The relevance of the concentrations found are noted in relation to other literature values. An earlier study was extended to include the determination of the concentration of stable elements in home-grown products in the vicinity of the Oak Ridge National Laboratory. Comparisons between the commercial and local food-stuff values are discussed

  3. Tissue- and stage-specific Wnt target gene expression is controlled subsequent to beta-catenin recruitment to cis-regulatory modules

    NARCIS (Netherlands)

    Nakamura, Y.; de Paiva Alves, E.; Veenstra, G.J.C.; Hoppler, S.

    2016-01-01

    Key signalling pathways, such as canonical Wnt/beta-catenin signalling, operate repeatedly to regulate tissue- and stage-specific transcriptional responses during development. Although recruitment of nuclear beta-catenin to target genomic loci serves as the hallmark of canonical Wnt signalling,

  4. Identification, occurrence, and validation of DRE and ABRE Cis-regulatory motifs in the promoter regions of genes of Arabidopsis thaliana.

    Science.gov (United States)

    Mishra, Sonal; Shukla, Aparna; Upadhyay, Swati; Sanchita; Sharma, Pooja; Singh, Seema; Phukan, Ujjal J; Meena, Abha; Khan, Feroz; Tripathi, Vineeta; Shukla, Rakesh Kumar; Shrama, Ashok

    2014-04-01

    Plants posses a complex co-regulatory network which helps them to elicit a response under diverse adverse conditions. We used an in silico approach to identify the genes with both DRE and ABRE motifs in their promoter regions in Arabidopsis thaliana. Our results showed that Arabidopsis contains a set of 2,052 genes with ABRE and DRE motifs in their promoter regions. Approximately 72% or more of the total predicted 2,052 genes had a gap distance of less than 400 bp between DRE and ABRE motifs. For positional orientation of the DRE and ABRE motifs, we found that the DR form (one in direct and the other one in reverse orientation) was more prevalent than other forms. These predicted 2,052 genes include 155 transcription factors. Using microarray data from The Arabidopsis Information Resource (TAIR) database, we present 44 transcription factors out of 155 which are upregulated by more than twofold in response to osmotic stress and ABA treatment. Fifty-one transcripts from the one predicted above were validated using semiquantitative expression analysis to support the microarray data in TAIR. Taken together, we report a set of genes containing both DRE and ABRE motifs in their promoter regions in A. thaliana, which can be useful to understand the role of ABA under osmotic stress condition. © 2013 Institute of Botany, Chinese Academy of Sciences.

  5. Rare (Earth Elements [score

    Directory of Open Access Journals (Sweden)

    Camilo Méndez

    2014-12-01

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

  6. Generalized finite elements

    International Nuclear Information System (INIS)

    Wachspress, E.

    2009-01-01

    Triangles and rectangles are the ubiquitous elements in finite element studies. Only these elements admit polynomial basis functions. Rational functions provide a basis for elements having any number of straight and curved sides. Numerical complexities initially associated with rational bases precluded extensive use. Recent analysis has reduced these difficulties and programs have been written to illustrate effectiveness. Although incorporation in major finite element software requires considerable effort, there are advantages in some applications which warrant implementation. An outline of the basic theory and of recent innovations is presented here. (authors)

  7. Elements beyond uranium

    International Nuclear Information System (INIS)

    Seaborg, G.T.; Loveland, W.D.

    1990-01-01

    This book is the 12th volume in a series on transuranium elements. Varied techniques for production of these elements, the methods used in the identification, and the exquisitely refined microchemical techniques required to deal wth samples sometimes involving only a few atoms are described in detail. The chapter on synthesis of the new elements is liberally laced with reminiscences of the proud progenitors as well as the criteria for the discovery of a new chemical element. The authors lament that the superheavy elements (elements in the region of atomic number 114) still elude detection even though their creation should be possible, and some, at least, should survive long enough to be detected. One chapter in the book is devoted to practical applictions of uranium, and the transuranic elements

  8. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Science.gov (United States)

    Fauteux, François; Strömvik, Martina V

    2009-01-01

    Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

  9. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Directory of Open Access Journals (Sweden)

    Fauteux François

    2009-10-01

    Full Text Available Abstract Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP gene promoters from three plant families, namely Brassicaceae (mustards, Fabaceae (legumes and Poaceae (grasses using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L. Heynh., soybean (Glycine max (L. Merr. and rice (Oryza sativa L. respectively. We have identified three conserved motifs (two RY-like and one ACGT-like in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination

  10. Limitless Analytic Elements

    Science.gov (United States)

    Strack, O. D. L.

    2018-02-01

    We present equations for new limitless analytic line elements. These elements possess a virtually unlimited number of degrees of freedom. We apply these new limitless analytic elements to head-specified boundaries and to problems with inhomogeneities in hydraulic conductivity. Applications of these new analytic elements to practical problems involving head-specified boundaries require the solution of a very large number of equations. To make the new elements useful in practice, an efficient iterative scheme is required. We present an improved version of the scheme presented by Bandilla et al. (2007), based on the application of Cauchy integrals. The limitless analytic elements are useful when modeling strings of elements, rivers for example, where local conditions are difficult to model, e.g., when a well is close to a river. The solution of such problems is facilitated by increasing the order of the elements to obtain a good solution. This makes it unnecessary to resort to dividing the element in question into many smaller elements to obtain a satisfactory solution.

  11. The solar element

    DEFF Research Database (Denmark)

    Kragh, Helge

    2009-01-01

    of the nineteenth century. In the modest form of a yellow spectral line known as D3, 'helium' was sometimes supposed to exist in the Sun's atmosphere, an idea which is traditionally ascribed to J. Norman Lockyer. Did Lockyer discover helium as a solar element? How was the suggestion received by chemists, physicists...... and astronomers in the period until the spring of 1895, when William Ramsay serendipitously found the gas in uranium minerals? The hypothetical element helium was fairly well known, yet Ramsay's discovery owed little or nothing to Lockyer's solar element. Indeed, for a brief while it was thought that the two...... elements might be different. The complex story of how helium became established as both a solar and terrestrial element involves precise observations as well as airy speculations. It is a story that is unique among the discovery histories of the chemical elements....

  12. The synthetic elements

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.C.

    1990-05-01

    Prior to 1940, the heaviest element known was uranium, discovered in 1789. Since that time the elements 93 through 109 have been synthesized and identified and the elements 43, 61, 85, and 87 which were missing form the periodic tables of the 1930's have been discovered. The techniques and problems involved in these discoveries and the placement of the transuranium elements in the periodic table will be discussed. The production and positive identification of elements heavier than Md (Z=101), which have very short half-lives and can only be produced an atom-at-a-time, are very difficult and there have been controversies concerning their discovery. Some of the new methods which have been developed and used in these studies will be described. The prospects for production of still heavier elements will be considered.

  13. The synthetic elements

    International Nuclear Information System (INIS)

    Hoffman, D.C.

    1990-05-01

    Prior to 1940, the heaviest element known was uranium, discovered in 1789. Since that time the elements 93 through 109 have been synthesized and identified and the elements 43, 61, 85, and 87 which were missing form the periodic tables of the 1930's have been discovered. The techniques and problems involved in these discoveries and the placement of the transuranium elements in the periodic table will be discussed. The production and positive identification of elements heavier than Md (Z=101), which have very short half-lives and can only be produced an atom-at-a-time, are very difficult and there have been controversies concerning their discovery. Some of the new methods which have been developed and used in these studies will be described. The prospects for production of still heavier elements will be considered

  14. Fuel element loading system

    International Nuclear Information System (INIS)

    Arya, S.P; s.

    1978-01-01

    A nuclear fuel element loading system is described which conveys a plurality of fuel rods to longitudinal passages in fuel elements. Conveyor means successively position the fuel rods above the longitudinal passages in axial alignment therewith and adapter means guide the fuel rods from the conveyor means into the longitudinal passages. The fuel elements are vibrated to cause the fuel rods to fall into the longitudinal passages through the adapter means

  15. Elements in biological AMS

    International Nuclear Information System (INIS)

    Vogel, J.S.; McAninch, J.; Freeman, S.

    1996-08-01

    AMS (Accelerator Mass Spectrometry) provides high detection sensitivity for isotopes whose half-lives are between 10 years and 100 million years. 14 C is the most developed of such isotopes and is used in tracing natural and anthropogenic organic compounds in the Earth's biosphere. Thirty-three elements in the main periodic table and 17 lanthanides or actinides have long lived isotopes, providing potential tracers for research in elemental biochemistry. Overlap of biologically interesting heavy elements and possible AMS tracers is discussed

  16. Analogs for transuranic elements

    International Nuclear Information System (INIS)

    Weimer, W.C.; Laul, J.C.; Kutt, J.C.

    1981-01-01

    A combined theoretical and experimental approach is being used to estimate the long-term environmental and biogeochemical behaviors of selected transuranic elements. The objective of this research is to estimate the effect that long-term (hundreds of years) environmental weathering has on the behavior of the transuranic elements americium and curium. This is achieved by investigating the actual behavior of naturally occurring rare earth elements, especially neodymium, that serve as transuranic analogs. Determination of the analog element behavior provides data that can be used to estimate the ultimate availability to man of transuranic materials released into the environment

  17. Chemistry of superheavy elements

    International Nuclear Information System (INIS)

    Schaedel, M.

    2012-01-01

    The chemistry of superheavy elements - or transactinides from their position in the Periodic Table - is summarized. After giving an overview over historical developments, nuclear aspects about synthesis of neutron-rich isotopes of these elements, produced in hot-fusion reactions, and their nuclear decay properties are briefly mentioned. Specific requirements to cope with the one-atom-at-a-time situation in automated chemical separations and recent developments in aqueous-phase and gas-phase chemistry are presented. Exciting, current developments, first applications, and future prospects of chemical separations behind physical recoil separators ('pre-separator') are discussed in detail. The status of our current knowledge about the chemistry of rutherfordium (Rf, element 104), dubnium (Db, element 105), seaborgium (Sg, element 106), bohrium (Bh, element 107), hassium (Hs, element 108), copernicium (Cn, element 112), and element 114 is discussed from an experimental point of view. Recent results are emphasized and compared with empirical extrapolations and with fully-relativistic theoretical calculations, especially also under the aspect of the architecture of the Periodic Table. (orig.)

  18. Seagrass leaf element content

    NARCIS (Netherlands)

    Vonk, J.A.; Smulders, Fee O.H.; Christianen, Marjolijn J.A.; Govers, Laura L.

    2017-01-01

    Knowledge on the role of seagrass leaf elements and in particular micronutrients and their ranges is limited. We present a global database, consisting of 1126 unique leaf values for ten elements, obtained from literature and unpublished data, spanning 25 different seagrass species from 28 countries.

  19. Berkeley new element program

    International Nuclear Information System (INIS)

    Ghiorso, A.

    1975-09-01

    The work done with element 106 is reviewed, and a new experiment which bears on the properties of the isotope of mass 260 with atomic number 104 is discussed. It is noted that in the case of element 106 a link is demonstrated to the granddaughter as well as the daughter

  20. Elemental Food for Thought

    Science.gov (United States)

    Cady, Susan

    2005-01-01

    One of the first tasks students learn in chemistry is to pronounce and spell the names of elements and learn their corresponding chemical symbols. Repetitive oral recitation is commonly used to learn this information, but games and puzzles can make this task creative, variable, and fun. Elemental Food for Thought is a puzzlelike activity that…

  1. Nuclear fuel element

    International Nuclear Information System (INIS)

    Mogard, J.H.

    1977-01-01

    A nuclear fuel element is disclosed for use in power producing nuclear reactors, comprising a plurality of axially aligned ceramic cylindrical fuel bodies of the sintered type, and a cladding tube of metal or metal alloys, wherein said cladding tube on its cylindrical inner surface is provided with a plurality of slightly protruding spacing elements distributed over said inner surface

  2. Proceedings of transuranium elements

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The identification of the first synthetic elements was established by chemical evidence. Conclusive proof of the synthesis of the first artificial element, technetium, was published in 1937 by Perrier and Segre. An essential aspect of their achievement was the prediction of the chemical properties of element 43, which had been missing from the periodic table and which was expected to have properties similar to those of manganese and rhenium. The discovery of other artificial elements, astatine and francium, was facilitated in 1939-1940 by the prediction of their chemical properties. A little more than 50 years ago, in the spring of 1940, Edwin McMillan and Philip Abelson synthesized element 93, neptunium, and confirmed its uniqueness by chemical means. On August 30, 1940, Glenn Seaborg, Arthur Wahl, and the late Joseph Kennedy began their neutron irradiations of uranium nitrate hexahydrate. A few months later they synthesized element 94, later named plutonium, by observing the alpha particles emitted from uranium oxide targets that had been bombarded with deuterons. Shortly thereafter they proved that is was the second transuranium element by establishing its unique oxidation-reduction behavior. The symposium honored the scientists and engineers whose vision and dedication led to the discovery of the transuranium elements and to the understanding of the influence of 5f electrons on their electronic structure and bonding. This volume represents a record of papers presented at the symposium

  3. Multiple Input - Multiple Output (MIMO) SAR

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  4. Ten key elements for implementing interprofessional learning in ...

    African Journals Online (AJOL)

    This paper discusses 10 key elements for the design and implementation of interprofessional education (IPE) in a skills centre. The elements are based on published literature as well as on the experience of an IPE initiative, simulating the management of a multiple-traumatised patient in the acute and rehabilitation phases, ...

  5. Discovery of element 112

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, S. [GSI, Darmstadt (Germany)

    1996-12-31

    The new elements 110, 111, and 112 were synthesized and unambiguously identified in experiments at SHIP. Due to strong shell effects the dominant decay mode is not fission, but emission of alpha particles. Theoretical investigations predict that maximum shell effects should exist in nuclei near proton number 114 and neutron number 184. Measurements give hope that isotopes of element 114 close to the island of spherical Superheavy Elements could be produced by fusion reactions using {sup 118}Pb as target. systematic studies of the reaction cross-sections indicate that transfer of nucleons is the important process to initiate the fusion.

  6. Elemental diffusion in stars

    International Nuclear Information System (INIS)

    Michaud, Georges; Montmerle, Thierry

    1977-01-01

    This paper is dealing with the origin of the elements in the universe. The scheme of nucleosynthesis is kept to explain the stellar generation of helium, carbon, etc... from the initial hydrogen; but a nonlinear theory is then elaborated to account for the anomalous abundances which were observed. The chemical elements would diffuse throughout the outer layers of a star under the action of the opposite forces of gravitation and radiation. This theory, with completing the nucleosynthesis, would contribute to give a consistent scheme of the elemental origin and abundances [fr

  7. Bridge element deterioration rates.

    Science.gov (United States)

    2008-10-01

    This report describes the development of bridge element deterioration rates using the NYSDOT : bridge inspection database using Markov chains and Weibull-based approaches. It is observed : that Weibull-based approach is more reliable for developing b...

  8. 2. Transuranic elements

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    Methods of sample collection, sample storage, sample procedures and radioanalytical procedures for transuranic elements in marine environment are reviewed and recommended. Alpha spectrometry and scintillation techniques are used for measurement of isotopic content. Separation processes for samples are described

  9. Heavy element research

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Heavy element research activities in metallurgy and ceramics during 1976 at Lawrence Berkeley Laboratory are reviewed. Topics include: microstructure, properties and alloy design; ceramic alloy program; high resolution and high voltage electron microscopy; and powder metallurgy

  10. Nuclear reactor fuel elements

    International Nuclear Information System (INIS)

    Hindle, E.D.

    1981-01-01

    An array of rods comprising zirconium alloy sheathed nuclear fuel pellets assembled to form a fuel element for a pressurised water reactor is claimed. The helium gas pressure within each rod differs substantially from that of its closest neighbours

  11. Nuclear reactor fuel elements

    International Nuclear Information System (INIS)

    Hindle, E.D.

    1984-01-01

    The fuel elements for a pressurised water reactor comprise arrays of rods of zirconium alloy sheathed nuclear fuel pellets. The helium gas pressure within each rod differs substantially from that of its closest neighbours

  12. Transposable elements in cancer.

    Science.gov (United States)

    Burns, Kathleen H

    2017-07-01

    Transposable elements give rise to interspersed repeats, sequences that comprise most of our genomes. These mobile DNAs have been historically underappreciated - both because they have been presumed to be unimportant, and because their high copy number and variability pose unique technical challenges. Neither impediment now seems steadfast. Interest in the human mobilome has never been greater, and methods enabling its study are maturing at a fast pace. This Review describes the activity of transposable elements in human cancers, particularly long interspersed element-1 (LINE-1). LINE-1 sequences are self-propagating, protein-coding retrotransposons, and their activity results in somatically acquired insertions in cancer genomes. Altered expression of transposable elements and animation of genomic LINE-1 sequences appear to be hallmarks of cancer, and can be responsible for driving mutations in tumorigenesis.

