WorldWideScience

Sample records for cis-regulatory elements controlling

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

    Science.gov (United States)

    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

    2011-07-01

    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.

  2. Separate elements of the TERMINAL FLOWER 1 cis-regulatory region integrate pathways to control flowering time and shoot meristem identity.

    Science.gov (United States)

    Serrano-Mislata, Antonio; Fernández-Nohales, Pedro; Doménech, María J; Hanzawa, Yoshie; Bradley, Desmond; Madueño, Francisco

    2016-09-15

    TERMINAL FLOWER 1 (TFL1) is a key regulator of Arabidopsis plant architecture that responds to developmental and environmental signals to control flowering time and the fate of shoot meristems. TFL1 expression is dynamic, being found in all shoot meristems, but not in floral meristems, with the level and distribution changing throughout development. Using a variety of experimental approaches we have analysed the TFL1 promoter to elucidate its functional structure. TFL1 expression is based on distinct cis-regulatory regions, the most important being located 3' of the coding sequence. Our results indicate that TFL1 expression in the shoot apical versus lateral inflorescence meristems is controlled through distinct cis-regulatory elements, suggesting that different signals control expression in these meristem types. Moreover, we identified a cis-regulatory region necessary for TFL1 expression in the vegetative shoot and required for a wild-type flowering time, supporting that TFL1 expression in the vegetative meristem controls flowering time. Our study provides a model for the functional organisation of TFL1 cis-regulatory regions, contributing to our understanding of how developmental pathways are integrated at the genomic level of a key regulator to control plant architecture. © 2016. Published by The Company of Biologists Ltd.

  3. Cis-regulatory elements: molecular mechanisms and evolutionary processes underlying divergence.

    Science.gov (United States)

    Wittkopp, Patricia J; Kalay, Gizem

    2011-12-06

    Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Prediction of Cis-Regulatory Elements Controlling Genes Differentially Expressed by Retinal and Choroidal Vascular Endothelial Cells.

    Science.gov (United States)

    Choi, Dongseok; Appukuttan, Binoy; Binek, Sierra J; Planck, Stephen R; Stout, J Timothy; Rosenbaum, James T; Smith, Justine R

    2008-01-01

    Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two emdothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., GCCR, HMGIY, HSF1, p53, VDR) or choroidal (i.e., E2F, YY1, ZF5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy.

  6. Computational identification of new structured cis-regulatory elements in the 3'-untranslated region of human protein coding genes.

    Science.gov (United States)

    Chen, Xiaowei Sylvia; Brown, Chris M

    2012-10-01

    Messenger ribonucleic acids (RNAs) contain a large number of cis-regulatory RNA elements that function in many types of post-transcriptional regulation. These cis-regulatory elements are often characterized by conserved structures and/or sequences. Although some classes are well known, given the wide range of RNA-interacting proteins in eukaryotes, it is likely that many new classes of cis-regulatory elements are yet to be discovered. An approach to this is to use computational methods that have the advantage of analysing genomic data, particularly comparative data on a large scale. In this study, a set of structural discovery algorithms was applied followed by support vector machine (SVM) classification. We trained a new classification model (CisRNA-SVM) on a set of known structured cis-regulatory elements from 3'-untranslated regions (UTRs) and successfully distinguished these and groups of cis-regulatory elements not been strained on from control genomic and shuffled sequences. The new method outperformed previous methods in classification of cis-regulatory RNA elements. This model was then used to predict new elements from cross-species conserved regions of human 3'-UTRs. Clustering of these elements identified new classes of potential cis-regulatory elements. The model, training and testing sets and novel human predictions are available at: http://mRNA.otago.ac.nz/CisRNA-SVM.

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

    Science.gov (United States)

    Mao, Grace; Brody, James P

    2007-11-09

    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 16bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16bp 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 0.014s(-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. Changes in Cis-regulatory Elements during Morphological Evolution

    Directory of Open Access Journals (Sweden)

    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.

  9. The identification of cis-regulatory elements: A review from a machine learning perspective.

    Science.gov (United States)

    Li, Yifeng; Chen, Chih-Yu; Kaye, Alice M; Wasserman, Wyeth W

    2015-12-01

    The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field.

  10. Deletion hotspots in AMACR promoter CpG island are cis-regulatory elements controlling the gene expression in the colon.

    Directory of Open Access Journals (Sweden)

    Xiang Zhang

    2009-01-01

    Full Text Available Alpha-methylacyl-coenzyme A racemase (AMACR regulates peroxisomal beta-oxidation of phytol-derived, branched-chain fatty acids from red meat and dairy products -- suspected risk factors for colon carcinoma (CCa. AMACR was first found overexpressed in prostate cancer but not in benign glands and is now an established diagnostic marker for prostate cancer. Aberrant expression of AMACR was recently reported in Cca; however, little is known about how this gene is abnormally activated in cancer. By using a panel of immunostained-laser-capture-microdissected clinical samples comprising the entire colon adenoma-carcinoma sequence, we show that deregulation of AMACR during colon carcinogenesis involves two nonrandom events, resulting in the mutually exclusive existence of double-deletion at CG3 and CG10 and deletion of CG12-16 in a newly identified CpG island within the core promoter of AMACR. The double-deletion at CG3 and CG10 was found to be a somatic lesion. It existed in histologically normal colonic glands and tubular adenomas with low AMACR expression and was absent in villous adenomas and all CCas expressing variable levels of AMACR. In contrast, deletion of CG12-16 was shown to be a constitutional allele with a frequency of 43% in a general population. Its prevalence reached 89% in moderately differentiated CCas strongly expressing AMACR but only existed at 14% in poorly differentiated CCas expressing little or no AMACR. The DNA sequences housing these deletions were found to be putative cis-regulatory elements for Sp1 at CG3 and CG10, and ZNF202 at CG12-16. Chromatin immunoprecipitation, siRNA knockdown, gel shift assay, ectopic expression, and promoter analyses supported the regulation by Sp1 and ZNF202 of AMACR gene expression in an opposite manner. Our findings identified key in vivo events and novel transcription factors responsible for AMACR regulation in CCas and suggested these AMACR deletions may have diagnostic/prognostic value for

  11. Dissection of cis-regulatory elements in the C. elegans Hox gene egl-5 promoter.

    Science.gov (United States)

    Teng, Yingqi; Girard, Lisa; Ferreira, Henrique B; Sternberg, Paul W; Emmons, Scott W

    2004-12-15

    Hox genes are highly conserved segmental identity genes well known for their complex expression patterns and divergent targets. Here we present an analysis of cis-regulatory elements in the Caenorhabditis elegans Hox gene egl-5, which is expressed in multiple tissues in the posterior region of the nematode. We have utilized phylogenetic footprinting to efficiently identify cis-regulatory elements and have characterized these with gfp reporters and tissue-specific rescue experiments. We have found that the complex expression pattern of egl-5 is the cumulative result of the activities of multiple tissue or local region-specific activator sequences that are conserved both in sequence and near-perfect order in the related nematode Caenorhabditis briggsae. Two conserved regulatory blocks analyzed in detail contain multiple sites for both positively and negatively acting factors. One of these regions may promote activation of egl-5 in certain cells via the Wnt pathway. Positively acting regions are repressed in inappropriate tissues by additional negative pathways acting at other sites within the promoter. Our analysis has allowed us to implicate several new regulatory factors significant to the control of egl-5 expression.

  12. A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors

    Directory of Open Access Journals (Sweden)

    Michael A. White

    2016-10-01

    Full Text Available Transcription factors often activate and repress different target genes in the same cell. How activation and repression are encoded by different arrangements of transcription factor binding sites in cis-regulatory elements is poorly understood. We investigated how sites for the transcription factor CRX encode both activation and repression in photoreceptors by assaying thousands of genomic and synthetic cis-regulatory elements in wild-type and Crx−/− retinas. We found that sequences with high affinity for CRX repress transcription, whereas sequences with lower affinity activate. This rule is modified by a cooperative interaction between CRX sites and sites for the transcription factor NRL, which overrides the repressive effect of high affinity for CRX. Our results show how simple rearrangements of transcription factor binding sites encode qualitatively different responses to a single transcription factor and explain how CRX plays multiple cis-regulatory roles in the same cell.

  13. [Role of genes and their cis-regulatory elements during animal morphological evolution].

    Science.gov (United States)

    Sun, Boyuan; Tu, Jianbo; Li, Ying; Yang, Mingyao

    2014-06-01

    Cis-regulatory hypothesis is one of the most important theories in evolutionary developmental biology (evo-devo), which claims that evolution of cis-regulatory elements (CREs) plays a key role during evolution of morphology. However, an increasing number of experimental results show that cis-regulatory hypothesis alone is not far enough to explain the complexity of evo-devo processes. Other modifications, including mutations of protein coding, gene and genome duplications, and flexibility of homeodomains and CREs, also cause the morphological changes in animals. In this review, we retrospect the recent results of evolution of CREs and genes associated with CREs and discuss new methods and trends for research in evo-devo.

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

    NARCIS (Netherlands)

    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

  15. Lessons from Domestication: Targeting Cis-Regulatory Elements for Crop Improvement.

    Science.gov (United States)

    Swinnen, Gwen; Goossens, Alain; Pauwels, Laurens

    2016-06-01

    Domestication of wild plant species has provided us with crops that serve our human nutritional needs. Advanced DNA sequencing has propelled the unveiling of underlying genetic changes associated with domestication. Interestingly, many changes reside in cis-regulatory elements (CREs) that control the expression of an unmodified coding sequence. Sequence variation in CREs can impact gene expression levels, but also developmental timing and tissue specificity of expression. When genes are involved in multiple pathways or active in several organs and developmental stages CRE modifications are favored in contrast to mutations in coding regions, due to the lack of detrimental pleiotropic effects. Therefore, learning from domestication, we propose that CREs are interesting targets for genome editing to create new alleles for plant breeding.

  16. Creation of cis-regulatory elements during sea urchin evolution by co-option and optimization of a repetitive sequence adjacent to the spec2a gene.

    Science.gov (United States)

    Dayal, Sandeep; Kiyama, Takae; Villinski, Jeffrey T; Zhang, Ning; Liang, Shuguang; Klein, William H

    2004-09-15

    The creation, preservation, and degeneration of cis-regulatory elements controlling developmental gene expression are fundamental genome-level evolutionary processes about which little is known. Here, we identify critical differences in cis-regulatory elements controlling the expression of the sea urchin aboral ectoderm-specific spec genes. We found multiple copies of a repetitive sequence element termed RSR in genomes of species within the Strongylocentrotidae family, but RSRs were not detected in genomes of species outside Strongylocentrotidae. spec genes in Strongylocentrotus purpuratus are invariably associated with RSRs, and the spec2a RSR functioned as a transcriptional enhancer and displayed greater activity than did spec1 or spec2c RSRs. Single-base pair differences at two cis-regulatory elements within the spec2a RSR increased the binding affinities of four transcription factors, SpCCAAT-binding factor at one element and SpOtx, SpGoosecoid, and SpGATA-E at another. The cis-regulatory elements to which these four factors bound were recent evolutionary acquisitions that acted to either activate or repress transcription, depending on the cell type. These elements were found in the spec2a RSR ortholog in Strongylocentrotus pallidus but not in RSR orthologs of Strongylocentrotus droebachiensis or Hemicentrotus pulcherrimus. Our results indicated that a dynamic pattern of cis-regulatory element evolution exists for spec genes despite their conserved aboral ectoderm expression.

  17. Identification of distal cis-regulatory elements at mouse mitoferrin loci using zebrafish transgenesis.

    Science.gov (United States)

    Amigo, Julio D; Yu, Ming; Troadec, Marie-Berengere; Gwynn, Babette; Cooney, Jeffrey D; Lambert, Amy J; Chi, Neil C; Weiss, Mitchell J; Peters, Luanne L; Kaplan, Jerry; Cantor, Alan B; Paw, Barry H

    2011-04-01

    Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of the Mfrn genes, we utilized genome-wide chromatin immunoprecipitation (ChIP) datasets for the major erythroid transcription factor GATA-1. We identified the CRMs that faithfully drive the expression of Mfrn1 during blood and heart development and Mfrn2 ubiquitously. Through in vivo analyses of the Mfrn-CRMs in zebrafish and mouse, we demonstrate their functional and evolutionary conservation. Using knockdowns with morpholinos and cell sorting analysis in transgenic zebrafish embryos, we show that GATA-1 directly regulates the expression of Mfrn1. Mutagenesis of individual GATA-1 binding cis elements (GBE) demonstrated that at least two of the three GBE within this CRM are functionally required for GATA-mediated transcription of Mfrn1. Furthermore, ChIP assays demonstrate switching from GATA-2 to GATA-1 at these elements during erythroid maturation. Our results provide new insights into the genetic regulation of mitochondrial function and iron homeostasis and, more generally, illustrate the utility of genome-wide ChIP analysis combined with zebrafish transgenesis for identifying long-range transcriptional enhancers that regulate tissue development.

  18. cis-Regulatory control of the initial neurogenic pattern of onecut gene expression in the sea urchin embryo.

    Science.gov (United States)

    Barsi, Julius C; Davidson, Eric H

    2016-01-01

    Specification of the ciliated band (CB) of echinoid embryos executes three spatial functions essential for postgastrular organization. These are establishment of a band about 5 cells wide which delimits and bounds other embryonic territories; definition of a neurogenic domain within this band; and generation within it of arrays of ciliary cells that bear the special long cilia from which the structure derives its name. In Strongylocentrotus purpuratus the spatial coordinates of the future ciliated band are initially and exactly determined by the disposition of a ring of cells that transcriptionally activate the onecut homeodomain regulatory gene, beginning in blastula stage, long before the appearance of the CB per se. Thus the cis-regulatory apparatus that governs onecut expression in the blastula directly reveals the genomic sequence code by which these aspects of the spatial organization of the embryo are initially determined. We screened the entire onecut locus and its flanking region for transcriptionally active cis-regulatory elements, and by means of BAC recombineered deletions identified three separated and required cis-regulatory modules that execute different functions. The operating logic of the crucial spatial control module accounting for the spectacularly precise and beautiful early onecut expression domain depends on spatial repression. Previously predicted oral ectoderm and aboral ectoderm repressors were identified by cis-regulatory mutation as the products of goosecoid and irxa genes respectively, while the pan-ectodermal activator SoxB1 supplies a transcriptional driver function.

  19. Recurrent modification of a conserved cis-regulatory element underlies fruit fly pigmentation diversity.

    Directory of Open Access Journals (Sweden)

    William A Rogers

    2013-08-01

    Full Text Available The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE, little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B and sex-determination (DSX transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Engineering Synthetic cis-Regulatory Elements for Simultaneous Recognition of Three Transcriptional Factors in Bacteria.

    Science.gov (United States)

    Amores, Gerardo Ruiz; Guazzaroni, María-Eugenia; Silva-Rocha, Rafael

    2015-12-18

    Recognition of cis-regulatory elements by transcription factors (TF) at target promoters is crucial to gene regulation in bacteria. In this process, binding of TFs to their cognate sequences depends on a set of physical interactions between these proteins and specific nucleotides in the operator region. Previously, we showed that in silico optimization algorithms are able to generate short sequences that are recognized by two different TFs of Escherichia coli, namely, CRP and IHF, thus generating an AND logic gate. Here, we expanded this approach in order to engineer DNA sequences that can be simultaneously recognized by three unrelated TFs (CRP, IHF, and Fis). Using in silico optimization and experimental validation strategies, we were able to obtain a candidate promoter (Plac-CFI1) regulated by only two TFs with an AND logic, thus demonstrating a limitation in the design. Subsequently, we modified the algorithm to allow the optimization of extended sequences, and were able to design two synthetic promoters (PCFI20-1 and PCFI22-5) that were functional in vivo. Expression assays in E. coli mutant strains for each TF revealed that while CRP positively regulates the promoter activities, IHF and Fis are strong repressors of both the promoter variants. Taken together, our results demonstrate the potential of in silico strategies in bacterial synthetic promoter engineering. Furthermore, the study also shows how small modifications in cis-regulatory elements can drastically affect the final logic of the resulting promoter.

  2. Identification of Distal cis-Regulatory Elements at Mouse Mitoferrin Loci Using Zebrafish Transgenesis▿

    OpenAIRE

    Amigo, J. D.; Yu, M.; Troadec, M.-B.; Gwynn, B; Cooney, J. D.; Lambert, A.J.; Chi, N. C.; Weiss, M J; Peters, L. L.; Kaplan, J; Cantor, Alan B.; Paw, Barry Htin

    2011-01-01

    Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of the Mfrn genes, we utilized genome-wide chromatin immunoprecipitation (ChIP) datasets for the major erythroid transcription factor GATA-1. We identified the CRMs that faithfully dr...

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

    Directory of Open Access Journals (Sweden)

    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

  4. Computational discovery of soybean promoter cis-regulatory elements for the construction of soybean cyst nematode inducible synthetic promoters

    Science.gov (United States)

    Computational methods offer great hope but limited accuracy in the prediction of functional cis-regulatory elements; improvements are needed to enable synthetic promoter design. We applied an ensemble strategy for de novo soybean cyst nematode (SCN)-inducible motif discovery among promoters of 18 co...

  5. Analysis of mammalian cis-regulatory DNA elements by homologous recombination.

    Science.gov (United States)

    Fiering, S; Bender, M A; Groudine, M

    1999-01-01

    The use of homologous recombination to modify and thereby functionally analyze cis-regulatory DNA elements in mammalian cells has become an important approach in mammalian gene expression research. We have emphasized the necessity of designing a system that allows the removal of selectable markers used in targeting and facilitates the further modification of the region under study. To perform these tasks, we presently favor making an initial HR-mediated replacement of the entire element under study with an active positive selectable marker in combination with either an inactive second positive selectable marker or an active negative selectable marker. The plug and socket system, in which an inactive selectable marker is complemented by HR, is the most dependable and well-characterized option for making secondary modifications. However, the double-replacement system has certain advantages, and the recently developed RMCE approach, which allows replacement of a negative selectable marker by site-specific recombinase-mediated insertion without using a positive selectable marker, will likely prove very valuable in future experiments. Each of the systems, or combinations thereof, should be considered in light of the specifics of any given experiment to select the most appropriate option. Although the emphasis of this article has been the analysis of cis-acting regulatory elements involved in transcription, these same approaches can be used to analyze other regulatory elements (e.g., origins of replication) and to make multiple subtle mutations in polypeptides.

  6. cis-regulatory elements involved in ultraviolet light regulation and plant defense.

    Science.gov (United States)

    Wingender, R; Röhrig, H; Höricke, C; Schell, J

    1990-10-01

    An elicitor-regulated transient expression system was established in soybean protoplasts that allowed the identification of cis-regulatory elements involved in plant defense. The 5' region of an ultraviolet (UV) light-inducible and elicitor-inducible chs gene (chs1) of soybean was subjected to deletion analysis with the help of chimeric chs-nptII/gus gene constructs. This analysis delimited the sequences necessary for elicitor inducibility to -175 and -134 of the chs1 promoter. The same soybean sequences were able to direct elicitor inducibility in parsley protoplasts, suggesting a conserved function of cis-acting elements involved in plant defense. In addition, this region of the soybean promoter also promotes UV light inducibility in parsley protoplasts. However, in contrast to the elicitor induction, correct regulation was not observed after UV light induction when sequences downstream of -75 were replaced by a heterologous minimal promoter. This result indicates that at least two cis-acting elements are involved in UV light induction.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Putative cis-regulatory elements associated with heat shock genes activated during excystation of Cryptosporidium parvum.

    Directory of Open Access Journals (Sweden)

    Benjamin Cohn

    Full Text Available BACKGROUND: Cryptosporidiosis is a ubiquitous infectious disease, caused by the protozoan parasites Cryptosporidium hominis and C. parvum, leading to acute, persistent and chronic diarrhea worldwide. Although the complications of this disease can be serious, even fatal, in immunocompromised patients of any age, they have also been found to lead to long term effects, including growth inhibition and impaired cognitive development, in infected immunocompetent children. The Cryptosporidium life cycle alternates between a dormant stage, the oocyst, and a highly replicative phase that includes both asexual vegetative stages as well as sexual stages, implying fine genetic regulatory mechanisms. The parasite is extremely difficult to study because it cannot be cultured in vitro and animal models are equally challenging. The recent publication of the genome sequence of C. hominis and C. parvum has, however, significantly advanced our understanding of the biology and pathogenesis of this parasite. METHODOLOGY/PRINCIPAL FINDINGS: Herein, our goal was to identify cis-regulatory elements associated with heat shock response in Cryptosporidium using a combination of in silico and real time RT-PCR strategies. Analysis with Gibbs-Sampling algorithms of upstream non-translated regions of twelve genes annotated as heat shock proteins in the Cryptosporidium genome identified a highly conserved over-represented sequence motif in eleven of them. RT-PCR analyses, described herein and also by others, show that these eleven genes bearing the putative element are induced concurrent with excystation of parasite oocysts via heat shock. CONCLUSIONS/SIGNIFICANCE: Our analyses suggest that occurrences of a motif identified in the upstream regions of the Cryptosporidium heat shock genes represent parts of the transcriptional apparatus and function as stress response elements that activate expression of these genes during excystation, and possibly at other stages in the life

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    Deb, Arindam; Kundu, Sudip

    2015-01-01

    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 sequences and suitable

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Prioritizing predicted cis-regulatory elements for co-expressed gene sets based on Lasso regression models.

    Science.gov (United States)

    Hu, Hong; Roqueiro, Damian; Dai, Yang

    2011-01-01

    Computational prediction of cis-regulatory elements for a set of co-expressed genes based on sequence analysis provides an overwhelming volume of potential transcription factor binding sites. It presents a challenge to prioritize transcription factors for regulatory functional studies. A novel approach based on the use of Lasso regression models is proposed to address this problem. We examine the ability of the Lasso model using time-course microarray data obtained from a comprehensive study of gene expression profiles in skin and mucosal wounds in mouse over all stages of wound healing.

  14. Distinct functional constraints partition sequence conservation in a cis-regulatory element.

    Directory of Open Access Journals (Sweden)

    Antoine Barrière

    2011-06-01

    Full Text Available Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter.

  15. Conserved Cis-Regulatory Modules Control Robustness in Msx1 Expression at Single-Cell Resolution

    Science.gov (United States)

    Vance, Keith W.; Woodcock, Dan J.; Reid, John E.; Bretschneider, Till; Ott, Sascha; Koentges, Georgy

    2015-01-01

    The process of transcription is highly stochastic leading to cell-to-cell variations and noise in gene expression levels. However, key essential genes have to be precisely expressed at the correct amount and time to ensure proper cellular development and function. Studies in yeast and bacterial systems have shown that gene expression noise decreases as mean expression levels increase, a relationship that is controlled by promoter DNA sequence. However, the function of distal cis-regulatory modules (CRMs), an evolutionary novelty of metazoans, in controlling transcriptional robustness and variability is poorly understood. In this study, we used live cell imaging of transfected reporters combined with a mathematical modelling and statistical inference scheme to quantify the function of conserved Msx1 CRMs and promoters in modulating single-cell real-time transcription rates in C2C12 mouse myoblasts. The results show that the mean expression–noise relationship is solely promoter controlled for this key pluripotency regulator. In addition, we demonstrate that CRMs modulate single-cell basal promoter rate distributions in a graded manner across a population of cells. This extends the rheostatic model of CRM action to provide a more detailed understanding of CRM function at single-cell resolution. We also identify a novel CRM transcriptional filter function that acts to reduce intracellular variability in transcription rates and show that this can be phylogenetically separable from rate modulating CRM activities. These results are important for understanding how the expression of key vertebrate developmental transcription factors is precisely controlled both within and between individual cells. PMID:26342140

  16. Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.

    Science.gov (United States)

    Infante, Carlos R; Mihala, Alexandra G; Park, Sungdae; Wang, Jialiang S; Johnson, Kenji K; Lauderdale, James D; Menke, Douglas B

    2015-10-12

    The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia.

  17. cis-Regulatory control of three cell fate-specific genes in vulval organogenesis of Caenorhabditis elegans and C. briggsae.

    Science.gov (United States)

    Kirouac, Martha; Sternberg, Paul W

    2003-05-01

    The great-grandprogeny of the Caenorhabditis elegans vulval precursor cells (VPCs) adopt one of the final vulA, B1, B2, C, D, E, and F cell fates in a precise spatial pattern. This pattern of vulval cell types is likely to depend on the cis-regulatory regions of the transcriptional targets of intercellular signals in vulval development. egl-17, zmp-1, and cdh-3 are expressed differentially in the developing vulva cells, providing a potential readout for different signaling pathways. To understand how such pathways interact to specify unique vulval cell types in a precise pattern, we have identified cis-regulatory regions sufficient to confer vulval cell type-specific regulation when fused in cis to the basal pes-10 promoter. We have identified the C. briggsae homologs of these three genes, with their corresponding control regions, and tested these regions in both C. elegans and C. briggsae. These regions of similarity in C. elegans and C. briggsae upstream of egl-17, zmp-1, and cdh-3 promote expression in vulval cells and the anchor cell (AC). By using the cis-regulatory analysis and phylogenetic footprinting, we have identified overrepresented sequences involved in conferring vulval and AC expression.

  18. Evaluation of combinatorial cis-regulatory elements for stable gene expression in chicken cells

    Directory of Open Access Journals (Sweden)

    Seo Hee W

    2010-09-01

    Full Text Available Abstract Background Recent successes in biotechnological application of birds are based on their unique physiological traits such as unlimited manipulability onto developing embryos and simple protein constituents of the eggs. However it is not likely that target protein is produced as kinetically expected because various factors affect target gene expression. Although there have been various attempts to minimize the silencing of transgenes, a generalized study that uses multiple cis-acting elements in chicken has not been made. The aim of the present study was to analyze whether various cis-acting elements can help to sustain transgene expression in chicken fibroblasts. Results We investigated the optimal transcriptional regulatory elements for enhancing stable transgene expression in chicken cells. We generated eight constructs that encode enhanced green fluorescent protein (eGFP driven by either CMV or CAG promoters (including the control, containing three types of key regulatory elements: a chicken lysozyme matrix attachment region (cMAR, 5'-DNase I-hypersensitive sites 4 (cHS4, and the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE. Then we transformed immortalized chicken embryonic fibroblasts with these constructs by electroporation, and after cells were expanded under G418 selection, analyzed mRNA levels and mean fluorescence intensity (MFI by quantitative real-time PCR and flow cytometry, respectively. We found that the copy number of each construct significantly decreased as the size of the construct increased (R2 = 0.701. A significant model effect was found in the expression level among various constructs in both mRNA and protein (P cis-acting elements decreased the level of gene silencing as well as the coefficient of variance of eGFP-expressing cells (P Conclusions Our current data show that an optimal combination of cis-acting elements and promoters/enhancers for sustaining gene expression in chicken cells

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

    Directory of Open Access Journals (Sweden)

    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

  20. A comparative analysis of the evolution, expression, and cis-regulatory element of polygalacturonase genes in grasses and dicots.

    Science.gov (United States)

    Liang, Ying; Yu, Youjian; Cui, Jinlong; Lyu, Meiling; Xu, Liai; Cao, Jiashu

    2016-11-01

    Cell walls are a distinguishing characteristic of plants essential to their survival. The pectin content of primary cell walls in grasses and dicots is distinctly different. Polygalacturonases (PGs) can degrade pectins and participate in multiple developmental processes of plants. This study comprehensively compared the evolution, expression, and cis-regulatory element of PGs in grasses and dicots. A total of 577 PGs identified from five grasses and five dicots fell into seven clades. Evolutionary analysis demonstrated the distinct differences between grasses and dicots in patterns of gene duplication and loss, and evolutionary rates. Grasses generally contained much fewer clade C and F members than dicots. We found that this disparity was the result of less duplication and more gene losses in grasses. More duplications occurred in clades D and E, and expression analysis showed that most of clade E members were expressed ubiquitously at a high overall level and clade D members were closely related to male reproduction in both grasses and dicots, suggesting their biological functions were highly conserved across species. In addition to the general role in reproductive development, PGs of clades C and F specifically played roles in root development in dicots, shedding light on organ differentiation between the two groups of plants. A regulatory element analysis of clade C and F members implied that possible functions of PGs in specific biological responses contributed to their expansion and preservation. This work can improve the knowledge of PGs in plants generally and in grasses specifically and is beneficial to functional studies.

  1. Characterization of "cis"-regulatory elements ("c"RE) associated with mammary gland function

    Science.gov (United States)

    The Bos taurus genome assembly has propelled dairy science into a new era; still, most of the information encoded in the genome has not yet been decoded. The human Encyclopedia of DNA Elements (ENCODE) project has spearheaded the identification and annotation of functional genomic elements in the hu...

  2. An arthropod cis-regulatory element functioning in sensory organ precursor development dates back to the Cambrian

    Directory of Open Access Journals (Sweden)

    Simpson Pat

    2010-09-01

    Full Text Available Abstract Background An increasing number of publications demonstrate conservation of function of cis-regulatory elements without sequence similarity. In invertebrates such functional conservation has only been shown for closely related species. Here we demonstrate the existence of an ancient arthropod regulatory element that functions during the selection of neural precursors. The activity of genes of the achaete-scute (ac-sc family endows cells with neural potential. An essential, conserved characteristic of proneural genes is their ability to restrict their own activity to single or a small number of progenitor cells from their initially broad domains of expression. This is achieved through a process called lateral inhibition. A regulatory element, the sensory organ precursor enhancer (SOPE, is required for this process. First identified in Drosophila, the SOPE contains discrete binding sites for four regulatory factors. The SOPE of the Drosophila asense gene is situated in the 5' UTR. Results Through a manual comparison of consensus binding site sequences we have been able to identify a SOPE in UTR sequences of asense-like genes in species belonging to all four arthropod groups (Crustacea, Myriapoda, Chelicerata and Insecta. The SOPEs of the spider Cupiennius salei and the insect Tribolium castaneum are shown to be functional in transgenic Drosophila. This would place the origin of this regulatory sequence as far back as the last common ancestor of the Arthropoda, that is, in the Cambrian, 550 million years ago. Conclusions The SOPE is not detectable by inter-specific sequence comparison, raising the possibility that other ancient regulatory modules in invertebrates might have escaped detection.

  3. Evaluation of phylogenetic footprint discovery for predicting bacterial cis-regulatory elements and revealing their evolution

    Directory of Open Access Journals (Sweden)

    van Helden Jacques

    2008-01-01

    Full Text Available Abstract Background The detection of conserved motifs in promoters of orthologous genes (phylogenetic footprints has become a common strategy to predict cis-acting regulatory elements. Several software tools are routinely used to raise hypotheses about regulation. However, these tools are generally used as black boxes, with default parameters. A systematic evaluation of optimal parameters for a footprint discovery strategy can bring a sizeable improvement to the predictions. Results We evaluate the performances of a footprint discovery approach based on the detection of over-represented spaced motifs. This method is particularly suitable for (but not restricted to Bacteria, since such motifs are typically bound by factors containing a Helix-Turn-Helix domain. We evaluated footprint discovery in 368 Escherichia coli K12 genes with annotated sites, under 40 different combinations of parameters (taxonomical level, background model, organism-specific filtering, operon inference. Motifs are assessed both at the levels of correctness and significance. We further report a detailed analysis of 181 bacterial orthologs of the LexA repressor. Distinct motifs are detected at various taxonomical levels, including the 7 previously characterized taxon-specific motifs. In addition, we highlight a significantly stronger conservation of half-motifs in Actinobacteria, relative to Firmicutes, suggesting an intermediate state in specificity switching between the two Gram-positive phyla, and thereby revealing the on-going evolution of LexA auto-regulation. Conclusion The footprint discovery method proposed here shows excellent results with E. coli and can readily be extended to predict cis-acting regulatory signals and propose testable hypotheses in bacterial genomes for which nothing is known about regulation.

  4. Global profiling of rice and poplar transcriptomes highlights key conserved circadian-controlled pathways and cis-regulatory modules.

    Directory of Open Access Journals (Sweden)

    Sergei A Filichkin

    Full Text Available BACKGROUND: Circadian clocks provide an adaptive advantage through anticipation of daily and seasonal environmental changes. In plants, the central clock oscillator is regulated by several interlocking feedback loops. It was shown that a substantial proportion of the Arabidopsis genome cycles with phases of peak expression covering the entire day. Synchronized transcriptome cycling is driven through an extensive network of diurnal and clock-regulated transcription factors and their target cis-regulatory elements. Study of the cycling transcriptome in other plant species could thus help elucidate the similarities and differences and identify hubs of regulation common to monocot and dicot plants. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of oligonucleotide microarrays and data mining pipelines, we examined daily rhythms in gene expression in one monocotyledonous and one dicotyledonous plant, rice and poplar, respectively. Cycling transcriptomes were interrogated under different diurnal (driven and circadian (free running light and temperature conditions. Collectively, photocycles and thermocycles regulated about 60% of the expressed nuclear genes in rice and poplar. Depending on the condition tested, up to one third of oscillating Arabidopsis-poplar-rice orthologs were phased within three hours of each other suggesting a high degree of conservation in terms of rhythmic gene expression. We identified clusters of rhythmically co-expressed genes and searched their promoter sequences to identify phase-specific cis-elements, including elements that were conserved in the promoters of Arabidopsis, poplar, and rice. CONCLUSIONS/SIGNIFICANCE: Our results show that the cycling patterns of many circadian clock genes are highly conserved across poplar, rice, and Arabidopsis. The expression of many orthologous genes in key metabolic and regulatory pathways is diurnal and/or circadian regulated and phased to similar times of day. Our results confirm

  5. 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

  6. Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells.

    Science.gov (United States)

    Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

    2017-03-23

    Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.

  7. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few.

  8. The contribution of cis-regulatory elements to head-to-head gene pairs’ co-expression pattern

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Transcription regulation is one of the most critical pipelines in biological process,in which cis-elements play the role as gene expression regulators.We attempt to deduce the principles underlying the co-expression of "head-to-head" gene pairs by analyzing activities or behaviors of the shared cis-elements.A network component analysis was performed to estimate the impact of cis-elements on gene promoters and their activities under different conditions.Our discoveries reveal how biological system uses those regulatory elements to control the expression pattern of "head-to-head" gene pairs and the whole transcription regulation system.

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

    Science.gov (United States)

    Hadas, Yoav; Nitzan, Noa; Furley, Andrew J W; Kozlov, Serguei V; Klar, Avihu

    2013-01-01

    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. 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.

  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. Cis-regulatory element-based genome-wide identification of DREB1/CBF targets in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Huan Zhao; Weizhong Liu; Yong Hu; Xianglin Liu; Yikun He

    2008-01-01

    Microarray analysis is used to identify transcriptional targets.However,the direct targets of transcription factors cannot be distin guished from indirect ones;further,genes with low-expression levels cannot be identified by this method.In the present study,we exploi the cis-element dehydration-responsive element(DRE)that is known to be responsible for the transcription of DRE binding factor](DREB1)targets in the promoter region of all Arabidopsis genes.Putative targets whose promoters contain the elements were verified by both microarray and reverse transcription-polymerase chain reaction(RT-PCR)analysis.Five new DREB 1/CBF direct targets were identified.Compared with traditional microarray analysis,our method is convenient and cost-effective for identifying the downstream targets of transcription factors.

  13. 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.

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

    Science.gov (United States)

    Karnik, Rahul; Beer, Michael A

    2015-01-01

    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.

  15. Kinetics of transcription initiation directed by multiple cis-regulatory elements on the glnAp2 promoter.

    Science.gov (United States)

    Wang, Yaolai; Liu, Feng; Wang, Wei

    2016-12-15

    Transcription initiation is orchestrated by dynamic molecular interactions, with kinetic steps difficult to detect. Utilizing a hybrid method, we aim to unravel essential kinetic steps of transcriptional regulation on the glnAp2 promoter, whose regulatory region includes two enhancers (sites I and II) and three low-affinity sequences (sites III-V), to which the transcriptional activator NtrC binds. By structure reconstruction, we analyze all possible organization architectures of the transcription apparatus (TA). The main regulatory mode involves two NtrC hexamers: one at enhancer II transiently associates with site V such that the other at enhancer I can rapidly approach and catalyze the σ(54)-RNA polymerase holoenzyme. We build a kinetic model characterizing essential steps of the TA operation; with the known kinetics of the holoenzyme interacting with DNA, this model enables the kinetics beyond technical detection to be determined by fitting the input-output function of the wild-type promoter. The model further quantitatively reproduces transcriptional activities of various mutated promoters. These results reveal different roles played by two enhancers and interpret why the low-affinity elements conditionally enhance or repress transcription. This work presents an integrated dynamic picture of regulated transcription initiation and suggests an evolutionarily conserved characteristic guaranteeing reliable transcriptional response to regulatory signals. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. 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.

  17. 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.

  18. The role of cis regulatory evolution in maize domestication.

    Science.gov (United States)

    Lemmon, Zachary H; Bukowski, Robert; Sun, Qi; Doebley, John F

    2014-11-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  19. The Role of cis Regulatory Evolution in Maize Domestication

    Science.gov (United States)

    Lemmon, Zachary H.; Bukowski, Robert; Sun, Qi; Doebley, John F.

    2014-01-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues. PMID:25375861

  20. The role of cis regulatory evolution in maize domestication.

    Directory of Open Access Journals (Sweden)

    Zachary H Lemmon

    2014-11-01

    Full Text Available Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem. Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  1. The role of cis regulatory evolution in maize domestication.

    Directory of Open Access Journals (Sweden)

    Zachary H Lemmon

    2014-11-01

    Full Text Available Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem. Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  2. Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora.

    Science.gov (United States)

    Steige, Kim A; Laenen, Benjamin; Reimegård, Johan; Scofield, Douglas G; Slotte, Tanja

    2017-01-31

    Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants, and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation (i) are under weaker purifying selection and (ii) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby transposable elements (TEs) and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.

  3. Combining computational prediction of cis-regulatory elements with a new enhancer assay to efficiently label neuronal structures in the medaka fish.

    Directory of Open Access Journals (Sweden)

    Emmanuel Mongin

    Full Text Available The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates.

  4. Cis-regulatory Mutations in the Caenorhabditis elegans Homeobox Gene Locus cog-1 Affect Neuronal Development

    Science.gov (United States)

    O'Meara, M. Maggie; Bigelow, Henry; Flibotte, Stephane; Etchberger, John F.; Moerman, Donald G.; Hobert, Oliver

    2009-01-01

    We apply here comparative genome hybridization as a novel tool to identify the molecular lesion in two Caenorhabditis elegans mutant strains that affect a neuronal cell fate decision. The phenotype of the mutant strains resembles those of the loss-of-function alleles of the cog-1 homeobox gene, an inducer of the fate of the gustatory neuron ASER. We find that both lesions map to the cis-regulatory control region of cog-1 and affect a phylogenetically conserved binding site for the C2H2 zinc-finger transcription factor CHE-1, a previously known regulator of cog-1 expression in ASER. Identification of this CHE-1-binding site as a critical regulator of cog-1 expression in the ASER in vivo represents one of the rare demonstrations of the in vivo relevance of an experimentally determined or predicted transcription-factor-binding site. Aside from the mutationally defined CHE-1-binding site, cog-1 contains a second, functional CHE-1-binding site, which in isolation is sufficient to drive reporter gene expression in the ASER but in an in vivo context is apparently insufficient for promoting appropriate ASER expression. The cis-regulatory control regions of other ASE-expressed genes also contain ASE motifs that can promote ASE neuron expression when isolated from their genomic context, but appear to depend on multiple ASE motifs in their normal genomic context. The multiplicity of cis-regulatory elements may ensure the robustness of gene expression. PMID:19189954

  5. A universal algorithm for genome-wide in silicio identification of biologically significant gene promoter putative cis-regulatory-elements; identification of new elements for reactive oxygen species and sucrose signaling in Arabidopsis.

    Science.gov (United States)

    Geisler, Matt; Kleczkowski, Leszek A; Karpinski, Stanislaw

    2006-02-01

    Short motifs of many cis-regulatory elements (CREs) can be found in the promoters of most Arabidopsis genes, and this raises the question of how their presence can confer specific regulation. We developed a universal algorithm to test the biological significance of CREs by first identifying every Arabidopsis gene with a CRE and then statistically correlating the presence or absence of the element with the gene expression profile on multiple DNA microarrays. This algorithm was successfully verified for previously characterized abscisic acid, ethylene, sucrose and drought responsive CREs in Arabidopsis, showing that the presence of these elements indeed correlates with treatment-specific gene induction. Later, we used standard motif sampling methods to identify 128 putative motifs induced by excess light, reactive oxygen species and sucrose. Our algorithm was able to filter 20 out of 128 novel CREs which significantly correlated with gene induction by either heat, reactive oxygen species and/or sucrose. The position, orientation and sequence specificity of CREs was tested in silicio by analyzing the expression of genes with naturally occurring sequence variations. In three novel CREs the forward orientation correlated with sucrose induction and the reverse orientation with sucrose suppression. The functionality of the predicted novel CREs was experimentally confirmed using Arabidopsis cell-suspension cultures transformed with short promoter fragments or artificial promoters fused with the GUS reporter gene. Our genome-wide analysis opens up new possibilities for in silicio verification of the biological significance of newly discovered CREs, and allows for subsequent selection of such CREs for experimental studies.

  6. Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework.

    Science.gov (United States)

    Maeso, Ignacio; Tena, Juan J

    2016-09-01

    Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements.

  7. Divergence in cis-regulatory sequences surrounding the opsin gene arrays of African cichlid fishes

    National Research Council Canada - National Science Library

    O'Quin, Kelly E; Smith, Daniel; Naseer, Zan; Schulte, Jane; Engel, Samuel D; Loh, Yong-Hwee E; Streelman, J Todd; Boore, Jeffrey L; Carleton, Karen L

    2011-01-01

    .... We use phylogenetic footprinting and shadowing to examine divergence in conserved non-coding elements, promoter sequences, and 3'-UTRs surrounding each opsin in search of candidate cis-regulatory...

  8. Statistical significance of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    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.

  9. Parallel evolution of chordate cis-regulatory code for development.

    Directory of Open Access Journals (Sweden)

    Laura Doglio

    2013-11-01

    Full Text Available Urochordates are the closest relatives of vertebrates and at the larval stage, possess a characteristic bilateral chordate body plan. In vertebrates, the genes that orchestrate embryonic patterning are in part regulated by highly conserved non-coding elements (CNEs, yet these elements have not been identified in urochordate genomes. Consequently the evolution of the cis-regulatory code for urochordate development remains largely uncharacterised. Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs are associated with largely the same key regulatory genes as vertebrate CNEs. Furthermore, some of the tested ciCNEs are able to activate reporter gene expression in both zebrafish and Ciona embryos, in a pattern that at least partially overlaps that of the gene they associate with, despite the absence of sequence identity. We also show that the ability of a ciCNE to up-regulate gene expression in vertebrate embryos can in some cases be localised to short sub-sequences, suggesting that functional cross-talk may be defined by small regions of ancestral regulatory logic, although functional sub-sequences may also be dispersed across the whole element. We conclude that the structure and organisation of cis-regulatory modules is very different between vertebrates and urochordates, reflecting their separate evolutionary histories. However, functional cross-talk still exists because the same repertoire of transcription factors has likely guided their parallel evolution, exploiting similar sets of binding sites but in different combinations.

  10. cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer Independent

    Directory of Open Access Journals (Sweden)

    Yue Huang

    2017-03-01

    Full Text Available Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets.

  11. cis-Regulatory Circuits Regulating NEK6 Kinase Overexpression in Transformed B Cells Are Super-Enhancer Independent.

    Science.gov (United States)

    Huang, Yue; Koues, Olivia I; Zhao, Jiang-Yang; Liu, Regina; Pyfrom, Sarah C; Payton, Jacqueline E; Oltz, Eugene M

    2017-03-21

    Alterations in distal regulatory elements that control gene expression underlie many diseases, including cancer. Epigenomic analyses of normal and diseased cells have produced correlative predictions for connections between dysregulated enhancers and target genes involved in pathogenesis. However, with few exceptions, these predicted cis-regulatory circuits remain untested. Here, we dissect cis-regulatory circuits that lead to overexpression of NEK6, a mitosis-associated kinase, in human B cell lymphoma. We find that only a minor subset of predicted enhancers is required for NEK6 expression. Indeed, an annotated super-enhancer is dispensable for NEK6 overexpression and for maintaining the architecture of a B cell-specific regulatory hub. A CTCF cluster serves as a chromatin and architectural boundary to block communication of the NEK6 regulatory hub with neighboring genes. Our findings emphasize that validation of predicted cis-regulatory circuits and super-enhancers is needed to prioritize transcriptional control elements as therapeutic targets.

  12. 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

    have been reported in ZRS, the underlying regulatory mechanism is still unknown. In this study, we analyzed the effect on transcription factor binding of a novel ZRS point mutation (463T>G) in a Pakistani family with preaxial polydactyly and triphalangeal thumb. Electrophoretical mobility shift assay......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...

  13. Evidence for the role of transposons in the recruitment of cis-regulatory motifs during the evolution of C4 photosynthesis.

    Science.gov (United States)

    Cao, Chensi; Xu, Jiajia; Zheng, Guangyong; Zhu, Xin-Guang

    2016-03-08

    C4 photosynthesis evolved from C3 photosynthesis and has higher light, water, and nitrogen use efficiencies. Several C4 photosynthesis genes show cell-specific expression patterns, which are required for these high resource-use efficiencies. However, the mechanisms underlying the evolution of cis-regulatory elements that control these cell-specific expression patterns remain elusive. In the present study, we tested the hypothesis that the cis-regulatory motifs related to C4 photosynthesis genes were recruited from non-photosynthetic genes and further examined potential mechanisms facilitating this recruitment. We examined 65 predicted bundle sheath cell-specific motifs, 17 experimentally validated cell-specific cis-regulatory elements, and 1,034 motifs derived from gene regulatory networks. Approximately 7, 5, and 1,000 of these three categories of motifs, respectively, were apparently recruited during the evolution of C4 photosynthesis. In addition, we checked 1) the distance between the acceptors and the donors of potentially recruited motifs in a chromosome, and 2) whether the potentially recruited motifs reside within the overlapping region of transposable elements and the promoter of donor genes. The results showed that 7, 4, and 658 of the potentially recruited motifs might have moved via the transposable elements. Furthermore, the potentially recruited motifs showed higher binding affinity to transcription factors compared to randomly generated sequences of the same length as the motifs. This study provides molecular evidence supporting the hypothesis that transposon-driven recruitment of pre-existing cis-regulatory elements from non-photosynthetic genes into photosynthetic genes plays an important role during C4 evolution. The findings of the present study coincide with the observed repetitive emergence of C4 during evolution.

  14. A Cis-Regulatory Map of the Drosophila Genome

    Science.gov (United States)

    Nègre, Nicolas; Brown, Christopher D.; Ma, Lijia; Bristow, Christopher Aaron; Miller, Steven W.; Wagner, Ulrich; Kheradpour, Pouya; Eaton, Matthew L.; Loriaux, Paul; Sealfon, Rachel; Li, Zirong; Ishii, Haruhiko; Spokony, Rebecca F.; Chen, Jia; Hwang, Lindsay; Cheng, Chao; Auburn, Richard P.; Davis, Melissa B.; Domanus, Marc; Shah, Parantu K.; Morrison, Carolyn A.; Zieba, Jennifer; Suchy, Sarah; Senderowicz, Lionel; Victorsen, Alec; Bild, Nicholas A.; Grundstad, A. Jason; Hanley, David; MacAlpine, David M.; Mannervik, Mattias; Venken, Koen; Bellen, Hugo; White, Robert; Russell, Steven; Grossman, Robert L.; Ren, Bing; Gerstein, Mark; Posakony, James W.; Kellis, Manolis; White, Kevin P.

    2011-01-01

    Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide 1,2 has successfully identified specific subtypes of regulatory elements 3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb-Response Elements 4, chromatin states 5, transcription factor binding sites (TFBS) 6–9, PolII regulation 8, and insulator elements 10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome based on more than 300 chromatin immuno-precipitation (ChIP) datasets for eight chromatin features, five histone deacetylases (HDACs) and thirty-eight site-specific transcription factors (TFs) at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and we validated a subset of predictions for promoters, enhancers, and insulators in vivo. We also identified nearly 2,000 genomic regions of dense TF binding associated with chromatin activity and accessibility. We discovered hundreds of new TF co-binding relationships and defined a TF network with over 800 potential regulatory relationships. PMID:21430782

  15. Abundant raw material for cis-regulatory evolution in humans

    Science.gov (United States)

    Rockman, Matthew V.; Wray, Gregory A.

    2002-01-01

    Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (human phenotypic variation.

  16. Abundant raw material for cis-regulatory evolution in humans

    Science.gov (United States)

    Rockman, Matthew V.; Wray, Gregory A.

    2002-01-01

    Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (human phenotypic variation.

  17. The cis-regulatory logic of the mammalian photoreceptor transcriptional network.

    Directory of Open Access Journals (Sweden)

    Timothy H-C Hsiau

    Full Text Available The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation.

  18. 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.

  19. Identifying cis-regulatory sequences by word profile similarity.

    Directory of Open Access Journals (Sweden)

    Garmay Leung

    Full Text Available BACKGROUND: Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples. METHODOLOGY/PRINCIPAL FINDINGS: We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila. CONCLUSIONS/SIGNIFICANCE: Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl.gov/downloads/wph.tar.gz.

  20. Computational methods for the detection of cis-regulatory modules.

    Science.gov (United States)

    Van Loo, Peter; Marynen, Peter

    2009-09-01

    Metazoan transcription regulation occurs through the concerted action of multiple transcription factors that bind co-operatively to cis-regulatory modules (CRMs). The annotation of these key regulators of transcription is lagging far behind the annotation of the transcriptome itself. Here, we give an overview of existing computational methods to detect these CRMs in metazoan genomes. We subdivide these methods into three classes: CRM scanners screen sequences for CRMs based on predefined models that often consist of multiple position weight matrices (PWMs). CRM builders construct models of similar CRMs controlling a set of co-regulated or co-expressed genes. CRM genome screeners screen sequences or complete genomes for CRMs as homotypic or heterotypic clusters of binding sites for any combination of transcription factors. We believe that CRM scanners are currently the most advanced methods, although their applicability is limited. Finally, we argue that CRM builders that make use of PWM libraries will benefit greatly from future advances and will prove to be most instrumental for the annotation of regulatory regions in metazoan genomes.

  1. Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6.

    Science.gov (United States)

    Cleves, Phillip A; Ellis, Nicholas A; Jimenez, Monica T; Nunez, Stephanie M; Schluter, Dolph; Kingsley, David M; Miller, Craig T

    2014-09-23

    Developmental genetic studies of evolved differences in morphology have led to the hypothesis that cis-regulatory changes often underlie morphological evolution. However, because most of these studies focus on evolved loss of traits, the genetic architecture and possible association with cis-regulatory changes of gain traits are less understood. Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts. Comparing laboratory-reared developmental time courses of a low-toothed marine population and this high-toothed benthic population reveals that increases in tooth number and tooth plate area and decreases in tooth spacing arise at late juvenile stages. Genome-wide linkage mapping identifies largely separate sets of quantitative trait loci affecting different aspects of dental patterning. One large-effect quantitative trait locus controlling tooth number fine-maps to a genomic region containing an excellent candidate gene, Bone morphogenetic protein 6 (Bmp6). Stickleback Bmp6 is expressed in developing teeth, and no coding changes are found between the high- and low-toothed populations. However, quantitative allele-specific expression assays of Bmp6 in developing teeth in F1 hybrids show that cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development. Collectively, our data support a model where a late-acting cis-regulatory up-regulation of Bmp6 expression underlies a significant increase in tooth number in derived benthic sticklebacks.

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

    Science.gov (United States)

    Lewis, James J; van der Burg, Karin R L; Mazo-Vargas, Anyi; Reed, Robert D

    2016-09-13

    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.

  3. Divergence in cis-regulatory sequences surrounding the opsin gene arrays of African cichlid fishes

    Directory of Open Access Journals (Sweden)

    Streelman J Todd

    2011-05-01

    Full Text Available Abstract Background Divergence within cis-regulatory sequences may contribute to the adaptive evolution of gene expression, but functional alleles in these regions are difficult to identify without abundant genomic resources. Among African cichlid fishes, the differential expression of seven opsin genes has produced adaptive differences in visual sensitivity. Quantitative genetic analysis suggests that cis-regulatory alleles near the SWS2-LWS opsins may contribute to this variation. Here, we sequence BACs containing the opsin genes of two cichlids, Oreochromis niloticus and Metriaclima zebra. We use phylogenetic footprinting and shadowing to examine divergence in conserved non-coding elements, promoter sequences, and 3'-UTRs surrounding each opsin in search of candidate cis-regulatory sequences that influence cichlid opsin expression. Results We identified 20 conserved non-coding elements surrounding the opsins of cichlids and other teleosts, including one known enhancer and a retinal microRNA. Most conserved elements contained computationally-predicted binding sites that correspond to transcription factors that function in vertebrate opsin expression; O. niloticus and M. zebra were significantly divergent in two of these. Similarly, we found a large number of relevant transcription factor binding sites within each opsin's proximal promoter, and identified five opsins that were considerably divergent in both expression and the number of transcription factor binding sites shared between O. niloticus and M. zebra. We also found several microRNA target sites within the 3'-UTR of each opsin, including two 3'-UTRs that differ significantly between O. niloticus and M. zebra. Finally, we examined interspecific divergence among 18 phenotypically diverse cichlids from Lake Malawi for one conserved non-coding element, two 3'-UTRs, and five opsin proximal promoters. We found that all regions were highly conserved with some evidence of CRX transcription

  4. In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression.

    Science.gov (United States)

    Zagrijchuk, Elizaveta A; Sabirov, Marat A; Holloway, David M; Spirov, Alexander V

    2014-04-01

    Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes.

  5. In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

    Science.gov (United States)

    Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

    2014-01-01

    Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

  6. 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.

  7. Rapid evolution of cis-regulatory sequences via local point mutations

    Science.gov (United States)

    Stone, J. R.; Wray, G. A.

    2001-01-01

    Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

  8. Are Interactions between cis-Regulatory Variants Evidence for Biological Epistasis or Statistical Artifacts?

    Science.gov (United States)

    Fish, Alexandra E; Capra, John A; Bush, William S

    2016-10-06

    The importance of epistasis-or statistical interactions between genetic variants-to the development of complex disease in humans has been controversial. Genome-wide association studies of statistical interactions influencing human traits have recently become computationally feasible and have identified many putative interactions. However, statistical models used to detect interactions can be confounded, which makes it difficult to be certain that observed statistical interactions are evidence for true molecular epistasis. In this study, we investigate whether there is evidence for epistatic interactions between genetic variants within the cis-regulatory region that influence gene expression after accounting for technical, statistical, and biological confounding factors. We identified 1,119 (FDR = 5%) interactions that appear to regulate gene expression in human lymphoblastoid cell lines, a tightly controlled, largely genetically determined phenotype. Many of these interactions replicated in an independent dataset (90 of 803 tested, Bonferroni threshold). We then performed an exhaustive analysis of both known and novel confounders, including ceiling/floor effects, missing genotype combinations, haplotype effects, single variants tagged through linkage disequilibrium, and population stratification. Every interaction could be explained by at least one of these confounders, and replication in independent datasets did not protect against some confounders. Assuming that the confounding factors provide a more parsimonious explanation for each interaction, we find it unlikely that cis-regulatory interactions contribute strongly to human gene expression, which calls into question the relevance of cis-regulatory interactions for other human phenotypes. We additionally propose several best practices for epistasis testing to protect future studies from confounding. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Nucleotide sequence conservation of novel and established cis-regulatory sites within the tyrosine hydroxylase gene promoter.

    Science.gov (United States)

    Wang, Meng; Banerjee, Kasturi; Baker, Harriet; Cave, John W

    2015-02-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis and its gene proximal promoter ( electromobility shift assays showed that brain-region specific complexes assemble on these motifs. These studies also identified a non-canonical CRE binding (CREB) protein recognition element in the proximal promoter. Together, these studies provide a detailed analysis of evolutionary conservation within the TH promoter and identify potential cis-regulatory motifs that underlie a core set of regulatory mechanisms in mammals.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. A primer on regression methods for decoding cis-regulatory logic

    Energy Technology Data Exchange (ETDEWEB)

    Das, Debopriya; Pellegrini, Matteo; Gray, Joe W.

    2009-03-03

    The rapidly emerging field of systems biology is helping us to understand the molecular determinants of phenotype on a genomic scale [1]. Cis-regulatory elements are major sequence-based determinants of biological processes in cells and tissues [2]. For instance, during transcriptional regulation, transcription factors (TFs) bind to very specific regions on the promoter DNA [2,3] and recruit the basal transcriptional machinery, which ultimately initiates mRNA transcription (Figure 1A). Learning cis-Regulatory Elements from Omics Data A vast amount of work over the past decade has shown that omics data can be used to learn cis-regulatory logic on a genome-wide scale [4-6]--in particular, by integrating sequence data with mRNA expression profiles. The most popular approach has been to identify over-represented motifs in promoters of genes that are coexpressed [4,7,8]. Though widely used, such an approach can be limiting for a variety of reasons. First, the combinatorial nature of gene regulation is difficult to explicitly model in this framework. Moreover, in many applications of this approach, expression data from multiple conditions are necessary to obtain reliable predictions. This can potentially limit the use of this method to only large data sets [9]. Although these methods can be adapted to analyze mRNA expression data from a pair of biological conditions, such comparisons are often confounded by the fact that primary and secondary response genes are clustered together--whereas only the primary response genes are expected to contain the functional motifs [10]. A set of approaches based on regression has been developed to overcome the above limitations [11-32]. These approaches have their foundations in certain biophysical aspects of gene regulation [26,33-35]. That is, the models are motivated by the expected transcriptional response of genes due to the binding of TFs to their promoters. While such methods have gathered popularity in the computational domain

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

    Directory of Open Access Journals (Sweden)

    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.

  13. SMCis: An Effective Algorithm for Discovery of Cis-Regulatory Modules

    Science.gov (United States)

    Guo, Haitao; Huo, Hongwei; Yu, Qiang

    2016-01-01

    The discovery of cis-regulatory modules (CRMs) is a challenging problem in computational biology. Limited by the difficulty of using an HMM to model dependent features in transcriptional regulatory sequences (TRSs), the probabilistic modeling methods based on HMMs cannot accurately represent the distance between regulatory elements in TRSs and are cumbersome to model the prevailing dependencies between motifs within CRMs. We propose a probabilistic modeling algorithm called SMCis, which builds a more powerful CRM discovery model based on a hidden semi-Markov model. Our model characterizes the regulatory structure of CRMs and effectively models dependencies between motifs at a higher level of abstraction based on segments rather than nucleotides. Experimental results on three benchmark datasets indicate that our method performs better than the compared algorithms. PMID:27637070

  14. Massively parallel cis-regulatory analysis in the mammalian central nervous system.

    Science.gov (United States)

    Shen, Susan Q; Myers, Connie A; Hughes, Andrew E O; Byrne, Leah C; Flannery, John G; Corbo, Joseph C

    2016-02-01

    Cis-regulatory elements (CREs, e.g., promoters and enhancers) regulate gene expression, and variants within CREs can modulate disease risk. Next-generation sequencing has enabled the rapid generation of genomic data that predict the locations of CREs, but a bottleneck lies in functionally interpreting these data. To address this issue, massively parallel reporter assays (MPRAs) have emerged, in which barcoded reporter libraries are introduced into cells, and the resulting barcoded transcripts are quantified by next-generation sequencing. Thus far, MPRAs have been largely restricted to assaying short CREs in a limited repertoire of cultured cell types. Here, we present two advances that extend the biological relevance and applicability of MPRAs. First, we adapt exome capture technology to instead capture candidate CREs, thereby tiling across the targeted regions and markedly increasing the length of CREs that can be readily assayed. Second, we package the library into adeno-associated virus (AAV), thereby allowing delivery to target organs in vivo. As a proof of concept, we introduce a capture library of about 46,000 constructs, corresponding to roughly 3500 DNase I hypersensitive (DHS) sites, into the mouse retina by ex vivo plasmid electroporation and into the mouse cerebral cortex by in vivo AAV injection. We demonstrate tissue-specific cis-regulatory activity of DHSs and provide examples of high-resolution truncation mutation analysis for multiplex parsing of CREs. Our approach should enable massively parallel functional analysis of a wide range of CREs in any organ or species that can be infected by AAV, such as nonhuman primates and human stem cell-derived organoids.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Overview Article: Identifying transcriptional cis-regulatory modules in animal genomes

    Science.gov (United States)

    Suryamohan, Kushal; Halfon, Marc S.

    2014-01-01

    Gene expression is regulated through the activity of transcription factors and chromatin modifying proteins acting on specific DNA sequences, referred to as cis-regulatory elements. These include promoters, located at the transcription initiation sites of genes, and a variety of distal cis-regulatory modules (CRMs), the most common of which are transcriptional enhancers. Because regulated gene expression is fundamental to cell differentiation and acquisition of new cell fates, identifying, characterizing, and understanding the mechanisms of action of CRMs is critical for understanding development. CRM discovery has historically been challenging, as CRMs can be located far from the genes they regulate, have few readily-identifiable sequence characteristics, and for many years were not amenable to high-throughput discovery methods. However, the recent availability of complete genome sequences and the development of next-generation sequencing methods has led to an explosion of both computational and empirical methods for CRM discovery in model and non-model organisms alike. Experimentally, CRMs can be identified through chromatin immunoprecipitation directed against transcription factors or histone post-translational modifications, identification of nucleosome-depleted “open” chromatin regions, or sequencing-based high-throughput functional screening. Computational methods include comparative genomics, clustering of known or predicted transcription factor binding sites, and supervised machine-learning approaches trained on known CRMs. All of these methods have proven effective for CRM discovery, but each has its own considerations and limitations, and each is subject to a greater or lesser number of false-positive identifications. Experimental confirmation of predictions is essential, although shortcomings in current methods suggest that additional means of validation need to be developed. PMID:25704908

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Rearrangements of 2.5 kilobases of noncoding DNA from the Drosophila even-skipped locus define predictive rules of genomic cis-regulatory logic.

    Directory of Open Access Journals (Sweden)

    Ah-Ram Kim

    Full Text Available Rearrangements of about 2.5 kilobases of regulatory DNA located 5' of the transcription start site of the Drosophila even-skipped locus generate large-scale changes in the expression of even-skipped stripes 2, 3, and 7. The most radical effects are generated by juxtaposing the minimal stripe enhancers MSE2 and MSE3 for stripes 2 and 3 with and without small "spacer" segments less than 360 bp in length. We placed these fusion constructs in a targeted transformation site and obtained quantitative expression data for these transformants together with their controlling transcription factors at cellular resolution. These data demonstrated that the rearrangements can alter expression levels in stripe 2 and the 2-3 interstripe by a factor of more than 10. We reasoned that this behavior would place tight constraints on possible rules of genomic cis-regulatory logic. To find these constraints, we confronted our new expression data together with previously obtained data on other constructs with a computational model. The model contained representations of thermodynamic protein-DNA interactions including steric interference and cooperative binding, short-range repression, direct repression, activation, and coactivation. The model was highly constrained by the training data, which it described within the limits of experimental error. The model, so constrained, was able to correctly predict expression patterns driven by enhancers for other Drosophila genes; even-skipped enhancers not included in the training set; stripe 2, 3, and 7 enhancers from various Drosophilid and Sepsid species; and long segments of even-skipped regulatory DNA that contain multiple enhancers. The model further demonstrated that elevated expression driven by a fusion of MSE2 and MSE3 was a consequence of the recruitment of a portion of MSE3 to become a functional component of MSE2, demonstrating that cis-regulatory "elements" are not elementary objects.

  19. Understanding the Dynamics of Gene Regulatory Systems; Characterisation and Clinical Relevance of cis-Regulatory Polymorphisms

    Directory of Open Access Journals (Sweden)

    Philip Cowie

    2013-01-01

    Full Text Available Modern genetic analysis has shown that most polymorphisms associated with human disease are non-coding. Much of the functional information contained in the non-coding genome consists of cis-regulatory sequences (CRSs that are required to respond to signal transduction cues that direct cell specific gene expression. It has been hypothesised that many diseases may be due to polymorphisms within CRSs that alter their responses to signal transduction cues. However, identification of CRSs, and the effects of allelic variation on their ability to respond to signal transduction cues, is still at an early stage. In the current review we describe the use of comparative genomics and experimental techniques that allow for the identification of CRSs building on recent advances by the ENCODE consortium. In addition we describe techniques that allow for the analysis of the effects of allelic variation and epigenetic modification on CRS responses to signal transduction cues. Using specific examples we show that the interactions driving these elements are highly complex and the effects of disease associated polymorphisms often subtle. It is clear that gaining an understanding of the functions of CRSs, and how they are affected by SNPs and epigenetic modification, is essential to understanding the genetic basis of human disease and stratification whilst providing novel directions for the development of personalised medicine.

  20. A transposon-based chromosomal engineering method to survey a large cis-regulatory landscape in mice.

    Science.gov (United States)

    Kokubu, Chikara; Horie, Kyoji; Abe, Koichiro; Ikeda, Ryuji; Mizuno, Sumi; Uno, Yoshihiro; Ogiwara, Sanae; Ohtsuka, Masato; Isotani, Ayako; Okabe, Masaru; Imai, Kenji; Takeda, Junji

    2009-08-01

    A large cis-regulatory landscape is a common feature of vertebrate genomes, particularly at key developmental gene loci with finely tuned expression patterns. Existing genetic tools for surveying large genomic regions of interest spanning over hundreds of kilobases are limited. Here we propose a chromosomal engineering strategy exploiting the local hopping trait of the Sleeping Beauty transposon in the mouse genome. We generated embryonic stem cells with a targeted integration of the transposon vector, carrying an enhancer-detecting lacZ reporter and loxP cassette, into the developmentally critical Pax1 gene locus, followed by efficient local transpositions, nested deletion formation and derivation of embryos by tetraploid complementation. Comparative reporter expression analysis among different insertion/deletion embryos substantially facilitated long-range cis-regulatory element mapping in the genomic neighborhood and demonstrated the potential of the transposon-based approach as a versatile tool for exploration of defined genomic intervals of functional or clinical relevance, such as disease-associated microdeletions.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Conserved cis-regulatory modules in promoters of genes encoding wheat high-molecular-weight glutenin subunits.

    Science.gov (United States)

    Ravel, Catherine; Fiquet, Samuel; Boudet, Julie; Dardevet, Mireille; Vincent, Jonathan; Merlino, Marielle; Michard, Robin; Martre, Pierre

    2014-01-01

    The concentration and composition of the gliadin and glutenin seed storage proteins (SSPs) in wheat flour are the most important determinants of its end-use value. In cereals, the synthesis of SSPs is predominantly regulated at the transcriptional level by a complex network involving at least five cis-elements in gene promoters. The high-molecular-weight glutenin subunits (HMW-GS) are encoded by two tightly linked genes located on the long arms of group 1 chromosomes. Here, we sequenced and annotated the HMW-GS gene promoters of 22 electrophoretic wheat alleles to identify putative cis-regulatory motifs. We focused on 24 motifs known to be involved in SSP gene regulation. Most of them were identified in at least one HMW-GS gene promoter sequence. A common regulatory framework was observed in all the HMW-GS gene promoters, as they shared conserved cis-regulatory modules (CCRMs) including all the five motifs known to regulate the transcription of SSP genes. This common regulatory framework comprises a composite box made of the GATA motifs and GCN4-like Motifs (GLMs) and was shown to be functional as the GLMs are able to bind a bZIP transcriptional factor SPA (Storage Protein Activator). In addition to this regulatory framework, each HMW-GS gene promoter had additional motifs organized differently. The promoters of most highly expressed x-type HMW-GS genes contain an additional box predicted to bind R2R3-MYB transcriptional factors. However, the differences in annotation between promoter alleles could not be related to their level of expression. In summary, we identified a common modular organization of HMW-GS gene promoters but the lack of correlation between the cis-motifs of each HMW-GS gene promoter and their level of expression suggests that other cis-elements or other mechanisms regulate HMW-GS gene expression.

  3. Studying the functional conservation of cis-regulatory modules and their transcriptional output

    Directory of Open Access Journals (Sweden)

    Bailey Timothy L

    2008-04-01

    Full Text Available Abstract Background Cis-regulatory modules (CRMs are distinct, genomic regions surrounding the target gene that can independently activate the promoter to drive transcription. The activation of a CRM is controlled by the binding of a certain combination of transcription factors (TFs. It would be of great benefit if the transcriptional output mediated by a specific CRM could be predicted. Of equal benefit would be identifying in silico a specific CRM as the driver of the expression in a specific tissue or situation. We extend a recently developed biochemical modeling approach to manage both prediction tasks. Given a set of TFs, their protein concentrations, and the positions and binding strengths of each of the TFs in a putative CRM, the model predicts the transcriptional output of the gene. Our approach predicts the location of the regulating CRM by using predicted TF binding sites in regions near the gene as input to the model and searching for the region that yields a predicted transcription rate most closely matching the known rate. Results Here we show the ability of the model on the example of one of the CRMs regulating the eve gene, MSE2. A model trained on the MSE2 in D. melanogaster was applied to the surrounding sequence of the eve gene in seven other Drosophila species. The model successfully predicts the correct MSE2 location and output in six out of eight Drosophila species we examine. Conclusion The model is able to generalize from D. melanogaster to other Drosophila species and accurately predicts the location and transcriptional output of MSE2 in those species. However, we also show that the current model is not specific enough to function as a genome-wide CRM scanner, because it incorrectly predicts other genomic regions to be MSE2s.

  4. Studying the functional conservation of cis-regulatory modules and their transcriptional output.

    Science.gov (United States)

    Bauer, Denis C; Bailey, Timothy L

    2008-04-29

    Cis-regulatory modules (CRMs) are distinct, genomic regions surrounding the target gene that can independently activate the promoter to drive transcription. The activation of a CRM is controlled by the binding of a certain combination of transcription factors (TFs). It would be of great benefit if the transcriptional output mediated by a specific CRM could be predicted. Of equal benefit would be identifying in silico a specific CRM as the driver of the expression in a specific tissue or situation. We extend a recently developed biochemical modeling approach to manage both prediction tasks. Given a set of TFs, their protein concentrations, and the positions and binding strengths of each of the TFs in a putative CRM, the model predicts the transcriptional output of the gene. Our approach predicts the location of the regulating CRM by using predicted TF binding sites in regions near the gene as input to the model and searching for the region that yields a predicted transcription rate most closely matching the known rate. Here we show the ability of the model on the example of one of the CRMs regulating the eve gene, MSE2. A model trained on the MSE2 in D. melanogaster was applied to the surrounding sequence of the eve gene in seven other Drosophila species. The model successfully predicts the correct MSE2 location and output in six out of eight Drosophila species we examine. The model is able to generalize from D. melanogaster to other Drosophila species and accurately predicts the location and transcriptional output of MSE2 in those species. However, we also show that the current model is not specific enough to function as a genome-wide CRM scanner, because it incorrectly predicts other genomic regions to be MSE2s.

  5. MotifCombinator: a web-based tool to search for combinations of cis-regulatory motifs

    Directory of Open Access Journals (Sweden)

    Tsunoda Tatsuhiko

    2007-03-01

    Full Text Available Abstract Background A combination of multiple types of transcription factors and cis-regulatory elements is often required for gene expression in eukaryotes, and the combinatorial regulation confers specific gene expression to tissues or environments. To reveal the combinatorial regulation, computational methods are developed that efficiently infer combinations of cis-regulatory motifs that are important for gene expression as measured by DNA microarrays. One promising type of computational method is to utilize regression analysis between expression levels and scores of motifs in input sequences. This type takes full advantage of information on expression levels because it does not require that the expression level of each gene be dichotomized according to whether or not it reaches a certain threshold level. However, there is no web-based tool that employs regression methods to systematically search for motif combinations and that practically handles combinations of more than two or three motifs. Results We here introduced MotifCombinator, an online tool with a user-friendly interface, to systematically search for combinations composed of any number of motifs based on regression methods. The tool utilizes well-known regression methods (the multivariate linear regression, the multivariate adaptive regression spline or MARS, and the multivariate logistic regression method for this purpose, and uses the genetic algorithm to search for combinations composed of any desired number of motifs. The visualization systems in this tool help users to intuitively grasp the process of the combination search, and the backup system allows users to easily stop and restart calculations that are expected to require large computational time. This tool also provides preparatory steps needed for systematic combination search – i.e., selecting single motifs to constitute combinations and cutting out redundant similar motifs based on clustering analysis. Conclusion

  6. 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

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Conservation of shh cis-regulatory architecture of the coelacanth is consistent with its ancestral phylogenetic position

    Directory of Open Access Journals (Sweden)

    Lang Michael

    2010-11-01

    Full Text Available Abstract Background The modern coelacanth (Latimeria is the extant taxon of a basal sarcopterygian lineage and sister group to tetrapods. Apart from certain apomorphic traits, its morphology is characterized by a high degree of retention of ancestral vertebrate structures and little morphological change. An insight into the molecular evolution that may explain the unchanged character of Latimeria morphology requires the analysis of the expression patterns of developmental regulator genes and their cis-regulatory modules (CRMs. Results We describe the comparative and functional analysis of the sonic hedgehog (shh genomic region of Latimeria menadoensis. Several putative enhancers in the Latimeria shh locus have been identified by comparisons to sarcopterygian and actinopterygian extant species. Specific sequence conservation with all known actinopterygian enhancer elements has been detected. However, these elements are selectively missing in more recently diverged actinopterygian and sarcopterygian species. The functionality of the putative Latimeria enhancers was confirmed by reporter gene expression analysis in transient transgenic zebrafish and chick embryos. Conclusions Latimeria shh CRMs represent the ancestral set of enhancers that have emerged before the split of lobe-finned and ray-finned fishes. In contrast to lineage-specific losses and differentiations in more derived lineages, Latimeria shh enhancers reveal low levels of sequence diversification. High overall sequence conservation of shh conserved noncoding elements (CNE is consistent with the general trend of high levels of conservation of noncoding DNA in the slowly evolving Latimeria genome.

  10. Expression-guided in silico evaluation of candidate cis regulatory codes for Drosophila muscle founder cells.

    Directory of Open Access Journals (Sweden)

    Anthony A Philippakis

    2006-05-01

    Full Text Available While combinatorial models of transcriptional regulation can be inferred for metazoan systems from a priori biological knowledge, validation requires extensive and time-consuming experimental work. Thus, there is a need for computational methods that can evaluate hypothesized cis regulatory codes before the difficult task of experimental verification is undertaken. We have developed a novel computational framework (termed "CodeFinder" that integrates transcription factor binding site and gene expression information to evaluate whether a hypothesized transcriptional regulatory model (TRM; i.e., a set of co-regulating transcription factors is likely to target a given set of co-expressed genes. Our basic approach is to simultaneously predict cis regulatory modules (CRMs associated with a given gene set and quantify the enrichment for combinatorial subsets of transcription factor binding site motifs comprising the hypothesized TRM within these predicted CRMs. As a model system, we have examined a TRM experimentally demonstrated to drive the expression of two genes in a sub-population of cells in the developing Drosophila mesoderm, the somatic muscle founder cells. This TRM was previously hypothesized to be a general mode of regulation for genes expressed in this cell population. In contrast, the present analyses suggest that a modified form of this cis regulatory code applies to only a subset of founder cell genes, those whose gene expression responds to specific genetic perturbations in a similar manner to the gene on which the original model was based. We have confirmed this hypothesis by experimentally discovering six (out of 12 tested new CRMs driving expression in the embryonic mesoderm, four of which drive expression in founder cells.

  11. The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron

    Science.gov (United States)

    Etchberger, John F.; Lorch, Adam; Sleumer, Monica C.; Zapf, Richard; Jones, Steven J.; Marra, Marco A.; Holt, Robert A.; Moerman, Donald G.; Hobert, Oliver

    2007-01-01

    Taste receptor cells constitute a highly specialized cell type that perceives and conveys specific sensory information to the brain. The detailed molecular composition of these cells and the mechanisms that program their fate are, in general, poorly understood. We have generated serial analysis of gene expression (SAGE) libraries from two distinct populations of single, isolated sensory neuron classes, the gustatory neuron class ASE and the thermosensory neuron class AFD, from the nematode Caenorhabditis elegans. By comparing these two libraries, we have identified >1000 genes that define the ASE gustatory neuron class on a molecular level. This set of genes contains determinants of the differentiated state of the ASE neuron, such as a surprisingly complex repertoire of transcription factors (TFs), ion channels, neurotransmitters, and receptors, as well as seven-transmembrane receptor (7TMR)-type putative gustatory receptor genes. Through the in vivo dissection of the cis-regulatory regions of several ASE-expressed genes, we identified a small cis-regulatory motif, the “ASE motif,” that is required for the expression of many ASE-expressed genes. We demonstrate that the ASE motif is a binding site for the C2H2 zinc finger TF CHE-1, which is essential for the correct differentiation of the ASE gustatory neuron. Taken together, our results provide a unique view of the molecular landscape of a single neuron type and reveal an important aspect of the regulatory logic for gustatory neuron specification in C. elegans. PMID:17606643

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Establishment of the methods for searching eukaryotic gene cis-regulatory modules.

    Science.gov (United States)

    Zhong, Dong; Zhang, Zhen-shu; Liu, Yu-hu; Zheng, Guo-qing; Liu, Xiao-yi; Lu, Yang; Zhao, Gui-jun; Xu, An-long

    2004-02-01

    On the basis of the knowledge of eukaryotic gene regulation, we modified the method in three aspects: (1) Searching the cis-regulatory modules (CRM) according Fasta or Blast sequence with multiple sequence and low E value, followed by mutual scoring of these sequence with Smith-Waterman algorithms and finally by clustering analysis; (2) Searching the transcription factor-binding site using International Union of Pure and Applied Chemistry, Position-Weight Matrix(PWM) and Dyed method; (3) Designing and implementation of data analysis based on the software in Windows 2000 and UNIX using object-oriented technology. The results of analysis of the major histocompatibility complex gene family show that this procedure may accurately locate the regions that contain some of the CRMs.

  14. Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4.

    Science.gov (United States)

    Hanikenne, Marc; Talke, Ina N; Haydon, Michael J; Lanz, Christa; Nolte, Andrea; Motte, Patrick; Kroymann, Juergen; Weigel, Detlef; Krämer, Ute

    2008-05-15

    Little is known about the types of mutations underlying the evolution of species-specific traits. The metal hyperaccumulator Arabidopsis halleri has the rare ability to colonize heavy-metal-polluted soils, and, as an extremophile sister species of Arabidopsis thaliana, it is a powerful model for research on adaptation. A. halleri naturally accumulates and tolerates leaf concentrations as high as 2.2% zinc and 0.28% cadmium in dry biomass. On the basis of transcriptomics studies, metal hyperaccumulation in A. halleri has been associated with more than 30 candidate genes that are expressed at higher levels in A. halleri than in A. thaliana. Some of these genes have been genetically mapped to broad chromosomal segments of between 4 and 24 cM co-segregating with Zn and Cd hypertolerance. However, the in planta loss-of-function approaches required to demonstrate the contribution of a given candidate gene to metal hyperaccumulation or hypertolerance have not been pursued to date. Using RNA interference to downregulate HMA4 (HEAVY METAL ATPASE 4) expression, we show here that Zn hyperaccumulation and full hypertolerance to Cd and Zn in A. halleri depend on the metal pump HMA4. Contrary to a postulated global trans regulatory factor governing high expression of numerous metal hyperaccumulation genes, we demonstrate that enhanced expression of HMA4 in A. halleri is attributable to a combination of modified cis-regulatory sequences and copy number expansion, in comparison to A. thaliana. Transfer of an A. halleri HMA4 gene to A. thaliana recapitulates Zn partitioning into xylem vessels and the constitutive transcriptional upregulation of Zn deficiency response genes characteristic of Zn hyperaccumulators. Our results demonstrate the importance of cis-regulatory mutations and gene copy number expansion in the evolution of a complex naturally selected extreme trait. The elucidation of a natural strategy for metal hyperaccumulation enables the rational design of technologies

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

    Science.gov (United States)

    He, Xin; Ling, Xu; Sinha, Saurabh

    2009-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Evolutionary processes acting on candidate cis-regulatory regions in humans inferred from patterns of polymorphism and divergence.

    Directory of Open Access Journals (Sweden)

    Dara G Torgerson

    2009-08-01

    Full Text Available Analysis of polymorphism and divergence in the non-coding portion of the human genome yields crucial information about factors driving the evolution of gene regulation. Candidate cis-regulatory regions spanning more than 15,000 genes in 15 African Americans and 20 European Americans were re-sequenced and aligned to the chimpanzee genome in order to identify potentially functional polymorphism and to characterize and quantify departures from neutral evolution. Distortions of the site frequency spectra suggest a general pattern of selective constraint on conserved non-coding sites in the flanking regions of genes (CNCs. Moreover, there is an excess of fixed differences that cannot be explained by a Gamma model of deleterious fitness effects, suggesting the presence of positive selection on CNCs. Extensions of the McDonald-Kreitman test identified candidate cis-regulatory regions with high probabilities of positive and negative selection near many known human genes, the biological characteristics of which exhibit genome-wide trends that differ from patterns observed in protein-coding regions. Notably, there is a higher probability of positive selection in candidate cis-regulatory regions near genes expressed in the fetal brain, suggesting that a larger portion of adaptive regulatory changes has occurred in genes expressed during brain development. Overall we find that natural selection has played an important role in the evolution of candidate cis-regulatory regions throughout hominid evolution.

  18. On the mechanistic nature of epistasis in a canonical cis-regulatory element

    OpenAIRE

    Lagator, Mato; Paix?o, Tiago; Barton, Nicholas H; Bollback, Jonathan P.; Guet, C?lin C.

    2017-01-01

    eLife digest Mutations are changes to DNA that provide the raw material upon which evolution can act. Therefore, to understand evolution, we need to know the effects of mutations, and how those mutations interact with each other (a phenomenon referred to as epistasis). So far, few mathematical models allow scientists to predict the effects of mutations, and even fewer are able to predict epistasis. Biological systems are complex and consist of many proteins and other molecules. Genes are the ...

  19. New cis-regulatory elements in the Rht-D1b locus region of wheat

    Science.gov (United States)

    Fifteen gene-containing BACs with accumulated length of 1.82-Mb from the Rht-D1b locus region weresequenced and compared in detail with the orthologous regions of rice, sorghum, and maize. Our results show that Rht-D1b represents a conserved genomic region as implied by high gene sequence identity...

  20. Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.

    Directory of Open Access Journals (Sweden)

    Jonas Carlsson Almlöf

    Full Text Available We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52 were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10(-7 to 9.5×10(-89. The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.

  1. 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

  2. Identification of High-Impact cis-Regulatory Mutations Using Transcription Factor Specific Random Forest Models.

    Directory of Open Access Journals (Sweden)

    Dmitry Svetlichnyy

    2015-11-01

    Full Text Available Cancer genomes contain vast amounts of somatic mutations, many of which are passenger mutations not involved in oncogenesis. Whereas driver mutations in protein-coding genes can be distinguished from passenger mutations based on their recurrence, non-coding mutations are usually not recurrent at the same position. Therefore, it is still unclear how to identify cis-regulatory driver mutations, particularly when chromatin data from the same patient is not available, thus relying only on sequence and expression information. Here we use machine-learning methods to predict functional regulatory regions using sequence information alone, and compare the predicted activity of the mutated region with the reference sequence. This way we define the Predicted Regulatory Impact of a Mutation in an Enhancer (PRIME. We find that the recently identified driver mutation in the TAL1 enhancer has a high PRIME score, representing a "gain-of-target" for MYB, whereas the highly recurrent TERT promoter mutation has a surprisingly low PRIME score. We trained Random Forest models for 45 cancer-related transcription factors, and used these to score variations in the HeLa genome and somatic mutations across more than five hundred cancer genomes. Each model predicts only a small fraction of non-coding mutations with a potential impact on the function of the encompassing regulatory region. Nevertheless, as these few candidate driver mutations are often linked to gains in chromatin activity and gene expression, they may contribute to the oncogenic program by altering the expression levels of specific oncogenes and tumor suppressor genes.

  3. Cis-regulatory underpinnings of human GLI3 expression in embryonic craniofacial structures and internal organs.

    Science.gov (United States)

    Abbasi, Amir A; Minhas, Rashid; Schmidt, Ansgar; Koch, Sabine; Grzeschik, Karl-Heinz

    2013-10-01

    The zinc finger transcription factor Gli3 is an important mediator of Sonic hedgehog (Shh) signaling. During early embryonic development Gli3 participates in patterning and growth of the central nervous system, face, skeleton, limb, tooth and gut. Precise regulation of the temporal and spatial expression of Gli3 is crucial for the proper specification of these structures in mammals and other vertebrates. Previously we reported a set of human intronic cis-regulators controlling almost the entire known repertoire of endogenous Gli3 expression in mouse neural tube and limbs. However, the genetic underpinning of GLI3 expression in other embryonic domains such as craniofacial structures and internal organs remain elusive. Here we demonstrate in a transgenic mice assay the potential of a subset of human/fish conserved non-coding sequences (CNEs) residing within GLI3 intronic intervals to induce reporter gene expression at known regions of endogenous Gli3 transcription in embryonic domains other than central nervous system (CNS) and limbs. Highly specific reporter expression was observed in craniofacial structures, eye, gut, and genitourinary system. Moreover, the comparison of expression patterns directed by these intronic cis-acting regulatory elements in mouse and zebrafish embryos suggests that in accordance with sequence conservation, the target site specificity of a subset of these elements remains preserved among these two lineages. Taken together with our recent investigations, it is proposed here that during vertebrate evolution the Gli3 expression control acquired multiple, independently acting, intronic enhancers for spatiotemporal patterning of CNS, limbs, craniofacial structures and internal organs.

  4. Network discovery pipeline elucidates conserved time-of-day-specific cis-regulatory modules.

    Directory of Open Access Journals (Sweden)

    Todd P Michael

    2008-02-01

    Full Text Available Correct daily phasing of transcription confers an adaptive advantage to almost all organisms, including higher plants. In this study, we describe a hypothesis-driven network discovery pipeline that identifies biologically relevant patterns in genome-scale data. To demonstrate its utility, we analyzed a comprehensive matrix of time courses interrogating the nuclear transcriptome of Arabidopsis thaliana plants grown under different thermocycles, photocycles, and circadian conditions. We show that 89% of Arabidopsis transcripts cycle in at least one condition and that most genes have peak expression at a particular time of day, which shifts depending on the environment. Thermocycles alone can drive at least half of all transcripts critical for synchronizing internal processes such as cell cycle and protein synthesis. We identified at least three distinct transcription modules controlling phase-specific expression, including a new midnight specific module, PBX/TBX/SBX. We validated the network discovery pipeline, as well as the midnight specific module, by demonstrating that the PBX element was sufficient to drive diurnal and circadian condition-dependent expression. Moreover, we show that the three transcription modules are conserved across Arabidopsis, poplar, and rice. These results confirm the complex interplay between thermocycles, photocycles, and the circadian clock on the daily transcription program, and provide a comprehensive view of the conserved genomic targets for a transcriptional network key to successful adaptation.

  5. 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.

  6. 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.

  7. 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

    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...

  8. Ancient polymorphism and functional variation in the primate MHC-DQA1 5' cis-regulatory region.

    Science.gov (United States)

    Loisel, Dagan A; Rockman, Matthew V; Wray, Gregory A; Altmann, Jeanne; Alberts, Susan C

    2006-10-31

    Precise regulation of MHC gene expression is critical to vertebrate immune surveillance and response. Polymorphisms in the 5' proximal promoter region of the human class II gene HLA-DQA1 have been shown to influence its transcriptional regulation and may contribute to the pathogenesis of autoimmune diseases. We investigated the evolutionary history of this cis-regulatory region by sequencing the DQA1 5' proximal promoter region in eight nonhuman primate species. We observed unexpectedly high levels of sequence variation and multiple strong signatures of balancing selection in this region. Specifically, the considerable DQA1 promoter region diversity was characterized by abundant shared (or trans-species) polymorphism and a pronounced lack of fixed differences between species. The majority of transcription factor binding sites in the DQA1 promoter region were polymorphic within species, and these binding site polymorphisms were commonly shared among multiple species despite evidence for negative selection eliminating a significant fraction of binding site mutations. We assessed the functional consequences of intraspecific promoter region diversity using a cell line-based reporter assay and detected significant differences among baboon DQA1 promoter haplotypes in their ability to drive transcription in vitro. The functional differentiation of baboon promoter haplotypes, together with the significant deviations from neutral sequence evolution, suggests a role for balancing selection in the evolution of DQA1 transcriptional regulation in primates.

  9. Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period

    Science.gov (United States)

    Tena, Juan J.; González-Aguilera, Cristina; Fernández-Miñán, Ana; Vázquez-Marín, Javier; Parra-Acero, Helena; Cross, Joe W.; Rigby, Peter W.J.; Carvajal, Jaime J.; Wittbrodt, Joachim; Gómez-Skarmeta, José L.; Martínez-Morales, Juan R.

    2014-01-01

    The complex relationship between ontogeny and phylogeny has been the subject of attention and controversy since von Baer’s formulations in the 19th century. The classic concept that embryogenesis progresses from clade general features to species-specific characters has often been revisited. It has become accepted that embryos from a clade show maximum morphological similarity at the so-called phylotypic period (i.e., during mid-embryogenesis). According to the hourglass model, body plan conservation would depend on constrained molecular mechanisms operating at this period. More recently, comparative transcriptomic analyses have provided conclusive evidence that such molecular constraints exist. Examining cis-regulatory architecture during the phylotypic period is essential to understand the evolutionary source of body plan stability. Here we compare transcriptomes and key epigenetic marks (H3K4me3 and H3K27ac) from medaka (Oryzias latipes) and zebrafish (Danio rerio), two distantly related teleosts separated by an evolutionary distance of 115–200 Myr. We show that comparison of transcriptome profiles correlates with anatomical similarities and heterochronies observed at the phylotypic stage. Through comparative epigenomics, we uncover a pool of conserved regulatory regions (≈700), which are active during the vertebrate phylotypic period in both species. Moreover, we show that their neighboring genes encode mainly transcription factors with fundamental roles in tissue specification. We postulate that these regulatory regions, active in both teleost genomes, represent key constrained nodes of the gene networks that sustain the vertebrate body plan. PMID:24709821

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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 ch

  13. Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes.

    Directory of Open Access Journals (Sweden)

    Joseph C Maranville

    2011-07-01

    Full Text Available Glucocorticoids (GCs mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor. Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1 and that influence the secretion of IL6.

  14. Extensive cis-regulatory variation robust to environmental perturbation in Arabidopsis.

    Science.gov (United States)

    Cubillos, Francisco A; Stegle, Oliver; Grondin, Cécile; Canut, Matthieu; Tisné, Sébastien; Gy, Isabelle; Loudet, Olivier

    2014-11-01

    cis- and trans-acting factors affect gene expression and responses to environmental conditions. However, for most plant systems, we lack a comprehensive map of these factors and their interaction with environmental variation. Here, we examined allele-specific expression (ASE) in an F1 hybrid to study how alleles from two Arabidopsis thaliana accessions affect gene expression. To investigate the effect of the environment, we used drought stress and developed a variance component model to estimate the combined genetic contributions of cis- and trans-regulatory polymorphisms, environmental factors, and their interactions. We quantified ASE for 11,003 genes, identifying 3318 genes with consistent ASE in control and stress conditions, demonstrating that cis-acting genetic effects are essentially robust to changes in the environment. Moreover, we found 1618 genes with genotype x environment (GxE) interactions, mostly cis x E interactions with magnitude changes in ASE. We found fewer trans x E interactions, but these effects were relatively less robust across conditions, showing more changes in the direction of the effect between environments; this confirms that trans-regulation plays an important role in the response to environmental conditions. Our data provide a detailed map of cis- and trans-regulation and GxE interactions in A. thaliana, laying the ground for mechanistic investigations and studies in other plants and environments.

  15. Extensive cis-Regulatory Variation Robust to Environmental Perturbation in Arabidopsis[W

    Science.gov (United States)

    Cubillos, Francisco A.; Stegle, Oliver; Grondin, Cécile; Canut, Matthieu; Tisné, Sébastien; Gy, Isabelle

    2014-01-01

    cis- and trans-acting factors affect gene expression and responses to environmental conditions. However, for most plant systems, we lack a comprehensive map of these factors and their interaction with environmental variation. Here, we examined allele-specific expression (ASE) in an F1 hybrid to study how alleles from two Arabidopsis thaliana accessions affect gene expression. To investigate the effect of the environment, we used drought stress and developed a variance component model to estimate the combined genetic contributions of cis- and trans-regulatory polymorphisms, environmental factors, and their interactions. We quantified ASE for 11,003 genes, identifying 3318 genes with consistent ASE in control and stress conditions, demonstrating that cis-acting genetic effects are essentially robust to changes in the environment. Moreover, we found 1618 genes with genotype x environment (GxE) interactions, mostly cis x E interactions with magnitude changes in ASE. We found fewer trans x E interactions, but these effects were relatively less robust across conditions, showing more changes in the direction of the effect between environments; this confirms that trans-regulation plays an important role in the response to environmental conditions. Our data provide a detailed map of cis- and trans-regulation and GxE interactions in A. thaliana, laying the ground for mechanistic investigations and studies in other plants and environments. PMID:25428981

  16. Expression, subcellular localization, and cis-regulatory structure of duplicated phytoene synthase genes in melon (Cucumis melo L.).

    Science.gov (United States)

    Qin, Xiaoqiong; Coku, Ardian; Inoue, Kentaro; Tian, Li

    2011-10-01

    Carotenoids perform many critical functions in plants, animals, and humans. It is therefore important to understand carotenoid biosynthesis and its regulation in plants. Phytoene synthase (PSY) catalyzes the first committed and rate-limiting step in carotenoid biosynthesis. While PSY is present as a single copy gene in Arabidopsis, duplicated PSY genes have been identified in many economically important monocot and dicot crops. CmPSY1 was previously identified from melon (Cucumis melo L.), but was not functionally characterized. We isolated a second PSY gene, CmPSY2, from melon in this work. CmPSY2 possesses a unique intron/exon structure that has not been observed in other plant PSYs. Both CmPSY1 and CmPSY2 are functional in vitro, but exhibit distinct expression patterns in different melon tissues and during fruit development, suggesting differential regulation of the duplicated melon PSY genes. In vitro chloroplast import assays verified the plastidic localization of CmPSY1 and CmPSY2 despite the lack of an obvious plastid target peptide in CmPSY2. Promoter motif analysis of the duplicated melon and tomato PSY genes and the Arabidopsis PSY revealed distinctive cis-regulatory structures of melon PSYs and identified gibberellin-responsive motifs in all PSYs except for SlPSY1, which has not been reported previously. Overall, these data provide new insights into the evolutionary history of plant PSY genes and the regulation of PSY expression by developmental and environmental signals that may involve different regulatory networks.

  17. Cis-regulatory variants affect CHRNA5 mRNA expression in populations of African and European ancestry.

    Directory of Open Access Journals (Sweden)

    Jen-Chyong Wang

    Full Text Available Variants within the gene cluster encoding α3, α5, and β4 nicotinic receptor subunits are major risk factors for substance dependence. The strongest impact on risk is associated with variation in the CHRNA5 gene, where at least two mechanisms are at work: amino acid variation and altered mRNA expression levels. The risk allele of the non-synonymous variant (rs16969968; D398N primarily occurs on the haplotype containing the low mRNA expression allele. In populations of European ancestry, there are approximately 50 highly correlated variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster and the adjacent PSMA4 gene region that are associated with CHRNA5 mRNA levels. It is not clear which of these variants contribute to the changes in CHRNA5 transcript level. Because populations of African ancestry have reduced linkage disequilibrium among variants spanning this gene cluster, eQTL mapping in subjects of African ancestry could potentially aid in defining the functional variants that affect CHRNA5 mRNA levels. We performed quantitative allele specific gene expression using frontal cortices derived from 49 subjects of African ancestry and 111 subjects of European ancestry. This method measures allele-specific transcript levels in the same individual, which eliminates other biological variation that occurs when comparing expression levels between different samples. This analysis confirmed that substance dependence associated variants have a direct cis-regulatory effect on CHRNA5 transcript levels in human frontal cortices of African and European ancestry and identified 10 highly correlated variants, located in a 9 kb region, that are potential functional variants modifying CHRNA5 mRNA expression levels.

  18. A Generalized Linear Model for Decomposing Cis-regulatory, Parent-of-Origin, and Maternal Effects on Allele-Specific Gene Expression

    Directory of Open Access Journals (Sweden)

    Yasuaki Takada

    2017-07-01

    Full Text Available Joint quantification of genetic and epigenetic effects on gene expression is important for understanding the establishment of complex gene regulation systems in living organisms. In particular, genomic imprinting and maternal effects play important roles in the developmental process of mammals and flowering plants. However, the influence of these effects on gene expression are difficult to quantify because they act simultaneously with cis-regulatory mutations. Here we propose a simple method to decompose cis-regulatory (i.e., allelic genotype, genomic imprinting [i.e., parent-of-origin (PO], and maternal [i.e., maternal genotype (MG] effects on allele-specific gene expression using RNA-seq data obtained from reciprocal crosses. We evaluated the efficiency of method using a simulated dataset and applied the method to whole-body Drosophila and mouse trophoblast stem cell (TSC and liver RNA-seq data. Consistent with previous studies, we found little evidence of PO and MG effects in adult Drosophila samples. In contrast, we identified dozens and hundreds of mouse genes with significant PO and MG effects, respectively. Interestingly, a similar number of genes with significant PO effect were detect in mouse TSCs and livers, whereas more genes with significant MG effect were observed in livers. Further application of this method will clarify how these three effects influence gene expression levels in different tissues and developmental stages, and provide novel insight into the evolution of gene expression regulation.

  19. The Role of Cis-Regulatory Motifs and Genetical Control of Expression in the Divergence of Yeast Duplicate Genes

    National Research Council Canada - National Science Library

    Leach, Lindsey J; Zhang, Ze; Lu, Chenqi; Kearsey, Michael J; Luo, Zewei

    2007-01-01

    Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear...

  20. A distal intergenic region controls pancreatic endocrine differentiation by acting as a transcriptional enhancer and as a polycomb response element

    Science.gov (United States)

    Pardanaud-Glavieux, Corinne; García-Hurtado, Javier; Sauty, Claire; Guerci, Aline; Ferrer, Jorge

    2017-01-01

    Lineage-selective expression of developmental genes is dependent on the interplay between activating and repressive mechanisms. Gene activation is dependent on cell-specific transcription factors that recognize transcriptional enhancer sequences. Gene repression often depends on the recruitment of Polycomb group (PcG) proteins, although the sequences that underlie the recruitment of PcG proteins, also known as Polycomb response elements (PREs), remain poorly understood in vertebrates. While distal PREs have been identified in mammals, a role for positive-acting enhancers in PcG-mediated repression has not been described. Here we have used a highly efficient procedure based on lentiviral-mediated transgenesis to carry out in vivo fine-mapping of, cis-regulatory sequences that control lineage-specific activation of Neurog3, a master regulator of pancreatic endocrine differentiation. Our findings reveal an enhancer region that is sufficient to drive correct spacio-temporal expression of Neurog3 and demonstrate that this same region serves as a PRE in alternative lineages where Neurog3 is inactive. PMID:28225770

  1. Genome-wide identification of enhancer elements.

    Science.gov (United States)

    Tulin, Sarah; Barsi, Julius C; Bocconcelli, Carlo; Smith, Joel

    2016-01-01

    We present a prospective genome-wide regulatory element database for the sea urchin embryo and the modified chromosome capture-related methodology used to create it. The method we developed is termed GRIP-seq for genome-wide regulatory element immunoprecipitation and combines features of chromosome conformation capture, chromatin immunoprecipitation, and paired-end next-generation sequencing with molecular steps that enrich for active cis-regulatory elements associated with basal transcriptional machinery. The first GRIP-seq database, available to the community, comes from S. purpuratus 24 hpf embryos and takes advantage of the extremely well-characterized cis-regulatory elements in this system for validation. In addition, using the GRIP-seq database, we identify and experimentally validate a novel, intronic cis-regulatory element at the onecut locus. We find GRIP-seq signal sensitively identifies active cis-regulatory elements with a high signal-to-noise ratio for both distal and intronic elements. This promising GRIP-seq protocol has the potential to address a rate-limiting step in resolving comprehensive, predictive network models in all systems.

  2. Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene.

    Science.gov (United States)

    Boucneau, Joachim; De Schepper, Sofie; Vuylsteke, Marnik; Van Hummelen, Paul; Naeyaert, Jean-Marie; Lambert, Jo

    2005-08-01

    One of the major primary features of the neurocutaneous genetic disorder Neurofibromatosis type 1 are the hyperpigmentary café-au-lait macules where disregulation of melanocyte biology is supposed to play a key etiopathogenic role. To gain better insight into the possible role of the tumor suppressor gene NF1, a transcriptomic microarray analysis was performed on human NF1 heterozygous (NF1+/-) melanocytes of a Neurofibromatosis type 1 patient and NF1 wild type (NF1+/+) melanocytes of a healthy control patient, both cultured from normally pigmented skin and hyperpigmented lesional café-au-lait skin. From the magnitude of gene effects, we found that gene expression was affected most strongly by genotype and less so by lesional type. A total of 137 genes had a significant twofold or more up- (72) or downregulated (65) expression in NF1+/- melanocytes compared with NF1+/+ melanocytes. Melanocytes cultured from hyperpigmented café-au-lait skin showed 37 upregulated genes whereas only 14 were downregulated compared with normal skin melanocytes. In addition, significant genotype xlesional type interactions were observed for 465 genes. Differentially expressed genes were mainly involved in regulating cell proliferation and cell adhesion. A high number of transcription factor genes, among which a specific subset important in melanocyte lineage development, were downregulated in the cis-regulatory network governing the activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. Although the results presented have been obtained with a restricted number of patients (one NF1 patient and one control) and using cDNA microarrays that may limit their interpretation, the data nevertheless addresses for the first time the effect of a heterozygous NF1 gene on the expression of the human melanocyte transcriptome and has generated several interesting candidate genes helpful in elucidating the etiopathology of café-au-lait macules in NF1 patients.

  3. A cis-regulatory mutation in troponin-I of Drosophila reveals the importance of proper stoichiometry of structural proteins during muscle assembly.

    Science.gov (United States)

    Firdaus, Hena; Mohan, Jayaram; Naz, Sarwat; Arathi, Prabhashankar; Ramesh, Saraf R; Nongthomba, Upendra

    2015-05-01

    Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.

  4. Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline.

    Directory of Open Access Journals (Sweden)

    Emily L Landeen

    2016-07-01

    Full Text Available The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation, including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline. In the male germline of Drosophila melanogaster, a novel but poorly understood form of sex chromosome-specific transcriptional regulation occurs that is distinct from canonical sex chromosome dosage compensation or meiotic inactivation. Previous work shows that expression of reporter genes driven by testis-specific promoters is considerably lower-approximately 3-fold or more-for transgenes inserted into X chromosome versus autosome locations. Here we characterize this transcriptional suppression of X-linked genes in the male germline and its evolutionary consequences. Using transgenes and transpositions, we show that most endogenous X-linked genes, not just testis-specific ones, are transcriptionally suppressed several-fold specifically in the Drosophila male germline. In wild-type testes, this sex chromosome-wide transcriptional suppression is generally undetectable, being effectively compensated by the gene-by-gene evolutionary recruitment of strong promoters on the X chromosome. We identify and experimentally validate a promoter element sequence motif that is enriched upstream of the transcription start sites of hundreds of testis-expressed genes; evolutionarily conserved across species; associated with strong gene expression levels in testes; and overrepresented on the X chromosome. These findings show that the expression of X-linked genes in the Drosophila testes reflects a balance between chromosome-wide epigenetic transcriptional suppression and long-term compensatory adaptation by sex-linked genes. Our results have broad implications for the evolution of gene expression in the Drosophila male germline and for genome evolution.

  5. Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline.

    Science.gov (United States)

    Landeen, Emily L; Muirhead, Christina A; Wright, Lori; Meiklejohn, Colin D; Presgraves, Daven C

    2016-07-01

    The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation, including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline. In the male germline of Drosophila melanogaster, a novel but poorly understood form of sex chromosome-specific transcriptional regulation occurs that is distinct from canonical sex chromosome dosage compensation or meiotic inactivation. Previous work shows that expression of reporter genes driven by testis-specific promoters is considerably lower-approximately 3-fold or more-for transgenes inserted into X chromosome versus autosome locations. Here we characterize this transcriptional suppression of X-linked genes in the male germline and its evolutionary consequences. Using transgenes and transpositions, we show that most endogenous X-linked genes, not just testis-specific ones, are transcriptionally suppressed several-fold specifically in the Drosophila male germline. In wild-type testes, this sex chromosome-wide transcriptional suppression is generally undetectable, being effectively compensated by the gene-by-gene evolutionary recruitment of strong promoters on the X chromosome. We identify and experimentally validate a promoter element sequence motif that is enriched upstream of the transcription start sites of hundreds of testis-expressed genes; evolutionarily conserved across species; associated with strong gene expression levels in testes; and overrepresented on the X chromosome. These findings show that the expression of X-linked genes in the Drosophila testes reflects a balance between chromosome-wide epigenetic transcriptional suppression and long-term compensatory adaptation by sex-linked genes. Our results have broad implications for the evolution of gene expression in the Drosophila male germline and for genome evolution.

  6. 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.

  7. Exact p-value calculation for heterotypic clusters of regulatory motifs and its application in computational annotation of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Roytberg Mikhail A

    2007-10-01

    Full Text Available Abstract Background cis-Regulatory modules (CRMs of eukaryotic genes often contain multiple binding sites for transcription factors. The phenomenon that binding sites form clusters in CRMs is exploited in many algorithms to locate CRMs in a genome. This gives rise to the problem of calculating the statistical significance of the event that multiple sites, recognized by different factors, would be found simultaneously in a text of a fixed length. The main difficulty comes from overlapping occurrences of motifs. So far, no tools have been developed allowing the computation of p-values for simultaneous occurrences of different motifs which can overlap. Results We developed and implemented an algorithm computing the p-value that s different motifs occur respectively k1, ..., ks or more times, possibly overlapping, in a random text. Motifs can be represented with a majority of popular motif models, but in all cases, without indels. Zero or first order Markov chains can be adopted as a model for the random text. The computational tool was tested on the set of cis-regulatory modules involved in D. melanogaster early development, for which there exists an annotation of binding sites for transcription factors. Our test allowed us to correctly identify transcription factors cooperatively/competitively binding to DNA. Method The algorithm that precisely computes the probability of simultaneous motif occurrences is inspired by the Aho-Corasick automaton and employs a prefix tree together with a transition function. The algorithm runs with the O(n|Σ|(m|ℋ MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFlecsaaa@3762@| + K|σ|K ∏i ki time complexity, where n is the length of the text, |Σ| is the alphabet size, m is the

  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. Re...

  9. The disruption of a novel limb cis-regulatory element of SHH is associated with autosomal dominant preaxial polydactyly-hypertrichosis.

    Science.gov (United States)

    Petit, Florence; Jourdain, Anne-Sophie; Holder-Espinasse, Muriel; Keren, Boris; Andrieux, Joris; Duterque-Coquillaud, Martine; Porchet, Nicole; Manouvrier-Hanu, Sylvie; Escande, Fabienne

    2016-01-01

    The expression gradient of the morphogen Sonic Hedgehog (SHH) is crucial in establishing the number and the identity of the digits during anteroposterior patterning of the limb. Its anterior ectopic expression is responsible for preaxial polydactyly (PPD). Most of these malformations are due to the gain-of-function of the Zone of Polarizing Activity Regulatory Sequence, the only limb-specific enhancer of SHH known to date. We report a family affected with a novel condition associating PPD and hypertrichosis of the upper back, following an autosomal dominant mode of inheritance. This phenotype is consistent with deregulation of SHH expression during limb and follicle development. In affected members, we identified a 2 kb deletion located ~240 kb upstream from the SHH promoter. The deleted sequence is capable of repressing the transcriptional activity of the SHH promoter in vitro, consistent with a silencer activity. We hypothesize that the deletion of this silencer could be responsible for SHH deregulation during development, leading to a PPD-hypertrichosis phenotype.

  10. Arabidopsis Flower and Embryo Developmental Genes are Repressed in Seedlings by Different Combinations of Polycomb Group Proteins in Association with Distinct Sets of Cis-regulatory Elements.

    Science.gov (United States)

    Wang, Hua; Liu, Chunmei; Cheng, Jingfei; Liu, Jian; Zhang, Lei; He, Chongsheng; Shen, Wen-Hui; Jin, Hong; Xu, Lin; Zhang, Yijing

    2016-01-01

    Polycomb repressive complexes (PRCs) play crucial roles in transcriptional repression and developmental regulation in both plants and animals. In plants, depletion of different members of PRCs causes both overlapping and unique phenotypic defects. However, the underlying molecular mechanism determining the target specificity and functional diversity is not sufficiently characterized. Here, we quantitatively compared changes of tri-methylation at H3K27 in Arabidopsis mutants deprived of various key PRC components. We show that CURLY LEAF (CLF), a major catalytic subunit of PRC2, coordinates with different members of PRC1 in suppression of distinct plant developmental programs. We found that expression of flower development genes is repressed in seedlings preferentially via non-redundant role of CLF, which specifically associated with LIKE HETEROCHROMATIN PROTEIN1 (LHP1). In contrast, expression of embryo development genes is repressed by PRC1-catalytic core subunits AtBMI1 and AtRING1 in common with PRC2-catalytic enzymes CLF or SWINGER (SWN). This context-dependent role of CLF corresponds well with the change in H3K27me3 profiles, and is remarkably associated with differential co-occupancy of binding motifs of transcription factors (TFs), including MADS box and ABA-related factors. We propose that different combinations of PRC members distinctively regulate different developmental programs, and their target specificity is modulated by specific TFs.

  11. Arabidopsis Flower and Embryo Developmental Genes are Repressed in Seedlings by Different Combinations of Polycomb Group Proteins in Association with Distinct Sets of Cis-regulatory Elements.

    Directory of Open Access Journals (Sweden)

    Hua Wang

    2016-01-01

    Full Text Available Polycomb repressive complexes (PRCs play crucial roles in transcriptional repression and developmental regulation in both plants and animals. In plants, depletion of different members of PRCs causes both overlapping and unique phenotypic defects. However, the underlying molecular mechanism determining the target specificity and functional diversity is not sufficiently characterized. Here, we quantitatively compared changes of tri-methylation at H3K27 in Arabidopsis mutants deprived of various key PRC components. We show that CURLY LEAF (CLF, a major catalytic subunit of PRC2, coordinates with different members of PRC1 in suppression of distinct plant developmental programs. We found that expression of flower development genes is repressed in seedlings preferentially via non-redundant role of CLF, which specifically associated with LIKE HETEROCHROMATIN PROTEIN1 (LHP1. In contrast, expression of embryo development genes is repressed by PRC1-catalytic core subunits AtBMI1 and AtRING1 in common with PRC2-catalytic enzymes CLF or SWINGER (SWN. This context-dependent role of CLF corresponds well with the change in H3K27me3 profiles, and is remarkably associated with differential co-occupancy of binding motifs of transcription factors (TFs, including MADS box and ABA-related factors. We propose that different combinations of PRC members distinctively regulate different developmental programs, and their target specificity is modulated by specific TFs.

  12. β-amylase-like proteins function as transcription factors in Arabidopsis, controlling shoot growth and development.