  13. Divergent picornavirus IRES elements

    DEFF Research Database (Denmark)

    Belsham, Graham

    2009-01-01

    Internal ribosome entry site (IRES) elements were first identified about 20 years ago within the 5' untranslated region of picornavirus RNAs. They direct a cap-independent mechanism of translation initiation on the viral RNA. Within the picornavirus family it is now known that there are four...... classes of IRES element which vary in size (450-270nt), they also have different, complex, secondary structures and distinct requirements for cellular proteins to allow them to function. This review describes the features of each class of picornavirus IRES element but focuses on the characteristics...... of the most recently described group, initially identified within the porcine teschovirus-1 RNA, which has strong similarities to the IRES elements from within the genomes of hepatitis C virus and the pestiviruses which are members of the flavivirus family. The selection of the initiation codon...

  14. Novel porcine repetitive elements

    Directory of Open Access Journals (Sweden)

    Nonneman Dan J

    2006-12-01

    Full Text Available Abstract Background Repetitive elements comprise ~45% of mammalian genomes and are increasingly known to impact genomic function by contributing to the genomic architecture, by direct regulation of gene expression and by affecting genomic size, diversity and evolution. The ubiquity and increasingly understood importance of repetitive elements contribute to the need to identify and annotate them. We set out to identify previously uncharacterized repetitive DNA in the porcine genome. Once found, we characterized the prevalence of these repeats in other mammals. Results We discovered 27 repetitive elements in 220 BACs covering 1% of the porcine genome (Comparative Vertebrate Sequencing Initiative; CVSI. These repeats varied in length from 55 to 1059 nucleotides. To estimate copy numbers, we went to an independent source of data, the BAC-end sequences (Wellcome Trust Sanger Institute, covering approximately 15% of the porcine genome. Copy numbers in BAC-ends were less than one hundred for 6 repeat elements, between 100 and 1000 for 16 and between 1,000 and 10,000 for 5. Several of the repeat elements were found in the bovine genome and we have identified two with orthologous sites, indicating that these elements were present in their common ancestor. None of the repeat elements were found in primate, rodent or dog genomes. We were unable to identify any of the replication machinery common to active transposable elements in these newly identified repeats. Conclusion The presence of both orthologous and non-orthologous sites indicates that some sites existed prior to speciation and some were generated later. The identification of low to moderate copy number repetitive DNA that is specific to artiodactyls will be critical in the assembly of livestock genomes and studies of comparative genomics.

  15. Fuel element store

    International Nuclear Information System (INIS)

    Wieser, R.

    1987-01-01

    The spherical fuel elements are stored dry in cans. The cans themselves are stacked in parallel storage shafts, which are combined into a rectangular storage space. The storage space is made earthquake-proof by surrounding it with concrete. It consists of a ceiling assembled from several steel parts, which is connected to the floor by support elements. A cooling air ventilation station supplies the individual storage shaft and therefore the cans with cooling air via incoming and outgoing pipes. (DG) [de

  16. Intrusion detection system elements

    International Nuclear Information System (INIS)

    Eaton, M.J.; Mangan, D.L.

    1980-09-01

    This report highlights elements required for an intrusion detection system and discusses problems which can be encountered in attempting to make the elements effective. Topics discussed include: sensors, both for exterior detection and interior detection; alarm assessment systems, with the discussion focused on video assessment; and alarm reporting systems, including alarm communication systems and dislay/console considerations. Guidance on careful planning and design of a new or to-be-improved system is presented

  17. Structural elements design manual

    CERN Document Server

    Draycott, Trevor

    2012-01-01

    Gives clear explanations of the logical design sequence for structural elements. The Structural Engineer says: `The book explains, in simple terms, and with many examples, Code of Practice methods for sizing structural sections in timber, concrete,masonry and steel. It is the combination into one book of section sizing methods in each of these materials that makes this text so useful....Students will find this an essential support text to the Codes of Practice in their study of element sizing'.

  18. Atoms, molecules & elements

    CERN Document Server

    Graybill, George

    2007-01-01

    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  19. On-stream chemical element monitor

    International Nuclear Information System (INIS)

    Averitt, O.R.; Dorsch, R.R.

    1979-01-01

    An apparatus and method for on-stream chemical element monitoring are described wherein a multiplicity of sample streams are flowed continuously through individual analytical cells and fluorescence analyses are performed on the sample streams in sequence, together with a method of controlling the time duration of each analysis as a function of the concomitant radiation exposure of a preselected perforate reference material interposed in the sample-radiation source path

  20. Peridynamic Multiscale Finite Element Methods

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Timothy [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bond, Stephen D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Littlewood, David John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Moore, Stan Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-12-01

    The problem of computing quantum-accurate design-scale solutions to mechanics problems is rich with applications and serves as the background to modern multiscale science research. The prob- lem can be broken into component problems comprised of communicating across adjacent scales, which when strung together create a pipeline for information to travel from quantum scales to design scales. Traditionally, this involves connections between a) quantum electronic structure calculations and molecular dynamics and between b) molecular dynamics and local partial differ- ential equation models at the design scale. The second step, b), is particularly challenging since the appropriate scales of molecular dynamic and local partial differential equation models do not overlap. The peridynamic model for continuum mechanics provides an advantage in this endeavor, as the basic equations of peridynamics are valid at a wide range of scales limiting from the classical partial differential equation models valid at the design scale to the scale of molecular dynamics. In this work we focus on the development of multiscale finite element methods for the peridynamic model, in an effort to create a mathematically consistent channel for microscale information to travel from the upper limits of the molecular dynamics scale to the design scale. In particular, we first develop a Nonlocal Multiscale Finite Element Method which solves the peridynamic model at multiple scales to include microscale information at the coarse-scale. We then consider a method that solves a fine-scale peridynamic model to build element-support basis functions for a coarse- scale local partial differential equation model, called the Mixed Locality Multiscale Finite Element Method. Given decades of research and development into finite element codes for the local partial differential equation models of continuum mechanics there is a strong desire to couple local and nonlocal models to leverage the speed and state of the

  1. Fuel element transport container

    International Nuclear Information System (INIS)

    Benna, P.; Neuenfeldt, W.

    1979-01-01

    The reprocessing system includes a large number of waterfilled ponds next to each other for the intermediate storage of fuel elements from LWR's. The fuel element transport device is allocated to a middle pond. The individual ponds are separated from each other by walls, and are only accessible from the middle pond via narrow passages. The transport device includes a telescopic running rail for a trolley with a grab device for the fuel element. The running rail is supported in turn by a second trolley, which can be moved by wheels on rails. Part of the drive of the first trolley is arranged on the second one. Using this transport device, adjacent ponds can be served through the passage openings. (DG) [de

  2. Nuclear fuel element

    International Nuclear Information System (INIS)

    Hirayama, Satoshi; Kawada, Toshiyuki; Matsuzaki, Masayoshi.

    1980-01-01

    Purpose: To provide a fuel element for reducing the mechanical interactions between a fuel-cladding tube and the fuel element and for alleviating the limits of the operating conditions of a reactor. Constitution: A fuel element having mainly uranium dioxide consists of a cylindrical outer pellet and cylindrical inner pellet inserted into the outer pellet. The outer pellet contains two or more additives selected from aluminium oxide, beryllium oxide, magnesium oxide, silicon oxide, sodium oxide, phosphorus oxide, calcium oxide and iron oxide, and the inner pellet contains nuclear fuel substance solely or one additive selected from calcium oxide, silicon oxide, aluminium oxide, magnesium oxide, zirconium oxide and iron oxide. The outer pellet of the fuel thus constituted is reduced in mechanical strength and also in the mechanical interactions with the cladding tube, and the plastic fluidity of the entire pellet is prevented by the inner pellet increased in the mechanical strength. (Kamimura, M.)

  3. Creativity Management Key Elements

    Directory of Open Access Journals (Sweden)

    Rosa María Fuchs Ángeles

    2015-09-01

    Full Text Available Organizations are constantly looking towards innovation. In order to reach it they must foment creativity. This paper analyzes a series of elements considered in the organizational creativity management and proposes a model with the indispensable factors that organizations should consider to reach it. These elements are: culture and organizational environment, strategy, structure, communication, relation with customers, human resources (recruiting, training, job design, compensation, promotion, and performance evaluation, long term orientation and the organizational life cycle. Having the analysis of those elements as a basis, the indispensable pillars on management creativity are identified. The proposed model is based on 5 pillars: the alignment between strategic, culture and organizational structure, called by the authors 'Holy Trinity'; intern publicity; customer’s voice; recognition and a look towards future. Finally, the case of an innovative Peruvian enterprise is presented from the model’s perspective and the study conclusions.

  4. Fuel Element Technical Manual

    Energy Technology Data Exchange (ETDEWEB)

    Burley, H.H. [ed.

    1956-08-01

    It is the purpose of the Fuel Element Technical Manual to Provide a single document describing the fabrication processes used in the manufacture of the fuel element as well as the technical bases for these processes. The manual will be instrumental in the indoctrination of personnel new to the field and will provide a single data reference for all personnel involved in the design or manufacture of the fuel element. The material contained in this manual was assembled by members of the Engineering Department and the Manufacturing Department at the Hanford Atomic Products Operation between the dates October, 1955 and June, 1956. Arrangement of the manual. The manual is divided into six parts: Part I--introduction; Part II--technical bases; Part III--process; Part IV--plant and equipment; Part V--process control and improvement; and VI--safety.

  5. Plasmacytoma Infiltrating Leiomyoma in Multiple Myeloma

    Science.gov (United States)

    2018-01-19

    REPORT TYPE 3. DATES COVERED (From - To) 01/19/2018 Poster 01/19/2018-01/21/2018 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Plasmacytoma...Infiltrating Leiomyoma in Multiple Myeloma Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Capt Eden, Rina Se. TASK NUMBER Sf

  6. Fast Output-sensitive Matrix Multiplication

    DEFF Research Database (Denmark)

    Jacob, Riko; Stöckel, Morten

    2015-01-01

    We consider the problem of multiplying two $U \\times U$ matrices $A$ and $C$ of elements from a field $\\F$. We present a new randomized algorithm that can use the known fast square matrix multiplication algorithms to perform fewer arithmetic operations than the current state of the art for output...

  7. Neutron activation analysis of trace elements in Japanese hormesis cosmetics

    International Nuclear Information System (INIS)

    Furuta, E.; Nakahara, H.; Hatsukawa, Y.; Matsue, H.; Sakane, H.

    2008-01-01

    In Japan, cosmetics claiming hormesis effect are available through Internet. Although these cosmetics show the contents, they never mention the minor elements and radioactive sources. The existence of radioisotopes, however, was observed by measurements of the gamma-rays with a HPGe detector. In this study, in order to clarify the contents of trace elements, the hormesis cosmetics including radioactive sources were analyzed using INAA, PGAA and NAA with multiple gamma-ray detection (NAAMG). Nineteen elements were analyzed quantitatively in hormesis cosmetics by INAA, PGAA and NAAMG and 16 elements were detected qualitatively by SEM-EPMA. (author)

  8. Elements of social security

    DEFF Research Database (Denmark)

    Hansen, Hans

    Elements of Social Security is a comparative study of important elements of the social security systems in Denmark (DK), Sweden (S), Finland (FIN), Austria (A), Germany (D), the Netherlands (NL), Great Britain (GB) and Canada (CAN). It should be emphasized that Germany is the former West Germany...... (Alte Länder). This is the 9th and last edition of the publication,covering income levels and rules for social security and personal taxation for 1999. Basis for the projections to 1999 income levels is the 1998 data (in some cases 1999 data)for OECD's Taxing Wages as reported by national experts....

  9. Bibliography on transuranium elements

    International Nuclear Information System (INIS)

    Sood, D.D.

    1991-01-01

    A selective bibliography of prominent publications on transuranium elements is compiled. Heading papers, symposia proceedings and the textbooks are included in the bibliography. The bibliography is arranged under the headings: (1)Books, Symposia Proceedings, Reviews etc., (2)Discovery, (3)Weighable Isolation, (4)Metal Preparation, (5)Nuclear Properties, (6)Plutonium as Reactor Fuel, (7)Fuel Reprocessing, (8)Solid State Chemistry, Thermochemistry and Spectroscopy, (9)Radiation Safety, (10)Applications, and (11)Some Typical Indian Papers. Total number of references cited are 298. The bibliography, though selective, will serve as a starting point for comprehensive literature search on transuranium elements. (author)

  10. Finite elements and approximation

    CERN Document Server

    Zienkiewicz, O C

    2006-01-01

    A powerful tool for the approximate solution of differential equations, the finite element is extensively used in industry and research. This book offers students of engineering and physics a comprehensive view of the principles involved, with numerous illustrative examples and exercises.Starting with continuum boundary value problems and the need for numerical discretization, the text examines finite difference methods, weighted residual methods in the context of continuous trial functions, and piecewise defined trial functions and the finite element method. Additional topics include higher o

  11. Elements of Social Security

    DEFF Research Database (Denmark)

    Hansen, Hans

    Elements of Social Security contains an overview of important benefit schemes in Denmark, Sweden, Finland, Austria, Germany, the Netherlands, Great Britain and Canada. The schemes are categorized according to common sets of criteria and compared. Stylized cases illustrate the impact on disposable...

  12. Elements of Social Security

    DEFF Research Database (Denmark)

    Hansen, Hans

    Elements of Social Security contains an overview of important benefit schemes in Denmark, Sweden, Finland, Germany, the Netherlands, Great Britain and Canada. The schemes are categorized according to common sets of criteria and compared. Stylized cases illustrate the impact on disposable income...

  13. Elements of Social Security

    DEFF Research Database (Denmark)

    Hansen, Hans

    Elements of Social Security contains an overview of important benefit schemes in Denmark, Sweden, Finland, Germany, Great Britain, the Netherlands and Canada. The schemes are categorized according to common sets of criteria and compared. Stylized cases illustrate the impact on disposable income...

  14. Water, the intangible element

    NARCIS (Netherlands)

    Schotting, R.J.

    2009-01-01

    Water is the key to life. No living creature can survive without water. Too much water or polluted water are serious threats to mankind. Managing this intangible element is complex, not only in wet deltaic regions but also in the (semi-)arid regions of the world. Combined efforts of the

  15. Movies and Literary Elements.

    Science.gov (United States)

    Keller, Rodney D.

    1987-01-01

    Recommends using movie clips to stimulate students' interest in reading a novel as well as to teach elements of fiction such as plot, character, setting, symbol, irony, and theme. Describes each clip and provides study questions. Includes a listing of movies made from books. (NH)

  16. Elements of Architecture

    DEFF Research Database (Denmark)

    Elements of Architecture explores new ways of engaging architecture in archaeology. It conceives of architecture both as the physical evidence of past societies and as existing beyond the physical environment, considering how people in the past have not just dwelled in buildings but have existed...

  17. Inside finite elements

    CERN Document Server

    Weiser, Martin

    2016-01-01

    All relevant implementation aspects of finite element methods are discussed in this book. The focus is on algorithms and data structures as well as on their concrete implementation. Theory is covered as far as it gives insight into the construction of algorithms. Throughout the exercises a complete FE-solver for scalar 2D problems will be implemented in Matlab/Octave.

  18. Plants' essential chemical elements

    Science.gov (United States)

    Kevin T. Smith

    2007-01-01

    Every garden center and hardware store sells fertilizer guaranteed to "feed" plants. In a strict sense, we can't feed plants. Food contains an energy source. Green plants capture solar energy and make their own food through photosynthesis! Photosynthesis and other metabolic processes require chemical elements in appropriate doses for plants to survive...

  19. Elements of relativity theory

    International Nuclear Information System (INIS)

    Lawden, D.F.

    1985-01-01

    The book on elements of relativity theory is intended for final year school students or as an early university course in mathematical physics. Special principle of relativity, lorentz transformation, velocity transformations, relativistic mechanics, and general theory of relativity, are all discussed. (U.K.)

  20. Photovoltaic radiation detector element

    International Nuclear Information System (INIS)

    Agouridis, D.C.

    1980-01-01

    A radiation detector element is formed of a body of semiconductor material, a coating on the body which forms a photovoltaic junction therewith, and a current collector consisting of narrow metallic strips, the aforesaid coating having an opening therein in the edge of which closely approaches but is spaced from the current collector strips

  1. Multiple-Ring Digital Communication Network

    Science.gov (United States)

    Kirkham, Harold

    1992-01-01

    Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.

  2. Writing analytic element programs in Python.

    Science.gov (United States)

    Bakker, Mark; Kelson, Victor A

    2009-01-01

    The analytic element method is a mesh-free approach for modeling ground water flow at both the local and the regional scale. With the advent of the Python object-oriented programming language, it has become relatively easy to write analytic element programs. In this article, an introduction is given of the basic principles of the analytic element method and of the Python programming language. A simple, yet flexible, object-oriented design is presented for analytic element codes using multiple inheritance. New types of analytic elements may be added without the need for any changes in the existing part of the code. The presented code may be used to model flow to wells (with either a specified discharge or drawdown) and streams (with a specified head). The code may be extended by any hydrogeologist with a healthy appetite for writing computer code to solve more complicated ground water flow problems. Copyright © 2009 The Author(s). Journal Compilation © 2009 National Ground Water Association.

  3. Element-topology-independent preconditioners for parallel finite element computations

    Science.gov (United States)

    Park, K. C.; Alexander, Scott

    1992-01-01

    A family of preconditioners for the solution of finite element equations are presented, which are element-topology independent and thus can be applicable to element order-free parallel computations. A key feature of the present preconditioners is the repeated use of element connectivity matrices and their left and right inverses. The properties and performance of the present preconditioners are demonstrated via beam and two-dimensional finite element matrices for implicit time integration computations.