    Science.gov (United States)

    Reinhold, Heike; Soyk, Sebastian; Simková, Klára; Hostettler, Carmen; Marafino, John; Mainiero, Samantha; Vaughan, Cara K; Monroe, Jonathan D; Zeeman, Samuel C

    2011-04-01

    Plants contain β-amylase-like proteins (BAMs; enzymes usually associated with starch breakdown) present in the nucleus rather than targeted to the chloroplast. They possess BRASSINAZOLE RESISTANT1 (BZR1)-type DNA binding domains--also found in transcription factors mediating brassinosteroid (BR) responses. The two Arabidopsis thaliana BZR1-BAM proteins (BAM7 and BAM8) bind a cis-regulatory element that both contains a G box and resembles a BR-responsive element. In protoplast transactivation assays, these BZR1-BAMs activate gene expression. Structural modeling suggests that the BAM domain's glucan binding cleft is intact, but the recombinant proteins are at least 1000 times less active than chloroplastic β-amylases. Deregulation of BZR1-BAMs (the bam7bam8 double mutant and BAM8-overexpressing plants) causes altered leaf growth and development. Of the genes upregulated in plants overexpressing BAM8 and downregulated in bam7bam8 plants, many carry the cis-regulatory element in their promoters. Many genes that respond to BRs are inversely regulated by BZR1-BAMs. We propose a role for BZR1-BAMs in controlling plant growth and development through crosstalk with BR signaling. Furthermore, we speculate that BZR1-BAMs may transmit metabolic signals by binding a ligand in their BAM domain, although diurnal changes in the concentration of maltose, a candidate ligand produced by chloroplastic β-amylases, do not influence their transcription factor function.

  13. Analyses of fugu hoxa2 genes provide evidence for subfunctionalization of neural crest cell and rhombomere cis-regulatory modules during vertebrate evolution.

    Science.gov (United States)

    McEllin, Jennifer A; Alexander, Tara B; Tümpel, Stefan; Wiedemann, Leanne M; Krumlauf, Robb

    2016-01-15

    Hoxa2 gene is a primary player in regulation of craniofacial programs of head development in vertebrates. Here we investigate the evolution of a Hoxa2 neural crest enhancer identified originally in mouse by comparing and contrasting the fugu hoxa2a and hoxa2b genes with their orthologous teleost and mammalian sequences. Using sequence analyses in combination with transgenic regulatory assays in zebrafish and mouse embryos we demonstrate subfunctionalization of regulatory activity for expression in hindbrain segments and neural crest cells between these two fugu co-orthologs. hoxa2a regulatory sequences have retained the ability to mediate expression in neural crest cells while those of hoxa2b include cis-elements that direct expression in rhombomeres. Functional dissection of the neural crest regulatory potential of the fugu hoxa2a and hoxa2b genes identify the previously unknown cis-element NC5, which is implicated in generating the differential activity of the enhancers from these genes. The NC5 region plays a similar role in the ability of this enhancer to mediate reporter expression in mice, suggesting it is a conserved component involved in control of neural crest expression of Hoxa2 in vertebrate craniofacial development.

  14. Adaptive Mixed Finite Element Methods for Parabolic Optimal Control Problems

    OpenAIRE

    Zuliang Lu

    2011-01-01

    We will investigate the adaptive mixed finite element methods for parabolic optimal control problems. The state and the costate are approximated by the lowest-order Raviart-Thomas mixed finite element spaces, and the control is approximated by piecewise constant elements. We derive a posteriori error estimates of the mixed finite element solutions for optimal control problems. Such a posteriori error estimates can be used to construct more efficient and reliable adaptive mixed finite element ...

  15. The nuclear OXPHOS genes in insecta: a common evolutionary origin, a common cis-regulatory motif, a common destiny for gene duplicates

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2007-11-01

    Full Text Available Abstract Background When orthologous sequences from species distributed throughout an optimal range of divergence times are available, comparative genomics is a powerful tool to address problems such as the identification of the forces that shape gene structure during evolution, although the functional constraints involved may vary in different genes and lineages. Results We identified and annotated in the MitoComp2 dataset the orthologs of 68 nuclear genes controlling oxidative phosphorylation in 11 Drosophilidae species and in five non-Drosophilidae insects, and compared them with each other and with their counterparts in three vertebrates (Fugu rubripes, Danio rerio and Homo sapiens and in the cnidarian Nematostella vectensis, taking into account conservation of gene structure and regulatory motifs, and preservation of gene paralogs in the genome. Comparative analysis indicates that the ancestral insect OXPHOS genes were intron rich and that extensive intron loss and lineage-specific intron gain occurred during evolution. Comparison with vertebrates and cnidarians also shows that many OXPHOS gene introns predate the cnidarian/Bilateria evolutionary split. The nuclear respiratory gene element (NRG has played a key role in the evolution of the insect OXPHOS genes; it is constantly conserved in the OXPHOS orthologs of all the insect species examined, while their duplicates either completely lack the element or possess only relics of the motif. Conclusion Our observations reinforce the notion that the common ancestor of most animal phyla had intron-rich gene, and suggest that changes in the pattern of expression of the gene facilitate the fixation of duplications in the genome and the development of novel genetic functions.

  16. Integration of bioinformatics and synthetic promoters leads to the discovery of novel elicitor-responsive cis-regulatory sequences in Arabidopsis.

    Science.gov (United States)

    Koschmann, Jeannette; Machens, Fabian; Becker, Marlies; Niemeyer, Julia; Schulze, Jutta; Bülow, Lorenz; Stahl, Dietmar J; Hehl, Reinhard

    2012-09-01

    A combination of bioinformatic tools, high-throughput gene expression profiles, and the use of synthetic promoters is a powerful approach to discover and evaluate novel cis-sequences in response to specific stimuli. With Arabidopsis (Arabidopsis thaliana) microarray data annotated to the PathoPlant database, 732 different queries with a focus on fungal and oomycete pathogens were performed, leading to 510 up-regulated gene groups. Using the binding site estimation suite of tools, BEST, 407 conserved sequence motifs were identified in promoter regions of these coregulated gene sets. Motif similarities were determined with STAMP, classifying the 407 sequence motifs into 37 families. A comparative analysis of these 37 families with the AthaMap, PLACE, and AGRIS databases revealed similarities to known cis-elements but also led to the discovery of cis-sequences not yet implicated in pathogen response. Using a parsley (Petroselinum crispum) protoplast system and a modified reporter gene vector with an internal transformation control, 25 elicitor-responsive cis-sequences from 10 different motif families were identified. Many of the elicitor-responsive cis-sequences also drive reporter gene expression in an Agrobacterium tumefaciens infection assay in Nicotiana benthamiana. This work significantly increases the number of known elicitor-responsive cis-sequences and demonstrates the successful integration of a diverse set of bioinformatic resources combined with synthetic promoter analysis for data mining and functional screening in plant-pathogen interaction.

  17. A New Approach to Sequence Analysis Exemplified by Identification of cis-Elements in Abscisic Acid Inducible Promoters

    DEFF Research Database (Denmark)

    Busk, Peter Kamp; Hallin, Peter Fischer; Salomon, Jesper

    Identification of cis-regulatory elements in DNA promoters by computational approaches are a great help in genome-wide elucidation of signal transduction, transcriptional regulation and gene expression. However, to accomplish this has proven a difficult problem in computational genomics in part d...

  18. An "in-out" strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: analysis of the beta-globin locus control region.

    Science.gov (United States)

    Fiering, S; Kim, C G; Epner, E M; Groudine, M

    1993-01-01

    The human beta-globin locus control region (LCR) is a complex DNA regulatory element that controls the expression of the cis-linked beta-like globin genes located in the 55 kilobases 3' of the LCR. We have initiated the functional analysis of the LCR by homologous recombination in murine erythroleukemia cell somatic hybrids that carry a single copy of human chromosome 11 on which the beta-globin locus is situated. High-level expression of the human beta-globin gene normally occurs when these hybrid cells are induced to differentiate. We have reported that the insertion of an expressed selectable marker gene (driven by the Friend virus enhancer/promoter) into the LCR disrupts the LCR-mediated regulation of globin transcription. In these cells, beta-globin is no longer expressed when the cells differentiate; instead, expression of the selectable marker gene increases significantly after differentiation. Since present techniques for homologous recombination require the insertion of a selectable marker, further progress in using homologous recombination to analyze the LCR depends on deletion of the selectable marker and demonstration that the locus functions normally after the insertion, expression, and deletion of the selectable marker. Here we show that after precise deletion of the selectable marker by using the FLP recombinase/FRT (FLP recombinase target) system, the locus functions as it did before the homologous recombination event. These studies demonstrate the feasibility of using homologous recombination to analyze the LCR in particular, and other complex cis-regulatory DNA elements in general, in their normal chromosomal context. Images Fig. 2 Fig. 3 Fig. 4 PMID:8378321

  19. Design of a Novel Current Balanced Voltage Controlled Delay Element

    Directory of Open Access Journals (Sweden)

    Pooja Saxena

    2014-04-01

    Full Text Available This paper presents a design of fast voltage controlled delay element based on modified version of low noise Current Balanced Logic (CBL. This delay element provides identical rising and falling edge delays controlled by the single control voltage. The post layout tunable delay range is from 140 ps to 800 ps over control voltage range of 0 to 2.1 V. An analysis for the delay element is also presented, which is in agreement with the simulated delays. A Delay Lock Loop (DLL is designed using this delay element to verify its performance.

  20. Microcomputer Control of a Hydraulic Power Element.

    Science.gov (United States)

    1986-12-01

    Electrohydraulic (EHD) Servovalves .................... 9 3. Advantages of EHD Servovalves .......................................... 10 4. Control System Types ................................. 10...positional control with less error. [Ref. 3:pp. 1-21 4. Control System Types Control systems are the means by which servovalves can be used to obtain a

  1. Finite element models applied in active structural acoustic control

    NARCIS (Netherlands)

    Oude Nijhuis, Marco H.H.; Boer, de André; Rao, Vittal S.

    2002-01-01

    This paper discusses the modeling of systems for active structural acoustic control. The finite element method is applied to model structures including the dynamics of piezoelectric sensors and actuators. A model reduction technique is presented to make the finite element model suitable for controll

  2. Have humans lost control: The elusive X-controlling element.

    Science.gov (United States)

    Peeters, Samantha B; Yang, Christine; Brown, Carolyn J

    2016-08-01

    The process of X-chromosome inactivation (XCI) randomly silences one of two X chromosomes in normal female cells. The ability to predict if there is a preference for one of the two Xs to be chosen (and survive) more often as the active X has important repercussions in human health and X-linked disease. Mice have a genetic component that modulates non-random skewing called the X-controlling element (Xce). Although the nature of the locus and its mechanisms of action are still under investigation, it is clear that different mouse strains carry unique Xce alleles on their X chromosomes, resulting in distinct skewing phenotypes in the F1 progeny of hybrid crosses. Whether a similar mechanism exists in humans is unclear, and challenges to identifying such a locus include the complexity and diversity of the human genome, the restricted time points and tissue(s) of examination in human subjects, and the lack of a model system recapitulating XCI in early development. In this review we consider the evidence for such a controlling locus in humans, in addition to discussing if we have the power to recognize it given the contribution of selective growth in causing skewed patterns of XCI.

  3. LINC-NIRVANA piston control elements

    Science.gov (United States)

    Brix, Mario; Pott, Jörg-Uwe; Bertram, Thomas; Rost, Steffen; Borelli, Jose Luis; Herbst, Thomas M.; Kuerster, Martin; Rohloff, Ralf-Rainer

    2010-07-01

    We review the status of hardware developments related to the Linc-Nirvana optical path difference (OPD) control. The status of our telescope vibration measurements is given. We present the design concept of a feed-forward loop to damp the impact of telescope mirror vibrations on the OPD seen by Linc-Nirvana. At the focus of the article is a description of the actuator of the OPD control loop. The weight and vibration optimized construction of this actuator (aka piston mirror) and its mount has a complex dynamical behavior, which prevents classical PI feedback control from delivering fast and precise motion of the mirror surface. Therefore, an H-; optimized control strategy will be applied, custom designed for the piston mirror. The effort of realizing a custom controller on a DSP to drive the piezo is balanced by the outlook of achieving more than 5x faster servo bandwidths. The laboratory set-up to identify the system, and verify the closed loop control performance is presented. Our goal is to achieve 30 Hz closed-loop control bandwidth at a precision of 30 nm.

  4. Sequences upstream of the homologous cis-elements of the Adh adult enhancer of Drosophila are required for maximal levels of Adh gene transcription in adults of Scaptodrosophila lebanonensis.

    Science.gov (United States)

    Papaceit, Montserrat; Orengo, Dorcas; Juan, Elvira

    2004-01-01

    The evolution of cis-regulatory elements is of particular interest for our understanding of the evolution of gene regulation. The Adh gene of Drosophilidae shows interspecific differences in tissue-specific expression and transcript levels during development. In Scaptodrosophila lebanonensis adults, the level of distal transcripts is maximal between the fourth and eighth day after eclosion and is around five times higher than that in D. melanogaster Adh(S). To examine whether these quantitative differences are regulated by sequences lying upstream of the distal promoter, we performed in vitro deletion mutagenesis of the Adh gene of S. lebanonensis, followed by P-element-mediated germ-line transformation. All constructs included, as a cotransgene, a modified Adh gene of D. melanogaster (dAdh) in a fixed position and orientation that acted as a chromosomal position control. Using this approach, we have identified a fragment of 1.5 kb in the 5' region, 830 bp upstream of the distal start site, which is required to achieve maximal levels of distal transcript in S. lebanonensis. The presence of this fragment produces a 3.5-fold higher level of distal mRNA (as determined by real time quantitative PCR) compared with the D. melanogaster dAdh cotransgene. This region contains the degenerated end of a minisatellite sequence expanding farther upstream and does not correspond to the Adh adult enhancer (AAE) of D. melanogaster. Indeed, the cis-regulatory elements of the AAE have been identified by phylogenetic footprinting within the region 830 bp upstream of the distal start site of S. lebanonensis. Furthermore, the deletions Delta-830 and Delta-2358 yield the same pattern of tissue-specific expression, indicating that all tissue-specific elements are contained within the region 830 bp upstream of the distal start site. PMID:15166155

  5. Hydrothermal analysis in engineering using control volume finite element method

    CERN Document Server

    Sheikholeslami, Mohsen

    2015-01-01

    Control volume finite element methods (CVFEM) bridge the gap between finite difference and finite element methods, using the advantages of both methods for simulation of multi-physics problems in complex geometries. In Hydrothermal Analysis in Engineering Using Control Volume Finite Element Method, CVFEM is covered in detail and applied to key areas of thermal engineering. Examples, exercises, and extensive references are used to show the use of the technique to model key engineering problems such as heat transfer in nanofluids (to enhance performance and compactness of energy systems),

  6. 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.

  7. Elements of active vibration control for rotating machinery

    Science.gov (United States)

    Ulbrich, Heinz

    1990-01-01

    The success or failure of active vibration control is determined by the availability of suitable actuators, modeling of the entire system including all active elements, positioning of the actuators and sensors, and implementation of problem-adapted control concepts. All of these topics are outlined and their special problems are discussed in detail. Special attention is given to efficient modeling of systems, especially for considering the active elements. Finally, design methods for and the application of active vibration control on rotating machinery are demonstrated by several real applications.

  8. Boundary control of parabolic systems - Finite-element approximation

    Science.gov (United States)

    Lasiecka, I.

    1980-01-01

    The finite element approximation of a Dirichlet type boundary control problem for parabolic systems is considered. An approach based on the direct approximation of an input-output semigroup formula is applied. Error estimates are derived for optimal state and optimal control, and it is noted that these estimates are actually optimal with respect to the approximation theoretic properties.

  9. Analytical techniques and quality control in biomedical trace element research

    DEFF Research Database (Denmark)

    Heydorn, K.

    1994-01-01

    The small number of analytical results in trace element research calls for special methods of quality control. It is shown that when the analytical methods are in statistical control, only small numbers of duplicate or replicate results are needed to ascertain the absence of systematic errors cau...

  10. Histone H3 K27 acetylation marks a potent enhancer element on the adipogenic master regulator gene Pparg2

    Science.gov (United States)

    Ramlee, Muhammad Khairul; Zhang, Qiongyi; Idris, Muhammad; Peng, Xu; Sim, Choon Kiat; Han, Weiping; Xu, Feng

    2014-01-01

    PPARγ2 is expressed almost exclusively in adipose tissue and plays a central role in adipogenesis. Despite intensive studies over the last 2 decades, the mechanism regulating the expression of the Pparg2 gene, especially the role of cis-regulatory elements, is still not completely understood. Here, we report a comprehensive investigation of the enhancer elements within the murine Pparg2 gene. Utilizing the combined techniques of sequence conservation analysis and chromatin marker examination, we identified a potent enhancer element that augmented the expression of a reporter gene under the control of the Pparg2 promoter by 20-fold. This enhancer element was first identified as highly conserved non-coding sequence 10 (CNS10) and was later shown to be enriched with the enhancer marker H3 K27 acetylation. Further studies identified a binding site for p300 as the essential enhancer element in CNS10. Moreover, p300 physically binds to CNS10 and is required for the enhancer activity of CNS10. The depletion of p300 by siRNA resulted in significantly impaired activation of Pparg2 at the early stages of 3T3-L1 adipogenesis. In summary, our study identified a novel enhancer element on the murine Pparg2 gene and suggested a novel mechanism for the regulation of Pparg2 expression by p300 in 3T3-L1 adipogenesis. PMID:25485585

  11. Analytical techniques and quality control in biomedical trace element research

    DEFF Research Database (Denmark)

    Heydorn, K.

    1994-01-01

    The small number of analytical results in trace element research calls for special methods of quality control. It is shown that when the analytical methods are in statistical control, only small numbers of duplicate or replicate results are needed to ascertain the absence of systematic errors cau....../kg. Measurement compatibility is obtained by control of traceability to certified reference materials, (C) 1994 Wiley-Liss, Inc....

  12. Finite element modeling and feedback control of piezoelectric smart structures

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Presents the general formula derived with a smart beam structure bonded with piezoelectric material using the piezoelectricity theory, elastic mechanism and Hamilton principle for eleetromechanically coupled piezoelectric fi nite element and dynamic equations, the second order dynamic model built, and the expression of state space, and the analysis of conventional speed and position feedback and the design of optimum feedback controller for output, the fi nite element models built for a piezoelectric cantilever beam, and the feedback controller designed eventually, and concludes with simulation results that the vibration suppression obtained is very satisfactory and the algorithms proposed are very useful.

  13. 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. PMID:28005945

  14. Element Tracking Strategies for Hot Strip Laminar Cooling Control

    Institute of Scientific and Technical Information of China (English)

    HAN Bin; ZHANG Zhong-ping; LIU Xiang-hua; WANG Guo-dong

    2005-01-01

    Feedforward control is the core to control function in the cooling process of hot strip. One of the most important tasks in feedforward control is to determine the arrival time of the strip at various locations on the runout table for effective control. Based on the principles of element tracking and tracking strategies for variable rolling speed and constant rolling speed, a simple diagonal tracking method for an existing hot strip mill was proposed and tested. The test results show that the proposed strategies are effective for improving tracking control.

  15. A weak Hamiltonian finite element method for optimal control problems

    Science.gov (United States)

    Hodges, Dewey H.; Bless, Robert R.

    1990-01-01

    A temporal finite element method based on a mixed form of the Hamiltonian weak principle is developed for dynamics and optimal control problems. The mixed form of Hamilton's weak principle contains both displacements and momenta as primary variables that are expanded in terms of nodal values and simple polynomial shape functions. Unlike other forms of Hamilton's principle, however, time derivatives of the momenta and displacements do not appear therein; instead, only the virtual momenta and virtual displacements are differentiated with respect to time. Based on the duality that is observed to exist between the mixed form of Hamilton's weak principle and variational principles governing classical optimal control problems, a temporal finite element formulation of the latter can be developed in a rather straightforward manner. Several well-known problems in dynamics and optimal control are illustrated. The example dynamics problem involves a time-marching problem. As optimal control examples, elementary trajectory optimization problems are treated.

  16. Weak Hamiltonian finite element method for optimal control problems

    Science.gov (United States)

    Hodges, Dewey H.; Bless, Robert R.

    1991-01-01

    A temporal finite element method based on a mixed form of the Hamiltonian weak principle is developed for dynamics and optimal control problems. The mixed form of Hamilton's weak principle contains both displacements and momenta as primary variables that are expanded in terms of nodal values and simple polynomial shape functions. Unlike other forms of Hamilton's principle, however, time derivatives of the momenta and displacements do not appear therein; instead, only the virtual momenta and virtual displacements are differentiated with respect to time. Based on the duality that is observed to exist between the mixed form of Hamilton's weak principle and variational principles governing classical optimal control problems, a temporal finite element formulation of the latter can be developed in a rather straightforward manner. Several well-known problems in dynamics and optimal control are illustrated. The example dynamics problem involves a time-marching problem. As optimal control examples, elementary trajectory optimization problems are treated.

  17. Conserved stem-loop structures in the HIV-1 RNA region containing the A3 3' splice site and its cis-regulatory element: possible involvement in RNA splicing.

    Science.gov (United States)

    Jacquenet, S; Ropers, D; Bilodeau, P S; Damier, L; Mougin, A; Stoltzfus, C M; Branlant, C

    2001-01-15

    The HIV-1 transcript is alternatively spliced to over 30 different mRNAs. Whether RNA secondary structure can influence HIV-1 RNA alternative splicing has not previously been examined. Here we have determined the secondary structure of the HIV-1/BRU RNA segment, containing the alternative A3, A4a, A4b, A4c and A5 3' splice sites. Site A3, required for tat mRNA production, is contained in the terminal loop of a stem-loop structure (SLS2), which is highly conserved in HIV-1 and related SIVcpz strains. The exon splicing silencer (ESS2) acting on site A3 is located in a long irregular stem-loop structure (SLS3). Two SLS3 domains were protected by nuclear components under splicing condition assays. One contains the A4c branch points and a putative SR protein binding site. The other one is adjacent to ESS2. Unexpectedly, only the 3' A residue of ESS2 was protected. The suboptimal A3 polypyrimidine tract (PPT) is base paired. Using site-directed mutagenesis and transfection of a mini-HIV-1 cDNA into HeLa cells, we found that, in a wild-type PPT context, a mutation of the A3 downstream sequence that reinforced SLS2 stability decreased site A3 utilization. This was not the case with an optimized PPT. Hence, sequence and secondary structure of the PPT may cooperate in limiting site A3 utilization.

  18. An Electronically Controlled 8-Element Switched Beam Planar Array

    KAUST Repository

    Sharawi, Mohammad S.

    2015-02-24

    An 8-element planar antenna array with electronically controlled switchable-beam pattern is proposed. The planar antenna array consists of patch elements and operates in the 2.45 GHz ISM band. The array is integrated with a digitally controlled feed network that provides the required phases to generate 8 fixed beams covering most of the upper hemisphere of the array. Unlike typical switchable beam antenna arrays, which operate only in one plane, the proposed design is the first to provide full 3D switchable beams with simple control. Only a 3-bit digital word is required for the generation of the 8 different beams. The integrated array is designed on a 3-layer PCB on a Taconic substrate (RF60A). The total dimensions of the fabricated array are 187.1 × 261.3 × 1.3mm3.

  19. A replication-time-controlling sequence element in Schizosaccharomyces pombe.

    Science.gov (United States)

    Tripathi, Vishnu P; Dubey, Dharani D

    2017-08-01

    Eukaryotic replication origins are highly variable in their activity and replication timing. The nature and role of cis-acting regulatory sequences that control chromosomal replication timing is not well defined. In the fission yeast, Schizosaccharomyces pombe, a 200-bp late-replication-enforcing element (LRE), has been shown to enforce late replication of ARS elements in plasmids. Here, we show that a short (133-bp) fragment of the LRE (shLRE) is required for causing late replication of adjoining origins in its native as well as in an ectopic early-replicating chromosomal location. Active from both sides of an early-replicating origin, the shLRE is a bona fide cis-acting regulatory element that imposes late replication timing in the chromosome.

  20. A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans.

    Science.gov (United States)

    Doitsidou, Maria; Flames, Nuria; Topalidou, Irini; Abe, Namiko; Felton, Terry; Remesal, Laura; Popovitchenko, Tatiana; Mann, Richard; Chalfie, Martin; Hobert, Oliver

    2013-06-15

    Terminal differentiation programs in the nervous system are encoded by cis-regulatory elements that control the expression of terminal features of individual neuron types. We decoded the regulatory information that controls the expression of five enzymes and transporters that define the terminal identity of all eight dopaminergic neurons in the nervous system of the Caenorhabditis elegans hermaphrodite. We show that the tightly coordinated, robust expression of these dopaminergic enzymes and transporters ("dopamine pathway") is ensured through a combinatorial cis-regulatory signature that is shared by all dopamine pathway genes. This signature is composed of an Ets domain-binding site, recognized by the previously described AST-1 Ets domain factor, and two distinct types of homeodomain-binding sites that act in a partially redundant manner. Through genetic screens, we identified the sole C. elegans Distalless/Dlx ortholog, ceh-43, as a factor that acts through one of the homeodomain sites to control both induction and maintenance of terminal dopaminergic fate. The second type of homeodomain site is a Pbx-type site, which is recognized in a partially redundant and neuron subtype-specific manner by two Pbx factors, ceh-20 and ceh-40, revealing novel roles of Pbx factors in the context of terminal neuron differentiation. Taken together, we revealed a specific regulatory signature and cognate, terminal selector-type transcription factors that define the entire dopaminergic nervous system of an animal. Dopaminergic neurons in the mouse olfactory bulb express a similar combinatorial transcription factor collective of Ets/Dlx/Pbx factors, suggesting deep phylogenetic conservation of dopaminergic regulatory programs.

  1. 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.

  2. Whorl-specific expression of the SUPERMAN gene of Arabidopsis is mediated by cis elements in the transcribed region.

    Science.gov (United States)

    Ito, Toshiro; Sakai, Hajime; Meyerowitz, Elliot M

    2003-09-02

    The SUPERMAN (SUP) gene of Arabidopsis is involved in controlling cell proliferation in stamen and carpel primordia and in ovules during flower development. The SUP gene encodes a transcription factor with a C2H2-type zinc finger motif, a serine/proline-rich domain, a basic domain, and a leucine-zipper-like domain and is expressed in a very limited region in stamen primordia and in the developing ovary during flower development. The SUP gene is susceptible to methylation, resulting in epigenetic gene silencing. To understand how the SUP gene is expressed spatially and temporally in its restricted domain, and why methylation of the transcribed region affects early-stage SUP expression, we have identified the SUP cis regulatory elements by characterizing SUP gene fusions. These studies show that the SUP gene has discrete upstream promoter elements required for expression in stamen primordia in early stages and in the ovary in later stages. The promoter activity for stamen primordia is modulated by several positive and negative elements located in the transcribed and translated regions. Several regulatory elements in the transcribed region correlate with the areas of the gene that are heavily methylated in epigenetic alleles; these data provide a possible explanation of how methylation of the transcribed region represses transcription.

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

    Directory of Open Access Journals (Sweden)

    Evelyn N Kouwenhoven

    2010-08-01

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

  4. Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development

    Science.gov (United States)

    Sanges, Remo; Hadzhiev, Yavor; Gueroult-Bellone, Marion; Roure, Agnes; Ferg, Marco; Meola, Nicola; Amore, Gabriele; Basu, Swaraj; Brown, Euan R.; De Simone, Marco; Petrera, Francesca; Licastro, Danilo; Strähle, Uwe; Banfi, Sandro; Lemaire, Patrick; Birney, Ewan; Müller, Ferenc; Stupka, Elia

    2013-01-01

    Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups. Our results show that all but one element are conserved in non-syntenic regions between vertebrate and tunicate genomes, while being syntenic among vertebrates. Nevertheless, in all the groups, they are significantly associated with transcription factors showing specific functions fundamental to animal development, such as multicellular organism development and sequence-specific DNA binding. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as ‘Olfactores conserved non-coding elements’. PMID:23393190

  5. Elliptical formation control based on relative orbit elements

    Institute of Scientific and Technical Information of China (English)

    Yin Jianfeng; Han Chao

    2013-01-01

    A new set of relative orbit elements (ROEs) is used to derive a new elliptical formation flying model. In-plane and out-of-plane motions can be completely decoupled, which benefits ellip-tical formation design. The inverse transformation of the state transition matrix is derived to study the relative orbit control strategy. Impulsive feedback control laws are developed for both in-plane and out-of-plane relative motions. Control of in-plane and out-of-plane relative motions can be completely decoupled using the ROE-based feedback control law. A tangential impulsive control method is proposed to study the relationship of fuel consumption and maneuvering positions. An optimal analytical along-track impulsive control strategy is then derived. Different typical orbit maneuvers, including formation establishment, reconfiguration, long-distance maneuvers, and for-mation keeping, are taken as examples to demonstrate the performance of the proposed control laws. The effects of relative measurement errors are also considered to validate the high accuracy of the proposed control method.

  6. Evolutionary conservation of sequence elements controlling cytoplasmic polyadenylylation.

    Science.gov (United States)

    Verrotti, A C; Thompson, S R; Wreden, C; Strickland, S; Wickens, M

    1996-08-20

    Cytoplasmic polyadenylylation is an evolutionarily conserved mechanism involved in the translational activation of a set of maternal messenger RNAs (mRNAs) during early development. In this report, we show by interspecies injections that Xenopus and mouse use the same regulatory sequences to control cytoplasmic poly(A) addition during meiotic maturation. Similarly, Xenopus and Drosophila embryos exploit functionally conserved signals to regulate polyadenylylation during early post-fertilization development. These experiments demonstrate that the sequence elements that govern cytoplasmic polyadenylylation, and hence one form of translational activation, function across species. We infer that the requisite regulatory sequence elements, and likely the trans-acting components with which they interact, have been conserved since the divergence of vertebrates and arthropods.

  7. Evolution of anterior Hox regulatory elements among chordates

    Directory of Open Access Journals (Sweden)

    Natale Alfonso

    2011-11-01

    Full Text Available Abstract Background The Hox family of transcription factors has a fundamental role in segmentation pathways and axial patterning of embryonic development and their clustered organization is linked with the regulatory mechanisms governing their coordinated expression along embryonic axes. Among chordates, of particular interest are the Hox paralogous genes in groups 1-4 since their expression is coupled to the control of regional identity in the anterior nervous system, where the highest structural diversity is observed. Results To investigate the degree of conservation in cis-regulatory components that form the basis of Hox expression in the anterior nervous system, we have used assays for transcriptional activity in ascidians and vertebrates to compare and contrast regulatory potential. We identified four regulatory sequences located near the CiHox1, CiHox2 and CiHox4 genes of the ascidian Ciona intestinalis which direct neural specific domains of expression. Using functional assays in Ciona and vertebrate embryos in combination with sequence analyses of enhancer fragments located in similar positions adjacent to Hox paralogy group genes, we compared the activity of these four Ciona cis-elements with a series of neural specific enhancers from the amphioxus Hox1-3 genes and from mouse Hox paralogous groups 1-4. Conclusions This analysis revealed that Kreisler and Krox20 dependent enhancers critical in segmental regulation of the hindbrain appear to be specific for the vertebrate lineage. In contrast, neural enhancers that function as Hox response elements through the action of Hox/Pbx binding motifs have been conserved during chordate evolution. The functional assays reveal that these Hox response cis-elements are recognized by the regulatory components of different and extant species. Together, our results indicate that during chordate evolution, cis-elements dependent upon Hox/Pbx regulatory complexes, are responsible for key aspects of

  8. Temperature control system for optical elements in astronomical instrumentation

    Science.gov (United States)

    Verducci, Orlando; de Oliveira, Antonio C.; Ribeiro, Flávio F.; Vital de Arruda, Márcio; Gneiding, Clemens D.; Fraga, Luciano

    2014-07-01

    Extremely low temperatures may damage the optical components assembled inside of an astronomical instrument due to the crack in the resin or glue used to attach lenses and mirrors. The environment, very cold and dry, in most of the astronomical observatories contributes to this problem. This paper describes the solution implemented at SOAR for remotely monitoring and controlling temperatures inside of a spectrograph, in order to prevent a possible damage of the optical parts. The system automatically switches on and off some heat dissipation elements, located near the optics, as the measured temperature reaches a trigger value. This value is set to a temperature at which the instrument is not operational to prevent malfunction and only to protect the optics. The software was developed with LabVIEWTM and based on an object-oriented design that offers flexibility and ease of maintenance. As result, the system is able to keep the internal temperature of the instrument above a chosen limit, except perhaps during the response time, due to inertia of the temperature. This inertia can be controlled and even avoided by choosing the correct amount of heat dissipation and location of the thermal elements. A log file records the measured temperature values by the system for operation analysis.

  9. Joint Forward Operating Base Elements of Command and Control

    Science.gov (United States)

    Summers, William C.

    2002-01-01

    Since the 1986 Goldwater-Nichols Act directed the Chairman of the Joint Chiefs of Staff to develop doctrine for the joint employment of the armed forces, tactics, techniques, and procedures have evolved at different rates depending on the competency. Whereas the command of joint air forces is well prescribed within the structure of the air operations center and its associated leadership, command of air assets at a joint forward operating base lacks guidance. Today, the United States prosecutes an air war over Afghanistan from bases in Uzbekistan, Pakistan, and Afghanistan. Elements of the United States Army, Air Force, and Marines combine at these geographically minute locations, each bringing a certain complement of support and command and control. Evidence from operations during the 1999 air war for Kosovo at Tirana Rinas Airport in Albania suggests that when these service elements meet at the airfield for the first time, there are problems associated with local procedure. At best, time is wasted creating local joint systems to overcome the difficulties. At worst, safety and mission accomplishment are jeopardized. This thesis will address the need to develop doctrine and a jointly integrated organization to support the command and control function at a forward operating base.

  10. An adaptive transposable element insertion in the regulatory region of the EO gene in the domesticated silkworm, Bombyx mori.

    Science.gov (United States)

    Sun, Wei; Shen, Yi-Hong; Han, Min-Jin; Cao, Yun-Feng; Zhang, Ze

    2014-12-01

    Although there are many studies to show a key role of transposable elements (TEs) in adaptive evolution of higher organisms, little is known about the molecular mechanisms. In this study, we found that a partial TE (Taguchi) inserted in the cis-regulatory region of the silkworm ecdysone oxidase (EO) gene, which encodes a crucial enzyme to reduce the titer of molting hormone (20-hydroxyecdysone, 20E). The TE insertion occurred during domestication of silkworm and the frequency of the TE insertion in the domesticated silkworm (Bombyx mori) is high, 54.24%. The linkage disequilibrium in the TE inserted strains of the domesticated silkworm was elevated. Molecular population genetics analyses suggest that this TE insertion is adaptive for the domesticated silkworm. Luminescent reporter assay shows that the TE inserted in the cis-regulatory region of the EO gene functions as a 20E-induced enhancer of the gene expression. Further, phenotypic bioassay indicates that the silkworm with the TE insertion exhibited more stable developmental phenotype than the silkworm without the TE insertion when suffering from food shortage. Thus, the inserted TE in the cis-regulatory region of the EO gene increased developmental uniformity of silkworm individuals through regulating 20E metabolism, partially explaining transformation of a domestication developmental trait in the domesticated silkworm. Our results emphasize the exceptional role of gene expression regulation in developmental transition of domesticated animals.

  11. Light element controlled iron isotope fractionation in planetary cores

    Science.gov (United States)

    Shahar, A.; Hillgren, V. J.; Horan, M. F.; Duke, L.; Mock, T. D.

    2013-12-01

    Using iron isotope fractionations measured in planetary and meteorite samples to trace planetary differentiation or formation has yielded contradictory results. Iron from high-Ti lunar basalts is more enriched in 57Fe/54Fe than mantle-derived terrestrial samples, in contrast to the isotopic similarity for almost every other element between the Earth and Moon. SNC (Shergottite, Nakhlite, Chassigny) and HED (Howardite, Eucrite, Diogenite) meteorites, which are thought to be derived from the mantles of Mars and Vesta, respectively, show no isotopic fractionation relative to chondrites. While the Bulk Silicate Earth (BSE) value is debated, recent work has shown effectively that basalts (mid-ocean ridge basalts, terrestrial basalts, and ocean island basalts) are enriched in 57Fe/54Fe relative to chondrites, but the causes of that fractionation are unclear (Craddock et al. 2013). Angrites, basaltic achondrite meteorites, also show enrichment in δ57Fe (Wang et al. 2012). Possible mechanisms include high-pressure core formation, oxidation during perovskite disproportionation, evaporation during the giant impact, and mantle melting. It is important to reconcile why the Earth's basalts are enriched in 57Fe/54Fe but the meteorites from Mars and Vesta are not. One possible explanation is that Mars and Vesta are smaller and the lower pressure attenuated the potential Fe fractionation during core formation. A second possibility is that the intrinsic oxidation states of the planets are causing the differences. However, another option is that the light elements (e.g. S, C, O, H, Si) in the cores of differentiated bodies control the iron isotope fractionation during differentiation. We have conducted experiments at 1 GPa and 1650-1800°C in a piston cylinder apparatus to address how sulfur, carbon and silicon alloyed with iron affect the iron isotopic fractionation between metallic alloy and silicate melt. We find that sulfur has the greatest effect on the iron isotopic

  12. Automatic control of finite element models for temperature-controlled radiofrequency ablation

    Directory of Open Access Journals (Sweden)

    Haemmerich Dieter

    2005-07-01

    Full Text Available Abstract Background The finite element method (FEM has been used to simulate cardiac and hepatic radiofrequency (RF ablation. The FEM allows modeling of complex geometries that cannot be solved by analytical methods or finite difference models. In both hepatic and cardiac RF ablation a common control mode is temperature-controlled mode. Commercial FEM packages don't support automating temperature control. Most researchers manually control the applied power by trial and error to keep the tip temperature of the electrodes constant. Methods We implemented a PI controller in a control program written in C++. The program checks the tip temperature after each step and controls the applied voltage to keep temperature constant. We created a closed loop system consisting of a FEM model and the software controlling the applied voltage. The control parameters for the controller were optimized using a closed loop system simulation. Results We present results of a temperature controlled 3-D FEM model of a RITA model 30 electrode. The control software effectively controlled applied voltage in the FEM model to obtain, and keep electrodes at target temperature of 100°C. The closed loop system simulation output closely correlated with the FEM model, and allowed us to optimize control parameters. Discussion The closed loop control of the FEM model allowed us to implement temperature controlled RF ablation with minimal user input.

  13. 40 CFR 57.402 - Elements of the supplementary control system.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS (CONTINUED) PRIMARY NONFERROUS SMELTER ORDERS Supplementary Control System Requirements § 57.402 Elements of the supplementary control system. Each supplementary control system shall contain the following... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Elements of the supplementary control...

  14. 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.

  15. Human Robotic Systems (HRS): Controlling Robots over Time Delay Element

    Data.gov (United States)

    National Aeronautics and Space Administration — This element involves the development of software that enables easier commanding of a wide range of NASA relevant robots through the Robot Application Programming...

  16. Cancer specificity of promoters of the genes controlling cell proliferation.

    Science.gov (United States)

    Kashkin, Kirill; Chernov, Igor; Stukacheva, Elena; Monastyrskaya, Galina; Uspenskaya, Natalya; Kopantzev, Eugene; Sverdlov, Eugene

    2015-02-01

    Violation of proliferation control is a common feature of cancer cells. We put forward the hypothesis that promoters of genes involved in the control of cell proliferation should possess intrinsic cancer specific activity. We cloned promoter regions of CDC6, POLD1, CKS1B, MCM2, and PLK1 genes into pGL3 reporter vector and studied their ability to drive heterologous gene expression in transfected cancer cells of different origin and in normal human fibroblasts. Each promoter was cloned in short (335-800 bp) and long (up to 2.3 kb) variants to cover probable location of core and whole promoter regulatory elements. Cloned promoters were significantly more active in cancer cells than in normal fibroblasts that may indicate their cancer specificity. Both versions of CDC6 promoters were shown to be most active while the activities of others were close to that of BIRC5 gene (survivin) gene promoter. Long and short variants of each cloned promoter demonstrated very similar cancer specificity with the exception of PLK1-long promoter that was substantially more specific than its short variant and other promoters under study. The data indicate that most of the important cis-regulatory transcription elements responsible for intrinsic cancer specificity are located in short variants of the promoters under study. CDC6 short promoter may serve as a promising candidate for transcription targeted cancer gene therapy.

  17. 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.

  18. Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle

    Science.gov (United States)

    Yue, Jia-Xing; Kozmikova, Iryna; Ono, Hiroki; Nossa, Carlos W.; Kozmik, Zbynek; Putnam, Nicholas H.; Yu, Jr-Kai; Holland, Linda Z.

    2016-01-01

    Cephalochordates, the sister group of vertebrates + tunicates, are evolving particularly slowly. Therefore, genome comparisons between two congeners of Branchiostoma revealed so many conserved noncoding elements (CNEs), that it was not clear how many are functional regulatory elements. To more effectively identify CNEs with potential regulatory functions, we compared noncoding sequences of genomes of the most phylogenetically distant cephalochordate genera, Asymmetron and Branchiostoma, which diverged approximately 120–160 million years ago. We found 113,070 noncoding elements conserved between the two species, amounting to 3.3% of the genome. The genomic distribution, target gene ontology, and enriched motifs of these CNEs all suggest that many of them are probably cis-regulatory elements. More than 90% of previously verified amphioxus regulatory elements were re-captured in this study. A search of the cephalochordate CNEs around 50 developmental genes in several vertebrate genomes revealed eight CNEs conserved between cephalochordates and vertebrates, indicating sequence conservation over >500 million years of divergence. The function of five CNEs was tested in reporter assays in zebrafish, and one was also tested in amphioxus. All five CNEs proved to be tissue-specific enhancers. Taken together, these findings indicate that even though Branchiostoma and Asymmetron are distantly related, as they are evolving slowly, comparisons between them are likely optimal for identifying most of their tissue-specific cis-regulatory elements laying the foundation for functional characterizations and a better understanding of the evolution of developmental regulation in cephalochordates. PMID:27412606

  19. Multiphase control volume finite element simulations of fractured reservoirs

    Science.gov (United States)

    Fu, Yao

    With rapid evolution of hardware and software techniques in energy sector, reservoir simulation has become a powerful tool for field development planning and reservoir management. Many of the widely used commercial simulators were originally designed for structured grids and implemented with finite difference method (FDM). In recent years, technical advances in griding, fluid modeling, linear solver, reservoir and geological modeling, etc. have created new opportunities. At the same time, new reservoir simulation technology is required for solving large-scale heterogeneous problems. A three-dimensional, three-phase black-oil reservoir simulator has been developed using the control volume finite element (CVFE) formulation. Flux-based upstream weighting is employed to ensure flux continuity. The CVFE method is embedded in a fully-implicit formulation. State-of-the-art parallel, linear solvers are used. The implementation takes the advantages of object-oriented programming capabilities of C++ to provide maximum reuse and extensibility for future students. The results from the simulator have excellent agreement with those from commercial simulators. The convergence properties of the new simulator are verified using the method of manufactured solutions. The pressure and saturation solutions are verified to be first-order convergent as expected. The efficiency of the simulators and their capability to handle real large-scale field models are improved by implementing the models in parallel. Another aspect of the work dealt with multiphase flow of fractured reservoirs was performed. The discrete-fracture model is implemented in the simulator. Fractures and faults are represented by lines and planes in two- and three-dimensional spaces, respectively. The difficult task of generating an unstructured mesh for complex domains with fractures and faults is accomplished in this study. Applications of this model for two-phase and three-phase simulations in a variety of fractured

  20. Dynamic Epigenetic Control of Highly Conserved Noncoding Elements

    KAUST Repository

    Seridi, Loqmane

    2014-10-07

    Background Many noncoding genomic loci have remained constant over long evolutionary periods, suggesting that they are exposed to strong selective pressures. The molecular functions of these elements have been partially elucidated, but the fundamental reason for their extreme conservation is still unknown. Results To gain new insights into the extreme selection of highly conserved noncoding elements (HCNEs), we used a systematic analysis of multi-omic data to study the epigenetic regulation of such elements during the development of Drosophila melanogaster. At the sequence level, HCNEs are GC-rich and have a characteristic oligomeric composition. They have higher levels of stable nucleosome occupancy than their flanking regions, and lower levels of mononucleosomes and H3.3, suggesting that these regions reside in compact chromatin. Furthermore, these regions showed remarkable modulations in histone modification and the expression levels of adjacent genes during development. Although HCNEs are primarily initiated late in replication, about 10% were related to early replication origins. Finally, HCNEs showed strong enrichment within lamina-associated domains. Conclusion HCNEs have distinct and protective sequence properties, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. These observations indicate that such elements are likely to have essential cellular functions, and offer insights into their epigenetic properties.

  1. Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.

    Science.gov (United States)

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-12-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.

  2. Controlling gene expression by DNA mechanics: emerging insights and challenges

    OpenAIRE

    Levens, David; Baranello, Laura; Kouzine, Fedor

    2016-01-01

    Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and o...

  3. Analysis of Three-Phase Thyristor Phase Control Circuit with Series RLC Elements

    OpenAIRE

    Himei, Toyoji; Nakanishi, Sen-ichiro; Funabiki, Shigeyuki; Komatsubara, Hitoshi; Kurose, Osamu

    1983-01-01

    An ac phase control circuit by thyristor is widely used in industry, The characteristics of the singlephase circuit with series RLC elements are numerically analyzed, and is reported the interesting phenomenon of step-up voltage without transformer. However, the performance of three phase phase control circuit with series RLC elements is not made clear. In this paper, the performance of three-phasecontrol circuit of a balanced and an unbalanced load with series RLC elements is described. The ...

  4. Quality Assessment and Control of Finite Element Solutions.

    Science.gov (United States)

    1986-05-01

    34Computation of Stress Field Parameters in Areas of Steep Stress Gradients," Communciations in Applied Numerical Methods , Vol. 2, 1986, pp. 133-137. 56. Szabo...Methods for Second Derivatives in Finite Element Approximation of Linear Elasticity Problems," Communications in Applied % Numerical Methods , Vol. 1, 1985...Procedures," Communications in Applied Numerical Methods , Vol. 1, 1985, pp. 3-9. 176. Fletcher, C. A. J., Computational Galerkin Methods, Springer

  5. 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 provid

  6. Non-destructive control of cladding thickness of fuel elements for research reactors

    Energy Technology Data Exchange (ETDEWEB)

    Karlov, Y.; Zhukov, Y.; Chashchin, S

    1997-07-01

    The control method of fuel elements for research reactors by means of measuring beta particles back scattering made it possible to perform complete automatic non-destructive control of internal and external claddings at our plant. This control gives high guarantees of the fuel element correspondence to the requirements. The method can be used to control the three-layer items of different geometry, including plates. (author)

  7. Controlling inclusive cross sections in parton shower + matrix element merging

    Energy Technology Data Exchange (ETDEWEB)

    Plaetzer, Simon

    2012-11-15

    We propose an extension of matrix element plus parton shower merging at tree level to preserve inclusive cross sections obtained from the merged and showered sample. Implementing this constraint generates approximate next-to-leading order (NLO) contributions similar to the LoopSim approach. We then show how full NLO, or in principle even higher order, corrections can be added consistently, including constraints on inclusive cross sections to account for yet missing parton shower accuracy at higher logarithmic order. We also show how NLO accuracy below the merging scale can be obtained.

  8. Training elements at different levels in the strategies for control of schistosomiasis

    DEFF Research Database (Denmark)

    Ørnbjerg, Niels; Simonsen, P. E.; Furu, Peter

    1989-01-01

    Recently acquired comprehensive knowledge concerning the epidemiology of schistosomiasis has provided the background for the establishment of schistosomiasis control strategies. However, the planning, implementation, and maintenance of such control programmes requires sufficient numbers of well t...... trained personnel at the local, district and central levels. Training of health personnel as well as motivation of the community are fundamental and essential elements in any schistosomiasis control programme. The training elements and approaches are discussed....

  9. Auto and cross regulatory elements control Onecut expression in the ascidian nervous system.

    Science.gov (United States)

    Pezzotti, Maria Rosa; Locascio, Annamaria; Racioppi, Claudia; Fucci, Laura; Branno, Margherita

    2014-06-15

    The expression pattern of Onecut genes in the central and peripheral nervous systems is highly conserved in invertebrates and vertebrates but the regulatory networks in which they are involved are still largely unknown. The presence of three gene copies in vertebrates has revealed the functional roles of the Onecut genes in liver, pancreas and some populations of motor neurons. Urochordates have only one Onecut gene and are the closest living relatives of vertebrates and thus represent a good model system to understand its regulatory network and involvement in nervous system formation. In order to define the Onecut genetic cascade, we extensively characterized the Onecut upstream cis-regulatory DNA in the ascidian Ciona intestinalis. Electroporation experiments using a 2.5kb genomic fragment and of a series of deletion constructs identified a small region of 262bp able to reproduce most of the Onecut expression profile during embryonic development. Further analyses, both bioinformatic and in vivo using transient transgenes, permitted the identification of transcription factors responsible for Onecut endogenous expression. We provide evidence that Neurogenin is a direct activator of Onecut and that an autoregulatory loop is responsible for the maintenance of its expression. Furthermore, for the first time we propose the existence of a direct connection among Neurogenin, Onecut and Rx transcription factors in photoreceptor cell formation.

  10. Superconvergence of semidiscrete finite element methods for bilinear parabolic optimal control problems.

    Science.gov (United States)

    Tang, Yuelong; Hua, Yuchun

    2017-01-01

    In this paper, a semidiscrete finite element method for solving bilinear parabolic optimal control problems is considered. Firstly, we present a finite element approximation of the model problem. Secondly, we bring in some important intermediate variables and their error estimates. Thirdly, we derive a priori error estimates of the approximation scheme. Finally, we obtain the superconvergence between the semidiscrete finite element solutions and projections of the exact solutions. A numerical example is presented to verify our theoretical results.

  11. Controlling Excited-State Contamination in Nucleon Matrix Elements

    CERN Document Server

    Yoon, Boram; Bhattacharya, Tanmoy; Engelhardt, Michael; Green, Jeremy; Joó, Bálint; Lin, Huey-Wen; Negele, John; Orginos, Kostas; Pochinsky, Andrew; Richards, David; Syritsyn, Sergey; Winter, Frank

    2016-01-01

    We present a detailed analysis of methods to reduce statistical errors and excited-state contamination in the calculation of matrix elements of quark bilinear operators in nucleon states. All the calculations were done on a 2+1 flavor ensemble with lattices of size $32^3 \\times 64$ generated using the rational hybrid Monte Carlo algorithm at $a=0.081$~fm and with $M_\\pi=312$~MeV. The statistical precision of the data is improved using the all-mode-averaging method. We compare two methods for reducing excited-state contamination: a variational analysis and a two-state fit to data at multiple values of the source-sink separation $t_{\\rm sep}$. We show that both methods can be tuned to significantly reduce excited-state contamination and discuss their relative advantages and cost-effectiveness. A detailed analysis of the size of source smearing used in the calculation of quark propagators and the range of values of $t_{\\rm sep}$ needed to demonstrate convergence of the isovector charges of the nucleon to the $t_...

  12. Controlling excited-state contamination in nucleon matrix elements

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Boram; Gupta, Rajan; Bhattacharya, Tanmoy; Engelhardt, Michael; Green, Jeremy; Joó, Bálint; Lin, Huey-Wen; Negele, John; Orginos, Kostas; Pochinsky, Andrew; Richards, David; Syritsyn, Sergey; Winter, Frank

    2016-06-01

    We present a detailed analysis of methods to reduce statistical errors and excited-state contamination in the calculation of matrix elements of quark bilinear operators in nucleon states. All the calculations were done on a 2+1 flavor ensemble with lattices of size $32^3 \\times 64$ generated using the rational hybrid Monte Carlo algorithm at $a=0.081$~fm and with $M_\\pi=312$~MeV. The statistical precision of the data is improved using the all-mode-averaging method. We compare two methods for reducing excited-state contamination: a variational analysis and a two-state fit to data at multiple values of the source-sink separation $t_{\\rm sep}$. We show that both methods can be tuned to significantly reduce excited-state contamination and discuss their relative advantages and cost-effectiveness. A detailed analysis of the size of source smearing used in the calculation of quark propagators and the range of values of $t_{\\rm sep}$ needed to demonstrate convergence of the isovector charges of the nucleon to the $t_{\\rm sep} \\to \\infty $ estimates is presented.

  13. Controlling excited-state contamination in nucleon matrix elements

    Science.gov (United States)

    Yoon, Boram; Gupta, Rajan; Bhattacharya, Tanmoy; Engelhardt, Michael; Green, Jeremy; Joó, Bálint; Lin, Huey-Wen; Negele, John; Orginos, Kostas; Pochinsky, Andrew; Richards, David; Syritsyn, Sergey; Winter, Frank; Nucleon Matrix Elements NME Collaboration

    2016-06-01

    We present a detailed analysis of methods to reduce statistical errors and excited-state contamination in the calculation of matrix elements of quark bilinear operators in nucleon states. All the calculations were done on a 2 +1 -flavor ensemble with lattices of size 323×64 generated using the rational hybrid Monte Carlo algorithm at a =0.081 fm and with Mπ=312 MeV . The statistical precision of the data is improved using the all-mode-averaging method. We compare two methods for reducing excited-state contamination: a variational analysis and a 2-state fit to data at multiple values of the source-sink separation tsep. We show that both methods can be tuned to significantly reduce excited-state contamination and discuss their relative advantages and cost effectiveness. A detailed analysis of the size of source smearing used in the calculation of quark propagators and the range of values of tsep needed to demonstrate convergence of the isovector charges of the nucleon to the tsep→∞ estimates is presented.

  14. The interrelations amongst control system elements in public sector organizations.

    NARCIS (Netherlands)

    Verbeeten, F.H.M.

    2013-01-01

    The aim of this study is to explain the decisions that public sector organizations make with regard to the design and use of their management control system. New Public Management, based on economics theory, suggests that employees in the public sector should be freed from traditional bureaucratic

  15. Controlling the microstructure of binary carbide films with elemental substitutions

    Science.gov (United States)

    Feller, K.; Haider, M.; Hodges, A.; Spreng, R.; Posbergh, E.; Woodward, H.; Lofland, S. E.; Hettinger, J. D.; Heon, M.; Gogotsi, Y.

    2011-03-01

    We report on experiments to control the microstructure of textured binary carbide thin films deposited by reactive magnetron sputter deposition. Controlling the microstructure in these materials is important as the microstructure of these films provides a template for the resulting carbide-derived carbon (CDC) film and impacts their performance. Specifically, a combinatorial approach is used to add chromium to TiC films creating a compositional gradient as a function of position. We present a measurement of surface roughness as a function of material composition. The resulting materials, (Ti 1-x Cr x) C films, are significantly smoother than their pure TiC counterparts and the resulting CDC's have correlated defects which will improve the performance of the CDC in supercapacitor applications. This work was supported by Rowan University and NSF under contract DMR-0503711.

  16. ELEMENTS OF CONTROL OVER HIERARCHIE SYSTEMS WITH ASSUMED HIERARCHY

    Directory of Open Access Journals (Sweden)

    Kushnir N. V.

    2015-05-01

    Full Text Available The article presents a mathematical model of control over dynamic hierarchy system. The model was proposed for dealing with systems with assumed order in the technical problem of predicting destructions depending onto the amount of defects on different scale levels. The problem of the closest to a certain point of shelf life of hierarchy system is solved. The example of approach control during the given time is given. The problem concerns mathematic programming. Formulation of multi-parameter vector optimization criteria (improvement with its own hierarchy and the formal exercise of multi-criteria optimization of the model parameters. The research can achieve clarity about the conditions under which the structure is preserved. Managing sustainable development system with a given level of the hierarchy for the technical systems can only be achieved in keeping

  17. Evolutionary conservation of sequence elements controlling cytoplasmic polyadenylylation.

    OpenAIRE

    1996-01-01

    Cytoplasmic polyadenylylation is an evolutionarily conserved mechanism involved in the translational activation of a set of maternal messenger RNAs (mRNAs) during early development. In this report, we show by interspecies injections that Xenopus and mouse use the same regulatory sequences to control cytoplasmic poly(A) addition during meiotic maturation. Similarly, Xenopus and Drosophila embryos exploit functionally conserved signals to regulate polyadenylylation during early post-fertilizati...