  4. Four-terminal circuit element with photonic core

    Science.gov (United States)

    Sampayan, Stephen

    2017-08-29

    A four-terminal circuit element is described that includes a photonic core inside of the circuit element that uses a wide bandgap semiconductor material that exhibits photoconductivity and allows current flow through the material in response to the light that is incident on the wide bandgap material. The four-terminal circuit element can be configured based on various hardware structures using a single piece or multiple pieces or layers of a wide bandgap semiconductor material to achieve various designed electrical properties such as high switching voltages by using the photoconductive feature beyond the breakdown voltages of semiconductor devices or circuits operated based on electrical bias or control designs. The photonic core aspect of the four-terminal circuit element provides unique features that enable versatile circuit applications to either replace the semiconductor transistor-based circuit elements or semiconductor diode-based circuit elements.

  5. An efficient finite element solution for gear dynamics

    International Nuclear Information System (INIS)

    Cooley, C G; Parker, R G; Vijayakar, S M

    2010-01-01

    A finite element formulation for the dynamic response of gear pairs is proposed. Following an established approach in lumped parameter gear dynamic models, the static solution is used as the excitation in a frequency domain solution of the finite element vibration model. The nonlinear finite element/contact mechanics formulation provides accurate calculation of the static solution and average mesh stiffness that are used in the dynamic simulation. The frequency domain finite element calculation of dynamic response compares well with numerically integrated (time domain) finite element dynamic results and previously published experimental results. Simulation time with the proposed formulation is two orders of magnitude lower than numerically integrated dynamic results. This formulation admits system level dynamic gearbox response, which may include multiple gear meshes, flexible shafts, rolling element bearings, housing structures, and other deformable components.

  6. Archaeal extrachromosomal genetic elements

    DEFF Research Database (Denmark)

    Wang, Haina; Peng, Nan; Shah, Shiraz Ali

    2015-01-01

    SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spind......SUMMARY: Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes...... on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade....

  7. Nuclear fuel element

    Energy Technology Data Exchange (ETDEWEB)

    Armijo, J S; Coffing, L F

    1979-04-05

    The fuel element with circular cross-section for BWR and PWR consists of a core surrounded by a compound jacket container where there is a gap between the core and jacket during operation in the reactor. The core consists of U, Pu, Th compounds and mixtures of these. The compound jacket consists of zircaloy 2 or 4. In order to for example prevent the corrosion of the compound jacket, its inner surface has a metal barrier with smaller neutron absorbers than the jacket material in the form of a zirconium sponge. The zirconium of this metal barrier has impurities of various elements in the order of magnitude of 1000 to 5000 ppm. The oxygen content is in the range of 200 to 1200 ppm and the thickness of the metal barrier is 1-30% of the thickness of the jacket.

  8. Nuclear reactor fuel element

    International Nuclear Information System (INIS)

    D'Eye, R.W.M.; Shennan, J.V.; Ford, L.H.

    1977-01-01

    Fuel element with particles from ceramic fissionable material (e.g. uranium carbide), each one being coated with pyrolitically deposited carbon and all of them being connected at their points of contact by means of an individual crossbar. The crossbar consists of silicon carbide produced by reaction of silicon metal powder with the carbon under the influence of heat. Previously the silicon metal powder together with the particles was kneaded in a solvent and a binder (e.g. epoxy resin in methyl ethyl ketone plus setting agent) to from a pulp. The reaction temperature lies at 1750 0 C. The reaction itself may take place in a nitrogen atmosphere. There will be produced a fuel element with a high overall thermal conductivity. (DG) [de

  9. Elements of quantum optics

    CERN Document Server

    Meystre, Pierre

    2007-01-01

    Elements of Quantum Optics gives a self-contained and broad coverage of the basic elements necessary to understand and carry out research in laser physics and quantum optics, including a review of basic quantum mechanics and pedagogical introductions to system-reservoir interactions and to second quantization. The text reveals the close connection between many seemingly unrelated topics, such as probe absorption, four-wave mixing, optical instabilities, resonance fluorescence and squeezing. It also comprises discussions of cavity quantum electrodynamics and atom optics. The 4th edition includes a new chapter on quantum entanglement and quantum information, as well as added discussions of the quantum beam splitter, electromagnetically induced transparency, slow light, and the input-output formalism needed to understand many problems in quantum optics. It also provides an expanded treatment of the minimum-coupling Hamiltonian and a simple derivation of the Gross-Pitaevskii equation, an important gateway to rese...

  10. Periodic table of elements

    International Nuclear Information System (INIS)

    Fluck, E.; Heumann, K.G.

    1985-01-01

    Following a recommendation by the International Union for Pure and Applied Chemistry (IUPAC), the groups of the periodic table shall be numbered from 1 to 18, instead of I to VIII as before. The recommendations has been approved of by the Committee on Nomenclature of the American Chemical Society. The new system abandons the distinction between main groups (a) and auxiliary groups (b), which in the past frequently has been the reason for misunderstandings between European and American chemists, due to different handling. The publishing house VCH Verlagsgesellschaft recently produced a new periodic table that shows the old and the new numbering system together at a glance, so that chemists will have time to get familiar with the new system. In addition the new periodic table represents an extensive data compilation arranged by elements. The front page lists the chemical properties of elements, the back page their physical properties. (orig./EF) [de

  11. Nuclear fuel elements

    International Nuclear Information System (INIS)

    Kawada, Toshiyuki; Hirayama, Satoshi; Yoneya, Katsutoshi.

    1980-01-01

    Purpose: To enable load-depending operation as well as moderation for the restriction of operation conditions in the present nuclear reactors, by specifying the essential ingredients and the total weight of the additives to UO 2 fuel substances. Constitution: Two or more additives selected from Al 2 O 3 , B 2 O, CaO, MgO, SiO 2 , Na 2 O and P 2 O 5 are added by the total weight of 2 - 5% to fuel substances consisting of UO 2 or a mixture of UO 2 and PuO 2 . When the mixture is sintered, the strength of the fuel elements is decreased and the fuel-cladding interactions due to the difference in the heat expansion coefficients between the ceramic fuel elements and the metal claddings are decreased to a substantially harmless degree. (Horiuchi, T.)

  12. Nuclear fuel elements

    International Nuclear Information System (INIS)

    Nakai, Keiichi

    1983-01-01

    Purpose: To decrease the tensile stresses resulted in a fuel can as well as prevent decladding of fuel pellets into the bore holes by decreasing the inner pressure within the nuclear fuel element. Constitution: A fuel can is filled with hollow fuel pellets, inserted with a spring for retaining the hollow fuel pellets with an appropriate force and, thereafter, closely sealed at the both ends with end plugs. A cylindrical body is disposed into the bore holes of the hollow fuel pellets. Since initial sealing gases and/or gaseous nuclear fission products can thus be excluded from the bore holes where the temperature is at the highest level, the inner pressure of the nuclear fuel element can be reduced to decrease the tensile strength resulted to the fuel can. Furthermore, decladding of fuel pellets into the bore holes can be prevented. (Moriyama, K.)

  13. Generalized internal multiple imaging

    KAUST Repository

    Zuberi, Mohammad Akbar Hosain

    2014-12-04

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green\\'s function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green\\'s function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green\\'s function and renders the higher order internal multiple image for display on a display device.

  14. MultipleColposcopyJCO

    Science.gov (United States)

    Performing multiple biopsies during a procedure known as colposcopy—visual inspection of the cervix—is more effective than performing only a single biopsy of the worst-appearing area for detecting cervical cancer precursors. This multiple biopsy approach

  15. Salmonella Infections - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Salmonella Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Salmonella Infections - Multiple Languages To use the sharing features ...

  16. Health Literacy - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Health Literacy URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Health Literacy - Multiple Languages To use the sharing features on ...

  17. Cosmetic Dentistry - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Cosmetic Dentistry URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Cosmetic Dentistry - Multiple Languages To use the sharing features on ...

  18. Atrial Fibrillation - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  19. Zika Virus - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Zika Virus URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Zika Virus - Multiple Languages To use the sharing features on ...

  20. Elder Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Elder Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Elder Abuse - Multiple Languages To use the sharing features on ...

  1. Herbal Medicine - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Herbal Medicine URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Herbal Medicine - Multiple Languages To use the sharing features on ...

  2. Generalized internal multiple imaging

    KAUST Repository

    Zuberi, Mohammad Akbar Hosain; Alkhalifah, Tariq

    2014-01-01

    Various examples are provided for generalized internal multiple imaging (GIMI). In one example, among others, a method includes generating a higher order internal multiple image using a background Green's function and rendering the higher order internal multiple image for presentation. In another example, a system includes a computing device and a generalized internal multiple imaging (GIMI) application executable in the computing device. The GIMI application includes logic that generates a higher order internal multiple image using a background Green's function and logic that renders the higher order internal multiple image for display on a display device. In another example, a non-transitory computer readable medium has a program executable by processing circuitry that generates a higher order internal multiple image using a background Green's function and renders the higher order internal multiple image for display on a display device.

  3. Domestic Violence - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Domestic Violence URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Domestic Violence - Multiple Languages To use the sharing features on ...

  4. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  5. Diabetic Foot - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Diabetic Foot URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Diabetic Foot - Multiple Languages To use the sharing features on ...

  6. Child Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Child Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Child Abuse - Multiple Languages To use the sharing features on ...

  7. Fatigue and Multiple Sclerosis

    Science.gov (United States)

    ... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  8. Rotavirus Infections - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Rotavirus Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Rotavirus Infections - Multiple Languages To use the sharing features ...

  9. Nuclear fuel elements

    International Nuclear Information System (INIS)

    Ainsworth, K.F.

    1979-01-01

    A nuclear fuel element is described having a cluster of nuclear fuel pins supported in parallel, spaced apart relationship by transverse cellular braces within coaxial, inner and outer sleeves, the inner sleeve being in at least two separate axial lengths, each of the transverse braces having a peripheral portion which is clamped peripherally between the ends of the axial lengths of the inner sleeve. (author)

  10. Sensor for ionizable elements

    International Nuclear Information System (INIS)

    Berkey, E.; Reed, W.A. III; Hickam, W.M.

    1977-01-01

    Sensor to detect thermally ionizable elements or molucules in air, water vapour or oxygen or to be used as alkali leak detector in vacuum systems, e.g. in the pipe system of a liquid-metal cooled FBR. The sensor consists of an filament made of thorium-containing iridium as cathode with a temperature upto 1000 0 C and an anode sheet of molybdenum, nickel or stainless steal. (ORU) [de

  11. Nuclear reactor fuel elements

    International Nuclear Information System (INIS)

    Butterfield, C.E.; Waite, E.

    1982-01-01

    A nuclear reactor fuel element comprising a column of vibration compacted fuel which is retained in consolidated condition by a thimble shaped plug. The plug is wedged into gripping engagement with the wall of the sheath by a wedge. The wedge material has a lower coefficient of expansion than the sheath material so that at reactor operating temperature the retainer can relax sufficient to accommodate thermal expansion of the column of fuel. (author)

  12. OXIDATION OF TRANSURANIC ELEMENTS

    Science.gov (United States)

    Moore, R.L.

    1959-02-17

    A method is reported for oxidizing neptunium or plutonium in the presence of cerous values without also oxidizing the cerous values. The method consists in treating an aqueous 1N nitric acid solution, containing such cerous values together with the trivalent transuranic elements, with a quantity of hydrogen peroxide stoichiometrically sufficient to oxidize the transuranic values to the hexavalent state, and digesting the solution at room temperature.

  13. Transportation of radioactive elements

    International Nuclear Information System (INIS)

    Thubert, Francis; Rentien, Guy; Jacquet, Michel

    1981-01-01

    The production and marketing of artificial radioactive elements engaged in by the 'Office des Rayonnements Ionisants' requires the use of specially designed packagings and assorted means of transport. The authors begin by describing the different kinds of products involved and the forms of packagings needed, and go on to discuss the various means of transport used, underlining the fact that, in terms of number and gravity, the incidents that have occurred to date have indeed been few and far between [fr

  14. Vented nuclear fuel element

    International Nuclear Information System (INIS)

    Oguma, M.; Hirose, Y.

    1976-01-01

    A description is given of a vented nuclear fuel element having a plenum for accumulation of fission product gases and plug means for delaying the release of the fission product gases from the plenum, the plug means comprising a first porous body wettable with a liquid metal and a second porous body non-wettable with the liquid metal, the first porous body being impregnated with the liquid metal and in contact with the liquid metal

  15. Helium the disappearing element

    CERN Document Server

    Sears, Wheeler M

    2015-01-01

    The subject of the book is helium, the element, and its use in myriad applications including MRI machines, particle accelerators, space telescopes, and of course balloons and blimps. It was at the birth of our Universe, or the Big Bang, where the majority of cosmic helium was created; and stellar helium production continues. Although helium is the second most abundant element in the Universe, it is actually quite rare here on Earth and only exists because of radioactive elements deep within the Earth. This book includes a detailed history of the discovery of helium, of the commercial industry built around it, how the helium we actually encounter is produced within the Earth, and the state of the helium industry today. The gas that most people associate with birthday party balloons is running out. “Who cares?” you might ask. Well, without helium, MRI machines could not function, rockets could not go into space, particle accelerators such as those used by CERN could not operate, fiber optic cables would not...

  16. Elements of quantum information

    International Nuclear Information System (INIS)

    Schleich, W.P.

    2007-01-01

    Elements of Quantum Information introduces the reader to the fascinating field of quantum information processing, which lives on the interface between computer science, physics, mathematics, and engineering. This interdisciplinary branch of science thrives on the use of quantum mechanics as a resource for high potential modern applications. With its wide coverage of experiments, applications, and specialized topics - all written by renowned experts - Elements of Quantum Information provides and indispensable, up-to-date account of the state of the art of this rapidly advancing field and takes the reader straight up to the frontiers of current research. The articles have first appeared as a special issue of the journal 'Fortschritte der Physik / Progress of Physics'. Since then, they have been carefully updated. The book will be an inspiring source of information and insight for anyone researching and specializing in experiments and theory of quantum information. Topics addressed in Elements of Quantum Information include - Cavity Quantum Electrodynamics - Segmented Paul Traps - Cold Atoms and Bose-Einstein Condensates in Microtraps, Optical Lattices, and on Atom Chips - Rydberg Gases - Factorization of Numbers with Physical Systems - Entanglement of Continuous Variables - NMR and Solid State Quantum Computation - Quantum Algorithms and Quantum Machines - Complexity Theory - Quantum Crytography. (orig.)

  17. Using Finite Element Method

    Directory of Open Access Journals (Sweden)

    M.H.R. Ghoreishy

    2008-02-01

    Full Text Available This research work is devoted to the footprint analysis of a steel-belted radial tyre (185/65R14 under vertical static load using finite element method. Two models have been developed in which in the first model the tread patterns were replaced by simple ribs while the second model was consisted of details of the tread blocks. Linear elastic and hyper elastic (Arruda-Boyce material models were selected to describe the mechanical behavior of the reinforcing and rubbery parts, respectively. The above two finite element models of the tyre were analyzed under inflation pressure and vertical static loads. The second model (with detailed tread patterns was analyzed with and without friction effect between tread and contact surfaces. In every stage of the analysis, the results were compared with the experimental data to confirm the accuracy and applicability of the model. Results showed that neglecting the tread pattern design not only reduces the computational cost and effort but also the differences between computed deformations do not show significant changes. However, more complicated variables such as shape and area of the footprint zone and contact pressure are affected considerably by the finite element model selected for the tread blocks. In addition, inclusion of friction even in static state changes these variables significantly.

  18. Study of Superheavy Elements

    International Nuclear Information System (INIS)

    Hofmann, Sigurd

    2007-01-01

    The nuclear shell model predicts that the next doubly magic shell-closure beyond 208 Pb is at a proton number Z = 114, 120, or 126 and at a neutron number N = 172 or 184. The outstanding aim of experimental investigations is the exploration of this region of spherical 'SuperHeavy Elements' (SHEs). Experimental methods are described, which allowed for the identification of elements produced on a cross-section level of about 1 pb. The decay data reveal that for the heaviest elements, the dominant decay mode is alpha emission, not fission. Decay properties as well as reaction cross-sections are compared with results of theoretical investigations. Finally, plans are presented for the further development of the experimental set-up and the application of new techniques, as for instance the precise mass measurement of the produced nuclei using ion traps. At increased sensitivity, the detailed exploration of the region of spherical SHEs will start, after first steps on the island were made in recent years. (Author)

  19. Probabilistic finite elements

    Science.gov (United States)

    Belytschko, Ted; Wing, Kam Liu

    1987-01-01

    In the Probabilistic Finite Element Method (PFEM), finite element methods have been efficiently combined with second-order perturbation techniques to provide an effective method for informing the designer of the range of response which is likely in a given problem. The designer must provide as input the statistical character of the input variables, such as yield strength, load magnitude, and Young's modulus, by specifying their mean values and their variances. The output then consists of the mean response and the variance in the response. Thus the designer is given a much broader picture of the predicted performance than with simply a single response curve. These methods are applicable to a wide class of problems, provided that the scale of randomness is not too large and the probabilistic density functions possess decaying tails. By incorporating the computational techniques we have developed in the past 3 years for efficiency, the probabilistic finite element methods are capable of handling large systems with many sources of uncertainties. Sample results for an elastic-plastic ten-bar structure and an elastic-plastic plane continuum with a circular hole subject to cyclic loadings with the yield stress on the random field are given.