  18. State of the Art Report for Development of Control Element Drive Mechanism of the APR+ Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Seon; Choi, Suhn; Song, Chul Hwa

    2008-10-15

    Recently newly-developed nuclear reactors with increased safety and enhanced performance by developed countries in the nuclear area are competing in the global nuclear market. Several reactors, for example AP600 and AP1000 by Westinghouse Electric Co. in USA, EPR by Areva in Europe, APWR by Mitsubishi Heavy Industry in Japan in the pressurized power reactor, are competing to preoccupy the nuclear market during Nuclear Renaissance. Dedicated control element drive mechanism with enhanced performance and increased safety are developed for these new reactors. And load follow capability is required, and it is estimated that load follow requirement make design requirement of a control element drive mechanism harsh. It is necessary to review the current technical state of a control element drive mechanism. This work is aimed to review the design characteristics of a past and current control element drive mechanism for a nuclear reactor and to check the direction and goal of CEDM design development recently.

  19. Controlling Elements In The Distribution Policy Of A Company

    Directory of Open Access Journals (Sweden)

    Pelau Corina

    2008-04-01

    Full Text Available In a permanent changing environment, the measurement and monitorisation of the performance of a company has become one of the key issues for its success. This fact increases the capacity of each company to adapt to the conditions of the environment, because only by a permanent monitorisation of the performance, a company can discover both its strenghts and its weaknesses and in time, it can react according to these. This paper concentrates on the controlling and performance measurement of the distribution policy of a company. It analyses both the efficacity and efficency of the distribution channels as well as the succes of the logistics activity.

  20. Repair, Evaluation, Maintenance, and Rehabilitation Research Program: Elements of Floating-Debris Control Systems

    Science.gov (United States)

    1988-09-01

    a variety of materials from plastic bottles to sage brush, but it is t’quialy wood in soiw shape or form--from whole trees to lawn furniture. The...REPAIR, EVALUATION, MAINTENANCE, AND REHABILITATION’RESEARCH PROGRAM TECHNICAL REPORT REMVR-HY-3 ELEMENTS O F FLOATING- DEBRIS CONTROL SYSTEMS’ by...TITLE (Include Security Classification) Elements of Floating- Debris Control Systems 12. PERSONAL AUTHOR(S) Perham, Roscoe E. 13a. TYPE OF REPORT 13b TIME

  1. Application of the control volume mixed finite element method to a triangular discretization

    Science.gov (United States)

    Naff, R.L.

    2012-01-01

    A two-dimensional control volume mixed finite element method is applied to the elliptic equation. Discretization of the computational domain is based in triangular elements. Shape functions and test functions are formulated on the basis of an equilateral reference triangle with unit edges. A pressure support based on the linear interpolation of elemental edge pressures is used in this formulation. Comparisons are made between results from the standard mixed finite element method and this control volume mixed finite element method. Published 2011. This article is a US Government work and is in the public domain in the USA. ?? 2012 John Wiley & Sons, Ltd. This article is a US Government work and is in the public domain in the USA.

  2. Elements of Clean-room Technology and Contamination Control

    Directory of Open Access Journals (Sweden)

    J.C. Kapoor

    2003-07-01

    Full Text Available The heart of the clean room is the high efticiency particualte air (HEPA/ultra-low penetration air (ULPA filter, which provides the highest level of air cleaning ever achieved by a singleprocess step. Filter technology has seen tremendous growth in terms of ultimate performance and air handling capacity. Mere installation of ULPA filters of 99.99995 per cent efficiency for 0.2 um aerosol is not sufficient for achieving the desired performance of a clean room. Other design aspects like flow fields, face velocity, number of air changes, make-up air fractions and precise control of other environmental parameters (temperature, humidity, airflow, noise, vibrations, electrostatic discharge, etc. are equally important.

  3. Reconfigurable Array of Radiating Elements (RARE) controlled by light

    Science.gov (United States)

    Sadovnik, Lev

    1994-01-01

    The parameters of a silicon - dielectric - metal microstrip line were compared with those of a metal - dielectric - metal microstrip line from an actual FLAPS antenna. The proposed structure has higher losses; this is caused by the electrical conductivity of the illuminated silicon electrode being lower than is the case with a line using a copper top electrode. However, the value of these conductive losses is on the same order as the radiative losses in the microstrip line used in FLAPS antenna. These results point to the feasibility of using the proposed type of a microstrip line in a light-controlled reconfigurable MMW antenna with reasonable energy losses and with a reasonable light flux.

  4. Development of an hp-version finite element method for computational optimal control

    Science.gov (United States)

    Hodges, Dewey H.; Warner, Michael S.

    1993-01-01

    The purpose of this research effort was to begin the study of the application of hp-version finite elements to the numerical solution of optimal control problems. Under NAG-939, the hybrid MACSYMA/FORTRAN code GENCODE was developed which utilized h-version finite elements to successfully approximate solutions to a wide class of optimal control problems. In that code the means for improvement of the solution was the refinement of the time-discretization mesh. With the extension to hp-version finite elements, the degrees of freedom include both nodal values and extra interior values associated with the unknown states, co-states, and controls, the number of which depends on the order of the shape functions in each element. One possible drawback is the increased computational effort within each element required in implementing hp-version finite elements. We are trying to determine whether this computational effort is sufficiently offset by the reduction in the number of time elements used and improved Newton-Raphson convergence so as to be useful in solving optimal control problems in real time. Because certain of the element interior unknowns can be eliminated at the element level by solving a small set of nonlinear algebraic equations in which the nodal values are taken as given, the scheme may turn out to be especially powerful in a parallel computing environment. A different processor could be assigned to each element. The number of processors, strictly speaking, is not required to be any larger than the number of sub-regions which are free of discontinuities of any kind.

  5. SUPERCONVERGENCE ANALYSIS OF FINITE ELEMENT METHODS FOR OPTIMAL CONTROL PROBLEMS OF THE STATIONARY BENARD TYPE

    Institute of Scientific and Technical Information of China (English)

    Yanzhen Chang; Danping Yang

    2008-01-01

    In this paper, we consider the finite element approximation of the distributed optimal control problems of the stationary Bénard type under the pointwise control constraint. The states and the co-states are approximated by polynomial functions of lowest-order mixed finite element space or piecewise linear functions and the control is approximated by piecewise constant functions. We give the superconvergence analysis for the control; it is proved that the approximation has a second-order rate of convergence. We further give the superconvergence analysis for the states and the co-states. Then we derive error estimates in L∞-norm and optimal error estimates in L2-norm.

  6. Key Elements Controlling Oil Accumulation within the Tight Sandstones

    Institute of Scientific and Technical Information of China (English)

    Haiyan Hu; Zhiping Zeng; Jianzhang Liu

    2015-01-01

    Tight oil sandstone reservoirs with low porosity and permeability, which are an uncon-ventional petroleum resource, have been discovered in the Jurassic intervals of the central Junggar Ba-sin, the northwestern China. To reveal the accumulation mechanism, a relatively comprehensive re-search was conducted, including oil-source correlation, porosity evolution, and hydrocarbon charging history. The results show that crude oil of these tight sandstone reservoirs were mainly from Permian source rocks with some contribution from Jurassic source rocks. The reservoirs were buried at shallow depth (5%). In contrast, the sandstone reservoir had already become tight and did not provide available space to ac-cumulate oil due to severe compaction and cementation when hydrocarbon from Jurassic source rock filled, evidenced by low GOI values (<5%). Therefore, reservoir porosity controls the oil accumulation within tight sandstone. Whether tight sandstone reservoirs accumulate oil depends on the reservoir quality when hydrocarbons charge. Before the exploration of tight oil sandstone reservoirs, it should be required to investigate the relationship between oil charging history and porosity evolution to reduce the exploration risk and figure out the available targets.

  7. Computational methods to dissect cis-regulatory transcriptional networks

    Indian Academy of Sciences (India)

    Vibha Rani

    2007-12-01

    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 deciphering the regulation of metazoan genes as well as interpreting the results of high-throughput screening. The integration of computer science with biology has expedited molecular modelling and processing of large-scale data inputs such as microarrays, analysis of genomes, transcriptomes and proteomes. Many bioinformaticians have developed various algorithms for predicting transcriptional regulatory mechanisms from the sequence, gene expression and interaction data. This review contains compiled information of various computational methods adopted to dissect gene expression pathways.

  8. Finite Element Analysis of Adaptive-Stiffening and Shape-Control SMA Hybrid Composites

    Science.gov (United States)

    Gao, Xiujie; Burton, Deborah; Turner, Travis L.; Brinson, Catherine

    2005-01-01

    Shape memory alloy hybrid composites with adaptive-stiffening or morphing functions are simulated using finite element analysis. The composite structure is a laminated fiber-polymer composite beam with embedded SMA ribbons at various positions with respect to the neutral axis of the beam. Adaptive stiffening or morphing is activated via selective resistance heating of the SMA ribbons or uniform thermal loads on the beam. The thermomechanical behavior of these composites was simulated in ABAQUS using user-defined SMA elements. The examples demonstrate the usefulness of the methods for the design and simulation of SMA hybrid composites. Keywords: shape memory alloys, Nitinol, ABAQUS, finite element analysis, post-buckling control, shape control, deflection control, adaptive stiffening, morphing, constitutive modeling, user element

  9. Systematic Integrated Process Design and Control of Reactive Distillation Processes Involving Multi-elements

    DEFF Research Database (Denmark)

    Mansouri, Seyed Soheil; Sales-Cruz, Mauricio; Huusom, Jakob Kjøbsted

    2016-01-01

    In this work, integrated process design and control of reactive distillation processes that involve multiple elements (more than two) is addressed through a computer-aided hierarchical decomposition-based framework. Multiple elements are encountered for reactive systems when four or more compounds...... (including inert compounds) are encountered. The reactive distillation design methods and tools which are similar in concept to design of binary non-reactive distillations and binary reactive distillations are used for design of multi-element reactive distillation processes, such as driving force approach...

  10. Sequential construction of a model for modular gene expression control, applied to spatial patterning of the Drosophila gene hunchback.

    Science.gov (United States)

    Spirov, Alexander V; Myasnikova, Ekaterina M; Holloway, David M

    2016-04-01

    Gene network simulations are increasingly used to quantify mutual gene regulation in biological tissues. These are generally based on linear interactions between single-entity regulatory and target genes. Biological genes, by contrast, commonly have multiple, partially independent, cis-regulatory modules (CRMs) for regulator binding, and can produce variant transcription and translation products. We present a modeling framework to address some of the gene regulatory dynamics implied by this biological complexity. Spatial patterning of the hunchback (hb) gene in Drosophila development involves control by three CRMs producing two distinct mRNA transcripts. We use this example to develop a differential equations model for transcription which takes into account the cis-regulatory architecture of the gene. Potential regulatory interactions are screened by a genetic algorithms (GAs) approach and compared to biological expression data.

  11. Active Vibration Control of a Railway Vehicle Carbody Using Piezoelectric Elements

    Science.gov (United States)

    Molatefi, Habibollah; Ayoubi, Pejman; Mozafari, Hozhabr

    2017-07-01

    In recent years and according to modern transportation development, rail vehicles are manufactured lighter to achieve higher speed and lower transportation costs. On the other hand, weight reduction of rail vehicles leads to increase the structural vibration. In this study, Active Vibration Control of a rail vehicle using piezoelectric elements is investigated. The optimal control employed as the control approach regard to the first two modes of vibration. A simplified Car body structure is modeled in Matlab using the finite element theory by considering six DOF beam element and then the Eigen functions and mode shapes are derived. The surface roughness of different classes of rail tracks have been obtained using random vibration theory and applied to the secondary suspension as the excitation of the structure; Then piezoelectric mounted where the greatest moments were captured. The effectiveness of Piezoelectric in structural vibrations attenuation of car body is demonstrated through the state space equations and its effect on modal coefficient.

  12. MATTER-ELEMENT MODELING OF PARALLEL STRUCTURE AND APPLICATION ABOUT EXTENSION PID CONTROL SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Rongde LU; Zonghai CHEN

    2006-01-01

    This article describes in detail a new method via the extension predictable algorithm of the matter-element model of parallel structure tuning the parameters of the extension PID controller. In comparison with fuzzy and extension PID controllers, the proposed extension PID predictable controller shows higher control gains when system states are away from equilibrium, and retains a lower profile of control signals at the same time. Consequently, better control performance is achieved. Through the proposed tuning formula, the weighting factors of an extension-logic predictable controller can be systematically selected according to the control plant. An experimental example through industrial field data and site engineers' experience demonstrates the superior performance of the proposed controller over the fuzzy controller.

  13. Integrated Evaluation of Air Traffic Controller Workload Based on Matter-Element Analysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ming; HAN Song-chen

    2008-01-01

    A model for evaluating the controller workload was presented based on matter-element analysis, particularly from a man-machine-environment system engineering perspective. On the basis of a questionnaire survey, 18 kinds of indexes which influence the controller workload were determined. By establishing the classical field and node field of the controller workload, the correlation function of the controller workload grade was obtained; then the correlation degree and estimated grade of controller workload were given. A case study verifies the feasibility of the proposed evaluation method.

  14. Application of Energy Finite Element Method in Active Vibration Control of Piezoelectric Intelligent Beam

    Directory of Open Access Journals (Sweden)

    Jinhua Xie

    2012-01-01

    Full Text Available Based on the transmission and equilibrium relationship of vibration energy in beam-like structures, the Galerkin weighted residual method was applied to equation discretization. An equivalent transformation of feedback element was suggested to develop the Energy Finite Element model of a composite piezoelectric cantilever beam driven by harmonic excitation on lateral direction, with both systems with and without time delay being studied and the power input estimation of harmonic excitation was discussed for the resolution of Energy Finite Element function. Then the energy density solutions of the piezoelectric coupling beam through Energy Finite Element Method (EFEM and classical wave theory were compared to verify the EFEM model, which presented a good accordance. Further investigation was undertaken about the influence of control parameters including the feedback gain and arrangement of piezoelectric patches on characteristics of system energy density distribution.

  15. Thermoelectric properties control due to doping level and sintering conditions for FGM thermoelectric element

    CERN Document Server

    Kajikawa, T; Shiraishi, K; Ohmori, M; Hirai, T

    1999-01-01

    Thermoelectric performance is determined with three factors, namely, Seebeck coefficient, electrical resistivity and thermal conductivity. For metal and single crystalline semiconductor, those factors have close interrelation each $9 other. However, as the sintered thermoelectric element has various levels of superstructure from macro scale and micro scale in terms of the thermoelectric mechanism, the relationship among them is more complex than that for the $9 melt- grown element, so it is suggested that the control of the temperature dependence of thermoelectric properties is possible to enhance the thermoelectric performance for wide temperature range due to FGM approach. The research $9 objective is to investigate the characteristics of the thermoelectric properties for various doping levels and hot-pressed conditions to make the thermoelectric elements for which the temperature dependence of the performance is $9 controlled due to FGM approach varying the doping levels and sintering conditions. By usage ...

  16. ELEMENT DESIGN FOR AN INKJET SYSTEM OF HYDROSTATIC GAS BEARING CONTROL

    Directory of Open Access Journals (Sweden)

    T. E. Il'ina

    2015-09-01

    Full Text Available Subject of Study. The paper discusses the concept of inkjet systems application, also known as pneumonics, for automatic hydrostatic gas bearing control. Inkjet systems have the advantages over traditional control systems in those problems where the speed of traditional mechanical, electrical or hydraulic servomotors is not enough. Control of the shaft position in gas bearing with forced gas supply into the gap between the shaft and the bearing is typical for this class of problems. In this case, control means the pressure changing or flow rate of gas supplied to the gap by at least one of three axes at a frequency higher than the nominal speed of the shaft. Thus, high speed of response is required from the system. The objective of this work is to design a discrete jet element, testing of its geometry and switching characteristics. Main Results. The discrete inkjet element for oil-free non-contact transmission working on the refrigerant was designed. Relay transition process was modeled in the inkjet element with the use of numerical methods. The switching time has reached 0.2-0.3 ms; this is one order less than the requirements of aircraft control systems, which typically operate at a frequency of about 200 Hz. It is shown that periodic oscillations with high frequency occur when the control signal is injected with insufficient level of pressure. Therefore, a separate design task is to determine the minimum pressure allowable in the control channel.

  17. Finite element based design of software for integrated passive and active vibration control

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Presents the design scheme developed for design of software forIntegrated Passive and Active Vibration Control(IPAVC) and the coding of a prototyne system, and the selection of the famous finite element program MSC/NASTRAN as an important module of software to deal with large and complicated structures and systems with an example to demonstrate the prototype system.

  18. Analysis and Application of Advanced Control Strategies to a Heating Element Nonlinear Model

    Science.gov (United States)

    Turhan, C.; Simani, S.; Zajic, I.; Gokcen Akkurt, G.

    2017-01-01

    This paper presents the design of different control strategies applied to a heating element nonlinear model. The description of this heating element was obtained exploiting a data-driven and physically meaningful nonlinear continuous-time model, which represents a test-bed used in passive air conditioning for sustainable housing applications. This model has low complexity while achieving high simulation performance. The physical meaningfulness of the model provides an enhanced insight into the performance and functionality of the system. In return, this information can be used during the system simulation and improved model- based and data-driven control designs for tight temperature regulation. The main purpose of this study is thus to give several examples of viable and practical designs of control schemes with application to this heating element model. Moreover, extensive simulations and Monte- Carlo analysis are the tools for assessing experimentally the main features of the proposed control schemes, in the presence of modelling and measurement errors. These developed control methods are also compared in order to evaluate advantages and drawbacks of the considered solutions. Finally, the exploited simulation tools can serve to highlight the potential application of the proposed control strategies to real air conditioning systems.

  19. Optically Controlled Reconfigurable Antenna Array Based on E-Shaped Elements

    Directory of Open Access Journals (Sweden)

    Arismar Cerqueira Sodré Junior

    2014-01-01

    Full Text Available This work presents the development of optically controlled reconfigurable antenna arrays. They are based on two patch elements with E-shaped slots, a printed probe, and a photoconductive switch made from an intrinsic silicon die. Numerical simulations and experiments have been shown to be in agreement, and both demonstrate that the frequency response of the antenna arrays can be efficiently reconfigured over two different frequency ISM bands, namely, 2.4 and 5 GHz. A measured gain of 12.5 dBi has been obtained through the use of two radiating elements printed in a low-cost substrate and a dihedral corner reflector.

  20. SerumTrace Elements in Febrile Seizure: A Case-Control Study

    Science.gov (United States)

    NAMAKIN, Kokab; ZARDAST, Mahmoud; SHARIFZADEH, Golamreza; BIDAR, Toktam; ZARGARIAN, Samaneh

    2016-01-01

    Objective Febrile seizure (FS) is one of the most common neurological problems during childhood.Pathogenesis of febrile convulsion is unknown. This study investigated some trace elements among children admitted with FS compared with thoseof febrile without seizure attacks. Materials & Methods This case-control study was conducted on48 children (6 months to 5 yrold) diagnosed with febrile seizure as the cases and 48 age-matched febrile children as the control group. Serum levels of magnesium, calcium, sodium, potassium, and serum zinc were measured. Statistical analysis was performed with SPSS (version 15) using Student t-test. Results There were no significant differences between the cases and controls in terms of gender or age. The means of serum level of zinc, sodium, calcium and magnesium in the case group was lower than those of the control group. There was no significant difference onserum potassium mean level between the case and control groups. Conclusion Deficiency of trace elements was correlated significantly with febrile convulsion, while further investigations on trace elements are required. PMID:27375757

  1. Systematic Integrated Process Design and Control of Binary Element Reactive Distillation Processes

    DEFF Research Database (Denmark)

    Mansouri, Seyed Soheil; Sales-Cruz, Mauricio; Huusom, Jakob Kjøbsted

    2016-01-01

    In this work, integrated process design and control of reactive distillation processes is considered through a computer-aided framework. First, a set of simple design methods for reactive distillation column that are similar in concept to non-reactive distillation design methods are extended....... It is shown that the same design-control principles that apply to a non-reacting binary system of compounds are also valid for a reactive binary system of elements for distillation columns. Application of this framework shows that designing the reactive distillation process at the maximum driving force...... results in a feasible and reliable design of the process as well as the controller structure....

  2. Integrated Process Design and Control of Multi-element Reactive Distillation Processes

    DEFF Research Database (Denmark)

    Mansouri, Seyed Soheil; Sales-Cruz, Mauricio; Huusom, Jakob Kjøbsted

    2016-01-01

    In this work, integrated process design and control of reactive distillation processes involving multi-elements is presented. The reactive distillation column is designed using methods and tools which are similar in concept to non-reactive distillation design methods, such as driving force approach......-state analysis it is shown that it has the least energy consumption and carbon footprint. Next, through analytical and dynamic analysis it is verified that the control structure, disturbance rejection and the controllability at the maximum driving force is the best compared to any other design alternative which...

  3. Finite element analysis of welding residual stress of aero engine blisk by controlling heat input

    Institute of Scientific and Technical Information of China (English)

    Zhang Xueqiu; Yang Jianguo; Chen Xuhui; Fang Hongyuan; Qu Shen; Wang Licheng

    2009-01-01

    In order to improve aero engine performance, it is necessary to reduce the welding residual stress of aero engine blisk. In this paper, finite element method was employed to simulate electron beam welding process of blisk, in accordance with the deducing formula (p = kh) , the heat input is changed with the weld depth to control welding residual stress of blisk. The calculation results show that welding residual stress of blisk can be controlled effectively by reducing the heat input on the conditions of meeting the demand of weld penetration and guaranteeing the welding quality, a new theoretical method and some numerical data are provided for controlling welding residual stress of blisk.

  4. Exploring the controls on element ratios in middle Eocene samples of the benthic foraminifera Oridorsalis umbonatus

    Directory of Open Access Journals (Sweden)

    C. F. Dawber

    2012-12-01

    Full Text Available Culturing studies and empirically based core top calibrations have been used to infer that elemental ratios in benthic foraminifera can be used as proxies to reconstruct past variations in bottom water temperature and saturation state (Δ [CO32−]. However the mechanisms linking elemental ratios to these parameters are poorly constrained. Here, we explore the environmental parameters influencing the incorporation of B, Li, Sr and Mg in Oridorsalis umbonatus in early Cenozoic sediments from Ocean Drilling Program Site 1209. We investigate the influence of middle Eocene variations in intermediate water Δ [CO32−] using relationships developed from core top samples. The fidelity of bottom water Δ[CO32−] reconstructions based on single element ratios is assessed by comparing the X/Ca-based reconstructions to each other and to carbon cycle proxy records (benthic foraminifera δ13C, organic carbon content, foraminifera dissolution indices, and a seawater δ18O reconstruction for Site 1209. Discrepancies in the reconstructed Δ[CO32−] values based on these different metal ratios suggest that there are still gaps in our understanding of the parameters influencing X/Ca and demonstrate that caution is required when interpreting palaeo-reconstructions that are derived from a single elemental ratio. The downcore record of O. umbonatus Mg/Ca does not exhibit any similarities with the Li/Ca, B/Ca and Sr/Ca records, suggesting that the environmental parameters influencing Mg/Ca may be different for this species, consistent with temperature as the strongest control on this elemental ratio. This hypothesis is supported by the coefficients of multiple linear regression models on published Mg/Ca data. An incomplete understanding of the controls on elemental incorporation into benthic foraminifera hinders our ability to confidently quantify changes in saturation state using single X/Ca reconstructions over a range of timescales.

  5. Factors Controlling the Distribution of Transitional Metal Elements in Marine Hydrogenic Ferromanganese Crusts

    Institute of Scientific and Technical Information of China (English)

    JIANG Xuejun; YAO De; LIN Xuehui; ZHAI Shikui

    2009-01-01

    A series of selective dissolution experiments were conducted on the hydrogemc ferromanganese crusts collected near Line Island to study the geochemistry of Mn, Fe, Cu, Co, Ni and Ti. Despite of the fact that the very close intergrowth between amorphous ferric oxyhydroxides and δ-MnO2 exists in the hydrogenic ferromanganese crusts, there is no isomorphous substitution between iron and manganese. This is because the two elements in oxides have different crystal chemistry and geochemistry, such assertion being in agreement with the results of selective dissolution experiments. Transitional metal elements such as Cu, Co, Ni and Ti are enriched in different phases, i.e. Ni and Co are incorporated into δ-MnO2 while Cu and T1 are incorporated into ferric oxyhy-droxides. The distributions of the elements in amorphous ferric oxyhydroxides and δ-MnO2 are controlled by the existing states of the elements in the seawater and the crystal chemistry and geochenustry of these elements/ions in oxides.

  6. 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.

  7. Controls on Fe(II)-Activated Trace Element Release from Goethite and Hematite

    Energy Technology Data Exchange (ETDEWEB)

    Frierdich, Andrew J.; Catalano, Jeffrey G. (WU)

    2012-03-26

    Electron transfer and atom exchange (ETAE) between aqueous Fe(II) and Fe(III) oxides induces surface growth and dissolution that affects trace element fate and transport. We have recently demonstrated Ni(II) cycling through goethite and hematite (adsorbed Ni incorporates into the mineral structure and preincorporated Ni releases to solution) during Fe(II)-Fe(III) ETAE. However, the chemical parameters affecting net trace element release remain unknown. Here, we examine the chemical controls on Ni(II) and Zn(II) release from Ni- and Zn-substituted goethite and hematite during reaction with Fe(II). Release follows a rate law consistent with surface reaction limited mineral dissolution and suggests that release occurs near sites of Fe(III) reductive dissolution during Fe(II)-Fe(III) ETAE. Metal substituent type affects reactivity; Zn release is more pronounced from hematite than goethite, whereas the opposite trend occurs for Ni. Buildup of Ni or Zn in solution inhibits further release but this resumes upon fluid exchange, suggesting that sustained release is possible under flow conditions. Mineral and aqueous Fe(II) concentrations as well as pH strongly affect sorbed Fe(II) concentrations, which directly control the reaction rates and final metal concentrations. Our results demonstrate that structurally incorporated trace elements are mobilized from iron oxides into fluids without abiotic or microbial net iron reduction. Such release may affect micronutrient availability, contaminant transport, and the distribution of redox-inactive trace elements in natural and engineered systems.

  8. Active magnetic bearing control loop modeling for a finite element rotordynamics code

    Science.gov (United States)

    Genta, Giancarlo; Delprete, Cristiana; Carabelli, Stefano

    1994-05-01

    A mathematical model of an active electromagnetic bearing which includes the actuator, the sensor and the control system is developed and implemented in a specialized finite element code for rotordynamic analysis. The element formulation and its incorporation in the model of the machine are described in detail. A solution procedure, based on a modal approach in which the number of retained modes is controlled by the user, is then shown together with other procedures for computing the steady-state response to both static and unbalance forces. An example of application shows the numerical results obtained on a model of an electric motor suspended on a five active-axis magnetic suspension. The comparison of some of these results with the experimental characteristics of the actual system shows the ability of the present model to predict its performance.

  9. Trace elements, oxidative stress and glycemic control in young people with type 1 diabetes mellitus.

    Science.gov (United States)

    Lin, Ching-Chiang; Huang, Hsiu-Hua; Hu, Chiung-Wen; Chen, Bai-Hsiun; Chong, Inn-Wen; Chao, Yu-Ying; Huang, Yeou-Lih

    2014-01-01

    Trace elements and oxidative stress are associated with glycemic control and diabetic complications in type 1 diabetes mellitus. In this study, we analyzed the levels of serum copper, zinc, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and urinary MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 33 type 1 diabetic patients with optimal and suboptimal glycemic control (HbA1Cdiabetic controls to evaluate the differences between these markers in different glycemic control states. Diabetic patients, especially poor-glycemic-control subjects (HbA1C≥9%), exhibited significantly lower levels of serum zinc and increased levels of serum copper (and, therefore, increased serum copper-to-zinc ratios), serum SOD, blood MDA, and urinary MDA and 8-OHdG, relative to non-diabetic subjects. Furthermore, significant correlations existed in these patients between the serum copper, serum copper-to-zinc ratio, and urinary MDA (all pdiabetic complications in patients with type 1 diabetes mellitus.

  10. Classical-Wigner Phase Space Approximation to Cumulative Matrix Elements in Coherent Control

    OpenAIRE

    McQuarrie, B. R.; Abrashkevich, Dmitri G.; Brumer, Paul

    2003-01-01

    The classical limit of the Wigner-Weyl representation is used to approximate products of bound-continuum matrix elements that are fundamental to many coherent control computations. The range of utility of the method is quantified through an examination of model problems, single-channel Na_2 dissociation and multi-arrangement channel photodissociation of CH_2IBr. Very good agreement with the exact quantum results is found for a wide range of system parameters.

  11. Aggregate-Scale Variation in Iron Biogeochemistry Controls Element Cycling from Nitrogen to Uranium

    Science.gov (United States)

    Fendorf, S. E.; Ying, S.; Jones, L. C.; Jones, M. E.

    2014-12-01

    Iron exerts a major control on element cycling in soils by serving as a prominent sorbent (principally when present as an oxide phase) and as an electron acceptor (in the ferric-form) or donor (ferrous-form) in both chemical and microbially-mediated reactions. Within the aggregated structure of soils, steep chemical gradients arise from the supply of oxygen and nutrients along macropores that are rapidly consumed (relative to supply) within the micropore domains of aggregate interiors. As a consequence, iron undergoes a dynamic biogeochemical cycle whereby ferric (hydr)oxides form within aggregate exteriors while ferrous-iron generation dominates within interior regions. Further, inter-aggregate cycling of iron can transpire through the supply of electron donors and acceptors, linked with diffusive controlled response to gradients. Coupling to iron transformation are the varying retention of adsorptives such as lead and phosphorus and the redox alterations of elements from nitrogen to uranium. Nitrate, for example, diffusing into aggregate interiors encounters ferrous-iron fronts where the ensuring oxidation of Fe(II)-coupled to nitrate reduction transpires. The outcome of aggregate-scale iron transformations, described within this presentation, is fundamental controls on the cycling of redox active elements from nutrients such as carbon and nitrogen to contaminants such arsenic and uranium.

  12. Integrating finite elements with optimal control to simulate active vibrations attenuation

    Science.gov (United States)

    Woods, S.; Szyszkowski, W.

    2016-12-01

    Continuous mechanical systems controlled by discrete actuators are inherently under-actuated and involve second-order non-holonomic constraints. A method of simulating optimal vibrations attenuation for such systems is proposed, in which the system is modeled by the finite elements (with possibly a large number of DOFs) and Pontryagin's Principle is applied to control several significant vibration modes by a small number of discrete actuators. For an assumed set of actuators the complete dynamic response of the system can be obtained, as well as the rate and effort parameters to evaluate efficiency of the whole attenuation process.

  13. Control of electro-rheological fluid based resistive torque elements for use in active rehabilitation devices

    Science.gov (United States)

    Nikitczuk, Jason; Weinberg, Brian; Mavroidis, Constantinos

    2007-04-01

    In this paper we present control algorithms for novel electro-rheological fluid based resistive torque generation elements that will be used to drive the joint of a new type of portable and controllable active knee rehabilitation orthotic device (AKROD) for iso-inertial, isokinetic, and isometric exercising as well as gait retraining. The AKROD is composed of straps and rigid components for attachment to the leg, with a central hinge mechanism where a gear system is connected. The key features of AKROD include: a compact, lightweight design with highly tunable torque capabilities through a variable damper component, full portability with on-board power, control circuitry, and sensors (encoder and torque), and real-time capabilities for closed loop computer control for optimizing gait retraining. The variable damper component is achieved through an electro-rheological fluid (ERF) element that connects to the output of the gear system. Using the electrically controlled rheological properties of ERFs, compact brakes capable of supplying high resistive and controllable torques are developed. In this project, a prototype for the AKROD has been developed and tested. The AKROD's ERF resistive actuator was tested in laboratory experiments using a custom-made ERF testing apparatus (ETA). ETA provides a computer-controlled environment to test ERF brakes and actuators in various conditions and scenarios including emulating the interaction between human muscles involved with the knee and the AKROD's ERF actuators/brakes. The AKROD's ERF resistive actuator was tested in closed loop torque control experiments. A hybrid (non-linear, adaptive) proportional-integral (PI) torque controller was implemented to achieve this goal.

  14. Thermal Effects on Vibration and Control of Piezocomposite Kirchhoff Plate Modeled by Finite Elements Method

    Directory of Open Access Journals (Sweden)

    M. Sanbi

    2015-01-01

    Full Text Available Theoretical and numerical results of the modeling of a smart plate are presented for optimal active vibration control. The smart plate consists of a rectangular aluminum piezocomposite plate modeled in cantilever configuration with surface bonded thermopiezoelectric patches. The patches are symmetrically bonded on top and bottom surfaces. A generic thermopiezoelastic theory for piezocomposite plate is derived, using linear thermopiezoelastic theory and Kirchhoff assumptions. Finite element equations for the thermopiezoelastic medium are obtained by using the linear constitutive equations in Hamilton’s principle together with the finite element approximations. The structure is modelled analytically and then numerically and the results of simulations are presented in order to visualize the states of their dynamics and the state of control. The optimal control LQG-Kalman filter is applied. By using this model, the study first gives the influences of the actuator/sensor pair placement and size on the response of the smart plate. Second, the effects of thermoelastic and pyroelectric couplings on the dynamics of the structure and on the control procedure are studied and discussed. It is shown that the effectiveness of the control is not affected by the applied thermal gradient and can be applied with or without this gradient at any time of plate vibrations.

  15. Growth rate and resource imbalance interactively control biomass stoichiometry and elemental quotas of aquatic bacteria.

    Science.gov (United States)

    Godwin, Casey M; Whitaker, Emily A; Cotner, James B

    2017-03-01

    The effects of resource stoichiometry and growth rate on the elemental composition of biomass have been examined in a wide variety of organisms, but the interaction among these effects is often overlooked. To determine how growth rate and resource imbalance affect bacterial carbon (C): nitrogen (N): phosphorus (P) stoichiometry and elemental content, we cultured two strains of aquatic heterotrophic bacteria in chemostats at a range of dilution rates and P supply levels (C:P of 100:1 to 10,000:1). When growing below 50% of their maximum growth rate, P availability and dilution rate had strong interactive effects on biomass C:N:P, elemental quotas, cell size, respiration rate, and growth efficiency. In contrast, at faster growth rates, biomass stoichiometry was strongly homeostatic in both strains (C:N:P of 70:13:1 and 73:14:1) and elemental quotas of C, N, and P were tightly coupled (but not constant). Respiration and cell size increased with both growth rate and P limitation, and P limitation induced C accumulation and excess respiration. These results show that bacterial biomass stoichiometry is relatively constrained when all resources are abundant and growth rates are high, but at low growth rates resource imbalance is relatively more important than growth rate in controlling bacterial biomass composition. © 2016 by the Ecological Society of America.

  16. Deformation Control of Deep Excavation Pit and Numerical Simulation with Finite Element Method

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The authors firstly introduce deformation control of deep excavation pit in detail, and then put forward new conceptions such as: effective coefficient of excavation pit, effective area, ineffective area and critical line, and also put forward the referential criteria of deformation control. The System of Optimization Design with Deformation Control of Deep Excavation Pit and Numerical Simulation with Finite Element Method (SDCDEFEM) is also briefly introduced. Factors influencing deformation of excavation pit are analyzed by the system. The measured and simulated data of maximum deformations (settlement, displacement and upheaval) and their positions are analyzed and discussed. The statistic formula estimating maximum deformations and their positions was gained, and economical-effective measures of deformation control were brought forward.

  17. Drug Control: Observations on Elements of the Federal Drug Control Strategy. Report to Congressional Requesters.

    Science.gov (United States)

    General Accounting Office, Washington, DC. General Government Div.

    Although the United States government invests vast sums of money in the war on drugs, the availability of drugs and the number of persons using illegal drugs are still serious problems. Information that Congress can use in improving drug control strategies is provided here. Some of the report's highlights include current research on promising…

  18. Analysis and Implementation of an Open Programmable Router Based on Forwarding and Control Element Separation

    Institute of Scientific and Technical Information of China (English)

    Wei-Ming Wang; Li-Gang Dong; Bin Zhuge

    2008-01-01

    A router architecture based upon ForCES (Forwarding and Control Element Separation), which is being standardized by IETF ForCES working group, gains its competitive advantage over traditional router architectures in flexibility, programmability, and cost-effectiveness. In this paper, design and implementation of a ForCES-based router (ForTER) is illustrated. Firstly, the implementation architecture of ForTER is discussed. Then, a layered software model,which well illustrates ForCES features, is proposed. Based on the model, design and implementation of Control Element (CE) and Forwarding Element (FE) in ForTER are introduced in detail. Moreover, security for ForTER is considered and an algorithm to prevent DoS attacks is presented. Lastly, experiments of ForTER are illustrated for routing and running routing protocols, network management, DoS attack prevention, etc. The experimental results show the feasibility of the ForTER design. Consequently, the ForTER implementation basically testifies the feasibility of ForCES architecture and some IETF ForCES specifications.

  19. Controlled chemical modification of the internal surface of photonic crystal fibers for application as biosensitive elements

    Science.gov (United States)

    Pidenko, Sergey A.; Burmistrova, Natalia A.; Pidenko, Pavel S.; Shuvalov, Andrey A.; Chibrova, Anastasiya A.; Skibina, Yulia S.; Goryacheva, Irina Y.

    2016-10-01

    Photonic crystal fibers (PCF) are one of the most promising materials for creation of constructive elements for bio-, drug and contaminant sensing based on unique optical properties of the PCF as effective nanosized optical signal collectors. In order to provide efficient and controllable binding of biomolecules, the internal surface of glass hollow core photonic crystal fibers (HC-PCF) has been chemically modified with silanol groups and functionalized with (3-aminopropyl) triethoxysilane (APTES). The shift of local maxima in the HC-PCF transmission spectrum has been selected as a signal for estimating the amount of silanol groups on the HC-PCF inner surface. The relationship between amount of silanol groups on the HC-PCF inner surface and efficiency of following APTES functionalization has been evaluated. Covalent binding of horseradish peroxidase (chosen as a model protein) on functionalized PCF inner surface has been performed successively, thus verifying the possibility of creating a biosensitive element.

  20. Two-dimensional wood drying stress simulation using control-volume mixed finite element methods (CVFEM

    Directory of Open Access Journals (Sweden)

    Carlos Salinas

    2011-05-01

    Full Text Available  The work was aimed at simulating two-dimensional wood drying stress using the control-volume finite element method (CVFEM. Stress/strain was modeled by moisture content gradients regarding shrinkage and mechanical sorption in a cross-section of wood. CVFEM was implemented with triangular finite elements and lineal interpolation of the independent variable which were programmed in Fortran 90 language. The model was validated by contrasting results with similar ones available in the specialised literature. The present model’s results came from isothermal (20ºC drying of quaking aspen (Populus tremuloides: two-dimensional distribution of stress/strain and water content, 40, 80, 130, 190 and 260 hour drying time and evolution of normal stress (2.5 <σ͓ ͓ < 1.2, MPa, from the interior to the exterior of wood. 

  1. Identifying microwave magnetic resonance in chiral elements for creation of controlled matched absorbing metastructures

    Science.gov (United States)

    Kraftmakher, G. A.; Butylkin, V. S.; Kazantsev, Yu. N.; Mal'tsev, V. P.; Temirov, Yu. Sh.

    2017-01-01

    It has been suggested a method for identifying and separating magnetic and electric microwave resonance responses of conductive chiral and bianisotropic elements by reflection of electromagnetic waves in the standing and traveling-wave modes. It has been observed experimentally (in waveguide) and confirmed numerically (in free space) that magnetic resonance, which is excited by microwave magnetic field h, and electric resonances, excited by electric field E, show drastically different resonance curves of reflection. These distinctions allow to identifying the magnetic resonance response and using magnetically excited elements for broadband matching of absorbers instead of traditional quarter-wavelength layer. We have fabricated and investigated matched absorbing metastructures which are controlled by voltage as well by light of remote laser pointer.

  2. Regulation of the Il4 Gene Is Independently Controlled by Proximal and Distal 3′ Enhancers in Mast Cells and Basophils▿

    OpenAIRE

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-01-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3′ element con...

  3. Trace elements in tourmalines from massive sulfide deposits and tourmalinites: Geochemical controls and exploration applications

    Science.gov (United States)

    Griffin, W.L.; Slack, J.F.; Ramsden, A.R.; Win, T.T.; Ryan, C.G.

    1996-01-01

    Trace element contents of tourmalines from massive sulfide deposits and tourmalinites have been determined in situ by proton microprobe; >390 analyses were acquired from 32 polished thin sections. Concentrations of trace elements in the tourmalines vary widely, from zones are relatively homogeneous, suggesting that these trace elements are contained within the crystal structure of the tourmaline, and are not present in inclusions. The highest base metal contents are in ore-related tourmaline samples from Kidd Creek (Ontario), Broken Hill (Australia), and Sazare (Japan). Tourmaline data from these and many other massive sulfide deposits cluster by sample and display broadly linear trends on Zn vs. Fe plots, suggesting chemical control by temperature and hydrothermal and/or metamorphic fluid-mineral equilibria. Significant Ni occurs only in samples from the Kidd Creek Cu-Zn-Pb-Ag deposit, which is associated with a large footwall ultramafic body. An overall antithetic relationship between Zn and Ni probably reflects fluid source controls. Mn is correlated with Fe in tourmalines from barren associations, and possibly in some tourmalines associated with sulfide vein deposits. Sn increases systematically with Fe content irrespective of association; the highest values are found in schorls from granites. Other trace elements are generally uncorrelated with major element concentrations (e.g., Sr-Ca). Base metal proportions in the tourmalines show systematic patterns on ternary Cu-Pb-Zn diagrams that correlate well with the major commodity metals in the associated massive sulfide deposits. For example, data for tourmalines from Cu-Zn deposits (e.g., Ming mine, Newfoundland) fall mainly on the Cu-Zn join, whereas those from Pb-Zn deposits (e.g., Broken Hill, Australia) plot on the Pb-Zn join; no data fall on the Cu-Pb join, consistent with the lack of this metal association in massive sulfide deposits. The systematic relationship between base metal proportions in the

  4. CRMs for quality control of determinations of chemical forms of elements in support to EU legislation.

    Science.gov (United States)

    Quevauviller, P

    1996-03-01

    The concern for the control of toxic chemical forms of elements in the environment is reflected by an increasing number of analyses performed by research and routine laboratories. The European Commission has recognised the need to include some of these species in the list of dangerous substances to be monitored, e.g. in the marine environment or in groundwater. However, in most cases, the specifications are far from being sufficient in respect to the chemical forms of the element to be determined. Furthermore, these determinations are in most cases based on multi-step analytical techniques which are often prone to errors (e.g. at the extraction, derivatization or separation steps). Certified reference materials (CRMs) certified for their content in chemical forms of elements are, therefore, necessary to ensure the accuracy of these measurements and hence the respect of the regulations. However, the lack of CRMs for speciation analysis hampers the quality control of determinations which in turn leads to an incomparability of data produced; so far the number of CRMs produced by international organisations, e.g. NIST (USA), NIES (Japan), NRCC (Canada) and BCR (Belgium), is very limited and concerns mainly compounds such as e.g. methyl-mercury and butyltin compounds in biological matrices or sediments. The Standards, Measurements and Testing Programme (formerly BCR) of the European Commission has started a series of projects for the improvement of speciation analysis in environmental matrices, the final aim of which being the production of a variety of environmental CRMs. The existing EU legislation involving chemical forms of elements is presented, the requirements for the preparation of CRMs for speciation analysis are discussed and an update of the most recent CRMs produced within the Standards, Measurements and Testing Programme (SM&T) is given.

  5. Finite element based model predictive control for active vibration suppression of a one-link flexible manipulator.

    Science.gov (United States)

    Dubay, Rickey; Hassan, Marwan; Li, Chunying; Charest, Meaghan

    2014-09-01

    This paper presents a unique approach for active vibration control of a one-link flexible manipulator. The method combines a finite element model of the manipulator and an advanced model predictive controller to suppress vibration at its tip. This hybrid methodology improves significantly over the standard application of a predictive controller for vibration control. The finite element model used in place of standard modelling in the control algorithm provides a more accurate prediction of dynamic behavior, resulting in enhanced control. Closed loop control experiments were performed using the flexible manipulator, instrumented with strain gauges and piezoelectric actuators. In all instances, experimental and simulation results demonstrate that the finite element based predictive controller provides improved active vibration suppression in comparison with using a standard predictive control strategy. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  6. Multiphase flow through porous media: an adaptive control volume finite element formulation

    Science.gov (United States)

    Mostaghimi, P.; Tollit, B.; Gorman, G.; Neethling, S.; Pain, C.

    2012-12-01

    Accurate modeling of multiphase flow in porous media is of great importance in a wide range of applications in science and engineering. We have developed a numerical scheme which employs an implicit pressure explicit saturation (IMPES) algorithm for the temporal discretization of the governing equations. The saturation equation is spatially discretized using a node centered control volume method on an unstructured finite element mesh. The face values are determined through an upwind scheme. The pressure equation is spatially discretized using a continuous control volume finite element method (CV-FEM) to achieve consistency with the discrete saturation equation. The numerical simulation is implemented in Fluidity, an open source and general purpose fluid simulator capable of solving a number of different governing equations for fluid flow and accompanying field equations on arbitrary unstructured meshes. The model is verified against the Buckley-Leverett problem where a quasi-analytical solution is available. We discuss the accuracy and the order of convergence of the scheme. We demonstrate the scheme for modeling multiphase flow in a synthetic heterogeneous porous medium along with the use of anisotropic mesh adaptivity to control local solution errors and increase computational efficiency. The adaptive method is also used to simulate two-phase flow in heap leaching, an industrial mining process, where the flow of the leaching solution is gravitationally dominated. Finally we describe the extension of the developed numerical scheme for simulation of flow in multiscale fractured porous media and its capability to model the multiscale characterization of flow in full scale.

  7. Simulation of viscous flows using a multigrid-control volume finite element method

    Energy Technology Data Exchange (ETDEWEB)

    Hookey, N.A. [Memorial Univ., Newfoundland (Canada)

    1994-12-31

    This paper discusses a multigrid control volume finite element method (MG CVFEM) for the simulation of viscous fluid flows. The CVFEM is an equal-order primitive variables formulation that avoids spurious solution fields by incorporating an appropriate pressure gradient in the velocity interpolation functions. The resulting set of discretized equations is solved using a coupled equation line solver (CELS) that solves the discretized momentum and continuity equations simultaneously along lines in the calculation domain. The CVFEM has been implemented in the context of both FMV- and V-cycle multigrid algorithms, and preliminary results indicate a five to ten fold reduction in execution times.

  8. Contact position controlling for two-dimensional motion bodies by the boundary element method

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    An algorithm is presented for controlling two-dimensional motion contact bodies with conforming discretization. Since a kind of special boundary element is utilized in the algorithm, the displacement compatibility and traction equilibrium conditions at nodes can be satisfied simultaneously in arbitrary locations of the contact interface. In addition, a method is also proposed in which the contact boundary location can be moved flexibly on the possible contact boundary. This method is effective to deal with moving and rolling contact problems on a possible larger moving or rolling contact region. Numerical examples show effectiveness of the presented scheme.

  9. New implantable therapeutic device for the control of an atrial fibrillation attack using the Peltier element.

    Science.gov (United States)

    Yambe, Tomoyuki; Sumiyoshi, Taketada; Koga, Chihiro; Shiraishi, Yasuyuki; Miura, Hidekazu; Sugita, Norihiro; Tanaka, Akira; Yoshizawa, Makoto

    2012-01-01

    For the development of the new therapeutic device for the atrial fibrillation, implantable cooling device using Peltier element was developed in this study. An implantable cooling device had been consisted from Peltier element with transcutaneous energy transmission system (TETS). 1st coil can be contacted from outside of the body, when the patients will feel palpitation. Electrical current will be induced to the implanted 2nd coil. Peltier element will able to cool the surface of the atrium. For the confirmation of the effect of the cooling device, trial manufacture model was developed. Animal experiments using six healthy adult goats after animal ethical committee allowance was carried out. Fourth intercostals space had been opened after anesthesia inhalation, and various sensors had been inserted. AF was induced by the electrical current with battery. As the results, AF had been recovered to the normal sinus rhythm after cooling in all six goats. So, this cooling system for the control of AF showed evident effect in these experiments. Smaller size cooling device has been under development aiming at totally implantable type. Catheter type cooling device for the insertion by the use of fiber-scope type is now under planning for the clinical application. This new type device may be able to become good news for the patients with uncontrollable AF.

  10. Control of the necrosed tissue volume during noninvasive ultrasound surgery using a 16-element phased array.

    Science.gov (United States)

    Fan, X; Hynynen, K

    1995-03-01

    Focused high-power ultrasound beams are well suited for noninvasive local destruction of deep target volumes. In order to avoid cavitation and to utilize only thermal tissue damage, high frequencies (1-5 MHz) are used in ultrasonic surgery. However, the focal spots generated by sharply focused transducers become so small that only small tumors can be treated in a reasonable time. Phased array ultrasound transducers can be employed to electronically scan a focal spot or to produce multiple foci in the desired region to increase the treated volume. In this article, theoretical and experimental studies of spherically curved square-element phased arrays for use in ultrasonic surgery were performed. The simulation results were compared with experimental results from a 16-element array. It was shown that the phased array could control the necrosed tissue volume by using closely spaced multiple foci. The phased array can also be used to enlarge a necrosed tissue volume in only one direction at a time, i.e., lateral or longitudinal. The spherically curved 16 square-element phased array can produce useful results by varying the phase and amplitude setting. Four focal points can be easily generated with a distance of two or four wavelengths between the two closest peaks. The maximum necrosed tissue volume generated by the array can be up to sixteen times the volume induced by a similar spherical transducer. Therefore the treatment time could be reduced compared with single transducer treatment.

  11. Biogeochemical interactions control a temporal succession in the elemental composition of marine communities

    KAUST Repository

    Martiny, Adam C.

    2015-11-23

    Recent studies have revealed clear regional differences in the particulate organic matter composition and stoichiometry of plankton communities. In contrast, less is known about potential mechanisms and patterns of temporal changes in the elemental composition of marine systems. Here, we monitored weekly changes in environmental conditions, phytoplankton abundances, and particulate organic carbon, nitrogen, and phosphorus concentrations over a 3-yr period. We found that variation in the particulate organic matter (POM) concentrations and ratios were related to seasonal oscillations of environmental conditions and phytoplankton abundances. Periods with low temperature, high nutrient concentrations and a dominance of large phytoplankton corresponded to low C : N : P and vice-versa for warmer periods during the summer and fall. In addition to seasonal changes, we observed a multiyear increase in POM C : P and N : P that might be associated with the Pacific Decadal Oscillation. Finally, there was substantial short-term variability in all factors but similar linkages between environmental variability and elemental composition as observed on seasonal and interannual time-scales. Using a feed-forward neural network, we could explain a large part of the variation in POM concentrations and ratios based on changes in environmental conditions and phytoplankton abundances. The apparent links across all time-scales between changes in physics, chemistry, phytoplankton, and POM concentrations and ratios suggest we have identified key controls of the elemental composition of marine communities in this region.

  12. A Space-Time Finite Element Model for Design and Control Optimization of Nonlinear Dynamic Response

    Directory of Open Access Journals (Sweden)

    P.P. Moita

    2008-01-01

    Full Text Available A design and control sensitivity analysis and multicriteria optimization formulation is derived for flexible mechanical systems. This formulation is implemented in an optimum design code and it is applied to the nonlinear dynamic response. By extending the spatial domain to the space-time domain and treating the design variables as control variables that do not change with time, the design space is included in the control space. Thus, one can unify in one single formulation the problems of optimum design and optimal control. Structural dimensions as well as lumped damping and stiffness parameters plus control driven forces, are considered as decision variables. The dynamic response and its sensitivity with respect to the design and control variables are discretized via space-time finite elements, and are integrated at-once, as it is traditionally used for static response. The adjoint system approach is used to determine the design sensitivities. Design optimization numerical examples are performed. Nonlinear programming and optimality criteria may be used for the optimization process. A normalized weighted bound formulation is used to handle multicriteria problems.

  13. System of the optic-electronic sensors for control position of the radio telescope elements

    Science.gov (United States)

    Konyakhin, Igor; Stepashkin, Ivan; Petrochenko, Andrey

    2016-04-01

    A promising area of modern astronomy is the study of the field of millimeter waves. The use of this band is due to a large extent the spectrum characteristics of the propagation of waves in the atmosphere, short wavelength. Currently, Russia jointly with Uzbekistan is implementing a project to build a radio astronomy observatory on the Suffa plateau (Uzbekistan). The main instrument of the observatory is fully steerable radio telescope RT-70 type. Main mirror telescope is a fragment of an axisymmetric parabolic with a focal length of 21 m, consisting of 1200 reflecting panels; main mirror diameter - 70 m; diameter of counter reflector - 3 m. A feature of the radio telescope as a means of research in the millimeter wavelength range are high for the quality requirements parabolic surface of the primary mirror (standard deviation of points on the surface of the theoretical parabolic is not more than 0.05 mm), to the stability of the mutual arrangement of the primary mirror and the counter reflector (not more than 0, 07 mm) for precision guidance in the corners of the mirror system azimuth and elevation (margin of error 1.5-2"). Weight of structure, temperature changes and air shock result in significant deformation elements radio telescope construction (progressive linear displacements of points of the surface of the main mirror), reaching in the marginal zone of 30 mm; counter reflector shift of up to 60 mm; Unlike the angular position of the axis of the beam pattern of the radio telescope of the measured angle transducers can reach 10 ". Therefore, to ensure the required quality of the reflective elements RT-70 systems, as well as the implementation of precision-guided munitions needs complex measuring deformation elements telescope design. This article deals with the construction of opto-electronic system of remote optoelectronic displacement sensor control elements mirror telescope system.

  14. Application of finite element method and SPICE simulation for design optimization of oven-controlled crystal oscillators.

    Science.gov (United States)

    Hillerich, B; Nagler, O

    2001-11-01

    Thermal finite element method (FEM) calculations and SPICE-based dynamic thermal models are used to simulate and optimize the static and dynamic performance of miniaturized oven-controlled crystal oscillators (OCXOs). FEM can be used to generate the values of the SPICE circuit elements. Good agreement is achieved between simulation and measurement. Several application examples, including directly heated OCXOs, are discussed.

  15. Preliminary study of trace element emissions and control during coal combustion

    Institute of Scientific and Technical Information of China (English)

    ZHANG Junying; ZHAO Yongchun; DING Feng; ZENG Hancai; ZHENG Chuguang

    2007-01-01

    Hazardous trace element emissions have caused serious harm to human health in China.Several typical high-toxic trace element coals were collected from different districts and were used to investigate the emission characteristics of toxic trace elements (As,Se,Cr,Hg) and to explore preliminary control methods.Coal combustion tests were conducted in several bench-scale furnaces including drop tube furnace (DTF),circulating fluidized bed (CFB) combustion furnace,and fixed-bed combustion furnace.Calcium oxide was used to control the emission of arsenic and selenium.The granular activated carbons (AC) and activatedcarbon fibers (ACF) were used to remove mercury in the flue gas from coal combustion.The chemical composition and trace element contents of ash and particulate matter (PM)were determined by X-ray fluorescence (XRF) spectrometry and inductively coupled plasma-atomic emission spectrometry (ICP-AES),respectively.The speciation and concentration of mercury were investigated using the Ontario-Hydro method.X-ray diffraction spectrometry (XRD) was used to determine the mineral composition of production during combustion experiments.With the addition of a calciumbased sorbent,arsenic concentration in PM1 sharply decreased from 0.25-0.11 mg/m3.In fixed-bed combustion of coal,the retention rates of selenium volatiles were between 11.6% and 50.7% using lime.In the circulating fluidized-bed combustion of coal,the content of selenium in ash from the chimney was reduced to one-fourth of its original value and that in leaching water from the chimney decreased by two orders of magnitude using lime.Calcium-based sorbent is an effective additive to control the emission of As and Se during coal combustion.The emission of chromium is influenced by the occurrence mode of Cr in coal.Chromium emission in PM2.5 during coal combustion is 55.5 and 34.7 μg/m3 for Shenbei coal and mixed Pingdingshan coal,respectively.The adsorptive capacity of granular activated carbon for Hg0 is

  16. Multiple Regulatory Elements in the Arabidopsis NIA1 Promoter Act Synergistically to Form a Nitrate Enhancer1[W][OA

    Science.gov (United States)

    Wang, Rongchen; Guan, Peizhu; Chen, Mingsheng; Xing, Xiujuan; Zhang, Yali; Crawford, Nigel M.