  20. New functionalities in abundant element oxides: ubiquitous element strategy

    International Nuclear Information System (INIS)

    Hosono, Hideo; Hayashi, Katsuro; Kamiya, Toshio; Atou, Toshiyuki; Susaki, Tomofumi

    2011-01-01

    While most ceramics are composed of ubiquitous elements (the ten most abundant elements within the Earth's crust), many advanced materials are based on rare elements. A 'rare-element crisis' is approaching owing to the imbalance between the limited supply of rare elements and the increasing demand. Therefore, we propose a 'ubiquitous element strategy' for materials research, which aims to apply abundant elements in a variety of innovative applications. Creation of innovative oxide materials and devices based on conventional ceramics is one specific challenge. This review describes the concept of ubiquitous element strategy and gives some highlights of our recent research on the synthesis of electronic, thermionic and structural materials using ubiquitous elements. (topical review)

  1. A saturation screen for cis-acting regulatory DNA in the Hox genes of Ciona intestinalis

    Energy Technology Data Exchange (ETDEWEB)

    Keys, David N.; Lee, Byung-in; Di Gregorio, Anna; Harafuji, Naoe; Detter, Chris; Wang, Mei; Kahsai, Orsalem; Ahn, Sylvia; Arellano, Andre; Zhang, Quin; Trong, Stephan; Doyle, Sharon A.; Satoh, Noriyuki; Satou, Yutaka; Saiga, Hidetoshi; Christian, Allen; Rokhsar, Dan; Hawkins, Trevor L.; Levine, Mike; Richardson, Paul

    2005-01-05

    A screen for the systematic identification of cis-regulatory elements within large (>100 kb) genomic domains containing Hox genes was performed by using the basal chordate Ciona intestinalis. Randomly generated DNA fragments from bacterial artificial chromosomes containing two clusters of Hox genes were inserted into a vector upstream of a minimal promoter and lacZ reporter gene. A total of 222 resultant fusion genes were separately electroporated into fertilized eggs, and their regulatory activities were monitored in larvae. In sum, 21 separable cis-regulatory elements were found. These include eight Hox linked domains that drive expression in nested anterior-posterior domains of ectodermally derived tissues. In addition to vertebrate-like CNS regulation, the discovery of cis-regulatory domains that drive epidermal transcription suggests that C. intestinalis has arthropod-like Hox patterning in the epidermis.

  2. Neutron Multiplicity Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Frame, Katherine Chiyoko [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-28

    Neutron multiplicity measurements are widely used for nondestructive assay (NDA) of special nuclear material (SNM). When combined with isotopic composition information, neutron multiplicity analysis can be used to estimate the spontaneous fission rate and leakage multiplication of SNM. When combined with isotopic information, the total mass of fissile material can also be determined. This presentation provides an overview of this technique.

  3. The transuranium elements: From neptunium and plutonium to element 112

    International Nuclear Information System (INIS)

    Hoffman, D.C.

    1996-01-01

    Beginning in the 1930's, both chemists and physicists became interested in synthesizing new artificial elements. The first transuranium element, Np, was synthesized in 1940. Over the past six decades, 20 transuranium elements have been produced. A review of the synthesis is given. The procedure of naming the heavy elements is also discussed. It appears feasible to produce elements 113 and 114. With the Berkeley Gas-filled Separator, it should be possible to reach the superheavy elements in the region of the spherical Z=114 shell, but with fewer neutrons than the N=184 spherical shell. 57 refs, 6 figs

  4. Gas sensor with multiple internal reference electrodes and sensing electrodes

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a potentiometric gas sensor, or potentiometric gas detection element, with multiple internal reference electrodes and multiple sensing electrodes for determining the concentrations of gas components in a gaseous mixture. The sensor for gas detection comprises: a solid...

  5. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes

    DEFF Research Database (Denmark)

    Siepel, Adam; Bejerano, Gill; Pedersen, Jakob Skou

    2005-01-01

    We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide multiple alignments of five vertebrate species (human, mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments of four insect species (three...... species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo......-HMM to the data by maximum likelihood, subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based on this model. The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and substantially...

  6. Division algebras with integral elements

    International Nuclear Information System (INIS)

    Koca, M.; Ozdes, N.

    1988-06-01

    Pairing two elements of a given division algebra furnished with a multiplication rule leads to an algebra of higher dimension restricted by 8. This fact is used to obtain the roots of SO(4) and SP(2) from the roots ±1 of SU(2) and the weights ±1/2 of its spinor representation. The root lattice of SO(8) described by 24 integral quaternions are obtained by pairing two sets of roots of SP(2). The root system of F 4 is constructed in terms of 24 integral and 24 ''half-integral'' quaternions. The root lattice of E 8 expressed as 240 integral octonions are obtained by pairing two sets of roots of F 4 . 24 integral quaternions of SO(8) forming a discrete subgroup of SU(2) is shown to be the automorphism group of the root lattices of SO(8), F 4 and E 8 . The roots of maximal subgroups SO(16), E 7 XSU(2), E 6 XSU(3), SU(9) and SU(5)XSU(5) of E 8 are identified with a simple method. Subsets of the discrete subgroup of SU(2) leaving maximal subgroups of E 8 are obtained. Constructions of E 8 root lattice with integral octonions in 7 distinct ways are made. Magic square of integral lattices of Goddard, Nahm, Olive, Ruegg and Schwimmer are derived. Possible physical applications are suggested. (author). 16 refs, 6 figs, 5 tabs

  7. Neutron multiplication measurement instrument

    International Nuclear Information System (INIS)

    Nixon, K.V.; Dowdy, E.J.; France, S.W.; Millegan, D.R.; Robba, A.A.

    1983-01-01

    The Advanced Nuclear Technology Group of the Los Alamos National Laboratory is now using intelligent data-acquisition and analysis instrumentation for determining the multiplication of nuclear material. Earlier instrumentation, such as the large NIM-crate systems, depended on house power and required additional computation to determine multiplication or to estimate error. The portable, battery-powered multiplication measurement unit, with advanced computational power, acquires data, calculates multiplication, and completes error analysis automatically. Thus, the multiplication is determined easily and an available error estimate enables the user to judge the significance of results

  8. Elements of social action

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2011-01-01

    Full Text Available Because of the significant analytical advantages, the author prefers social action as initial sociological concept in the relation to social phenomenon. Its basic elements are: actors, subjects and tools, needs and interests, values and norms, positions and roles. Actors set in motion and unify the rest of elements, guide to the magic triangle of sociology (movement, change, order, reaffirm actor paradigm to systemic paradigm. Subjects and tools materialize an action and its overestimate results in technological determinism or (by means of property as institutional appropriation of nature in the (unclassed historical type of society. Needs and interests are the basis of person's motivation and starting point for depth analysis of sociability. The expansion of legitimate interests circle develops techniques of normative regulation. Values and norms guide to institutional-organizational, positions to vertical and roles to horizontal structure. Values give the meaning to the action as well as to human existence, they are orientations of motivate system of personality but also basic aspect of society. As abstractions, values are latent background of norms and they tell to us what to do, and norms how to do something. Norms are specified instructions for suitable behavior Without normative order, not to be possible the satisfying of needs and the conciliation of interests. Riches, power and prestige are components of social position, and legal status is the determination of rights and obligations of the position. Roles are normative expectation of behavior. Toward kinds of sanctions roles are classified. Roles but also other elements of social action are starting point for sociological analysis of legal norms and institutes. On the other side, the observation of legal component of social actions enriches, strengths and precises sociological analysis of them.

  9. Analytical elements of mechanics

    CERN Document Server

    Kane, Thomas R

    2013-01-01

    Analytical Elements of Mechanics, Volume 1, is the first of two volumes intended for use in courses in classical mechanics. The books aim to provide students and teachers with a text consistent in content and format with the author's ideas regarding the subject matter and teaching of mechanics, and to disseminate these ideas. The book opens with a detailed exposition of vector algebra, and no prior knowledge of this subject is required. This is followed by a chapter on the topic of mass centers, which is presented as a logical extension of concepts introduced in connection with centroids. A

  10. Improved nuclear fuel element

    International Nuclear Information System (INIS)

    Klepfer, H.H.

    1974-01-01

    A nuclear fuel element is described which comprises: 1) an elongated clad container, 2) a layer of high lubricity material being disposed in and adjacent to the clad container, 3) a low neutron capture cross section metal liner being disposed in the clad container and adjacent to the layer, 4) a central core of a body of nuclear fuel material disposed in and partially filling the container and forming an internal cavity in the container, 5) an enclosure integrally secured and sealed at each end of the container, and a nuclear fuel material retaining means positioned in the cavity. (author)

  11. Elements of real analysis

    CERN Document Server

    Sprecher, David A

    2010-01-01

    This classic text in introductory analysis delineates and explores the intermediate steps between the basics of calculus and the ultimate stage of mathematics: abstraction and generalization.Since many abstractions and generalizations originate with the real line, the author has made it the unifying theme of the text, constructing the real number system from the point of view of a Cauchy sequence (a step which Dr. Sprecher feels is essential to learn what the real number system is).The material covered in Elements of Real Analysis should be accessible to those who have completed a course in

  12. Nuclear reactor fuel elements

    International Nuclear Information System (INIS)

    Hindle, E. D.

    1984-01-01

    An array of rods is assembled to form a fuel element for a pressurized water reactor, the rods comprising zirconium alloy sheathed nuclear fuel pellets and containing helium. The helium gas pressure is selected for each rod so that it differs substantially from the helium gas pressure in its closest neighbors. In a preferred arrangement the rods are arranged in a square lattice and the helium gas pressure alternates between a relatively high value and a relatively low value so that each rod has as its closest neighbors up to four rods containing helium gas at the other pressure value

  13. Nuclear reactor fuel elements

    Energy Technology Data Exchange (ETDEWEB)

    Hindle, E. D.

    1984-10-16

    An array of rods is assembled to form a fuel element for a pressurized water reactor, the rods comprising zirconium alloy sheathed nuclear fuel pellets and containing helium. The helium gas pressure is selected for each rod so that it differs substantially from the helium gas pressure in its closest neighbors. In a preferred arrangement the rods are arranged in a square lattice and the helium gas pressure alternates between a relatively high value and a relatively low value so that each rod has as its closest neighbors up to four rods containing helium gas at the other pressure value.

  14. Osteoporosis and trace elements

    DEFF Research Database (Denmark)

    Aaseth, J.; Boivin, G.; Andersen, Ole

    2012-01-01

    More than 200 million people are affected by osteoporosis worldwide, as estimated by 2 million annual hip fractures and other debilitating bone fractures (vertebrae compression and Colles' fractures). Osteoporosis is a multi-factorial disease with potential contributions from genetic, endocrine...... in new bone and results in a net gain in bone mass, but may be associated with a tissue of poor quality. Aluminum induces impairment of bone formation. Gallium and cadmium suppresses bone turnover. However, exact involvements of the trace elements in osteoporosis have not yet been fully clarified...

  15. [Healthcare marketing elements].

    Science.gov (United States)

    Ameri, Cinzia; Fiorini, Fulvio

    2014-01-01

    Marketing puts its foundation on a few key concepts: need-demand, product-service, satisfaction, exchange, market, or business structure manufacturing / supply. The combination of these elements allows you to build an effective marketing strategy. Crucial in this respect is to remember the Porter matrix, which shows that for a correct analysis of the relevant market is necessary to refer to the "five forces at play", ie: customers, competitors, new entrants and substitutes threat. Another key lever for proper marketing oriented approach is the continuous and constant monitoring of the application, anticipating their dissatisfactions.

  16. Technical Elements (CCT1)

    DEFF Research Database (Denmark)

    Thomsen, Kirsten Engelund; Wittchen, Kim Bjarne

    2017-01-01

    Many of the aspects dealt with in the CA EPBD are closely interlinked with each other and may refer to both new and existing buildings, as well as to inspection and certification. This is also true for technical aspects, such as the calculation methodologies, and how to include technical systems......’ efficiency or how to integrate renewable energy within them. The central team for Technical Elements deals with issues of a technical nature, which are common to new and existing buildings, and/or with minimum demands, certification and inspection. This report focuses on the implementation of Articles 3, 4...

  17. Optical Finite Element Processor

    Science.gov (United States)

    Casasent, David; Taylor, Bradley K.

    1986-01-01

    A new high-accuracy optical linear algebra processor (OLAP) with many advantageous features is described. It achieves floating point accuracy, handles bipolar data by sign-magnitude representation, performs LU decomposition using only one channel, easily partitions and considers data flow. A new application (finite element (FE) structural analysis) for OLAPs is introduced and the results of a case study presented. Error sources in encoded OLAPs are addressed for the first time. Their modeling and simulation are discussed and quantitative data are presented. Dominant error sources and the effects of composite error sources are analyzed.

  18. Elements of energy conversion

    CERN Document Server

    Russell, Charles R

    2013-01-01

    Elements of Energy Conversion brings together scattered information on the subject of energy conversion and presents it in terms of the fundamental thermodynamics that apply to energy conversion by any process. Emphasis is given to the development of the theory of heat engines because these are and will remain most important power sources. Descriptive material is then presented to provide elementary information on all important energy conversion devices. The book contains 10 chapters and opens with a discussion of forms of energy, energy sources and storage, and energy conversion. This is foll

  19. Nuclear fuel element

    International Nuclear Information System (INIS)

    Iwano, Yoshihiko.

    1993-01-01

    Microfine cracks having a depth of less than 10% of a pipe thickness are disposed radially from a central axis each at an interval of less than 100 micron over the entire inner circumferential surface of a zirconium alloy fuel cladding tube. For manufacturing such a nuclear fuel element, the inside of the cladding tube is at first filled with an electrolyte solution of potassium chloride. Then, electrolysis is conducted using the cladding tube as an anode and the electrolyte solution as a cathode, and the inner surface of the cladding tube with a zirconium dioxide layer having a predetermined thickness. Subsequently, the cladding tube is laid on a smooth steel plate and lightly compressed by other smooth steel plate to form microfine cracks in the zirconium dioxide layer on the inner surface of the cladding tube. Such a compressing operation is continuously applied to the cladding tube while rotating the cladding tube. This can inhibit progress of cracks on the inner surface of the cladding tube, thereby enabling to prevent failure of the cladding tube even if a pellet/cladding tube mechanical interaction is applied. Accordingly, reliability of the nuclear fuel elements is improved. (I.N.)

  20. Heavy-element nucleosynthesis

    International Nuclear Information System (INIS)

    Mathews, G.J.

    1990-01-01

    New measurements and theoretical studies of nuclear properties, together with new astronomical data on the growth of heavy-element abundances during the early history of the Galaxy, now provide a clearer picture of where in nature the elements heavier than iron are produced by rapid (r-process) and show (s-process) neutron capture reactions. The nuclear data suggest that the r-process involves a high-neutron-density beta-flow equilibrium environment and that the s-process may have occurred at a temperature and neutron density consistent with a 13 C(α,n) 16 0 neutron source. The astronomical data, when compared with simple galactic chemical evolution modes, suggests that the r-process is associated with type II supernovae and that the neutron source must be manufactured by the star. Low-mass type II supernovae are proposed as the most important contributors to the r-process. A 13 C neutron source in intermediate-mass stars is proposed for the s-process. 64 refs., 7 figs

  1. Improved nuclear fuel element

    International Nuclear Information System (INIS)

    1980-01-01

    The invention is of a nuclear fuel element which comprises a central core of a body of nuclear fuel material selected from the group consisting of compounds of uranium, plutonium, thorium and mixtures thereof, and an elongated composite cladding container comprising a zirconium alloy tube containing constituents other than zirconium in an amount greater than about 5000 parts per million by weight and an undeformed metal barrier of moderate purity zirconium bonded to the inside surface of the alloy tube. The container encloses the core so as to leave a gap between the container and the core during use in a nuclear reactor. The metal barrier is of moderate purity zirconium with an impurity level on a weight basis of at least 1000ppm and less than 5000ppm. Impurity levels of specific elements are given. Variations of the invention are also specified. The composite cladding reduces chemical interaction, minimizes localized stress and strain corrosion and reduces the likelihood of a splitting failure in the zirconium alloy tube. Other benefits are claimed. (U.K.)

  2. Tipping elements in the Arctic marine ecosystem.

    Science.gov (United States)

    Duarte, Carlos M; Agustí, Susana; Wassmann, Paul; Arrieta, Jesús M; Alcaraz, Miquel; Coello, Alexandra; Marbà, Núria; Hendriks, Iris E; Holding, Johnna; García-Zarandona, Iñigo; Kritzberg, Emma; Vaqué, Dolors

    2012-02-01

    The Arctic marine ecosystem contains multiple elements that present alternative states. The most obvious of which is an Arctic Ocean largely covered by an ice sheet in summer versus one largely devoid of such cover. Ecosystems under pressure typically shift between such alternative states in an abrupt, rather than smooth manner, with the level of forcing required for shifting this status termed threshold or tipping point. Loss of Arctic ice due to anthropogenic climate change is accelerating, with the extent of Arctic sea ice displaying increased variance at present, a leading indicator of the proximity of a possible tipping point. Reduced ice extent is expected, in turn, to trigger a number of additional tipping elements, physical, chemical, and biological, in motion, with potentially large impacts on the Arctic marine ecosystem.

  3. NIH Common Data Elements Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIH Common Data Elements (CDE) Repository has been designed to provide access to structured human and machine-readable definitions of data elements that have...

  4. Joining elements of silicon carbide

    International Nuclear Information System (INIS)

    Olson, B.A.

    1979-01-01

    A method of joining together at least two silicon carbide elements (e.g.in forming a heat exchanger) is described, comprising subjecting to sufficiently non-oxidizing atmosphere and sufficiently high temperature, material placed in space between the elements. The material consists of silicon carbide particles, carbon and/or a precursor of carbon, and silicon, such that it forms a joint joining together at least two silicon carbide elements. At least one of the elements may contain silicon. (author)

  5. Thermal expansion: Metallic elements and alloys. [Handbook

    Science.gov (United States)

    Touloukian, Y. S.; Kirby, R. K.; Taylor, R. E.; Desai, P. D.

    1975-01-01

    The introductory sections of the work are devoted to the theory of thermal expansion of solids and to methods for the measurement of the linear thermal expansion of solids (X-ray methods, high speed methods, interferometry, push-rod dilatometry, etc.). The bulk of the work is devoted to numerical data on the thermal linear expansion of all the metallic elements, a large number of intermetallics, and a large number of binary alloy systems and multiple alloy systems. A comprehensive bibliography is provided along with an index to the materials examined.

  6. Microelectromechanical resonator based digital logic elements

    KAUST Repository

    Hafiz, Md Abdullah Al

    2016-10-20

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. However, its full realization has been hindered by the difficulty in realizing complex combinational logics, in which the logic function is constructed by cascading multiple smaller logic blocks. In this work we report an alternative approach for implementation of digital logic core elements, multiplexer and demultiplexer, which can be used to realize combinational logic circuits by suitable concatenation. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  7. Microelectromechanical resonator based digital logic elements

    KAUST Repository

    Hafiz, Md Abdullah Al; Kosuru, Lakshmoji; Younis, Mohammad I.; Fariborzi, Hossein

    2016-01-01

    Micro/nano-electromechanical resonator based mechanical computing has recently attracted significant attention. However, its full realization has been hindered by the difficulty in realizing complex combinational logics, in which the logic function is constructed by cascading multiple smaller logic blocks. In this work we report an alternative approach for implementation of digital logic core elements, multiplexer and demultiplexer, which can be used to realize combinational logic circuits by suitable concatenation. Toward this, shallow arch shaped microresonators are electrically connected and their resonance frequencies are tuned based on an electrothermal frequency modulation scheme. This study demonstrates that by reconfiguring the same basic building block, the arch microresonator, complex logic circuits can be realized.

  8. Accurate scaling on multiplicity

    International Nuclear Information System (INIS)

    Golokhvastov, A.I.

    1989-01-01

    The commonly used formula of KNO scaling P n =Ψ(n/ ) for descrete distributions (multiplicity distributions) is shown to contradict mathematically the condition ΣP n =1. The effect is essential even at ISR energies. A consistent generalization of the concept of similarity for multiplicity distributions is obtained. The multiplicity distributions of negative particles in PP and also e + e - inelastic interactions are similar over the whole studied energy range. Collider data are discussed. 14 refs.; 8 figs

  9. Element stacking method for topology optimization with material-dependent boundary and loading conditions

    DEFF Research Database (Denmark)

    Yoon, Gil Ho; Park, Y.K.; Kim, Y.Y.

    2007-01-01

    A new topology optimization scheme, called the element stacking method, is developed to better handle design optimization involving material-dependent boundary conditions and selection of elements of different types. If these problems are solved by existing standard approaches, complicated finite...... element models or topology optimization reformulation may be necessary. The key idea of the proposed method is to stack multiple elements on the same discretization pixel and select a single or no element. In this method, stacked elements on the same pixel have the same coordinates but may have...... independent degrees of freedom. Some test problems are considered to check the effectiveness of the proposed stacking method....

  10. Trace element emissions from coal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-09-15

    Trace elements are emitted during coal combustion. The quantity, in general, depends on the physical and chemical properties of the element itself, the concentration of the element in the coal, the combustion conditions and the type of particulate control device used, and its collection efficiency as a function of particle size. Some trace elements become concentrated in certain particle streams following combustion such as bottom ash, fly ash, and flue gas particulate matter, while others do not. Various classification schemes have been developed to describe this partitioning behaviour. These classification schemes generally distinguish between: Class 1: elements that are approximately equally concentrated in the fly ash and bottom ash, or show little or no fine particle enrichment, examples include Mn, Be, Co and Cr; Class 2: elements that are enriched in the fly ash relative to bottom ash, or show increasing enrichment with decreasing particle size, examples include As, Cd, Pb and Sb; Class 3: elements which are emitted in the gas phase (primarily Hg (not discussed in this review), and in some cases, Se). Control of class 1 trace elements is directly related to control of total particulate matter emissions, while control of the class 2 elements depends on collection of fine particulates. Due to the variability in particulate control device efficiencies, emission rates of these elements can vary substantially. The volatility of class 3 elements means that particulate controls have only a limited impact on the emissions of these elements.

  11. REACTOR FUEL ELEMENTS TESTING CONTAINER

    Science.gov (United States)

    Whitham, G.K.; Smith, R.R.

    1963-01-15

    This patent shows a method for detecting leaks in jacketed fuel elements. The element is placed in a sealed tank within a nuclear reactor, and, while the reactor operates, the element is sparged with gas. The gas is then led outside the reactor and monitored for radioactive Xe or Kr. (AEC)

  12. Free Material Design with Multiple Load Cases

    DEFF Research Database (Denmark)

    Pedersen, Pauli; Pedersen, Niels Leergaard

    2012-01-01

    Multiple load cases and the consideration of strength is a reality that most structural designs are exposed to. Improved possibility to produce specific materials, say by fiber lay-up, put focus on research on free material optimization. A formulation for such design problems together with a prac......Multiple load cases and the consideration of strength is a reality that most structural designs are exposed to. Improved possibility to produce specific materials, say by fiber lay-up, put focus on research on free material optimization. A formulation for such design problems together...... with a practical recursive design procedure is presented and illustrated with examples. The presented finite element analysis involve many elements as well as many load cases. Separating the local amount of material from a description with unit trace for the local anisotropy, gives the free materials formulation...... a more physical interpretation of the material constraint....

  13. Nuclear criticality assessment of Oak Ridge research fuel element storage

    International Nuclear Information System (INIS)

    Thomas, J.T.

    1978-06-01

    Spent and partially spent Oak Ridge Research Reactor (ORR) fuel elements are retained in the storage section of the ORR pool facility. Determination of a maximum expected neutron multiplication factor for the storage area is accomplished by a validated calculational method. The KENO Monte Carlo code and the Hansen-Roach 16-group neutron cross section sets were validated by calculations of critical experiments performed with early ORR fuel elements and with SPERT-D fuel elements. Calculations of various fuel element arrangements are presented which confirm the subcriticality previously inferred from critical experiments and indicate the k/sub eff/ would not exceed 0.85, were the storage area to be filled to capacity with storage racks containing elements with the fissionable material loading increased to 350 g of 235 U

  14. Modal Testing of Seven Shuttle Cargo Elements for Space Station

    Science.gov (United States)

    Kappus, Kathy O.; Driskill, Timothy C.; Parks, Russel A.; Patterson, Alan (Technical Monitor)

    2001-01-01

    From December 1996 to May 2001, the Modal and Control Dynamics Team at NASA's Marshall Space Flight Center (MSFC) conducted modal tests on seven large elements of the International Space Station. Each of these elements has been or will be launched as a Space Shuttle payload for transport to the International Space Station (ISS). Like other Shuttle payloads, modal testing of these elements was required for verification of the finite element models used in coupled loads analyses for launch and landing. The seven modal tests included three modules - Node, Laboratory, and Airlock, and four truss segments - P6, P3/P4, S1/P1, and P5. Each element was installed and tested in the Shuttle Payload Modal Test Bed at MSFC. This unique facility can accommodate any Shuttle cargo element for modal test qualification. Flexure assemblies were utilized at each Shuttle-to-payload interface to simulate a constrained boundary in the load carrying degrees of freedom. For each element, multiple-input, multiple-output burst random modal testing was the primary approach with controlled input sine sweeps for linearity assessments. The accelerometer channel counts ranged from 252 channels to 1251 channels. An overview of these tests, as well as some lessons learned, will be provided in this paper.

  15. Accelerator vacuum system elements

    International Nuclear Information System (INIS)

    Sivokon', V.V.; Kobets, A.F.; Shvetsov, V.A.; Sivokon', L.V.

    1980-01-01

    Some elements of vacuum systems are investigated. Considerable attention has been given to the investigation into peculiarities in pumping out of a ionoguide for transportation of an accelerated charged particles beam the spread of which often attains a considerable length. The number of pumps over the ionoguide length is experimentally determined. It is shown that as a result of ionoguide warm-up the pumping out time is considerably reduced maximum permissible pressure is decreased by two orders and lesser rate of pump pumping out is required. The investigations have shown that when operating the ionoguide there is no necessity in setting up seals between the ionoguide and magnetodischarged pump. The causes of the phenomenon in which the pressure near the pump is greater than in the end of the ionoguide, are impurities carried in by the pump into the ionoguide volume and the pumping out capacity of the pressure converter

  16. Ucla, escuela elemental

    Directory of Open Access Journals (Sweden)

    Neutra, Richard J.

    1962-03-01

    Full Text Available La Escuela Elemental de Preparación de la Universidad de California, en Los Angeles, está dedicada a la educación e investigación y preparación del profesorado de la infancia. Se ha construido en un paraje maravilloso, de frondosa vegetación, frente a un terreno bastante quebrado, circunstancia que presta mayor encanto al conjunto, construido con gran pericia y adaptación al paisaje a base de una dominante horizontalidad, con materiales sencillos (ladrillos, hierro y madera y gran comunicación con la naturaleza mediante grandes cristaleras correderas que ensanchan las clases y las suplementan hacia el jardín de acuerdo con las nuevas normas y prácticas docentes.

  17. Improved nuclear fuel element

    International Nuclear Information System (INIS)

    1974-01-01

    A nuclear fuel element for use in the core of a nuclear reactor is disclosed and has a metal liner disposed between the cladding and the nuclear fuel material and a high lubricity material in the form of a coating disposed between the liner and the cladding. The liner preferably has a thickness greater than the longest fission product recoil distance and is composed of a low neutron capture cross-section material. The liner is preferably composed of zirconium, an alloy of zirconium, niobium or an alloy of niobium. The liner serves as a preferential reaction site for volatile impurities and fission products and protects the cladding from contact and reaction with such impurities and fission products. The high lubricity material acts as an interface between the liner and the cladding and reduces localized stresses on the cladding due to fuel expansion and cracking of the fuel

  18. Probabilistic fracture finite elements

    Science.gov (United States)

    Liu, W. K.; Belytschko, T.; Lua, Y. J.

    1991-05-01

    The Probabilistic Fracture Mechanics (PFM) is a promising method for estimating the fatigue life and inspection cycles for mechanical and structural components. The Probability Finite Element Method (PFEM), which is based on second moment analysis, has proved to be a promising, practical approach to handle problems with uncertainties. As the PFEM provides a powerful computational tool to determine first and second moment of random parameters, the second moment reliability method can be easily combined with PFEM to obtain measures of the reliability of the structural system. The method is also being applied to fatigue crack growth. Uncertainties in the material properties of advanced materials such as polycrystalline alloys, ceramics, and composites are commonly observed from experimental tests. This is mainly attributed to intrinsic microcracks, which are randomly distributed as a result of the applied load and the residual stress.

  19. Nuclear fuel elements

    International Nuclear Information System (INIS)

    Obara, Hiroshi.

    1981-01-01

    Purpose: To suppress iodine release thereby prevent stress corrosion cracks in fuel cans by dispersing ferrous oxide at the outer periphery of sintered uranium dioxide pellets filled and sealed within zirconium alloy fuel cans of fuel elements. Constitution: Sintered uranium dioxide pellets to be filled and sealed within a zirconium alloy fuel can are prepared either by mixing ferric oxide powder in uranium dioxide powder, sintering and then reducing at low temperature or by mixing iron powder in uranium dioxide powder, sintering and then oxidizing at low temperature. In this way, ferrous oxide is dispersed on the outer periphery of the sintered uranium dioxide pellets to convert corrosive fission products iodine into iron iodide, whereby the iodine release is suppressed and the stress corrosion cracks can be prevented in the fuel can. (Moriyama, K.)

  20. Nuclear fuel element

    International Nuclear Information System (INIS)

    Hirama, H.

    1978-01-01

    A nuclear fuel element comprises an elongated tube having upper and lower end plugs fixed to both ends thereof and nuclear fuel pellets contained within the tube. The fuel pellets are held against the lower end plug by a spring which is supported by a setting structure. The setting structure is maintained at a proper position at the middle of the tube by a wedge effect caused by spring force exerted by the spring against a set of balls coacting with a tapered member of the setting structure thereby wedging the balls against the inner wall of the tube, and the setting structure is moved free by pushing with a push bar against the spring force so as to release the wedge effect

  1. Finite element modelling

    International Nuclear Information System (INIS)

    Tonks, M.R.; Williamson, R.; Masson, R.

    2015-01-01

    The Finite Element Method (FEM) is a numerical technique for finding approximate solutions to boundary value problems. While FEM is commonly used to solve solid mechanics equations, it can be applied to a large range of BVPs from many different fields. FEM has been used for reactor fuels modelling for many years. It is most often used for fuel performance modelling at the pellet and pin scale, however, it has also been used to investigate properties of the fuel material, such as thermal conductivity and fission gas release. Recently, the United Stated Department Nuclear Energy Advanced Modelling and Simulation Program has begun using FEM as the basis of the MOOSE-BISON-MARMOT Project that is developing a multi-dimensional, multi-physics fuel performance capability that is massively parallel and will use multi-scale material models to provide a truly predictive modelling capability. (authors)

  2. Heavy-element research

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The status is reported of studies on the solid-state chemistry of the actinides and lanthanides, spectroscopy of actinide compounds, and dynamic chemical description of actinide elements in solution. Phase studies were done on Rb 2 UO 4 , K 2 UO 4 , Li 2 UO 4 , and Es 2 U 2 O 7 . The lithium neptunate (VI) system was investigated and the existence of Li 2 NpO 4 was established. In oxidation-reduction studies it was shown that Am(III) can be electrolytically oxidized to Am(IV) in strong H 3 PO 4 , but Cf(III) and Pr(III) do not oxidize. The low-temperature absorption spectrum of thin films of NpBr 3 was investigated. (U.S.)

  3. ELEMENTAL FORMS OF HOSPITALITY

    Directory of Open Access Journals (Sweden)

    Maximiliano Emanuel Korstanje

    2010-11-01

    Full Text Available Modern studies emphasized on the needs of researching the hospitality as relevant aspects of tourism and hospitality fields. Anyway, these approaches are inextricably intertwined to the industry of tourism and do not take seriously the anthropological and sociological roots of hospitality. In fact, the hotel seems to be a partial sphere of hospitality at all. Under this context, the present paper explores the issue of hospitality enrooted in the political and economic indo-European principle of free-transit which is associated to a much broader origin.  Starting from the premise etymologically hostel and hospital share similar origins, we follow the contributions of J Derrida to determine the elements that formed the hospitality up to date.