    2010-01-01

    To accommodate fluctuating nutrient levels in the soil, plants modulate their metabolism and root development via signaling mechanisms that rapidly reprogram the plant transcriptome. In the case of nitrate, over 1,000 genes are induced or repressed within minutes of nitrate exposure. To identify cis-regulatory elements that mediate these responses, an enhancer screen was performed in transgenic Arabidopsis (Arabidopsis thaliana) plants. A 1.8-kb promoter fragment from the nitrate reductase gene NIA1 was identified that acts as a nitrate enhancer when fused to a 35S minimal promoter. Enhancer activity was localized to a 180-bp fragment, and this activity could be enhanced by the addition of a 131-bp fragment from the nitrite reductase promoter. A promoter construct containing the 180- and 131-bp fragments was also induced by nitrite and repressed by ammonium, indicating that it was responsive to multiple nitrogen signals. To identify specific regulatory elements within the 180-bp NIA1 fragment, a transient expression system using agroinfiltration of Nicotiana benthamiana was developed. Deletion analysis identified three elements corresponding to predicted binding motifs for homeodomain/E-box, Myb, and Alfin1 transcription factors. A fully active promoter showing nitrate and nitrite enhancer activity equivalent to that of the wild-type 180-bp fragment could be built from these three elements if the spacing between the homeodomain/E-box and Myb-Alfin1 sites was equivalent to that of the native promoter. These findings were validated in transgenic Arabidopsis plants and identify a cis-regulatory module containing three elements that comprise a nitrate enhancer in the NIA1 promoter. PMID:20668061

  17. Regulatory elements and transcriptional control of chicken vasa homologue (CVH) promoter in chicken primordial germ cells.

    Science.gov (United States)

    Jin, So Dam; Lee, Bo Ram; Hwang, Young Sun; Lee, Hong Jo; Rim, Jong Seop; Han, Jae Yong

    2017-01-01

    Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis- and trans-regulatory elements. Studies on gene structures of chicken vasa homologue (CVH), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells. However, very limited studies are available on regulatory elements that control germ cell-specific expression in chicken. Therefore, we investigated the intricate regulatory mechanism(s) that governs transcriptional control of CVH. We constructed green fluorescence protein (GFP) or luciferase reporter vectors containing the various 5' flanking regions of CVH gene. From the 5' deletion and fragmented assays in chicken PGCs, we have identified a CVH promoter that locates at -316 to +275 base pair fragment with the highest luciferase activity. Additionally, we confirmed for the first time that the 5' untranslated region (UTR) containing intron 1 is required for promoter activity of the CVH gene in chicken PGCs. Furthermore, using a transcription factor binding prediction, transcriptome analysis and siRNA-mediated knockdown, we have identified that a set of transcription factors play a role in the PGC-specific CVH gene expression. These results demonstrate that cis-elements and transcription factors localizing in the 5' flanking region including the 5' UTR and an intron are important for transcriptional regulation of the CVH gene in chicken PGCs. Finally, this information will contribute to research studies in areas of reproductive biology, constructing of germ cell-specific synthetic promoter for tracing primordial germ cells as well as

  18. Design development of linear pulse motor type control element drive mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Ho; Yu, Je Yong; Kim, Jong In [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-10-01

    The integral reactor SMART is designed for soluble boron free operation and nuclear heating during reactor startup. These design features require the CEDM to have fine-step movement capability as well as high reliability for the fine reactivity control. This report describes the design characteristics of linear pulse motor (LPM) type control element drive mechanism which meets the SMART design requirements. Following items are discussed in this report : - Design concept of LPM type CEDM -Design Requirements - System descriptions -Materials -Design of linear pulse motor -Design of position indicator -Manufacturability of LPM. The results of this report are to be utilized as the starting point for design development of CEDM for SMART. 13 refs., 38 figs., 2 tabs. (Author)

  19. Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression

    DEFF Research Database (Denmark)

    Pinto, Rita; Hansen, Lars; Hintze, John Birger Hjalmar

    2017-01-01

    Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven...... to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii......) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide...

  20. Fast Microwave-Induced Thermoacoustic Tomography Based on Multi-Element Phase-Controlled Focus Technique

    Institute of Scientific and Technical Information of China (English)

    ZENG Lü-Ming; XING Da; GU Huai-Min; YANG Di-Wu; YANG Si-Hua; XIANG Liang-Zhong

    2006-01-01

    @@ We develop a fast microwave-induced thermoacoustic tomography system based on a 320-element phase-controlled focus linear transducer array. A 1.2-GHz microwave generator transmits microwave with a pulse width of 0.5 μs and an incident energy density of 0.45 m J/cm2, and the microwave energy is delivered by a rectangular waveguide with a cross section of (80.01 ± 0.02) × 10-4 m2. Compared to single transducer collection, the system with the multi-element linear transducer array can eliminate the mechanical rotation of the transducer, hence can effectively reduce the image blurring and improve the image resolution. Using a phase-controlled focus technique to collect thermoacoustic signals, the data need not be averaged because of a high signal-to-noise ratio, resulting in a total data acquisition time of less than 5s. The system thus provides a rapid and reliable approach to thermoacoustic imaging, which can potentially be developed as a powerful diagnostic tool for early-stage breast caners.

  1. Control element for controlling a hot gas piston engine, and a hot gas engine with such a control element. Regelelement zur Regelung einer Heissgaskolbenmaschine sowie ein Heissgasmotor mit einem derartigen Regelelement

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, H.A.

    1981-09-10

    The invention refers to a control element for controlling a hot gas piston engine, which contains a movable part, which takes up a certain position depending on the engine speed and with one or more adjustable valves for removing or introducing the working medium from or into the working part of the engine. The purpose of the invention is to create a robust and cheap control element, which emits a signal proportional to speed, by which the engine can be controlled and which is not mechanically connected to the crankshaft. According to the invention, the problem is solved by the part consisting of a movable wall, which separates 2 closed spaces, which are connected together by a capillary tube and where the first space on one side of the movable wall is connected to the working space of the hot gas piston engine by a first non-return valve allowing flow in the direction of the first space, and the second space on the other side of this wall is connected to the same working space by a second non-return valve preventing flow in the direction of the second space, where the gaseous working medium is in the working space and where cyclic pressure changes occur, and where further there is a spring loaded element, which exerts forces on the movable wall in the direction of the first space.

  2. Infection control in hemodialysis units: A quick access to essential elements

    Directory of Open Access Journals (Sweden)

    Ayman Karkar

    2014-01-01

    Full Text Available Infection is the most common cause of hospitalization and the second most common cause of mortality among hemodialysis (HD patients, after cardiovascular disease. HD patients as well as the dialysis staff are vulnerable to contracting health-care-associated infections (HAIs due to frequent and prolonged exposure to many possible contaminants in the dialysis environment. The extracorporeal nature of the therapy, the associated common environmental conditions and the immune compromised status of HD patients are major predisposing factors. The evident increased potential for transmission of infections in the HD settings led to the creation and implementation of specific and stricter infection prevention and control measures in addition to the usual standard precautions. Different international organizations have generated guidelines and recommendations on infection prevention and control for implementation in the HD settings. These include the Centers for Disease Control and Prevention (CDC, the Association of Professionals in Infection Control (APIC, the Kidney Disease Outcomes Quality Initiative (K/DOQI, the European Best Practice Guidelines/European Renal Best Practice (EBPG/ERBP and the Kidney Disease: Improving Global Outcomes (KDIGO. However, these guidelines are extensive and sometimes vary among different guideline-producing bodies. Our aim in this review is to facilitate the access, increase the awareness and encourage implementation among dialysis providers by reviewing, extracting and comparing the essential elements of guidelines and recommendations on infection prevention and control in HD units.

  3. Numerical Modeling of Cavitating Venturi: A Flow Control Element of Propulsion System

    Science.gov (United States)

    Majumdar, Alok; Saxon, Jeff (Technical Monitor)

    2002-01-01

    In a propulsion system, the propellant flow and mixture ratio could be controlled either by variable area flow control valves or by passive flow control elements such as cavitating venturies. Cavitating venturies maintain constant propellant flowrate for fixed inlet conditions (pressure and temperature) and wide range of outlet pressures, thereby maintain constant, engine thrust and mixture ratio. The flowrate through the venturi reaches a constant value and becomes independent of outlet pressure when the pressure at throat becomes equal to vapor pressure. In order to develop a numerical model of propulsion system, it is necessary to model cavitating venturies in propellant feed systems. This paper presents a finite volume model of flow network of a cavitating venturi. The venturi was discretized into a number of control volumes and mass, momentum and energy conservation equations in each control volume are simultaneously solved to calculate one-dimensional pressure, density, and flowrate and temperature distribution. The numerical model predicts cavitations at the throat when outlet pressure was gradually reduced. Once cavitation starts, with further reduction of downstream pressure, no change in flowrate is found. The numerical predictions have been compared with test data and empirical equation based on Bernoulli's equation.

  4. Dc microgrid stabilization through fuzzy control of interleaved, heterogeneous storage elements

    Science.gov (United States)

    Smith, Robert David

    As microgrid power systems gain prevalence and renewable energy comprises greater and greater portions of distributed generation, energy storage becomes important to offset the higher variance of renewable energy sources and maximize their usefulness. One of the emerging techniques is to utilize a combination of lead-acid batteries and ultracapacitors to provide both short and long-term stabilization to microgrid systems. The different energy and power characteristics of batteries and ultracapacitors imply that they ought to be utilized in different ways. Traditional linear controls can use these energy storage systems to stabilize a power grid, but cannot effect more complex interactions. This research explores a fuzzy logic approach to microgrid stabilization. The ability of a fuzzy logic controller to regulate a dc bus in the presence of source and load fluctuations, in a manner comparable to traditional linear control systems, is explored and demonstrated. Furthermore, the expanded capabilities (such as storage balancing, self-protection, and battery optimization) of a fuzzy logic system over a traditional linear control system are shown. System simulation results are presented and validated through hardware-based experiments. These experiments confirm the capabilities of the fuzzy logic control system to regulate bus voltage, balance storage elements, optimize battery usage, and effect self-protection.

  5. The significance of oxygen as oxides and hydroxides in controlling the abundance and residence times of elements in seawater

    Digital Repository Service at National Institute of Oceanography (India)

    DileepKumar, M.

    A model is presented which signifies the role of oxygen (as oxides and hydroxides) in controlling the composition of seawater. respective concentration and residence times for the unknown elements can be estimated. Geometric and statistical indices...

  6. Heavy Metal Control in Domestic Rubbish by Source Screening and Suitability of Nutrient Elements as Turfgrass Medium

    Institute of Scientific and Technical Information of China (English)

    DUO Li-an; ZHAO Shu-lan; GAO Yu-bao

    2005-01-01

    This paper, probing into heavy metal control in domestic rubbish by source screening and nutrient element analysis, revealed the feasibility of source control of heavy metals and the suitability of rubbish as turfgrass medium. Heavy metals in domestic rubbish were controlled by source screening before composting. The study consisted of a control with garden soil. The contents of main mineral elements and heavy metals in rubbish compost and control were determined by the method of ICP-AES. The results showed that heavy metal concentrations in rubbish were lower than those in garden soil, and little difference occurred between rubbish and garden soil in main mineral element concentrations. Based on this, it was concluded that rubbish compost was favorable for using as turfgrass medium and heavy metal control in rubbish by source screening was effective.

  7. Development and program implementation of elements for identification of the electromagnet condition for movable element position control

    Science.gov (United States)

    Leukhin, R. I.; Shaykhutdinov, D. V.; Shirokov, K. M.; Narakidze, N. D.; Vlasov, A. S.

    2017-02-01

    Developing the experimental design of new electromagnetic constructions types in engineering industry enterprises requires solutions of two major problems: regulator’s parameters setup and comprehensive testing of electromagnets. A weber-ampere characteristic as a data source for electromagnet condition identification was selected. Present article focuses on development and implementation of the software for electromagnetic drive control system based on the weber-ampere characteristic measuring. The software for weber-ampere characteristic data processing based on artificial neural network is developed. Results of the design have been integrated into the program code in LabVIEW environment. The license package of LabVIEW graphic programming was used. The hardware is chosen and possibility of its use for control system implementation was proved. The trained artificial neural network defines electromagnetic drive effector position with minimal error. Developed system allows to control the electromagnetic drive powered by the voltage source, the current source and hybrid sources.

  8. Evaluating knee replacement mechanics during ADL with PID-controlled dynamic finite element analysis.

    Science.gov (United States)

    Fitzpatrick, Clare K; Baldwin, Mark A; Clary, Chadd W; Maletsky, Lorin P; Rullkoetter, Paul J

    2014-01-01

    Validated computational knee simulations are valuable tools for design phase development of knee replacement devices. Recently, a dynamic finite element (FE) model of the Kansas knee simulator was kinematically validated during gait and deep flexion cycles. In order to operate the computational simulator in the same manner as the experiment, a proportional-integral-derivative (PID) controller was interfaced with the FE model to control the quadriceps actuator excursion and produce a target flexion profile regardless of implant geometry or alignment conditions. The controller was also expanded to operate multiple actuators simultaneously in order to produce in vivo loading conditions at the joint during dynamic activities. Subsequently, the fidelity of the computational model was improved through additional muscle representation and inclusion of relative hip-ankle anterior-posterior (A-P) motion. The PID-controlled model was able to successfully recreate in vivo loading conditions (flexion angle, compressive joint load, medial-lateral load distribution or varus-valgus torque, internal-external torque, A-P force) for deep knee bend, chair rise, stance-phase gait and step-down activities.

  9. Transposable element recruitments in the mammalian placenta: impacts and mechanisms.

    Science.gov (United States)

    Emera, Deena; Wagner, Günter P

    2012-07-01

    Transposable elements (TEs) are mobile DNA elements found at high frequency in mammalian genomes. Although these elements are generally perceived as genomic parasites, they have the potential to influence host genome function in many beneficial ways. This article discusses the role TEs have played in the evolution of the placenta and pregnancy in viviparous mammals. Using examples from our own research and the literature, we argue that frequent recruitment of TEs, in particular of retroelements, has facilitated the extreme diversification of tissues at the maternal-fetal interface. We also discuss the mechanisms by which TEs have been recruited for functions during pregnancy. We argue that retroelements are pre-adapted to becoming cis-regulatory elements for host genomes because they need to utilize host regulatory signals for their own life cycle. However, although TEs contain some of the signals necessary for host functions upon insertion, they often require modification before acquiring a biological role in a host tissue. We discuss the process by which one TE was transformed into a promoter for prolactin expression in the endometrium, describing a model for TE domestication called 'epistatic capture'.

  10. FINITE ELEMENT NUMERICAL SIMULATION OF THREE-DIMENSIONAL SEEPAGE CONTROL FOR DEEP FOUNDATION PIT DEWATERING

    Institute of Scientific and Technical Information of China (English)

    LUO Zu-jiang; ZHANG Ying-ying; WU Yong-xia

    2008-01-01

    For deep foundation pit dewatering in the Yangtze River Delta, it is easy to make a dramatic decrease of the underground water level surrounding the dewatering area and cause land subsidence and geologic disasters. In this work, a three-dimensional finite element simulation method was applied in the forth subway of Dongjiadu tunnel repair foundation pit dewatering in Shanghai. In order to control the decrease of the underground water level around the foundation pit, the foundation pit dewatering method was used to design the optimization project of dewatering ,which was simulated under these conditions that the aquifers deposited layer by layer, the bottom of the aquifers went deep to 144.45 m, the retaining wall of foundation pit shield went deep to 65 m, the filters of the extraction wells were located between 44 m to 59 m, the water level in the deep foundation pit was decreased by 34 m, and the maximum decrease of water level outside the foundation pit was 3 m. It is shown that the optimization project and the practical case are consistent with each other. Accordingly, the three-dimensional finite element numerical simulation is the basic theory of optimization design of engineering structures of dewatering in deep foundation pit in such areas.

  11. A parallel finite-element method for three-dimensional controlled-source electromagnetic forward modelling

    Science.gov (United States)

    Puzyrev, Vladimir; Koldan, Jelena; de la Puente, Josep; Houzeaux, Guillaume; Vázquez, Mariano; Cela, José María

    2013-05-01

    We present a nodal finite-element method that can be used to compute in parallel highly accurate solutions for 3-D controlled-source electromagnetic forward-modelling problems in anisotropic media. Secondary coupled-potential formulation of Maxwell's equations allows to avoid the singularities introduced by the sources, while completely unstructured tetrahedral meshes and mesh refinement support an accurate representation of geological and bathymetric complexity and improve the solution accuracy. Different complex iterative solvers and an efficient pre-conditioner based on the sparse approximate inverse are used for solving the resulting large sparse linear system of equations. Results are compared with the ones of other researchers to check the accuracy of the method. We demonstrate the performance of the code in large problems with tens and even hundreds of millions of degrees of freedom. Scalability tests on massively parallel computers show that our code is highly scalable.

  12. Spectral finite element method wave propagation, diagnostics and control in anisotropic and inhomogeneous structures

    CERN Document Server

    Gopalakrishnan, Srinivasan; Roy Mahapatra, Debiprosad

    2008-01-01

    The use of composites and Functionally Graded Materials (FGMs) in structural applications has increased. FGMs allow the user to design materials for a specified functionality and have many uses in structural engineering. However, the behaviour of these structures under high-impact loading is not well understood. This book is the first to apply the Spectral Finite Element Method (SFEM) to inhomogeneous and anisotropic structures in a unified and systematic manner. It focuses on some of the problems with this media which were previously thought unmanageable. Types of SFEM for regular and damaged 1-D and 2-D waveguides, solution techniques, methods of detecting the presence of damages and their locations, and methods for controlling the wave propagation responses are discussed. Tables, figures and graphs support the theory and case studies are included. This book is of value to senior undergraduates and postgraduates studying in this field, and researchers and practicing engineers in structural integrity.

  13. HEP - A semaphore-synchronized multiprocessor with central control. [Heterogeneous Element Processor

    Science.gov (United States)

    Gilliland, M. C.; Smith, B. J.; Calvert, W.

    1976-01-01

    The paper describes the design concept of the Heterogeneous Element Processor (HEP), a system tailored to the special needs of scientific simulation. In order to achieve high-speed computation required by simulation, HEP features a hierarchy of processes executing in parallel on a number of processors, with synchronization being largely accomplished by hardware. A full-empty-reserve scheme of synchronization is realized by zero-one-valued hardware semaphores. A typical system has, besides the control computer and the scheduler, an algebraic module, a memory module, a first-in first-out (FIFO) module, an integrator module, and an I/O module. The architecture of the scheduler and the algebraic module is examined in detail.

  14. 3D Finite Element Analysis of HMA Overlay Mix Design to Control Reflective Cracking

    CERN Document Server

    Ghauch, Ziad G

    2011-01-01

    One of the most common rehabilitation techniques of deteriorated pavements is the placement of an HMA overlay on top of the existing Asphalt Concrete (AC) or Portland Cement Concrete (PCC) pavement. However, shortly after pavement resurfacing, HMA overlays exhibit a cracking pattern similar to that of the underlying pavement. This phenomenon is known as reflective cracking. This study examines the effectiveness of several HMA overlay mix design strategies for the purpose of controlling the development of reflective cracking. A parametric study was conducted using a 3D Finite Element (FE) model of a rigid pavement section including a Linear Viscoelastic (LVE) model for Hot Mix Asphalt (HMA) materials and non-uniform tire-pavement contact stresses. Results obtained show that for the intermediate and surface courses, using a Dense Graded (DG) or Polymer Modified (PM) asphalt mixture instead of a Standard Binder (SB) mixture results in reduced tensile stresses at the bottom of the HMA overlay but higher levels of...

  15. Mini tomato production in organic system under greenhouse with partial control of meteorological elements

    Directory of Open Access Journals (Sweden)

    Haroldo F. de Araujo

    Full Text Available ABSTRACT The objective of this research was to evaluate the meteorological elements of the environments and the production components of mini tomato crop in organic system in different forms of cultivation, biofertilizer doses and technological levels of protected environments. The research was conducted in completely randomized design in a 3 x 2 x 5 factorial scheme, corresponding to three greenhouses (A - climatized, B - mobile screen and C - fixed screen, two forms of cultivation (pots and beds and five doses of a commercial biofertilizer (0, 50, 100, 150 and 200% of dose indicated, with five replicates. The treatments affected the analyzed variables, except for biofertilizer doses and interaction of treatments. Air temperature was unchanged among the environments and the mean and minimum relative humidity were within the control range in the climatized greenhouse. The greenhouse with mobile screen showed the best production results for the cultivation in beds and the biofertilizer doses were indifferent for all treatments.

  16. Drosophila p53 controls Notch expression and balances apoptosis and proliferation.

    Science.gov (United States)

    Simón, Rocío; Aparicio, Ricardo; Housden, Ben E; Bray, Sarah; Busturia, Ana

    2014-10-01

    A balance between cell proliferation and apoptosis is important for normal development and tissue homeostasis. Under stress conditions, the conserved tumor suppressor and transcription factor Dp53 induces apoptosis to contribute to the maintenance of homeostasis. However, in some cases Dp53-induced apoptosis results in the proliferation of surrounding non-apoptotic cells. To gain insight into the Dp53 function in the control of apoptosis and proliferation, we studied the interaction between the Drosophila Dp53 and Notch genes. We present evidence that simultaneous reduction of Dp53 and Notch function synergistically increases the wing phenotype of Notch heterozygous mutant flies. Further, we found that a Notch cis-regulatory element is responsive to loss and gain of Dp53 function and that over-expression of Dp53 up-regulates Notch mRNA and protein expression. These findings suggest not only that Dp53 and Notch act together to control wing development but also indicate that Dp53 transcriptionally regulates Notch expression. Moreover, using Notch  gain and loss of function mutations we examined the relevance of Dp53 and Notch interactions in the process of Dp53-apoptosis induced proliferation. Results show that proliferation induced by Dp53 over-expression is dependent on Notch, thus identifying Notch as a new player in Dp53-induced proliferation. Interestingly, we found that Dp53-induced Notch activation and proliferation occurs even under conditions where apoptosis was inhibited. Our findings highlight the conservation between flies and vertebrates of the Dp53 and Notch cross-talk and suggest that Dp53 has a dual role regulating cell death and proliferation gene networks to control the homeostatic balance between apoptosis and proliferation.

  17. A Priori Error Estimates of Mixed Finite Element Methods for General Linear Hyperbolic Convex Optimal Control Problems

    Directory of Open Access Journals (Sweden)

    Zuliang Lu

    2014-01-01

    Full Text Available The aim of this work is to investigate the discretization of general linear hyperbolic convex optimal control problems by using the mixed finite element methods. The state and costate are approximated by the k order (k≥0 Raviart-Thomas mixed finite elements and the control is approximated by piecewise polynomials of order k. By applying the elliptic projection operators and Gronwall’s lemma, we derive a priori error estimates of optimal order for both the coupled state and the control approximation.

  18. Dynamics and control of robotic spacecrafts for the transportation of flexible elements

    Science.gov (United States)

    Wen, Hao; Chen, Ti; Yu, Bensong; Jin, Dongping

    2016-09-01

    The technology of robotic spacecrafts has been identified as one of the most appealing solutions to the on-orbit construction of large space structures in future space missions. As a prerequisite of a successful on-orbit construction, it is needed to use small autonomous spacecrafts for the transportation of flexible elements. To this end, the paper presents an energy-based scheme to control a couple of robotic spacecrafts carrying a flexible slender structure to its desired position. The flexible structure is modelled as a long beam based on the formulation of absolute nodal coordinates to account for the geometrical nonlinearity due to large displacement. Meanwhile, the robotic spacecrafts are actuated on their rigid-body degrees of freedom and modelled as two rigid bodies attached to the flexible beam. The energy-based controller is designed using the technique of energy shaping and damping injection such that translational and rotational maneuvers can be achieved with the suppression of the flexible vibrations of the beam. Finally, numerical case studies are performed to demonstrate the proposed schemes.

  19. Elemental and Isotopic Incorporation into the Aragonitic Shells of Arctica Islandica: Insights from Temperature Controlled Experiments

    Science.gov (United States)

    Wanamaker, A. D.; Gillikin, D. P.

    2014-12-01

    The long-lived ocean quahog, Arctica islandica, is a fairly well developed and tested marine proxy archive, however, the utility of elemental ratios in A. islandica shell material as environmental proxies remains questionable. To further evaluate the influence of seawater temperature on elemental and isotopic incorporation during biomineralization, A. islandica shells were grown at constant temperatures under two regimes during a 16-week period from March 27 to July 21, 2011. Seawater from the Darling Marine Center in Walpole, Maine was pumped into temperature and flow controlled tanks that were exposed to ambient food and salinity conditions. A total of 20 individual juvenile clams with an average shell height of 36 mm were stained with calcein (a commonly used biomarker) and cultured at 10.3 ± 0.3 °C for six weeks. After this, shell heights were measured and the clams were again stained with calcein and cultured at 15.0 ± 0.4 °C for an additional 9.5 weeks. The average shell growth during the first phase of the experiment was 2.4 mm with a linear extension rate of 0.40 mm/week. The average shell growth during the second phase of the experiment was 3.2 mm with an extension rate of 0.34 mm/week. Average salinity values were 30.2 ± 0.7 and 30.7 ±0.7 in the first and second phases of the experiment, respectively. Oxygen isotopes from the cultured seawater were collected throughout the experiment and provide the basis for establishing if shells grew in oxygen isotopic equilibrium. Elemental ratios (primarily Ba/Ca, Mg/Ca, Sr/Ca) in the aragonitic shells were determined via laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), while stable oxygen and carbon isotope ratios were measured using continuous flow isotope ratio mass spectrometry. Continuous sampling within and across the temperature conditions (from 10 °C to 15 °C) coupled with the calcein markings provides the ability to place each sample into a precise temporal framework. The

  20. "Braingame Brian": Toward an Executive Function Training Program with Game Elements for Children with ADHD and Cognitive Control Problems.

    Science.gov (United States)

    Prins, Pier J M; Brink, Esther Ten; Dovis, Sebastiaan; Ponsioen, Albert; Geurts, Hilde M; de Vries, Marieke; van der Oord, Saskia

    2013-02-01

    In the area of childhood attention-deficit hyperactivity disorder, there is an urgent need for new, innovative, and child-focused treatments. A computerized executive functioning training with game elements aimed at enhancing self-control was developed. The first results are promising, and the next steps involve replication with larger samples, evaluating transfer of training effects to daily life, and enhancing motivation through more gaming elements.

  1. Subtask 4.8 - Fate and Control of Mercury and Trace Elements

    Energy Technology Data Exchange (ETDEWEB)

    Pavlish, John; Lentz, Nicholas; Martin, Christopher; Ralston, Nicholas; Zhuang, Ye; Hamre, Lucinda

    2011-12-31

    The Center for Air Toxic Metals® (CATM®) Program at the Energy & Environmental Research Center (EERC) continues to focus on vital basic and applied research related to the fate, behavior, measurement, and control of trace metals, especially mercury, and the impact that these trace metals have on human health and the environment. For years, the CATM Program has maintained an international perspective, performing research and providing results that apply to both domestic and international audiences, with reports distributed in the United States and abroad. In addition to trace metals, CATM’s research focuses on other related emissions and issues that impact trace metal releases to the environment, such as SOx, NOx, CO2, ash, and wastewater streams. Of paramount interest and focus has been performing research that continues to enable the power and industrial sectors to operate in an environmentally responsible manner to meet regulatory standards. The research funded by the U.S. Department of Energy’s (DOE’s) National Energy Technology Laboratory (NETL) through CATM has allowed significant strides to be made to gain a better understanding of trace metals and other emissions, improve sampling and measurement techniques, fill data gaps, address emerging technical issues, and develop/test control technologies that allow industry to cost-effectively meet regulatory standards. The DOE NETL–CATM research specifically focused on the fate and control of mercury and trace elements in power systems that use CO2 control technologies, such as oxycombustion and gasification systems, which are expected to be among those technologies that will be used to address climate change issues. In addition, research addressed data gaps for systems that use conventional and multipollutant control technologies, such as electrostatic precipitators, selective catalytic reduction units, flue gas desulfurization systems, and flue gas

  2. Using Large-Scale Roughness Elements to Control Sand and Dust Flux at the Keeler Dunes, Keeler, CA

    Science.gov (United States)

    Gillies, John; McCarley-Holder, Grace

    2014-05-01

    Controlling dust emission from areas that subsequently degrade air quality and threaten human and animal health and reduce the quality of life for people residing in proximity to such sources is necessary, but also challenging. Recent research has indicated that arrays of large roughness elements (height >0.3 m) can be used effectively to modulate sand transport and the associated dust emissions. Prediction of the rate of sand flux reduction as a function of downwind distance upon entering an array of roughness elements, and the equilibrium flux reduction in the interior of the array is possible using the known geometric properties of the roughness elements, their number, and published relationships. Air quality in the town of Keeler, CA (36 deg 29' 17.92" N, 117 deg 52' 24.62" W) is degraded by levels of particulate matter elements composed of solid elements and managed vegetation to meet sand and dust flux reduction criteria. This project has two major goals: 1) to demonstrate that solid roughness elements placed on areas of the Keeler Dunes immediately arrest sand movement to specified levels (target of 85% reduction), and 2) to assess whether native plant species, planted in the sheltered area of the solid roughness elements can effectively thrive and subsequently replace the solid roughness to achieve the desired sand flux reduction control efficiency. This poster describes the results related mostly to objective one, as considerable time has to pass before sufficient data will be obtained to evaluate the success of the planted and managed vegetation to achieve a control level provided by the solid element roughness array.

  3. 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.

  4. HANGING NODES IN THE UNIFYING THEORY OF A POSTERIORI FINITE ELEMENT ERROR CONTROL

    Institute of Scientific and Technical Information of China (English)

    C.Carstensen; Jun Hu

    2009-01-01

    A unified a posteriori error analysis has been developed in [18,21-23] to analyze the finite element error a posteriori under a universal roof.This paper contributes to the finite element meshes with hanging nodes which are required for local mesh-refining.The twodimensional 1-irregular triangulations into triangles and parallelograms and their combinations are considered with conforming and nonconforming finite element methods named after or by Courant,Q1,Crouzeix-Raviart,Han,Rannacher-Turek,and others for the a posteriori error analysis for triangulations with hanging nodes of degree≤1 which are fundamental for local mesh refinement in self-adaptive finite element discretisations.

  5. Sedimentological control on Mn, and other trace elements, in groundwater of the Bengal delta.

    Science.gov (United States)

    McArthur, J M; Sikdar, P K; Nath, B; Grassineau, N; Marshall, J D; Banerjee, D M

    2012-01-17

    To reveal what controls the concentration and distribution of possibly hazardous (Mn, U, Se, Cd, Bi, Pb) and nonhazardous (Fe, V, Mo, PO(4)) trace elements in groundwater of the Bengal delta, we mapped their concentrations in shallow groundwater (sedimentology and sources of water. Areas of less negative δ(18)O reveal recharge by sources of evaporated water. Concentrations of Fe, As, Mo, and PO(4) are high in palaeo-channel groundwaters and low in palaeo-interfluvial groundwaters. Concentrations of U, V, and Mn, are low in palaeo-channel groundwaters and high in palaeo-interfluvial groundwaters. Concentrations of Fe and Mn are highest (18 and 6 mg/L respectively) at dual reduction-fronts that form strip interfaces at depth around the edges of palaeo-interfluvial aquifers. The fronts form as focused recharge carries dissolved organic carbon into the aquifer margins, which comprise brown, iron-oxide bearing, sand. At the Mn-reduction front, concentrations of V and Mo reach peak concentrations of 3 μg/L. At the Fe-reduction front, concentrations of PO(4) and As reach concentrations 3 mg/L and 150 μg/L respectively. Many groundwaters contain >10 mg/L of Cl, showing that they are contaminated by Cl of anthropogenic origin and that organic matter from in situ sanitation may contribute to driving reduction.

  6. Utilization of air pollution control residues for the stabilization/solidification of trace element contaminated soil.

    Science.gov (United States)

    Travar, I; Kihl, A; Kumpiene, J

    2015-12-01

    The aim of this study was to evaluate the stabilization/solidification (S/S) of trace element-contaminated soil using air pollution control residues (APCRs) prior to disposal in landfill sites. Two soil samples (with low and moderate concentrations of organic matter) were stabilized using three APCRs that originated from the incineration of municipal solid waste, bio-fuels and a mixture of coal and crushed olive kernels. Two APCR/soil mixtures were tested: 30% APCR/70% soil and 50% APCR/50% soil. A batch leaching test was used to study immobilization of As and co-occurring metals Cr, Cu, Pb and Zn. Solidification was evaluated by measuring the unconfined compression strength (UCS). Leaching of As was reduced by 39-93% in APCR/soil mixtures and decreased with increased amounts of added APCR. Immobilization of As positively correlated with the amount of Ca in the APCR and negatively with the amount of soil organic matter. According to geochemical modelling, the precipitation of calcium arsenate (Ca3(AsO4)2/4H2O) and incorporation of As in ettringite (Ca6Al2(SO4)3(OH)12 · 26H2O) in soil/APCR mixtures might explain the reduced leaching of As. A negative effect of the treatment was an increased leaching of Cu, Cr and dissolved organic carbon. Solidification of APCR/soil was considerably weakened by soil organic matter.

  7. An implicit control-volume finite element method for well-reservoir modelling

    Science.gov (United States)

    Pavlidis, Dimitrios; Salinas, Pablo; Xie, Zhihua; Pain, Christopher; Matar, Omar

    2016-11-01

    Here a novel implicit approach (embodied within the IC-Ferst) is presented for modelling wells with potentially a large number of laterals within reservoirs. IC-Ferst is a conservative and consistent, control-volume finite element method (CV-FEM) model and fully unstructured/geology conforming meshes with anisotropic mesh adaptivity. As far as the wells are concerned, a multi-phase/multi-well approach, where well systems are represented as phases, is taken here. Phase volume fraction conservation equations are solved for in both the reservoir and the wells, in addition, the field within wells is also solved for. A second novel aspect of the work is the combination of modelling and resolving of the motherbore and laterals. In this case wells do not have to be explicitly discretised in space. This combination proves to be accurate (in many situations) as well as computationally efficient. The method is applied to a number of multi-phase reservoir problems in order to gain an insight into the effectiveness, in terms of production rate, of perforated laterals. Model results are compared with semi-analytical solutions for simple cases and industry-standard codes for more complicated cases. EPSRC UK Programme Grant MEMPHIS (EP/K003976/1).

  8. Transcriptional Control of Steroid Biosynthesis Genes in the Drosophila Prothoracic Gland by Ventral Veins Lacking and Knirps

    Science.gov (United States)

    Dorry, Elad; Komura-Kawa, Tatsuya; Fujimoto, Yoshinori; Troelsen, Jesper T.; Herder, Rachel; O'Connor, Michael B.; Niwa, Ryusuke; Rewitz, Kim F.

    2014-01-01

    Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development. PMID:24945799

  9. Transcriptional control of steroid biosynthesis genes in the Drosophila prothoracic gland by ventral veins lacking and knirps.

    Directory of Open Access Journals (Sweden)

    E Thomas Danielsen

    2014-06-01

    Full Text Available Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl and the nuclear receptor Knirps (Kni, have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld, controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development.

  10. Controls on Highly Siderophile Element Concentrations in Martian Basalt: Sulfide Saturation and Under-Saturation

    Science.gov (United States)

    Righter, Kevin

    2009-01-01

    Highly siderophile elements (HSE; Re, Au and the platinum group elements) in shergottites exhibit a wide range from very high, similar to the terrestrial mantle, to very low, similar to sulfide saturated mid ocean ridge basalt (e.g., [1]). This large range has been difficult to explain without good constraints on sulfide saturation or under-saturation [2]. A new model for prediction of sulfide saturation places new constraints on this problem [3]. Shergottite data: For primitive shergottites, pressure and temperature estimates are between 1.2-1.5 GPa, and 1350-1470 C [4]. The range of oxygen fugacities is from FMQ-2 to IW, where the amount of Fe2O3 is low and thus does not have a significant effect on the S saturation values. Finally, the bulk compositions of shergottites have been reported in many recent studies (e.g., [5]). All of this information will be used to test whether shergottites are sulfide saturated [3]. Modeling values and results: The database for HSE partition coefficients has been growing with many new data for silicates and oxides [6-8] to complement a large sulfide database [9- 11]. Combining these data with simple batch melting models allows HSE contents of mantle melts to be estimated for sulfide-bearing vs. sulfide-free mantle. Combining such models with fractional crystallization modeling (e.g., [12]) allows HSE contents of more evolved liquids to be modeled. Most primitive shergottites have high HSE contents (and low S contents) that can be explained by sulfide under-saturated melting of the mantle. An exception is Dhofar 019 which has high S contents and very low HSE contents suggesting sulfide saturation. Most evolved basaltic shergottites have lower S contents than saturation, and intermediate HSE contents that can be explained by olivine, pyroxene, and chromite fractionation. An exception is EET A79001 lithology B, which has very low HSE contents and S contents higher than sulfide saturation values . evidence for sulfide saturation

  11. Wnt3a signal pathways activate MyoD expression by targeting cis-elements inside and outside its distal enhancer.

    Science.gov (United States)

    Pan, Yu Chih; Wang, Xiao Wen; Teng, Han Feng; Wu, Yi Ju; Chang, Hsuan Chia; Chen, Shen Liang

    2015-03-18

    Wnt proteins are secreted cytokines and several Wnts are expressed in the developing somites and surrounding tissues. Without proper Wnt stimulation, the organization of the dermomyotome and myotome can become defective. These Wnt signals received by somitic cells can lead to activation of Pax3/Pax7 and myogenic regulatory factors (MRFs), especially Myf5 and MyoD. However, it is currently unknown whether Wnts activate Myf5 and MyoD through direct targeting of their cis-regulatory elements or via indirect pathways. To clarify this issue, in the present study, we tested the regulation of MyoD cis-regulatory elements by Wnt3a secreted from human embryonic kidney (HEK)-293T cells. We found that Wnt3a activated the MyoD proximal 6.0k promoter (P6P) only marginally, but highly enhanced the activity of the composite P6P plus distal enhancer (DE) reporter through canonical and non-canonical pathways. Further screening of the intervening fragments between the DE and the P6P identified a strong Wnt-response element (WRE) in the upstream -8 to -9k region (L fragment) that acted independently of the DE, but was dependent on the P6P. Deletion of a Pax3/Pax7-targeted site in the L fragment significantly reduced its response to Wnt3a, implying that Wnt3a activates the L fragment partially through Pax3/Pax7 action. Binding of β-catenin and Pax7 to their target sites in the DE and the L fragment respectively was also demonstrated by ChIP. These observations demonstrated the first time that Wnt3a can directly activate MyoD expression through targeting cis-elements in the DE and the L fragment.

  12. Thermoelastic and Pyroelectric Couplings Effects on Dynamics and Active Control of Smart Piezolaminated Beam Modeled by Finite Element Method

    Directory of Open Access Journals (Sweden)

    M. Sanbi

    2014-01-01

    Full Text Available Smart structures with integrated sensors, actuators, and control electronics are of importance to the next generation high-performance structural systems. In this study, thermopiezoelastic characteristics of piezoelectric beam continua are studied and applications of the theory to active structures in sensing and optimal control are discussed. Using linear thermopiezoelastic theory and Timoshenko assumptions, a generic thermopiezoelastic theory for piezolaminated composite beam is derived. Finite element equations for the thermopiezoelastic media are obtained by using the linear constitutive equations in Hamilton's principle together with the finite element approximations. The structure consists of a modeling of cantilevered piezolaminated Timoshenko beam with integrated thermopiezoelectric elements between two aluminium layers. The structure is modelled analytically and then numerically and the results of simulations are presented in order to visualize the states of their dynamics and the state of control. The optimal control LQG accompanied by the Kalman filter is applied. The effects of thermoelastic and pyroelectric couplings on the dynamics of the structure and on the control procedure are studied and discussed. We show that the control procedure cannot be perturbed by applying a thermal gradient and the control can be applied at any time during the period of vibration of the beam.

  13. High User Control in Game Design Elements Increases Compliance and In-game Performance in a Memory Training Game.

    Science.gov (United States)

    Nagle, Aniket; Riener, Robert; Wolf, Peter

    2015-01-01

    Computer games are increasingly being used for training cognitive functions like working memory and attention among the growing population of older adults. While cognitive training games often include elements like difficulty adaptation, rewards, and visual themes to make the games more enjoyable and effective, the effect of different degrees of afforded user control in manipulating these elements has not been systematically studied. To address this issue, two distinct implementations of the three aforementioned game elements were tested among healthy older adults (N = 21, 69.9 ± 6.4 years old) playing a game-like version of the n-back task on a tablet at home for 3 weeks. Two modes were considered, differentiated by the afforded degree of user control of the three elements: user control of difficulty vs. automatic difficulty adaptation, difficulty-dependent rewards vs. automatic feedback messages, and user choice of visual theme vs. no choice. The two modes ("USER-CONTROL" and "AUTO") were compared for frequency of play, duration of play, and in-game performance. Participants were free to play the game whenever and for however long they wished. Participants in USER-CONTROL exhibited significantly higher frequency of playing, total play duration, and in-game performance than participants in AUTO. The results of the present study demonstrate the efficacy of providing user control in the three game elements, while validating a home-based study design in which participants were not bound by any training regimen, and could play the game whenever they wished. The results have implications for designing cognitive training games that elicit higher compliance and better in-game performance, with an emphasis on home-based training.

  14. Novel Design of Orifice Type Control Element for Mitigating Instabilities Project

    Data.gov (United States)

    National Aeronautics and Space Administration — An orifice element is commonly used in liquid rocket engine test facilities either as a flow metering device, or to provide a large reduction in pressure over a very...

  15. Novel Design of Orifice Type Control Element for Mitigating Instabilities Project

    Data.gov (United States)

    National Aeronautics and Space Administration — An orifice element is commonly used in liquid rocket engine test facilities to provide a large reduction in pressure over a very small distance in the piping system....

  16. Inductively coupled plasma-atomic emission spectroscopy: a computer controlled, scanning monochromator system for the rapid determination of the elements

    Energy Technology Data Exchange (ETDEWEB)

    Floyd, M.A.

    1980-03-01

    A computer controlled, scanning monochromator system specifically designed for the rapid, sequential determination of the elements is described. The monochromator is combined with an inductively coupled plasma excitation source so that elements at major, minor, trace, and ultratrace levels may be determined, in sequence, without changing experimental parameters other than the spectral line observed. A number of distinctive features not found in previously described versions are incorporated into the system here described. Performance characteristics of the entire system and several analytical applications are discussed.

  17. An adaptive control volume finite element method for simulation of multi-scale flow in heterogeneous porous media

    Science.gov (United States)

    Mostaghimi, P.; Percival, J. R.; Pavlidis, D.; Gorman, G.; Jackson, M.; Neethling, S.; Pain, C. C.

    2013-12-01

    Numerical simulation of multiphase flow in porous media is of importance in a wide range of applications in science and engineering. We present a novel control volume finite element method (CVFEM) to solve for multi-scale flow in heterogeneous geological formations. It employs a node centred control volume approach to discretize the saturation equation, while a control volume finite element method is applied for the pressure equation. We embed the discrete continuity equation into the pressure equation and assure that the continuity is exactly enforced. Anisotropic mesh adaptivity is used to accurately model the fine grained features of multiphase flow. The adaptive algorithm uses a metric tensor field based on solution error estimates to locally control the size and shape of elements in the metric. Moreover, it uses metric advection between adaptive meshes in order to predict the future required density of mesh thereby reducing numerical dispersion at the saturation front. The scheme is capable of capturing multi-scale heterogeneity such as those in fractured porous media through the use of several constraints on the element size in different regions of porous media. We show the application of our method for simulation of flow in some challenging benchmark problems. For flow in fractured reservoirs, the scheme adapts the mesh as the flow penetrates through the fracture and the matrix. The constraints for the element size within the fracture are smaller by several orders of magnitude than the generated mesh within the matrix. We show that the scheme captures the key multi-scale features of flow while preserving the geometry. We demonstrate that mesh adaptation can be used to accurately simulate flow in heterogeneous porous media at low computational cost.

  18. Adaptive Finite Element Modeling of Marine Controlled-Source Electromagnetic Fields in Two-Dimensional General Anisotropic Media

    Institute of Scientific and Technical Information of China (English)

    LI Yuguo; LUO Ming; PEI Jianxin

    2013-01-01

    In this paper,we extend the scope of numerical simulations of marine controlled-source electromagnetic (CSEM) fields in a particular case of anisotropy (dipping anisotropy) to the general case of anisotropy by using an adaptive finite element approach.In comparison to a dipping anisotropy case,the first order spatial derivatives of the strike-parallel components arise in the partial differential equations for generally anisotropic media,which cause a non-symmetric linear system of equations for finite element modeling.The adaptive finite element method is employed to obtain numerical solutions on a sequence of refined unstructured triangular meshes,which allows for arbitrary model geometries including bathymetry and dipping layers.Numerical results of a 2D anisotropic model show both anisotropy strike and dipping angles have great influence on the marine CSEM responses.

  19. Numerical and Experimental Study on Integration of Control Actions into the Finite Element Solutions in Smart Structures

    Directory of Open Access Journals (Sweden)

    L. Malgaca

    2009-01-01

    Full Text Available Piezoelectric smart structures can be modeled using commercial finite element packages. Integration of control actions into the finite element model solutions (ICFES can be done in ANSYS by using parametric design language. Simulation results can be obtained easily in smart structures by this method. In this work, cantilever smart structures consisting of aluminum beams and lead-zirconate-titanate (PZT patches are considered. Two cases are studied numerically and experimentally in parallel. In the first case, a smart structure with a single PZT patch is used for the free vibration control under an initial tip displacement. In the second case, a smart structure with two PZT patches is used for the forced vibration control under harmonic excitation, where one of the PZT patches is used as vibration generating shaker while the other is used as vibration controlling actuator. For the two cases, modal analyses are done using chirp signals; Control OFF and Control ON responses in the time domain are obtained for various controller gains. A non-contact laser displacement sensor and strain gauges are utilized for the feedback signals. It is observed that all the simulation results agree with the experimental results.

  20. Finite Element Analysis for Active-force Control on Vibration of a Flexible Single-link Manipulator

    Directory of Open Access Journals (Sweden)

    Abdul Kadir Muhammad

    2015-10-01

    Full Text Available The purposes of this research are to formulate the equations of motion of the system, to develop computational codes by a finite element analysis in order to perform dynamics simulation with vibration control, to propose an effective control scheme using active-force (AF control a flexible single-link manipulator. The system used in this paper consists of an aluminum beam as a flexible link, a clamp-part, a servo motor to rotate the link and a piezoelectric actuator to control vibration. Computational codes on time history responses, FFT (Fast Fourier Transform processing and eigenvalues-eigenvectors analysis were developed to calculate dynamic behavior of the link. Furthermore, the AF control was designed to drive the piezoelectric actuator. Calculated results have revealed that the vibration of the system can be suppressed effectively.

  1. 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.

  2. Temperature control of transfer roller's bearing based on finite element analysis

    Institute of Scientific and Technical Information of China (English)

    Peng ZHANG; Yourong LI; Han XIAO

    2009-01-01

    After a heat preservation cover is installed on the main rolling line, the heat dissipation environment of the transfer roller working on the heat preservation cover is changed. To ensure the normal production, a reasonable working jet capacity of the roller neck is derived. First, a globe model of the transfer roller is built for finite element analysis. Second, the sub-model of the fixed end bearing is built and the boundary condition of the sub-model is supplied by the results of the globe model. The analysis result of the sub-model shows that the temperature of the transfer roller bearing exceeds 85℃ a rolling periodicity later. With finite element analysis, the heat flux is obtained and the minimum working jet capacity is derived.

  3. Welding distortion control of automobile engine stator by finite element method

    Institute of Scientific and Technical Information of China (English)

    De-jun YAN; Xue-song LIU; Huan-yu XU; Jian-guo YANG; Hong-yuan FANG; Jing-yang LU

    2009-01-01

    In this paper, a thermal elastic-plastic finite element method (FEM) is used to simulate the plasma welding process in order to predict the welding distortion of automobile stator iron core. Six spatial symmetrical welding torches are adopted in the welding process so as to make the iron core rings welded firmly and the distortion symmetric. The effect of rigid clamp on actual welding process is replaced by the contact function between rigid body and deformation element in the MSC software, MARC. The welding process restrained by clamp and deformation analysis after the removal of clamp was successfully simulated. The predictions show good agree-ment with the test results when the rigid clamps are taken into account in the welding simulation, which satisfies the design requirement for manufacture.

  4. Unraveling the Organo-colloidal Control on Trace Element Distribution in Shallow Groundwaters : an Experimental Contribution

    Science.gov (United States)

    Dia, A.; Pedrot, M.; Davranche, M.; Pourret, O.; Petitjean, P.; Henin, O.; Le Coz-Bouhnik, M.

    2006-12-01

    Dissolved Organic Matter (DOM) is ubiquitous in aquatic environments and plays a key role in the geochemistry of major and trace elements - acting as a major carrier and transport phase - through complexation, adsorption, dissolution reactions. It both does interact with mineral phases modifying the exchange rates with solutions and constrain part of pollutant mobilities such as that of trace metals or hydrophobic organic compounds. Not only does association with DOM influences the mobility of metals through the soil/water system, it also regulates their chemical reactivity, bioavailability and toxicity. In order to study DOM-metal interactions and the role of the colloidal pool in such groundwaters, DOM-rich soil/water interactions were performed (at different pH) through columns. This was coupled with ultrafiltration in a range of molecular weight cut-off - 30, 10, 5 and 2kDalton - to distinguish between organically colloidal complexed metals and `free' metals. The Dissolved Organic Carbon (DOC) concentrations, the associated aromaticity were determined in the different fractions as well as the trace metal concentrations by ICP-MS. Ascending hierarchical classification was also performed to evidence DOC-trace element relationship. DOC distribution through time follows the same trend whichever was the pH. Three groups can be distinguished based on aromaticity and DOC data whichever can be the pH conditions. While K, Rb, Mg or Ca appear to behave as `free' ions, Th, U, REE, Fe or Al concentrations are correlated to DOC concentrations, suggesting that the organic colloidal pool dominates the carrying of these latter elements. Further studies dedicated to space- and time-linked variations of the joined colloidal pool and trace element distribution, will be then undertaken in waters recovered from different DOM-rich environments.

  5. Controlling gradient phase distributions in a model of active antenna array with locally coupled elements

    Science.gov (United States)

    Mishagin, K. G.; Shalfeev, V. D.

    2006-12-01

    The regime of synchronization with a certain gradient phase distribution and the possibility of controlling such distribution in a linear array of oscillators coupled by phase-locked loops (PLLs) have been theoretically studied. It is shown that a constant phase progression can be controlled by manipulating collective dynamics, with oscillator eigenfrequencies and coupling coefficients being the control parameters. The proposed principle of control, based on the nonlinear dynamics of PLL-coupled oscillators, can be used in solving the problems of phasing and controlled beam scanning in antenna arrays operating in different frequency bands.

  6. Mapping clinical phenotype data elements to standardized metadata repositories and controlled terminologies: the eMERGE Network experience.

    Science.gov (United States)

    Pathak, Jyotishman; Wang, Janey; Kashyap, Sudha; Basford, Melissa; Li, Rongling; Masys, Daniel R; Chute, Christopher G

    2011-01-01

    Systematic study of clinical phenotypes is important for a better understanding of the genetic basis of human diseases and more effective gene-based disease management. A key aspect in facilitating such studies requires standardized representation of the phenotype data using common data elements (CDEs) and controlled biomedical vocabularies. In this study, the authors analyzed how a limited subset of phenotypic data is amenable to common definition and standardized collection, as well as how their adoption in large-scale epidemiological and genome-wide studies can significantly facilitate cross-study analysis. The authors mapped phenotype data dictionaries from five different eMERGE (Electronic Medical Records and Genomics) Network sites studying multiple diseases such as peripheral arterial disease and type 2 diabetes. For mapping, standardized terminological and metadata repository resources, such as the caDSR (Cancer Data Standards Registry and Repository) and SNOMED CT (Systematized Nomenclature of Medicine), were used. The mapping process comprised both lexical (via searching for relevant pre-coordinated concepts and data elements) and semantic (via post-coordination) techniques. Where feasible, new data elements were curated to enhance the coverage during mapping. A web-based application was also developed to uniformly represent and query the mapped data elements from different eMERGE studies. Approximately 60% of the target data elements (95 out of 157) could be mapped using simple lexical analysis techniques on pre-coordinated terms and concepts before any additional curation of terminology and metadata resources was initiated by eMERGE investigators. After curation of 54 new caDSR CDEs and nine new NCI thesaurus concepts and using post-coordination, the authors were able to map the remaining 40% of data elements to caDSR and SNOMED CT. A web-based tool was also implemented to assist in semi-automatic mapping of data elements. This study emphasizes the

  7. Finite Element Analysis for Active-force Control on Vibration of a Flexible Single-link Manipulator

    Directory of Open Access Journals (Sweden)

    Abdul Kadir Muhammad

    2017-03-01

    Full Text Available The purposes of this research are to formulate theequations of motion of the system, to develop computationalcodes by a finite element analysis in order to perform dynamicssimulation with vibration control, to propose an effective controlscheme using active-force (AF control a flexible single-linkmanipulator. The system used in this paper consists of analuminum beam as a flexible link, a clamp-part, a servo motor torotate the link and a piezoelectric actuator to control vibration.Computational codes on time history responses, FFT (FastFourier Transform processing and eigenvalues-eigenvectorsanalysis were developed to calculate dynamic behavior of thelink. Furthermore, the AF control was designed to drive thepiezoelectric actuator. Calculated results have revealed that thevibration of the system can be suppressed effectively

  8. A Modular Framework for Modeling Hardware Elements in Distributed Engine Control Systems

    Science.gov (United States)

    Zinnecker, Alicia Mae; Culley, Dennis E.; Aretskin-Hariton, Eliot D.

    2014-01-01

    Progress toward the implementation of distributed engine control in an aerospace application may be accelerated through the development of a hardware-in-the-loop (HIL) system for testing new control architectures and hardware outside of a physical test cell environment. One component required in an HIL simulation system is a high-fidelity model of the control platform: sensors, actuators, and the control law. The control system developed for the Commercial Modular Aero-Propulsion System Simulation 40k (40,000 pound force thrust) (C-MAPSS40k) provides a verifiable baseline for development of a model for simulating a distributed control architecture. This distributed controller model will contain enhanced hardware models, capturing the dynamics of the transducer and the effects of data processing, and a model of the controller network. A multilevel framework is presented that establishes three sets of interfaces in the control platform: communication with the engine (through sensors and actuators), communication between hardware and controller (over a network), and the physical connections within individual pieces of hardware. This introduces modularity at each level of the model, encouraging collaboration in the development and testing of various control schemes or hardware designs. At the hardware level, this modularity is leveraged through the creation of a Simulink (R) library containing blocks for constructing smart transducer models complying with the IEEE 1451 specification. These hardware models were incorporated in a distributed version of the baseline C-MAPSS40k controller and simulations were run to compare the performance of the two models. The overall tracking ability differed only due to quantization effects in the feedback measurements in the distributed controller. Additionally, it was also found that the added complexity of the smart transducer models did not prevent real-time operation of the distributed controller model, a requirement of an HIL

  9. A Modular Framework for Modeling Hardware Elements in Distributed Engine Control Systems

    Science.gov (United States)

    Zinnecker, Alicia M.; Culley, Dennis E.; Aretskin-Hariton, Eliot D.