  4. Photo-switching element

    Energy Technology Data Exchange (ETDEWEB)

    Masaki, Yuichi

    1987-10-31

    Photo-input MOS transistor (Photo-switching element) cannot give enough ON/OFF ratio but requires an auxiliary condenser for a certain type of application. In addition, PN junction of amorphous silicon is not practical because it gives high leak current resulting in low electromotive force. In this invention, a solar cell was constructed with a lower electrode consisting of a transparent electro-conducting film, a photosensitive part consisting of an amorphous Si layer of p-i-n layer construction, and an upper metal electrode consisting of Cr or Nichrome, and a thin film transistor was placed on the solar cell, and further the upper metal electrode was co-used as a gate electrode of the thin film transistor; this set-up of this invention enabled to attain an efficient photo-electric conversion of the incident light, high electromotive force of the solar cell, and the transistor with high ON/OFF ratio. (3 figs)

  5. Non-Destructive Testing Methods Applied to Multi-Finned SAP Tubing for Nuclear-Fuel Elements; Essais Non Destructifs de Gaines a Ailettes, en Poudre d'Aluminium Frittee, pour Elements Combustibles; Nedestruktivnye metody ispytaniya rebristykh trub iz spechennogo alyuminikiog'o poroshka dlya yadernykh toplivnykh ehlementov; Metodos de Ensayo No Destructivo Aplicados a Tubos de SAP con Aletas Multiples Destinados a Elementos Combustibles

    Energy Technology Data Exchange (ETDEWEB)

    Lund, S. A. [Danish Central Welding Institution, Copenhagen (Denmark); Knudsen, P. [Danish Atomic Energy Commission, Research Establishment, Risoe (Denmark)

    1965-09-15

    The Danish Atomic Energy Commission has undertaken a design study oi an organic-cooled, heavy- water-moderated power reactor. The fuel element for the reactor is a 19-rod bundle; the fuel rods contain sintered uranium-dioxide pellets canned in 2-m long, helically-finned tubes of Sintered Aluminium Product (SAP). A very high quality of the canning tubes is necessary to obtain the optimum heat-transfer conditions and to maintain the integrity of the fuel element during reactor service. Two examples of tube design illustrate the narrow dimensional tolerances. In order to ensure an adequate quality of the canning tubes, a stringent quality control has been established, to a wide extent based upon non-destructive methods. An account is presented of the non-destructive techniques developed for measuring wall thickness and diameters and for detecting defects. The complex 24-finned cross-section prevents the application of ultrasonic or eddy-current methods for wall-thickness measurements. Therefore, a special recording beta-gauge has been developed, based upon the attenuation of beta radiation from a Sr{sup 90} source placed inside the tube. An ultrasonic immersion resonance method is used for the continuous recording of the wall thickness of the more simple 12-finned tube design. Inner and outer (across fin tips) diameters are continuously recorded by rapid air-gauge systems. Flaw detection is carried out by the ultrasonic pulse-echo immersion technique and by eddy-current inspection.. Transverse cracks can easily be detected by the ultrasonic method whereas inspection for longitudinal flaws has not appeared feasible with this method. Therefore, eddy-current inspection is applied in addition to the ultrasonic testing. (author) [French] La Commission de l'energie atomique danoise a entrepris l'etude d'un reacteur de puissance refroidi par un fluide organique et ralenti a l'eau lourde. L'element combustible est constitue par un assemblage de 19 barreaux; chaque barreau

  6. NF-Y loss triggers p53 stabilization and apoptosis in HPV18-positive cells by affecting E6 transcription.

    Science.gov (United States)

    Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol

    2016-07-19

    The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulates HPV18 transcription through the transactivation of multiple cellular transcription factors. NF-YA depletion inhibits the expression of E6 and E7 genes and re-establishes functional p53. The activation of p53 target genes in turn leads to apoptotic cell death. Finally, we show that NF-YA loss sensitizes HPV18-positive cells toward the DNA damaging agent Doxorubicin, via p53-mediated transcriptional response.

  7. Matrix multiplication operations with data pre-conditioning in a high performance computing architecture

    Science.gov (United States)

    Eichenberger, Alexandre E; Gschwind, Michael K; Gunnels, John A

    2013-11-05

    Mechanisms for performing matrix multiplication operations with data pre-conditioning in a high performance computing architecture are provided. A vector load operation is performed to load a first vector operand of the matrix multiplication operation to a first target vector register. A load and splat operation is performed to load an element of a second vector operand and replicating the element to each of a plurality of elements of a second target vector register. A multiply add operation is performed on elements of the first target vector register and elements of the second target vector register to generate a partial product of the matrix multiplication operation. The partial product of the matrix multiplication operation is accumulated with other partial products of the matrix multiplication operation.

  8. Operation characteristics of a multiple type MCFC

    Energy Technology Data Exchange (ETDEWEB)

    Kuroe, S.; Kamo, T. [Hitachi Research Lab., Hitachi, Ltd., Ibaraki-ken (Japan); Fujimura, H.; Kahara, T. [Hitachi, Ltd., Ibaraki-ken (Japan)

    1996-12-31

    Multiple type structure of MCFC of which the separator of the cell is divided by four element cells has been studied. For the stable operation of this type cell, the effect of gas flow rate and temperature distribution on the cell voltage should be clear. In order to clarify these characteristics, a small sized mimic model has been made and tested. The flow rate distribution for the four element cells were varied and cell voltage and temperature distribution were measured for each cell. The decrease in cell voltage and the increase in maximum temperature became remarkable when the apparent utilization factor for one element cell became over 100%. The calculated results agreed fairly good with test results.

  9. Core-Mantle Partitioning of Volatile Elements and the Origin of Volatile Elements in Earth and Moon

    Science.gov (United States)

    Righter, K.; Pando, K.; Danielson, L.; Nickodem, K.

    2014-01-01

    Depletions of siderophile elements in mantles have placed constraints on the conditions on core segregation and differentiation in bodies such as Earth, Earth's Moon, Mars, and asteroid 4 Vesta. Among the siderophile elements there are a sub-set that are also volatile (volatile siderophile elements or VSE; Ga, Ge, In, As, Sb, Sn, Bi, Zn, Cu, Cd), and thus can help to constrain the origin of volatile elements in these bodies, and in particular the Earth and Moon. One of the fundamental observations of the geochemistry of the Moon is the overall depletion of volatile elements relative to the Earth, but a satisfactory explanation has remained elusive. Hypotheses for Earth include addition during accretion and core formation and mobilized into the metallic core, multiple stage origin, or addition after the core formed. Any explanation for volatile elements in the Earth's mantle must also be linked to an explanation of these elements in the lunar mantle. New metal-silicate partitioning data will be applied to the origin of volatile elements in both the Earth and Moon, and will evaluate theories for exogenous versus endogenous origin of volatile elements.

  10. ALICE Photon Multiplicity Detector

    CERN Multimedia

    Nayak, T

    2013-01-01

    Photon Multiplicity Detector (PMD) measures the multiplicity and spatial distribution of photons in the forward region of ALICE on a event-by-event basis. PMD is a pre-shower detector having fine granularity and full azimuthal coverage in the pseudo-rapidity region 2.3 < η < 3.9.

  11. Body Weight - Multiple Languages

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Body Weight URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Body Weight - Multiple Languages To use the sharing features on this page, ...

  12. Multiplicity in difference geometry

    OpenAIRE

    Tomasic, Ivan

    2011-01-01

    We prove a first principle of preservation of multiplicity in difference geometry, paving the way for the development of a more general intersection theory. In particular, the fibres of a \\sigma-finite morphism between difference curves are all of the same size, when counted with correct multiplicities.

  13. Applying Multiple Intelligences

    Science.gov (United States)

    Christodoulou, Joanna A.

    2009-01-01

    The ideas of multiple intelligences introduced by Howard Gardner of Harvard University more than 25 years ago have taken form in many ways, both in schools and in other sometimes-surprising settings. The silver anniversary of Gardner's learning theory provides an opportunity to reflect on the ways multiple intelligences theory has taken form and…

  14. Formation of multiple networks

    DEFF Research Database (Denmark)

    Magnani, Matteo; Rossi, Luca

    2013-01-01

    we introduce the first network formation model for multiple networks. Network formation models are among the most popular tools in traditional network studies, because of both their practical and theoretical impact. However, existing models are not sufficient to describe the generation of multiple...

  15. Orchestrating Multiple Intelligences

    Science.gov (United States)

    Moran, Seana; Kornhaber, Mindy; Gardner, Howard

    2006-01-01

    Education policymakers often go astray when they attempt to integrate multiple intelligences theory into schools, according to the originator of the theory, Howard Gardner, and his colleagues. The greatest potential of a multiple intelligences approach to education grows from the concept of a profile of intelligences. Each learner's intelligence…

  16. Assessing Children's Multiplicative Thinking

    Science.gov (United States)

    Hurst, Chris; Hurrell, Derek

    2016-01-01

    Multiplicative thinking is a "big idea" of mathematics that underpins much of the mathematics learned beyond the early primary school years. This paper reports on a current study that utilises an interview tool and a written quiz to gather data about children's multiplicative thinking. The development of the tools and some of the…

  17. The Chemistry of Superheavy Elements

    CERN Document Server

    Schädel, M

    2003-01-01

    The chemistry of transactinide or superheavy elements has reached element 108. Preparations are under way to leap to element 112 and beyond. The current status of this atom-at-a-time chemical research and its future perspectives are reviewed from an experimental point of view together with some of the interesting results from n -rich nuclides near and at the N=162 neutron shell. Experimental techniques and important results enlightening typical chemical properties of elements 104 through 108 are presented in an exemplary way. From the results of these experiments it is justified to place these elements in the Periodic Table of the Elements in to groups 4 through 8, respectively. However, mainly due to the influence of relativistic effects, it is no longer possible to deduce detailed chemical properties of these superheavy elements simply from this position.

  18. Possibilities of Particle Finite Element Methods in Industrial Forming Processes

    Science.gov (United States)

    Oliver, J.; Cante, J. C.; Weyler, R.; Hernandez, J.

    2007-04-01

    The work investigates the possibilities offered by the particle finite element method (PFEM) in the simulation of forming problems involving large deformations, multiple contacts, and new boundaries generation. The description of the most distinguishing aspects of the PFEM, and its application to simulation of representative forming processes, illustrate the proposed methodology.

  19. Microlocal methods in the analysis of the boundary element method

    DEFF Research Database (Denmark)

    Pedersen, Michael

    1993-01-01

    The application of the boundary element method in numerical analysis is based upon the use of boundary integral operators stemming from multiple layer potentials. The regularity properties of these operators are vital in the development of boundary integral equations and error estimates. We show...

  20. Cognitive Load in Algebra: Element Interactivity in Solving Equations

    Science.gov (United States)

    Ngu, Bing Hiong; Chung, Siu Fung; Yeung, Alexander Seeshing

    2015-01-01

    Central to equation solving is the maintenance of equivalence on both sides of the equation. However, when the process involves an interaction of multiple elements, solving an equation can impose a high cognitive load. The balance method requires operations on both sides of the equation, whereas the inverse method involves operations on one side…

  1. EAF optimal managing elements

    Science.gov (United States)

    Ioana, A.; Constantin, N.; Dragna, E. C.

    2017-01-01

    Electric Arc Furnaces (EAF) is an important and complex aggregate. We present elements of EAF operating efficiency. The reliability of the EAF is mainly determined by electric circuit reliability and especially of the transformator of the furnace. This due to the fact that, in an electric steel plant, the objective „24 tapping/day” involves. Due to the complexity of the process, the EAF operation needs a computer usage and, in his componence, it must have two independent calculation units (UC1) and (UC2). Based on these two input sets (Σi1) and ((Σi2), the calculation unit (UC1) builds the general operation procedure based on mathematical methods. For that purpose, there are used the results of the 5 mathematical methods: the mathematical model to write-off the function objective (M.F.O.); the mathematical model of calculating the charge (M.C.C.); the mathematical model of conducting the effective melt (M.C.M.); the mathematical model of reheating the charge (M.R.C.); the mathematical model of blasting the reactive dusts (M.B.R.D.).

  2. Nuclear fuel element

    International Nuclear Information System (INIS)

    Armijo, J.S.

    1977-01-01

    A nuclear fuel element for use in the core of a nuclear reactor is disclosed which has a composite cladding having a substrate, a metal barrier metallurgically bonded to the inside surface of the substrate and an inner layer metallurgically bonded to the inside surface of the metal barrier. In this composite cladding, the inner layer and the metal barrier shield the substrate from any impurities or fission products from the nuclear fuel material held within the composite cladding. The metal barrier forms about 1 to about 4 percent of the thickness of the cladding and is comprised of a metal selected from the group consisting of niobium, aluminum, copper, nickel, stainless steel, and iron. The inner layer and then the metal barrier serve as reaction sites for volatile impurities and fission products and protect the substrate from contact and reaction with such impurities and fission products. The substrate and the inner layer of the composite cladding are selected from conventional cladding materials and preferably are a zirconium alloy. Also in a preferred embodiment the substrate and the inner layer are comprised of the same material, preferably a zirconium alloy. 19 claims, 2 figures

  3. Neutron absorbing element

    International Nuclear Information System (INIS)

    Kasai, Shigeo.

    1991-01-01

    The present invention concerns a neutron absorbing element of a neutron shielding member used for an LMFBR type reactor. The inside of a fuel can sealed at both of the upper and the lower ends thereof with plugs is partitioned into an upper and a lower chambers by an intermediate plug. A discharging hole is disposed at the upper end plug, which is in communication with the outside. A communication tube is disposed at the intermediate end plug and it is in communication with the lower chamber containing B 4 C pellets. A cylindrical support member having three porous plugs connected in series is disposed at the lower surface of the discharging hole provided at the upper end plug. Further, the end of the discharging hole is sealed with high temperature solder and He atmosphere is present at the inside of the fuel can. With such a constitution, the supporting differential pressure of the porous plugs can be made greater while discharging He gases generated from B 4 C to the outside. Further, the porous plugs can be surely wetted by coolants. Accordingly, it is possible to increase life time and shorten the size. (I.N.)

  4. Chemistry of transuranium elements

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    The half-wave amalgamation potential of No (element 102) was determined. Studies on the preparation and properties of Cf are reported; previously reported results on Es were confirmed. The heat of solution of Bk was measured. Spectroscopic and x-ray diffraction studies of Es-253 bromides are reported. Salicylate complexes with Sm(III), Am(III), Th(IV), and U(IV)O 2 were prepared; crystal data are given. Results of studies on the effect of secondary bonds on the strength of O double bond Np double bond O bonds are reported. The M series x rays of Np were measured. Anomalous spin--orbit splitting of the 4f level in the actinide series is reported. Progress is reported in studies on the Cf oxide system for oxygen pressures up to 760 mm and temperatures between 25 and 1000 0 C, as well as structural parameters of transplutonium oxysulfates and oxysulfides and actinide and lanthanide hydroxides. The electron paramagnetic resonance spectrum of 253 Es 2+ was observed in the cubic monocrystal hosts BaF 2 and SrCl 2

  5. Chemistry of the superheavy elements.

    Science.gov (United States)

    Schädel, Matthias

    2015-03-13

    The quest for superheavy elements (SHEs) is driven by the desire to find and explore one of the extreme limits of existence of matter. These elements exist solely due to their nuclear shell stabilization. All 15 presently 'known' SHEs (11 are officially 'discovered' and named) up to element 118 are short-lived and are man-made atom-at-a-time in heavy ion induced nuclear reactions. They are identical to the transactinide elements located in the seventh period of the periodic table beginning with rutherfordium (element 104), dubnium (element 105) and seaborgium (element 106) in groups 4, 5 and 6, respectively. Their chemical properties are often surprising and unexpected from simple extrapolations. After hassium (element 108), chemistry has now reached copernicium (element 112) and flerovium (element 114). For the later ones, the focus is on questions of their metallic or possibly noble gas-like character originating from interplay of most pronounced relativistic effects and electron-shell effects. SHEs provide unique opportunities to get insights into the influence of strong relativistic effects on the atomic electrons and to probe 'relativistically' influenced chemical properties and the architecture of the periodic table at its farthest reach. In addition, they establish a test bench to challenge the validity and predictive power of modern fully relativistic quantum chemical models. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. Experimental Study of Elements Promoting Mixing in Fuel Elements

    International Nuclear Information System (INIS)

    Silin, Nicolas; Juanico, Luis; Delmastro, Dario

    2003-01-01

    In the present work a thermal tracing technique is used to measure the increase of the mixing between subchannels in the presence of different mixing elements.As representative elements a spacer, a spacer with mixing vanes and turbulence promoter buttons were considered.The performance of these elements was evaluated by studying the behavior of a thermal trace in each case.Also the pressure drop for each case is presented.The results present a qualitative and quantitative guide for the application of each one of these appendages in future nuclear elements

  7. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik

    2002-01-01

    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion...... in the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

  8. A multiplicity logic unit

    International Nuclear Information System (INIS)

    Bialkowski, J.; Moszynski, M.; Zagorski, A.

    1981-01-01

    The logic diagram principle of operation and some details of the design of the multiplicity logic unit are presented. This unit was specially designed to fulfil the requirements of a multidetector arrangement for gamma-ray multiplicity measurements. The unit is equipped with 16 inputs controlled by a common coincidence gate. It delivers a linear output pulse with the height proportional to the multiplicity of coincidences and logic pulses corresponding to 0, 1, ... up to >= 5-fold coincidences. These last outputs are used to steer the routing unit working with the multichannel analyser. (orig.)

  9. Fission neutron multiplicity calculations

    International Nuclear Information System (INIS)

    Maerten, H.; Ruben, A.; Seeliger, D.