    2015-01-01

    Progress toward the implementation of distributed engine control in an aerospace application may be accelerated through the development of a hardware-in-the-loop (HIL) system for testing new control architectures and hardware outside of a physical test cell environment. One component required in an HIL simulation system is a high-fidelity model of the control platform: sensors, actuators, and the control law. The control system developed for the Commercial Modular Aero-Propulsion System Simulation 40k (C-MAPSS40k) provides a verifiable baseline for development of a model for simulating a distributed control architecture. This distributed controller model will contain enhanced hardware models, capturing the dynamics of the transducer and the effects of data processing, and a model of the controller network. A multilevel framework is presented that establishes three sets of interfaces in the control platform: communication with the engine (through sensors and actuators), communication between hardware and controller (over a network), and the physical connections within individual pieces of hardware. This introduces modularity at each level of the model, encouraging collaboration in the development and testing of various control schemes or hardware designs. At the hardware level, this modularity is leveraged through the creation of a SimulinkR library containing blocks for constructing smart transducer models complying with the IEEE 1451 specification. These hardware models were incorporated in a distributed version of the baseline C-MAPSS40k controller and simulations were run to compare the performance of the two models. The overall tracking ability differed only due to quantization effects in the feedback measurements in the distributed controller. Additionally, it was also found that the added complexity of the smart transducer models did not prevent real-time operation of the distributed controller model, a requirement of an HIL system.

  10. Multilevel Control System of Regional Power Consumption: Analysis of Infrastructure Elements Interconnections, Efficiency Evaluation

    Directory of Open Access Journals (Sweden)

    Marina Nikolaevna Myznikova

    2016-10-01

    Full Text Available Fundamental strategic programs in the spheres of power and economics adopted at various levels of management, are not always capable to solve the problem of power efficiency. The changes of systemic connections of economy and power elements are one of the basic problems of management at the regional level. The development of market relations has caused the growth of uncertainty factors at all levels of power consumption management. An insufficient estimation of system infrastructural interrelations and an individualization of organizational-economic relations of economic subjects and their localization, have generated the intersystem conflictness in distribution of power resources and have aggravated the problem of estimating power consumption efficiency at a systemic level. The restriction of application of the traditional management methods based on the principles of technological efficiency of the processes of energy manufacture and consumption, is connected with the information ruptures caused by the growth of factors of uncertainty and inconsistency of efficiency criteria. Application of modern methods of power consumption forecasting has a number of essential restrictions. At the present stage the management of power consumption in multilevel systems is aimed at realisation of system integrity and economic coordination of manufacture elements, transfer and consumption at regional level and demands working out of the new effective management methods based on the analysis of system interrelations. Allocation of system interrelations depends on features of development of electropower sector, active and passive elements of the structure of consumption, power balance. The analysis and estimation of interrelations of power and economic sphere allow to improve methodology of management of power consumption at the regional level in the conditions of uncertainty.

  11. Geometry control of long-span continuous girder concrete bridge during construction through finite element model updating

    Science.gov (United States)

    Wu, Jie; Yan, Quan-sheng; Li, Jian; Hu, Min-yi

    2016-04-01

    In bridge construction, geometry control is critical to ensure that the final constructed bridge has the consistent shape as design. A common method is by predicting the deflections of the bridge during each construction phase through the associated finite element models. Therefore, the cambers of the bridge during different construction phases can be determined beforehand. These finite element models are mostly based on the design drawings and nominal material properties. However, the accuracy of these bridge models can be large due to significant uncertainties of the actual properties of the materials used in construction. Therefore, the predicted cambers may not be accurate to ensure agreement of bridge geometry with design, especially for long-span bridges. In this paper, an improved geometry control method is described, which incorporates finite element (FE) model updating during the construction process based on measured bridge deflections. A method based on the Kriging model and Latin hypercube sampling is proposed to perform the FE model updating due to its simplicity and efficiency. The proposed method has been applied to a long-span continuous girder concrete bridge during its construction. Results show that the method is effective in reducing construction error and ensuring the accuracy of the geometry of the final constructed bridge.

  12. Controlled Synthesis of Polyions of Heavy Main-Group Elements in Ionic Liquids

    Directory of Open Access Journals (Sweden)

    Matthias F. Groh

    2016-09-01

    Full Text Available Ionic liquids (ILs have been proven to be valuable reaction media for the synthesis of inorganic materials among an abundance of other applications in different fields of chemistry. Up to now, the syntheses have remained mostly “black boxes”; and researchers have to resort to trial-and-error in order to establish a new synthetic route to a specific compound. This review comprises decisive reaction parameters and techniques for the directed synthesis of polyions of heavy main-group elements (fourth period and beyond in ILs. Several families of compounds are presented ranging from polyhalides over carbonyl complexes and selenidostannates to homo and heteropolycations.

  13. Finite Element Approach for the Design of Control Algorithms for Vertical Fin Buffeting Using Strain Actuation

    Science.gov (United States)

    2001-06-01

    constructed to represent the dynamics of the structure at L vacman filtr e argaimaru e tor of control variables the low frequencies of interest. The...system for control a Kalman filter in-series with a Linear Quadratic design purpose was state-space, where the first and the Regulator (full-state...frequencies. The Separation Theorem of the classic LQE-LQR Optimal Control theory was used to obtain the Kalman filter and the full- state feedback gains

  14. Reducing crosstalk in array structures by controlling the excitation voltage of individual elements: a feasibility study.

    Science.gov (United States)

    Bybi, A; Grondel, S; Assaad, J; Hladky-Hennion, A-C; Granger, C; Rguiti, M

    2013-08-01

    This paper describes a procedure to minimize crosstalk between the individual elements of a piezoelectric transducer array. A two-dimensional finite elements model was developed and the excitation voltages predicted by the model were applied to the array prototypes made of PZT 27 ceramic. Symmetric and asymmetric linear phased arrays operating at approximately 450 kHz were tested in the feasibility study. The studies were carried out at low frequency to facilitate the fabrication of the transducer arrays and to check the feasibility in this case. The novelty of our approach is to offer active cancellation of crosstalk in transducer arrays generating continuous waves, even in the presence of fabrication defects. The experimental results showed the validity of the approach and demonstrated that crosstalk can be reduced by about 6-10 dB. In ultrasonic imaging systems, this method could be introduced by using a multichannel generator providing electrical signals containing both phased signals required to focalize and deflect the acoustic beam associated with the correction signals.

  15. Ecosystem Composition Controls the Fate of Rare Earth Elements during Incipient Soil Genesis

    Science.gov (United States)

    Zaharescu, Dragos G.; Burghelea, Carmen I.; Dontsova, Katerina; Presler, Jennifer K.; Maier, Raina M.; Huxman, Travis; Domanik, Kenneth J.; Hunt, Edward A.; Amistadi, Mary K.; Gaddis, Emily E.; Palacios-Menendez, Maria A.; Vaquera-Ibarra, Maria O.; Chorover, Jon

    2017-02-01

    The rare earth elements (REE) are increasingly important in a variety of science and economic fields, including (bio)geosciences, paleoecology, astrobiology, and mining. However, REE distribution in early rock-microbe-plant systems has remained elusive. We tested the hypothesis that REE mass-partitioning during incipient weathering of basalt, rhyolite, granite and schist depends on the activity of microbes, vascular plants (Buffalo grass), and arbuscular mycorrhiza. Pore-water element abundances revealed a rapid transition from abiotic to biotic signatures of weathering, the latter associated with smaller aqueous loss and larger plant uptake. Abiotic dissolution was 39% of total denudation in plant-microbes-mycorrhiza treatment. Microbes incremented denudation, particularly in rhyolite, and this resulted in decreased bioavailable solid pools in this rock. Total mobilization (aqueous + uptake) was ten times greater in planted compared to abiotic treatments, REE masses in plant generally exceeding those in water. Larger plants increased bioavailable solid pools, consistent with enhanced soil genesis. Mycorrhiza generally had a positive effect on total mobilization. The main mechanism behind incipient REE weathering was carbonation enhanced by biotic respiration, the denudation patterns being largely dictated by mineralogy. A consistent biotic signature was observed in La:phosphate and mobilization: solid pool ratios, and in the pattern of denudation and uptake.

  16. Automated Tools for Clinical Research Data Quality Control using NCI Common Data Elements.

    Science.gov (United States)

    Hudson, Cody L; Topaloglu, Umit; Bian, Jiang; Hogan, William; Kieber-Emmons, Thomas

    2014-01-01

    Clinical research data generated by a federation of collection mechanisms and systems often produces highly dissimilar data with varying quality. Poor data quality can result in the inefficient use of research data or can even require the repetition of the performed studies, a costly process. This work presents two tools for improving data quality of clinical research data relying on the National Cancer Institute's Common Data Elements as a standard representation of possible questions and data elements to A: automatically suggest CDE annotations for already collected data based on semantic and syntactic analysis utilizing the Unified Medical Language System (UMLS) Terminology Services' Metathesaurus and B: annotate and constrain new clinical research questions though a simple-to-use "CDE Browser." In this work, these tools are built and tested on the open-source LimeSurvey software and research data analyzed and identified to contain various data quality issues captured by the Comprehensive Research Informatics Suite (CRIS) at the University of Arkansas for Medical Sciences.

  17. Low-level Control of Network Elements from an Agent Platform

    DEFF Research Database (Denmark)

    Hansen, Mads Stenhuus; Jensen, P.; Soldatos, J.;

    1999-01-01

    An important issue for the implementation of an agent system, which controls a telecommunications network, is to enable low-level access of the network devices by the agent platform, bypassing the control logic inherent in them. This issue has been coped with successfully in the IMPACT project...

  18. A SECOND ORDER CONTROL-VOLUME FINITE-ELEMENT LEAST-SQUARES STRATEGY FOR SIMULATING DIFFUSION IN STRONGLY ANISOTROPIC MEDIA

    Institute of Scientific and Technical Information of China (English)

    Jayantha Pasdunkorale A.; Ian W. Turner

    2005-01-01

    An unstructured mesh finite volume discretisation method for simulating diffusion in anisotropic media in two-dimensional space is discussed. This technique is considered as an extension of the fully implicit hybrid control-volume finite-element method and it retains the local continuity of the flux at the control volume faces. A least squares function reconstruction technique together with a new flux decomposition strategy is used to obtain an accurate flux approximation at the control volume face, ensuring that the overall accuracy of the spatial discretisation maintains second order. This paper highlights that the new technique coincides with the traditional shape function technique when the correction term is neglected and that it significantly increases the accuracy of the previous linear scheme on coarse meshes when applied to media that exhibit very strong to extreme anisotropy ratios. It is concluded that the method can be used on both regular and irregular meshes,and appears independent of the mesh quality.

  19. How Can Stress Be Controlled in Endodontically Treated Teeth? A 3D Finite Element Analysis

    Directory of Open Access Journals (Sweden)

    İhsan Yıkılgan

    2013-01-01

    Full Text Available The aim of this study was to analyze the stresses that develop by oblique and vertical forces in endodontically treated maxillary second premolars that were restored with resin composite. Additionally, in our study the effects of the different restorative approaches and use of different base materials on stress formation were analyzed using three-dimensional finite element stress analysis. For restoration, the models representing both cusp capping, palatinal cusp capping, standard MOD restoration, and use of woven fiber in occlusal part were prepared. In all models, oblique forces caused more stress than did vertical forces. Materials with low elastic moduli cause high amounts of stress, whereas materials with elastic moduli similar to that of dental tissues cause low amounts of stress. Additional approaches such as cusp capping, functional cusp capping, and woven fiber use do not affect stress formation on the tooth after endodontic treatment.

  20. Detection and characterization of regulatory elements using probabilistic conditional random field and hidden Markov models

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Xiaobo Zhou

    2013-01-01

    By altering the electrostatic charge of histones or providing binding sites to protein recognition molecules,Chromatin marks have been proposed to regulate gene expression,a property that has motivated researchers to link these marks to cis-regulatory elements.With the help of next generation sequencing technologies,we can now correlate one specific chromatin mark with regulatory elements (e.g.enhancers or promoters) and also build tools,such as hidden Markov models,to gain insight into mark combinations.However,hidden Markov models have limitation for their character of generative models and assume that a current observation depends only on a current hidden state in the chain.Here,we employed two graphical probabilistic models,namely the linear conditional random field model and multivariate hidden Markov model,to mark gene regions with different states based on recurrent and spatially coherent character of these eight marks.Both models revealed chromatin states that may correspond to enhancers and promoters,transcribed regions,transcriptional elongation,and low-signal regions.We also found that the linear conditional random field model was more effective than the hidden Markov model in recognizing regulatory elements,such as promoter-,enhancer-,and transcriptional elongation-associated regions,which gives us a better choice.

  1. 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.

  2. THE FINITE ELEMENT ANALYSIS OF THE CONTROLLED-SOURCE ELECTROMAGNETIC INDUCTION PROBLEMS BY FRACTIONAL-STEP PROJECTION METHOD

    Institute of Scientific and Technical Information of China (English)

    Chang-feng Ma

    2004-01-01

    This paper provides an convergence analysis of a fractional-step projection method for the controlled-source electromagnetic induction problems in heterogenous electrically conducting media by means of finite element approximations. Error estimates in finite time are given. And it is verified that provided the time step τ is sufficiently small, the proposed algorithm yields for finite time T an error of (O)(hs + τ) in the L2-norm for the magnetic field H, where h is the mesh size and 1/2 < s ≤ 1.

  3. 3D controlled-source electromagnetic modeling in anisotropic medium using edge-based finite element method

    DEFF Research Database (Denmark)

    Cai, Hongzhu; Xiong, Bin; Han, Muran

    2014-01-01

    This paper presents a linear edge-based finite element method for numerical modeling of 3D controlled-source electromagnetic data in an anisotropic conductive medium. We use a nonuniform rectangular mesh in order to capture the rapid change of diffusive electromagnetic field within the regions...... of anomalous conductivity and close to the location of the source. In order to avoid the source singularity, we solve Maxwell's equation with respect to anomalous electric field. The nonuniform rectangular mesh can be transformed to hexahedral mesh in order to simulate the bathymetry effect. The sparse system...

  4. Definition, technology readiness, and development cost of the orbit transfer vehicle engine integrated control and health monitoring system elements

    Science.gov (United States)

    Cannon, I.; Balcer, S.; Cochran, M.; Klop, J.; Peterson, S.

    1991-01-01

    An Integrated Control and Health Monitoring (ICHM) system was conceived for use on a 20 Klb thrust baseline Orbit Transfer Vehicle (OTV) engine. Considered for space used, the ICHM was defined for reusability requirements for an OTV engine service free life of 20 missions, with 100 starts and a total engine operational time of 4 hours. Functions were derived by flowing down requirements from NASA guidelines, previous OTV engine or ICHM documents, and related contracts. The elements of an ICHM were identified and listed, and these elements were described in sufficient detail to allow estimation of their technology readiness levels. These elements were assessed in terms of technology readiness level, and supporting rationale for these assessments presented. The remaining cost for development of a minimal ICHM system to technology readiness level 6 was estimated. The estimates are within an accuracy range of minus/plus 20 percent. The cost estimates cover what is needed to prepare an ICHM system for use on a focussed testbed for an expander cycle engine, excluding support to the actual test firings.

  5. Mineralogical controls on the partitioning of trace elements between smoke and ash during the combustion of tobacco

    Science.gov (United States)

    Stephens, W. E.; Calder, A.

    2003-04-01

    Tobacco smoke is a potential source of some toxic trace elements including inorganic carcinogens1,2. In order to understand the controls on trace elements in smoke and their potential toxic effects it is necessary to know their distribution between the various inorganic (mineral) and organic repositories in tobacco, the relative concentrations of these repositories, the effects of combustion on these repositories, and the role of particles in adsorbing and transporting trace elements. Few trace element data are available for any of these materials and the partitioning processes are poorly understood. We have applied Rietveld XRD to quantifying the major minerals the tobacco of all available cigarette references standards, as well as the most popular UK cigarette brands and a selection of international brands. Most common are calcium oxalate biominerals (up to 4% by dry weight), calcium carbonate, sylvite, and several silicate minerals typical of soils amounting to a few wt%. We have developed an accurate and rapid method for determining 23 trace elements in tobacco using polarised X-ray fluorescence spectrometry, and applied it to the same samples. Although the concentrations vary over about five orders of magnitude the abundance patterns for standards and brands are remarkably consistent. We present a model to account for these variations in which anthropogenic inputs of fertilisers, manufacturers’ additives and environmental pollution supplement natural sources based on soils and plant processes. Combustion of tobacco (400-900^oC) causes the oxalates (whewellite &weddellite) to decompose and other non-silicates react to form new phases such as fairchildite (K_2Ca(CO_3)_2) and arcanite (K_2SO_4). Ash amounts to ˜15% of the mass of unburned tobacco. Comparison of trace element concentrations in smoke with those in tobacco and ash indicates that a few metals, most notably Cd, may partition strongly into the smoke phase. It is noteworthy that Cd levels are higher

  6. Strong stimulation of recombinant protein production in Escherichia coli by combining stimulatory control elements in an expression cassette

    Directory of Open Access Journals (Sweden)

    Zwick Friederike

    2012-10-01

    Full Text Available Abstract Background The XylS/Pm expression system has been used to produce recombinant proteins at industrial levels in Escherichia coli. Activation of transcription from the Pm promoter takes place in the presence of benzoic acid or derivatives of it. Previous mutagenesis studies resulted in identification of several variants of the expression control elements xylS (X, Pm (P and the 5'-untranslated region (U that individually gave rise to strongly stimulated expression. The goal of this study was to test if combination of such stimulatory mutations in the same expression vectors would lead to further increase of expression levels. Results We combined X, P and U variants that were originally identified due to their ability to strongly stimulate expression of the reporter gene bla (resistance to penicillin. Combination of optimized elements stimulated bla expression up to 75-fold (X, P and U combined relative to the wild-type system, while accumulated transcript levels increased about 50-fold. This is much more than for the elements individually. We also tested combination of the variant elements on two other and unrelated genes, celB (encoding phosphoglucomutase and the human growth factor gene gm-csf. Protein production from these genes is much more efficient than from bla in the wild-type system, but expression was still significantly stimulated by the combination of X, P and U variants, although not to the same extent as for bla. We also integrated a single copy of the expression cassette with each gene into the E. coli chromosome and found that the expression level from this single copy was higher for bla than for the wild-type plasmid system, while it was lower for celB and gm-csf. Conclusion Our results show that combination of stimulatory expression control elements can be used to further increase production of different proteins in E. coli. For one reporter gene (bla this allowed for more protein production from a single gene copy

  7. Control rod drop analysis by finite element method using fluid-structure interaction for a pressurized water reactor power plant

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, K.H. [Korea Atomic Energy Research Institute, Daedukdaero 1045 Dukjin-Dong, Yusong-Ku, Daejeon 305-353 (Korea, Republic of)], E-mail: khyoon@kaeri.re.kr; Kim, J.Y.; Lee, K.H.; Lee, Y.H.; Kim, H.K. [Korea Atomic Energy Research Institute, Daedukdaero 1045 Dukjin-Dong, Yusong-Ku, Daejeon 305-353 (Korea, Republic of)

    2009-10-15

    The control rod drop analysis is very important for safety analysis. For seismic and loss of coolant accident event, the control rod assemblies shall be capable of traveling from a fully withdrawn position to 90% insertion without any blockage and within specified time and displacement limits. The analysis has been executed by analytical method using in-house code. In this method, several field data are needed. These data are obtained from nuclear, thermal-hydraulic and mechanical design groups, peculiar codes, those work groups need to cooperate together. Following the enhancement of a computer and development of the multi-physics analysis code, a new method for the control rod drop analysis is proposed by finite element method. This analysis model incorporates the structure and fluid parts, termed as a fluid and structure interaction (FSI). Because a control rod is submerged inside a guide tube of a fuel assembly, the FSI boundary condition is applied. In this model, it is assumed that the fluid is incompressible laminar flow. The structures are modeled with the solid elements because there is no deformation due to the fluid flow. The analysis two-dimensional plane model is created in the analysis with considering an axi-symmetric geometry. Therefore, the proposed analysis model will be very simple and the design data from other fields will be unnecessary. The analysis results are compared with those of the in-house code, which have been used for a commercial design. After validation, it is found that the present analysis gives a useful tool in the design of the control rod and fuel assembly.

  8. Combinatorial Gene Regulation through Kinetic Control of the Transcription Cycle.

    Science.gov (United States)

    Scholes, Clarissa; DePace, Angela H; Sánchez, Álvaro

    2017-01-25

    Cells decide when, where, and to what level to express their genes by "computing" information from transcription factors (TFs) binding to regulatory DNA. How is the information contained in multiple TF-binding sites integrated to dictate the rate of transcription? The dominant conceptual and quantitative model is that TFs combinatorially recruit one another and RNA polymerase to the promoter by direct physical interactions. Here, we develop a quantitative framework to explore kinetic control, an alternative model in which combinatorial gene regulation can result from TFs working on different kinetic steps of the transcription cycle. Kinetic control can generate a wide range of analog and Boolean computations without requiring the input TFs to be simultaneously bound to regulatory DNA. We propose experiments that will illuminate the role of kinetic control in transcription and discuss implications for deciphering the cis-regulatory "code."

  9. Collaborative study to improve the quality control of rare earth element determinations in environmental matrices

    NARCIS (Netherlands)

    Kramer, K.J.M.; Dorten, W.S.; Groenewoud, H. van het; Haan, E. de; Kramer, G.N.; Monteiro, L.; Muntau, H.; Quevauviller, P.

    1999-01-01

    In order to control the quality of rare earth determinations in environmental matrices, the Standards, Measurements and Testing Programme (formerly Community Bureau of Reference, BCR) of the European Commission has started a project, the final aim of which is to certify four types of matrices (tuna

  10. Influence of meteorological elements on balance control and pain in patients with symptomatic knee osteoarthritis

    Science.gov (United States)

    Peultier, Laetitia; Lion, Alexis; Chary-Valckenaere, Isabelle; Loeuille, Damien; Zhang, Zheng; Rat, Anne-Christine; Gueguen, René; Paysant, Jean; Perrin, Philippe P.

    2017-05-01

    This study aimed to determine if pain and balance control are related to meteorological modifications in patients with knee osteoarthritis (OA). One hundred and thirteen patients with knee OA (mean age = 65 ± 9 years old, 78 women) participated in this study. Static posturography was performed, sway area covered and sway path traveled by the center of foot pressure being recorded under six standing postural conditions that combine three visual situations (eyes open, eyes closed, vision altered) with two platform situations (firm and foam supports). Knee pain score was assessed using a visual analog scale. Balance control and pain measurements recorded in the morning were correlated with the meteorological data. Morning and daily values for temperature, precipitation, sunshine, height of rain in 1 h, wind speed, humidity, and atmospheric pressure were obtained from the nearest data collecting weather station. The relationship between postural control, pain, and weather variations were assessed for each patient on a given day with multiple linear regressions. A decrease of postural stability was observed when atmospheric pressure and maximum humidity decreased in the morning ( p < 0.05) and when atmospheric pressure decreased within a day ( p < 0.05). Patient's knee pain was more enhanced when it is warmer in the morning ( p < 0.05) and when it is wetter and warmer within a day ( p < 0.05). The relationship between weather, pain, and postural control can help patients and health professionals to better manage daily activities.

  11. An evaluation of controlled permeability formwork for long-term durability of structural concrete elements

    Energy Technology Data Exchange (ETDEWEB)

    Suryavanshi, A.K.; Swamy, R.N. [Univ. of Sheffield (United Kingdom). Dept. of Mechanical Engineering

    1997-07-01

    The long-term performance of a concrete slab (CPF slab) exposed to chloride ingress and atmospheric carbonation from the surface generated by controlled permeability formwork (CPF) is investigated. The results are compared with a similar slab exposed to long-term chloride ingress and atmospheric carbonation from the cast face (Control slab). Techniques such as X-ray diffraction (XRD) and differential thermal analyses (DTA) were employed to determine the resistance against carbonation while, mercury porosimetry was used for investigating the pore size distribution at the surface of the slabs. Amount of acid soluble chlorides was determined by using Volhard`s method. The CPF employed at the bottom of the mould was not fully effective in its intended purpose of generating a permanent and dense impermeable concrete layer adjacent to it when the design water-cement (w/c) ration of the concrete mix was 0.60. This resulted in an almost similar extent of carbonation at the surface for both CPF and control slabs as shown by XRD and DTA studies. Similarly, there were no significant differences in the amount of chlorides and their depths of penetration for both CPF and control slabs, although the former was marginally superior in chloride penetration resistance at the surface.

  12. Systematic Integrated Process Design and Control of Binary Element Reactive Distillation Processes

    DEFF Research Database (Denmark)

    Mansouri, Seyed Soheil; Sales-Cruz, Mauricio; Huusom, Jakob Kjøbsted

    2016-01-01

    In this work, integrated process design and control of reactive distillation processes is considered through a computer-aided framework. First, a set of simple design methods for reactive distillation column that are similar in concept to non-reactive distillation design methods are extended to d...

  13. Command and Control (C2) Survey of Short-Range Air Defense (SHORAD) Elements.

    Science.gov (United States)

    1985-07-01

    bounds on the responses are within +4.5 percentage points N or a frequency count of about 6 ( Scheaffer , Mendenhall, & Ott, 1979). Procedures The...air defense command and control (SHORAD G4 ) system. Aberdeen Proving Ground, MD: U.S. Army Human Engineering Laboratory. 9. Scheaffer , R. L

  14. OPTIMIZATION OF THE TEMPERATURE CONTROL SCHEME FOR ROLLER COMPACTED CONCRETE DAMS BASED ON FINITE ELEMENT AND SENSITIVITY ANALYSIS METHODS

    Directory of Open Access Journals (Sweden)

    Huawei Zhou

    2016-10-01

    Full Text Available Achieving an effective combination of various temperature control measures is critical for temperature control and crack prevention of concrete dams. This paper presents a procedure for optimizing the temperature control scheme of roller compacted concrete (RCC dams that couples the finite element method (FEM with a sensitivity analysis method. In this study, seven temperature control schemes are defined according to variations in three temperature control measures: concrete placement temperature, water-pipe cooling time, and thermal insulation layer thickness. FEM is employed to simulate the equivalent temperature field and temperature stress field obtained under each of the seven designed temperature control schemes for a typical overflow dam monolith based on the actual characteristics of a RCC dam located in southwestern China. A sensitivity analysis is subsequently conducted to investigate the degree of influence each of the three temperature control measures has on the temperature field and temperature tensile stress field of the dam. Results show that the placement temperature has a substantial influence on the maximum temperature and tensile stress of the dam, and that the placement temperature cannot exceed 15 °C. The water-pipe cooling time and thermal insulation layer thickness have little influence on the maximum temperature, but both demonstrate a substantial influence on the maximum tensile stress of the dam. The thermal insulation thickness is significant for reducing the probability of cracking as a result of high thermal stress, and the maximum tensile stress can be controlled under the specification limit with a thermal insulation layer thickness of 10 cm. Finally, an optimized temperature control scheme for crack prevention is obtained based on the analysis results.

  15. Distinct element modelling of fracture plan control in continuum and jointed rock mass in presplitting method of surface mining

    Institute of Scientific and Technical Information of China (English)

    Sharafisafa Mansour; Aliabadian Zeinab; Alizadeh Rezvan; Mortazavi Ali

    2014-01-01

    Controlled blasting techniques are used to control overbreak and to aid in the stability of the remaining rock formation. Presplitting is one of the most common methods which is used in many open pit mining and surface blast design. The purpose of presplitting is to form a fracture plane across which the radial cracks from the production blast cannot travel. The purpose of this study is to investigate of effect of pre-splitting on the generation of a smooth wall in continuum and jointed rock mass. The 2D distinct element code was used to simulate the presplitting in a rock slope. The blast load history as a function of time was applied to the inner wall of each blasthole. Important parameters that were considered in the analysis were stress tensor and fracturing pattern. The blast loading magnitude and blasthole spacing and jointing pattern were found to be very significant in the final results.

  16. Efficacy of five-element gymnastics in glucose and lipid control in Taiwanese patients with type 2 diabetes.

    Science.gov (United States)

    Huang, Chiu-Ling; Tai, Yen-Kuang; Yang, Yi-Hsin; Wang, Ruey-Hsia

    2012-08-01

    The purpose of this quasi-experimental study was to determine the efficacy of Five-Element Gymnastics (FEG) in controlling glycosylated hemoglobin (HbA1C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) at the 8th and the 16th weeks of intervention for patients with type 2 diabetes in Taiwan. FEG consolidates several traditional Chinese exercises including Qigong, Xiang Gong, and martial arts with gymnastics. The experimental group (n = 31) practiced FEG at home for 16 weeks. The control group (n = 35) maintained usual activities. FEG was associated with decrease of HbA1C, TG, and LDL-C levels at the 8th week and continuous decrease of HbA1C through the 16th week. FEG could be an exercise choice for patients with type 2 diabetes. Copyright © 2012 Wiley Periodicals, Inc.

  17. Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements.

    Directory of Open Access Journals (Sweden)

    Gene W Yeo

    2007-05-01

    Full Text Available Knowledge of the functional cis-regulatory elements that regulate constitutive and alternative pre-mRNA splicing is fundamental for biology and medicine. Here we undertook a genome-wide comparative genomics approach using available mammalian genomes to identify conserved intronic splicing regulatory elements (ISREs. Our approach yielded 314 ISREs, and insertions of ~70 ISREs between competing splice sites demonstrated that 84% of ISREs altered 5' and 94% altered 3' splice site choice in human cells. Consistent with our experiments, comparisons of ISREs to known splicing regulatory elements revealed that 40%-45% of ISREs might have dual roles as exonic splicing silencers. Supporting a role for ISREs in alternative splicing, we found that 30%-50% of ISREs were enriched near alternatively spliced (AS exons, and included almost all known binding sites of tissue-specific alternative splicing factors. Further, we observed that genes harboring ISRE-proximal exons have biases for tissue expression and molecular functions that are ISRE-specific. Finally, we discovered that for Nova1, neuronal PTB, hnRNP C, and FOX1, the most frequently occurring ISRE proximal to an alternative conserved exon in the splicing factor strongly resembled its own known RNA binding site, suggesting a novel application of ISRE density and the propensity for splicing factors to auto-regulate to associate RNA binding sites to splicing factors. Our results demonstrate that ISREs are crucial building blocks in understanding general and tissue-specific AS regulation and the biological pathways and functions regulated by these AS events.

  18. Using rare earth elements to control phosphorus and track manure in runoff.

    Science.gov (United States)

    Buda, Anthony R; Church, Clinton; Kleinman, Peter J A; Saporito, Lou S; Moyer, Barton G; Tao, Liang

    2010-01-01

    Concern over the enrichment of agricultural runoff with phosphorus (P) from land applied livestock manures has prompted the development of manure amendments that minimize P solubility. In this study, we amended poultry, dairy, and swine manures with two rare earth chlorides, lanthanum chloride (LaCl(3).7H(2)O) and ytterbium chloride (YbCl(3).6H(2)O), to evaluate their effects on P solubility in the manure following incubation in the laboratory as well as on the fate of P and rare earth elements (REEs) when manures were surface-applied to packed soil boxes and subjected to simulated rainfall. In terms of manure P solubility, La:water-extractable P (WEP) ratios close to 1:1 resulted in maximum WEP reduction of 95% in dairy manure and 98% in dry poultry litter. Results from the runoff study showed that REE applications to dry manures such as poultry litter were less effective in reducing dissolved reactive phosphorus (DRP) in runoff than in liquid manures and slurries, which was likely due to mixing limitations. The most effective reductions of DRP in runoff by REEs were observed in the alkaline pH soil, although reductions of DRP in runoff from the acidic soil were still >50%. Particulate REEs were strongly associated with particulate P in runoff, suggesting a potentially useful role in tracking the fate of P and other manure constituents from manure-amended soils. Finally, REEs that remained in soil following runoff had a tendency to precipitate WEP, especially in soils receiving manure amendments. The findings have valuable applications in water quality protection and the evaluation of P site assessment indices.

  19. Finite element analysis of controlling the TC4 thin plate weldment wave-like deformation by welding with impacting rotation

    Institute of Scientific and Technical Information of China (English)

    Zhang Yong; Yang Jianguo; Liu Xuesong; Fang Hongyuan

    2010-01-01

    The new technology of welding with impacting rotation is put forward to decrease the wave-like deformation of the TC4 thin plate weldment.The thermal stress and strain are vital to understand the mechanism of controlling the wave-like deformation.In order to know the development of internal thermal stress and strain,finite element method is utilized for the stress and strain are difficult to be investigated by experimental methods during the welding process.Temperature field,thermal stress evolution and distortion of thin plate are compared with the test results such as weld thermal cycle,residual stress sectioning measurement,and the deflection of the thin plate respectively.By the finite element analysis and test results verification,the mechanism of the technology to control the wave-like deformation is brought forward,non-uniform thermal elastic strain between compressive plastic region and elastic extensive region is diminished by a certain amount of extensive plastic deformation by welding with impacting rotation process.

  20. Discrete Element Modelling of the Influence of Reinforcement in Structurally Controlled Squeezing Mechanisms in a Hard Rock Mine

    Science.gov (United States)

    Karampinos, Efstratios; Hadjigeorgiou, John; Turcotte, Pascal

    2016-12-01

    Structurally defined squeezing mechanisms in hard rock mining often result in buckling failures and large deformations. In mining drives, the primary objective is to mitigate and manage, in a cost-effective way, as opposed to arrest the deformation. This paper is a contribution to an improved understanding of the impact of several reinforcement scenarios in structurally controlled deformations in hard rock mines. The influence of reinforcement in the 3D discrete element method is explored, extending previous numerical work that has captured the squeezing buckling mechanism driven by foliation and high stresses in the selected mine site. A comprehensive strategy for explicitly modelling rock reinforcement using the DEM was developed and implemented in a series of 3D numerical models. The models were calibrated based on field testing of reinforcement and observations at the LaRonde Mine. They were used to investigate the influence of different reinforcement strategies at different deformation stages. The numerical results were in agreement with the field observations and demonstrated the practical implications of using yielding reinforcement elements. This was supported by field data where the use of yielding bolts reduced the drift convergence and rehabilitation. The methodology is applicable to other mine sites facing structurally controlled large deformations.

  1. Investigation of processes controlling summertime gaseous elemental mercury oxidation at midlatitudinal marine, coastal, and inland sites

    Science.gov (United States)

    Ye, Zhuyun; Mao, Huiting; Lin, Che-Jen; Kim, Su Youn

    2016-07-01

    A box model incorporating a state-of-the-art chemical mechanism for atmospheric mercury (Hg) cycling was developed to investigate the oxidation of gaseous elemental mercury (GEM) at three locations in the northeastern United States: Appledore Island (AI; marine), Thompson Farm (TF; coastal, rural), and Pack Monadnock (PM; inland, rural, elevated). The chemical mechanism in this box model included the most up-to-date Hg and halogen chemistry. As a result, the box model was able to simulate reasonably the observed diurnal cycles of gaseous oxidized mercury (GOM) and chemical speciation bearing distinct differences between the three sites. In agreement with observations, simulated GOM diurnal cycles at AI and TF showed significant daytime peaks in the afternoon and nighttime minimums compared to flat GOM diurnal cycles at PM. Moreover, significant differences in the magnitude of GOM diurnal amplitude (AI > TF > PM) were captured in modeled results. At the coastal and inland sites, GEM oxidation was predominated by O3 and OH, contributing 80-99 % of total GOM production during daytime. H2O2-initiated GEM oxidation was significant (˜ 33 % of the total GOM) at the inland site during nighttime. In the marine boundary layer (MBL) atmosphere, Br and BrO became dominant GEM oxidants, with mixing ratios reaching 0.1 and 1 pptv, respectively, and contributing ˜ 70 % of the total GOM production during midday, while O3 dominated GEM oxidation (50-90 % of GOM production) over the remaining day when Br and BrO mixing ratios were diminished. The majority of HgBr produced from GEM+Br was oxidized by NO2 and HO2 to form brominated GOM species. Relative humidity and products of the CH3O2+BrO reaction possibly significantly affected the mixing ratios of Br or BrO radicals and subsequently GOM formation. Gas-particle partitioning could potentially be important in the production of GOM as well as Br and BrO at the marine site.

  2. Prediction of the lifetime of the elements of the safety and control rods of nuclear reactors

    Energy Technology Data Exchange (ETDEWEB)

    Voskoboinikov, V.V.; Emel' yanov, I. Ya.; Lineva, A.F.; Pushkin, S.N.; Semchenko, E.L.; Usov, P.P.

    1987-07-01

    The authors construct a mathematical model based on the analytical solution to such parameters as magnetic flux, alignment, sliding friction, erosion, abrasion, corrosion, and irradiation for the purpose of predicting the service life of electromagnetically driven control rods and their drives. The analytical solution was verified experimentally on a bench simulation where it was found that incorrect assembly and alignment not only serve as the largest contributors to shortened service life of the rods and drives but also render the calculations of the model invalid.

  3. RESEARCH OF ULTRASONIC SENSING AND MIXING ELEMENTS FOR CONTROL OF MAGNETORHEOLOGICAL FLUIDS STABILITY

    Directory of Open Access Journals (Sweden)

    E. Dragašius

    2011-01-01

    Full Text Available  Using of magnetorheological fluids (MRF can reduce energy costs and weight and increase the devices speed and lifetime. In order to fully use all the qualities of MRF properties one must from time to time mix them and measure their properties. These systems are still being designed and tested in the laboratories. There are many structures with rheological fluid, but in many devices fluids are sealed and mechanical mixing and direct measurement of fluid properties are not possible. Effective stability control system for the rheological fluids, which supports homogeneity of the fluid, is described

  4. 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.

  5. [The use of thermoelectric modules (Peltier elements) in the relative humidity control of a hyperbaric environment].

    Science.gov (United States)

    Stashkov, O A

    2002-01-01

    The author considers an option for automatic relative humidity control of a hyperbaric environment demonstrated in a pressure chamber for small animals. To achieve the purpose, a device has been developed to cool off gas mixture using the Peltier effect and then remove condensate. Experiments were performed with two different gas mixtures: O2-N2-He at 25.5 x 10(5) Pa and 30 degrees C and air at 6.9 x 10(5) Pa and 22 degrees C. The device enabled stabilization of relative humidity in the chamber at 30-40% without bio-objects and at 35-46% with bio-objects (Wistar rats).

  6. Study on Compressibility Control of Hyperelastic Material for Homogenization Method Using Mixed Finite Element Analysis

    Science.gov (United States)

    Okada, Jun-Ichi; Hisada, Toshiaki

    It is well known that the compressibility or incompressibility of biological tissue stems from its microscopic structure, which is generally composed of material with varied compressibility, including incompressibility. This paper proposes a framework for a homogenization method in which the compressibility/incompressibility of the macrostructure properly reflects that of the microstructure. The formulation is based on the mixed variational principle with a perturbed Lagrange-multiplier. It is shown that the rate of volumetric change of the macrostructure can be controlled through the homogenization procedure by introducing the constraint on the microstructure only. A couple of numerical examples are given to demonstrate the validity of the proposed method. By comparing the numerical results with theoretical solutions, the method is also confirmed to be free from locking.

  7. Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus

    National Research Council Canada - National Science Library

    Schmidt, Joshua M; Good, Robert T; Appleton, Belinda; Sherrard, Jayne; Raymant, Greta C; Bogwitz, Michael R; Martin, Jon; Daborn, Phillip J; Goddard, Mike E; Batterham, Philip; Robin, Charles

    2010-01-01

    The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change...

  8. Regulatory elements controlling pituitary-specific expression of the human prolactin gene.

    Science.gov (United States)

    Peers, B; Voz, M L; Monget, P; Mathy-Hartert, M; Berwaer, M; Belayew, A; Martial, J A

    1990-09-01

    We have performed transfection and DNase I footprinting experiments to investigate pituitary-specific expression of the human prolactin (hPRL) gene. When fused to the chloramphenicol acetyltransferase (CAT) reporter gene, 5,000 base pairs of the 5'-flanking sequences of the hPRL gene were able to drive high cat gene expression in prolactin-expressing GH3B6 cells specifically. Deletion analysis indicated that this pituitary-specific expression was controlled by three main positive regulatory regions. The first was located just upstream from the TATA box between coordinates -40 and -250 (proximal region). We have previously shown that three motifs of this region bind the pituitary-specific Pit-1 factor. The second positive region was located in the vicinity of coordinates -1300 to -1750 (distal region). DNase I footprinting assays revealed that eight DNA motifs of this distal region bound protein Pit-1 and that two other motifs were recognized by ubiquitous factors, one of which seems to belong to the AP-1 (jun) family. The third positive region was located further upstream, between -3500 and -5000 (superdistal region). This region appears to enhance transcription only in the presence of the distal region.

  9. G-quadruplexes as novel cis-elements controlling transcription during embryonic development.

    Science.gov (United States)

    David, Aldana P; Margarit, Ezequiel; Domizi, Pablo; Banchio, Claudia; Armas, Pablo; Calcaterra, Nora B

    2016-05-19

    G-quadruplexes are dynamic structures folded in G-rich single-stranded DNA regions. These structures have been recognized as a potential nucleic acid based mechanism for regulating multiple cellular processes such as replication, transcription and genomic maintenance. So far, their transcriptional role in vivo during vertebrate embryonic development has not yet been addressed. Here, we performed an in silico search to find conserved putative G-quadruplex sequences (PQSs) within proximal promoter regions of human, mouse and zebrafish developmental genes. Among the PQSs able to fold in vitro as G-quadruplex, those present in nog3, col2a1 and fzd5 promoters were selected for further studies. In cellulo studies revealed that the selected G-quadruplexes affected the transcription of luciferase controlled by the SV40 nonrelated promoter. G-quadruplex disruption in vivo by microinjection in zebrafish embryos of either small ligands or DNA oligonucleotides complementary to the selected PQSs resulted in lower transcription of the targeted genes. Moreover, zebrafish embryos and larvae phenotypes caused by the presence of complementary oligonucleotides fully resembled those ones reported for nog3, col2a1 and fzd5 morphants. To our knowledge, this is the first work revealing in vivo the role of conserved G-quadruplexes in the embryonic development, one of the most regulated processes of the vertebrates biology.

  10. Parameter optimization of measuring and control elements in the monitoring systems of complex technical objects

    Science.gov (United States)

    Nekrylov, Ivan; Korotaev, Valery; Blokhina, Anastasia; Kleshchenok, Maksim

    2017-06-01

    In the world is the widespread adoption of measuring equipment of new generation, which is characterized by small size, high automation level, a multi-channel, digital filtering, satellite synchronization, wireless communication, digital record in long-term memory with great resource, powered by long-lived sources, etc. However, modern equipment base of the Russian institutions and the level of development of technical facilities and measuring technologies lag far behind developed countries. For this reason, the vacated niches are actively developed by foreign companies. For example, more than 70% instrumentation performing works on the territory of Russia, equipped with imported equipment (products of Sweden and Germany companies); the amount of work performed with German equipment is more than 70% of the total volume of these works; more than 80% of industrial measurements are performed using HEXAGON equipment (Sweden). These trends show that the Russian sector of measuring technology gradually become import-dependent, which poses a threat to the economic security of the country and consistent with national priorities. The results of the research will allow to develop the theory of formation of control systems of the displacement with high accuracy and unattainable for the existing analogue ergonomic and weight characteristics combined with a comparable or lower cost. These advantages will allow you to be successful competition, and eventually to supplant the existing system, which had no fundamental changes in the last 20 years and, therefore, retained all the drawbacks: large size and weight, high power consumption, the dependence on magnetic fields

  11. Binding of TFIIIC to sine elements controls the relocation of activity-dependent neuronal genes to transcription factories.

    Directory of Open Access Journals (Sweden)

    Luca Crepaldi

    Full Text Available In neurons, the timely and accurate expression of genes in response to synaptic activity relies on the interplay between epigenetic modifications of histones, recruitment of regulatory proteins to chromatin and changes to nuclear structure. To identify genes and regulatory elements responsive to synaptic activation in vivo, we performed a genome-wide ChIPseq analysis of acetylated histone H3 using somatosensory cortex of mice exposed to novel enriched environmental (NEE conditions. We discovered that Short Interspersed Elements (SINEs located distal to promoters of activity-dependent genes became acetylated following exposure to NEE and were bound by the general transcription factor TFIIIC. Importantly, under depolarizing conditions, inducible genes relocated to transcription factories (TFs, and this event was controlled by TFIIIC. Silencing of the TFIIIC subunit Gtf3c5 in non-stimulated neurons induced uncontrolled relocation to TFs and transcription of activity-dependent genes. Remarkably, in cortical neurons, silencing of Gtf3c5 mimicked the effects of chronic depolarization, inducing a dramatic increase of both dendritic length and branching. These findings reveal a novel and essential regulatory function of both SINEs and TFIIIC in mediating gene relocation and transcription. They also suggest that TFIIIC may regulate the rearrangement of nuclear architecture, allowing the coordinated expression of activity-dependent neuronal genes.

  12. Binding of TFIIIC to sine elements controls the relocation of activity-dependent neuronal genes to transcription factories.

    Science.gov (United States)

    Crepaldi, Luca; Policarpi, Cristina; Coatti, Alessandro; Sherlock, William T; Jongbloets, Bart C; Down, Thomas A; Riccio, Antonella

    2013-01-01

    In neurons, the timely and accurate expression of genes in response to synaptic activity relies on the interplay between epigenetic modifications of histones, recruitment of regulatory proteins to chromatin and changes to nuclear structure. To identify genes and regulatory elements responsive to synaptic activation in vivo, we performed a genome-wide ChIPseq analysis of acetylated histone H3 using somatosensory cortex of mice exposed to novel enriched environmental (NEE) conditions. We discovered that Short Interspersed Elements (SINEs) located distal to promoters of activity-dependent genes became acetylated following exposure to NEE and were bound by the general transcription factor TFIIIC. Importantly, under depolarizing conditions, inducible genes relocated to transcription factories (TFs), and this event was controlled by TFIIIC. Silencing of the TFIIIC subunit Gtf3c5 in non-stimulated neurons induced uncontrolled relocation to TFs and transcription of activity-dependent genes. Remarkably, in cortical neurons, silencing of Gtf3c5 mimicked the effects of chronic depolarization, inducing a dramatic increase of both dendritic length and branching. These findings reveal a novel and essential regulatory function of both SINEs and TFIIIC in mediating gene relocation and transcription. They also suggest that TFIIIC may regulate the rearrangement of nuclear architecture, allowing the coordinated expression of activity-dependent neuronal genes.

  13. Finite element analysis on multi-step rolling process and controlling quality defect for steel wheel rim

    Directory of Open Access Journals (Sweden)

    Ping Lu

    2015-07-01

    Full Text Available To conduct an in-depth analysis of the wheel rim forming processes and effectively control rim forming quality defects, three-dimensional elastic–plastic finite element models of flaring and three rolling processes for 22.5 × 9.0-type steel wheel rim were established using ABAQUS software. Some key techniques in establishing models were investigated, such as methods of imposing boundary condition given by side guide wheels and enforcing load curve. The accuracy of the models was verified by comparing the simulation results with the point-cloud model of the actual produced rim in terms of exterior shape and thickness. Distributions and changes in the equivalent stress and equivalent plastic strain were analysed. The results indicate that the rim misalignment defect often occurs when the unequal width of the reserved material at the two ends of the rim is in the first rolling process. An improved die design is proposed. The results of the finite element analysis indicate that the improved dies are conducive to the flow of the material between the gap of the upper roller and the lower roller, and the difference in the rim width is significantly reduced.

  14. The ethics of blood testing as an element of doping control in sport.

    Science.gov (United States)

    Browne, A; Lachance, V; Pipe, A

    1999-04-01

    Sport authorities continue to confront a variety of perplexing issues as they attempt to address effectively and efficiently the problems posed by doping. The emergence of the phenomena of blood doping and the administration of erythropoietin have added to the challenges faced by doping control authorities. Some sport organizations have introduced blood tests in an attempt to deal with these issues despite the absence of any effective test for the detection of the administration of homologous blood products or eythropoietin. A number of ethical issues are raised by such developments. Even in the presence of an effective test it is suggested that the decision to implement a specific testing approach can be reached by considering the wishes of a hypothetical "Fair Competitor" and an analysis of the costs involved. In this respect the Fair Competitor assumes in the sport community the role that the "reasonable person" occupies in law, permitting an analysis of a proposed course of action. In making any decision regarding the implementation of any test, a Fair Competitor would be guided by considerations of the postulated advantage and incidence of a doping technique, the likelihood of false positive and negative results, the risk of unwanted consequences of a testing process, and a concern that a specific test not accelerate the likelihood of the use of other doping methods. This approach is applied to a consideration of the appropriateness of blood testing in sport. It is concluded, using such an analysis, that in their present state of development, blood tests should not be implemented. It is recognized that certain sport authorities currently use blood tests to exclude competitors whose blood values exceed certain predetermined levels on the grounds of concerns regarding health and safety. Screening of this kind is beyond the purview of this discussion.

  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. Evolution of metal hyperaccumulation required cis-regulatory changes and triplication of HMA4

    OpenAIRE

    Hanikenne, Marc; Talke, Ina N.; Haydon, Michael J.; Lanz, Christa; Nolte, Andrea; Motte, Patrick; Kroymann, Juergen; Weigel, Detlef; Krämer, Ute

    2008-01-01

    Little is known about the types of mutations underlying the evolution of species-specific traits. The metal hyperaccumulator Arabidopsis halleri has the rare ability to colonize heavy-metal-polluted soils, and, as an extremophile sister species of Arabidopsis thaliana, it is a powerful model for research on adaptation. A. halleri naturally accumulates and tolerates leaf concentrations as high as 2.2% zinc and 0.28% cadmium in dry biomass. On the basis of transcriptomics studies, metal hyperac...

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

    DEFF Research Database (Denmark)

    Wong, Wendy S W; Nielsen, Rasmus

    2007-01-01

    of the increasing availability of comparative genomic data. RESULTS: We develop a method for finding regulatory modules in Eukaryotic species using phylogenetic data. Using computer simulations and analysis of real data, we show that the use of phylogenetic hidden Markov model can lead to an increase in accuracy...

  18. Subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence

    National Research Council Canada - National Science Library

    Kleinjan, Dirk A; Bancewicz, Ruth M; Gautier, Philippe; Dahm, Ralf; Schonthaler, Helia B; Damante, Giuseppe; Seawright, Anne; Hever, Ann M; Yeyati, Patricia L; van Heyningen, Veronica; Coutinho, Pedro

    2008-01-01

    Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development...

  19. 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.

  20. Landscape of histone modifications in a sponge reveals the origin of animal cis-regulatory complexity

    Science.gov (United States)

    Gaiti, Federico; Jindrich, Katia; Fernandez-Valverde, Selene L; Roper, Kathrein E; Degnan, Bernard M; Tanurdžić, Miloš

    2017-01-01

    Combinatorial patterns of histone modifications regulate developmental and cell type-specific gene expression and underpin animal complexity, but it is unclear when this regulatory system evolved. By analysing histone modifications in a morphologically-simple, early branching animal, the sponge Amphimedonqueenslandica, we show that the regulatory landscape used by complex bilaterians was already in place at the dawn of animal multicellularity. This includes distal enhancers, repressive chromatin and transcriptional units marked by H3K4me3 that vary with levels of developmental regulation. Strikingly, Amphimedon enhancers are enriched in metazoan-specific microsyntenic units, suggesting that their genomic location is extremely ancient and likely to place constraints on the evolution of surrounding genes. These results suggest that the regulatory foundation for spatiotemporal gene expression evolved prior to the divergence of sponges and eumetazoans, and was necessary for the evolution of animal multicellularity. DOI: http://dx.doi.org/10.7554/eLife.22194.001 PMID:28395144

  1. Projection on Proper elements for code control: Verification, numerical convergence, and reduced models. Application to plasma turbulence simulations

    Science.gov (United States)

    Cartier-Michaud, T.; Ghendrih, P.; Sarazin, Y.; Abiteboul, J.; Bufferand, H.; Dif-Pradalier, G.; Garbet, X.; Grandgirard, V.; Latu, G.; Norscini, C.; Passeron, C.; Tamain, P.

    2016-02-01

    The Projection on Proper elements (PoPe) is a novel method of code control dedicated to (1) checking the correct implementation of models, (2) determining the convergence of numerical methods, and (3) characterizing the residual errors of any given solution at very low cost. The basic idea is to establish a bijection between a simulation and a set of equations that generate it. Recovering equations is direct and relies on a statistical measure of the weight of the various operators. This method can be used in any number of dimensions and any regime, including chaotic ones. This method also provides a procedure to design reduced models and quantify its ratio of cost to benefit. PoPe is applied to a kinetic and a fluid code of plasma turbulence.

  2. Gas-Phase Synthesis of Bimetallic Oxide Nanoparticles with Designed Elemental Compositions for Controlling the Explosive Reactivity of Nanoenergetic Materials

    Directory of Open Access Journals (Sweden)

    Ji Young Ahn

    2011-01-01

    Full Text Available We demonstrate a simple and viable method for controlling the energy release rate and pressurization rate of nanoenergetic materials by controlling the relative elemental compositions of oxidizers. First, bimetallic oxide nanoparticles (NPs with a homogeneous distribution of two different oxidizer components (CuO and Fe2O3 were generated by a conventional spray pyrolysis method. Next, the Al NPs employed as a fuel were mixed with CuO-Fe2O3 bimetallic oxide NPs by an ultrasonication process in ethanol solution. Finally, after the removal of ethanol by a drying process, the NPs were converted into energetic materials (EMs. The effects of the mass fraction of CuO in the CuO-Fe2O3 bimetallic oxide NPs on the explosive reactivity of the resulting EMs were examined by using a differential scanning calorimeter and pressure cell tester (PCT systems. The results clearly indicate that the energy release rate and pressurization rate of EMs increased linearly as the mass fraction of CuO in the CuO-Fe2O3 bimetallic oxide NPs increased. This suggests that the precise control of the stoichiometric proportions of the strong oxidizer (CuO and mild oxidizer (Fe2O3 components in the bimetallic oxide NPs is a key factor in tuning the explosive reactivity of EMs.

  3. Test functions for three-dimensional control-volume mixed finite-element methods on irregular grids

    Science.gov (United States)

    Naff, R.L.; Russell, T.F.; Wilson, J.D.; ,; ,; ,; ,; ,

    2000-01-01

    Numerical methods based on unstructured grids, with irregular cells, usually require discrete shape functions to approximate the distribution of quantities across cells. For control-volume mixed finite-element methods, vector shape functions are used to approximate the distribution of velocities across cells and vector test functions are used to minimize the error associated with the numerical approximation scheme. For a logically cubic mesh, the lowest-order shape functions are chosen in a natural way to conserve intercell fluxes that vary linearly in logical space. Vector test functions, while somewhat restricted by the mapping into the logical reference cube, admit a wider class of possibilities. Ideally, an error minimization procedure to select the test function from an acceptable class of candidates would be the best procedure. Lacking such a procedure, we first investigate the effect of possible test functions on the pressure distribution over the control volume; specifically, we look for test functions that allow for the elimination of intermediate pressures on cell faces. From these results, we select three forms for the test function for use in a control-volume mixed method code and subject them to an error analysis for different forms of grid irregularity; errors are reported in terms of the discrete L2 norm of the velocity error. Of these three forms, one appears to produce optimal results for most forms of grid irregularity.

  4. Strategic elements of steam cycle chemistry control practices at TXU's Comanche Peak steam electric station

    Energy Technology Data Exchange (ETDEWEB)

    Fellers, B.; Stevens, J.; Nichols, G. [TXU Electric (United States)

    2002-07-01

    Early industry experience defined the critical importance of Chemistry Control Practices to maintaining long-term performance of PWR steam generators. These lessons provided the impetus for a number of innovations and alternate practices at Comanche Peak. For example, advanced amine investigations and implementation of results provided record low iron transport and deposition. The benefits of the surface-active properties of dimethyl-amine exceeded initial expectations. Operation of pre-coat polishers and steam generator blowdown demineralizers in the amine cycle enabled optimization of amine concentrations and stable pH control. The strategy for coordinated control of oxygen and hydrazine dosing complemented the advanced amine program for protective oxide stabilization. Additionally, a proactive chemical cleaning was performed on Unit 1 to prevent degradations from general fouling of steam generator tube-tube support plate (TSP) and top-of-tubesheet (TTS) crevices. This paper shares the results of these innovations and practices. Also, the bases, theory, and philosophy supporting the strategic elements of program will be presented. (authors)

  5. SLURRY MIX EVAPORATOR BATCH ACCEPTABILITY AND TEST CASES OF THE PRODUCT COMPOSITION CONTROL SYSTEM WITH THORIUM AS A REPORTABLE ELEMENT

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, T.