    1991-01-01

    A model for calculating neutron multiplicities in nuclear fission is presented. It is based on the solution of the energy partition problem as function of mass asymmetry within a phenomenological approach including temperature-dependent microscopic energies. Nuclear structure effects on fragment de-excitation, which influence neutron multiplicities, are discussed. Temperature effects on microscopic energy play an important role in induced fission reactions. Calculated results are presented for various fission reactions induced by neutrons. Data cover the incident energy range 0-20 MeV, i.e. multiple chance fission is considered. (author). 28 refs, 13 figs

  10. Endogenous viral elements in animal genomes.

    Directory of Open Access Journals (Sweden)

    Aris Katzourakis

    2010-11-01

    Full Text Available Integration into the nuclear genome of germ line cells can lead to vertical inheritance of retroviral genes as host alleles. For other viruses, germ line integration has only rarely been documented. Nonetheless, we identified endogenous viral elements (EVEs derived from ten non-retroviral families by systematic in silico screening of animal genomes, including the first endogenous representatives of double-stranded RNA, reverse-transcribing DNA, and segmented RNA viruses, and the first endogenous DNA viruses in mammalian genomes. Phylogenetic and genomic analysis of EVEs across multiple host species revealed novel information about the origin and evolution of diverse virus groups. Furthermore, several of the elements identified here encode intact open reading frames or are expressed as mRNA. For one element in the primate lineage, we provide statistically robust evidence for exaptation. Our findings establish that genetic material derived from all known viral genome types and replication strategies can enter the animal germ line, greatly broadening the scope of paleovirological studies and indicating a more significant evolutionary role for gene flow from virus to animal genomes than has previously been recognized.

  11. Analog elements for transuranic chemistries

    International Nuclear Information System (INIS)

    Weimer, W.C.

    1982-01-01

    The analytical technique for measuring trace concentrations of the analog rare earth elements has been refined for optimal detection. The technique has been used to determine the rare earth concentrations in a series of geological and biological materials, including samples harvested from controlled lysimeter investigations. These studies have demonstrated that any of the trivalent rare earth elements may be used as analog elements for the trivalent transuranics, americium and curium

  12. Multiple sclerosis research

    International Nuclear Information System (INIS)

    Battaglia, M.A.

    1990-01-01

    This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

  13. Generalized internal multiple imaging

    KAUST Repository

    Zuberi, M. A. H.; Alkhalifah, Tariq Ali

    2014-01-01

    Internal multiples deteriorate the image when the imaging procedure assumes only single scattering, especially if the velocity model does not have sharp contrasts to reproduce such scattering in the Green’s function through forward modeling

  14. Connecting the Production Multiple

    DEFF Research Database (Denmark)

    Lichen, Alex Yu; Mouritsen, Jan

    &OP process itself is a fluid object, but there is still possibility to organise the messy Production. There are connections between the Production multiple and the managerial technology fluid. The fluid enacted the multiplicity of Production thus making it more difficult to be organised because there were...... in opposite directions. They are all part of the fluid object. There is no single chain of circulating references that makes the object a matter of fact. Accounting fluidity means that references drift back and forth and enact new realities also connected to the chain. In this setting future research may......This paper is about objects. It follows post ANT trajectories and finds that objects are multiple and fluid. Extant classic ANT inspired accounting research largely sees accounting inscriptions as immutable mobiles. Although multiplicity of objects upon which accounting acts has been explored...

  15. Multiple sex partner

    African Journals Online (AJOL)

    User

    intercourse, about 60% reported having a single sexual partner and 40% reported having multiple ... masturbation, start having sex at a younger age, have sex with married people and/or .... sex were considered unacceptable by 89 vs.

  16. Multiple Stages 2

    DEFF Research Database (Denmark)

    Andreasen, John

    Multiple stages 2: theatrical futures, set design, community plays, cultural capitals, democracy & drama, WWII dramas, performance on adoption, promenade about emigration, qualities in political theatre, performance analysis, dramaturgical education, Toulmin Variations...

  17. Rehabilitation and multiple sclerosis

    DEFF Research Database (Denmark)

    Dalgas, Ulrik

    2011-01-01

    In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

  18. Photoshop Elements 10 For Dummies

    CERN Document Server

    Obermeier, Barbara

    2011-01-01

    Perfect your photos and images with this "focused" guide to the latest version of Photoshop Elements For most of us, the professional-level Photoshop is overkill for our needs. Amateur photographers and photo enthusiasts turn to Photoshop Elements for a powerful but simpler way to edit and retouch their snapshots. Photoshop Elements 10 For Dummies, fully updated and revised for the latest release of this software product, helps you navigate Elements to create, edit, fix, share, and organize the high-quality images you desire. Full color pages bring the techniques to life and make taking great

  19. Generalized internal multiple imaging

    KAUST Repository

    Zuberi, M. A. H.

    2014-08-05

    Internal multiples deteriorate the image when the imaging procedure assumes only single scattering, especially if the velocity model does not have sharp contrasts to reproduce such scattering in the Green’s function through forward modeling. If properly imaged, internal multiples (internally scattered energy) can enhance the seismic image. Conventionally, to image internal multiples, accurate, sharp contrasts in the velocity model are required to construct a Green’s function with all the scattered energy. As an alternative, we have developed a generalized internal multiple imaging procedure that images any order internal scattering using the background Green’s function (from the surface to each image point), constructed from a smooth velocity model, usually used for conventional imaging. For the first-order internal multiples, the approach consisted of three steps, in which we first back propagated the recorded surface seismic data using the background Green’s function, then crosscorrelated the back-propagated data with the recorded data, and finally crosscorrelated the result with the original background Green’s function. This procedure images the contribution of the recorded first-order internal multiples, and it is almost free of the single-scattering recorded energy. The cost includes one additional crosscorrelation over the conventional single-scattering imaging application. We generalized this method to image internal multiples of any order separately. The resulting images can be added to the conventional single-scattering image, obtained, e.g., from Kirchhoff or reverse-time migration, to enhance the image. Application to synthetic data with reflectors illuminated by multiple scattering (double scattering) demonstrated the effectiveness of the approach.

  20. Neutron source multiplication method

    International Nuclear Information System (INIS)

    Clayton, E.D.

    1985-01-01

    Extensive use has been made of neutron source multiplication in thousands of measurements of critical masses and configurations and in subcritical neutron-multiplication measurements in situ that provide data for criticality prevention and control in nuclear materials operations. There is continuing interest in developing reliable methods for monitoring the reactivity, or k/sub eff/, of plant operations, but the required measurements are difficult to carry out and interpret on the far subcritical configurations usually encountered. The relationship between neutron multiplication and reactivity is briefly discussed and data presented to illustrate problems associated with the absolute measurement of neutron multiplication and reactivity in subcritical systems. A number of curves of inverse multiplication have been selected from a variety of experiments showing variations observed in multiplication during the course of critical and subcritical experiments where different methods of reactivity addition were used, with different neutron source detector position locations. Concern is raised regarding the meaning and interpretation of k/sub eff/ as might be measured in a far subcritical system because of the modal effects and spectrum differences that exist between the subcritical and critical systems. Because of this, the calculation of k/sub eff/ identical with unity for the critical assembly, although necessary, may not be sufficient to assure safety margins in calculations pertaining to far subcritical systems. Further study is needed on the interpretation and meaning of k/sub eff/ in the far subcritical system

  1. MULTIPLE SPINAL CANAL MENINGIOMAS

    Directory of Open Access Journals (Sweden)

    Nandigama Pratap Kumar

    2016-10-01

    Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

  2. Rare-earth elements

    Science.gov (United States)

    Van Gosen, Bradley S.; Verplanck, Philip L.; Seal, Robert R.; Long, Keith R.; Gambogi, Joseph; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

    2017-12-19

    The rare-earth elements (REEs) are 15 elements that range in atomic number from 57 (lanthanum) to 71 (lutetium); they are commonly referred to as the “lanthanides.” Yttrium (atomic number 39) is also commonly regarded as an REE because it shares chemical and physical similarities and has affinities with the lanthanides. Although REEs are not rare in terms of average crustal abundance, the concentrated deposits of REEs are limited in number.Because of their unusual physical and chemical properties, the REEs have diverse defense, energy, industrial, and military technology applications. The glass industry is the leading consumer of REE raw materials, which are used for glass polishing and as additives that provide color and special optical properties to the glass. Lanthanum-based catalysts are used in petroleum refining, and cerium-based catalysts are used in automotive catalytic converters. The use of REEs in magnets is a rapidly increasing application. Neodymium-iron-boron magnets, which are the strongest known type of magnets, are used when space and weight are restrictions. Nickel-metal hydride batteries use anodes made of a lanthanum-based alloys.China, which has led the world production of REEs for decades, accounted for more than 90 percent of global production and supply, on average, during the past decade. Citing a need to retain its limited REE resources to meet domestic requirements as well as concerns about the environmental effects of mining, China began placing restrictions on the supply of REEs in 2010 through the imposition of quotas, licenses, and taxes. As a result, the global rare-earth industry has increased its stockpiling of REEs; explored for deposits outside of China; and promoted new efforts to conserve, recycle, and substitute for REEs. New mine production began at Mount Weld in Western Australia, and numerous other exploration and development projects noted in this chapter are ongoing throughout the world.The REE-bearing minerals are

  3. Element Verification and Comparison in Sierra/Solid Mechanics Problems

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Yuki; Roth, William

    2016-05-01

    The goal of this project was to study the effects of element selection on the Sierra/SM solutions to five common solid mechanics problems. A total of nine element formulations were used for each problem. The models were run multiple times with varying spatial and temporal discretization in order to ensure convergence. The first four problems have been compared to analytical solutions, and all numerical results were found to be sufficiently accurate. The penetration problem was found to have a high mesh dependence in terms of element type, mesh discretization, and meshing scheme. Also, the time to solution is shown for each problem in order to facilitate element selection when computer resources are limited.

  4. On diversity performance of two-element coupling element based antenna structure for mobile terminal

    DEFF Research Database (Denmark)

    Al-Hadi, Azremi Abdullah; Toivanen, Juha; Laitinen, Tommi

    2010-01-01

    .1 and the diversity gain is equal to 10.2 dB at 99% reliability level using selection combining technique across simulation and both measurement methods. The measurement techniques are compared to show how accurately the diversity performance of a mobile terminal antenna can be estimated.......In wireless communication systems, multipath interference has a significant impact on system design and performance. Fast fading is caused by the coherent summation of one or more echoes from many reflection points reaching the receive antenna. Antenna diversity can be used to mitigate multipath...... fading. The main challenge of antenna diversity in practical application is the integration of multiple antennas on a small ground plane. Two-element antenna structure based on coupling element antenna concept for diversity application has been studied in previous work and it has shown to be feasible...

  5. Computation of subsonic flow around airfoil systems with multiple separation

    Science.gov (United States)

    Jacob, K.

    1982-01-01

    A numerical method for computing the subsonic flow around multi-element airfoil systems was developed, allowing for flow separation at one or more elements. Besides multiple rear separation also sort bubbles on the upper surface and cove bubbles can approximately be taken into account. Also, compressibility effects for pure subsonic flow are approximately accounted for. After presentation the method is applied to several examples and improved in some details. Finally, the present limitations and desirable extensions are discussed.

  6. Rack for nuclear fuel elements

    International Nuclear Information System (INIS)

    Rubinstein, H.J.; Gordon, C.B.; Robison, A.; Clark, P.M.

    1977-01-01

    Disclosed is a rack for storing spent nuclear fuel elements in which a plurality of aligned rows of upright enclosures of generally square cross-sectional areas contain vertically disposed spent fuel elements. Each fuel element is supported at the lower end thereof by a respective support that rests on the floor of the spent fuel pool for a nuclear power plant. An open rack frame is employed as an upright support for the enclosures containing the spent fuel elements. Legs at the lower corners of the frame rest on the floor of the pool to support the frame. In one exemplary embodiment, the support for the fuel element is in the form of a base on which a fuel element rests and the base is supported by legs. In another exemplary embodiment, each fuel element is supported on the pool floor by a self-adjusting support in the form of a base on which a fuel element rests and the base rests on a ball or swivel joint for self-alignment. The lower four corners of the frame are supported by legs adjustable in height for leveling the frame. Each adjustable frame leg is in the form of a base resting on the pool floor and the base supports a threaded post. The threaded post adjustably engages a threaded column on which rests the lower end of the frame. 16 claims, 14 figures

  7. Thermal insulation of fuel elements

    International Nuclear Information System (INIS)

    Dubrovcak, P.; Pec, V.; Pitonak, J.

    1978-01-01

    The claim of the invention concerns thermal insulation of fuel elements heated for measurement of uranium fuel physical properties. For this, layers of aluminium film and of glass fibre are wound onto the inner tube of the element cladding. The space between the inner and the outer tubes is evacuated and the tubes are spaced using spacer wires. (M.S.)

  8. On symmetric pyramidal finite elements

    Czech Academy of Sciences Publication Activity Database

    Liu, L.; Davies, K. B.; Yuan, K.; Křížek, Michal

    2004-01-01

    Roč. 11, 1-2 (2004), s. 213-227 ISSN 1492-8760 R&D Projects: GA AV ČR IAA1019201 Institutional research plan: CEZ:AV0Z1019905 Keywords : mesh generation * finite element method * composite elements Subject RIV: BA - General Mathematics Impact factor: 0.108, year: 2004

  9. Fluid element in SAP IV

    International Nuclear Information System (INIS)

    Yilmaz, C.; Akkas, N.

    1979-01-01

    In previous studies a fluid element is incorporated in the widely used general purpose finite element program SAPIV. This type of problem is of interest in the design of nuclear components involving geometric complexities and nonlinearities. The elasticity matrix of a general-purpose finite element program is modified in such a way that it becomes possible to idealize fluid as a structural finite element with zero shear modulus and a given bulk modules. Using the modified version of SAPIV, several solid-fluid interactions problems are solved. The numerical solutions are compared with the available analytical solutions. They are shown to be in reasonable aggrement. It is also shown that by solving an exterior-fluid interaction problem, the pressure wave propagation in the acoustic medium can be solved with the same approach. In this study, two of the problem not studied in the previous work will be presented. These problems are namely the effects of the link elements used at solid-fluid interfaces and of the concentrated loads on the response of the fluid medium. Truss elements are used as the link elements. After these investigations, it is decided that general purpose finite element programs with slight modifications can be used in the safety analysis of nuclear reactor plants. By this procedure it is possible to handle two-dimensional plane strain and tridimensional axisymmetric problems of this type. (orig.)

  10. Chemical experiments with superheavy elements.

    Science.gov (United States)

    Türler, Andreas

    2010-01-01

    Unnoticed by many chemists, the Periodic Table of the Elements has been extended significantly in the last couple of years and the 7th period has very recently been completed with eka-Rn (element 118) currently being the heaviest element whose synthesis has been reported. These 'superheavy' elements (also called transactinides with atomic number > or = 104 (Rf)) have been artificially synthesized in fusion reactions at accelerators in minute quantities of a few single atoms. In addition, all isotopes of the transactinide elements are radioactive and decay with rather short half-lives. Nevertheless, it has been possible in some cases to investigate experimentally chemical properties of transactinide elements and even synthesize simple compounds. The experimental investigation of superheavy elements is especially intriguing, since theoretical calculations predict significant deviations from periodic trends due to the influence of strong relativistic effects. In this contribution first experiments with hassium (Hs, atomic number 108), copernicium (Cn, atomic number 112) and element 114 (eka-Pb) are reviewed.

  11. Repetitive elements in parasitic protozoa

    Directory of Open Access Journals (Sweden)

    Clayton Christine

    2010-05-01

    Full Text Available Abstract A recent paper published in BMC Genomics suggests that retrotransposition may be active in the human gut parasite Entamoeba histolytica. This adds to our knowledge of the various types of repetitive elements in parasitic protists and the potential influence of such elements on pathogenicity. See research article http://www.biomedcentral.com/1471-2164/11/321

  12. Fatty acid elongase 1 (FAE1) promoter as a candidate for genetic ...

    African Journals Online (AJOL)

    As an important cis-regulatory element, a promoter plays a key role in plant gene expression and regulation, and has been widely used in plant genetic engineering. The fatty acid elongase 1 (FAE1) promoter was isolated from Arabidopsis thaliana. Sequence analysis showed that the FAE1 promoter contains two Skn-1 ...

  13. Trace elements in human milk

    Energy Technology Data Exchange (ETDEWEB)

    Parr, R M [International Atomic Energy Agency, Vienna (Austria). Div. of Life Sciences

    1983-06-01

    Trace elements are those elements having a concentration lower than 10 ppm in body fluids or tissues. A total of 24 elements, both trace and minor elements, present in human milk have been analysed in this study, employing neutron activation analysis and absorption spectroscopy. The analyses have been carried out collaboratively by several different laboratories and the Agency which has also served as a coordinating centre. Although the evaluation of the results, altogether 8500 separate values, is still in progress, enough evidence is already available, however, to show some very interesting differences between different study areas and, in some cases, between different socio-economic groups within a single country. The main value of these data will probably be to throw new light on the nutritional requirements of young babies for trace elements.

  14. Massively Parallel Finite Element Programming

    KAUST Repository

    Heister, Timo

    2010-01-01

    Today\\'s large finite element simulations require parallel algorithms to scale on clusters with thousands or tens of thousands of processor cores. We present data structures and algorithms to take advantage of the power of high performance computers in generic finite element codes. Existing generic finite element libraries often restrict the parallelization to parallel linear algebra routines. This is a limiting factor when solving on more than a few hundreds of cores. We describe routines for distributed storage of all major components coupled with efficient, scalable algorithms. We give an overview of our effort to enable the modern and generic finite element library deal.II to take advantage of the power of large clusters. In particular, we describe the construction of a distributed mesh and develop algorithms to fully parallelize the finite element calculation. Numerical results demonstrate good scalability. © 2010 Springer-Verlag.