    2010-10-07

    The Defense Waste Processing Facility (DWPF), which is operated by Savannah River Remediation, LLC (SRR), has recently begun processing Sludge Batch 6 (SB6) by combining it with Frit 418 at a nominal waste loading (WL) of 36%. A unique feature of the SB6/Frit 418 glass system, as compared to the previous glass systems processed in DWPF, is that thorium will be a reportable element (i.e., concentrations of elemental thorium in the final glass product greater than 0.5 weight percent (wt%)) for the resulting wasteform. Several activities were initiated based upon this unique aspect of SB6. One of these was an investigation into the impact of thorium on the models utilized in DWPF's Product Composition and Control System (PCCS). While the PCCS is described in more detail below, for now note that it is utilized by Waste Solidification Engineering (WSE) to evaluate the acceptability of each batch of material in the Slurry Mix Evaporator (SME) before this material is passed on to the melter. The evaluation employs models that predict properties associated with processability and product quality from the composition of vitrified samples of the SME material. The investigation of the impact of thorium on these models was conducted by Peeler and Edwards [1] and led to a recommendation that DWPF can process the SB6/Frit 418 glass system with ThO{sub 2} concentrations up to 1.8 wt% in glass. Questions also arose regarding the handling of thorium in the SME batch acceptability process as documented by Brown, Postles, and Edwards [2]. Specifically, that document is the technical bases of PCCS, and while Peeler and Edwards confirmed the reliability of the models, there is a need to confirm that the current implementation of DWPF's PCCS appropriately handles thorium as a reportable element. Realization of this need led to a Technical Task Request (TTR) prepared by Bricker [3] that identified some specific SME-related activities that the Savannah River National Laboratory

  6. Differential trypanosome surface coat regulation by a CCCH protein that co-associates with procyclin mRNA cis-elements.

    Directory of Open Access Journals (Sweden)

    Pegine Walrad

    2009-02-01

    Full Text Available The genome of Trypanosoma brucei is unusual in being regulated almost entirely at the post-transcriptional level. In terms of regulation, the best-studied genes are procyclins, which encode a family of major surface GPI-anchored glycoproteins (EP1, EP2, EP3, GPEET that show differential expression in the parasite's tsetse-fly vector. Although procyclin mRNA cis-regulatory sequences have provided the paradigm for post-transcriptional control in kinetoplastid parasites, trans-acting regulators of procyclin mRNAs are unidentified, despite intensive effort over 15 years. Here we identify the developmental regulator, TbZFP3, a CCCH-class predicted RNA binding protein, as an isoform-specific regulator of Procyclin surface coat expression in trypanosomes. We demonstrate (i that endogenous TbZFP3 shows sequence-specific co-precipitation of EP1 and GPEET, but not EP2 and EP3, procyclin mRNA isoforms, (ii that ectopic overexpression of TbZFP3 does not perturb the mRNA abundance of procyclin transcripts, but rather that (iii their protein expression is regulated in an isoform-specific manner, as evidenced by mass spectrometric analysis of the Procyclin expression signature in the transgenic cell lines. The TbZFP3 mRNA-protein complex (TbZFP3mRNP is identified as a trans-regulator of differential surface protein expression in trypanosomes. Moreover, its sequence-specific interactions with procyclin mRNAs are compatible with long-established predictions for Procyclin regulation. Combined with the known association of TbZFP3 with the translational apparatus, this study provides a long-sought missing link between surface protein cis-regulatory signals and the gene expression machinery in trypanosomes.

  7. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes.

    Science.gov (United States)

    Thayer, Mathew J

    2012-09-01

    Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.

  8. Element composition and mineralogical characterisation of air pollution control residue from UK energy-from-waste facilities.

    Science.gov (United States)

    Bogush, Anna; Stegemann, Julia A; Wood, Ian; Roy, Amitava

    2015-02-01

    Air pollution control (APC) residues from energy-from-waste (EfW) are alkaline (corrosive) and contain high concentrations of metals, such as zinc and lead, and soluble salts, such as chlorides and sulphates. The EPA 3050B-extractable concentrations of 66 elements, including critical elements of strategic importance for advanced electronics and energy technologies, were determined in eight APC residues from six UK EfW facilities. The concentrations of Ag (6-15 mg/kg) and In (1-13 mg/kg), as well as potential pollutants, especially Zn (0.26-0.73 wt.%), Pb (0.05-0.2 wt.%), As, Cd, Cu, Mo, Sb, Sn and Se were found to be enriched in all APC residues compared to average crustal abundances. Results from a combination of scanning electron microscopy with energy dispersive X-ray spectroscopy and also powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy give an exceptionally full understanding of the mineralogy of these residues, which is discussed in the context of other results in the literature. The present work has shown that the bulk of the crystalline phases present in the investigated APC residues include Ca-based phases, such as CaCl(x)OH(2-x), CaCO3, Ca(OH)2, CaSO4, and CaO, as well as soluble salts, such as NaCl and KCl. Poorly-crystalline aragonite was identified by FTIR. Sulphur appears to have complex redox speciation, presenting as both anhydrite and hannebachite in some UK EfW APC residues. Hazardous elements (Zn and Pb) were widely associated with soluble Ca- and Cl-bearing phases (e.g. CaCl(x)OH(2-x) and sylvite), as well as unburnt organic matter and aluminosilicates. Specific metal-bearing minerals were also detected in some samples: e.g., Pb present as cerussite; Zn in gahnite, zincowoodwardite and copper nickel zinc oxide; Cu in tenorite, copper nickel zinc oxide and fedotovite. Aluminium foil pieces were present and abundantly covered by fine phases, particularly in any cracks, probably in the form of Friedel's salt

  9. Evolutionary Novelty in a Butterfly Wing Pattern through Enhancer Shuffling

    National Research Council Canada - National Science Library

    Wallbank, Richard W R; Baxter, Simon W; Pardo-Diaz, Carolina; Hanly, Joseph J; Martin, Simon H; Mallet, James; Dasmahapatra, Kanchon K; Salazar, Camilo; Joron, Mathieu; Nadeau, Nicola; McMillan, W Owen; Jiggins, Chris D

    2016-01-01

    .... Phylogenetic analysis of the two elements demonstrated that they have distinct evolutionary histories and that novel adaptive morphological variation was created by shuffling these cis-regulatory...

  10. Controlled cobalt doping in the spinel structure of magnetosome magnetite: New evidences from element- and site-specific XMCD analyses

    Science.gov (United States)

    Pan, Y.; LI, J.; Menguy, N.; Arrio, M. A.; Sainctavit, P.; Juhin, A.; Wang, Y.; Chen, H.; Bunau, O.; Otero, E.; Ohresser, P.

    2016-12-01

    Controlled cobalt doping in the spinel structure of magnetosome magnetite: New evidences from element- and site-specific XMCD analyses Jinhua Li1,2*, Nicolas Menguy2,3, Marie-Anne Arrio3, Philippe Sainctavit3,4, Amélie Juhin3, Yinzhao Wang1,2, Haitao Chen5, Oana Bunau3, Edwige Otero4, Philippe Ohresser4, Yongxin Pan1,21Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029, China. 2France-China Biomineralization and Nano-structures Laboratory, Chinese Academy of Sciences, Beijing 100029, China. 3IMPMC, CNRS UMR 7590, Sorbonne Universités, MNHN, UPMC, IRD UMR 206, 75005 Paris, France. 4Synchrotron SOLEIL, L'Orme des Merisiers Saint-Aubin, 91192 Gif-sur-Yvette Cedex, France. 5Institute of Deep-Sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China *To whom correspondence may be addressed. Email: lijinhua@mail.iggcas.ac.cnThe biomineralization of magnetite nanocrystals (called magnetosomes) by magnetotactic bacteria (MTB) has attracted intense interest in biology, geology and materials science. Great efforts have been recently made in producing transition metal-doped magnetosomes with modified magnetic properties for a range of applications. However, the coordination chemistry and magnetism of such metal-doped magnetosomes still remains largely unknown. Here, we present new evidences from X-ray magnetic circular dichroism (XMCD) for element- and site-specific magnetic analyses that cobalt is incorporated in the spinel structure of the magnetosomes within Magnetospirillum magneticum AMB-1 through the replacement of Fe2+ ions by Co2+ ions in octahedral (Oh) sites of magnetite. Compared with non-doped one, cobalt-doped magnetosome sample has lower Verwey transition temperature and larger magnetic coercivity, related to the amount of doped cobalt. This study this study indicates a biologically controlled process on cobalt doping and magnetic alteration by MTB system

  11. [Exploration of quality control of inorganic elements in Chinese herbal medicines for stimulating blood circulation and relaxing muscles and joints by atomic absorption spectrophotometry].

    Science.gov (United States)

    Zhang, Qi-feng; Fan, Mei-mei; Wang, Guan-min; Tu, Long-fei; Wang, Cheng

    2007-12-01

    Researches have shown the close relationships between inorganic elements and curative efficiencies of various Chinese herbal medicines. Yet, in studies of chemical composition and quality control of Chinese herbal medicines for stimulating blood circulation and relaxing muscles and joints, inorganic substances are often overlooked. In order to improve and reestablish the standard of quality control of Chinese herbal medicines, the authors attempted a method that would incorporate the composition of inorganic elements as part of the quality control. In the present study, the authors used atomic absorption spectrophotometry to measure the contents of fifteen inorganic elements, namely, Cu, Ca, Fe, K, Mg, Mo, Ni, Sr, V, Mn, Zn, Na, Cr, Cd, and Hg, in several Chinese herbal medicines, including Da Huo Luo Wan. The authors then discussed the relationship between these inorganic elements and curative efficiencies of these Chinese herbal medicines. By comparing the levels of inorganic elements found in Da Huo Luo Wan with those found in other Chinese herbal medicines used in the study, it was revealed that trace elements, Fe, Cu, Mn, and Zn, contribute to the curative efficiency of Da Huo Luo Wan. The authors' results showed that the amounts of trace elements Fe, Cu, Mn and Zn found in Chinese herbal medicine Da Huo Luo Wan are related to the following curative effects of Da Huo Luo Wan: relieving rheumatism, rectifying breathing and alleviating phlegm, stimulating blood circulation and relaxing muscles and joints. The measurement and analysis of inorganic elements in Da Huo Luo Wan will also provide evidences and references for the fingerprint establishment of Da Huo Luo Wan in the future.

  12. 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.

  13. Flexible Holographic Fabrication of 3D Photonic Crystal Templates with Polarization Control through a 3D Printed Reflective Optical Element

    Directory of Open Access Journals (Sweden)

    David Lowell

    2016-07-01

    Full Text Available In this paper, we have systematically studied the holographic fabrication of three-dimensional (3D structures using a single 3D printed reflective optical element (ROE, taking advantage of the ease of design and 3D printing of the ROE. The reflective surface was setup at non-Brewster angles to reflect both s- and p-polarized beams for the interference. The wide selection of reflective surface materials and interference angles allow control of the ratio of s- and p-polarizations, and intensity ratio of side-beam to central beam for interference lithography. Photonic bandgap simulations have also indicated that both s and p-polarized waves are sometimes needed in the reflected side beams for maximum photonic bandgap size and certain filling fractions of dielectric inside the photonic crystals. The flexibility of single ROE and single exposure based holographic fabrication of 3D structures was demonstrated with reflective surfaces of ROEs at non-Brewster angles, highlighting the capability of the ROE technique of producing umbrella configurations of side beams with arbitrary angles and polarizations and paving the way for the rapid throughput of various photonic crystal templates.

  14. Finite element analysis and cellular studies on advanced, controlled porous structures with subsurface continuity in bio-implantable titanium alloys.

    Science.gov (United States)

    Lambert, P; Ankem, S; Wyatt, Z; Ferlin, K M; Fisher, J

    2014-01-01

    Highly-porous metallic implant onlay materials (specifically those containing surface pores that intersect beneath the onlay surface) have been investigated recently for their potential to reduce bone resorption and to improve the overall stability of the implant. In the current study, sub-surface interconnectivity of high-aspect-ratio pores was created directly in the substrate of an implant material using wire electrical discharge machining (EDM). This technique was used to produce intersecting pores with diameters of 180-250 μm on a clinically relevant implant material—commercially pure (CP) Grade 4 Ti—with a very high degree of control over pore morphology. These pores resulted in no significant microstructural modification to the surrounding Ti, and the inner pore surfaces could be thermally oxidized to produce a microrough, bioactive TiO2 layer. Finite element analysis of Ti models containing these EDM-attainable intersecting pore geometries suggested they produce higher bone/implant interface strengths and lower susceptibility to stress shielding of the surrounding bone as compared with models containing simpler surface geometries. In vitro experiments using mesenchymal stem cells (MSCs) demonstrated mineralized tissue ingrowth of ∼ 300 μm into EDM-produced pores. This amount of ingrowth is expected to allow for full interlocking of mineralized tissue and implant given the proper pore structure design.

  15. Evaluation of toxic elements in scalp hair samples of myocardial infarction patients at different stages as related to controls.

    Science.gov (United States)

    Afridi, Hassan Imran; Kazi, Tasneem Gul; Kazi, Naveed; Kandhro, Ghulam Abbas; Baig, Jameel Ahmed; Shah, Abdul Qadir; Jamali, Mohammad Khan; Arain, Mohammad Balal

    2010-04-01

    In the present study, the association of arsenic, cadmium, lead, and nickel between scalp hair samples and mortality from myocardial infarction (MI) patients at first, second, and third heart attack was studied. The biological samples of 130 MI patients (77 male and 53 female) age ranged (45-60 years), were collected and 61 healthy persons of same age group (33 male and 28 female) was selected as control subjects. The toxic elements (TEs) in biological samples were assessed by the electrothermal atomic absorption spectrophotometry prior to microwave-assisted acid digestion. The validity of methodology was checked by the certified human hair reference material (BCR 397). It was observed during the study that 78% of 32 patients of the third MI, age >50 years were expired. In these subjects, the level of As, Cd, Ni, and Pb were increased by 10.6%, 19.5%, 15.7%, and 9.8% in the scalp hair as compared to those who tolerated third MI attack (p = 0.12). The high level of toxic metals may play a role in the development of heart disease in the subjects of this study.

  16. Increasing the dynamic control space of mammalian transcription devices by combinatorial assembly of homologous regulatory elements from different bacterial species.

    Science.gov (United States)

    Bacchus, William; Weber, Wilfried; Fussenegger, Martin

    2013-01-01

    Prokaryotic transcriptional regulatory elements are widely utilized building blocks for constructing regulatory genetic circuits adapted for mammalian cells and have found their way into a broad range of biotechnological applications. Prokaryotic transcriptional repressors, fused to eukaryotic transactivation or repression domains, compose the transcription factor, which binds and adjusts transcription from chimeric promoters containing the repressor-specific operator sequence. Escherichia coli and Chlamydia trachomatis share common features in the regulatory mechanism of the biosynthesis of l-tryptophan. The repressor protein TrpR of C. trachomatis regulates the trpRBA operon and the TrpR of E. coli regulates the trpEDCBA operon, both requiring l-tryptophan as a co-repressor. Fusion of these bacterial repressors to the VP16 transactivation domain of Herpes simplex virus creates synthetic transactivators that could bind and activate chimeric promoters, assembled by placing repressor-specific operator modules adjacent to a minimal promoter, in an l-tryptophan-adjustable manner. Combinations of different transactivator and promoter variants from the same or different bacterial species resulted in a multitude of regulatory systems where l-tryptophan regulation properties, background noise, and maximal gene expression levels were significantly diverse. Different l-tryptophan analogues showed diverse regulatory capacity depending on the promoter/transactivator combination. We believe the systems approach to rationally choose promoters, transactivators and inducer molecules, to obtain desired and predefined genetic expression dynamics and control profiles, will significantly advance the design of new regulatory circuits as well as improving already existing ones. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Analysis of double stub tuner control stability in a many element phased array antenna with strong cross-coupling

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, G. M.; Fitzgerald, E.; Johnson, D. K.; Kanojia, A. D.; Koert, P.; Lin, Y.; Murray, R.; Shiraiwa, S.; Terry, D. R.; Wukitch, S. J. [MIT Plasma Science and Fusion Center, Cambridge, MA 02139 (United States); Hillairet, J. [CEA-IRFM, Saint-Paul-lez-Durance (France)

    2014-02-12

    Active stub tuning with a fast ferrite tuner (FFT) allows for the system to respond dynamically to changes in the plasma impedance such as during the L-H transition or edge localized modes (ELMs), and has greatly increased the effectiveness of fusion ion cyclotron range of frequency systems. A high power waveguide double-stub tuner is under development for use with the Alcator C-Mod lower hybrid current drive (LHCD) system. Exact impedance matching with a double-stub is possible for a single radiating element under most load conditions, with the reflection coefficient reduced from Γ to Γ{sup 2} in the “forbidden region.” The relative phase shift between adjacent columns of a LHCD antenna is critical for control of the launched n{sub ∥} spectrum. Adding a double-stub tuning network will perturb the phase of the forward wave particularly if the unmatched reflection coefficient is high. This effect can be compensated by adjusting the phase of the low power microwave drive for each klystron amplifier. Cross-coupling of the reflected power between columns of the launcher must also be considered. The problem is simulated by cascading a scattering matrix for the plasma provided by a linear coupling model with the measured launcher scattering matrix and that of the FFTs. The solution is advanced in an iterative manner similar to the time-dependent behavior of the real system. System performance is presented under a range of edge density conditions from under-dense to over-dense and a range of launched n{sub ∥}.

  18. From soil water to surface water - how the riparian zone controls element transport from a boreal forest to a stream

    Science.gov (United States)

    Lidman, Fredrik; Boily, Åsa; Laudon, Hjalmar; Köhler, Stephan J.

    2017-06-01

    Boreal headwaters are often lined by strips of highly organic soils, which are the last terrestrial environment to leave an imprint on discharging groundwater before it enters a stream. Because these riparian soils are so different from the Podzol soils that dominate much of the boreal landscape, they are known to have a major impact on the biogeochemistry of important elements such as C, N, P and Fe and the transfer of these elements from terrestrial to aquatic ecosystems. For most elements, however, the role of the riparian zone has remained unclear, although it should be expected that the mobility of many elements is affected by changes in, for example, pH, redox potential and concentration of organic carbon as they are transported through the riparian zone. Therefore, soil water and groundwater was sampled at different depths along a 22 m hillslope transect in the Krycklan catchment in northern Sweden using soil lysimeters and analysed for a large number of major and trace elements (Al, As, B, Ba, Ca, Cd, Cl, Co, Cr, Cs, Cu, Fe, K, La, Li, Mg, Mn, Na, Ni, Pb, Rb, Se, Si, Sr, Th, Ti, U, V, Zn, Zr) and other parameters such as sulfate and total organic carbon (TOC). The results showed that the concentrations of most investigated elements increased substantially (up to 60 times) as the water flowed from the uphill mineral soils and into the riparian zone, largely as a result of higher TOC concentrations. The stream water concentrations of these elements were typically somewhat lower than in the riparian zone, but still considerably higher than in the uphill mineral soils, which suggests that riparian soils have a decisive impact on the water quality of boreal streams. The degree of enrichment in the riparian zone for different elements could be linked to the affinity for organic matter, indicating that the pattern with strongly elevated concentrations in riparian soils is typical for organophilic substances. One likely explanation is that the solubility of many

  19. Quantification of Gaseous Elemental Mercury Dry Deposition to Environmental Surfaces using Mercury Stable Isotopes in a Controlled Environment

    Science.gov (United States)

    Rutter, A. P.; Schauer, J. J.; Shafer, M. M.; Olson, M.; Robinson, M.; Vanderveer, P.; Creswell, J. E.; Parman, A.; Mallek, J.; Gorski, P.

    2009-12-01

    Andrew P. Rutter (1) * *, James J, Schauer (1,2) *, Martin M. Shafer(1,2), Michael R. Olson (1), Michael Robinson (1), Peter Vanderveer (3), Joel Creswell (1), Justin L. Mallek (1), Andrew M. Parman (1) (1) Environmental Chemistry and Technology Program, 660 N. Park St, Madison, WI 53705. (2) Wisconsin State Laboratory of Hygiene, 2601 Agriculture Drive, Madison, WI 53718. (3) Biotron, University of Wisconsin - Madison, 2115 Observatory Drive, Madison, WI 53706 * Correspond author(jjschauer@wisc.edu) * *Presenting author (aprutter@wisc.edu) Abstract Gaseous elemental mercury (GEM) is the predominant component of atmospheric mercury outside of arctic depletion events, and locations where anthropogenic point sources are not influencing atmospheric concentrations. GEM constitutes greater than 99% of the mercury mass in most rural and remote locations. While dry and wet deposition of atmospheric mercury is thought to be dominated by oxidized mercury (a.k.a. reactive mercury), only small GEM uptake to environmental surfaces could impact the input of mercury to terrestrial and aquatic ecosystems. Dry deposition and subsequent re-emission of gaseous elemental mercury is a pathway from the atmosphere that remains only partially understood from a mechanistic perspective. In order to properly model GEM dry deposition and re-emission an understanding of its dependence on irradiance, temperature, and relative humidity must be measured and parameterized for a broad spectrum of environmental surfaces colocated with surrogate deposition surfaces used to make field based dry deposition measurements. Measurements of isotopically enriched GEM dry deposition were made with a variety of environmental surfaces in a controlled environment room at the University of Wisconsin Biotron. The experimental set up allowed dry deposition components which are not easily separated in the field to be decoupled. We were able to isolate surface transfer processes from variabilities caused by

  20. Controllable circuit

    DEFF Research Database (Denmark)

    2010-01-01

    A switch-mode power circuit comprises a controllable element and a control unit. The controllable element is configured to control a current in response to a control signal supplied to the controllable element. The control unit is connected to the controllable element and provides the control...

  1. Dry deposition of gaseous elemental mercury to plants and soils using mercury stable isotopes in a controlled environment

    Science.gov (United States)

    Rutter, Andrew P.; Schauer, James J.; Shafer, Martin M.; Creswell, Joel E.; Olson, Michael R.; Robinson, Michael; Collins, Ryan M.; Parman, Andrew M.; Katzman, Tanya L.; Mallek, Justin L.

    2011-02-01

    Uptake of gaseous elemental mercury (Hg 0(g)) by three plant species and two soil types was measured using mercury vapor enriched in the 198 isotope ( 198Hg 0(g)). The plant species and soil types were: White Ash ( Fraxinus Americana; WA); White Spruce ( Picea Glauca; WS); Kentucky Bluegrass ( Poa Partensis; KYBG); Plano Silt Loam (4% organic matter; PSL); and Plainfield Sand/Sparta Loamy Sand (1.25-1.5% organic matter: PS). The plants and soils were exposed to isotopically enriched Hg 0(g) in a 19 m 3 controlled environment room for 7 days under optimal plant growth conditions (20 °C, 140 Wm -2 between 300 nm and 700 nm; 70% RH) and atmospherically relevant Hg 0(g) concentrations. Mercury was recovered from the samples using acidic digestions and surface leaches, and then analyzed for enrichments in 198Hg by ICPMS. The method was sensitivity enough that statistically significant enrichments in 198Hg were measured in the plant foliage at the end of Day 1. Whole leaf digestions and surface-selective leaches revealed that accumulative uptake was predominantly to the interior of the leaf under the conditions studied. Uptake fluxes for WA increased between the first and third days and remained constant thereafter (WA; Day 1 = 7 ± 2 × 10 -5 ng m -2 s -1; Days 3-7 = 1.3 ± 0.1 × 10 -4 ng m -2 s -1; where m 2 refers to one sided leaf area). KYBG demonstrated similar behavior although no Day 3 measurement was available (Day 1 = 7.5 ± 0.5 × 10 -5 ng m -2 s -1; Day 7 = 1.2 ± 0.1 × 10 -4 ng m -2 s -1). Fluxes to White Spruce were lower, with little difference between Days 1 and 3 followed by a decrease at Day 7 (WS; Days 1-3 = 5 ± 2 × 10 -5 ng m -2 s -1; Day 7 = 2.4 ± 0.2 × 10 -5 ng m -2 s -1). Uptake of Hg to soils was below the method detection limit for those media (PSL = 3 × 10 -2 ng m -2 s -1; PS = 3 × 10 -3 ng m -2 s -1) over the 7 day study period. Foliar resistances calculated for each species compared well to previous studies.

  2. Major and trace element geochemistry of Bay of Bengal sediments: Implications to provenances and their controlling factors

    Digital Repository Service at National Institute of Oceanography (India)

    Tripathy, G.R.; Singh, S.K.; Ramaswamy, V.

    –interglacial period. Factor analysis of these geochemical dataset ascertains dominant role of riverine supply of sediments in regulating the geochemistry of SK187/PC33 sediments. The Al-normalized major (K and Ti) and trace elemental (Cu and Cr) ratios of these marine...

  3. The quality control of fruit juices by using the stable isotope ratios and trace metal elements concentrations

    Science.gov (United States)

    Magdas, D. A.; Dehelean, A.; Puscas, R.; Cristea, G.; Tusa, F.; Voica, C.

    2012-02-01

    In the last years, a growing number of research articles detailing the use of natural abundance light stable isotopes variations and trace metal elements concentration as geographic "tracers" to determine the provenance of food have been published. These investigations exploit the systematic global variations of stable hydrogen, oxygen and carbon isotope ratios in (combination) relation with trace metal element concentrations. The trace metal elements content of plants and also their light stable isotopic ratios are mainly related to the geological and pedoclimatic characteristics of the site of growth. The interpretation of such analysis requires an important number of data for authentic natural juices regarding the same seasonal and regional origin, because the isotopic analysis parameters of fruit juices show remarkable variability depending on climatologically factors. In this work was mesured H, C, O stable isotope ratios and the concentrations of 16 elements (P, K, Mg, Na, Ca, Cu, Cr, Ni, Zn, Pb, Co, As, Cd, Mn, Fe and Hg) from 12 single strength juices. The natural variations that appear due to different environmental and climatic conditions are presented and discussed.

  4. 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.

  5. 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.

  6. Permafrost coverage, watershed area and season control of dissolved carbon and major elements in western Siberian rivers

    Directory of Open Access Journals (Sweden)

    O. S. Pokrovsky

    2015-07-01

    Full Text Available Analysis of dissolved organic and inorganic carbon (DOC and DIC, respectively, pH, Na, K, Ca, Mg, Cl, SO4 and Si in ~ 100 large and small rivers (2 of western Siberia sampled in winter, spring, summer and autumn over a more than 1500 km latitudinal gradient allowed for establishing the main environmental factors controlling the transport of dissolved river components in this environmentally important region, comprising continuous, discontinuous, sporadic and permafrost-free zones. There was significant latitudinal trend consisting in general decrease of DOC, DIC, SO4, and major cation (Ca, Mg, Na, K concentrations northward, reflecting the interplay between groundwater feeding (detectable mostly in the permafrost-free zone, south of 60° N and surface flux (in the permafrost-bearing zone. The trend of inorganic components was mostly pronounced in winter and less visible in spring, whereas for DOC, the trend of concentration decrease with latitude was absent in winter, and less pronounced in the spring flood than in the summer baseflow. The latitudinal trends persisted over all river watershed sizes, from 10 000 km2. This suggested that in addition to groundwater feeding of the river, there was a significant role of surface and shallow subsurface flow linked to plant litter degradation and peat leaching. Environmental factors are ranked by their increasing effect on DOC, DIC, δ13CDIC, and major elements in western Siberian rivers as the following: watershed area −2 yr−1 until 61° N, decreased two-fold in the discontinuous permafrost zone (62–66° N, and increased again to 3 t km−2 yr−1 in the continuous permafrost zone (67° N. The DIC, Mg, K and Ca followed this pattern. The total dissolved cation flux (TDS_c ranged from 1.5 to 5.5 t km−2 yr−1, similar to that in central Siberian rivers of the continuous permafrost region. While Si concentration was almost unaffected by the latitude over all seasons, the Si flux systematically

  7. 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 human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  8. A new approach to evaluate factors controlling elemental sediment–seawater distribution coefficients (K{sub d}) in coastal regions, Japan

    Energy Technology Data Exchange (ETDEWEB)

    Takata, Hyoe, E-mail: takata@kaiseiken.or.jp [Marine Ecology Research Institute, Central Laboratory, Onjuku, Chiba (Japan); National Institute of Radiological Sciences, Chiba City, Chiba (Japan); Aono, Tatsuo; Tagami, Keiko; Uchida, Shigeo [National Institute of Radiological Sciences, Chiba City, Chiba (Japan)

    2016-02-01

    In numerical models to simulate the dispersion of anthropogenic radionuclides in the marine environment, the sediment–seawater distribution coefficient (K{sub d}) for various elements is an important parameter. In coastal regions, K{sub d} values are largely dependent on hydrographic conditions and physicochemical characteristics of sediment. Here we report K{sub d} values for 36 elements (Na, Mg, Al, K, Ca, V, Mn, Fe, Co, Ni, Cu, Se, Rb, Sr, Y, Mo, Cd, I, Cs, rare earth elements, Pb, {sup 232}Th and {sup 238}U) in seawater and sediment samples from 19 Japanese coastal regions, and we examine the factors controlling the variability of these K{sub d} values by investigating their relationships to hydrographic conditions and sediment characteristics. There was large variability in K{sub d} values for Al, Mn, Fe, Co, Ni, Cu, Se, Cd, I, Pb and Th. Variations of K{sub d} for Al, Mn, Fe, Co, Pb and Th appear to be controlled by hydrographic conditions. Although K{sub d} values for Ni, Cu, Se, Cd and I depend mainly on grain size, organic matter content, and the concentrations of hydrous oxides/oxides of Fe and Mn in sediments, heterogeneity in the surface characteristics of sediment particles appears to hamper evaluation of the relative importance of these factors. Thus, we report a new approach to evaluate the factors contributing to variability in K{sub d} for an element. By this approach, we concluded that the K{sub d} values for Cu, Se, Cd and I are controlled by grain size and organic matter in sediments, and the K{sub d} value for Ni is dependent on grain size and on hydrous oxides/oxides of Fe and Mn. - Highlights: • K{sub d}s for 36 elements were determined in 19 Japanese coastal regions. • K{sub d}s for several elements appeared to be controlled by multiple factors in sediments. • We evaluated these factors based on physico-chemical characteristics of sediments.

  9. Controlling the leakage of liquid bismuth cathode elements in ceramic crucibles used for the electrowinning process in pyroprocessing

    Science.gov (United States)

    Kim, Dae-Young; Hwang, Il-Soon; Lee, Jong-Hyeon

    2016-09-01

    Pyroprocessing has shown promise as an alternative to wet processing for the recycling of transuranics with a high proliferation resistance. However, a critical issue for pyroprocessing is the ceramic crucibles used in the electrowinning process. These ceramic crucibles are frequently damaged by thermal stress, which results in significant volumes of crucible waste that must be properly disposed. Transuranic waste (TRU) elements intrude throughout the pores of a damaged crucible. The volume of generated radioactive waste is a concern when dealing with nuclear power plants and decontamination issues. In this study, laser treatment and sintering were performed on the crucibles to minimize the TRU elements trapped within. Secondary ion mass spectroscopy was used to measure the intrusion depth of Li in the surface-treated ceramics.

  10. Urban soil geochemistry in Athens, Greece: The importance of local geology in controlling the distribution of potentially harmful trace elements.

    Science.gov (United States)

    Argyraki, Ariadne; Kelepertzis, Efstratios

    2014-06-01

    Understanding urban soil geochemistry is a challenging task because of the complicated layering of the urban landscape and the profound impact of large cities on the chemical dispersion of harmful trace elements. A systematic geochemical soil survey was performed across Greater Athens and Piraeus, Greece. Surface soil samples (0-10cm) were collected from 238 sampling sites on a regular 1×1km grid and were digested by a HNO3-HCl-HClO4-HF mixture. A combination of multivariate statistics and Geographical Information System approaches was applied for discriminating natural from anthropogenic sources using 4 major elements, 9 trace metals, and 2 metalloids. Based on these analyses the lack of heavy industry in Athens was demonstrated by the influence of geology on the local soil chemistry with this accounting for 49% of the variability in the major elements, as well as Cr, Ni, Co, and possibly As (median values of 102, 141, 16 and 24mg kg(-1) respectively). The contribution to soil chemistry of classical urban contaminants including Pb, Cu, Zn, Sn, Sb, and Cd (medians of 45, 39, 98, 3.6, 1.7 and 0.3mg kg(-1) respectively) was also observed; significant correlations were identified between concentrations and urbanization indicators, including vehicular traffic, urban land use, population density, and timing of urbanization. Analysis of soil heterogeneity and spatial variability of soil composition in the Greater Athens and Piraeus area provided a representation of the extent of anthropogenic modifications on natural element loadings. The concentrations of Ni, Cr, and As were relatively high compared to those in other cities around the world, and further investigation should characterize and evaluate their geochemical reactivity.

  11. An element

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, K.; Iidzima, K.

    1983-03-30

    An anode of a light metal is used in the element, along with an electrolyte which consists of an ether solvent and an ionogenic additive in the form of a salt of dithiocarbamic acid. The element has good discharge characteristics.

  12. Assessment and Accommodation of Thermal Expansion of the Internal Active Thermal Control System Coolant During Launch to On-Orbit Activation of International Space Station Elements

    Science.gov (United States)

    Edwards, Darryl; Ungar, Eugene K.; Holt, James M.

    2002-01-01

    The International Space Station (ISS) employs an Internal Active Thermal Control System (IATCS) comprised of several single-phase water coolant loops. These coolant loops are distributed throughout the ISS pressurized elements. The primary element coolant loops (i.e. U.S. Laboratory module) contain a fluid accumulator to accomodate thermal expansion of the system. Other element coolant loops are parasitic (i.e. Airlock), have no accumulator, and require an alternative approach to insure that the system maximum design pressure (MDP) is not exceeded during the Launch to Activation (LTA) phase. During this time the element loops is a stand alone closed system. The solution approach for accomodating thermal expansion was affected by interactions of system components and their particular limitations. The mathematical solution approach was challenged by the presence of certain unknown or not readily obtainable physical and thermodynamic characteristics of some system components and processes. The purpose of this paper is to provide a brief description of a few of the solutions that evolved over time, a novel mathematical solution to eliminate some of the unknowns or derive the unknowns experimentally, and the testing and methods undertaken.

  13. Demonstration of frequency control and CW diode laser injection control of a titanium-doped sapphire ring laser with no internal optical elements

    Science.gov (United States)

    Bair, Clayton H.; Brockman, Philip; Hess, Robert V.; Modlin, Edward A.

    1988-01-01

    Theoretical and experimental frequency narrowing studies of a Ti:sapphire ring laser with no intracavity optical elements are reported. Frequency narrowing has been achieved using a birefringent filter between a partially reflecting reverse wave suppressor mirror and the ring cavity output mirror. Results of CW diode laser injection seeding are reported.

  14. Major Element Compositions and Rare—earth Element Abundaces of Cenozoic Basalts in Eastern China:Implications for a Pressure Control over LREE/HREE Fractionation in Continental Basalt

    Institute of Scientific and Technical Information of China (English)

    刘丛强; AKIMASAMASUDA; 等

    1992-01-01

    Major element compositions and rare-earth element (REE) and transition element(Ni,Cr and V) abundances have been determined on 44 basalt samples from eastern China.These basalts have SiO2 contents ranging from 38.63 to 55.24(wt.%),and Na2O+K2O from 3.1 to 9.4(wt.%).Ni and Cr abundances are largely variable,respectively falling in ranges 60-605 and 78-1150 ppm.REE abundances,especially light rare-earth elements(LREE), are highly variable.La/Sm and La/Yb ratios vary 2.8 to 7.6 and 1.8 to 8.1. Although the segregation mainly of olivine and clinopyroxene is requested to account for the vari-able and low MgO,CaO/Al2O3,Cr and Ni characteristic of these basalts studied here,the differ-ences in REE composition of the basalts are still related mainly to the partial melting process.Obvious varations in REE abundances could be principally attributed to the partial melting process.Obvious variations in REE abundances could be principally attributed to the partial melting processes that took place at different depths,in spite of some variations caused by the fractional crystallization processes.REE abundances and La/Sm and La/Yb ratios systematically decrease with increasing SiO2,which probably indicated that the basaltic magma derived from a deeper level has higher LREE and LREE/HREE ratios than that from a shallower level.As viewed from the fact that the DYb/DLa ratios of clinopyroxenes in the basaltic system increase with increasing pressure,the increase of LREE/HUEE ratios with increasing melting depth can be interpreted as the pressure dependence of bulk DHREE/DLREE ratios of silicate minerals,in addition to the pressure control over the melting degree.

  15. A Retroviral Promoter and a Cellular Enhancer Define a Bipartite Element Which Controls env ERVWE1 Placental Expression

    Science.gov (United States)

    Prudhomme, Sarah; Oriol, Guy; Mallet, François

    2004-01-01

    The HERV-W family contains hundreds of loci diversely expressed in several physiological and pathological contexts. A unique locus termed ERVWE1 encodes an envelope glycoprotein (syncytin) involved in hominoid placental physiology. Here we show that syncytin expression is regulated by a bipartite element consisting of a cyclic AMP (cAMP)-inducible long terminal repeat (LTR) retroviral promoter adjacent to a cellular enhancer conferring a high level of expression and placental tropism. Deletion mutant analysis showed that the ERVWE1 5′ LTR contains binding sites essential for basal placental activity in the region from positions +1 to +125. The region from positions +125 to +310 represents a cAMP-responsive core HERV-W promoter active in all cell types. Site-directed mutagenesis analysis highlighted the complexity of U3 regulation. ERVWE1 placenta-specific positive (e.g., T240) and negative (e.g., G71) regulatory sites were identified, as were essential sites required for basic activity (e.g., A247). The flanking sequences of the ERVWE1 provirus contain several putative regulatory elements. The upstream HERV-H and HERV-P LTRs were found to be inactive. Conversely, the 436-bp region located between the HERV-P LTR and ERVWE1 was shown to be an upstream regulatory element (URE) which is significantly active in placenta cells. This URE acts as a tissue-specific enhancer. Genetic and functional analyses of hominoid UREs revealed large differences between UREs of members of the Hominidae and the Hylobatidae. These data allowed the identification of a positive regulatory region from positions −436 to −128, a mammalian apparent LTR retrotransposon negative regulatory region from positions −128 to −67, and a trophoblast-specific enhancer (TSE) from positions −67 to −35. Putative AP-2, Sp-1, and GCMa binding sites are essential constituents of the 33-bp TSE. PMID:15507602

  16. A biophysical model for identifying splicing regulatory elements and their interactions.

    Directory of Open Access Journals (Sweden)

    Ji Wen

    Full Text Available Alternative splicing (AS of precursor mRNA (pre-mRNA is a crucial step in the expression of most eukaryotic genes. Splicing factors (SFs play an important role in AS regulation by binding to the cis-regulatory elements on the pre-mRNA. Although many splicing factors (SFs and their binding sites have been identified, their combinatorial regulatory effects remain to be elucidated. In this paper, we derive a biophysical model for AS regulation that integrates combinatorial signals of cis-acting splicing regulatory elements (SREs and their interactions. We also develop a systematic framework for model inference. Applying the biophysical model to a human RNA-Seq data set, we demonstrate that our model can explain 49.1%-66.5% variance of the data, which is comparable to the best result achieved by biophysical models for transcription. In total, we identified 119 SRE pairs between different regions of cassette exons that may regulate exon or intron definition in splicing, and 77 SRE pairs from the same region that may arise from a long motif or two different SREs bound by different SFs. Particularly, putative binding sites of polypyrimidine tract-binding protein (PTB, heterogeneous nuclear ribonucleoprotein (hnRNP F/H and E/K are identified as interacting SRE pairs, and have been shown to be consistent with the interaction models proposed in previous experimental results. These results show that our biophysical model and inference method provide a means of quantitative modeling of splicing regulation and is a useful tool for identifying SREs and their interactions. The software package for model inference is available under an open source license.

  17. Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency.

    Directory of Open Access Journals (Sweden)

    Mart Ustav

    Full Text Available Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1, which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR. Duplication or triplication of the natural 4 bp 5'-CGGG-3' spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters.

  18. Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives.

    Science.gov (United States)

    Maranhão, Geraldo Neves De A; Brito, Alaan Ubaiara; Leal, Anderson Marques; Fonseca, Jéssica Kelly Silva; Macêdo, Wilson Negrão

    2015-09-22

    In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD) for use in Photovoltaic Pumping Systems (PVPS) is proposed. The fuzzy logic system (FLS) used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR) is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC) voltage level in the VSD with a good performance.

  19. Using LDR as Sensing Element for an External Fuzzy Controller Applied in Photovoltaic Pumping Systems with Variable-Speed Drives

    Directory of Open Access Journals (Sweden)

    Geraldo Neves De A. Maranhão

    2015-09-01

    Full Text Available In the present paper, a fuzzy controller applied to a Variable-Speed Drive (VSD for use in Photovoltaic Pumping Systems (PVPS is proposed. The fuzzy logic system (FLS used is embedded in a microcontroller and corresponds to a proportional-derivative controller. A Light-Dependent Resistor (LDR is used to measure, approximately, the irradiance incident on the PV array. Experimental tests are executed using an Arduino board. The experimental results show that the fuzzy controller is capable of operating the system continuously throughout the day and controlling the direct current (DC voltage level in the VSD with a good performance.

  20. A Novel Peroxisome Proliferator Response Element Modulates Hepatic Low Density Lipoprotein Receptor Gene Transcription in Response to PPARδ Activation

    Science.gov (United States)

    Shende, Vikram R.; Singh, Amar Bahadur; Liu, Jingwen

    2016-01-01

    The hepatic expression of LDLR gene is regulated primarily at the transcriptional level by a sterol-regulatory element (SRE) in its proximal promoter region which is the site of action of SRE-binding protein 2 (SREBP2). However whether additional cis-regulatory elements contribute to LDLR transcription has not been fully explored. We investigated the function of a putative PPAR-response element (PPRE) sequence motif located at −768 to −752 bases upstream of the transcription start site of human LDLR gene in response to PPARδ activation. Promoter luciferase reporter analyses showed that treating HepG2 cells with PPARδ agonist L165041 markedly increased the activity of a full-length LDLR promoter construct (pLDLR-1192) without any effects on the shorter promoter reporter pLDLR-234 that contains only the core regulatory elements SRE-1 and SP1 sites. Importantly, mutation of the PPRE sequence greatly attenuated the induction of the full-length LDLR promoter activity by L165041 without affecting rosuvastatin mediated transactivation. Electrophoretic mobility shift and chromatin immunoprecipitation assays further confirmed the binding of PPARδ to the LDLR-PPRE site. Treating HepG2 cells with L165041 elevated the mRNA and protein expressions of LDLR without affecting the LDLR mRNA decay rate. The induction of LDLR expression by PPARδ agonist was further observed in liver tissue of mice and hamsters treated with L165041. Altogether, our studies identify a novel PPRE-mediated regulatory mechanism for LDLR transcription and suggest that combined treatment of statin with PPARδ agonists may have advantageous effects on LDLR expression. PMID:26443862

  1. A novel peroxisome proliferator response element modulates hepatic low-density lipoprotein receptor gene transcription in response to PPARδ activation.

    Science.gov (United States)

    Shende, Vikram R; Singh, Amar Bahadur; Liu, Jingwen

    2015-12-15

    The hepatic expression of low-density lipoprotein (LDL) receptor (LDLR) gene is regulated primarily at the transcriptional level by a sterol-regulatory element (SRE) in its proximal promoter region which is the site of action of SRE-binding protein 2 (SREBP2). However whether additional cis-regulatory elements contribute to LDLR transcription has not been fully explored. We investigated the function of a putative peroxisome proliferator-activated receptor (PPAR)-response element (PPRE) sequence motif located at -768 to -752 bases upstream of the transcription start site of human LDLR gene in response to PPARδ activation. Promoter luciferase reporter analyses showed that treating HepG2 cells with PPARδ agonist L165041 markedly increased the activity of a full-length LDLR promoter construct (pLDLR-1192) without any effects on the shorter promoter reporter pLDLR-234 that contains only the core regulatory elements SRE-1 and SP1 sites. Importantly, mutation of the PPRE sequence greatly attenuated the induction of the full-length LDLR promoter activity by L165041 without affecting rosuvastatin (RSV)-mediated transactivation. EMSA and ChIP assay further confirmed the binding of PPARδ to the LDLR-PPRE site. Treating HepG2 cells with L165041 elevated the mRNA and protein expressions of LDLR without affecting the LDLR mRNA decay rate. The induction of LDLR expression by PPARδ agonist was further observed in liver tissue of mice and hamsters treated with L165041. Altogether, our studies identify a novel PPRE-mediated regulatory mechanism for LDLR transcription and suggest that combined treatment of statin with PPARδ agonists may have advantageous effects on LDLR expression.

  2. Genome-wide prediction of transcriptional regulatory elements of human promoters using gene expression and promoter analysis data

    Directory of Open Access Journals (Sweden)

    Kim Seon-Young

    2006-07-01

    Full Text Available Abstract Background A complete understanding of the regulatory mechanisms of gene expression is the next important issue of genomics. Many bioinformaticians have developed methods and algorithms for predicting transcriptional regulatory mechanisms from sequence, gene expression, and binding data. However, most of these studies involved the use of yeast which has much simpler regulatory networks than human and has many genome wide binding data and gene expression data under diverse conditions. Studies of genome wide transcriptional networks of human genomes currently lag behind those of yeast. Results We report herein a new method that combines gene expression data analysis with promoter analysis to infer transcriptional regulatory elements of human genes. The Z scores from the application of gene set analysis with gene sets of transcription factor binding sites (TFBSs were successfully used to represent the activity of TFBSs in a given microarray data set. A significant correlation between the Z scores of gene sets of TFBSs and individual genes across multiple conditions permitted successful identification of many known human transcriptional regulatory elements of genes as well as the prediction of numerous putative TFBSs of many genes which will constitute a good starting point for further experiments. Using Z scores of gene sets of TFBSs produced better predictions than the use of mRNA levels of a transcription factor itself, suggesting that the Z scores of gene sets of TFBSs better represent diverse mechanisms for changing the activity of transcription factors in the cell. In addition, cis-regulatory modules, combinations of co-acting TFBSs, were readily identified by our analysis. Conclusion By a strategic combination of gene set level analysis of gene expression data sets and promoter analysis, we were able to identify and predict many transcriptional regulatory elements of human genes. We conclude that this approach will aid in decoding

  3. Geomorphic controls on mineral weathering, elemental transport, and production of mineral surface area in a schist bedrock weathering profile, Piedmont Pennsylvania

    Science.gov (United States)

    Wenell, B.; Yoo, K.; Aufdenkampe, A. K.; Mahoney, J. B.; Lepak, L.

    2013-12-01

    We assess a deep chemical weathering profile in the context of geomorphic evolution in the Laurels Schist, a late proterozoic greenschist formation in the Christina River Basin Critical Zone Observatory located in the Piedmont region in southeastern Pennsylvania. Two 21-meter deep rotosonic drill cores were sampled at the ridge top and footslope positions in a first-order, forested watershed. The top meter was sampled at high-resolution in a soil pit adjacent to each drill core and along a hillslope transect to assess geomorphic controls on the weathering profile. Weathering processes in soil and saprolite were examined by observing changes in mineralogy, including the emergence of secondary phyllosilicate and oxide minerals; measuring specific surface area of bulk soil and saprolite; and by quantifying elemental mass changes of major and minor rock-forming elements. Mineral profiles were assessed using clay and bulk XRD, and reveal that kaolinite, a common secondary phyllosilicate, is present above 1.5 meters in the weathering profile. Specific surface area (SSA) values decrease with increasing depth to a critical depth around 2 meters, where the values of untreated (carbon-loaded) and muffled (carbon removed by heating) mineral grains converge to baseline SSA values below 10 m2g-1, indicating that carbon is sorbed with mineral surface area in the upper 2 meters. Immobile element concentrations decrease with increasing depth up to 3 meters, indicating that the preferential removal of mobile elements extends beyond the depth of C-mineral adsorption. Variability of immobile elements in the deep weathering profile reveal variations that could be the result of weathering in fractures but are more likely inherited by the rock composition and particle size of pre-metamorphosed parent rock.

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

    Science.gov (United States)

    Pridans, Clare; Lillico, Simon; Whitelaw, Bruce; Hume, David A

    2014-01-01

    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. PMID:26015955

  5. 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.

  6. Control of oxygen vacancies and Ce{sup +3} concentrations in doped ceria nanoparticles via the selection of lanthanide element

    Energy Technology Data Exchange (ETDEWEB)

    Shehata, N., E-mail: nader83@vt.edu; Meehan, K.; Hudait, M.; Jain, N. [Virginia Tech, Bradley Department of Electrical and Computer Engineering (United States)

    2012-10-15

    The effect of lanthanides that have positive association energies with oxygen vacancies, such as samarium and neodymium, and the elements with negative association energies, such as holmium and erbium, on ionization state of cerium and, consequentially, the oxygen vacancy concentration in doped ceria nanoparticles are investigated in this article. Structural and optical characterizations of the doped and undoped ceria nanoparticles, synthesized using chemical precipitation, are carried out using transmission electron microscopy, X-ray diffractometry, optical absorption spectroscopy, and fluorescence spectroscopy. It is deduced that the negative association energy dopants decrease the conversion of Ce{sup +4} into Ce{sup +3} and, hence, scavenge the oxygen vacancies, evidenced by the observed increase in the allowed direct bandgap, decrease in the integrated fluorescence intensity, and increased the size of doped nanoparticles. The opposite trends are obtained when the positive association dopants are used. It is concluded that the determining factor as to whether a lanthanide dopant in ceria acts as a generator or scavenger of oxygen vacancies in ceria nanoparticles is the sign of the association energy between the element and the oxygen vacancies. The ability to tailor the ionization state of cerium and the oxygen vacancy concentration in ceria has applications in a broad range of fields, which include catalysis, biomedicine, electronics, and environmental sensing.

  7. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.

    Science.gov (United States)

    Appel, Elena; Weissmann, Sarit; Salzberg, Yehuda; Orlovsky, Kira; Negreanu, Varda; Tsoory, Michael; Raanan, Calanit; Feldmesser, Ester; Bernstein, Yael; Wolstein, Orit; Levanon, Ditsa; Groner, Yoram

    2016-12-01

    The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3. Using transgenic mice expressing BAC reporters spanning the Runx3 locus, we discovered three REs-dubbed R1, R2, and R3-that cross-talk with promoter-2 (P2) to drive TrkC neuron-specific Runx3 transcription. Deletion of single or multiple elements either in the BAC transgenics or by CRISPR/Cas9-mediated endogenous ablation established the REs' ability to promote and/or repress Runx3 expression in developing sensory neurons. Our analysis reveals that an intricate combinatorial interplay among the three REs governs Runx3 expression in distinct subtypes of TrkC neurons while concomitantly extinguishing its expression in non-TrkC neurons. These findings provide insights into the mechanism regulating cell type-specific expression and subtype diversification of TrkC neurons in developing DRGs. © 2016 Appel et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Importance of vertical geochemical processes in controlling the oceanic profiles of dissolved rare earth elements in the northeastern Indian Ocean

    Science.gov (United States)

    Nozaki, Yoshiyuki; Alibo, Dia Sotto

    2003-01-01

    Vertical profiles of dissolved rare earth elements (REEs) were obtained in the Bay of Bengal and the Andaman Sea. The REE concentrations at various depths in the Bay of Bengal are the highest in the Indian Ocean. This is attributable ultimately to the large outflow of the Ganges-Brahmaputra and Irrawaddy rivers, but the dissolved REE flux to surface waters alone cannot explain the large and near-constant REE enrichment throughout the entire water column. The underlying fan sediments serve as not a source but a sink for dissolved REE(III)s. Absence of excess 228Ra in the deep waters suggests that lateral input of dissolved REEs from slope sediments is also small in these regions. Partial (rivers and lateral surface currents and subsequently settle through the water column, appears to be a predominant source for the dissolved REEs. Vertical profiles showing an almost linear increase with depth are common features for the light and middle REEs everywhere, but their concentration levels are variable from basin to basin and from element to element. This suggests that their oceanic distributions respond quickly to the variation of particle flux and its REE composition through reversible exchange equilibrium with suspended and sinking particles much like the case for Th. The relative importance of the vertical geochemical processes of reversible scavenging over the horizontal basin-scale ocean circulation with passive regeneration like nutrients decreases systematically from the light to the heavy REEs. Using a model, the mean oceanic residence times of REEs in the Bay of Bengal are estimated to range from 37 years for Ce to 140-1510 years for the strictly trivalent REEs. In the deep water of the Andaman Sea, isolated from the Bay of Bengal by the Andaman-Nicobar Ridge (maximum sill depth of ˜1800 m), the REE concentrations are almost uniform presumably due to rapid vertical mixing. The REE(III) concentrations are similar to that of ˜1250 m depth water in the Bay of

  9. Application of Element Model Technology in Warehouse Control Systems%元模型建模技术在仓库控制系统中的应用

    Institute of Scientific and Technical Information of China (English)

    潘森

    2014-01-01

    In this paper, in view of the demand of the automated warehouses for warehouse control software, we analyzed the inadequacy of the development of the warehouse control systems, and then realized a warehouse control system driven and based on the element model.%针对自动化仓库在仓储控制软件方面的需求,分析了目前仓库控制系统发展上的不足,采用MDA的元模型驱动方法,实现一种基于元模型驱动的仓库控制系统,从而使仓库控制系统具有灵活性、可扩展性。

  10. Introduction of fractional elements for improvising the performance of PID controller for heating furnace using AMIGO tuning technique

    Directory of Open Access Journals (Sweden)

    Amlan Basu

    2016-09-01

    Full Text Available The paper demonstrates about melioration of integer order and fractional order model of heating furnace. Both models are being placed in closed loop along with the proportional integral derivative (PID controller and fractional order proportional integral derivative (FOPID controller so that the various time domain performance characteristics of the heating furnace can be meliorated. The tuning parameters (Kp, Ki and Kd of the controllers has been found using the Astrom-Hagglund tuning technique and the differ-integrals (λ and μ are found using the Nelder-Mead optimisation technique.

  11. Performance of a monolith biotrickling filter treating high concentrations of H2S from mimic biogas and elemental sulfur plugging control using pigging.

    Science.gov (United States)

    Qiu, Xintong; Deshusses, Marc A

    2017-08-08

    A novel biotrickling filter using a 3D-printed honeycomb-monolith as its filter bed has been proposed and studied in this work and a solution to bed-clogging problems using pigging was demonstrated. The inlet H2S concentration in the mimic biogas was controlled around 1000 ppmv and the empty bed gas residence time (EBRT) was 41 s corresponding to a loading rate of 127 g S-H2S m(-3) h(-1). The influence of different H2S/O2 ratios on the removal performance and fate of sulfur end-products was investigated. The results indicated that at a H2S/O2 molar ratio of 1:2, an average removal efficiency of 95% and an elimination capacity of 122 g H2S m(-3) h(-1) was obtained. Under all conditions investigated, elemental sulfur (rather than sulfate) was the dominant end-product which mostly accumulated in the bed. However, the monolith bed design reduced the risk of clogging by elemental sulfur, while bed pigging was shown to be an effective means to remove excess biomass and elemental sulfur accumulated inside the bed and extend the life of the system indefinitely. Altogether, these findings could lead to significant process improvement for biological sweetening of biogas or for removing biomass in biotrickling filters at risk of plugging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Trace element and isotopic geochemistry of Cretaceous magmatism in NE Asia: Spatial zonation, temporal evolution, and tectonic controls

    Science.gov (United States)

    Tikhomirov, Petr L.; Kalinina, Elena A.; Moriguti, Takuya; Makishima, Akio; Kobayashi, Katsura; Nakamura, Eizo

    2016-11-01

    Results of a comprehensive geochemical study (major and trace elements, and isotopes of Sr, Nd, Pb, Hf) of Cretaceous volcanic rocks from the Chukotka area in northeastern Russia are presented. Synthesis of available geological and geochronological data suggests diachronous onset of activity of the Okhotsk-Chukotka volcanic belt (OCVB), the largest magmatic province in the region. The OCVB consists of ca. 106 km3 of volcanic rocks. At 106-105 Ma, subduction-related magmatism initiated in the southern and central segments of the OCVB. In the Central and Northern Chukotka areas, where the northern OCVB is exposed, onset of arc magmatism occurred ca. 10 m.y. after extension-related magmatism of the Chaun igneous province at 109-104 Ma. Mafic rocks from the OCVB yield (87Sr/86Sr)80 Ma of 0.7033 to 0.7047, εNd80 Ma of 0.0 to 7.10, εHf80 Ma of 4.12 to 12.88, (206Pb/204Pb)80 Ma of 18.11 to 18.42, and (208Pb/204Pb)80 Ma of 37.96 to 38.21. Volcanic rocks from the Chaun province, as well as OCVB rocks from Northern Chukotka, originate from a relatively enriched source and have (87Sr/86Sr)80 Ma of 0.7088 to 0.7100, εNd80 Ma of - 5.81 to - 3.42, εHf80 Ma of - 3.40 to - 0.25, (206Pb/204Pb)80 Ma of 18.69 to 18.90, and (208Pb/204Pb)80 Ma of 38.65 to 38.86. No definitive across-arc elemental or isotopic zonation of the OCVB has been revealed, probably because of wide-scale crustal melting and subsequent contamination of mantle-derived melts. However, there is a clear along-arc isotopic zonation. In our interpretation, this results from heterogeneity of the subcontinental lithospheric mantle, which likely was a major contributor to the magma source. The similar isotopic signatures of silicic (dominantly crust-derived) and mafic (mantle-derived) volcanic rocks in each OCVB segment imply that remelting of juvenile mafic underplated material was the main process responsible for the crust-derived magma generation. These data from the major Cretaceous magmatic provinces of northeast

  13. Biomechanics of a posture-controlling cervical artificial disc: mechanical, in vitro, and finite-element analysis.

    Science.gov (United States)

    Crawford, Neil R; Arnett, Jeffery D; Butters, Joshua A; Ferrara, Lisa A; Kulkarni, Nikhil; Goel, Vijay K; Duggal, Neil

    2010-06-01

    Different methods have been described by numerous investigators for experimentally assessing the kinematics of cervical artificial discs. However, in addition to understanding how artificial discs affect range of motion, it is also clinically relevant to understand how artificial discs affect segmental posture. The purpose of this paper is to describe novel considerations and methods for experimentally assessing cervical spine postural control in the laboratory. These methods, which include mechanical testing, cadaveric testing, and computer modeling studies, are applied in comparing postural biomechanics of a novel postural control arthroplasty (PCA) device versus standard ball-and-socket (BS) and ball-in-trough (BT) arthroplasty devices. The overall body of evidence from this group of tests supports the conclusion that the PCA device does control posture to a particular lordotic position, whereas BS and BT devices move freely through their ranges of motion.

  14. A pilot double-blind, randomized, placebo-controlled trial of the efficacy of trace elements in the treatment of endometriosis-related pain: study design and methodology

    Directory of Open Access Journals (Sweden)

    Oberweis D

    2016-02-01

    Full Text Available Didier Oberweis,1 Patrick Madelenat,2 Michelle Nisolle,3 Etienne Demanet4 1Department of Gynecology and Obstetrics, CHU de Charleroi, Hôpital André Vésale, Montigny-le-Tilleul, Belgium; 2Private Consultation, Paris, France; 3Department of Gynecology and Obstetrics, CHR Citadelle, Liège, 4Clinical Research Unit, Charleroi, Belgium Abstract: Endometriosis is one of the most common benign gynecological disorders, affecting almost 10%–15% of all women of reproductive age and >30% of infertile women. The pathology is associated with various distressing symptoms, particularly pelvic pain, which adversely affect patients' quality of life. It is an estrogen-dependent disease. There is evidence both in animals and in humans that metal ions can activate the estrogen receptors. They are defined as a variety of xenoestrogens, called metalloestrogens, which could act as endocrine disruptors. Therefore, it could be considered to act on this gynecological disorder using food supplements containing trace elements (ie, nutripuncture. The assumption is that they could modulate estrogen receptors and thus influence the tropism and the survival of cells involved in endometriosis. By a modulation of the antioxidant system, they might also interact with various parameters influencing tissue biochemistry. The objective of this article is to describe and discuss the design and methodology of an ongoing double-blind, randomized, placebo-controlled study aiming to evaluate the efficacy of metal trace elements on the reduction of pain and improvement of quality of life, in patients with a revised American Fertility Society Score Stages II–IV endometriosis, combined or not with adenomyosis, during a treatment period of 4 months. Trace elements or placebo is proposed in the absence of any other treatment or as an add-on to current therapies, such as sexual hormones, nonsteroidal anti-inflammatory drugs, and surgery. A placebo run-in period of one menstrual cycle or

  15. Elements of metabolic control in children with type 1 diabetes before and after introduction to insulin analogues

    OpenAIRE

    Baloš Ljiljana; Sajić Silvija; Zdravković Vera

    2011-01-01

    Introduction. Diabetes mellitus type 1 (T1DM) in children is characterized by unstable course. A significant number of studies shows that introduction to insulin analogues treatment aims towards better control of the disease. Objective. The assessment of metabolic control in children with T1DM that were introduced to insulin analogue treatment after many years of treatment with classic (human) insulin. Methods. The study included 59 patients 2-19 years old (12.9±3.8) with T1DM, transfer...

  16. 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.

  17. INFORMATION AND COMMUNICATION IN BANKS - KEY ELEMENTS OF THE INTERNAL CONTROL SYSTEM #8211; AN EMPIRICAL ANALYSIS BETWEEN ROMANIAN, AMERICAN AND CANADIAN MODELS OF CONTROL

    Directory of Open Access Journals (Sweden)

    Bota-Avram Cristina

    2009-05-01

    Full Text Available The purpose of this paper is to focus on one of the most important aspect of the internal control in banking system #8211; information and communication - trying to identify on which of the two well-known international models of control (COSO or CoCo i

  18. Guided ultrasonic waves in the cylindrical layer-substrate structures. Application to the control of the massive machine elements with cylindrical cavities

    Science.gov (United States)

    El Ouahdani, M.; Sidki, M.; Ramdani, A.

    2005-12-01

    This paper presents a study of the ultrasonic wave propagation in a cylindrical layer-substrate structure of an infinite length. We determine the dispersion curves of the structure, the displacements field in the structure and the impact of the contact quality between the layer and the substrate. The industrial application aimed by our study is the control of the massive machine elements with cylindrical cavities coated and exposed to corrosion. The obtained results show that some modes of propagation are insensitive to the layer thickness. Therefore, these modes can be generated during the ultrasonic control of the layer. In addition, for the dimensions considered here, the second mode of propagation is the most adapted for the detection of defects in the vicinity of the internal layer wall. In addition, our study shows the possibility of characterization of the quality of contact between the layer and the substrate from the analysis of dispersion curves of the structure.

  19. Permafrost coverage, watershed area and season control of dissolved carbon and major elements in western Siberian rivers

    Science.gov (United States)

    Pokrovsky, O. S.; Manasypov, R. M.; Loiko, S.; Shirokova, L. S.; Krivtzov, I. A.; Pokrovsky, B. G.; Kolesnichenko, L. G.; Kopysov, S. G.; Zemtzov, V. A.; Kulizhsky, S. P.; Vorobiev, S. N.; Kirpotin, S. N.

    2015-07-01

    Analysis of dissolved organic and inorganic carbon (DOC and DIC, respectively), pH, Na, K, Ca, Mg, Cl, SO4 and Si in ~ 100 large and small rivers ( 10 000 km2. This suggested that in addition to groundwater feeding of the river, there was a significant role of surface and shallow subsurface flow linked to plant litter degradation and peat leaching. Environmental factors are ranked by their increasing effect on DOC, DIC, δ13CDIC, and major elements in western Siberian rivers as the following: watershed area water flow path (deep vs. surface) but has to be considered in the context of different climate, plant biomass productivity, unfrozen peat thickness and peat chemical composition. It can be anticipated that, under climate warming in western Siberia, the maximal change will occur in small (ionic composition, and this change will be mostly pronounced in summer and autumn. The wintertime concentrations and spring flood fluxes and concentrations are unlikely to be appreciably affected by the change of the active layer depth and terrestrial biomass productivity. Assuming a conservative precipitation scenario and rising temperature over next few centuries, the annual fluxes of DOC and K in the discontinuous permafrost zone may see a maximum increase by a factor of 2, whereas for DIC and Mg, this increase may achieve a factor of 3. The fluxes of Ca and TDSc may increase by a factor of 5. At the same time, Si fluxes will either remain constant or decrease two-fold in the permafrost-bearing zone relative to the permafrost-free zone of western Siberia.

  20. Replacement of the human cytomegalovirus promoter with fish enhancer and core elements to control the expression of the G gene of viral haemorrhagic septicemia virus (VHSV).

    Science.gov (United States)

    Martinez-Lopez, A; Chinchilla, B; Encinas, P; Gomez-Casado, E; Estepa, A; Coll, J M

    2012-12-15

    This work explores some of the possibilities to replace human cytomegalovirus (CMV) core and/or enhancer promoter control elements to create new expression vectors for use with fish. The work is relevant to fish vaccination, since DNA vaccines use eukaryotic expression plasmids controlled by the human cytomegalovirus (CMV) promoter to be effective against novirhabdoviruses, such as viral haemorrhagic septicemia virus (VHSV), one of the most devastating fish viral European diseases. To reduce possible homologous recombination with fish genome, core and enhancer sequences from fish origin, such as trout interferon-inducible myxovirus protein (Mx), zebrafish retrovirus long terminal repeat (LTR) and carp β-actin (AE6), were combined with those of CMV to design alternative hybrid promoters. The substitution of CMV core and/or enhancer with the corresponding elements of Mx or the LTR core maintained a similar in vitro protein G expression level than that obtained by using the CMV promoter. Vectors using the dsRNA-inducible Mx enhancer followed either by the LTR or the AE6 cores showed the highest in vitro protein G expression levels. Furthermore, synthetic constructs using the Mx enhancer maintained their polyI:C induction capabilities despite the core used. Some of these hybrid promoters might contribute to the development of all-fish-vectors for DNA vaccines while others might be useful for more basic studies.

  1. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

  2. The alr-groEL1 operon in Mycobacterium tuberculosis: an interplay of multiple regulatory elements

    Science.gov (United States)

    Bhat, Aadil H.; Pathak, Deepika; Rao, Alka

    2017-01-01

    Threonylcarbamoyladenosine is a universally conserved essential modification of tRNA that ensures translational fidelity in cellular milieu. TsaD, TsaB and TsaE are identified as tRNA-A37-threonylcarbamoyl (t6A)-transferase enzymes that have been reconstituted in vitro, in few bacteria recently. However, transcriptional organization and regulation of these genes are not known in any of these organisms. This study describes the intricate architecture of a complex multicistronic alr-groEL1 operon, harboring essential genes, namely tsaD, tsaB, tsaE, groES, groEL1, and alr (required for cell wall synthesis), and rimI encoding an N-α- acetyltransferase in Mycobacterium tuberculosis. Using northern blotting, RT-PCR and in vivo fluorescence assays, genes alr to groEL1 were found to constitute an ~6.3 kb heptacistronic operon with multiple internal promoters and an I-shaped intrinsic hairpin-like cis-regulatory element. A strong promoter PtsaD within the coding sequence of rimI gene is identified in M. tuberculosis, in addition. The study further proposes an amendment in the known bicistronic groESL1 operon annotation by providing evidence that groESL1 is co-transcribed as sub-operon of alr-groEL1 operon. The architecture of alr-groEL1 operon, conservation of the genetic context and a mosaic transcriptional profile displayed under various stress conditions convincingly suggest the involvement of this operon in stress adaptation in M. tuberculosis. PMID:28256563

  3. 尿有形成分质控品的研制和观察%Development and observation of quality control material of urinary formed elements

    Institute of Scientific and Technical Information of China (English)

    王青; 胡晓波; 宋颖; 沈薇; 李泳; 李栋成; 许蕾

    2011-01-01

    目的 制备一种重复性好、稳定期长的尿有形成分质控品,有助于日常检验工作中对尿中有形成分进行质量控制.方法 按美国临床实验室标准化协会(CLSI)GP16-A3文件要求收集不同肾病患者的尿液,固定后分装保存.使用具备流式细胞术、显微摄影法和染色技术原理的设备,观察红细胞(RBC)、白细胞(WBC)、上皮细胞、管型和细菌存在与否和形态保持情况;按CLSI EP25文件要求观察各类有形成分的稳定性;同时配制高、中、低3种不同浓度质控品进行精密度检测.结果 有形成分质控品中所含RBC、WBC、上皮细胞、管型和细菌等有形成分的形态保持良好,易于辨认.重复性较好,RBC变异系数(CV)为4.4%~7.8%,WBC为4.3%~14.3%,上皮细胞为4.8%~14.4%,管型为16.9%~23.3%;稳定期可达130 d.结论 制备的尿有形成分质控品含有RBC、WBC、上皮细胞、管型和细菌等有形成分,且有较好的重复性和稳定性,适用于临床尿有形成分质控之用途.%Objective To prepare a quality control material of urinary formed elements with good repeatability and stability, and improve the quality control of urinary formed elements in the routine urine test. Methods According to Clinical and Laboratory Standards Institute (CLSI) GP16-A3, a variety of urine samples from the kidney disease patients was collected, stabilized and stored. By means of flow cytometry, microscopy and staining technique, the existence and storage state of red blood cells (RBC), whit blood cells ( WBC), epithelial cell, casts and bacteria were observed in terms of CLSI EP25 requirement. Meanwhile, the control materials with high, medium and low concentrations were prepared to measure precision. Results The quality control material of urinary formed elements presented good holdings and easily identified feature of RBC, WBC, epithelial cell, casts and bacteria. The results of coefficient of variation (CV) were as follows: RBC 4

  4. Interplay between estrogen response element sequence and ligands controls in vivo binding of estrogen receptor to regulated genes.

    Science.gov (United States)

    Krieg, Adam J; Krieg, Sacha A; Ahn, Bonnie S; Shapiro, David J

    2004-02-06

    To examine the role of the estrogen response element (ERE) sequence in binding of liganded estrogen receptor (ER) to promoters, we analyzed in vivo interaction of liganded ER with the imperfect ERE in the pS2 gene and the composite estrogen-responsive unit (ERU) in the proteinase inhibitor 9 (PI-9) gene. In transient transfections of ER-positive HepG2-ER7 cells, PI-9 was strongly induced by estrogen, moxestrol (MOX), and 4-hydroxytamoxifen (OHT). PI-9 was not induced by raloxifene or ICI 182,780. Quantitative reverse transcriptase-PCR showed that moxestrol strongly induced cellular PI-9 and pS2 mRNAs, whereas OHT moderately induced PI-9 mRNA and weakly induced pS2 mRNA. Chromatin immunoprecipitation experiments demonstrated strong and similar association of 17beta-estradiol-hERalpha and MOX-hERalpha with the PI-9 ERU and with the pS2 ERE. Binding of MOX-hERalpha to the PI-9 ERU and the pS2 ERE was rapid and continuous. Although MOX-hERalpha bound strongly to the PI-9 ERU and less well to the pS2 ERE in chromatin immunoprecipitation, gel shift assays showed that estrogen-hERalpha binds with higher affinity to the deproteinized pS2 ERE than to the PI-9 ERU. Across a broad range of OHT concentrations, OHT-hERalpha associated strongly with the pS2 ERE and weakly with the PI-9 ERU. ICI-hERalpha bound poorly to the PI-9 ERU and effectively to the pS2 ERE. Raloxifene-hERalpha and MOX-hERalpha exhibited similar binding to the PI-9 ERU and the pS2 ERE. These studies demonstrate that ER ligand and ERE sequence work together to regulate in vivo binding of ER to estrogen-responsive promoters.

  5. Elements of metabolic control in children with type 1 diabetes before and after introduction to insulin analogues

    Directory of Open Access Journals (Sweden)

    Baloš Ljiljana

    2011-01-01

    Full Text Available Introduction. Diabetes mellitus type 1 (T1DM in children is characterized by unstable course. A significant number of studies shows that introduction to insulin analogues treatment aims towards better control of the disease. Objective. The assessment of metabolic control in children with T1DM that were introduced to insulin analogue treatment after many years of treatment with classic (human insulin. Methods. The study included 59 patients 2-19 years old (12.9±3.8 with T1DM, transferred from treatment with human insulin to insulin analogues treatment. Data were obtained directly from patients and their parents, as well as from medical records. Results. The introduction to insulin analogues treatment, leads to a decrease in the value of glycolized haemoglobin (HbA1c after 6 months (9.27±1.68% vs 8.63±1:26%, p=0.06. Average daily dose of insulin expressed per IU/kg of classic and insulin analogue (1.04±0.38 vs 1.03±0.30; p>0.05, remained almost the same. In 39 examinees (66.1%, 6 months before the introduction to insulin analogue treatment, severe hypoglicemia was registered and 6 months after the introduction to insulin analogue treatment it appeared in only two examinees (3.4% (p<0.001. Ketoacidosis, 6 months before introduction to insulin analogues treatment, appeared in 16 examinees (27.1%, while 6 months after it was not registered (p<0.001. Conclusion. The use of insulin analogue treatment in childhood provides adequate metabolic control and substantially reduces the risk of acute complications (severe hypoglicemia, ketoacidosis.

  6. EXECUTION, INTERNAL MONITORING, BUDGET VALUATION AND FINANCIAL CONTROLELEMENTS OF DMINISTRATION OF LEGAL PERSONS WITHOUT PATRIMONIAL PURPOSE

    Directory of Open Access Journals (Sweden)

    DANIELA MARIOARA POPOVICI

    2012-11-01

    Full Text Available In order to elaborate a functional budget, namely the functionality to allow the nonprofit organization to cash the programmed income on time and assign hereto the corresponding destination as expenses, must be considered certain stages that the manager of organization with the help of functional compartment have to meet. These are: planning, execution, monitoring, evaluation and reaction, we refer here to the last four, but laying emphasis on the financial administration control function. We shall refer in this article to the characteristics which are given by the spending the public money in the partnerships of non-profit organizations with entities financed from public funds.

  7. The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

    Science.gov (United States)

    Katzenberger, Rebeccah J; Rach, Elizabeth A; Anderson, Ashley K; Ohler, Uwe; Wassarman, David A

    2012-01-01

    To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5' untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the

  8. Flow Element Models

    DEFF Research Database (Denmark)

    Heiselberg, Per; Nielsen, Peter V.

    Air distribution in ventilated rooms is a flow process that can be divided into different elements such as supply air jets, exhaust flows, thermal plumes, boundary layer flows, infiltration and gravity currents. These flow elements are isolated volumes where the air movement is controlled...... by a restricted number of parameters, and the air movement is fairly independent of the general flow in the enclosure. In many practical situations, the most convenient· method is to design the air distribution system using flow element theory....

  9. Using a smokeless tobacco control mass media campaign and other synergistic elements to address social inequalities in India.

    Science.gov (United States)

    Turk, Tahir; Murukutla, Nandita; Gupta, Shefali; Kaur, Jagdish; Mullin, Sandra; Saradhi, Ranjana; Chaturvedi, Pankaj

    2012-03-01

    The burden of tobacco-related morbidity and mortality in India is substantial, with smokeless tobacco being the predominant form of tobacco use. Use of smokeless tobacco (for example gutkha, paan, khaini, and pan masala) is linked to a host of socioeconomic and cultural factors including gender, regional differences, educational level, and income disparities. Given the scale of the problem, a national social marketing campaign was developed and implemented. The creative approach used testimonials from a surgeon and patients at Tata Memorial Hospital in Mumbai. The communication message approach was designed to reflect the realities of disfiguring, disabling, and fatal cancers caused by smokeless tobacco. Evaluation of the campaign identified significant differences across a range of campaign behavioral predictors by audience segments aware of the campaign versus those who were "campaign unaware". Significant findings were also identified regarding vulnerable groups by gender (female/male) and rural/urban disparities. Findings are discussed in relation to the powerful impact of using graphic, emotive, and testimonial imagery for tobacco control with socially disadvantaged groups.

  10. Concepts as elements for consideration of safety-related automatic control; Begriffe als Betrachtungsgrundlagen der sicherheitsgerichteten Automatisierungstechnik

    Energy Technology Data Exchange (ETDEWEB)

    Schrick, D. van [Wuppertal Univ. (Gesamthochschule) (Germany). Fachbereich 14 - Sicherheitstechnik

    1999-07-01

    After referring to a survey article by L. Litz on the fundamentals of safety-related automatic control published in the at-Volume 2/98, the relevance of a supplementarily detailed discussion of the concepts fault, failure, disturbance, default and concepts associated to them is emphasized. The systematic field-overlapping structuring of the relevant set of concepts for non-desired technical phenomena in technical systems is carried out with symbols for such phenomena and, with respect to the aspects causality, temporality, modality and locality, it is described thereafter. The symbol-based and aspect-dependent structuring of concepts results from considerations of the definitions for the concepts of the relevant set of concepts given in German-language guidelines and standards. The result of the guideline and standard-overlapping structuring of concepts reveals the opportunity for an adaptation of the results of standardization to a field-overlapping use of language by consensus. (orig.) [German] Nach Bezugnahme auf den im at-Schwerpunktheft 2/98 erschienen Uebersichtsartikel von L. Litz zu den Grundlagen der sicherheitsgerichteten Automatisierungstechnik, wird die Bedeutsamkeit einer ergaenzenden ausfuehrlichen Diskussion der Begriffe Fehler, Ausfall, Stoerung, Versagen und der mit ihnen assoziierten Begriffe fuer nichterwuenschte technische Phaenomene in technischen Systemen hervorgehoben. Die systematische fachuebergreifende Ordnung der relevanten Begriffsmenge erfolgt mit Symbolen fuer diese Phaenomene und wird hinsichtlich der Aspekte Kausalitaet, Temporalitaet, Modalitaet und Lokalitaet anschliessend beschrieben. Die symbolgestuetzte und aspektabhaengige Begriffsordnung ergibt sich unter Beruecksichtigung der in den deutschsprachigen Richtlinien und Normen angegebenen Definitionen fuer Begriffe der relevanten Begriffsmenge. Das Ergebnis der richtlinien- und normenuebergreifenden Begriffsordnung offenbart eine Moeglichkeit zur Anpassung der Normungsergebnisse

  11. DESIGNING A DIFFRACTIVE OPTICAL ELEMENT FOR CONTROLLING THE BEAM PROFILE IN A THREE-DIMENSIONAL SPACE USING THE SIMULATED ANNEALING ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    LIANG WEN-XI; ZHANG JING-JUAN; L(U) JUN-FENG; LIAO RUI

    2001-01-01

    We have designed a spatially quantized diffractive optical element (DOE) for controlling the beam profile in a three-dimensional space with the help of the simulated annealing (SA) algorithm. In this paper, we investigate the annealing schedule and the neighbourhood which are the deterministic parameters of the process that warrant the quality of the SA algorithm. The algorithm is employed to solve the discrete stochastic optimization problem of the design of a DOE. The objective function which constrains the optimization is also studied. The computed results demonstrate that the procedure of the algorithm converges stably to an optimal solution close to the global optimum with an acceptable computing time. The results meet the design requirement well and are applicable.

  12. PoPe (Projection on Proper elements) for code control: verification, numerical convergence and reduced models. Application to plasma turbulence simulations

    CERN Document Server

    Cartier-Michaud, T; Sarazin, Y; Abiteboul, J; Bufferand, H; Dif-Pradalier, G; Garbet, X; Grandgirard, V; Latu, G; Norscini, C; Passeron, C; Tamain, P

    2015-01-01

    The Projection on Proper elements (PoPe) is a novel method of code control dedicated to 1) checking the correct implementation of models, 2) determining the convergence of numerical methods and 3) characterizing the residual errors of any given solution at very low cost. The basic idea is to establish a bijection between a simulation and a set of equations that generate it. Recovering equations is direct and relies on a statistical measure of the weight of the various operators. This method can be used in any dimensions and any regime, including chaotic ones. This method also provides a procedure to design reduced models and quantify the ratio costs to benefits. PoPe is applied to a kinetic and a fluid code of plasma turbulence.

  13. Climate and cave control on Pleistocene/Holocene calcite-to-aragonite transitions in speleothems from Morocco: Elemental and isotopic evidence

    Science.gov (United States)

    Wassenburg, Jasper A.; Immenhauser, Adrian; Richter, Detlev K.; Jochum, Klaus Peter; Fietzke, Jan; Deininger, Michael; Goos, Manuela; Scholz, Denis; Sabaoui, Abdellah

    2012-09-01

    The occurrence of aragonite in speleothems has commonly been related to high dripwater Mg/Ca ratios, because Mg is known to be a growth inhibitor for calcite. Laboratory aragonite precipitation experiments, however, suggested a more complex array of controlling factors. Here, we present data from Pleistocene to Holocene speleothems collected from both a dolostone and a limestone cave in northern Morocco. These stalagmites exhibit both lateral and stratigraphic calcite-to-aragonite transitions. Aragonite fabrics are well-preserved and represent primary features. In order to shed light on the factors that control alternating calcite and aragonite precipitation, elemental (Mg, Sr, Ba, U, P, Y, Pb, Al, Ti and Th) abundances were measured using LA-ICP-MS, and analysed with Principal Component Analysis. Samples were analyzed at 100-200 μm resolution across stratigraphic and lateral transitions. Carbon and oxygen isotope ratios were analysed at 100 μm resolution covering stratigraphic calcite-to-aragonite transitions. Results show that the precipitation of aragonite was driven by a decrease in effective rainfall, which enhanced prior calcite precipitation. Different geochemical patterns are observed between calcite and aragonite when comparing data from the Grotte de Piste and Grotte Prison de Chien. This may be explained by the increased dripwater Mg/Ca ratio and enhanced prior aragonite precipitation in the dolostone cave versus lower dripwater Mg/Ca ratio and prior calcite precipitation in the limestone cave. A full understanding for the presence of lateral calcite-to-aragonite transitions is not reached. Trace elemental analysis, however, does suggest that different crystallographic parameters (ionic radius, amount of crystal defect sites, adsorption potential) may have a direct effect on the incorporation of Sr, Mg, Ba, Al, Ti, Th and possibly Y and P.

  14. Expression of Trypanosoma cruzi surface antigen FL-160 is controlled by elements in the 3' untranslated, the 3' intergenic, and the coding regions.

    Science.gov (United States)

    Weston, D; La Flamme, A C; Van Voorhis, W C

    1999-07-30

    The FL-160 surface antigen gene family of T. cruzi consists of hundreds of members of 160 kDa glycoproteins expressed in trypomastigotes, but not in epimastigotes. Steady-state levels of FL-160 mRNA were 80 to 100-fold higher in trypomastigotes than in epimastigotes, yet transcription rates were equivalent between the lifecycle stages. Luciferase reporter constructs demonstrated that the 3' untranslated region (UTR) and intergenic region (IR) following the coding sequence of FL-160 was sufficient to generate 8-fold higher luciferase expression in trypomastigotes compared with epimastigotes. Transfection of 3' UTR/IR deletion constructs revealed cis-acting elements which conferred a trypomastigote-specific expression pattern similar to that of FL-160. Parasites treated with translation and transcription inhibitors, cyclohexamide and Actinomycin D, respectively, displayed a stage-specific pattern of FL-160 mRNA degradation. Epimastigotes, but not trypomastigotes, treated with the inhibitors accumulated a 1.4 Kb FL-160 cleavage product. The cleavage site mapped to a 31 base poly-purine tract in the FL-160 coding region. The first 526 aa of FL-160, containing the 31 base poly-purine tract and several smaller tracts, were fused to green fluorescent protein (GFP) and expressed from the T. cruzi tubulin locus. Stable transformants expressed 4-fold more FL-160:GFP fusion mRNA and 12-fold more fusion protein in the trypomastigote stage than in the epimastigote stage suggesting post-transcriptional and translational control elements. These data reveal at least two distinct control mechanisms for trypomastigote-specific expression of FL-160 surface glycoproteins, one involving the 3' UTR/IR and one involving the coding region of FL-160.

  15. Powerful identification of cis-regulatory SNPs in human primary monocytes using allele-specific gene expression.

    Directory of Open Access Journals (Sweden)

    Jonas Carlsson Almlöf

    Full Text Available A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs by genome-wide allele-specific gene expression (ASE analysis with that of traditional expression quantitative trait locus (eQTL mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.

  16. A cis-regulatory antisense RNA represses translation in Vibrio cholerae through extensive complementarity and proximity to the target locus.

    Science.gov (United States)

    Chang, Howard; Replogle, John Michael; Vather, Naomi; Tsao-Wu, Maya; Mistry, Ronak; Liu, Jane M

    2015-01-01

    As with all facultative pathogens, Vibrio cholerae must optimize its cellular processes to adapt to different environments with varying carbon sources and to environmental stresses. More specifically, in order to metabolize mannitol, V. cholerae must regulate the synthesis of MtlA, a mannitol transporter protein produced exclusively in the presence of mannitol. We previously showed that a cis-acting small RNA (sRNA) expressed by V. cholerae, MtlS, appears to post-transcriptionally downregulate the expression of mtlA and is produced in the absence of mannitol. We hypothesized that since it is complementary to the 5' untranslated region (UTR) of mtlA mRNA, MtlS may affect synthesis of MtlA by forming an mtlA-MtlS complex that blocks translation of the mRNA through occlusion of its ribosome binding site. To test this hypothesis, we used in vitro translation assays in order to examine the role MtlS plays in mtlA regulation and found that MtlS is sufficient to suppress translation of transcripts harboring the 5' UTR of mtlA. However, in a cellular context, the 5' UTR of mtlA is not sufficient for targeted repression by endogenous MtlS; additional segments from the coding region of mtlA play a role in the ability of the sRNA to regulate translation of mtlA mRNA. Additionally, proximity of transcription sites between the sRNA and mRNA significantly affects the efficacy of MtlS.

  17. The meta-epigenomic structure of purified human stem cell populations is defined at cis-regulatory sequences

    Science.gov (United States)

    Zhao, Yong Mei; Golden, Aaron; Mar, Jessica C.; Einstein, Francine H.; Greally, John M.

    2014-01-01

    The mechanism and significance of epigenetic variability in the same cell type between healthy individuals are not clear. Here, we purify human CD34+ hematopoietic stem and progenitor cells (HSPCs) from different individuals and find that there is increased variability of DNA methylation at loci with properties of promoters and enhancers. The variability is especially enriched at candidate enhancers near genes transitioning between silent and expressed states, and encoding proteins with leukocyte differentiation properties. Our findings of increased variability at loci with intermediate DNA methylation values, at candidate “poised” enhancers, and at genes involved in HSPC lineage commitment suggest that CD34+ cell subtype heterogeneity between individuals is a major mechanism for the variability observed. Epigenomic studies performed on cell populations, even when purified, are testing collections of epigenomes, or meta-epigenomes. Our findings show that meta-epigenomic approaches to data analysis can provide insights into cell subpopulation structure. PMID:25327398

  18. 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.

  19. Finite Element Analysis of the Control Arm beneath Vehicle' s Suspension%汽车悬架下控制臂的有限元分析

    Institute of Scientific and Technical Information of China (English)

    何小静; 上官文斌

    2012-01-01

    The finite element model of lower control arm beneath vehicle' s suspension was established. In static analysis of the model, inertia relief principle was introduced to eliminate the stress concentration effect of the constraint reaction force on the structural strength of the control arm. In this method, the acceleration due to the unbalanced loads was calculated. The static stiffness properties of the control arm were analyzed. The breaking load and buckling load of the suspension control arm under the conditions of tension and compression were calculated respectively. The results demonstrate that the static stiffness and strength characteristics of the control arm can meet the design requirements.%以某一具体的悬架下控制臂为研究对象,建立悬架控制臂有限元仿真模型.在有限元静力分析过程中,引入惯性释放原理,计算不平衡外力作用下结构的运动(加速度),通过惯性力构造一个平衡的力系,从而消除约束点反力对控制臂结构强度计算造成的应力集中影响.分析汽车悬架控制臂的静刚度特性,对悬架控制臂分别在拉、压工况下进行拉溃力和压溃力有限元分析.分析结果表明,此悬架控制臂满足静刚度特件和强度特性设计要求.

  20. Hydrothermal replacement of biogenic and abiogenic aragonite by Mg-carbonates - Relation between textural control on effective element fluxes and resulting carbonate phase

    Science.gov (United States)

    Jonas, Laura; Müller, Thomas; Dohmen, Ralf; Immenhauser, Adrian; Putlitz, Benita

    2017-01-01

    Dolomitization, i.e., the secondary replacement of calcite or aragonite (CaCO3) by dolomite (CaMg[CO3]2), is one of the most volumetrically important carbonate diagenetic processes. It occurs under near surface and shallow burial conditions and can significantly modify rock properties through changes in porosity and permeability. Dolomitization fronts are directly coupled to fluid pathways, which may be related to the initial porosity/permeability of the precursor limestone, an existing fault network or secondary porosity/permeability created through the replacement reaction. In this study, the textural control on the replacement of biogenic and abiogenic aragonite by Mg-carbonates, that are typical precursor phases in the dolomitization process, was experimentally studied under hydrothermal conditions. Aragonite samples with different textural and microstructural properties exhibiting a compact (inorganic aragonite single crystal), an intermediate (bivalve shell of Arctica islandica) and open porous structure (skeleton of coral Porites sp.) were reacted with a solution of 0.9 M MgCl2 and 0.015 M SrCl2 at 200 °C. The replacement of aragonite by a Ca-bearing magnesite and a Mg-Ca carbonate of non-stoichiometric dolomitic composition takes place via a dissolution-precipitation process and leads to the formation of a porous reaction front that progressively replaces the aragonite precursor. The reaction leads to the development of porosity within the reaction front and distinctive microstructures such as gaps and cavities at the reaction interface. The newly formed reaction rim consists of chemically distinct phases separated by sharp boundaries. It was found that the number of phases and their chemical variation decreases with increasing initial porosity and reactive surface area. This observation is explained by variations in effective element fluxes that result in differential chemical gradients in the fluid within the pore space of the reaction rim. Observed

  1. Element Research.

    Science.gov (United States)

    Herald, Christine

    2001-01-01

    Describes a research assignment for 8th grade students on the elements of the periodic table. Students use web-based resources and a chemistry handbook to gather information, construct concept maps, and present the findings to the full class using the mode of their choice: a humorous story, a slideshow or gameboard, a brochure, a song, or skit.…

  2. A randomized controlled trial on the effects of jujube fruit on the concentrations of some toxic trace elements in human milk

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2016-01-01

    Full Text Available Background: This study aims to investigate the concentrations of lead, cadmium, and arsenic in the human milk, and to assess the effect of jujube fruit consumption by lactating mothers in reducing the concentration of these heavy metals in their milk. Materials and Methods: This randomized controlled trial was conducted in 2014 among forty postpartum mothers in Isfahan, the second largest and polluted city in Iran. Mothers were randomized into two groups; the intervention group received 15 g/day of fresh jujube fruit, and the controls received routine care for 8 weeks. Results: In the beginning, the concentrations of lead, cadmium, and arsenic were high, without significant difference between groups. The mean (standard deviation concentrations of lead, cadmium, and arsenic were 29.49 (16.6, 4.65 (3.51, and 1.23 (0.63 μg/L, respectively. The smoothed empirical distribution of environmental pollutants showed that in both groups the mean values and variance of toxic metals decreased after 8 weeks, with a sharper decline in the intervention group. Quantile regression analysis showed that in the intervention group, lead concentration decreased by 2.54 μg/L at the 90th quintile, and cadmium decreased by 0.19 μg/Lat 75th quintile; without significant change in arsenic level. The corresponding figures were not significant in the control group. Conclusion: The concentrations of heavy metals were high in human milk, and the consumption of jujube fruit had some beneficial effects in reducing these harmful elements. Pregnant and lactating mothers should be advised to reduce their exposure to environmental pollutants, and consumption of some natural medicinal foods can be useful in reducing the concentration of pollutants in human milk. Because of numerous benefits of breast milk, in spite of the existence of some toxic trace elements, breastfeeding must be encouraged because such contaminants are also found in water and formula. The impact of the current

  3. The Drosophila Translational Control Element (TCE is required for high-level transcription of many genes that are specifically expressed in testes.

    Directory of Open Access Journals (Sweden)

    Rebeccah J Katzenberger

    Full Text Available To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE. The TCE functions in the 5' untranslated region of Mst(3CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and

  4. Statistical elements in calculations procedures for air quality control; Elementi di statistica nelle procedure di calcolo per il controllo della qualita' dell'aria

    Energy Technology Data Exchange (ETDEWEB)

    Mura, M.C. [Istituto Superiore di Sanita' , Laboratorio di Igiene Ambientale, Rome (Italy)

    2001-07-01

    The statistical processing of data resulting from the monitoring of chemical atmospheric pollution aimed at air quality control is presented. The form of procedural models may offer a practical instrument to the operators in the sector. The procedural models are modular and can be easily integrated with other models. They include elementary calculation procedures and mathematical methods for statistical analysis. The calculation elements have been developed by probabilistic induction so as to relate them to the statistical analysis. The calculation elements have been developed by probabilistic induction so as to relate them to the statistical models, which are the basis of the methods used for the study and the forecast of atmospheric pollution. This report is part of the updating and training activity that the Istituto Superiore di Sanita' has been carrying on for over twenty years, addressed to operators of the environmental field. [Italian] Il processo di elaborazione statistica dei dati provenienti dal monitoraggio dell'inquinamento chimico dell'atmosfera, finalizzato al controllo della qualita' dell'aria, e' presentato in modelli di procedure al fine di fornire un sintetico strumento di lavoro agli operatori del settore. I modelli di procedure sono modulari ed integrabili. Includono gli elementi di calcolo elementare ed i metodi statistici d'analisi. Gli elementi di calcolo sono sviluppati con metodo d'induzione probabilistica per collegarli ai modelli statistici, che sono alla base dei metodi d'analisi nello studio del fenomeno dell'inquinamento atmosferico anche a fini previsionali. Il rapporto si inserisce nell'attivita' di aggiornamento e di formazione che fin dagli anni ottanta l'Istituto Superiore di Sanita' indirizza agli operatori del settore ambientale.

  5. The Schizosaccharomyces pombe inv1+ regulatory region is unusually large and contains redundant cis-acting elements that function in a SAGA- and Swi/Snf-dependent fashion.

    Science.gov (United States)

    Ahn, Sejin; Spatt, Dan; Winston, Fred

    2012-08-01

    The Schizosaccharomyces pombe inv1(+) gene encodes invertase, the enzyme required for hydrolysis of sucrose and raffinose. Transcription of inv1(+) is regulated by glucose levels, with transcription tightly repressed in high glucose and strongly induced in low glucose. To understand this regulation, we have analyzed the inv1(+) cis-regulatory region and the requirement for the trans-acting coactivators SAGA and Swi/Snf. Surprisingly, deletion of the entire 1-kilobase intergenic region between the inv1(+) TATA element and the upstream open reading frame SPCC191.10 does not significantly alter regulation of inv1(+) transcription. However, a longer deletion that extends through SPCC191.10 abolishes inv1(+) induction in low glucose. Additional analysis demonstrates that there are multiple, redundant regulatory regions spread over 1.5 kb 5' of inv1(+), including within SPCC191.10, that can confer glucose-mediated transcriptional regulation to inv1(+). Furthermore, SPCC191.10 can regulate inv1(+) transcription in an orientation-independent fashion and from a distance as great as 3 kb. With respect to trans-acting factors, both SAGA and Swi/Snf are recruited to SPCC191.10 and to other locations in the large inv1(+) regulatory region in a glucose-dependent fashion, and both are required for inv1(+) derepression. Taken together, these results demonstrate that inv1(+) regulation in S. pombe occurs via the use of multiple regulatory elements and that activation can occur over a great distance, even from elements within other open reading frames.

  6. Improved recombinant antibody production by CHO cells using a production enhancer DNA element with repeated transgene integration at a predetermined chromosomal site.

    Science.gov (United States)

    Kawabe, Yoshinori; Inao, Takanori; Komatsu, Shodai; Huang, Guan; Ito, Akira; Omasa, Takeshi; Kamihira, Masamichi

    2017-03-01

    Chinese hamster ovary (CHO) cells are one of the most useful host cell lines for the production of biopharmaceutical proteins. Although a series of production processes have been refined to improve protein productivity and cost performance, establishing producer cells is still time-consuming and labor-intensive. Recombinase-mediated site-specific gene integration into a predetermined chromosomal locus may enable predictable protein expression, reducing the laborious process of cell screening. We previously developed an accumulative site-specific gene integration system (AGIS) using Cre recombinase and mutated loxP sites for transgene integration and amplification in the CHO cell genome. Epigenetic modifier elements such as insulators are effective DNA cis-regulatory elements for stabilizing transgene expression. Here, we attempted to enhance transgene expression in recombinant CHO cells generated by AGIS using a production enhancer DNA element (PE) derived from the CHO genome. The PE was introduced into an expression unit for a recombinant scFv-Fc antibody. The effect on scFv-Fc productivity of PE position and orientation within the transgene was evaluated, while keeping the background chromosomal structure constant. For the optimal PE arrangement, scFv-Fc productivity was enhanced 2.6-fold compared with an expression unit without a PE. The enhancing effect of the PE on transgene expression was also observed when two or three PE-flanked expression units were inserted as tandem repeats. These results indicate that AGIS using the PE-flanked expression unit is a promising approach for establishing producer cell lines for biopharmaceutical protein production.

  7. Multiple Herbicide Resistance in Lolium multiflorum and Identification of Conserved Regulatory Elements of Herbicide Resistance Genes

    Science.gov (United States)

    Mahmood, Khalid; Mathiassen, Solvejg K.; Kristensen, Michael; Kudsk, Per

    2016-01-01

    Herbicide resistance is a ubiquitous challenge to herbicide sustainability and a looming threat to control weeds in crops. Recently four genes were found constituently over-expressed in herbicide resistant individuals of Lolium rigidum, a close relative of Lolium multiflorum. These include two cytochrome P450s, one nitronate monooxygenase and one glycosyl-transferase. Higher expressions of these four herbicide metabolism related (HMR) genes were also observed after herbicides exposure in the gene expression databases, indicating them as reliable markers. In order to get an overview of herbicidal resistance status of L. multiflorum L, 19 field populations were collected. Among these populations, four populations were found to be resistant to acetolactate synthase (ALS) inhibitors while three exhibited resistance to acetyl-CoA carboxylase (ACCase) inhibitors in our initial screening and dose response study. The genotyping showed the presence of mutations Trp-574-Leu and Ile-2041-Asn in ALS and ACCase, respectively, and qPCR experiments revealed the enhanced expression of HMR genes in individuals of certain resistant populations. Moreover, co-expression networks and promoter analyses of HMR genes in O. sativa and A. thaliana resulted in the identification of a cis-regulatory motif and zinc finger transcription factors. The identified transcription factors were highly expressed similar to HMR genes in response to xenobiotics whereas the identified motif is known to play a vital role in coping with environmental stresses and maintaining genome stability. Overall, our findings provide an important step forward toward a better understanding of metabolism-based herbicide resistance that can be utilized to devise novel strategies of weed management. PMID:27547209

  8. Multiple Herbicide Resistance in Lolium multiflorum and Identification of Conserved Regulatory Elements of Herbicide Resistance Genes.

    Science.gov (United States)

    Mahmood, Khalid; Mathiassen, Solvejg K; Kristensen, Michael; Kudsk, Per

    2016-01-01

    Herbicide resistance is a ubiquitous challenge to herbicide sustainability and a looming threat to control weeds in crops. Recently four genes were found constituently over-expressed in herbicide resistant individuals of Lolium rigidum, a close relative of Lolium multiflorum. These include two cytochrome P450s, one nitronate monooxygenase and one glycosyl-transferase. Higher expressions of these four herbicide metabolism related (HMR) genes were also observed after herbicides exposure in the gene expression databases, indicating them as reliable markers. In order to get an overview of herbicidal resistance status of L. multiflorum L, 19 field populations were collected. Among these populations, four populations were found to be resistant to acetolactate synthase (ALS) inhibitors while three exhibited resistance to acetyl-CoA carboxylase (ACCase) inhibitors in our initial screening and dose response study. The genotyping showed the presence of mutations Trp-574-Leu and Ile-2041-Asn in ALS and ACCase, respectively, and qPCR experiments revealed the enhanced expression of HMR genes in individuals of certain resistant populations. Moreover, co-expression networks and promoter analyses of HMR genes in O. sativa and A. thaliana resulted in the identification of a cis-regulatory motif and zinc finger transcription factors. The identified transcription factors were highly expressed similar to HMR genes in response to xenobiotics whereas the identified motif is known to play a vital role in coping with environmental stresses and maintaining genome stability. Overall, our findings provide an important step forward toward a better understanding of metabolism-based herbicide resistance that can be utilized to devise novel strategies of weed management.

  9. Multiple herbicide resistance in Lolium multiflorum and identification of conserved regulatory elements of herbicide resistance genes

    Directory of Open Access Journals (Sweden)

    Khalid Mahmood

    2016-08-01

    Full Text Available Herbicide resistance is a ubiquitous challenge to herbicide sustainability and a looming threat to control weeds in crops. Recently four genes were found constituently over-expressed in herbicide resistant individuals of Lolium rigidum, a close relative of L. multiflorum. These include two cytochrome P450s, one nitronate monooxygenase and one glycosyl-transferase. Higher expressions of these four herbicide metabolism related (HMR genes were also observed after herbicides exposure in the gene expression databases, indicating them a reliable marker. In order to get an overview of herbicidal resistance status of Lolium multiflorum L, 19 field populations were collected. Among these populations, four populations were found to be resistant to acetolactate synthase (ALS inhibitors while three exhibited resistance to acetyl-CoA carboxylase (ACCase inhibitors in our initial screening and dose response study. The genotyping showed the presence of mutations Trp-574-Leu and Ile-2041-Asn in ALS and ACCase, respectively and qPCR experiments revealed the enhanced expression of HMR genes in individuals of certain resistant populations. Moreover, co-expression networks and promoter analyses of HMR genes in O.sativa and A.thaliana resulted in the identification of a cis-regulatory motif and zinc finger transcription factors. The identified transcription factors were highly expressed similar to HMR genes in response to xenobiotics whereas the identified motif known to play a vital role in coping with environmental stresses and maintaining genome stability. Overall, our findings provide an important step forward towards a better understanding of metabolism-based herbicide resistance that can be utilized to devise novel strategies of weed management.

  10. A modification of a conventional feed water three-element control strategy to solve problems of drum level control; Una modificacion de un sistema convencional de control de agua de alimentacion de tres elementos para resolver problemas de control de nivel del tambor

    Energy Technology Data Exchange (ETDEWEB)

    Delgadillo Valencia, Miguel Angel; Hernandez Cuellar, Maria Aurora [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2008-07-01

    A control strategy for the drum level control of a combined cycle power plant is presented. This strategy is based on the conventional three element system with variable proportional gain in the master and slave controllers. The dynamic behavior of the proposed strategy is compared with a former one showing a better answer especially at full load (generated electric energy) with the supplementary fire (duct burners or after burners) in operation. When the feed water control valve is near its full opening, this strategy can avoid as much as possible the saturation of the control signal to the valve, with elimination of the permanent oscillation of the controlled variable (drum level). The control system behavior also shows good stability from start up to full load, including the transition from one to three elements operating mode and vice verse, as well as the duct burners' ignition. Similar stability is shown during the stop of the Heat Recovery Steam Generator (HRSG) from full load with duct fire in operation to the HRSG out of service. Due to the performance of the blocks communication software of the commercial equipment in use, a transition band of the steam flow signal is proposed, in order to assure a three to one or one to three element bump less transfer operation. Simulation laboratory tests were applied to the proposed control strategy with a simplified dynamic process model, before the control system was put into operation in site. Real process runs and the control-tune parameters are presented. [Spanish] Estudios de investigacion muestran interes en resolver problemas de inestabilidad de control de nivel, en generadores de vapor de plantas generadoras de energia electrica, disenando modelos del fenomeno del nivel del domo, para establecer una estrategia de control para sistemas de control de agua de alimentacion. Sin embargo, una estrategia de control basada en un modelo puede ser dificil de entender para los ingenieros de control, especialmente

  11. DNA element downstream of the κB site in the Lcn2 promoter is required for transcriptional activation by IκBζ and NF-κB p50.

    Science.gov (United States)

    Kohda, Akira; Yamazaki, Soh; Sumimoto, Hideki

    2014-08-01

    The nuclear protein IκBζ activates transcription of a subset of NF-κB-dependent innate immune genes such as Lcn2 encoding the antibacterial protein lipocalin-2. IκBζ functions as a coactivator via its interaction with NF-κB p50, which contains a DNA-binding Rel-homology domain but lacks a transcriptional activation domain. However cis-regulatory elements involved in IκBζ function have remained unknown. Here, we show that, although IκBζ by itself is unable to associate with the Lcn2 promoter, IκBζ interacts with the promoter via p50 binding to the NF-κB-binding site (κB site) and the interaction also requires the pyrimidine-rich site (CCCCTC) that localizes seven bases downstream of the κB site. The pyrimidine-rich site is also essential for IκBζ-mediated activation of the Lcn2 gene. Introduction of both sites into an IκBζ-independent gene culminates in IκBζ-p50-DNA complex formation and transcriptional activation. Furthermore, spacing between the two sites is crucial for both IκBζ-DNA interaction and IκBζ-mediated gene activation. Thus, the pyrimidine-rich IκBζ-responsive site plays an essential role in productive interaction of IκBζ with the p50-DNA complex.

  12. Controlling gene expression by DNA mechanics: emerging insights and challenges.

    Science.gov (United States)

    Levens, David; Baranello, Laura; Kouzine, Fedor

    2016-11-01

    Transcription initiation is a major control point for the precise regulation of gene expression. Our knowledge of this process has been mainly derived from protein-centric studies wherein cis-regulatory DNA sequences play a passive role, mainly in arranging the protein machinery to coalesce at the transcription start sites of genes in a spatial and temporal-specific manner. However, this is a highly dynamic process in which molecular motors such as RNA polymerase II (RNAPII), helicases, and other transcription factors, alter the level of mechanical force in DNA, rather than simply a set of static DNA-protein interactions. The double helix is a fiber that responds to flexural and torsional stress, which if accumulated, can affect promoter output as well as change DNA and chromatin structure. The relationship between DNA mechanics and the control of early transcription initiation events has been under-investigated. Genomic techniques to display topological stress and conformational variation in DNA across the mammalian genome provide an exciting new insight on the role of DNA mechanics in the early stages of the transcription cycle. Without understanding how torsional and flexural stresses are generated, transmitted, and dissipated, no model of transcription will be complete and accurate.

  13. Thermal treatment of stabilized air pollution control residues in a waste incinerator pilot plant. Part 1: Fate of elements and dioxins.

    Science.gov (United States)

    Bergfeldt, Brita; Jay, Klaus; Seifert, Helmuth; Vehlow, Jürgen; Christensen, Thomas H; Baun, Dorthe L; Mogensen, Erhardt P B

    2004-02-01

    Air pollution control (APC) residues from municipal solid waste incinerator plants that are treated by means of the Ferrox process can be more safely disposed of due to reduction of soluble salts and stabilization of heavy metals in an iron oxide matrix. Further stabilization can be obtained by thermal treatment inside a combustion chamber of a municipal solid waste incinerator. The influence of the Ferrox products on the combustion process, the quality of the residues, and the partitioning of heavy metals between the various solids and the gas have been investigated in the Karlsruhe TAM-ARA pilot plant for waste incineration. During the experiments only few parameters were influenced. An increase in the SO2 concentration in the raw gas and slightly lower temperatures in the fuel bed could be observed compared with reference tests. Higher contents of Fe and volatile heavy metals such as Zn, Cd, Pb and partly Hg in the Ferrox products lead to increased concentration of these elements in the solid residues of the co-feeding tests. Neither the burnout nor the PCDD/F formation was altered by the addition of the Ferrox products. Co-feeding of treated APC residues seems to be a feasible approach for obtaining a single solid residue from waste incineration.

  14. Executive function training with game elements for obese children: a novel treatment to enhance self-regulatory abilities for weight-control.

    Science.gov (United States)

    Verbeken, Sandra; Braet, Caroline; Goossens, Lien; van der Oord, Saskia

    2013-06-01

    For obese children behavioral treatment results in only small changes in relative weight and frequent relapse. The current study investigated the effects of an Executive Functioning (EF) training with game-elements on weight loss maintenance in obese children, over and above the care as usual in an inpatient treatment program. Forty-four children (aged 8-14 years) who were in the final months of a 10-months inpatient treatment program in a medical paediatric centre were randomized to either the 6 week EF-training condition or to a care as usual only control group. The EF-training consisted of a 25-session training of inhibition and working memory. Treatment outcomes were child performances on cognitive tasks of inhibition and working memory and childcare worker ratings on EF-symptoms as well as weight loss maintenance after leaving the clinic. Children in the EF-training condition showed significantly more improvement than the children in the care as usual only group on the working memory task as well as on the childcare worker reports of working memory and meta-cognition. They were also more capable to maintain their weight loss until 8 weeks post-training. This study shows promising evidence for the efficacy of an EF-training as weight stabilization intervention in obese children.

  15. p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23 is controlled via a CHR promoter element bound by DREAM and MMB complexes.

    Directory of Open Access Journals (Sweden)

    Martin Fischer

    Full Text Available The microtubule-dependent molecular motor KIF23 (Kinesin family member 23 is one of two components of the centralspindlin complex assembled during late stages of mitosis. Formation of this complex is known as an essential step for cytokinesis. Here, we identified KIF23 as a new transcriptional target gene of the tumor suppressor protein p53. We showed that p53 reduces expression of KIF23 on the mRNA as well as the protein level in different cell types. Promoter reporter assays revealed that this repression results from downregulation of KIF23 promoter activity. CDK inhibitor p21(WAF1/CIP1 was shown to be necessary to mediate p53-dependent repression. Furthermore, we identified the highly conserved cell cycle genes homology region (CHR in the KIF23 promoter to be strictly required for p53-dependent repression as well as for cell cycle-dependent expression of KIF23. Cell cycle- and p53-dependent regulation of KIF23 appeared to be controlled by differential binding of DREAM and MMB complexes to the CHR element. With this study, we describe a new mechanism for transcriptional regulation of KIF23. Considering the strongly supporting function of KIF23 in cytokinesis, its p53-dependent repression may contribute to the prevention of uncontrolled cell growth.

  16. p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23) is controlled via a CHR promoter element bound by DREAM and MMB complexes.

    Science.gov (United States)

    Fischer, Martin; Grundke, Inga; Sohr, Sindy; Quaas, Marianne; Hoffmann, Saskia; Knörck, Arne; Gumhold, Catalina; Rother, Karen

    2013-01-01

    The microtubule-dependent molecular motor KIF23 (Kinesin family member 23) is one of two components of the centralspindlin complex assembled during late stages of mitosis. Formation of this complex is known as an essential step for cytokinesis. Here, we identified KIF23 as a new transcriptional target gene of the tumor suppressor protein p53. We showed that p53 reduces expression of KIF23 on the mRNA as well as the protein level in different cell types. Promoter reporter assays revealed that this repression results from downregulation of KIF23 promoter activity. CDK inhibitor p21(WAF1/CIP1) was shown to be necessary to mediate p53-dependent repression. Furthermore, we identified the highly conserved cell cycle genes homology region (CHR) in the KIF23 promoter to be strictly required for p53-dependent repression as well as for cell cycle-dependent expression of KIF23. Cell cycle- and p53-dependent regulation of KIF23 appeared to be controlled by differential binding of DREAM and MMB complexes to the CHR element. With this study, we describe a new mechanism for transcriptional regulation of KIF23. Considering the strongly supporting function of KIF23 in cytokinesis, its p53-dependent repression may contribute to the prevention of uncontrolled cell growth.