  15. Massively Parallel Finite Element Programming

    KAUST Repository

    Heister, Timo; Kronbichler, Martin; Bangerth, Wolfgang

    2010-01-01

    Today's large finite element simulations require parallel algorithms to scale on clusters with thousands or tens of thousands of processor cores. We present data structures and algorithms to take advantage of the power of high performance computers in generic finite element codes. Existing generic finite element libraries often restrict the parallelization to parallel linear algebra routines. This is a limiting factor when solving on more than a few hundreds of cores. We describe routines for distributed storage of all major components coupled with efficient, scalable algorithms. We give an overview of our effort to enable the modern and generic finite element library deal.II to take advantage of the power of large clusters. In particular, we describe the construction of a distributed mesh and develop algorithms to fully parallelize the finite element calculation. Numerical results demonstrate good scalability. © 2010 Springer-Verlag.

  16. Multiple primary cancer

    International Nuclear Information System (INIS)

    Jung, Gyu Sik; Lee, Ouk; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duck

    1989-01-01

    It is rare for one human being to be afflicted with more than one cancer. However with further advances in therapeutic regimens, histopathologic observation, diagnostic modalities, and increased curiosity, there are increasing number of case reports of multiple primary cancer. The present study evaluates 25 histologically confirmed cases of multiple primary cancer from 1974 to 1988 at Kosin Medical Center. The most frequent site of the first primary cancer in male was stomach and in female, uterine cervix. The first primary cancer in female occurred in endocrine-related organs (breast, uterus and thyroid) in 63.6 percent. Synchronous cancers are diagnosed simultaneously or within an interval of about six months and synchronous cancers were 16 out of 25 cases. Metachronous cancers are diagnosed at interval of more than six months. There were 9 metachronous cancers and average interval between the first and second primary cancer was 22.8 months. The incidence of multiple primary cancer was 0.11 percent. The average age was 51.9 years at the time of the first primary cancer (53.1 years in male and 50.3 years in female). CT scan was most helpful in early detection of multiple primary cancers facilitating biopsy and surgery. Multiple primary cancers are beyond the medical curiosity. Early diagnosis of the disease and careful follow-up study, based on an awareness of the possibility of second cancers, will substantially increase the survival of these patients

  17. The Future Multiple

    DEFF Research Database (Denmark)

    Spaniol, Matthew Jon; Rowland, Nicholas James

    2015-01-01

    /value – The original contribution is in demonstrating how plural futures and the singular future co-exist in practice. Thus, an eclipse of the future by futures can only ever be partial. For “futures” to be conceptually potent, “the future” must be at least provisionally believable and occasionally useful. Otherwise......, if “the future” were so preposterous an idea, then “futures” would cease to be a critical alternative to it. Futures needs the future; they are relationally bound together in a multiplicity. This paper considers what such a logical reality implies for a field that distances itself from the future and self......). Multiplicity, as a post-ANT sensibility, helps one make sense of the empirical materials. This paper examines the possibility that rather than being alternatives to one another, plural futures and the singular future might co-exist in practice, and, thus, constitute a multiplicity. Design...

  18. Hadron multiplicities at COMPASS

    Energy Technology Data Exchange (ETDEWEB)

    Du Fresne von Hohenesche, Nicolas [Institut fuer Kernphysik, Universitaet Mainz, Johann-Joachim-Becher-Weg 45, 55128 Mainz (Germany); Collaboration: COMPASS Collaboration

    2014-07-01

    Quark fragmentation functions (FF) D{sub q}{sup h}(z,Q{sup 2}) describe final-state hadronization of quarks q into hadrons h. The FFs can be extracted from hadron multiplicities produced in semi-inclusive deep inelastic scattering. The COMPASS collaboration has recently measured charged hadron multiplicities for identified pions and kaons using a 160 GeV/c muon beam impinging on an iso-scalar target. The data cover a large kinematical range and provide an important input for global QCD analyses of world data at NLO, aiming at the determination of FFs in particular in the strange quark sector. The newest results from COMPASS on pion and kaon multiplicities will be presented.

  19. Complex finite element sensitivity method for creep analysis

    International Nuclear Information System (INIS)

    Gomez-Farias, Armando; Montoya, Arturo; Millwater, Harry

    2015-01-01

    The complex finite element method (ZFEM) has been extended to perform sensitivity analysis for mechanical and structural systems undergoing creep deformation. ZFEM uses a complex finite element formulation to provide shape, material, and loading derivatives of the system response, providing an insight into the essential factors which control the behavior of the system as a function of time. A complex variable-based quadrilateral user element (UEL) subroutine implementing the power law creep constitutive formulation was incorporated within the Abaqus commercial finite element software. The results of the complex finite element computations were verified by comparing them to the reference solution for the steady-state creep problem of a thick-walled cylinder in the power law creep range. A practical application of the ZFEM implementation to creep deformation analysis is the calculation of the skeletal point of a notched bar test from a single ZFEM run. In contrast, the standard finite element procedure requires multiple runs. The value of the skeletal point is that it identifies the location where the stress state is accurate, regardless of the certainty of the creep material properties. - Highlights: • A novel finite element sensitivity method (ZFEM) for creep was introduced. • ZFEM has the capability to calculate accurate partial derivatives. • ZFEM can be used for identification of the skeletal point of creep structures. • ZFEM can be easily implemented in a commercial software, e.g. Abaqus. • ZFEM results were shown to be in excellent agreement with analytical solutions

  20. Platinum-group elements

    Science.gov (United States)

    Zientek, Michael L.; Loferski, Patricia J.; Parks, Heather L.; Schulte, Ruth F.; Seal, Robert R.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

    2017-12-19

    The platinum-group elements (PGEs)—platinum, palladium, rhodium, ruthenium, iridium, and osmium—are metals that have similar physical and chemical properties and tend to occur together in nature. PGEs are indispensable to many industrial applications but are mined in only a few places. The availability and accessibility of PGEs could be disrupted by economic, environmental, political, and social events. The United States net import reliance as a percentage of apparent consumption is about 90 percent.PGEs have many industrial applications. They are used in catalytic converters to reduce carbon monoxide, hydrocarbon, and nitrous oxide emissions in automobile exhaust. The chemical industry requires platinum or platinum-rhodium alloys to manufacture nitric oxide, which is the raw material used to manufacture explosives, fertilizers, and nitric acid. In the petrochemical industry, platinum-supported catalysts are needed to refine crude oil and to produce aromatic compounds and high-octane gasoline. Alloys of PGEs are exceptionally hard and durable, making them the best known coating for industrial crucibles used in the manufacture of chemicals and synthetic materials. PGEs are used by the glass manufacturing industry in the production of fiberglass and flat-panel and liquid crystal displays. In the electronics industry, PGEs are used in computer hard disks, hybridized integrated circuits, and multilayer ceramic capacitors.Aside from their industrial applications, PGEs are used in such other fields as health, consumer goods, and finance. Platinum, for example, is used in medical implants, such as pacemakers, and PGEs are used in cancer-fighting drugs. Platinum alloys are an ideal choice for jewelry because of their white color, strength, and resistance to tarnish. Platinum, palladium, and rhodium in the form of coins and bars are also used as investment commodities, and various financial instruments based on the value of these PGEs are traded on major exchanges

  1. A universal encoding scheme for MIMO transmission using a single active element for PSK modulation schemes

    DEFF Research Database (Denmark)

    Alrabadi, Osama; Papadias, C.B.; Kalis, A.

    2009-01-01

    A universal scheme for encoding multiple symbol streams using a single driven element (and consequently a single radio frequency (RF) frontend) surrounded by parasitic elements (PE) loaded with variable reactive loads, is proposed in this paper. The proposed scheme is based on creating a MIMO sys...

  2. Multiplicities and parton dynamics

    International Nuclear Information System (INIS)

    Knuteson, R.O.

    1987-01-01

    The production of strongly interacting particles from the annihilation of electrons and positrons at high energies is studied, with emphasis on the multiplicity, or number, of particles produced. A probabilistic branching model based on the leading log approximation in QCD is formulated to predict the evolution of particle number with the energy of collision. Direct integration of a master equation for the probabilities allows a comparison to the experimentally observed particle distribution. The production of strongly interacting particles from proton-antiproton collisions is also considered. A model for the production of particles from parton-parton collisions is presented and the growth in multiplicity with energy demonstrated

  3. Sentencing Multiple Crimes

    DEFF Research Database (Denmark)

    Most people assume that criminal offenders have only been convicted of a single crime. However, in reality almost half of offenders stand to be sentenced for more than one crime.The high proportion of multiple crime offenders poses a number of practical and theoretical challenges for the criminal......, and psychology offer their perspectives to the volume. A comprehensive examination of the dynamics involved with sentencing multiple offenders has the potential to be a powerful tool for legal scholars and professionals, particularly given the practical importance of the topic and the relative dearth of research...

  4. High-multiplicity processes

    International Nuclear Information System (INIS)

    Shelkov, G.; Sisakyan, A.; Mandzhavidze, I.

    1999-01-01

    We wish to demonstrate that investigation of asymptotically high multiplicity (AHM) hadron reactions may solve, or at least clear up, a number of problems unsolvable by other ways. We would lean upon the idea: (i) the reactions final state entropy is proportional to multiplicity and, by this reason, just in the AHM domain one may expect the equilibrium final state and (ii) the AHM final state is cold because of the energy-momentum conservation laws. This means that the collective phenomena may become important in the AHM domain. The possibility of hard processes dominance is considered also

  5. Chemistry of the heaviest elements

    International Nuclear Information System (INIS)

    Hoffman, D.C.

    1996-01-01

    Studies of the chemical properties of the elements at the uppermost end of the periodic table are discussed. Some historical perspective is given, but major emphasis is on recent studies. Isotopes of these elements are short-lived and, therefore, must be studied near the site of production. They must be produced with charged-particle beams at accelerators rather than via neutron capture. The use of radioactive heavy actinide targets is often required and the number of atoms produced is so small that any chemistry to be performed must be done on an ''atom-at-a-time'' basis. Furthermore, a knowledge of their nuclear properties is required in order to identify and detect them. To date, both gas and aqueous phase properties of elements as heavy as element 104 (rutherfordium) and element 105 (hahnium) have been investigated, even though their longest-lived known isotopes have half-lives of only 65 and 35 seconds, respectively. The experimental results show that their chemical properties cannot be simply extrapolated from the known properties of their lighter homologs in the periodic table, emphasizing the importance of obtaining additional experimental information for the heaviest elements to compare with predictions and help assess the influence of relativistic effects. The feasibility of the extension of chemical studies to still heavier elements is also discussed. (orig.)

  6. Long identical multispecies elements in plant and animal genomes.

    Science.gov (United States)

    Reneker, Jeff; Lyons, Eric; Conant, Gavin C; Pires, J Chris; Freeling, Michael; Shyu, Chi-Ren; Korkin, Dmitry

    2012-05-08

    Ultraconserved elements (UCEs) are DNA sequences that are 100% identical (no base substitutions, insertions, or deletions) and located in syntenic positions in at least two genomes. Although hundreds of UCEs have been found in animal genomes, little is known about the incidence of ultraconservation in plant genomes. Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes. Among six animal genomes, we found the previously known syntenic UCEs as well as previously undescribed nonsyntenic elements. In contrast, among six plant genomes, we only found nonsyntenic LIMEs. LIMEs can also be classified as either simple (repetitive) or complex (nonrepetitive), they may occur in multiple copies in a genome, and they are often spread across multiple chromosomes. Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number. Further analyses of plant LIMEs revealed their functional diversity, encompassing elements found near rRNA and enzyme-coding genes, as well as those found in transposons and noncoding DNA. We conclude that despite the common presence of LIMEs in both animal and plant lineages, the evolutionary processes involved in the creation and maintenance of these elements differ in the two groups and are likely attributable to several mechanisms, including transfer of genetic material from organellar to nuclear genomes, de novo sequence manufacturing, and purifying selection.

  7. Hydrogen in CANDU fuel elements

    International Nuclear Information System (INIS)

    Sejnoha, R.; Manzer, A.M.; Surette, B.A.

    1995-01-01

    Unirradiated and irradiated CANDU fuel cladding was tested to compare the role of stress-corrosion cracking and of hydrogen in the development of fuel defects. The results of the tests are compared with information on fuel performance in-reactor. The role of hydriding (deuteriding) from the coolant and from the fuel element inside is discussed, and the control of 'hydrogen gas' content in the element is confirmed as essential for defect-free fuel performance. Finally, implications for fuel element design are discussed. (author)

  8. Origin of the chemical elements

    Energy Technology Data Exchange (ETDEWEB)

    Tayler, R J

    1984-05-01

    The subject is discussed in relation to the composition of initially created matter and changes which have occurred during the life history of the universe, with particular reference to our galaxy and nearby galaxies. Headings are: observations of element abundances (stars, gas clouds in our own and nearby galaxies, hot gas in galaxy clusters, the solar system); the originally created matter (Big Bang theory and early nuclear reactions); processes changing observed composition (galactic evolution; nuclear fusion reactions in stellar interiors; chemical composition of a highly evolved massive star); supernovae (production of heavy elements); chemical evolution of the galaxy; production of very heavy elements (s process, r process).

  9. Increased burnup of fuel elements

    International Nuclear Information System (INIS)

    Ahlf, J.

    1983-01-01

    The specialists' group for fuel elements of the Kerntechnische Gesellschaft e.V. held a meeting on ''Increased Burnup of Fuel Elements'' on 9th and 10th of November 1982 at the GKSS Research Center Geesthacht. Most papers dealt with the problems of burnup increase of fuel elements for light water reactors with respect to fuel manufacturing, power plant operation and reprocessing. Review papers were given on the burnup limits for high temperature gas cooled reactors and sodium fast breeder reactors. The meeting ended with a presentation of the technical equipment of the hot laboratory of the GKSS and the programs which are in progress there. (orig.) [de

  10. [Delivery in multiple pregnancies].

    Science.gov (United States)

    Colla, F; D'Addato, F; Grio, R

    2001-04-01

    A knowledge of clinical physiognomy in pathologies related to multiple births is indispensable for improving maternal and feto-neonatal prognosis. This study is a contribution to the solution of this problem. A meta-analysis of data for multiple births at Department B of the Gynecology and Obstetrics Clinic at the University of Turi during the decade 1989-1998 was carried out, focusing on the arrangement and presentation of fetuses, the various types of birth, the gestational age at which birth occurred, the weight of neonates, neonatal mortality and maternal morbidity. Out of 11,523 births, there were a total of 194 (1.68%) multiple births, including 190 sets of twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred 1500 g). The perinatal mortality rate was 3.82%. Maternal complications mainly occurred during the placental state, in the immediate postpartum and in puerperio. The authors feel that a more careful medical and social assistance, preventive hospitalisation, early recognition of the risk, constant monitoring for the optimal timing of birth, and lastly, qualified medical assistance during labour (expert gynecologist, trained obstetric staff) with other medical personnel (anesthetist, neonatal specialist) represent winning strategies to solve the problems arising during multiple pregnancies.

  11. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... breast and ascending colon. KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous. Multiple Primary Tumors. MA Adeyanju, AA Ilori. Address for correspondence: Dr. MA Adeyanju,. Department of Surgery, Federal Medical Centre, Ebute Metta,. Lagos, Nigeria. E-mail: mbadeyanju@yahoo.

  12. Back Pain - Multiple Languages

    Science.gov (United States)

    ... List of All Topics All Back Pain - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated on 31 May 2018

  13. Anemia - Multiple Languages

    Science.gov (United States)

    ... XYZ List of All Topics All Anemia - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated on 30 April 2018

  14. Allergy - Multiple Languages

    Science.gov (United States)

    ... XYZ List of All Topics All Allergy - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated on 23 May 2018

  15. Alcohol - Multiple Languages

    Science.gov (United States)

    ... XYZ List of All Topics All Alcohol - Multiple Languages To use the sharing features on this page, please enable JavaScript. Arabic (العربية) ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated on 16 April 2018

  16. Immunomodulation of multiple myeloma.

    Science.gov (United States)

    Tohnya, Tanyifor M; Figg, William D

    2004-11-01

    Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

  17. Seizures in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Uyttenboogaart, Maarten; Polman, Susan; De Keyser, Jacques

    Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the

  18. Multiple Primary Cancer Monograph

    Science.gov (United States)

    To identify groups of cancer survivors that are at increased risk for multiple primary cancers, investigators led an effort to provide the first comprehensive population-based analysis of the risk of subsequent cancer in the U.S., resulting in a monograph.

  19. Reduced multiplication modules

    Indian Academy of Sciences (India)

    if M is a von Neumann regular module (VNM); i.e., every principal submodule of M is a summand submodule. Also if M is an injective R-module, then M is a VNM. Keywords. Multiplication module; reduced module; minimal prime submodule;. Zariski topology; extremally disconnected. 1. Introduction. In this paper all rings are ...

  20. Zinc in multiple sclerosis

    DEFF Research Database (Denmark)

    Bredholt, Mikkel; Fredriksen, Jette Lautrup

    2016-01-01

    In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS...