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Sample records for regulatory elements fused

  1. Fused Regression for Multi-source Gene Regulatory Network Inference.

    Directory of Open Access Journals (Sweden)

    Kari Y Lam

    2016-12-01

    Full Text Available Understanding gene regulatory networks is critical to understanding cellular differentiation and response to external stimuli. Methods for global network inference have been developed and applied to a variety of species. Most approaches consider the problem of network inference independently in each species, despite evidence that gene regulation can be conserved even in distantly related species. Further, network inference is often confined to single data-types (single platforms and single cell types. We introduce a method for multi-source network inference that allows simultaneous estimation of gene regulatory networks in multiple species or biological processes through the introduction of priors based on known gene relationships such as orthology incorporated using fused regression. This approach improves network inference performance even when orthology mapping and conservation are incomplete. We refine this method by presenting an algorithm that extracts the true conserved subnetwork from a larger set of potentially conserved interactions and demonstrate the utility of our method in cross species network inference. Last, we demonstrate our method's utility in learning from data collected on different experimental platforms.

  2. 30 CFR 75.601-3 - Short circuit protection; dual element fuses; current ratings; maximum values.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Short circuit protection; dual element fuses... Trailing Cables § 75.601-3 Short circuit protection; dual element fuses; current ratings; maximum values. Dual element fuses having adequate current-interrupting capacity shall meet the requirements for short...

  3. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

  4. A unified architecture of transcriptional regulatory elements

    DEFF Research Database (Denmark)

    Andersson, Robin; Sandelin, Albin Gustav; Danko, Charles G.

    2015-01-01

    Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However...... and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements....

  5. Towards a culturally independent participatory design method: Fusing game elements into the design process

    DEFF Research Database (Denmark)

    Jensen, Mika Yasuoka; Nakatani, Momoko; Ohno, Takehiko

    2013-01-01

    Historically, Participatory Design (PD) was introduced and applied in the Scandinavian and American context as a practical design method for collective creativity and stakeholder involvement. In this paper, by fusing game elements into PD, we suggest a first step towards a culturally independent ...... imply that the introduction of game elements allows PD to be effectively utilized in culturally diverse settings.......Historically, Participatory Design (PD) was introduced and applied in the Scandinavian and American context as a practical design method for collective creativity and stakeholder involvement. In this paper, by fusing game elements into PD, we suggest a first step towards a culturally independent PD...... method called the ICT Service Design Game to ease the prevailing concern that PD has limited applicability in other cultural settings. We conduct four experiments on ICT Service Design Game in Scandinavia and Asia to evaluate its feasibility. The experiments identify some differences in the PD process...

  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. Modular arrangement of regulatory RNA elements.

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-03-04

    Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed.

  8. RNA regulatory elements and polyadenylation in plants

    Directory of Open Access Journals (Sweden)

    Arthur G. Hunt

    2012-01-01

    Full Text Available Alternative poly(A site choice (also known as alternative polyadenylation, or APA has the potential to affect gene expression in qualitative and quantitative ways. Alternative polyadenylation may affect as many as 82% of all expressed genes in a plant. The consequences of APA include the generation of transcripts with differing 3’-UTRs (and thus differing potential regulatory potential and of transcripts with differing protein-coding potential. Genome-wide studies of possible APA suggest a linkage with pre-mRNA splicing, and indicate a coincidence of and perhaps cooperation between RNA regulatory elements that affect splicing efficiency and the recognition of novel intronic poly(A sites. These studies also raise the possibility of the existence of a novel class of polyadenylation-related cis elements that are distinct from the well-characterized plant polyadenylation signal. Many potential APA events, however, have not been associated with identifiable cis elements. The present state of the field reveals a broad scope of APA, and also numerous opportunities for research into mechanisms that govern both choice and regulation of poly(A sites in plants.

  9. Transcription factor trapping by RNA in gene regulatory elements.

    Science.gov (United States)

    Sigova, Alla A; Abraham, Brian J; Ji, Xiong; Molinie, Benoit; Hannett, Nancy M; Guo, Yang Eric; Jangi, Mohini; Giallourakis, Cosmas C; Sharp, Phillip A; Young, Richard A

    2015-11-20

    Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs. Copyright © 2015, American Association for the Advancement of Science.

  10. Thermal analysis of fused deposition modeling process using infrared thermography imaging and finite element modeling

    Science.gov (United States)

    Zhou, Xunfei; Hsieh, Sheng-Jen

    2017-05-01

    After years of development, Fused Deposition Modeling (FDM) has become the most popular technique in commercial 3D printing due to its cost effectiveness and easy-to-operate fabrication process. Mechanical strength and dimensional accuracy are two of the most important factors for reliability of FDM products. However, the solid-liquid-solid state changes of material in the FDM process make it difficult to monitor and model. In this paper, an experimental model was developed to apply cost-effective infrared thermography imaging method to acquire temperature history of filaments at the interface and their corresponding cooling mechanism. A three-dimensional finite element model was constructed to simulate the same process using element "birth and death" feature and validated with the thermal response from the experimental model. In 6 of 9 experimental conditions, a maximum of 13% difference existed between the experimental and numerical models. This work suggests that numerical modeling of FDM process is reliable and can facilitate better understanding of bead spreading and road-to-road bonding mechanics during fabrication.

  11. Comparative analysis of regulatory elements in different germin-like ...

    African Journals Online (AJOL)

    It was observed that these promoters have important regulatory elements, which are involved in various important functions. These elements have been compared on the basis of location, copy number, and distributed on positive and negative strands. It was also observed that some of these elements are common and ...

  12. REDfly: a Regulatory Element Database for Drosophila.

    Science.gov (United States)

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

    2006-02-01

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

  13. Both positive and negative regulatory elements mediate expression of a photoregulated CAB gene from Nicotiana plumbaginifolia.

    Science.gov (United States)

    Castresana, C; Garcia-Luque, I; Alonso, E; Malik, V S; Cashmore, A R

    1988-01-01

    We have analyzed promoter regulatory elements from a photoregulated CAB gene (Cab-E) isolated from Nicotiana plumbaginifolia. These studies have been performed by introducing chimeric gene constructs into tobacco cells via Agrobacterium tumefaciens-mediated transformation. Expression studies on the regenerated transgenic plants have allowed us to characterize three positive and one negative cis-acting elements that influence photoregulated expression of the Cab-E gene. Within the upstream sequences we have identified two positive regulatory elements (PRE1 and PRE2) which confer maximum levels of photoregulated expression. These sequences contain multiple repeated elements related to the sequence-ACCGGCCCACTT-. We have also identified within the upstream region a negative regulatory element (NRE) extremely rich in AT sequences, which reduces the level of gene expression in the light. We have defined a light regulatory element (LRE) within the promoter region extending from -396 to -186 bp which confers photoregulated expression when fused to a constitutive nopaline synthase ('nos') promoter. Within this region there is a 132-bp element, extending from -368 to -234 bp, which on deletion from the Cab-E promoter reduces gene expression from high levels to undetectable levels. Finally, we have demonstrated for a full length Cab-E promoter conferring high levels of photoregulated expression, that sequences proximal to the Cab-E TATA box are not replaceable by corresponding sequences from a 'nos' promoter. This contrasts with the apparent equivalence of these Cab-E and 'nos' TATA box-proximal sequences in truncated promoters conferring low levels of photoregulated expression. Images PMID:2901343

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

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    Le Roch Karine G

    2008-02-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  16. Evolutionary conservation of regulatory elements in vertebrate HOX gene clusters

    Energy Technology Data Exchange (ETDEWEB)

    Santini, Simona; Boore, Jeffrey L.; Meyer, Axel

    2003-12-31

    Due to their high degree of conservation, comparisons of DNA sequences among evolutionarily distantly-related genomes permit to identify functional regions in noncoding DNA. Hox genes are optimal candidate sequences for comparative genome analyses, because they are extremely conserved in vertebrates and occur in clusters. We aligned (Pipmaker) the nucleotide sequences of HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human and mouse (over 500 million years of evolutionary distance). We identified several highly conserved intergenic sequences, likely to be important in gene regulation. Only a few of these putative regulatory elements have been previously described as being involved in the regulation of Hox genes, while several others are new elements that might have regulatory functions. The majority of these newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac). The conserved intergenic regions located between the most rostrally expressed genes in the developing embryo are longer and better retained through evolution. We document that presumed regulatory sequences are retained differentially in either A or A clusters resulting from a genome duplication in the fish lineage. This observation supports both the hypothesis that the conserved elements are involved in gene regulation and the Duplication-Deletion-Complementation model.

  17. Co-suppression of sterol-regulatory element binding protein ...

    African Journals Online (AJOL)

    Administrator

    2011-06-22

    Jun 22, 2011 ... In Arabidopsis,. At5g35220 gene being sterol regulatory element-binding protein site 2, protease and metalloendopeptidase activity were required for chloroplast development and play a role in regulation of endodermal plastid size and number that are involved in ethylene-dependent gravitropism of light-.

  18. Identification of germline transcriptional regulatory elements in Aedes aegypti

    Science.gov (United States)

    Akbari, Omar S.; Papathanos, Philippos A.; Sandler, Jeremy E.; Kennedy, Katie; Hay, Bruce A.

    2014-02-01

    The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UDMEL, and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

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

    Science.gov (United States)

    Xue, Shifeng; Barna, Maria

    2015-01-01

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

  20. XRF determination of trace and major elements using a single-fused disc

    International Nuclear Information System (INIS)

    Thomas, I.R.; Haukka, M.T.

    1978-01-01

    A new fusion method using lithium metaborate, suitable for the determination of major and trace elements by X-ray fluorescence analysis (XRF), has proven to be of comparable accuracy to other XRF methods for the ten major rock-forming oxides. The very low dilution allows determination of trace elements with a decrease in sensitivity of about a factor of 2 compared with XRF determination using pressed-powder pellets. A feature of the method is the flexibility of sample preparation allowed: the matrix-correction parameters may be used for a wide range of dilutions (sample/flux ratios), no 'Loss' correction is necessary, and imperfect or inhomogeneous discs may be crushed and pressed pellets made of the glass powder when required. Considerable savings in the time during preparation, analysis and correction of results are possible with current automation because of streamlining procedures

  1. Massive contribution of transposable elements to mammalian regulatory sequences.

    Science.gov (United States)

    Rayan, Nirmala Arul; Del Rosario, Ricardo C H; Prabhakar, Shyam

    2016-09-01

    Barbara McClintock discovered the existence of transposable elements (TEs) in the late 1940s and initially proposed that they contributed to the gene regulatory program of higher organisms. This controversial idea gained acceptance only much later in the 1990s, when the first examples of TE-derived promoter sequences were uncovered. It is now known that half of the human genome is recognizably derived from TEs. It is thus important to understand the scope and nature of their contribution to gene regulation. Here, we provide a timeline of major discoveries in this area and discuss how transposons have revolutionized our understanding of mammalian genomes, with a special emphasis on the massive contribution of TEs to primate evolution. Our analysis of primate-specific functional elements supports a simple model for the rate at which new functional elements arise in unique and TE-derived DNA. Finally, we discuss some of the challenges and unresolved questions in the field, which need to be addressed in order to fully characterize the impact of TEs on gene regulation, evolution and disease processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

    Science.gov (United States)

    Gazestani, Vahid H; Salavati, Reza

    2015-01-01

    Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

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

    Science.gov (United States)

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

    2015-12-01

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

  4. rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

    Science.gov (United States)

    Guo, Liyuan; Wang, Jing

    2018-01-04

    Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. 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.

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

    Science.gov (United States)

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

    2004-07-01

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

  7. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

    OpenAIRE

    Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

    2006-01-01

    Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

  8. Basic elements of a regulatory programme for radiation safety

    International Nuclear Information System (INIS)

    Bilbao, A.A.

    2000-01-01

    In this lecture the objectives of IAEA TECDOC 1067: Organization and implementation of a national regulatory infrastructure governing protection against ionizing radiation and the safety of sources (1999) is presented

  9. The nomenclature of MHC class I gene regulatory regions - the case of two different downstream regulatory elements

    Czech Academy of Sciences Publication Activity Database

    Hatina, J.; Jansa, Petr; Forejt, Jiří

    2001-01-01

    Roč. 37, 12-13 (2001), s. 799-800 ISSN 0161-5890 Institutional research plan: CEZ:AV0Z5052915 Keywords : MHC I gene regulatory elements Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.973, year: 2001

  10. Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

    OpenAIRE

    Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

    2011-01-01

    An oligonucleotide representing a regulatory element of human thymidylate synthase mRNA has been crystallized as a dimer. The structure of the asymmetric dimer has been determined at 1.97 Å resolution.

  11. MicroRNAs as regulatory elements in psoriasis

    Directory of Open Access Journals (Sweden)

    Liu Yuan

    2016-01-01

    Full Text Available Psoriasis is a chronic, autoimmune, and complex genetic disorder that affects 23% of the European population. The symptoms of Psoriatic skin are inflammation, raised and scaly lesions. microRNA, which is short, nonprotein-coding, regulatory RNAs, plays critical roles in psoriasis. microRNA participates in nearly all biological processes, such as cell differentiation, development and metabolism. Recent researches reveal that multitudinous novel microRNAs have been identified in skin. Some of these substantial novel microRNAs play as a class of posttranscriptional gene regulator in skin disease, such as psoriasis. In order to insight into microRNAs biological functions and verify microRNAs biomarker, we review diverse references about characterization, profiling and subtype of microRNAs. Here we will share our opinions about how and which microRNAs are as regulatory in psoriasis.

  12. Discovery of regulatory elements is improved by a discriminatory approach

    DEFF Research Database (Denmark)

    Valen, Eivind; Sandelin, Albin; Winther, Ole

    2009-01-01

    , but contemporary methods are challenged by the size and diversity of regulatory regions in higher metazoans. Two key issues are the small amount of information contained in a pattern compared to the large promoter regions and the repetitive characteristics of genomic DNA, which both lead to "pattern drowning''. We...... demonstrate higher accuracy than the best of contemporary methods, high robustness when extending the length of the input sequences and a strong correlation between our objective function and the correct solution. Using a large background set of real promoters instead of a simplified model leads to higher...

  13. Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

    Science.gov (United States)

    Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

    2005-02-01

    cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

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

    International Nuclear Information System (INIS)

    Mao, Grace; Brody, James P.

    2007-01-01

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

  15. Predictive modelling of gene expression from transcriptional regulatory elements.

    Science.gov (United States)

    Budden, David M; Hurley, Daniel G; Crampin, Edmund J

    2015-07-01

    Predictive modelling of gene expression provides a powerful framework for exploring the regulatory logic underpinning transcriptional regulation. Recent studies have demonstrated the utility of such models in identifying dysregulation of gene and miRNA expression associated with abnormal patterns of transcription factor (TF) binding or nucleosomal histone modifications (HMs). Despite the growing popularity of such approaches, a comparative review of the various modelling algorithms and feature extraction methods is lacking. We define and compare three methods of quantifying pairwise gene-TF/HM interactions and discuss their suitability for integrating the heterogeneous chromatin immunoprecipitation (ChIP)-seq binding patterns exhibited by TFs and HMs. We then construct log-linear and ϵ-support vector regression models from various mouse embryonic stem cell (mESC) and human lymphoblastoid (GM12878) data sets, considering both ChIP-seq- and position weight matrix- (PWM)-derived in silico TF-binding. The two algorithms are evaluated both in terms of their modelling prediction accuracy and ability to identify the established regulatory roles of individual TFs and HMs. Our results demonstrate that TF-binding and HMs are highly predictive of gene expression as measured by mRNA transcript abundance, irrespective of algorithm or cell type selection and considering both ChIP-seq and PWM-derived TF-binding. As we encourage other researchers to explore and develop these results, our framework is implemented using open-source software and made available as a preconfigured bootable virtual environment. © The Author 2014. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Identification of conserved regulatory elements by comparative genome analysis

    Directory of Open Access Journals (Sweden)

    Jareborg Niclas

    2003-05-01

    Full Text Available Abstract Background For genes that have been successfully delineated within the human genome sequence, most regulatory sequences remain to be elucidated. The annotation and interpretation process requires additional data resources and significant improvements in computational methods for the detection of regulatory regions. One approach of growing popularity is based on the preferential conservation of functional sequences over the course of evolution by selective pressure, termed 'phylogenetic footprinting'. Mutations are more likely to be disruptive if they appear in functional sites, resulting in a measurable difference in evolution rates between functional and non-functional genomic segments. Results We have devised a flexible suite of methods for the identification and visualization of conserved transcription-factor-binding sites. The system reports those putative transcription-factor-binding sites that are both situated in conserved regions and located as pairs of sites in equivalent positions in alignments between two orthologous sequences. An underlying collection of metazoan transcription-factor-binding profiles was assembled to facilitate the study. This approach results in a significant improvement in the detection of transcription-factor-binding sites because of an increased signal-to-noise ratio, as demonstrated with two sets of promoter sequences. The method is implemented as a graphical web application, ConSite, which is at the disposal of the scientific community at http://www.phylofoot.org/. Conclusions Phylogenetic footprinting dramatically improves the predictive selectivity of bioinformatic approaches to the analysis of promoter sequences. ConSite delivers unparalleled performance using a novel database of high-quality binding models for metazoan transcription factors. With a dynamic interface, this bioinformatics tool provides broad access to promoter analysis with phylogenetic footprinting.

  17. 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.

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

    Science.gov (United States)

    Sim, B C; Hui, K M

    1994-12-01

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

  19. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

    Directory of Open Access Journals (Sweden)

    Jumpei Ito

    2017-07-01

    Full Text Available Human endogenous retroviruses (HERVs and other long terminal repeat (LTR-type retrotransposons (HERV/LTRs have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs. Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG, embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2, hematopoietic TFs (e.g., SPI1 (PU1, GATA1/2, and TAL1, and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/. This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into

  20. In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana.

    Science.gov (United States)

    Ibraheem, Omodele; Botha, Christiaan E J; Bradley, Graeme

    2010-12-01

    The regulation of gene expression involves a multifarious regulatory system. Each gene contains a unique combination of cis-acting regulatory sequence elements in the 5' regulatory region that determines its temporal and spatial expression. Cis-acting regulatory elements are essential transcriptional gene regulatory units; they control many biological processes and stress responses. Thus a full understanding of the transcriptional gene regulation system will depend on successful functional analyses of cis-acting elements. Cis-acting regulatory elements present within the 5' regulatory region of the sucrose transporter gene families in rice (Oryza sativa Japonica cultivar-group) and Arabidopsis thaliana, were identified using a bioinformatics approach. The possible cis-acting regulatory elements were predicted by scanning 1.5kbp of 5' regulatory regions of the sucrose transporter genes translational start sites, using Plant CARE, PLACE and Genomatix Matinspector professional databases. Several cis-acting regulatory elements that are associated with plant development, plant hormonal regulation and stress response were identified, and were present in varying frequencies within the 1.5kbp of 5' regulatory region, among which are; A-box, RY, CAT, Pyrimidine-box, Sucrose-box, ABRE, ARF, ERE, GARE, Me-JA, ARE, DRE, GA-motif, GATA, GT-1, MYC, MYB, W-box, and I-box. This result reveals the probable cis-acting regulatory elements that possibly are involved in the expression and regulation of sucrose transporter gene families in rice and Arabidopsis thaliana during cellular development or environmental stress conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Bagger, Frederik Otzen; Lauridsen, Felicia Kathrine Bratt

    2016-01-01

    Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak......-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show...... four ENCODE cell lines and four hematopoietic differentiation stages, we identified several enhancers whose regulatory activity is stage specific and correlates positively with the expression of proximal genes in a particular stage. In conclusion, our results demonstrate that PVP patterns delineate...

  3. 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

  4. Identification of functional elements and regulatory circuits by Drosophila modENCODE.

    Science.gov (United States)

    Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V; Kheradpour, Pouya; Negre, Nicolas; Eaton, Matthew L; Landolin, Jane M; Bristow, Christopher A; Ma, Lijia; Lin, Michael F; Washietl, Stefan; Arshinoff, Bradley I; Ay, Ferhat; Meyer, Patrick E; Robine, Nicolas; Washington, Nicole L; Di Stefano, Luisa; Berezikov, Eugene; Brown, Christopher D; Candeias, Rogerio; Carlson, Joseph W; Carr, Adrian; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Tolstorukov, Michael Y; Will, Sebastian; Alekseyenko, Artyom A; Artieri, Carlo; Booth, Benjamin W; Brooks, Angela N; Dai, Qi; Davis, Carrie A; Duff, Michael O; Feng, Xin; Gorchakov, Andrey A; Gu, Tingting; Henikoff, Jorja G; Kapranov, Philipp; Li, Renhua; MacAlpine, Heather K; Malone, John; Minoda, Aki; Nordman, Jared; Okamura, Katsutomo; Perry, Marc; Powell, Sara K; Riddle, Nicole C; Sakai, Akiko; Samsonova, Anastasia; Sandler, Jeremy E; Schwartz, Yuri B; Sher, Noa; Spokony, Rebecca; Sturgill, David; van Baren, Marijke; Wan, Kenneth H; Yang, Li; Yu, Charles; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca; Ahmad, Kami; Andrews, Justen; Berger, Bonnie; Brenner, Steven E; Brent, Michael R; Cherbas, Lucy; Elgin, Sarah C R; Gingeras, Thomas R; Grossman, Robert; Hoskins, Roger A; Kaufman, Thomas C; Kent, William; Kuroda, Mitzi I; Orr-Weaver, Terry; Perrimon, Norbert; Pirrotta, Vincenzo; Posakony, James W; Ren, Bing; Russell, Steven; Cherbas, Peter; Graveley, Brenton R; Lewis, Suzanna; Micklem, Gos; Oliver, Brian; Park, Peter J; Celniker, Susan E; Henikoff, Steven; Karpen, Gary H; Lai, Eric C; MacAlpine, David M; Stein, Lincoln D; White, Kevin P; Kellis, Manolis

    2010-12-24

    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

  5. 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.

  6. Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.

    Science.gov (United States)

    Berghoff, Bork A; Hoekzema, Mirthe; Aulbach, Lena; Wagner, E Gerhart H

    2017-03-01

    Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity. © 2016 John Wiley & Sons Ltd.

  7. Deciphering RNA regulatory elements in trypanosomatids: one piece at a time or genome-wide?

    Science.gov (United States)

    Gazestani, Vahid H; Lu, Zhiquan; Salavati, Reza

    2014-05-01

    Morphological and metabolic changes in the life cycle of Trypanosoma brucei are accomplished by precise regulation of hundreds of genes. In the absence of transcriptional control, RNA-binding proteins (RBPs) shape the structure of gene regulatory maps in this organism, but our knowledge about their target RNAs, binding sites, and mechanisms of action is far from complete. Although recent technological advances have revolutionized the RBP-based approaches, the main framework for the RNA regulatory element (RRE)-based approaches has not changed over the last two decades in T. brucei. In this Opinion, after highlighting the current challenges in RRE inference, we explain some genome-wide solutions that can significantly boost our current understanding about gene regulatory networks in T. brucei. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome.

    Science.gov (United States)

    Klann, Tyler S; Black, Joshua B; Chellappan, Malathi; Safi, Alexias; Song, Lingyun; Hilton, Isaac B; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

    2017-06-01

    Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. CRISPR-Cas9-based epigenome editing technologies have enabled precise perturbation of the activity of specific regulatory elements. Here we describe CRISPR-Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. Using dCas9 KRAB repressor and dCas9 p300 activator constructs and lentiviral single guide RNA libraries to target DNase I hypersensitive sites surrounding a gene of interest, we carried out both loss- and gain-of-function screens to identify regulatory elements for the β-globin and HER2 loci in human cells. CERES readily identified known and previously unidentified regulatory elements, some of which were dependent on cell type or direction of perturbation. This technology allows the high-throughput functional annotation of putative regulatory elements in their native chromosomal context.

  9. PlantCARE, a plant cis-acting regulatory element database

    OpenAIRE

    Rombauts, Stephane; Déhais, Patrice; Van Montagu, Marc; Rouzé, Pierre

    1999-01-01

    PlantCARE is a database of plant cis- acting regulatory elements, enhancers and repressors. Besides the transcription motifs found on a sequence, it also offers a link to the EMBL entry that contains the full gene sequence as well as a description of the conditions in which a motif becomes functional. The information on these sites is given by matrices, consensus and individual site sequences on particular genes, depending on the available information. PlantCARE is a relational database avail...

  10. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.

    Science.gov (United States)

    Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A

    2015-07-01

    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2018-01-01

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

  12. 5' Region of the human interleukin 4 gene: structure and potential regulatory elements

    Energy Technology Data Exchange (ETDEWEB)

    Eder, A; Krafft-Czepa, H; Krammer, P H

    1988-01-25

    The lymphokine Interleukin 4 (IL-4) is secreted by antigen or mitogen activated T lymphocytes. IL-4 stimulates activation and differentiation of B lymphocytes and growth of T lymphocytes and mast cells. The authors isolated the human IL-4 gene from a lambda EMBL3 genomic library. As a probe they used a synthetic oligonucleotide spanning position 40 to 79 of the published IL-4 cDNA sequence. The 5' promoter region contains several sequence elements which may have a cis-acting regulatory function for IL-4 gene expression. These elements include a TATA-box, three CCAAT-elements (two are on the non-coding strand) and an octamer motif. A comparison of the 5' flanking region of the human murine IL-4 gene (4) shows that the region between position -306 and +44 is highly conserved (83% homology).

  13. 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.

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

    OpenAIRE

    Kreiman, Gabriel

    2004-01-01

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

  15. FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis

    Directory of Open Access Journals (Sweden)

    Goranovič Dušan

    2012-10-01

    Full Text Available Abstract Background FK506 (Tacrolimus is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it is reasonable to expect complex regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on the final yield of target product and can play an important role in development of industrial bioprocesses. Results Three putative regulatory elements, namely fkbR, belonging to the LysR-type family, fkbN, a large ATP-binding regulator of the LuxR family (LAL-type and allN, a homologue of AsnC family regulatory proteins, were identified in the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488, a progenitor of industrial strains used for production of FK506. Inactivation of fkbN caused a complete disruption of FK506 biosynthesis, while inactivation of fkbR resulted in about 80% reduction of FK506 yield. No functional role in the regulation of the FK506 gene cluster has been observed for the allN gene. Using RT-PCR and a reporter system based on a chalcone synthase rppA, we demonstrated, that in the wild type as well as in fkbN- and fkbR-inactivated strains, fkbR is transcribed in all stages of cultivation, even before the onset of FK506 production, whereas fkbN expression is initiated approximately with the initiation of FK506 production. Surprisingly, inactivation of fkbN (or fkbR does not abolish the transcription of the genes in the FK506 gene cluster in general, but may reduce expression of some of the tested biosynthetic genes. Finally, introduction of a second copy of the fkbR or fkbN genes under the control of the strong ermE* promoter into the wild type strain resulted in 30% and 55% of yield improvement, respectively. Conclusions Our results clearly demonstrate the positive regulatory role of fkbR and fkbN genes in FK506 biosynthesis in S. tsukubaensis NRRL 18488. We

  16. 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

  17. Effects of sterol regulatory element-binding protein (SREBP in chickens

    Directory of Open Access Journals (Sweden)

    Alipour Fahimeh

    2012-02-01

    Full Text Available Abstract Sterol regulatory element binding protein- 1 and -2 (SREBP-1 and -2 are key transcription factors involved in the biosynthesis of cholesterol and fatty acids. The SREBP have mostly been studied in rodents in which lipogenesis is regulated in both liver and adipose tissue. There is, though, a paucity of information on birds, in which lipogenesis occurs essentially in the liver as in humans. Since a prelude to the investigation of the role of SREBP in lipid metabolism regulation in chicken, we review Size and Tissue expression Pattern of SREBP and role of this protein in chickens.

  18. Genome-wide discovery of drug-dependent human liver regulatory elements.

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    Robin P Smith

    2014-10-01

    Full Text Available Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR and three active regulatory marks (p300, H3K4me1, H3K27ac on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4% that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

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

    Science.gov (United States)

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

    1993-01-01

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

  20. Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements.

    Science.gov (United States)

    Hayes, James E; Trynka, Gosia; Vijai, Joseph; Offit, Kenneth; Raychaudhuri, Soumya; Klein, Robert J

    2015-01-01

    Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkin's lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well.

  1. Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

    2017-11-10

    Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31 + CD144 + ), cardiac progenitor cells (Sca-1 + ), fibroblasts (DDR2 + ), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering

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

    Science.gov (United States)

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

    2013-10-01

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

  3. Orientation-dependent interaction between Drosophila insulators is a property of this class of regulatory elements.

    Science.gov (United States)

    Kyrchanova, Olga; Chetverina, Darya; Maksimenko, Oksana; Kullyev, Andrey; Georgiev, Pavel

    2008-12-01

    Insulators are defined as a class of regulatory elements that delimit independent transcriptional domains within eukaryotic genomes. According to previous data, an interaction (pairing) between some Drosophila insulators can support distant activation of a promoter by an enhancer. Here, we have demonstrated that pairs of well-studied insulators such as scs-scs, scs'-scs', 1A2-1A2 and Wari-Wari support distant activation of the white promoter by the yeast GAL4 activator in an orientation-dependent manner. The same is true for the efficiency of the enhancer that stimulates white expression in the eyes. In all insulator pairs tested, stimulation of the white gene was stronger when insulators were inserted between the eye enhancer or GAL4 and the white promoter in opposite orientations relative to each other. As shown previously, Zw5, Su(Hw) and dCTCF proteins are required for the functioning of different insulators that do not interact with each other. Here, strong functional interactions have been revealed between DNA fragments containing binding sites for either Zw5 or Su(Hw) or dCTCF protein but not between heterologous binding sites [Zw5-Su(Hw), dCTCF-Su(Hw), or dCTCF-Zw5]. These results suggest that insulator proteins can support selective interactions between distant regulatory elements.

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

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    Arindam Deb

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

  5. The 3' untranslated region of human Cyclin-Dependent Kinase 5 Regulatory subunit 1 contains regulatory elements affecting transcript stability

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    Ratti Antonia

    2007-12-01

    Full Text Available Abstract Background CDK5R1 plays a central role in neuronal migration and differentiation during central nervous system development. CDK5R1 has been implicated in neurodegenerative disorders and proposed as a candidate gene for mental retardation. The remarkable size of CDK5R1 3'-untranslated region (3'-UTR suggests a role in post-transcriptional regulation of CDK5R1 expression. Results The bioinformatic study shows a high conservation degree in mammals and predicts several AU-Rich Elements (AREs. The insertion of CDK5R1 3'-UTR into luciferase 3'-UTR causes a decreased luciferase activity in four transfected cell lines. We identified 3'-UTR subregions which tend to reduce the reporter gene expression, sometimes in a cell line-dependent manner. In most cases the quantitative analysis of luciferase mRNA suggests that CDK5R1 3'-UTR affects mRNA stability. A region, leading to a very strong mRNA destabilization, showed a significantly low half-life, indicating an accelerated mRNA degradation. The 3' end of the transcript, containing a class I ARE, specifically displays a stabilizing effect in neuroblastoma cell lines. We also observed the interaction of the stabilizing neuronal RNA-binding proteins ELAV with the CDK5R1 transcript in SH-SY5Y cells and identified three 3'-UTR sub-regions showing affinity for ELAV proteins. Conclusion Our findings evince the presence of both destabilizing and stabilizing regulatory elements in CDK5R1 3'-UTR and support the hypothesis that CDK5R1 gene expression is post-transcriptionally controlled in neurons by ELAV-mediated mechanisms. This is the first evidence of the involvement of 3'-UTR in the modulation of CDK5R1 expression. The fine tuning of CDK5R1 expression by 3'-UTR may have a role in central nervous system development and functioning, with potential implications in neurodegenerative and cognitive disorders.

  6. 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

  7. Genome-wide identification of regulatory elements and reconstruction of gene regulatory networks of the green alga Chlamydomonas reinhardtii under carbon deprivation.

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    Flavia Vischi Winck

    Full Text Available The unicellular green alga Chlamydomonas reinhardtii is a long-established model organism for studies on photosynthesis and carbon metabolism-related physiology. Under conditions of air-level carbon dioxide concentration [CO2], a carbon concentrating mechanism (CCM is induced to facilitate cellular carbon uptake. CCM increases the availability of carbon dioxide at the site of cellular carbon fixation. To improve our understanding of the transcriptional control of the CCM, we employed FAIRE-seq (formaldehyde-assisted Isolation of Regulatory Elements, followed by deep sequencing to determine nucleosome-depleted chromatin regions of algal cells subjected to carbon deprivation. Our FAIRE data recapitulated the positions of known regulatory elements in the promoter of the periplasmic carbonic anhydrase (Cah1 gene, which is upregulated during CCM induction, and revealed new candidate regulatory elements at a genome-wide scale. In addition, time series expression patterns of 130 transcription factor (TF and transcription regulator (TR genes were obtained for cells cultured under photoautotrophic condition and subjected to a shift from high to low [CO2]. Groups of co-expressed genes were identified and a putative directed gene-regulatory network underlying the CCM was reconstructed from the gene expression data using the recently developed IOTA (inner composition alignment method. Among the candidate regulatory genes, two members of the MYB-related TF family, Lcr1 (Low-CO 2 response regulator 1 and Lcr2 (Low-CO2 response regulator 2, may play an important role in down-regulating the expression of a particular set of TF and TR genes in response to low [CO2]. The results obtained provide new insights into the transcriptional control of the CCM and revealed more than 60 new candidate regulatory genes. Deep sequencing of nucleosome-depleted genomic regions indicated the presence of new, previously unknown regulatory elements in the C. reinhardtii genome

  8. A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism.

    Science.gov (United States)

    Visootsat, Akasit; Payungporn, Sunchai; T-Thienprasert, Nattanan P

    2015-12-01

    Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.

  9. Fusion algebra and fusing matrices

    International Nuclear Information System (INIS)

    Gao Yihong; Li Miao; Yu Ming.

    1989-09-01

    We show that the Wilson line operators in topological field theories form a fusion algebra. In general, the fusion algebra is a relation among the fusing (F) matrices. In the case of the SU(2) WZW model, some special F matrix elements are found in this way, and the remaining F matrix elements are then determined up to a sign. In addition, the S(j) modular transformation of the one point blocks on the torus is worked out. Our results are found to agree with those obtained from the quantum group method. (author). 24 refs

  10. Regulatory inspection practices on fuel elements and core lay-out at NPPs

    International Nuclear Information System (INIS)

    Van Binnebeek, J.J.; Liuhto, Pekka; Badel, D.; Klonk, H.; Seidel, F.; Fichtinger, G.; Manzella, P.; Koizumi, Hiroyoshi; Delgado, Jose Luis; Gutierrez Ruiz, Luis Miguel; Bouvrie, E. des; Gil, J.; Forsberg, Staffan; Wand, H.; Warren, Tom; Gallo, R.

    1998-01-01

    The basic description of the reactor core of a nuclear power plant (NPP) is an important part of the Safety Analysis Report in all countries. Due to increased interest by regulatory authorities in the Member countries, in 1996 WGIP proposed looking at inspection aspects on fuel elements and core lay-out at nuclear power plants. The CNRA subsequently approved proceeding with this report. The report deals primarily with inspection practices and inspection requirements during nuclear power plant (NPP) operation with special emphasis on refuelling procedures. All license related topics, such as fuel and core design (mechanical, neutronic, thermal-hydraulic), as well as inspection philosophy and practices on fuel fabrication are included as appropriate serving as background information and may not be completely described. WGIP members describe their country's inspection programme according to the structure of a questionnaire (appendix 1). The individual contributions are contained in the appendix 2 and are compiled within the main chapters (1 through 3). Report Structure: 1. Licensing and Quality Assurance (QA) requirements for nuclear fuel; 2. Regulatory inspection programme during NPP operation and refuelling outages; 3. Procedures for inspection practices and inspection programme. Appendix: Questionnaire and Country specific contributions. Contributions are presented by Belgium, Finland, France, Germany, Hungary, Italy, Japan, Mexico, The Netherlands, Spain, Sweden, Switzerland, United Kingdom, USA

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

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    Junhua Li

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-04-19

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

  13. Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6

    International Nuclear Information System (INIS)

    Wu, Tzyy-Choou.

    1989-01-01

    The structure and function of the transcriptional regulatory region of human papillomavirus type 6 (HPV-6) has been investigated. To investigate tissue specific gene expression, a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in plastic-embedded tissue sections of genital and respiratory tract papillomata by using in situ hybridization and immunoperoxidase assays has been developed. This method, using ultrathin sections and strand-specific 3 H labeled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution, and the modified immunocytochemistry provides better sensitivity. The results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. To study the tissue tropism of HPV-6 at the level of regulation of viral gene expression, the polymerase chain reaction was used to isolate the noncoding region (NCR) of HPV-6 in independent isolates. Nucleotide sequence analysis of molecularly cloned DNA identified base substitutions, deletions/insertions and tandem duplications. Transcriptional regulatory elements in the NCR were assayed in recombinant plasmids containing the bacterial gene for chloramphenicol acetyl transferase

  14. Regulatory elements involved in tax-mediated transactivation of the HTLV-I LTR.

    Science.gov (United States)

    Seeler, J S; Muchardt, C; Podar, M; Gaynor, R B

    1993-10-01

    HTLV-I is the etiologic agent of adult T-cell leukemia. In this study, we investigated the regulatory elements and cellular transcription factors which function in modulating HTLV-I gene expression in response to the viral transactivator protein, tax. Transfection experiments into Jurkat cells of a variety of site-directed mutants in the HTLV-1 LTR indicated that each of the three motifs A, B, and C within the 21-bp repeats, the binding sites for the Ets family of proteins, and the TATA box all influenced the degree of tax-mediated activation. Tax is also able to activate gene expression of other viral and cellular promoters. Tax activation of the IL-2 receptor and the HIV-1 LTR is mediated through NF-kappa B motifs. Interestingly, sequences in the 21-bp repeat B and C motifs contain significant homology with NF-kappa B regulatory elements. We demonstrated that an NF-kappa B binding protein, PRDII-BF1, but not the rel protein, bound to the B and C motifs in the 21-bp repeat. PRDII-BF1 was also able to stimulate activation of HTLV-I gene expression by tax. The role of the Ets proteins on modulating tax activation was also studied. Ets 1 but not Ets 2 was capable of increasing the degree of tax activation of the HTLV-I LTR. These results suggest that tax activates gene expression by either direct or indirect interaction with several cellular transcription factors that bind to the HTLV-I LTR.

  15. HBVRegDB: Annotation, comparison, detection and visualization of regulatory elements in hepatitis B virus sequences

    Directory of Open Access Journals (Sweden)

    Firth Andrew E

    2007-12-01

    Full Text Available Abstract Background The many Hepadnaviridae sequences available have widely varied functional annotation. The genomes are very compact (~3.2 kb but contain multiple layers of functional regulatory elements in addition to coding regions. Key regions are subject to purifying selection, as mutations in these regions will produce non-functional viruses. Results These genomic sequences have been organized into a structured database to facilitate research at the molecular level. HBVRegDB is a comparative genomic analysis tool with an integrated underlying sequence database. The database contains genomic sequence data from representative viruses. In addition to INSDC and RefSeq annotation, HBVRegDB also contains expert and systematically calculated annotations (e.g. promoters and comparative genome analysis results (e.g. blastn, tblastx. It also contains analyses based on curated HBV alignments. Information about conserved regions – including primary conservation (e.g. CDS-Plotcon and RNA secondary structure predictions (e.g. Alidot – is integrated into the database. A large amount of data is graphically presented using the GBrowse (Generic Genome Browser adapted for analysis of viral genomes. Flexible query access is provided based on any annotated genomic feature. Novel regulatory motifs can be found by analysing the annotated sequences. Conclusion HBVRegDB serves as a knowledge database and as a comparative genomic analysis tool for molecular biologists investigating HBV. It is publicly available and complementary to other viral and HBV focused datasets and tools http://hbvregdb.otago.ac.nz. The availability of multiple and highly annotated sequences of viral genomes in one database combined with comparative analysis tools facilitates detection of novel genomic elements.

  16. Human polyomavirus JCV late leader peptide region contains important regulatory elements

    International Nuclear Information System (INIS)

    Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh; Khalili, Kamel; Safak, Mahmut

    2006-01-01

    Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader

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

    Science.gov (United States)

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

    2012-09-01

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

  18. FARE-CAFE: a database of functional and regulatory elements of cancer-associated fusion events.

    Science.gov (United States)

    Korla, Praveen Kumar; Cheng, Jack; Huang, Chien-Hung; Tsai, Jeffrey J P; Liu, Yu-Hsuan; Kurubanjerdjit, Nilubon; Hsieh, Wen-Tsong; Chen, Huey-Yi; Ng, Ka-Lok

    2015-01-01

    Chromosomal translocation (CT) is of enormous clinical interest because this disorder is associated with various major solid tumors and leukemia. A tumor-specific fusion gene event may occur when a translocation joins two separate genes. Currently, various CT databases provide information about fusion genes and their genomic elements. However, no database of the roles of fusion genes, in terms of essential functional and regulatory elements in oncogenesis, is available. FARE-CAFE is a unique combination of CTs, fusion proteins, protein domains, domain-domain interactions, protein-protein interactions, transcription factors and microRNAs, with subsequent experimental information, which cannot be found in any other CT database. Genomic DNA information including, for example, manually collected exact locations of the first and second break points, sequences and karyotypes of fusion genes are included. FARE-CAFE will substantially facilitate the cancer biologist's mission of elucidating the pathogenesis of various types of cancer. This database will ultimately help to develop 'novel' therapeutic approaches. Database URL: http://ppi.bioinfo.asia.edu.tw/FARE-CAFE. © The Author(s) 2015. Published by Oxford University Press.

  19. Identification of functional elements and regulatory circuits by Drosophila modENCODE

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V.; Kheradpour, Pouya; Negre, Nicolas; Eaton, Matthew L.; Landolin, Jane M.; Bristow, Christopher A.; Ma, Lijia; Lin, Michael F.; Washietl, Stefan; Arshinoff, Bradley I.; Ay, Ferhat; Meyer, Patrick E.; Robine, Nicolas; Washington, Nicole L.; Stefano, Luisa Di; Berezikov, Eugene; Brown, Christopher D.; Candeias, Rogerio; Carlson, Joseph W.; Carr, Adrian; Jungreis, Irwin; Marbach, Daniel; Sealfon, Rachel; Tolstorukov, Michael Y.; Will, Sebastian; Alekseyenko, Artyom A.; Artieri, Carlo; Booth, Benjamin W.; Brooks, Angela N.; Dai, Qi; Davis, Carrie A.; Duff, Michael O.; Feng, Xin; Gorchakov, Andrey A.; Gu, Tingting; Henikoff, Jorja G.; Kapranov, Philipp; Li, Renhua; MacAlpine, Heather K.; Malone, John; Minoda, Aki; Nordman, Jared; Okamura, Katsutomo; Perry, Marc; Powell, Sara K.; Riddle, Nicole C.; Sakai, Akiko; Samsonova, Anastasia; Sandler, Jeremy E.; Schwartz, Yuri B.; Sher, Noa; Spokony, Rebecca; Sturgill, David; van Baren, Marijke; Wan, Kenneth H.; Yang, Li; Yu, Charles; Feingold, Elise; Good, Peter; Guyer, Mark; Lowdon, Rebecca; Ahmad, Kami; Andrews, Justen; Berger, Bonnie; Brenner, Steven E.; Brent, Michael R.; Cherbas, Lucy; Elgin, Sarah C. R.; Gingeras, Thomas R.; Grossman, Robert; Hoskins, Roger A.; Kaufman, Thomas C.; Kent, William; Kuroda, Mitzi I.; Orr-Weaver, Terry; Perrimon, Norbert; Pirrotta, Vincenzo; Posakony, James W.; Ren, Bing; Russell, Steven; Cherbas, Peter; Graveley, Brenton R.; Lewis, Suzanna; Micklem, Gos; Oliver, Brian; Park, Peter J.; Celniker, Susan E.; Henikoff, Steven; Karpen, Gary H.; Lai, Eric C.; MacAlpine, David M.; Stein, Lincoln D.; White, Kevin P.; Kellis, Manolis

    2010-12-22

    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation. Several years after the complete genetic sequencing of many species, it is still unclear how to translate genomic information into a functional map of cellular and developmental programs. The Encyclopedia of DNA Elements (ENCODE) (1) and model organism ENCODE (modENCODE) (2) projects use diverse genomic assays to comprehensively annotate the Homo sapiens (human), Drosophila melanogaster (fruit fly), and Caenorhabditis elegans (worm) genomes, through systematic generation and computational integration of functional genomic data sets. Previous genomic studies in flies have made seminal contributions to our understanding of basic biological mechanisms and genome functions, facilitated by genetic, experimental, computational, and manual annotation of the euchromatic and heterochromatic genome (3), small genome size, short life cycle, and a deep knowledge of development, gene function, and chromosome biology. The functions

  20. Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

    Directory of Open Access Journals (Sweden)

    Yoichiro Shibata

    2012-06-01

    Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

  1. Functional Use Database (FUse)

    Data.gov (United States)

    U.S. Environmental Protection Agency — There are five different files for this dataset: 1. A dataset listing the reported functional uses of chemicals (FUse) 2. All 729 ToxPrint descriptors obtained from...

  2. Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

    Science.gov (United States)

    Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William

    2017-05-01

    Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m 2 ) and controls (28.58 ± 2.62 kg/m 2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m 2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element

  3. Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

    Science.gov (United States)

    Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

    2012-09-01

    Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.

  4. Casein kinase 1 regulates sterol regulatory element-binding protein (SREBP) to control sterol homeostasis.

    Science.gov (United States)

    Brookheart, Rita T; Lee, Chih-Yung S; Espenshade, Peter J

    2014-01-31

    Sterol homeostasis is tightly controlled by the sterol regulatory element-binding protein (SREBP) transcription factor that is highly conserved from fungi to mammals. In fission yeast, SREBP functions in an oxygen-sensing pathway to promote adaptation to decreased oxygen supply that limits oxygen-dependent sterol synthesis. Low oxygen stimulates proteolytic cleavage of the SREBP homolog Sre1, generating the active transcription factor Sre1N that drives expression of sterol biosynthetic enzymes. In addition, low oxygen increases the stability and DNA binding activity of Sre1N. To identify additional signals controlling Sre1 activity, we conducted a genetic overexpression screen. Here, we describe our isolation and characterization of the casein kinase 1 family member Hhp2 as a novel regulator of Sre1N. Deletion of Hhp2 increases Sre1N protein stability and ergosterol levels in the presence of oxygen. Hhp2-dependent Sre1N degradation by the proteasome requires Hhp2 kinase activity, and Hhp2 binds and phosphorylates Sre1N at specific residues. Our results describe a role for casein kinase 1 as a direct regulator of sterol homeostasis. Given the role of mammalian Hhp2 homologs, casein kinase 1δ and 1ε, in regulation of the circadian clock, these findings may provide a mechanism for coordinating circadian rhythm and lipid metabolism.

  5. Coordinate Regulation of Yeast Sterol Regulatory Element-binding Protein (SREBP) and Mga2 Transcription Factors.

    Science.gov (United States)

    Burr, Risa; Stewart, Emerson V; Espenshade, Peter J

    2017-03-31

    The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeast Schizosaccharomyces pombe in a manner analogous to the mammalian sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 transcription factors. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, whereas Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1. Therefore, it is unclear whether and how these two related pathways are coordinated to maintain lipid balance in fission yeast. Previously, we showed that Sre1 cleavage is defective in the absence of mga2 Here, we report that this defect is due to deficient unsaturated fatty acid synthesis, resulting in aberrant membrane transport. This defect is recapitulated by treatment with the fatty acid synthase inhibitor cerulenin and is rescued by addition of exogenous unsaturated fatty acids. Furthermore, sterol synthesis inhibition blocks Mga2 pathway activation. Together, these data demonstrate that Sre1 and Mga2 are each regulated by the lipid product of the other transcription factor pathway, providing a source of coordination for these two branches of lipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. DREAM (Downstream Regulatory Element Antagonist Modulator contributes to synaptic depression and contextual fear memory

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2010-01-01

    Full Text Available Abstract The downstream regulatory element antagonist modulator (DREAM, a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM, we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD but not long-term potentiation (LTP, was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory.

  7. Understanding Epistatic Interactions between Genes Targeted by Non-coding Regulatory Elements in Complex Diseases

    Directory of Open Access Journals (Sweden)

    Min Kyung Sung

    2014-12-01

    Full Text Available Genome-wide association studies have proven the highly polygenic architecture of complex diseases or traits; therefore, single-locus-based methods are usually unable to detect all involved loci, especially when individual loci exert small effects. Moreover, the majority of associated single-nucleotide polymorphisms resides in non-coding regions, making it difficult to understand their phenotypic contribution. In this work, we studied epistatic interactions associated with three common diseases using Korea Association Resource (KARE data: type 2 diabetes mellitus (DM, hypertension (HT, and coronary artery disease (CAD. We showed that epistatic single-nucleotide polymorphisms (SNPs were enriched in enhancers, as well as in DNase I footprints (the Encyclopedia of DNA Elements [ENCODE] Project Consortium 2012, which suggested that the disruption of the regulatory regions where transcription factors bind may be involved in the disease mechanism. Accordingly, to identify the genes affected by the SNPs, we employed whole-genome multiple-cell-type enhancer data which discovered using DNase I profiles and Cap Analysis Gene Expression (CAGE. Assigned genes were significantly enriched in known disease associated gene sets, which were explored based on the literature, suggesting that this approach is useful for detecting relevant affected genes. In our knowledge-based epistatic network, the three diseases share many associated genes and are also closely related with each other through many epistatic interactions. These findings elucidate the genetic basis of the close relationship between DM, HT, and CAD.

  8. Nsite, NsiteH and NsiteM Computer Tools for Studying Tran-scription Regulatory Elements

    KAUST Repository

    Shahmuradov, Ilham

    2015-07-02

    Summary: Gene transcription is mostly conducted through interactions of various transcription factors and their binding sites on DNA (regulatory elements, REs). Today, we are still far from understanding the real regulatory content of promoter regions. Computer methods for identification of REs remain a widely used tool for studying and understanding transcriptional regulation mechanisms. The Nsite, NsiteH and NsiteM programs perform searches for statistically significant (non-random) motifs of known human, animal and plant one-box and composite REs in a single genomic sequence, in a pair of aligned homologous sequences and in a set of functionally related sequences, respectively.

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

    Science.gov (United States)

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

    2009-07-01

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

  10. Defective distal regulatory element at the 5' upstream of rat prolactin gene of steroid-nonresponsive GH-subclone.

    Science.gov (United States)

    Kumar, V; Wong, D T; Pasion, S G; Biswas, D K

    1987-12-08

    The prolactin-nonproducing (PRL-) GH cell strains (rat pituitary tumor cells in culture). GH12C1 and F1BGH12C1, do not respond to steroid hormones estradiol or hydrocortisone (HC). However, the stimulatory effect of estradiol and the inhibitory effect of hydrocortisone on prolactin synthesis can be demonstrated in the prolactin-producing GH cell strain, GH4C1. In this investigation we have examined the 5' end flanking region of rat prolactin (rat PRL) gene of steroid-responsive, GH4C1 cells to identify the positive and negative regulatory elements and to verify the status of these elements in steroid-nonresponsive F1BGH12C1 cells. Results presented in this report demonstrate that the basel level expression of the co-transferred Neo gene (neomycin phosphoribosyl transferase) is modulated by the distal upstream regulatory elements of rat PRL gene in response to steroid hormones. The expression of adjacent Neo gene is inhibited by dexamethasone and is stimulated by estradiol in transfectants carrying distal regulatory elements (SRE) of steroid-responsive cells. These responses are not observed in transfectants with the rat PRL upstream sequences derived from steroid-nonresponsive cells. The basal level expression of the host cell alpha-2 tubulin gene is not affected by dexamethasone. We report here the identification of the distal steroid regulatory element (SRE) located between 3.8 and 7.8 kb upstream of the transcription initiation site of rat PRL gene. Both the positive and the negative effects of steroid hormones can be identified within this upstream sequence. This distal SRE appears to be nonfunctional in steroid-nonresponsive cells. Though the proximal SRE is functional, the defect in the distal SRE makes the GH substrain nonresponsive to steroid hormones. These results suggest that both the proximal and the distal SREs are essential for the mediation of action of steroid hormones in GH cells.

  11. Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulate Myelination in Zebrafish

    Directory of Open Access Journals (Sweden)

    Yuhei Nishimura

    2016-07-01

    Full Text Available Oligodendrocytes are major myelin-producing cells and play essential roles in the function of a healthy nervous system. However, they are also one of the most vulnerable neural cell types in the central nervous system (CNS, and myelin abnormalities in the CNS are found in a wide variety of neurological disorders, including multiple sclerosis, adrenoleukodystrophy, and schizophrenia. There is an urgent need to identify small molecular weight compounds that can stimulate myelination. In this study, we performed comparative transcriptome analysis to identify pharmacodynamic effects common to miconazole and clobetasol, which have been shown to stimulate myelination by mouse oligodendrocyte progenitor cells (OPCs. Of the genes differentially expressed in both miconazole- and clobetasol-treated mouse OPCs compared with untreated cells, we identified differentially expressed genes (DEGs common to both drug treatments. Gene ontology analysis revealed that these DEGs are significantly associated with the sterol biosynthetic pathway, and further bioinformatics analysis suggested that sterol regulatory element binding factors (SREBFs might be key upstream regulators of the DEGs. In silico screening of a public database for chemicals associated with SREBF activation identified fenofibrate, a peroxisome proliferator-activated receptor α (PPARα agonist, as a drug that increases the expression of known SREBF targets, raising the possibility that fenofibrate may also stimulate myelination. To test this, we performed in vivo imaging of zebrafish expressing a fluorescent reporter protein under the control of the myelin basic protein (mbp promoter. Treatment of zebrafish with fenofibrate significantly increased expression of the fluorescent reporter compared with untreated zebrafish. This increase was attenuated by co-treatment with fatostatin, a specific inhibitor of SREBFs, confirming that the fenofibrate effect was mediated via SREBFs. Furthermore, incubation

  12. Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

    Directory of Open Access Journals (Sweden)

    Andreas Bitter

    2015-01-01

    Full Text Available Background/Aims: Sterol regulatory element-binding protein (SREBP 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

  13. Fuse Modeling for Reliability Study of Power Electronic Circuits

    DEFF Research Database (Denmark)

    Bahman, Amir Sajjad; Iannuzzo, Francesco; Blaabjerg, Frede

    2017-01-01

    This paper describes a comprehensive modeling approach on reliability of fuses used in power electronic circuits. When fuses are subjected to current pulses, cyclic temperature stress is introduced to the fuse element and will wear out the component. Furthermore, the fuse may be used in a large......, and rated voltage/current are opposed to shift in time to effect early breaking during the normal operation of the circuit. Therefore, in such cases, a reliable protection required for the other circuit components will not be achieved. The thermo-mechanical models, fatigue analysis and thermo...

  14. Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA-protein binding sites.

    Science.gov (United States)

    Li, Yang Eric; Xiao, Mu; Shi, Binbin; Yang, Yu-Cheng T; Wang, Dong; Wang, Fei; Marcia, Marco; Lu, Zhi John

    2017-09-08

    Crosslinking immunoprecipitation sequencing (CLIP-seq) technologies have enabled researchers to characterize transcriptome-wide binding sites of RNA-binding protein (RBP) with high resolution. We apply a soft-clustering method, RBPgroup, to various CLIP-seq datasets to group together RBPs that specifically bind the same RNA sites. Such combinatorial clustering of RBPs helps interpret CLIP-seq data and suggests functional RNA regulatory elements. Furthermore, we validate two RBP-RBP interactions in cell lines. Our approach links proteins and RNA motifs known to possess similar biochemical and cellular properties and can, when used in conjunction with additional experimental data, identify high-confidence RBP groups and their associated RNA regulatory elements.

  15. Exploding metallic fuse physics experiments

    International Nuclear Information System (INIS)

    Goforth, J.H.; Hackett, K.E.; Lindemuth, I.R.; Lopez, E.A.; McCullough, W.F.; Dona, H.; Reinovsky, R.E.

    1986-01-01

    The ultimate practicality of inductive pulse compression systems as drivers for energetic plasma implosions hinges on the development of a suitable opening switch capable of interrupting tons of megamp currents in time scales of a few hundred nanoseconds while withstanding L(dI/dt) voltages of a megavolt or more. 1. Exploding metallic foils (fuses) are a candidate for switching elements in the inductive store pulsed power systems used in the Los Alamos and Air Force Weapons Laboratory foil implosion X-ray source generation programs. To verify or modify new theoretical and computational predictions about the electrical and hydrodynamic behavior of exploding metallic foils used as fuses. The authors have initiated a new series of small scale capacitor bank driven fuse experiments. The experiments represent an extension of previous experiments, but in the new series a foil geometry more amenable to theoretical and computational analysis is used. The metallic foil (aluminum or copper) is laminated between two thin layers of insulating material (mylar or kaptan). Adjacent to one layer of insulation is a much heavier backing insulator (polyethylene) whereas air is adjacent to the other layer. Because of the differing masses on the two sides of the foil, the foil expansion and hydrodynamic motion is essentially one-sided and the layer of insulation on the expanding side becomes a readily-characterizable ''flyer'' which provides a controlled amount of hydrodynamic tamping. In addition to the usual voltage, current, and dI/dt electrical measurements, time-resolved spectrometer measurements are used to determine the temperature of the expanding metallic foil. Post-shot examination of the flyer and the insulation impacted by the flyer gives insight into the experimental behavior

  16. Elements of a regulatory strategy for the consideration of future human actions in safety assessments

    Energy Technology Data Exchange (ETDEWEB)

    Wilmot, R.D.; Wickham, S.M.; Galson, D.A. [Galson Sciences Ltd, Oakham (United Kingdom)

    1999-09-01

    The objective of this report is to discuss issues that should be considered in the development of a regulatory strategy for assessing future human actions in any forthcoming license application for a deep repository for spent fuel in Sweden and for sites of other repositories. The report comprises an outline of key issues concerning the treatment of future human actions in safety assessment, reviews of regulatory developments, recent safety assessments and supporting studies, and international initiatives on the treatment of future human actions in safety assessment, and the principal elements of a regulatory strategy. Performance assessments (PAs) are generally accepted as providing illustrations of system performance under given sets of assumptions. The results of PAs are clearer and easier tounderstand if certain large uncertainties are accounted for by determining performance under several different sets of assumptions or scenarios, each of which defines a possible evolution of the disposal system. A number of assumptions can be made that would restrict the scope of an assessment without reducing the credibility of the corresponding safety case. Reducing speculation about technological development, by assuming that the techniques used in future human activities are similar to those currently in use in the region or at similar sites, will simplify the assessment. A distinction is generally made between inadvertent and intentional intrusion, with intentional activities excluded because society cannot protect future populations from their own actions if they understand the potential consequences. A division of human activities into 'recent and ongoing' and 'future' activities considers not only the timing of the activities but also the degree of control or influence that can be imposed on them. Recent and ongoing human activities are those that affect an area beyond the immediate vicinity of the disposal facility and which neither the proponent

  17. Elements of a regulatory strategy for the consideration of future human actions in safety assessments

    International Nuclear Information System (INIS)

    Wilmot, R.D.; Wickham, S.M.; Galson, D.A.

    1999-09-01

    The objective of this report is to discuss issues that should be considered in the development of a regulatory strategy for assessing future human actions in any forthcoming license application for a deep repository for spent fuel in Sweden and for sites of other repositories. The report comprises an outline of key issues concerning the treatment of future human actions in safety assessment, reviews of regulatory developments, recent safety assessments and supporting studies, and international initiatives on the treatment of future human actions in safety assessment, and the principal elements of a regulatory strategy. Performance assessments (PAs) are generally accepted as providing illustrations of system performance under given sets of assumptions. The results of PAs are clearer and easier to understand if certain large uncertainties are accounted for by determining performance under several different sets of assumptions or scenarios, each of which defines a possible evolution of the disposal system. A number of assumptions can be made that would restrict the scope of an assessment without reducing the credibility of the corresponding safety case. Reducing speculation about technological development, by assuming that the techniques used in future human activities are similar to those currently in use in the region or at similar sites, will simplify the assessment. A distinction is generally made between inadvertent and intentional intrusion, with intentional activities excluded because society cannot protect future populations from their own actions if they understand the potential consequences. A division of human activities into 'recent and ongoing' and 'future' activities considers not only the timing of the activities but also the degree of control or influence that can be imposed on them. Recent and ongoing human activities are those that affect an area beyond the immediate vicinity of the disposal facility and which neither the proponent nor the regulator

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  19. Colored fused filament fabrication

    OpenAIRE

    Song, Haichuan; Lefebvre, Sylvain

    2017-01-01

    Filament fused fabrication is the method of choice for printing 3D models at low cost, and is the de-facto standard for hobbyists, makers and schools. Unfortunately, filament printers cannot truly reproduce colored objects. The best current techniques rely on a form of dithering exploiting occlusion, that was only demonstrated for shades of two base colors and that behaves differently depending on surface slope. We explore a novel approach for 3D printing colored objects, capable of creating ...

  20. Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function.

    Science.gov (United States)

    Wong, S W; Schaffer, P A

    1991-05-01

    Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.

  1. 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. © 2015. Published by The Company of Biologists Ltd.

  2. Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

    Science.gov (United States)

    Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

    2017-02-01

    Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches

    Science.gov (United States)

    Fujibuchi, Wataru; Anderson, John S. J.; Landsman, David

    2001-01-01

    Consensus pattern and matrix-based searches designed to predict cis-acting transcriptional regulatory sequences have historically been subject to large numbers of false positives. We sought to decrease false positives by incorporating expression profile data into a consensus pattern-based search method. We have systematically analyzed the expression phenotypes of over 6000 yeast genes, across 121 expression profile experiments, and correlated them with the distribution of 14 known regulatory elements over sequences upstream of the genes. Our method is based on a metric we term probabilistic element assessment (PEA), which is a ranking of potential sites based on sequence similarity in the upstream regions of genes with similar expression phenotypes. For eight of the 14 known elements that we examined, our method had a much higher selectivity than a naïve consensus pattern search. Based on our analysis, we have developed a web-based tool called PROSPECT, which allows consensus pattern-based searching of gene clusters obtained from microarray data. PMID:11574681

  4. PlantCARE, a database of plant cis-acting regulatory elements and a portal to tools for in silico analysis of promoter sequences

    OpenAIRE

    Lescot, Magali; Déhais, Patrice; Thijs, Gert; Marchal, Kathleen; Moreau, Yves; Van de Peer, Yves; Rouzé, Pierre; Rombauts, Stephane

    2002-01-01

    PlantCARE is a database of plant cis-acting regulatory elements, enhancers and repressors. Regulatory elements are represented by positional matrices, consensus sequences and individual sites on particular promoter sequences. Links to the EMBL, TRANSFAC and MEDLINE databases are provided when available. Data about the transcription sites are extracted mainly from the literature, supplemented with an increasing number of in silico predicted data. Apart from a general description for specific t...

  5. Sterols regulate 3β-hydroxysterol Δ24-reductase (DHCR24) via dual sterol regulatory elements: cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins.

    Science.gov (United States)

    Zerenturk, Eser J; Sharpe, Laura J; Brown, Andrew J

    2012-10-01

    3β-Hydroxysterol Δ24-reductase (DHCR24) catalyzes a final step in cholesterol synthesis, and has been ascribed diverse functions, such as being anti-apoptotic and anti-inflammatory. How this enzyme is regulated transcriptionally by sterols is currently unclear. Some studies have suggested that its expression is regulated by Sterol Regulatory Element Binding Proteins (SREBPs) while another suggests it is through the Liver X Receptor (LXR). However, these transcription factors have opposing effects on cellular sterol levels, so it is likely that one predominates. Here we establish that sterol regulation of DHCR24 occurs predominantly through SREBP-2, and identify the particular region of the DHCR24 promoter to which SREBP-2 binds. We demonstrate that sterol regulation is mediated by two sterol regulatory elements (SREs) in the promoter of the gene, assisted by two nearby NF-Y binding sites. Moreover, we present evidence that the dual SREs work cooperatively to regulate DHCR24 expression by comparison to two known SREBP target genes, the LDL receptor with one SRE, and farnesyl-diphosphate farnesyltransferase 1, with two SREs. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Identification of cis-acting regulatory elements in the human oxytocin gene promoter.

    Science.gov (United States)

    Richard, S; Zingg, H H

    1991-12-01

    The expression of hormone-inducible genes is determined by the interaction of trans-acting factors with hormone-inducible elements and elements mediating basal and cell-specific expression. We have shown earlier that the gene encoding the hypothalamic nonapeptide oxytocin (OT) is under the control of an estrogen response element (ERE). The present study was aimed at identifying cis-acting elements mediating basal expression of the OT gene. A construct containing sequences -381 to +36 of the human OT gene was linked to a reporter gene and transiently transfected into a series of neuronal and nonneuronal cell lines. Expression of this construct was cell specific: it was highest in the neuroblastoma-derived cell line, Neuro-2a, and lowest in NIH 3T3 and JEG-3 cells. By 5' deletion analysis, we determined that a segment from -49 to +36 was capable of mediating cells-pecific promoter activity. Within this segment, we identified three proximal promoter elements (PPE-1, PPE-2, and PPE-3) that are each required for promoter activity. Most notably, mutation of a conserved purine-rich element (GAGAGA) contained within PPE-2 leads to a 10-fold decrease in promoter strength. Gel mobility shift analysis with three different double-stranded oligonucleotides demonstrated that each proximal promoter element binds distinct nuclear factors. In each case, only the homologous oligonucleotide, but neither of the oligonucleotides corresponding to adjacent elements, was able to act as a competitor. Thus, a different set of factors appears to bind independently to each element. By reinserting the homologous ERE or a heterologous glucocorticoid response element upstream of intact or altered proximal promoter segments we determined that removal or mutation of proximal promoter elements decreases basal expression, but does not abrogate the hormone responsiveness of the promoter. In conclusion, these results indicate that an important component of the transcriptional activity of the OT

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

    Science.gov (United States)

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

    2017-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling.

    Directory of Open Access Journals (Sweden)

    Donghyuk Kim

    Full Text Available Genome-wide transcription start site (TSS profiles of the enterobacteria Escherichia coli and Klebsiella pneumoniae were experimentally determined through modified 5' RACE followed by deep sequencing of intact primary mRNA. This identified 3,746 and 3,143 TSSs for E. coli and K. pneumoniae, respectively. Experimentally determined TSSs were then used to define promoter regions and 5' UTRs upstream of coding genes. Comparative analysis of these regulatory elements revealed the use of multiple TSSs, identical sequence motifs of promoter and Shine-Dalgarno sequence, reflecting conserved gene expression apparatuses between the two species. In both species, over 70% of primary transcripts were expressed from operons having orthologous genes during exponential growth. However, expressed orthologous genes in E. coli and K. pneumoniae showed a strikingly different organization of upstream regulatory regions with only 20% identical promoters with TSSs in both species. Over 40% of promoters had TSSs identified in only one species, despite conserved promoter sequences existing in the other species. 662 conserved promoters having TSSs in both species resulted in the same number of comparable 5' UTR pairs, and that regulatory element was found to be the most variant region in sequence among promoter, 5' UTR, and ORF. In K. pneumoniae, 48 sRNAs were predicted and 36 of them were expressed during exponential growth. Among them, 34 orthologous sRNAs between two species were analyzed in depth, and the analysis showed that many sRNAs of K. pneumoniae, including pleiotropic sRNAs such as rprA, arcZ, and sgrS, may work in the same way as in E. coli. These results reveal a new dimension of comparative genomics such that a comparison of two genomes needs to be comprehensive over all levels of genome organization.

  10. Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Hannibal, Tine Dahlbæk; Bang-Berthelsen, Claus Heiner

    2014-01-01

    . In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites...

  11. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Science.gov (United States)

    Meier, Daniel; Schindler, Detlev

    2011-01-01

    The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  12. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Directory of Open Access Journals (Sweden)

    Daniel Meier

    Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  13. 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

  14. Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene.

    Science.gov (United States)

    Nomura, M; Tsujimura, A; Begum, N A; Matsumoto, M; Wabiko, H; Toyoshima, K; Seya, T

    2000-01-01

    The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3'-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8 kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein-silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46. PMID:11023821

  15. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    Science.gov (United States)

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

  16. Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Calcium Binding Properties and Allosteric Regulation of Downstream Regulatory Element Antagonist Modulator (DREAM).

    Science.gov (United States)

    Zhang, Jun; Li, Jing; Craig, Theodore A; Kumar, Rajiv; Gross, Michael L

    2017-07-18

    Downstream regulatory element antagonist modulator (DREAM) is an EF-hand Ca 2+ -binding protein that also binds to a specific DNA sequence, downstream regulatory elements (DRE), and thereby regulates transcription in a calcium-dependent fashion. DREAM binds to DRE in the absence of Ca 2+ but detaches from DRE under Ca 2+ stimulation, allowing gene expression. The Ca 2+ binding properties of DREAM and the consequences of the binding on protein structure are key to understanding the function of DREAM. Here we describe the application of hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis to investigate the Ca 2+ binding properties and the subsequent conformational changes of full-length DREAM. We demonstrate that all EF-hands undergo large conformation changes upon calcium binding even though the EF-1 hand is not capable of binding to Ca 2+ . Moreover, EF-2 is a lower-affinity site compared to EF-3 and -4 hands. Comparison of HDX profiles between wild-type DREAM and two EF-1 mutated constructs illustrates that the conformational changes in the EF-1 hand are induced by long-range structural interactions. HDX analyses also reveal a conformational change in an N-terminal leucine-charged residue-rich domain (LCD) remote from Ca 2+ -binding EF-hands. This LCD domain is responsible for the direct interaction between DREAM and cAMP response element-binding protein (CREB) and regulates the recruitment of the co-activator, CREB-binding protein. These long-range interactions strongly suggest how conformational changes transmit the Ca 2+ signal to CREB-mediated gene transcription.

  17. RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants.

    Science.gov (United States)

    Cho, Seok Keun; Ryu, Moon Young; Kim, Jong Hum; Hong, Jeong Soo; Oh, Tae Rin; Kim, Woo Taek; Yang, Seong Wook

    2017-08-01

    Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants. [BMB Reports 2017; 50(8): 393-400].

  18. Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2

    DEFF Research Database (Denmark)

    Dathe, Katarina; Kjaer, Klaus W; Brehm, Anja

    2009-01-01

    Autosomal-dominant brachydactyly type A2 (BDA2), a limb malformation characterized by hypoplastic middle phalanges of the second and fifth fingers, has been shown to be due to mutations in the Bone morphogenetic protein receptor 1B (BMPR1B) or in its ligand Growth and differentiation factor 5 (GDF5......). A linkage analysis performed in a mutation-negative family identified a novel locus for BDA2 on chromosome 20p12.3 that incorporates the gene for Bone morphogenetic protein 2 (BMP2). No point mutation was identified in BMP2, so a high-density array CGH analysis covering the critical interval...... within the identified duplication. Our results reveal an additional functional mechanism for the pathogenesis of BDA2, which is duplication of a regulatory element that affects the expression of BMP2 in the developing limb....

  19. A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid.

    Science.gov (United States)

    Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Mizuguchi, Kiyoshi; Shimano, Hitoshi

    2014-05-01

    The proteolytic cascade is the key step in transactivation of sterol regulatory element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis. Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined by transfection studies of cDNA-encoding mutants in which all the known cleavage sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was completely eliminated by mutation of cleavage sites. In contrast, the corresponding SREBP-1c mutants as well as wild type exhibited large amounts of cleaved products in the nuclear extracts from culture cells and murine liver in vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by sterols. This novel processing mechanism was affected by neither SREBP cleavage-activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but abolished by a serine protease inhibitor. Through analysis of deletion mutant, a site-2 protease recognition sequence (DRSR) was identified to be involved in this novel processing. These findings suggest that SREBP-1c cleavage could be subjected to a novel PUFA-regulated cleavage system in addition to the sterol-regulatory SCAP/Insig system.

  20. Fused salt electrolysis

    International Nuclear Information System (INIS)

    Ares, Osvaldo; Botbol, Jose.

    1989-01-01

    Working conditions for zirconium preparation by fused salt electrolysis were studied. For such purpose, a cell was built for operation under argon atmosphere. A graphite crucible served as anode, with steel cathodes. Proper design allowed cathode rechange under the inert atmosphere. Cathodic deposits of zirconium powder occluded salts from the bath. After washing with both water and hydrochloric acid, the metallic powder was consolidated by fusion. Optimum operating conditions were found to arise from an electrolyte of 12% potassium hexafluorzirconate -88% sodium chloride, at 820 deg C and 5 A/cm 2 cathodic current density. Deposits contained 35% of metal and current efficiency reached 66%. The powder contained up to 600 ppm of chlorine and 1.700 ppm of fluorine; after fusion, those amounts decreased to 2 ppm and 3 ppm respectively, with low proportion of metallic impurities. Though oxygen proportion was 4.500 ppm, it should be lowered by improving working conditions, as well as working on an ampler scale. (Author)

  1. In situ detection of a heat-shock regulatory element binding protein using a soluble short synthetic enhancer sequence

    Energy Technology Data Exchange (ETDEWEB)

    Harel-Bellan, A; Brini, A T; Farrar, W L [National Cancer Institute, Frederick, MD (USA); Ferris, D K [Program Resources, Inc., Frederick, MD (USA); Robin, P [Institut Gustave Roussy, Villejuif (France)

    1989-06-12

    In various studies, enhancer binding proteins have been successfully absorbed out by competing sequences inserted into plasmids, resulting in the inhibition of the plasmid expression. Theoretically, such a result could be achieved using synthetic enhancer sequences not inserted into plasmids. In this study, a double stranded DNA sequence corresponding to the human heat shock regulatory element was chemically synthesized. By in vitro retardation assays, the synthetic sequence was shown to bind specifically a protein in extracts from the human T cell line Jurkat. When the synthetic enhancer was electroporated into Jurkat cells, not only the enhancer was shown to remain undegraded into the cells for up to 2 days, but also its was shown to bind intracellularly a protein. The binding was specific and was modulated upon heat shock. Furthermore, the binding protein was shown to be of the expected molecular weight by UV crosslinking. However, when the synthetic enhancer element was co-electroporated with an HSP 70-CAT reporter construct, the expression of the reporter plasmid was consistently enhanced in the presence of the exogenous synthetic enhancer.

  2. An empirical model of Onecut binding activity at the sea urchin SM50 C-element gene regulatory region.

    Science.gov (United States)

    Otim, Ochan

    2017-01-01

    Studying the formation of endoskeleton in many species is complex and difficult. The sea urchin embryo offers an unparalleled platform for understanding this process because of the ease with which its skeletogenic mesenchyme cells can be manipulated. In this study, preliminary evidence from biochemical studies towards understanding the role of the Onecut transcription factor during sea urchin skeletogenic mesenchyme cell specification is presented. Based on the evidence, an empirical model is proposed showing how Onecut, together with associated co-factors, may be using the C-element of the SM50 gene regulatory region in advance of the sea urchin Strongylocentrotus purpuratus spicule development. In the model, Onecut recognizes and binds the DNA sequence CATCGATCTC in the C-element without temporal restriction. Onecut then utilizes different sets of co-factors to switch from its unknown function early in development (four cell stage to the mesenchyme blastula stage), to its known role in the oral-aboral boundary thereafter. At the writing of this report, definitive evidence as to whether the "early" factors are expressed in all cells except the micromere lineages, or whether the "late" factors are expressed in micromere descendants or ectodermal precursors only are lacking. The former would suggest a possible Onecut repression function for the early co-factors outside the micromere lineages; the latter scenario would suggest a Onecut activation function for the late co-factors in the presumptive ciliary band.

  3. 14q12 and severe Rett-like phenotypes: new clinical insights and physical mapping of FOXG1-regulatory elements

    Science.gov (United States)

    Allou, Lila; Lambert, Laetitia; Amsallem, Daniel; Bieth, Eric; Edery, Patrick; Destrée, Anne; Rivier, François; Amor, David; Thompson, Elizabeth; Nicholl, Julian; Harbord, Michael; Nemos, Christophe; Saunier, Aline; Moustaïne, Aissa; Vigouroux, Adeline; Jonveaux, Philippe; Philippe, Christophe

    2012-01-01

    The Forkhead box G1 (FOXG1) gene has been implicated in severe Rett-like phenotypes. It encodes the Forkhead box protein G1, a winged-helix transcriptional repressor critical for forebrain development. Recently, the core FOXG1 syndrome was defined as postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and dysgenesis of the corpus callosum. We present seven additional patients with a severe Rett-like neurodevelopment disorder associated with de novo FOXG1 point mutations (two cases) or 14q12 deletions (five cases). We expand the mutational spectrum in patients with FOXG1-related encephalopathies and precise the core FOXG1 syndrome phenotype. Dysgenesis of the corpus callosum and dyskinesia are not always present in FOXG1-mutated patients. We believe that the FOXG1 gene should be considered in severely mentally retarded patients (no speech-language) with severe acquired microcephaly (−4 to−6 SD) and few clinical features suggestive of Rett syndrome. Interestingly enough, three 14q12 deletions that do not include the FOXG1 gene are associated with phenotypes very reminiscent to that of FOXG1-mutation-positive patients. We physically mapped a putative long-range FOXG1-regulatory element in a 0.43 Mb DNA segment encompassing the PRKD1 locus. In fibroblast cells, a cis-acting regulatory sequence located more than 0.6 Mb away from FOXG1 acts as a silencer at the transcriptional level. These data are important for clinicians and for molecular biologists involved in the management of patients with severe encephalopathies compatible with a FOXG1-related phenotype. PMID:22739344

  4. Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Trnovská, J.; Kazdová, L.; Pravenec, Michal

    2014-01-01

    Roč. 63, č. 5 (2014), s. 587-590 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12061 Institutional support: RVO:67985823 Keywords : sterol regulatory element binding protein 2 * transgenic * spontaneously hypertensive rat * lipid metabolism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

  5. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

    Science.gov (United States)

    Dewhurst, Henry; Sundararaman, Niveda

    2016-01-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  6. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

    Science.gov (United States)

    Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

    2016-11-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  7. 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

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

    Science.gov (United States)

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

    2005-07-15

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

  9. Sterol regulatory element-binding proteins are regulators of the rat thyroid peroxidase gene in thyroid cells.

    Directory of Open Access Journals (Sweden)

    Christine Rauer

    Full Text Available Sterol regulatory element-binding proteins (SREBPs-1c and -2, which were initially discovered as master transcriptional regulators of lipid biosynthesis and uptake, were recently identified as novel transcriptional regulators of the sodium-iodide symporter gene in the thyroid, which is essential for thyroid hormone synthesis. Based on this observation that SREBPs play a role for thyroid hormone synthesis, we hypothesized that another gene involved in thyroid hormone synthesis, the thyroid peroxidase (TPO gene, is also a target of SREBP-1c and -2. Thyroid epithelial cells treated with 25-hydroxycholesterol, which is known to inhibit SREBP activation, had about 50% decreased mRNA levels of TPO. Similarly, the mRNA level of TPO was reduced by about 50% in response to siRNA mediated knockdown of both, SREBP-1 and SREBP-2. Reporter gene assays revealed that overexpression of active SREBP-1c and -2 causes a strong transcriptional activation of the rat TPO gene, which was localized to an approximately 80 bp region in the intron 1 of the rat TPO gene. In vitro- and in vivo-binding of both, SREBP-1c and SREBP-2, to this region in the rat TPO gene could be demonstrated using gel-shift assays and chromatin immunoprecipitation. Mutation analysis of the 80 bp region of rat TPO intron 1 revealed two isolated and two overlapping SREBP-binding elements from which one, the overlapping SRE+609/InvSRE+614, was shown to be functional in reporter gene assays. In connection with recent findings that the rat NIS gene is also a SREBP target gene in the thyroid, the present findings suggest that SREBPs may be possible novel targets for pharmacological modulation of thyroid hormone synthesis.

  10. RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.

    Science.gov (United States)

    Zhang, Honglian; Gan, Haiyun; Wang, Zhiquan; Lee, Jeong-Heon; Zhou, Hui; Ordog, Tamas; Wold, Marc S; Ljungman, Mats; Zhang, Zhiguo

    2017-01-19

    The histone chaperone HIRA is involved in depositing histone variant H3.3 into distinct genic regions, including promoters, enhancers, and gene bodies. However, how HIRA deposits H3.3 to these regions remains elusive. Through a short hairpin RNA (shRNA) screening, we identified single-stranded DNA binding protein replication protein A (RPA) as a regulator of the deposition of newly synthesized H3.3 into chromatin. We show that RPA physically interacts with HIRA to form RPA-HIRA-H3.3 complexes, and it co-localizes with HIRA and H3.3 at gene promoters and enhancers. Depletion of RPA1, the largest subunit of the RPA complex, dramatically reduces both HIRA association with chromatin and the deposition of newly synthesized H3.3 at promoters and enhancers and leads to altered transcription at gene promoters. These results support a model whereby RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Regulation of steroid 5-{alpha} reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Young-Kyo [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States); Zhu, Bing [Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0144 (United States); Jeon, Tae-Il [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States); Osborne, Timothy F., E-mail: tfosborn@uci.edu [Department of Molecular Biology and Biochemistry, 3244 McGaugh Hall, University of California, UC Irvine, Irvine, CA 92697-3900 (United States)

    2009-11-01

    In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.

  12. Sterol regulatory element-binding protein-1 participates in the regulation of fatty acid synthase expression in colorectal neoplasia.

    Science.gov (United States)

    Li, J N; Mahmoud, M A; Han, W F; Ripple, M; Pizer, E S

    2000-11-25

    Endogenous fatty acid synthesis has been observed in certain rapidly proliferating normal and neoplastic tissues. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the expression of lipogenic genes including fatty acid synthase (FAS), the major biosynthetic enzyme for fatty acid synthesis. We have previously shown that SREBP-1, FAS, and Ki-67, a proliferation marker, colocalized in the crypts of the fetal gastrointestinal tract epithelium. This study sought to determine whether SREBP-1 participates in the regulation of proliferation-associated fatty acid synthesis in colorectal neoplasia. An immunohistochemical analysis of SREBP-1, FAS, and Ki-67 expression in 25 primary human colorectal carcinoma specimens showed colocalization in 22 of these. To elucidate a functional linkage between SREBP-1 activation and proliferation-associated FA synthesis, SREBP-1 and FAS content were assayed during the adaptive response of cultured HCT116 colon carcinoma cells to pharmacological inhibition of FA synthesis. Cerulenin and TOFA each inhibited the endogenous synthesis of fatty acids in a dose-dependent manner and each induced increases in both precursor and mature forms of SREBP-1. Subsequently, both the transcriptional activity of the FAS promoter in a luciferase reporter gene construct and the FAS expression increased. These results demonstrate that tumor cells recognize and respond to a deficiency in endogenous fatty acid synthesis by upregulating both SREBP-1 and FAS expression and support the model that SREBP-1 participates in the transcriptional regulation of lipogenic genes in colorectal neoplasia. Copyright 2000 Academic Press.

  13. Regulation of steroid 5-α reductase type 2 (Srd5a2) by sterol regulatory element binding proteins and statin

    International Nuclear Information System (INIS)

    Seo, Young-Kyo; Zhu, Bing; Jeon, Tae-Il; Osborne, Timothy F.

    2009-01-01

    In this study, we show that sterol regulatory element binding proteins (SREBPs) regulate expression of Srd5a2, an enzyme that catalyzes the irreversible conversion of testosterone to dihydroxytestosterone in the male reproductive tract and is highly expressed in androgen-sensitive tissues such as the prostate and skin. We show that Srd5a2 is induced in livers and prostate from mice fed a chow diet supplemented with lovastatin plus ezitimibe (L/E), which increases the activity of nuclear SREBP-2. The three fold increase in Srd5a2 mRNA mediated by L/E treatment was accompanied by the induction of SREBP-2 binding to the Srd5a2 promoter detected by a ChIP-chip assay in liver. We identified a SREBP-2 responsive region within the first 300 upstream bases of the mouse Srd5a2 promoter by co-transfection assays which contain a site that bound SREBP-2 in vitro by an EMSA. Srd5a2 protein was also induced in cells over-expressing SREBP-2 in culture. The induction of Srd5a2 through SREBP-2 provides a mechanistic explanation for why even though statin therapy is effective in reducing cholesterol levels in treating hypercholesterolemia it does not compromise androgen production in clinical studies.

  14. Glycogen Synthase Kinase 3 Inactivation Induces Cell Senescence through Sterol Regulatory Element Binding Protein 1-Mediated Lipogenesis in Chang Cells.

    Science.gov (United States)

    Kim, You-Mie; Song, Insun; Seo, Yong-Hak; Yoon, Gyesoon

    2013-12-01

    Enhanced lipogenesis plays a critical role in cell senescence via induction of expression of the mature form of sterol regulatory element binding protein 1 (SREBP1), which contributes to an increase in organellar mass, one of the indicators of senescence. We investigated the molecular mechanisms by which signaling molecules control SREBP1-mediated lipogenesis and senescence. We developed cellular models for stress-induced senescence, by exposing Chang cells, which are immortalized human liver cells, to subcytotoxic concentrations (200 µM) of deferoxamine (DFO) and H2O2. In this model of stress-induced cell senescence using DFO and H2O2, the phosphorylation profile of glycogen synthase kinase 3α (GSK3α) and β corresponded closely to the expression profile of the mature form of SREBP-1 protein. Inhibition of GSK3 with a subcytotoxic concentration of the selective GSK3 inhibitor SB415286 significantly increased mature SREBP1 expression, as well as lipogenesis and organellar mass. In addition, GSK3 inhibition was sufficient to induce senescence in Chang cells. Suppression of GSK3 expression with siRNAs specific to GSK3α and β also increased mature SREBP1 expression and induced senescence. Finally, blocking lipogenesis with fatty acid synthase inhibitors (cerulenin and C75) and siRNA-mediated silencing of SREBP1 and ATP citrate lyase (ACL) significantly attenuated GSK3 inhibition-induced senescence. GSK3 inactivation is an important upstream event that induces SREBP1-mediated lipogenesis and consequent cell senescence.

  15. Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element

    International Nuclear Information System (INIS)

    Gaur, Naseem Akhtar; Manoharlal, Raman; Saini, Preeti; Prasad, Tulika; Mukhopadhyay, Gauranga; Hoefer, Milan; Morschhaeuser, Joachim; Prasad, Rajendra

    2005-01-01

    Resistance to azole antifungal drugs in clinical isolates of the human fungal pathogen Candida albicans is often caused by constitutive overexpression of the CDR1 gene, which encodes a multidrug efflux pump of the ABC transporter superfamily. To understand the relevance of a recently identified negative regulatory element (NRE) in the CDR1 promoter for the control of CDR1 expression in the clinical scenario, we investigated the effect of mutation or deletion of the NRE on CDR1 expression in two matched pairs of azole-sensitive and resistant clinical isolates of C. albicans. Expression of GFP or lacZ reporter genes from the wild type CDR1 promoter was much higher in the azole-resistant C. albicans isolates than in the azole-susceptible isolates, reflecting the known differences in CDR1 expression in these strains. Deletion or mutation of the NRE resulted in enhanced reporter gene expression in azole-sensitive strains, but did not further increase the already high CDR1 promoter activity in the azole-resistant strains. In agreement with these findings, electrophoretic mobility shift assays showed a reduced binding to the NRE of nuclear extracts from the resistant C. albicans isolates as compared with extracts from the sensitive isolates. These results demonstrate that the NRE is involved in maintaining CDR1 expression at basal levels and that this repression is overcome in azole-resistant clinical C. albicans isolates, resulting in constitutive CDR1 overexpression and concomitant drug resistance

  16. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of

  17. Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation.

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    Full Text Available Sterol regulatory element-binding protein-1 (SREBP-1 has been thought to be a critical factor that assists adipogenesis. During adipogenesis SREBP-1 stimulates lipogenic gene expression, and peroxisome proliferator-activated receptor γ (PPARγ enhances perilipin (plin gene expression, resulting in generating lipid droplets (LDs to store triacylglycerol (TAG in adipocytes. Plin coats adipocyte LDs and protects them from lipolysis. Here we show in white adipose tissue (WAT of plin-/- mice that nuclear active SREBP-1 and its target gene expression, but not nuclear SREBP-2, significantly decreased on attenuated LD formation. When plin-/- mouse embryonic fibroblasts (MEFs differentiated into adipocytes, attenuated LDs were formed and nuclear SREBP-1 decreased, but enforced plin expression restored them to their original state. Since LDs are largely derived from the endoplasmic reticulum (ER, alterations in the ER cholesterol content were investigated during adipogenesis of 3T3-L1 cells. The ER cholesterol greatly reduced in differentiated adipocytes. The ER cholesterol level in plin-/- WAT was significantly higher than that of wild-type mice, suggesting that increased LD formation caused a change in ER environment along with a decrease in cholesterol. When GFP-SREBP-1 fusion proteins were exogenously expressed in 3T3-L1 cells, a mutant protein lacking the S1P cleavage site was poorly processed during adipogenesis, providing evidence of the increased canonical pathway for SREBP processing in which SREBP-1 is activated by two cleavage enzymes in the Golgi. Therefore, LD biogenesis may create the ER microenvironment favorable for SREBP-1 activation. We describe the novel interplay between LD formation and SREBP-1 activation through a positive feedback loop.

  18. Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epithelium.

    Science.gov (United States)

    Rudolph, Michael C; Monks, Jenifer; Burns, Valerie; Phistry, Meridee; Marians, Russell; Foote, Monica R; Bauman, Dale E; Anderson, Steven M; Neville, Margaret C

    2010-12-01

    The lactating mammary gland synthesizes large amounts of triglyceride from fatty acids derived from the blood and from de novo lipogenesis. The latter is significantly increased at parturition and decreased when additional dietary fatty acids become available. To begin to understand the molecular regulation of de novo lipogenesis, we tested the hypothesis that the transcription factor sterol regulatory element binding factor (SREBF)-1c is a primary regulator of this system. Expression of Srebf1c mRNA and six of its known target genes increased ≥2.5-fold at parturition. However, Srebf1c-null mice showed only minor deficiencies in lipid synthesis during lactation, possibly due to compensation by Srebf1a expression. To abrogate the function of both isoforms of Srebf1, we bred mice to obtain a mammary epithelial cell-specific deletion of SREBF cleavage-activating protein (SCAP), the SREBF escort protein. These dams showed a significant lactation deficiency, and expression of mRNA for fatty acid synthase (Fasn), insulin-induced gene 1 (Insig1), mitochondrial citrate transporter (Slc25a1), and stearoyl-CoA desaturase 2 (Scd2) was reduced threefold or more; however, the mRNA levels of acetyl-CoA carboxylase-1α (Acaca) and ATP citrate lyase (Acly) were unchanged. Furthermore, a 46% fat diet significantly decreased de novo fatty acid synthesis and reduced the protein levels of ACACA, ACLY, and FASN significantly, with no change in their mRNA levels. These data lead us to conclude that two modes of regulation exist to control fatty acid synthesis in the mammary gland of the lactating mouse: the well-known SREBF1 system and a novel mechanism that acts at the posttranscriptional level in the presence of SCAP deletion and high-fat feeding to alter enzyme protein.

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

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    Varvara A Khoroshko

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

  20. Identification of Rbd2 as a candidate protease for sterol regulatory element binding protein (SREBP) cleavage in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinsil; Ha, Hye-Jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Kim, Sujin [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113 (Korea, Republic of); Choi, Ah-Reum [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of); Lee, Sook-Jeong [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Hoe, Kwang-Lae, E-mail: kwanghoe@cnu.ac.kr [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134 (Korea, Republic of); Kim, Dong-Uk, E-mail: kimdongu@kribb.re.kr [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141 (Korea, Republic of)

    2015-12-25

    Lipid homeostasis in mammalian cells is regulated by sterol regulatory element-binding protein (SREBP) transcription factors that are activated through sequential cleavage by Golgi Site-1 and Site-2 proteases. Fission yeast SREBP, Sre1, engages a different mechanism involving the Golgi Dsc E3 ligase complex, but it is not clearly understood exactly how Sre1 is proteolytically cleaved and activated. In this study, we screened the Schizosaccharomyces pombe non-essential haploid deletion collection to identify missing components of the Sre1 cleavage machinery. Our screen identified an additional component of the SREBP pathway required for Sre1 proteolysis named rhomboid protein 2 (Rbd2). We show that an rbd2 deletion mutant fails to grow under hypoxic and hypoxia-mimetic conditions due to lack of Sre1 activity and that this growth phenotype is rescued by Sre1N, a cleaved active form of Sre1. We found that the growth inhibition phenotype under low oxygen conditions is specific to the strain with deletion of rbd2, not any other fission yeast rhomboid-encoding genes. Our study also identified conserved residues of Rbd2 that are required for Sre1 proteolytic cleavage. All together, our results suggest that Rbd2 is a functional SREBP protease with conserved residues required for Sre1 cleavage and provide an important piece of the puzzle to understand the mechanisms for Sre1 activation and the regulation of various biological and pathological processes involving SREBPs. - Highlights: • An rbd2-deleted yeast strain shows defects in growth in response to low oxygen levels. • rbd2-deficient cells fail to generate cleaved Sre1 (Sre1N) under hypoxic conditions. • Expression of Sre1N rescues the rbd2 deletion mutant growth phenotype. • Rbd2 contains conserved residues potentially critical for catalytic activity. • Mutation of the conserved Rbd2 catalytic residues leads to defects in Sre1 cleavage.

  1. 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

  2. A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design.

    Science.gov (United States)

    Smith, Robin P; Riesenfeld, Samantha J; Holloway, Alisha K; Li, Qiang; Murphy, Karl K; Feliciano, Natalie M; Orecchia, Lorenzo; Oksenberg, Nir; Pollard, Katherine S; Ahituv, Nadav

    2013-07-18

    Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences. We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly. This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.

  3. Liquefier Dynamics in Fused Deposition

    DEFF Research Database (Denmark)

    Bellini, Anna; Guceri, Selcuk; Bertoldi, Maurizio

    2004-01-01

    Layered manufacturing (LM) is an evolution of rapid prototyping (RP) technology whereby a part is built in layers. Fused deposition modeling (FDM) is a particular LM technique in which each section is fabricated through vector style deposition of building blocks, called roads, which...

  4. Fused aromatic thienopyrazines: structure, properties and function

    KAUST Repository

    Mondal, Rajib; Ko, Sangwon; Bao, Zhenan

    2010-01-01

    Recent development of a fused aromatic thieno[3.4-b]pyrazine system and their application in optoelectronic devices are reviewed. Introduction of a fused aromatic unit followed by side chain engineering, dramatically enhanced the charge carrier

  5. Optimizing critical source control of five priority-regulatory trace elements from industrial wastewater in China: Implications for health management.

    Science.gov (United States)

    Wu, Wenjun; Wang, Jinnan; Yu, Yang; Jiang, Hongqiang; Liu, Nianlei; Bi, Jun; Liu, Miaomiao

    2018-04-01

    Anthropogenic emissions of toxic trace elements (TEs) have caused worldwide concern due to their adverse effects on human health and ecosystems. Based on a stochastic simulation of factors' probability distribution, we established a bottom-up model to estimate the amounts of five priority-regulatory TEs released to aquatic environments from industrial processes in China. Total TE emissions in China in 2010 were estimated at approximately 2.27 t of Hg, 310.09 t of As, 318.17 t of Pb, 79.72 t of Cd, and 1040.32 t of Cr. Raw chemicals, smelting, and mining were the leading sources of TE emissions. There are apparent regional differences in TE pollution. TE emissions are much higher in eastern and central China than in the western provinces and are higher in the south than in the north. This spatial distribution was characterized in detail by allocating the emissions to 10 km × 10 km grid cells. Furthermore, the risk control for the overall emission grid was optimized according to each cell's emission and risk rank. The results show that to control 80% of TE emissions from major sources, the number of top-priority control cells would be between 200 and 400, and less than 10% of the total population would be positively affected. Based on TE risk rankings, decreasing the population weighted risk would increase the number of controlled cells by a factor of 0.3-0.5, but the affected population would increase by a factor of 0.8-1.5. In this case, the adverse effects on people's health would be reduced significantly. Finally, an optimized strategy to control TE emissions is proposed in terms of a cost-benefit trade-off. The estimates in this paper can be used to help establish a regional TE inventory and cyclic simulation, and it can also play supporting roles in minimizing TE health risks and maximizing resilience. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

    Directory of Open Access Journals (Sweden)

    Carl O Olson

    Full Text Available MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum, whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute

  7. 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.

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

    Science.gov (United States)

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

    1995-07-01

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

  9. Regulatory elements in the promoter region of the rat gene encoding the acyl-CoA-binding protein

    DEFF Research Database (Denmark)

    Elholm, M; Bjerking, G; Knudsen, J

    1996-01-01

    for the ACBP DR-1 element. Addition of peroxisome proliferators (PP) to H4IIEC3 rat hepatoma cells led to an increase in the ACBP mRNA level, indicating that the DR-1 element could be a functional peroxisome proliferator responsive element (PPRE). Analysis of the ACBP promoter by transient transfection showed...

  10. Positive- and negative-acting regulatory elements contribute to the tissue-specific expression of INNER NO OUTER, a YABBY-type transcription factor gene in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Simon Marissa K

    2012-11-01

    Full Text Available Abstract Background The INNER NO OUTER (INO gene, which encodes a YABBY-type transcription factor, specifies and promotes the growth of the outer integument of the ovule in Arabidopsis. INO expression is limited to the abaxial cell layer of the developing outer integument of the ovule and is regulated by multiple regions of the INO promoter, including POS9, a positive element that when present in quadruplicate can produce low-level expression in the normal INO pattern. Results Significant redundancy in activity between different regions of the INO promoter is demonstrated. For specific regulatory elements, multimerization or the addition of the cauliflower mosaic virus 35S general enhancer was able to activate expression of reporter gene constructs that were otherwise incapable of expression on their own. A new promoter element, POS6, is defined and is shown to include sufficient positive regulatory information to reproduce the endogenous pattern of expression in ovules, but other promoter regions are necessary to fully suppress expression outside of ovules. The full-length INO promoter, but not any of the INO promoter deletions tested, is able to act as an enhancer-blocking insulator to prevent the ectopic activation of expression by the 35S enhancer. Sequence conservation between the promoter regions of Arabidopsis thaliana, Brassica oleracea and Brassica rapa aligns closely with the functional definition of the POS6 and POS9 regions, and with a defined INO minimal promoter. The B. oleracea INO promoter is sufficient to promote a similar pattern and level of reporter gene expression in Arabidopsis to that observed for the Arabidopsis promoter. Conclusions At least two independent regions of the INO promoter contain sufficient regulatory information to direct the specific pattern but not the level of INO gene expression. These regulatory regions act in a partially redundant manner to promote the expression in a specific pattern in the ovule and

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

    Directory of Open Access Journals (Sweden)

    Gizem Kalay

    2010-11-01

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

  12. Sterol regulatory element-binding proteins are regulators of the sodium/iodide symporter in mammary epithelial cells.

    Science.gov (United States)

    Wen, G; Pachner, L I; Gessner, D K; Eder, K; Ringseis, R

    2016-11-01

    The sodium/iodide symporter (NIS), which is essential for iodide concentration in the thyroid, is reported to be transcriptionally regulated by sterol regulatory element-binding proteins (SREBP) in rat FRTL-5 thyrocytes. The SREBP are strongly activated after parturition and throughout lactation in the mammary gland of cattle and are important for mammary epithelial cell synthesis of milk lipids. In this study, we tested the hypothesis that the NIS gene is regulated also by SREBP in mammary epithelial cells, in which NIS is functionally expressed during lactation. Regulation of NIS expression and iodide uptake was investigated by means of inhibition, silencing, and overexpression of SREBP and by reporter gene and DNA-binding assays. As a mammary epithelial cell model, the human MCF-7 cell line, a breast adenocarcinoma cell line, which shows inducible expression of NIS by all-trans retinoic acid (ATRA), and unlike bovine mammary epithelial cells, is widely used to investigate the regulation of mammary gland NIS and NIS-specific iodide uptake, was used. Inhibition of SREBP maturation by treatment with 25-hydroxycholesterol (5 µM) for 48h reduced ATRA (1 µM)-induced mRNA concentration of NIS and iodide uptake in MCF-7 cells by approximately 20%. Knockdown of SREBP-1c and SREBP-2 by RNA interference decreased the mRNA and protein concentration of NIS by 30 to 50% 48h after initiating knockdown, whereas overexpression of nuclear SREBP (nSREBP)-1c and nSREBP-2 increased the expression of NIS in MCF-7 cells by 45 to 60%, respectively, 48h after initiating overexpression. Reporter gene experiments with varying length of NIS promoter reporter constructs revealed that the NIS 5'-flanking region is activated by nSREBP-1c and nSREBP-2 approximately 1.5- and 4.5-fold, respectively, and activation involves a SREBP-binding motif (SRE) at -38 relative to the transcription start site of the NIS gene. Gel shift assays using oligonucleotides spanning either the wild-type or the

  13. Structural and functional analysis of mouse Msx1 gene promoter: sequence conservation with human MSX1 promoter points at potential regulatory elements.

    Science.gov (United States)

    Gonzalez, S M; Ferland, L H; Robert, B; Abdelhay, E

    1998-06-01

    Vertebrate Msx genes are related to one of the most divergent homeobox genes of Drosophila, the muscle segment homeobox (msh) gene, and are expressed in a well-defined pattern at sites of tissue interactions. This pattern of expression is conserved in vertebrates as diverse as quail, zebrafish, and mouse in a range of sites including neural crest, appendages, and craniofacial structures. In the present work, we performed structural and functional analyses in order to identify potential cis-acting elements that may be regulating Msx1 gene expression. To this end, a 4.9-kb segment of the 5'-flanking region was sequenced and analyzed for transcription-factor binding sites. Four regions showing a high concentration of these sites were identified. Transfection assays with fragments of regulatory sequences driving the expression of the bacterial lacZ reporter gene showed that a region of 4 kb upstream of the transcription start site contains positive and negative elements responsible for controlling gene expression. Interestingly, a fragment of 130 bp seems to contain the minimal elements necessary for gene expression, as its removal completely abolishes gene expression in cultured cells. These results are reinforced by comparison of this region with the human Msx1 gene promoter, which shows extensive conservation, including many consensus binding sites, suggesting a regulatory role for them.

  14. Regulatory elements in vivo in the promoter of the abscisic acid responsive gene rab17 from maize.

    Science.gov (United States)

    Busk, P K; Jensen, A B; Pagès, M

    1997-06-01

    The rab17 gene from maize is transcribed in late embryonic development and is responsive to abscisic acid and water stress in embryo and vegetative tissues. In vivo footprinting and transient transformation of rab17 were performed in embryos and vegetative tissues to characterize the cis-elements involved in regulation of the gene. By in vivo footprinting, protein binding was observed to nine elements in the promoter, which correspond to five putative ABREs (abscisic acid responsive elements) and four other sequences. The footprints indicated that distinct proteins interact with these elements in the two developmental stages. In transient transformation, six of the elements were important for high level expression of the rab17 promoter in embryos, whereas only three elements were important in leaves. The cis-acting sequences can be divided in embryo-specific, ABA-specific and leaf-specific elements on the basis of protein binding and the ability to confer expression of rab17. We found one positive, new element, called GRA, with the sequence CACTGGCCGCCC. This element was important for transcription in leaves but not in embryos. Two other non-ABRE elements that stimulated transcription from the rab17 promoter resemble previously described abscisic acid and drought-inducible elements. There were differences in protein binding and function of the five ABREs in the rab17 promoter. The possible reasons for these differences are discussed. The in vivo data obtained suggest that an embryo-specific pathway regulates transcription of the rab genes during development, whereas another pathway is responsible for induction in response to ABA and drought in vegetative tissues.

  15. ABO alleles are linked with haplotypes of an erythroid cell-specific regulatory element in intron 1 with a few exceptions attributable to genetic recombination.

    Science.gov (United States)

    Nakajima, T; Sano, R; Takahashi, Y; Watanabe, K; Kubo, R; Kobayashi, M; Takahashi, K; Takeshita, H; Kominato, Y

    2016-01-01

    Recent investigation of transcriptional regulation of the ABO genes has identified a candidate erythroid cell-specific regulatory element, named the +5·8-kb site, in the first intron of ABO. Six haplotypes of the site have been reported previously. The present genetic population study demonstrated that each haplotype was mostly linked with specific ABO alleles with a few exceptions, possibly as a result of hybrid formation between common ABO alleles. Thus, investigation of these haplotypes could provide a clue to further elucidation of ABO alleles. © 2015 International Society of Blood Transfusion.

  16. In silico analysis, mapping of regulatory elements and corresponding dna-protein interaction in polyphenol oxidase gene promoter from different rice varieties

    International Nuclear Information System (INIS)

    Mahmood, T.; Rehman, M.; Aziz, E.

    2015-01-01

    Polyphenol oxidase (PPO) is an important enzyme that has positive impact regarding plant resistance against different biotic and abiotic stresses. In the present study PPO promoter from six different rice varieties was amplified and then analyzed for cis- and trans-acting elements. The study revealed a total of 79 different cis-acting regulatory elements including 11 elements restricted to only one or other variety. Among six varieties Pakhal-Basmati had highest number (5) of these elements, whereas C-622 and Rachna-Basmati have no such sequences. Rachna-Basmati, IR-36-Basmati and Kashmir- Basmati had 1, 2 and 3 unique elements, respectively. Different elementsrelated to pathogen, salt and water stresses were found, which may be helpful in controlling PPO activity according to changing environment. Moreover, HADDOCK was used to understand molecular mechanism of PPO regulation and it was found that DNA-protein interactions are stabilized by many potential hydrogen bonds. Adenine and arginine were the most reactive residues in DNA and proteins respectively.Structural comparison of different protein-DNA complexes show that even a highly conserved transcriptional factor can adopt different conformations when they contact a different DNA binding sequence, however their stable interactions depend on the number of hydrogen bonds formed and distance. (author)

  17. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

    OpenAIRE

    Hamada, K; Gleason, S L; Levi, B Z; Hirschfeld, S; Appella, E; Ozato, K

    1989-01-01

    Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, bu...

  18. About a New Type of Fuse Based on the Controllable Fusing Effect

    Directory of Open Access Journals (Sweden)

    PLESCA, A.

    2009-06-01

    Full Text Available Fuses are among the best known of electrical devices and there are an extremely large number in use throughout the world. Beside of the advantageous features, the nowadays fuses have certain drawbacks. Therefore, a new type of fuse based on controllable fusing concept is proposed and a study as regards the total clearing time is done. The new concept has been validated through many experimental tests at different current values. The new type of fuse based on controllable fusing concept can be integrated within an overcurrent protection system especially to protect power semiconductors where the Joule integral criterion is better satisfied.

  19. High strength fused silica flexures manufactured by femtosecond laser

    Science.gov (United States)

    Bellouard, Yves; Said, Ali A.; Dugan, Mark; Bado, Philippe

    2009-02-01

    Flexures are mechanical elements used in micro- and precision-engineering to precisely guide the motion of micro-parts. They consist of slender bodies that deform elastically upon the application of a force. Although counter-intuitive at first, fused silica is an attractive material for flexure. Pending that the machining process does not introduce surface flaws that would lead to catastrophic failure, the material has a theoretically high ultimate tensile strength of several GPa. We report on high-aspect ratio fused silica flexures manufactured by femtosecond laser combined with chemical etching. Notch-hinges with thickness as small as twenty microns and aspect ratios comparable to aspect ratios obtained by Deep- Reactive-Ion-Etching (DRIE) were fabricated and tested under different loading conditions. Multiple fracture tests were performed for various loading conditions and the cracks morphologies were analyzed using Scanning Electron Microscopy. The manufactured elements show outstanding mechanical properties with flexural strengths largely exceeding those obtained with other technologies and materials. Fused silica flexures offer a mean to combine integrated optics with micro-mechanics in a single monolithic substrate. Waveguides and mechanical elements can be combined in a monolithic devices opening new opportunities for integrated opto-mechatronics devices.

  20. The effect of potentially toxic elements and sewage sludge on the activity of regulatory enzyme glutamate kinase

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, D.; Pavlík, Milan; Staszková, L.; Tlustoš, P.; Száková, J.; Balík, J.

    2007-01-01

    Roč. 53, č. 5 (2007), s. 201-206 ISSN 1214-1178 Institutional research plan: CEZ:AV0Z50380511 Keywords : Proline regulation * toxic elements * plant stress metabolism * chronic stress Subject RIV: ED - Physiology

  1. Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein.

    Science.gov (United States)

    Alexandre, C; Verrier, B

    1991-04-01

    Expression of the human c-fos proto-oncogene is activated in trans by the Tax protein encoded by human T-cell leukemia virus type-1 (HTLV-1). Indeed, we show here that a HeLa clone stably transfected by Tax expresses Fos at a high level. We also show that multiple elements of the human c-fos promoter, i.e. the v-sis conditioned medium inducible element (SIE), the dyad symmetry element (DSE) necessary for growth factor induction, the octanucleotide direct repeat element (DR), and the cyclic AMP response element (CRE) centred at -60, can all mediate Tax transactivation. In the DSE, the 10bp central core that binds the serum response factor (SRF) is, by itself, sufficient to mediate Tax transactivation. Moreover, a CRE-binding protein is involved in Tax activation through the CRE-60 element. Since Fos is a transregulator of cellular genes, our results suggest that the oncoprotein plays a crucial role in T-cell transformation by HTLV-1 in conjunction with other Tax-inducible genes.

  2. Use of low fusing alloy in dentistry.

    Science.gov (United States)

    Wee, A G; Schneider, R L; Aquilino, S A

    1998-11-01

    Low fusing alloy has been used in dentistry for remount procedures in both fixed and removable prosthodontics, in implant prosthodontics for the fabrication of solid implant casts, in maxillofacial prosthetics as oral radiation shields, and in dental research for its unique properties. Previously, the use of low fusing alloy was thought to offer a high degree of dimensional accuracy. However, multiple in vitro studies have shown that its presumed dimensional accuracy may be questionable. This article reviews the physical properties, metallurgical considerations of low fusing alloy, its applications in dentistry, and a safe, simple method of using low fusing alloy.

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

    Directory of Open Access Journals (Sweden)

    Mohammed Bakkali

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

  4. A hierarachical data structure representation for fusing multisensor information

    Energy Technology Data Exchange (ETDEWEB)

    Maren, A.J. [Tennessee Univ., Tullahoma, TN (United States). Space Inst.; Pap, R.M.; Harston, C.T. [Accurate Automation Corp., Chattanooga, TN (United States)

    1989-12-31

    A major problem with MultiSensor Information Fusion (MSIF) is establishing the level of processing at which information should be fused. Current methodologies, whether based on fusion at the data element, segment/feature, or symbolic levels, are each inadequate for robust MSIF. Data-element fusion has problems with coregistration. Attempts to fuse information using the features of segmented data relies on a Presumed similarity between the segmentation characteristics of each data stream. Symbolic-level fusion requires too much advance processing (including object identification) to be useful. MSIF systems need to operate in real-time, must perform fusion using a variety of sensor types, and should be effective across a wide range of operating conditions or deployment environments. We address this problem through developing a new representation level which facilitates matching and information fusion. The Hierarchical Data Structure (HDS) representation, created using a multilayer, cooperative/competitive neural network, meets this need. The HDS is an intermediate representation between the raw or smoothed data stream and symbolic interpretation of the data. it represents the structural organization of the data. Fused HDSs will incorporate information from multiple sensors. Their knowledge-rich structure aids top-down scene interpretation via both model matching and knowledge-based region interpretation.

  5. A hierarachical data structure representation for fusing multisensor information

    Energy Technology Data Exchange (ETDEWEB)

    Maren, A.J. (Tennessee Univ., Tullahoma, TN (United States). Space Inst.); Pap, R.M.; Harston, C.T. (Accurate Automation Corp., Chattanooga, TN (United States))

    1989-01-01

    A major problem with MultiSensor Information Fusion (MSIF) is establishing the level of processing at which information should be fused. Current methodologies, whether based on fusion at the data element, segment/feature, or symbolic levels, are each inadequate for robust MSIF. Data-element fusion has problems with coregistration. Attempts to fuse information using the features of segmented data relies on a Presumed similarity between the segmentation characteristics of each data stream. Symbolic-level fusion requires too much advance processing (including object identification) to be useful. MSIF systems need to operate in real-time, must perform fusion using a variety of sensor types, and should be effective across a wide range of operating conditions or deployment environments. We address this problem through developing a new representation level which facilitates matching and information fusion. The Hierarchical Data Structure (HDS) representation, created using a multilayer, cooperative/competitive neural network, meets this need. The HDS is an intermediate representation between the raw or smoothed data stream and symbolic interpretation of the data. it represents the structural organization of the data. Fused HDSs will incorporate information from multiple sensors. Their knowledge-rich structure aids top-down scene interpretation via both model matching and knowledge-based region interpretation.

  6. 30 CFR 57.6502 - Safety fuse.

    Science.gov (United States)

    2010-07-01

    ... blasthole detonates. (d) Fuse shall be cut and capped in dry locations. (e) Blasting caps shall be crimped... the primer and the explosive material are securely in place. (g) Safety fuse shall be ignited only... to be fired, electric initiation systems, igniter cord and connectors, or other nonelectric...

  7. 30 CFR 56.6502 - Safety fuse.

    Science.gov (United States)

    2010-07-01

    ... be cut and capped in dry locations. (e) Blasting caps shall be crimped to fuse only with implements... material are securely in place. (g) Safety fuse shall be ignited only with devices designed for that... initiation systems, igniter cord and connectors, or other nonelectric initiation systems shall be used...

  8. Transcriptome Analysis of an Insecticide Resistant Housefly Strain: Insights about SNPs and Regulatory Elements in Cytochrome P450 Genes.

    Science.gov (United States)

    Mahmood, Khalid; Højland, Dorte H; Asp, Torben; Kristensen, Michael

    2016-01-01

    Insecticide resistance in the housefly, Musca domestica, has been investigated for more than 60 years. It will enter a new era after the recent publication of the housefly genome and the development of multiple next generation sequencing technologies. The genetic background of the xenobiotic response can now be investigated in greater detail. Here, we investigate the 454-pyrosequencing transcriptome of the spinosad-resistant 791spin strain in relation to the housefly genome with focus on P450 genes. The de novo assembly of clean reads gave 35,834 contigs consisting of 21,780 sequences of the spinosad resistant strain. The 3,648 sequences were annotated with an enzyme code EC number and were mapped to 124 KEGG pathways with metabolic processes as most highly represented pathway. One hundred and twenty contigs were annotated as P450s covering 44 different P450 genes of housefly. Eight differentially expressed P450s genes were identified and investigated for SNPs, CpG islands and common regulatory motifs in promoter and coding regions. Functional annotation clustering of metabolic related genes and motif analysis of P450s revealed their association with epigenetic, transcription and gene expression related functions. The sequence variation analysis resulted in 12 SNPs and eight of them found in cyp6d1. There is variation in location, size and frequency of CpG islands and specific motifs were also identified in these P450s. Moreover, identified motifs were associated to GO terms and transcription factors using bioinformatic tools. Transcriptome data of a spinosad resistant strain provide together with genome data fundamental support for future research to understand evolution of resistance in houseflies. Here, we report for the first time the SNPs, CpG islands and common regulatory motifs in differentially expressed P450s. Taken together our findings will serve as a stepping stone to advance understanding of the mechanism and role of P450s in xenobiotic detoxification.

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

    Directory of Open Access Journals (Sweden)

    Yoav Hadas

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

  10. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Science.gov (United States)

    Poulin-Laprade, Dominic; Carraro, Nicolas; Burrus, Vincent

    2015-01-01

    Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  11. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Directory of Open Access Journals (Sweden)

    Dominic ePoulin-Laprade

    2015-08-01

    Full Text Available Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs of the SXT/R391 family (SRIs and IncA/C conjugative plasmids (ACPs are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e. SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  12. The transcriptional regulatory network mediated by banana (Musa acuminata) dehydration-responsive element binding (MaDREB) transcription factors in fruit ripening.

    Science.gov (United States)

    Kuang, Jian-Fei; Chen, Jian-Ye; Liu, Xun-Cheng; Han, Yan-Chao; Xiao, Yun-Yi; Shan, Wei; Tang, Yang; Wu, Ke-Qiang; He, Jun-Xian; Lu, Wang-Jin

    2017-04-01

    Fruit ripening is a complex, genetically programmed process involving the action of critical transcription factors (TFs). Despite the established significance of dehydration-responsive element binding (DREB) TFs in plant abiotic stress responses, the involvement of DREBs in fruit ripening is yet to be determined. Here, we identified four genes encoding ripening-regulated DREB TFs in banana (Musa acuminata), MaDREB1, MaDREB2, MaDREB3, and MaDREB4, and demonstrated that they play regulatory roles in fruit ripening. We showed that MaDREB1-MaDREB4 are nucleus-localized, induced by ethylene and encompass transcriptional activation activities. We performed a genome-wide chromatin immunoprecipitation and high-throughput sequencing (ChIP-Seq) experiment for MaDREB2 and identified 697 genomic regions as potential targets of MaDREB2. MaDREB2 binds to hundreds of loci with diverse functions and its binding sites are distributed in the promoter regions proximal to the transcriptional start site (TSS). Most of the MaDREB2-binding targets contain the conserved (A/G)CC(G/C)AC motif and MaDREB2 appears to directly regulate the expression of a number of genes involved in fruit ripening. In combination with transcriptome profiling (RNA sequencing) data, our results indicate that MaDREB2 may serve as both transcriptional activator and repressor during banana fruit ripening. In conclusion, our study suggests a hierarchical regulatory model of fruit ripening in banana and that the MaDREB TFs may act as transcriptional regulators in the regulatory network. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  13. GmWRKY53, a water- and salt-inducible soybean gene for rapid dissection of regulatory elements in BY-2 cell culture

    Science.gov (United States)

    Tripathi, Prateek; Rabara, Roel C.; Lin, Jun; Rushton, Paul J.

    2013-01-01

    Drought is the major cause of crop losses worldwide. Water stress-inducible promoters are important for understanding the mechanisms of water stress responses in crop plants. Here we utilized tobacco (Nicotiana tabacum L.) Bright Yellow 2 (BY-2) cell system in presence of polyethylene glycol, salt and phytohormones. Extension of the system to 85 mM NaCl led to inducibility of up to 10-fold with the water stress and salt responsive soybean GmWRKY53 promoter. Upon ABA and JA treatment fold inducibility was up to 5-fold and 14-fold, respectively. Thus, we hypothesize that GmWRKY53 could be used as potential model candidate for dissecting drought regulatory elements as well as understanding crosstalk utilizing a rapid heterologous system of BY-2 culture. PMID:23511199

  14. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression

    DEFF Research Database (Denmark)

    Eiberg, Hans; Troelsen, Jesper; Boyd, Mette

    2008-01-01

    The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region...... within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86...... founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color....

  15. Splicing Regulatory Elements and mRNA-abundance of dlg1 and capt, Genetically Interacting with dFMRP in Drosophila Brain

    Directory of Open Access Journals (Sweden)

    Maria Petrova

    2014-09-01

    Full Text Available To further understand the molecular and cellular mechanisms underlying the disease, we used the Drososphila FraX model and investigated a not well studied role of Drosophila Fragile X Mental Retardation Protein (dFMRP in alternative splicing of neuronal mRNAs to which it binds via a G-quartet sequence. By means of qRT-PCR we established the relative abundance of some isoforms of the gene dlg1, resulting from alternative exon skipping nearby a G-quartet and an exonic ESE-sequence, both acting as exonic splicing enhancers. We also investigated the relative mRNA-abundance of all capt-isoforms and the pre-mRNAs of both genes. We proposed a possible involvement of dFMRP in alternative splicing of genes, interacting with dfmr1. In the absence of dFMRP in larval and pupal brains, we found a change in the mRNA-level of one of the studied isoforms of dlg1 and of its pre-mRNA.We also established previously reported splicing regulatory elements and predicted computationally novel hexamere sequences in the exonic/intronic ends of both genes with p upative regulatory roles in alternative splicing.

  16. Identification of new TSGA10 transcript variants in human testis with conserved regulatory RNA elements in 5'untranslated region and distinct expression in breast cancer.

    Science.gov (United States)

    Salehipour, Pouya; Nematzadeh, Mahsa; Mobasheri, Maryam Beigom; Afsharpad, Mandana; Mansouri, Kamran; Modarressi, Mohammad Hossein

    2017-09-01

    Testis specific gene antigen 10 (TSGA10) is a cancer testis antigen involved in the process of spermatogenesis. TSGA10 could also play an important role in the inhibition of angiogenesis by preventing nuclear localization of HIF-1α. Although it has been shown that TSGA10 messenger RNA (mRNA) is mainly expressed in testis and some tumors, the transcription pattern and regulatory mechanisms of this gene remain largely unknown. Here, we report that human TSGA10 comprises at least 22 exons and generates four different transcript variants. It was identified that using two distinct promoters and splicing of exons 4 and 7 produced these transcript variants, which have the same coding sequence, but the sequence of 5'untanslated region (5'UTR) is different between them. This is significant because conserved regulatory RNA elements like upstream open reading frame (uORF) and putative internal ribosome entry site (IRES) were found in this region which have different combinations in each transcript variant and it may influence translational efficiency of them in normal or unusual environmental conditions like hypoxia. To indicate the transcription pattern of TSGA10 in breast cancer, expression of identified transcript variants was analyzed in 62 breast cancer samples. We found that TSGA10 tends to express variants with shorter 5'UTR and fewer uORF elements in breast cancer tissues. Our study demonstrates for the first time the expression of different TSGA10 transcript variants in testis and breast cancer tissues and provides a first clue to a role of TSGA10 5'UTR in regulation of translation in unusual environmental conditions like hypoxia. Copyright © 2017. Published by Elsevier B.V.

  17. Unraveling the regulatory network of IncA/C plasmid mobilization: When genomic islands hijack conjugative elements.

    Science.gov (United States)

    Carraro, Nicolas; Matteau, Dominick; Burrus, Vincent; Rodrigue, Sébastien

    2015-01-01

    Conjugative plasmids of the A/C incompatibility group (IncA/C) have become substantial players in the dissemination of multidrug resistance. These large conjugative plasmids are characterized by their broad host-range, extended spectrum of antimicrobials resistance, and prevalence in enteric bacteria recovered from both environmental and clinical settings. Until recently, relatively little was known about the basic biology of IncA/C plasmids, mostly because of the hindrance of multidrug resistance for molecular biology experiments. To circumvent this issue, we previously developed pVCR94ΔX, a convenient prototype that codes for a reduced set of antibiotic resistances. Using pVCR94ΔX, we then characterized the regulatory pathway governing IncA/C plasmid dissemination. We found that the expression of roughly 2 thirds of the genes encoded by this plasmid, including large operons involved in the conjugation process, depends on an FlhCD-like master activator called AcaCD. Beyond the mobility of IncA/C plasmids, AcaCD was also shown to play a key role in the mobilization of different classes of genomic islands (GIs) identified in various pathogenic bacteria. By doing so, IncA/C plasmids can have a considerable impact on bacterial genomes plasticity and evolution.

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

    Science.gov (United States)

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

    2004-03-01

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

  19. Porphyrins Fused with Unactivated Polycyclic Aromatic Hydrocarbons

    KAUST Repository

    Diev, Vyacheslav V.; Schlenker, Cody W.; Hanson, Kenneth; Zhong, Qiwen; Zimmerman, Jeramy D.; Forrest, Stephen R.; Thompson, Mark E.

    2012-01-01

    A systematic study of the preparation of porphyrins with extended conjugation by meso,β-fusion with polycyclic aromatic hydrocarbons (PAHs) is reported. The meso-positions of 5,15-unsubstituted porphyrins were readily functionalized with PAHs. Ring fusion using standard Scholl reaction conditions (FeCl 3, dichloromethane) occurs for perylene-substituted porphyrins to give a porphyrin β,meso annulated with perylene rings (0.7:1 ratio of syn and anti isomers). The naphthalene, pyrene, and coronene derivatives do not react under Scholl conditions but are fused using thermal cyclodehydrogenation at high temperatures, giving mixtures of syn and anti isomers of the meso,β-fused porphyrins. For pyrenyl-substituted porphyrins, a thermal method gives synthetically acceptable yields (>30%). Absorption spectra of the fused porphyrins undergo a progressive bathochromic shift in a series of naphthyl (λ max = 730 nm), coronenyl (λ max = 780 nm), pyrenyl (λ max = 815 nm), and perylenyl (λ max = 900 nm) annulated porphyrins. Despite being conjugated with unsubstituted fused PAHs, the β,meso-fused porphyrins are more soluble and processable than the parent nonfused precursors. Pyrenyl-fused porphyrins exhibit strong fluorescence in the near-infrared (NIR) spectral region, with a progressive improvement in luminescent efficiency (up to 13% with λ max = 829 nm) with increasing degree of fusion. Fused pyrenyl-porphyrins have been used as broadband absorption donor materials in photovoltaic cells, leading to devices that show comparatively high photovoltaic efficiencies. © 2011 American Chemical Society.

  20. Porphyrins Fused with Unactivated Polycyclic Aromatic Hydrocarbons

    KAUST Repository

    Diev, Vyacheslav V.

    2012-01-06

    A systematic study of the preparation of porphyrins with extended conjugation by meso,β-fusion with polycyclic aromatic hydrocarbons (PAHs) is reported. The meso-positions of 5,15-unsubstituted porphyrins were readily functionalized with PAHs. Ring fusion using standard Scholl reaction conditions (FeCl 3, dichloromethane) occurs for perylene-substituted porphyrins to give a porphyrin β,meso annulated with perylene rings (0.7:1 ratio of syn and anti isomers). The naphthalene, pyrene, and coronene derivatives do not react under Scholl conditions but are fused using thermal cyclodehydrogenation at high temperatures, giving mixtures of syn and anti isomers of the meso,β-fused porphyrins. For pyrenyl-substituted porphyrins, a thermal method gives synthetically acceptable yields (>30%). Absorption spectra of the fused porphyrins undergo a progressive bathochromic shift in a series of naphthyl (λ max = 730 nm), coronenyl (λ max = 780 nm), pyrenyl (λ max = 815 nm), and perylenyl (λ max = 900 nm) annulated porphyrins. Despite being conjugated with unsubstituted fused PAHs, the β,meso-fused porphyrins are more soluble and processable than the parent nonfused precursors. Pyrenyl-fused porphyrins exhibit strong fluorescence in the near-infrared (NIR) spectral region, with a progressive improvement in luminescent efficiency (up to 13% with λ max = 829 nm) with increasing degree of fusion. Fused pyrenyl-porphyrins have been used as broadband absorption donor materials in photovoltaic cells, leading to devices that show comparatively high photovoltaic efficiencies. © 2011 American Chemical Society.

  1. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

    Science.gov (United States)

    Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

    2017-07-10

    The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

  2. The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

    Science.gov (United States)

    Fabry, S; Müller, K; Lindauer, A; Park, P B; Cornelius, T; Schmitt, R

    1995-09-01

    The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II

  3. Optimizing Combinations of Flavonoids Deriving from Astragali Radix in Activating the Regulatory Element of Erythropoietin by a Feedback System Control Scheme

    Directory of Open Access Journals (Sweden)

    Hui Yu

    2013-01-01

    Full Text Available Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi, which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE, a critical regulator for erythropoietin (EPO transcription, in cultured human embryonic kidney fibroblast (HEK293T. By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction.

  4. Transcriptional Regulation in Ebola Virus: Effects of Gene Border Structure and Regulatory Elements on Gene Expression and Polymerase Scanning Behavior.

    Science.gov (United States)

    Brauburger, Kristina; Boehmann, Yannik; Krähling, Verena; Mühlberger, Elke

    2016-02-15

    The highly pathogenic Ebola virus (EBOV) has a nonsegmented negative-strand (NNS) RNA genome containing seven genes. The viral genes either are separated by intergenic regions (IRs) of variable length or overlap. The structure of the EBOV gene overlaps is conserved throughout all filovirus genomes and is distinct from that of the overlaps found in other NNS RNA viruses. Here, we analyzed how diverse gene borders and noncoding regions surrounding the gene borders influence transcript levels and govern polymerase behavior during viral transcription. Transcription of overlapping genes in EBOV bicistronic minigenomes followed the stop-start mechanism, similar to that followed by IR-containing gene borders. When the gene overlaps were extended, the EBOV polymerase was able to scan the template in an upstream direction. This polymerase feature seems to be generally conserved among NNS RNA virus polymerases. Analysis of IR-containing gene borders showed that the IR sequence plays only a minor role in transcription regulation. Changes in IR length were generally well tolerated, but specific IR lengths led to a strong decrease in downstream gene expression. Correlation analysis revealed that these effects were largely independent of the surrounding gene borders. Each EBOV gene contains exceptionally long untranslated regions (UTRs) flanking the open reading frame. Our data suggest that the UTRs adjacent to the gene borders are the main regulators of transcript levels. A highly complex interplay between the different cis-acting elements to modulate transcription was revealed for specific combinations of IRs and UTRs, emphasizing the importance of the noncoding regions in EBOV gene expression control. Our data extend those from previous analyses investigating the implication of noncoding regions at the EBOV gene borders for gene expression control. We show that EBOV transcription is regulated in a highly complex yet not easily predictable manner by a set of interacting cis

  5. Comparative evaluation of fiber fuse models

    International Nuclear Information System (INIS)

    Davis, D.D.; Mettler, S.C.; DiGiovanni, D.J.

    1997-01-01

    A phenomenon which results in the catastrophic destruction of the guiding properties of an optical fiber has been observed at laser power densities on the order of 3 x 10 6 watts/cm 2 in the core. This phenomenon is characterized by the propagation of a bright visible light from the point of initiation toward the laser source. The term 'fiber fuse' has been used because of the similarity in appearance to a burning fuse. The fiber fuse has been shown to start when the end of the fiber is contacted. It has also been initiated spontaneously from mechanical splices. This paper reports experimental data gathered on the fiber fuse and discusses their relationship to proposed physical mechanisms

  6. SINA: A test system for proximity fuses

    Science.gov (United States)

    Ruizenaar, M. G. A.

    1989-04-01

    SINA, a signal generator that can be used for testing proximity fuses, is described. The circuitry of proximity fuses is presented; the output signal of the RF circuit results from a mixing of the emitted signal and received signal that is Doppler shifted in frequency by the relative motion of the fuse with respect to the reflecting target of surface. With SINA, digitized and stored target and clutter signals (previously measured) can be transformed to Doppler signals, for example during a real flight. SINA can be used for testing fuse circuitry, for example in the verification of results of computer simulations of the low frequency Doppler signal processing. The software of SINA and its use are explained.

  7. Endodontic therapy for a fused mandibular molar.

    Science.gov (United States)

    Rotstein, I; Moshonov, J; Cohenca, N

    1997-06-01

    Variations in tooth morphology present a clinical challenge when endodontic treatment is required. A case of conservative endodontic therapy for a fused mandibular second and third molar is presented.

  8. 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.

  9. Transcription Factor NF-IL6 (C/EBPbeta) Activates the Expression of the Mouse MHC Class I H2-Kb Gene in Response to TNF-alpha via the Intragenic Downstream Regulatory Element

    Czech Academy of Sciences Publication Activity Database

    Hatina, J.; Jansa, Petr; Reischig, J.

    2002-01-01

    Roč. 22, - (2002), s. 741-749 ISSN 1079-9907 R&D Projects: GA MŠk(CZ) LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : Mouse MHC Class I Gene, Intragenic Downstream Regulatory Element Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.885, year: 2002

  10. 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

  11. Fused Bead Analysis of Diogenite Meteorites

    Science.gov (United States)

    Mittlefehldt, D.W.; Beck, B.W.; McSween, H.Y.; Lee, C.T. A.

    2009-01-01

    Bulk rock chemistry is an essential dataset in meteoritics and planetary science [1]. A common method used to obtain the bulk chemistry of meteorites is ICP-MS. While the accuracy, precision and low detection limits of this process are advantageous [2], the sample size used for analysis (approx.70 mg) can be a problem in a field where small and finite samples are the norm. Fused bead analysis is another bulk rock analytical technique that has been used in meteoritics [3]. This technique involves forming a glass bead from 10 mg of sample and measuring its chemistry using a defocused beam on a microprobe. Though the ICP-MS has lower detection limits than the microprobe, the fused bead method destroys a much smaller sample of the meteorite. Fused bead analysis was initially designed for samples with near-eutectic compositions and low viscosities. Melts generated of this type homogenize at relatively low temperatures and produce primary melts near the sample s bulk composition [3]. The application of fused bead analysis to samples with noneutectic melt compositions has not been validated. The purpose of this study is to test if fused bead analysis can accurately determine the bulk rock chemistry of non-eutectic melt composition meteorites. To determine this, we conduct two examinations of the fused bead. First, we compare ICP-MS and fused bead results of the same samples using statistical analysis. Secondly, we inspect the beads for the presence of crystals and chemical heterogeneity. The presence of either of these would indicate incomplete melting and quenching of the bead.

  12. Additive manufacturing of transparent fused quartz

    Science.gov (United States)

    Luo, Junjie; Hostetler, John M.; Gilbert, Luke; Goldstein, Jonathan T.; Urbas, Augustine M.; Bristow, Douglas A.; Landers, Robert G.; Kinzel, Edward C.

    2018-04-01

    This paper investigates a filament-fed process for additive manufacturing (AM) of fused quartz. Glasses such as fused quartz have significant scientific and engineering applications, which include optics, communications, electronics, and hermetic seals. AM has several attractive benefits such as increased design freedom, faster prototyping, and lower processing costs for small production volumes. However, current research into glass AM has focused primarily on nonoptical applications. Fused quartz is studied here because of its desirability for use in high-quality optics due to its high transmissivity and thermal stability. Fused quartz filaments are fed into a CO2 laser-generated molten region, smoothly depositing material onto the workpiece. Spectroscopy and pyrometry are used to measure the thermal radiation incandescently emitted from the molten region. The effects of the laser power and scan speed are determined by measuring the morphology of single tracks. Thin walls are printed to study the effects of layer-to-layer height. This information is used to deposit solid pieces including a cylindrical-convex shape capable of focusing visible light. The transmittance and index homogeneity of the printed fused quartz are measured. These results show that the filament-fed process has the potential to print transmissive optics.

  13. Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: correlation with development of hypercholesterolemia.

    Science.gov (United States)

    Kojima, Misaki; Degawa, Masakuni

    2006-01-01

    Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats. Copyright (c) 2006 John Wiley & Sons, Ltd.

  14. Association between single nucleotide polymorphisms of sterol regulatory element binding protein-2 gene and risk of knee osteoarthritis in a Chinese Han population.

    Science.gov (United States)

    Qiu, Xiao-Ming; Jin, Cheng-Tao; Wang, Wei

    2014-04-01

    To investigate associations between single nucleotide polymorphisms (SNPs) rs2228314 and rs2267443 in the sterol regulatory element binding protein-2 gene (SREBP-2) and knee osteoarthritis (OA) susceptibility in a Chinese Han population. SREBP-2 rs2228314 and rs2267443 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 402 patients with knee OA and 410 controls were enrolled in the study. GC and CC genotypes of rs2228314, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs2228314 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs2267443 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. SREBP-2 rs2228314 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.

  15. β-Hydroxybutyrate Facilitates Fatty Acids Synthesis Mediated by Sterol Regulatory Element-Binding Protein1 in Bovine Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Min Zhang

    2015-11-01

    Full Text Available Background/Aims: In dairy cows, β-hydroxybutyrate (BHBA is utilized as precursors of de novo synthesized fatty acids in mammary gland. Ketotic cows are characterized by excessive negative energy balance (NEB, which can further increase the blood BHBA concentration. Sterol regulatory element-binding protein1 (SREBP1 and cell death-inducing DNA fragmentation factor-alpha-like effector α (Cidea play crucial roles in lipid synthesis. Therefore, we hypothesized that BHBA could stimulate SREBP1/Cidea pathway to increase milk fat synthesis in bovine mammary epithelial cells. Methods: Bovine mammary epithelial cells were treated with different concentrations of BHBA and transfected with adenovirus to silence SREBP1 expression. The effects of BHBA on the lipid synthesis in bovine mammary epithelial cells were investigated. Results: The results showed that BHBA could significantly increase the expression of SREBP1, fatty acid synthase (FAS, acetyl-CoA carboxylase α (ACC-α, Cidea and diacylglycerol transferase-1 (DGAT-1, as well as the triglycerides (TG content in bovine mammary epithelial cells. BHBA treatment also increased the transfer of mature SREBP1 to nucleus compared with control group. However, SREBP1 silencing could significantly down-regulate the overexpression of FAS, ACC-α, Cidea and DGAT-1, as well as TG content induced by BHBA. Conclusion: The present data indicate that BHBA can significantly increase TG secretion mediated by SREBP1 in bovine mammary epithelial cells.

  16. A 3.0-kb deletion including an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene in an individual with the Bm phenotype.

    Science.gov (United States)

    Sano, R; Kuboya, E; Nakajima, T; Takahashi, Y; Takahashi, K; Kubo, R; Kominato, Y; Takeshita, H; Yamao, H; Kishida, T; Isa, K; Ogasawara, K; Uchikawa, M

    2015-04-01

    We developed a sequence-specific primer PCR (SSP-PCR) for detection of a 5.8-kb deletion (B(m) 5.8) involving an erythroid cell-specific regulatory element in intron 1 of the ABO blood group gene. Using this SSP-PCR, we performed genetic analysis of 382 individuals with Bm or ABm. The 5.8-kb deletion was found in 380 individuals, and disruption of the GATA motif in the regulatory element was found in one individual. Furthermore, a novel 3.0-kb deletion involving the element (B(m) 3.0) was demonstrated in the remaining individual. Comparisons of single-nucleotide polymorphisms and microsatellites in intron 1 between B(m) 5.8 and B(m) 3.0 suggested that these deletions occurred independently. © 2014 International Society of Blood Transfusion.

  17. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

    Science.gov (United States)

    Hamada, K; Gleason, S L; Levi, B Z; Hirschfeld, S; Appella, E; Ozato, K

    1989-11-01

    Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.

  18. Fusing Facial Features for Face Recognition

    Directory of Open Access Journals (Sweden)

    Jamal Ahmad Dargham

    2012-06-01

    Full Text Available Face recognition is an important biometric method because of its potential applications in many fields, such as access control, surveillance, and human-computer interaction. In this paper, a face recognition system that fuses the outputs of three face recognition systems based on Gabor jets is presented. The first system uses the magnitude, the second uses the phase, and the third uses the phase-weighted magnitude of the jets. The jets are generated from facial landmarks selected using three selection methods. It was found out that fusing the facial features gives better recognition rate than either facial feature used individually regardless of the landmark selection method.

  19. Fused aromatic thienopyrazines: structure, properties and function

    KAUST Repository

    Mondal, Rajib

    2010-01-01

    Recent development of a fused aromatic thieno[3.4-b]pyrazine system and their application in optoelectronic devices are reviewed. Introduction of a fused aromatic unit followed by side chain engineering, dramatically enhanced the charge carrier mobility in thin film transistor devices and mobilities up to 0.2 cm2/Vs were achieved. The optoelectronic properties of these fused aromatic thienopyrazine polymers (Eg = 1.3 to 1.6 eV, HOMO = -4.9 to -5.2 V) were tuned by introduction of various fused aromatic rings within thienopyrazine. By balancing the fundamental properties of these polymers, both high charge carrier mobilities and moderate PCEs in solar cells were achieved. Further, effects of copolymerizing units are discussed. Low band gap semiconducting polymer (Eg ∼ 1 eV) with high field effect mobility (0.044 cm2/Vs) was obtained using cyclopentadithiophene as copolymerizing unit. Finally, a molecular design approach to enhance the absorption coefficients is discussed, which resulted in improved power conversion efficiency in bulk heterojunction solar cells. © 2010 The Royal Society of Chemistry.

  20. Fungal Systematics and Evolution: FUSE 1

    NARCIS (Netherlands)

    Crous, Pedro W; Schumacher, René K; Wingfield, Michael J; Lombard, Lorenzo; Giraldo, Alejandra; Christensen, Martha; Gardiennet, Alain; Nakashima, Chiharu; Pereira, Olinto L; Smith, Alexander J; Groenewald, Johannes Z

    2015-01-01

    Fungal Systematics and Evolution (FUSE) is introduced as a new series to expedite the publication of issues relating to the epitypification of formerly described species, report new sexual-asexual connections, the merging of sexual and asexual gen¬era following the end of dual nomenclature, and to

  1. Investigation of fused silica dynamic behaviour

    International Nuclear Information System (INIS)

    Malaise, F.; Chevalier, J.M.; Bertron, I.; Malka, F.

    2006-01-01

    The survivability of the fused silica shields to shrapnel impacts is a key factor for the affordable operation of the intense laser irradiation future facility Laser Mega Joule (LMJ). This paper presents experimental data and computational modelling for LMJ fused silica upon shock wave loading and unloading. Gas-gun flyer plate impact and explosively driven tests have been conducted to investigate the dynamic behaviour of this material. Hugoniot states and the Hugoniot Elastic Limit of LMJ fused silica have been obtained. These experimental data are useful for determining some constitutive model constants of the 'Crack-Model', a continuum tensile and compressive failure model with friction based. This model has been improved by taking into account nonlinear elasticity. The numerical results obtained by performing computations of the previous tests and some ballistic impact tests are discussed. The numerical comparisons with the experimental data show good agreement. Further developments to simulate the permanent densification and the solid-to-solid phase transformation of fused silica are required. (authors)

  2. Demonstrating Earth Connections and Fuses Working Together

    Science.gov (United States)

    Harrison, Mark

    2017-01-01

    Earth wires and fuses work together in UK mains circuits to keep users safe from electric shocks and are taught in many school contexts. The subject can be quite abstract and difficult for pupils to grasp, and a simple but visually clear and direct demonstration is described which would be easy for most physics departments to build and which can…

  3. Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway.

    Science.gov (United States)

    Ding, Lili; Li, Jinmei; Song, Baoliang; Xiao, Xu; Huang, Wendong; Zhang, Binfeng; Tang, Xiaowen; Qi, Meng; Yang, Qiming; Yang, Qiaoling; Yang, Li; Wang, Zhengtao

    2014-11-01

    Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Honokiol reverses alcoholic fatty liver by inhibiting the maturation of sterol regulatory element binding protein-1c and the expression of its downstream lipogenesis genes

    International Nuclear Information System (INIS)

    Yin Huquan; Kim, Youn-Chul; Chung, Young-Suk; Kim, Young-Chul; Shin, Young-Kee; Lee, Byung-Hoon

    2009-01-01

    Ethanol induces hepatic steatosis via a complex mechanism that is not well understood. Among the variety of molecules that have been proposed to participate in this mechanism, the sterol regulatory element (SRE)-binding proteins (SREBPs) have been identified as attractive targets for therapeutic intervention. In the present study, we evaluated the effects of honokiol on alcoholic steatosis and investigated its possible effect on the inhibition of SREBP-1c maturation. In in vitro studies, H4IIEC3 rat hepatoma cells developed increased lipid droplets when exposed to ethanol, but co-treatment with honokiol reversed this effect. Honokiol inhibited the maturation of SREBP-1c and its translocation to the nucleus, the binding of nSREBP-1c to SRE or SRE-related sequences of its lipogenic target genes, and the expression of genes for fatty acid synthesis. In contrast, magnolol, a structural isomer of honokiol, had no effect on nSREBP-1c levels. Male Wistar rats fed with a standard Lieber-DeCarli ethanol diet for 4 weeks exhibited increased hepatic triglyceride and decreased hepatic glutathione levels, with concomitantly increased serum alanine aminotransferase and TNF-α levels. Daily administration of honokiol (10 mg/kg body weight) by gavage during the final 2 weeks of ethanol treatment completely reversed these effects on hepatotoxicity markers, including hepatic triglyceride, hepatic glutathione, and serum TNF-α, with efficacious abrogation of fat accumulation in the liver. Inhibition of SREBP-1c protein maturation and of the expression of Srebf1c and its target genes for hepatic lipogenesis were also observed in vivo. A chromatin immunoprecipitation assay demonstrated inhibition of specific binding of SREBP-1c to the Fas promoter by honokiol in vivo. These results demonstrate that honokiol has the potential to ameliorate alcoholic steatosis by blocking fatty acid synthesis regulated by SREBP-1c

  5. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada); Babiuk, Lorne A. [University of Alberta, Edmonton, Alberta (Canada); Liu, Qiang, E-mail: qiang.liu@usask.ca [Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5E3 (Canada)

    2010-11-19

    Research highlights: {yields} A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. {yields} HCV-3a NS5A increases mature SREBP-1c protein level. {yields} HCV-3a NS5A activates SREBP-1c transcription. {yields} Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. {yields} Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  6. The Hepatitis C Virus-induced NLRP3 Inflammasome Activates the Sterol Regulatory Element-binding Protein (SREBP) and Regulates Lipid Metabolism.

    Science.gov (United States)

    McRae, Steven; Iqbal, Jawed; Sarkar-Dutta, Mehuli; Lane, Samantha; Nagaraj, Abhiram; Ali, Naushad; Waris, Gulam

    2016-02-12

    Hepatitis C virus (HCV) relies on host lipids and lipid droplets for replication and morphogenesis. The accumulation of lipid droplets in infected hepatocytes manifests as hepatosteatosis, a common pathology observed in chronic hepatitis C patients. One way by which HCV promotes the accumulation of intracellular lipids is through enhancing de novo lipogenesis by activating the sterol regulatory element-binding proteins (SREBPs). In general, activation of SREBPs occurs during cholesterol depletion. Interestingly, during HCV infection, the activation of SREBPs occurs under normal cholesterol levels, but the underlying mechanisms are still elusive. Our previous study has demonstrated the activation of the inflammasome complex in HCV-infected human hepatoma cells. In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid droplet formation. NLRP3 inflammasome activation in HCV-infected cells enables caspase-1-mediated degradation of insulin-induced gene proteins. This subsequently leads to the transport of the SREBP cleavage-activating protein·SREBP complex from the endoplasmic reticulum to the Golgi, followed by proteolytic activation of SREBPs by S1P and S2P in the Golgi. Typically, inflammasome activation leads to viral clearance. Paradoxically, here we demonstrate how HCV exploits the NLRP3 inflammasome to activate SREBPs and host lipid metabolism, leading to liver disease pathogenesis associated with

  7. Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study

    Science.gov (United States)

    Pérez-Belmonte, Luis M.; Moreno-Santos, Inmaculada; Cabrera-Bueno, Fernando; Sánchez-Espín, Gemma; Castellano, Daniel; Such, Miguel; Crespo-Leiro, María G; Carrasco-Chinchilla, Fernando; Alonso-Pulpón, Luis; López-Garrido, Miguel; Ruiz-Salas, Amalio; Becerra-Muñoz, Víctor M.; Gómez-Doblas, Juan J.; de Teresa-Galván, Eduardo; Jiménez-Navarro, Manuel

    2017-01-01

    Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (pcardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target. PMID:28367087

  8. p75 Neurotrophin Receptor Signaling Activates Sterol Regulatory Element-binding Protein-2 in Hepatocyte Cells via p38 Mitogen-activated Protein Kinase and Caspase-3.

    Science.gov (United States)

    Pham, Dan Duc; Do, Hai Thi; Bruelle, Céline; Kukkonen, Jyrki P; Eriksson, Ove; Mogollón, Isabel; Korhonen, Laura T; Arumäe, Urmas; Lindholm, Dan

    2016-05-13

    Nerve growth factor (NGF) influences the survival and differentiation of a specific population of neurons during development, but its role in non-neuronal cells has been less studied. We observed here that NGF and its pro-form, pro-NGF, are elevated in fatty livers from leptin-deficient mice compared with controls, concomitant with an increase in low density lipoprotein receptors (LDLRs). Stimulation of mouse primary hepatocytes with NGF or pro-NGF increased LDLR expression through the p75 neurotrophin receptor (p75NTR). Studies using Huh7 human hepatocyte cells showed that the neurotrophins activate the sterol regulatory element-binding protein-2 (SREBP2) that regulates genes involved in lipid metabolism. The mechanisms for this were related to stimulation of p38 mitogen-activated protein kinase (p38 MAPK) and activation of caspase-3 and SREBP2 cleavage following NGF and pro-NGF stimulations. Cell fractionation experiments showed that caspase-3 activity was increased particularly in the membrane fraction that harbors SREBP2 and caspase-2. Experiments showed further that caspase-2 interacts with pro-caspase-3 and that p38 MAPK reduced this interaction and caused caspase-3 activation. Because of the increased caspase-3 activity, the cells did not undergo cell death following p75NTR stimulation, possibly due to concomitant activation of nuclear factor-κB (NF-κB) pathway by the neurotrophins. These results identify a novel signaling pathway triggered by ligand-activated p75NTR that via p38 MAPK and caspase-3 mediate the activation of SREBP2. This pathway may regulate LDLRs and lipid uptake particularly after injury or during tissue inflammation accompanied by an increased production of growth factors, including NGF and pro-NGF. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Hepatitis C virus nonstructural protein-5A activates sterol regulatory element-binding protein-1c through transcription factor Sp1

    International Nuclear Information System (INIS)

    Xiang, Zhonghua; Qiao, Ling; Zhou, Yan; Babiuk, Lorne A.; Liu, Qiang

    2010-01-01

    Research highlights: → A chimeric subgenomic HCV replicon expresses HCV-3a NS5A in an HCV-1b backbone. → HCV-3a NS5A increases mature SREBP-1c protein level. → HCV-3a NS5A activates SREBP-1c transcription. → Domain II of HCV-3a NS5A is more effective in SREBP-1c promoter activation. → Transcription factor Sp1 is required for SREBP-1c activation by HCV-3a NS5A. -- Abstract: Steatosis is an important clinical manifestation of hepatitis C virus (HCV) infection. The molecular mechanisms of HCV-associated steatosis are not well understood. Sterol regulatory element-binding protein-1c (SREBP-1c) is a key transcription factor which activates the transcription of lipogenic genes. Here we showed that the nuclear, mature SREBP-1c level increases in the nucleus of replicon cells expressing HCV-3a nonstructural protein-5A (NS5A). We further showed that HCV-3a NS5A up-regulates SREBP-1c transcription. Additional analysis showed that transcriptional factor Sp1 is involved in SREBP-1c activation by HCV-3a NS5A because inhibition of Sp1 activity by mithramycin A or a dominant-negative Sp1 construct abrogated SREBP-1c promoter activation by HCV-3a NS5A. In addition, chromatin immunoprecipitation (ChIP) assay demonstrated enhanced binding of Sp1 on the SREBP-1c promoter in HCV-3a NS5A replicon cells. These results showed that HCV-3a NS5A activates SREBP-1c transcription through Sp1. Taken together, our results suggest that HCV-3a NS5A is a contributing factor for steatosis caused by HCV-3a infection.

  10. Expression of 5 S rRNA genes linked to 35 S rDNA in plants, their epigenetic modification and regulatory element divergence

    Directory of Open Access Journals (Sweden)

    Garcia Sònia

    2012-06-01

    Full Text Available Abstract Background In plants, the 5 S rRNA genes usually occur as separate tandems (S-type arrangement or, less commonly, linked to 35 S rDNA units (L-type. The activity of linked genes remains unknown so far. We studied the homogeneity and expression of 5 S genes in several species from family Asteraceae known to contain linked 35 S-5 S units. Additionally, their methylation status was determined using bisulfite sequencing. Fluorescence in situ hybridization was applied to reveal the sub-nuclear positions of rDNA arrays. Results We found that homogenization of L-type units went to completion in most (4/6 but not all species. Two species contained major L-type and minor S-type units (termed Ls-type. The linked genes dominate 5 S rDNA expression while the separate tandems do not seem to be expressed. Members of tribe Anthemideae evolved functional variants of the polymerase III promoter in which a residing C-box element differs from the canonical angiosperm motif by as much as 30%. On this basis, a more relaxed consensus sequence of a plant C-box: (5’-RGSWTGGGTG-3’ is proposed. The 5 S paralogs display heavy DNA methylation similarly as to their unlinked counterparts. FISH revealed the close association of 35 S-5 S arrays with nucleolar periphery indicating that transcription of 5 S genes may occur in this territory. Conclusions We show that the unusual linked arrangement of 5 S genes, occurring in several plant species, is fully compatible with their expression and functionality. This extraordinary 5 S gene dynamics is manifested at different levels, such as variation in intrachromosomal positions, unit structure, epigenetic modification and considerable divergence of regulatory motifs.

  11. Fusing Open Source Intelligence and Handheld Situational Awareness - Benghazi Case Study

    Science.gov (United States)

    2014-10-01

    1 DM-0001694 Fusing Open Source Intelligence and Handheld Situational Awareness Benghazi Case Study Jeff Boleng, PhD Marc Novakouski Gene...command and control element at the CIA compound that would have been monitoring OSINT and other sources of intelligence before the attack and... Source Intelligence and Handheld Situational Awareness - Benghazi Case Study 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  12. The FUSE satellite is encased in a canister before being moved to the Launch Pad.

    Science.gov (United States)

    1999-01-01

    At Hangar AE, Cape Canaveral Air Station (CCAS), the last segment is lifted over the top of NASA's Far Ultraviolet Spectroscopic Explorer (FUSE) satellite already encased in a protective canister. The satellite will next be moved to Launch Pad 17A, CCAS, for its scheduled launch June 23 aboard a Boeing Delta II rocket. FUSE was developed by The Johns Hopkins University under contract to Goddard Space Flight Center, Greenbelt, Md., to investigate the origin and evolution of the lightest elements in the universe - hydrogen and deuterium. In addition, the FUSE satellite will examine the forces and process involved in the evolution of the galaxies, stars and planetary systems by investigating light in the far ultraviolet portion of the electromagnetic spectrum.

  13. Laser induced damage and fracture in fused silica vacuum windows

    International Nuclear Information System (INIS)

    Campbell, J.H.; Hurst, P.A.; Heggins, D.D.; Steele, W.A.; Bumpas, S.E.

    1996-11-01

    Laser-induced damage, that initiates catastrophic fracture, has been observed in large (≤61 cm dia) fused silica lenses that also serve as vacuum barriers in Nova and Beamlet lasers. If the elastic stored energy in the lens is high enough, the lens will fracture into many pieces (implosion). Three parameters control the degree of fracture in the vacuum barrier window: elastic stored energy (tensile stress), ratio of window thickness to flaw depth, and secondary crack propagation. Fracture experiments were conducted on 15-cm dia fused silica windows that contain surface flaws caused by laser damage. Results, combined with window failure data on Beamlet and Nova, were used to develop design criteria for a ''fail-safe'' lens (that may catastrophically fracture but not implode). Specifically, the window must be made thick enough so that the peak tensile stress is less than 500 psi (3.4 MPa) and the thickness/critical flaw size is less than 6. The air leak through the window fracture and into the vacuum must be rapid enough to reduce the load on the window before secondary crack growth occurs. Finite element stress calculations of a window before and immediately following fracture into two pieces show that the elastic stored energy is redistributed if the fragments ''lock'' in place and thereby bridge the opening. In such cases, the peak stresses at the flaw site can increase, leading to further (i.e. secondary) crack growth

  14. Electric fuses operation, a review: 2. Arcing period

    International Nuclear Information System (INIS)

    Bussière, W

    2012-01-01

    In the electric fuse operation the arcing period follows immediately the pre-arcing period depicted in Part 1 (Part 1. Pre-arcing period). The transition between these two operation steps is not fully understood at this time. To simplify the beginning of the arcing period can be identified with the electric arc ignition i.e. with the electrodes voltage drop. The consecutive plasma is of metallic type at the beginning of the arcing period and of metallic plus silica type with varying mixture up to the end of the arcing period. The energy brought by the fault current is withdrawn by means of the interaction between the electric arc and the arc quenching material (usually silica sand) whose morphometric properties influence the properties of the plasma column: composition, thermodynamic properties and transport coefficients of the plasma column depend on the porosity (and other morphometric properties) of the filler. The fuse element erosion also known as burn-back is responsible for the lengthening of the plasma column and the variations of the electric field. The whole of these processes is depicted by means of experimental results or modellings when possible.

  15. Nanodrilling of fused silica using nanosecond laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, P., E-mail: pierre.lorenz@iom-leipzig.de; Zajadacz, J.; Bayer, L.; Ehrhardt, M.; Zimmer, K.

    2015-10-01

    Graphical abstract: - Highlights: • Low-fluence irradiation of 10 nm Mo on SiO{sub 2} results in the formation of Mo droplets. • High-fluence irradiation of droplets results in the formation of holes in the SiO{sub 2}. • The process allows the formation of randomly distributed and periodic holes. • The randomly distributed hole density ρ{sub h} depends on the fluence (ρ{sub h} ≤ 1.3 μm{sup −2}). • The interaction of the laser beam with Mo/SiO{sub 2} was simulated by FEM. - Abstract: The fast laser drilling of dielectric surfaces with hole diameters in the sub-μm range and a high aspect ratio is a challenge for laser methods. In this study, a novel laser structuring method for the production of randomly and periodically distributed holes in a fused silica surface will be presented using a self-assembling process. A fused silica surface was covered with a 10 nm thick magnetron-sputtered molybdenum film. The metal film was irradiated by a KrF excimer laser (wavelength λ = 248 nm, pulse duration Δt{sub p} = 25 ns) with low laser fluences (Φ < 1 J/cm{sup 2}) and the laser-induced heating resulting in a melting of the metal film and finally in a self-assembled formation of randomly distributed metal droplets due to the surface tension of the metal liquid phase using a top hat beam profile. Furthermore, the usage of a periodically modulated laser beam profile allows the fabrication of periodically distributed droplet pattern. The multi-pulse irradiation of the laser-generated metal droplets with higher laser fluences results in a stepwise evaporation of the metal and in a partial evaporation of the fused silica near the metal droplets. Finally, the laser-induced stepwise evaporation process results in a formation of cone-like holes in the fused silica surface where the resultant holes are dependent on the size of the generated metal droplets and on the laser parameters. The “drilling” process allows the fabrication of holes with a depth up to 1

  16. Dihydropyridine-fused and pyridine-fused coumarins: Reduction on a glassy carbon electrode in dimethylformamide

    International Nuclear Information System (INIS)

    Nuñez-Vergara, Luis J.; Pardo-Jiménez, V.; Barrientos, C.; Olea-Azar, C.A.; Navarrete-Encina, P.A.; Squella, J.A.

    2012-01-01

    In this study, two series of dihydropyridine-fused and pyridine-fused coumarins were synthesised and electrochemically characterised in aprotic medium. In both series, the most easily reducible groups were the endocyclic carbonyl groups. The electrochemical mechanism for both types of compounds is strongly dependent on the experimental time-scale. Cyclic voltammetric (CV) reduction on a glassy carbon electrode (GCE) of the endocyclic carbonyl group of dihydropyridine-fused coumarins involves an ECEC mechanism with two electron transfer steps that are coupled with chemical reactions to produce the corresponding hemiacetal derivative. In the case of pyridine-fused coumarins, CV reduction of the endocyclic carbonyl group involves an EEC mechanism. ESR studies revealed the presence of a stabilised intermediate only for the pyridine-fused derivatives. Our theoretical study showed a spin density map of radical species delocalised mainly within the coumarin ring, indicating the reduction of the endocyclic carbonyl group. In the case of the dihydropyridine-fused derivatives, the mildly acid hydrogen of the dihydropyridine ring destabilises the radical via a father–son type reaction.

  17. 29 CFR 1926.907 - Use of safety fuse.

    Science.gov (United States)

    2010-07-01

    ... way shall be forbidden. (b) The hanging of a fuse on nails or other projections which will cause a...-called “drop fuse” method of dropping or pushing a primer or any explosive with a lighted fuse attached...

  18. Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

    Directory of Open Access Journals (Sweden)

    Andoh Y

    2013-01-01

    Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

  19. 30 CFR 57.12036 - Fuse removal or replacement.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fuse removal or replacement. 57.12036 Section 57.12036 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... Electricity Surface and Underground § 57.12036 Fuse removal or replacement. Fuses shall not be removed or...

  20. 30 CFR 56.12036 - Fuse removal or replacement.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fuse removal or replacement. 56.12036 Section 56.12036 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND... § 56.12036 Fuse removal or replacement. Fuses shall not be removed or replaced by hand in an energized...

  1. Optimization of codon composition and regulatory elements for expression of human insulin like growth factor-1 in transgenic chloroplasts and evaluation of structural identity and function.

    Science.gov (United States)

    Daniell, Henry; Ruiz, Gricel; Denes, Bela; Sandberg, Laurence; Langridge, William

    2009-04-03

    Transgenic chloroplasts are potential bioreactors for recombinant protein production, especially for achievement of high levels of protein expression and proper folding. Production of therapeutic proteins in leaves provides transgene containment by elimination of reproductive structures. Therefore, in this study, human Insulin like Growth Factor-1 is expressed in transgenic chloroplasts for evaluation of structural identity and function. Expression of the synthetic Insulin like Growth Factor 1 gene (IGF-1s, 60% AT) was observed in transformed E. coli. However, no native IGF-1 gene (IGF-1n, 41% AT) product was detected in the western blots in E. coli. Site-specific integration of the transgenes into the tobacco chloroplast genome was confirmed after transformation using PCR. Southern blot analysis confirmed that the transgenic lines were homoplasmic. The transgenic plant lines had IGF-1s expression levels of 11.3% of total soluble protein (TSP). The IGF-1n plants contained 9.5% TSP as IGF-1n, suggesting that the chloroplast translation machinery is more flexible than E. coli in codon preference and usage. The expression of IGF-1 was increased up to 32% TSP under continuous illumination by the chloroplast light regulatory elements. IgG-Sepharose affinity column chromatographic separation of Z domain containing chloroplast derived IGF-1 protein, single and two dimensional electrophoresis methods and mass spectrometer analysis confirmed the identity of human IGF-1 in transgenic chloroplasts. Two spots analyzed from 2-D focusing/phoresis acrylamide gel showed the correct amino acid sequence of human IGF-1 and the S. aureus Z-tag. Cell proliferation assays in human HU-3 cells demonstrated the biological activity of chloroplast derived IGF-1 even in the presence of the S. aureus Z tag. This study demonstrates that the human Insulin like Growth Factor-1 expressed in transgenic chloroplasts is identical to the native protein and is fully functional. The ability to use plant

  2. Optimization of codon composition and regulatory elements for expression of human insulin like growth factor-1 in transgenic chloroplasts and evaluation of structural identity and function

    Directory of Open Access Journals (Sweden)

    Sandberg Laurence

    2009-04-01

    Full Text Available Abstract Background Transgenic chloroplasts are potential bioreactors for recombinant protein production, especially for achievement of high levels of protein expression and proper folding. Production of therapeutic proteins in leaves provides transgene containment by elimination of reproductive structures. Therefore, in this study, human Insulin like Growth Factor-1 is expressed in transgenic chloroplasts for evaluation of structural identity and function. Results Expression of the synthetic Insulin like Growth Factor 1 gene (IGF-1s, 60% AT was observed in transformed E. coli. However, no native IGF-1 gene (IGF-1n, 41% AT product was detected in the western blots in E. coli. Site-specific integration of the transgenes into the tobacco chloroplast genome was confirmed after transformation using PCR. Southern blot analysis confirmed that the transgenic lines were homoplasmic. The transgenic plant lines had IGF-1s expression levels of 11.3% of total soluble protein (TSP. The IGF-1n plants contained 9.5% TSP as IGF-1n, suggesting that the chloroplast translation machinery is more flexible than E. coli in codon preference and usage. The expression of IGF-1 was increased up to 32% TSP under continuous illumination by the chloroplast light regulatory elements. IgG-Sepharose affinity column chromatographic separation of Z domain containing chloroplast derived IGF-1 protein, single and two dimensional electrophoresis methods and mass spectrometer analysis confirmed the identity of human IGF-1 in transgenic chloroplasts. Two spots analyzed from 2-D focusing/phoresis acrylamide gel showed the correct amino acid sequence of human IGF-1 and the S. aureus Z-tag. Cell proliferation assays in human HU-3 cells demonstrated the biological activity of chloroplast derived IGF-1 even in the presence of the S. aureus Z tag. Conclusion This study demonstrates that the human Insulin like Growth Factor-1 expressed in transgenic chloroplasts is identical to the native

  3. The challenges of treating a fused tooth

    OpenAIRE

    Baratto-Filho, Flares; Leonardi, Denise Piotto; Crozeta, Bruno Monguilhott; Baratto, Samantha Pugsley; Campos, Edson Alves; Tomazinho, Flavia Sens Fagundes; Deliberador, Tatiana Miranda

    2012-01-01

    This paper describes and discusses the multidisciplinary treatment involving a permanent maxillary lateral incisor fused to a supernumerary tooth, both presenting pulp necrosis and periapical lesion. A 15-year-old male patient sought treatment complaining of pain, swelling and mobility on the maxillary right lateral incisor. After clinical and radiographic examination, root canal preparation was performed according to the crown-down technique and a calcium hydroxide dressing was placed for 15...

  4. Fungal Systematics and Evolution: FUSE 1

    OpenAIRE

    Crous, Pedro W; Schumacher, René K; Wingfield, Michael J; Lombard, Lorenzo; Giraldo, Alejandra; Christensen, Martha; Gardiennet, Alain; Nakashima, Chiharu; Pereira, Olinto L; Smith, Alexander J; Groenewald, Johannes Z

    2015-01-01

    Fungal Systematics and Evolution (FUSE) is introduced as a new series to expedite the publication of issues relating to the epitypification of formerly described species, report new sexual-asexual connections, the merging of sexual and asexual gen¬era following the end of dual nomenclature, and to describe species or note interesting observations regarding fungi. This first paper includes 18 new combinations, 13 new species, three new genera and one new family. All taxa are ascomycetes, excep...

  5. Titanium metal obtention by fused salts electrolysis

    International Nuclear Information System (INIS)

    Perillo, P.M.; Ares, Osvaldo; Botbol, Jose.

    1989-01-01

    Potassium fluorotitanate dissolved in fused sodium chloride or potassium chloride may be electrolyzed under an inert gas atmosphere. Solid electrolysis products are formed on the cathode which contains titanium metal, sodium chloride, lower fluorotitanates and small quantities of alkali metal fluorotitanate. The extraction of titanium from the electrolysis products may be carried out by aqueous leaching (removal of chloride salts of alkali metals and a certain amount of fluorotitanates). Titanium metal obtained is relatively pure. (Author)

  6. Electrolysis of uranium tetrafluorure fused salts

    International Nuclear Information System (INIS)

    Perillo, P.M.; Botbol, J.

    1991-01-01

    Electrolytic preparation of U has been unsuccessful because the metal formed is in easily oxidized state. Electrolytic depositions were made under various conditions from fused NaCl-KCl baths containing UF 4 . X-ray diffraction studies were made of the products. The results indicate that mixed U with several oxides phases are produced. It was concluded that the method was unlikely to be efficient for the production of U metal. (Author) [es

  7. Helicopter Aircrew Training Using Fused Reality

    Science.gov (United States)

    2006-06-01

    PROCESS Blue screening involving human filming usually employs a blue or green backdrop, since skin contains little blue or green hue. These backdrops...Helicopter Aircrew Training Using Fused Reality 27 - 10 RTO-MP-HFM-136 a. b. c. d. e. f. Figure 13: Frames Showing Physical Object ( witch ... filming . However, when a user’s hands disrupt the light from a helmet-mounted light source, the shadows cast onto the distant background are diffuse and

  8. Outbursts In Symbiotic Binaries (FUSE 2000)

    Science.gov (United States)

    Kenyon, Scott J.; Sonneborn, George (Technical Monitor)

    2002-01-01

    During the past year, we made good progress on analysis of FUSE observations of the symbiotic binary Z And. For background, Z And is a binary system composed of a red giant and a hot component of unknown status. The orbital period is roughly 750 days. The hot component undergoes large-scale eruptions every 10-20 yr. An outburst began several years ago, triggering this FUSE opportunity. First, we obtained an excellent set of ground-based optical data in support, of the FUSE observations. We used FAST, a high throughput low resolution spectrograph on the 1.5-m telescope at Mt. Hopkins, Arizona. A 300 g/ mm grating blazed at 4750 A, a 3 in. slit, and a thinned Loral 512 x 2688 CCD gave us spectra covering 3800-7500 A at a resolution of 6 A. The wavelength solution for each spectrum has a probable error of +/- 0.5 A or better. Most of the resulting spectra have moderate signal-to-noise, S/.N approx. greater than 30 per pixel. The time coverage for these spectra is excellent. Typically, we acquired spectra every 1-2 nights during dark runs at Mt. Hopkins. These data cover most of the rise and all of the decline of the recent outburst. The spectra show a wealth of emission lines, including H I, He I, He II, [Fe V11], and the Raman scattering bands at 6830 A and 7088 A. The Raman bands and other high ionization features vary considerably throughout the outburst. These features will enable us to correlate variations in the FUSE spectra with variations in the optical spectra. Second, we began an analysis of FUSE spectra of Z And. We have carefully examined the spectra, identifying real features and defects. We have identified and measured fluxes for all strong emission lines, including the O VI doublet at 1032 A and 1038 A. These and several other strong emission lines display pronounced P Cygni absorption components indicative of outgrowing gas. We will attempt to correlate these velocities with similar profiles observed on optical spectra. The line velocities - together

  9. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  10. Reliability-oriented environmental thermal stress analysis of fuses in power electronics

    DEFF Research Database (Denmark)

    Bahman, A. S.; Iannuzzo, F.; Holmgaard, T.

    2017-01-01

    This paper investigates the thermo-mechanical stress experienced by axial lead fuses used in power electronics. Based on some experience, the approach used in this paper is pure thermal cycling, and the found failure mechanisms have been investigated through X-ray imaging. A two-step analysis, i...... element has been confirmed thanks to the analysis performed. Finally, the fatigue analysis is presented obtained by FEM-based fatigue tool....

  11. Fused Reality for Enhanced Flight Test Capabilities

    Science.gov (United States)

    Bachelder, Ed; Klyde, David

    2011-01-01

    The feasibility of using Fused Reality-based simulation technology to enhance flight test capabilities has been investigated. In terms of relevancy to piloted evaluation, there remains no substitute for actual flight tests, even when considering the fidelity and effectiveness of modern ground-based simulators. In addition to real-world cueing (vestibular, visual, aural, environmental, etc.), flight tests provide subtle but key intangibles that cannot be duplicated in a ground-based simulator. There is, however, a cost to be paid for the benefits of flight in terms of budget, mission complexity, and safety, including the need for ground and control-room personnel, additional aircraft, etc. A Fused Reality(tm) (FR) Flight system was developed that allows a virtual environment to be integrated with the test aircraft so that tasks such as aerial refueling, formation flying, or approach and landing can be accomplished without additional aircraft resources or the risk of operating in close proximity to the ground or other aircraft. Furthermore, the dynamic motions of the simulated objects can be directly correlated with the responses of the test aircraft. The FR Flight system will allow real-time observation of, and manual interaction with, the cockpit environment that serves as a frame for the virtual out-the-window scene.

  12. Establishment of the National Nuclear Regulatory Portal (NNRP) as the key element of the Global Nuclear Safety and Security Network and Regulatory Network (GNSSN/RegNet) for sharing of nuclear safety information and knowledge among the Global Expert Community

    International Nuclear Information System (INIS)

    Kuvshinnikov, A.V.

    2011-01-01

    The Global Nuclear Safety and Security Network (GNSSN) implements the concept of the Global Nuclear Safety and Security Framework (GNSSF) as outlined in INSAG 21. This is the framework of instruments and resources for achieving and maintaining worldwide a high level of safety and security at nuclear facilities and activities as stated in SF-1 and supporting safety standards or recommendations such as INSAG-12. National efforts are and should be augmented by the activities of a variety of international enterprises that facilitate safety and security. The IAEA standard GS-R-3 requires that information and knowledge is managed as a resource. Further strengthening of GNSSN in particular regulatory networking as intended by GNSSN/RegNet has to be based on current national priorities, on existing regional and thematic networks and on the established mechanisms of international co-operation as presented for example on the websites of the IAEA or the OECD-NEA. Current design and operation of RegNet are flexible enough to accommodate differences in national and international approaches and practices and to facilitate exchange and cooperation on regulatory matters. The main role of GNSSN/RegNet is sharing knowledge and bringing people together to enhance and promote nuclear safety and security. The objectives of GNSSN/RegNet: enhancing safety and security by international cooperation, sharing information and best practices, enabling adequate access to relevant safety and security information and promoting the dissemination of this information, implementing active collaboration in the relevant areas related to safety and security, such as joint projects, peer reviews, enabling synergies among existing networks and initiatives, informing the public on the relevant safety and security areas and the related international collaboration. In the RegNet part of the GNSSN exist the National Nuclear Regulatory Portal (NNRP) which is on one hand a part of the global RegNet and on the

  13. Fused upper central incisors: management of two clinical cases

    OpenAIRE

    Sfasciotti, Gian Luca; Marini, Roberta; Bossù, Maurizio; Ierardo, Gaetano; Annibali, Susanna

    2012-01-01

    This paper reports the management of two clinical cases, in which the upper right central incisor was fused with a supernumerary tooth and the upper left central incisor was macrodontic. A radiographic examination revealed that the fused teeth had two separate roots. Hemisectioning of the fused teeth was performed, the supernumerary portion was extracted and the remaining part was reshaped to remove any sharp margins and to achieve a normal morphology. The macrodontic central incisors were no...

  14. Generating User Interfaces with the FUSE-System

    OpenAIRE

    Frank Lonczewski; Siegfried Schreiber

    2017-01-01

    With the FUSE(Formal User interface Specification Environment)-System we present a methodology and a set of integrated tools for the automatic generation of graphical user interfaces. FUSE provides tool-based support for all phases (task-, user-, problem domain analysis, design of the logical user interface, design of user interface in a particular layout style) of the user interface development process. Based on a formal specification of dialogue- and layout guidelines, FUSE allows the autom...

  15. Cross-cohort analysis identifies a TEAD4 ↔ MYCN positive-feedback loop as the core regulatory element of high-risk neuroblastoma. | Office of Cancer Genomics

    Science.gov (United States)

    High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator (MR) proteins that were conserved across independent cohorts.

  16. A Radiographic Study of Fused and Geminated Tooth

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chul Jae; Lee, Sang Rae [Dept. of Oral Radiology, College of Dentistry, Kyunhee University, Seoul (Korea, Republic of)

    1990-02-15

    The incidence and several characteristic features of fused and geminated teeth were studied radiographically, with full mouth periapical radiogram and pantomogram, in 4201 patients of mixed dentition and 5358 patients of permanent dentition. The obtained results were as follows: 1. The prevalence was revealed to 2.86%, 0.32%, 0.33%, and 0.06% in deciduous fused tooth, permanent fused tooth, deciduous geminated tooth and permanent geminated tooth respectively, and these anomalies were occurred in female more than male. 2. Fused teeth were observed predominantly in lower anterior teeth area, especially in lateral incisor and canine region, and many cases of deciduous geminated tooth were observed in upper central incisor region. 3. Congenital missing rates of succedaneous tooth in deciduous fused teeth were 57.1%, 85.7%, 71.0%, 69.0% in upper right and left central-lateral incisor regions, lower right and left lateral incisor-canine regions, respectively. 4. Prevalence of dental caries was 42.3%, 18.8% and 5.6% in deciduous fused, deciduous geminated and permanent fused tooth, respectively. 5. In classifying of fused and geminated teeth into 9 type, by following appearance such as number of crown, root, pulp chamber and pulp canal of those teeth, it was more favorable that Type I (2 crown, 2 root, 2 pulp chamber, 2 pulp canal) in deciduous fused tooth and Type IX (1 crown, 1 root, 1 pulp chamber, 1 pulp canal) in permanent used tooth, deciduous and permanent geminated tooth.

  17. A Radiographic Study of Fused and Geminated Tooth

    International Nuclear Information System (INIS)

    Park, Chul Jae; Lee, Sang Rae

    1990-01-01

    The incidence and several characteristic features of fused and geminated teeth were studied radiographically, with full mouth periapical radiogram and pantomogram, in 4201 patients of mixed dentition and 5358 patients of permanent dentition. The obtained results were as follows: 1. The prevalence was revealed to 2.86%, 0.32%, 0.33%, and 0.06% in deciduous fused tooth, permanent fused tooth, deciduous geminated tooth and permanent geminated tooth respectively, and these anomalies were occurred in female more than male. 2. Fused teeth were observed predominantly in lower anterior teeth area, especially in lateral incisor and canine region, and many cases of deciduous geminated tooth were observed in upper central incisor region. 3. Congenital missing rates of succedaneous tooth in deciduous fused teeth were 57.1%, 85.7%, 71.0%, 69.0% in upper right and left central-lateral incisor regions, lower right and left lateral incisor-canine regions, respectively. 4. Prevalence of dental caries was 42.3%, 18.8% and 5.6% in deciduous fused, deciduous geminated and permanent fused tooth, respectively. 5. In classifying of fused and geminated teeth into 9 type, by following appearance such as number of crown, root, pulp chamber and pulp canal of those teeth, it was more favorable that Type I (2 crown, 2 root, 2 pulp chamber, 2 pulp canal) in deciduous fused tooth and Type IX (1 crown, 1 root, 1 pulp chamber, 1 pulp canal) in permanent used tooth, deciduous and permanent geminated tooth.

  18. Mechanical losses in thin fused silica fibres

    International Nuclear Information System (INIS)

    Bilenko, I A; Braginsky, V B; Lourie, S L

    2004-01-01

    Intracavity topology of the readout system for LIGO III project and table-top QND mechanical measurements under development require the use of small probe masses and suspensions with a very low level of internal losses. A good choice is to use thin fused silica fibres similar to LIGO II mirrors suspensions. Mechanical losses of silica fibres are investigated in this work through the study of quality factor dependence on diameter for pendulum and violin modes of oscillations with diameters ranging from 1.5 to 40 μm. The estimated values of effective mechanical loss angle show noticeably greater growth with lower diameters than might be expected while extrapolating known results of research done for thicker fibres

  19. Mechanical losses in thin fused silica fibres

    Energy Technology Data Exchange (ETDEWEB)

    Bilenko, I A; Braginsky, V B; Lourie, S L [Department of Oscillatory Physics, Physics Faculty, Moscow State University (Russian Federation)

    2004-03-07

    Intracavity topology of the readout system for LIGO III project and table-top QND mechanical measurements under development require the use of small probe masses and suspensions with a very low level of internal losses. A good choice is to use thin fused silica fibres similar to LIGO II mirrors suspensions. Mechanical losses of silica fibres are investigated in this work through the study of quality factor dependence on diameter for pendulum and violin modes of oscillations with diameters ranging from 1.5 to 40 {mu}m. The estimated values of effective mechanical loss angle show noticeably greater growth with lower diameters than might be expected while extrapolating known results of research done for thicker fibres.

  20. Understanding error generation in fused deposition modeling

    International Nuclear Information System (INIS)

    Bochmann, Lennart; Transchel, Robert; Wegener, Konrad; Bayley, Cindy; Helu, Moneer; Dornfeld, David

    2015-01-01

    Additive manufacturing offers completely new possibilities for the manufacturing of parts. The advantages of flexibility and convenience of additive manufacturing have had a significant impact on many industries, and optimizing part quality is crucial for expanding its utilization. This research aims to determine the sources of imprecision in fused deposition modeling (FDM). Process errors in terms of surface quality, accuracy and precision are identified and quantified, and an error-budget approach is used to characterize errors of the machine tool. It was determined that accuracy and precision in the y direction (0.08–0.30 mm) are generally greater than in the x direction (0.12–0.62 mm) and the z direction (0.21–0.57 mm). Furthermore, accuracy and precision tend to decrease at increasing axis positions. The results of this work can be used to identify possible process improvements in the design and control of FDM technology. (paper)

  1. Understanding error generation in fused deposition modeling

    Science.gov (United States)

    Bochmann, Lennart; Bayley, Cindy; Helu, Moneer; Transchel, Robert; Wegener, Konrad; Dornfeld, David

    2015-03-01

    Additive manufacturing offers completely new possibilities for the manufacturing of parts. The advantages of flexibility and convenience of additive manufacturing have had a significant impact on many industries, and optimizing part quality is crucial for expanding its utilization. This research aims to determine the sources of imprecision in fused deposition modeling (FDM). Process errors in terms of surface quality, accuracy and precision are identified and quantified, and an error-budget approach is used to characterize errors of the machine tool. It was determined that accuracy and precision in the y direction (0.08-0.30 mm) are generally greater than in the x direction (0.12-0.62 mm) and the z direction (0.21-0.57 mm). Furthermore, accuracy and precision tend to decrease at increasing axis positions. The results of this work can be used to identify possible process improvements in the design and control of FDM technology.

  2. Fusing Recommendations for Social Bookmarking Websites

    DEFF Research Database (Denmark)

    Bogers, Toine; van den Bosch, Antal

    2011-01-01

    Social bookmarking websites are rapidly growing in popularity. Recommender systems, a promising remedy to the information overload accompanying the explosive growth in content, are designed to identify which unseen content might be of interest to a particular user, based on his or her past...... that use tag overlap and metadata provide better results for social bookmarking data sets than the transaction patterns that are used traditionally in recommender systems research. In addition, we investigate how to fuse different recommendation approaches to further improve recommendation accuracy. We...... preferences. Most previous work in recommendation for social bookmarking suffers from a lack of comparisons between the different available approaches. In this article, we address this issue by comparing and evaluating eight recommendation approaches on four data sets from two domains. We find that approaches...

  3. BaroFuse, a novel pressure-driven, adjustable-throughput perfusion system for tissue maintenance and assessment

    Directory of Open Access Journals (Sweden)

    Austin Rountree

    2016-12-01

    Conclusions: The very low flow rates and simplicity of design and operation of the BaroFuse device allow for the efficient generation of large number of kinetic profiles in OCR and other endpoints lasting from hours to days. The use of flow enhances the ability to make measurements on primary tissue where some elements of native three-dimensional structure are preserved. We offer the BaroFuse as a powerful tool for physiological studies and for pharmaceutical assessment of drug effects as well as personalized medicine.

  4. Bilateral maxillary fused second and third molars: a rare occurrence.

    Science.gov (United States)

    Liang, Rui-Zhen; Wu, Jin-Tao; Wu, You-Nong; Smales, Roger J; Hu, Ming; Yu, Jin-Hua; Zhang, Guang-Dong

    2012-12-01

    This case report describes the diagnosis and endodontic therapy of maxillary fused second and third molars, using cone-beam computed tomography (CBCT). A 31-year-old Chinese male, with no contributory medical or family/social history, presented with throbbing pain in the maxillary right molar area following an unsuccessful attempted tooth extraction. Clinical examination revealed what appeared initially to be a damaged large extra cusp on the buccal aspect of the distobuccal cusp of the second molar. However, CBCT revealed that a third molar was fused to the second molar. Unexpectedly, the maxillary left third molar also was fused to the second molar, and the crown of an unerupted supernumerary fourth molar was possibly also fused to the apical root region of the second molar. Operative procedures should not be attempted without adequate radiographic investigation. CBCT allowed the precise location of the root canals of the right maxillary fused molar teeth to permit successful endodontic therapy, confirmed after 6 months.

  5. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

  7. Hepatic overexpression of cAMP-responsive element modulator α induces a regulatory T-cell response in a murine model of chronic liver disease

    NARCIS (Netherlands)

    Kuttkat, Nadine; Mohs, Antje; Ohl, Kim; Hooiveld, Guido; Longerich, Thomas; Tenbrock, Klaus; Cubero, Francisco Javier; Trautwein, Christian

    2016-01-01


    Objective Th17 cells are a subset of CD4+ T-helper cells characterised by interleukin 17 (IL-17) production, a cytokine that plays a crucial role in inflammation-associated diseases. The cyclic AMP-responsive element modulator-α (CREMα) is a central mediator of T-cell pathogenesis, which

  8. Executive function training with game elements for obese children: A novel treatment to enhance self-regulatory abilities for weight-control

    NARCIS (Netherlands)

    Verbeken, S.; Braet, C.; Goossens, L.; van der Oord, S.

    2013-01-01

    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

  9. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

  10. Elements to evaluate the intention in the non-compliance s or violations to the regulatory framework in the national nuclear facilities

    International Nuclear Information System (INIS)

    Espinosa V, J. M.; Gonzalez V, J. A.

    2013-10-01

    Inside the impact evaluation process to the safety of non-compliance s or violations, developed and implanted by the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS), the Guide for the Impact Evaluation to the Safety in the National Nuclear Facilities by Non-compliance s or Violations to the Regulatory Framework was developed, which indicates that in the determination of the severity (graveness level) of a non-compliance or violation, four factors are evaluated: real and potential consequences to the safety, the impact to the regulator process and the intention. The non-compliance s or intentional violations are of particular interest, since the development of the regulatory activities of the CNSNS considers that the personnel of the licensees, as well as their contractors, will act and will communicate with integrity and honesty. The CNSNS cannot tolerate intentional non-compliance s, for what this violations type can be considered of a level of more graveness that the subjacent non-compliance. To determine the severity of a violation that involves intention, the CNSNS also took in consideration factors as the position and the personnel's responsibilities involved in the violation, the graveness level of the non-compliance in itself, the offender's intention and the possible gain that would produce the non-compliance, if exists, either economic or of another nature. The CNSNS hopes the licensees take significant corrective actions in response to non-compliance s or intentional violations, these corrective actions should correspond to the violation graveness with the purpose of generating a dissuasive effect in the organizations of the licensees. The present article involves the legal framework that confers the CNSNS the attributions to impose administrative sanctions to its licensees, establishes the definition of the CNSNS about what constitutes a non-compliance or intentional violation and finally indicates the intention types (deliberate or

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

    Science.gov (United States)

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

    2017-08-01

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

  12. Ginsenoside F2 reduces hair loss by controlling apoptosis through the sterol regulatory element-binding protein cleavage activating protein and transforming growth factor-β pathways in a dihydrotestosterone-induced mouse model.

    Science.gov (United States)

    Shin, Heon-Sub; Park, Sang-Yong; Hwang, Eun-Son; Lee, Don-Gil; Mavlonov, Gafurjon Turdalievich; Yi, Tae-Hoo

    2014-01-01

    This study was conducted to test whether ginsenoside F2 can reduce hair loss by influencing sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and the transforming growth factor beta (TGF-β) pathway of apoptosis in dihydrotestosterone (DHT)-treated hair cells and in a DHT-induced hair loss model in mice. Results for ginsenoside F2 were compared with finasteride. DHT inhibits proliferation of hair cells and induces androgenetic alopecia and was shown to activate an apoptosis signal pathway both in vitro and in vivo. The cell-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the proliferation rates of DHT-treated human hair dermal papilla cells (HHDPCs) and HaCaTs increased by 48% in the ginsenoside F2-treated group and by 12% in the finasteride-treated group. Western blot analysis showed that ginsenoside F2 decreased expression of TGF-β2 related factors involved in hair loss. The present study suggested a hair loss related pathway by changing SCAP related apoptosis pathway, which has been known to control cholesterol metabolism. SCAP, sterol regulatory element-binding protein (SREBP) and caspase-12 expression in the ginsenoside F2-treated group were decreased compared to the DHT and finasteride-treated group. C57BL/6 mice were also prepared by injection with DHT and then treated with ginsenoside F2 or finasteride. Hair growth rate, density, thickness measurements and tissue histotological analysis in these groups suggested that ginsenoside F2 suppressed hair cell apoptosis and premature entry to catagen more effectively than finasteride. Our results indicated that ginsenoside F2 decreased the expression of TGF-β2 and SCAP proteins, which have been suggested to be involved in apoptosis and entry into catagen. This study provides evidence those factors in the SCAP pathway could be targets for hair loss prevention drugs.

  13. ELIMINATING NEGETIVE EFFECT OF INVERTER-BASED DGs ON FUSE-RECLOSER COORDINATION IN DISTRIBUTION SYSTEMS

    OpenAIRE

    shakarami, mahmoudreza; namdari, farhad; salehi, moslem

    2015-01-01

    Despite many advantages of distributed generation (DG) sources, they may have a negative effect on the protection of distribution systems. In a distribution system, fuse-recloser protection scheme is designed such that the recloser could operate faster than the fuse to prevent fuse burning; but, the presence of DGs in fault conditions may lead to increased fuse current and thus faster performance of the fuse than the recloser and lack of coordination. In this paper, effect of DGs on fuse-recl...

  14. Computational model of exploding metallic fuses for multimegajoule switching

    International Nuclear Information System (INIS)

    Lindemuth, I.R.; Brownell, J.H.; Greene, A.E.; Nickel, G.H.; Oliphant, T.A.; Weiss, D.L.

    1985-01-01

    A new model for determining the time-dependent behavior of exploding metallic fuses is formulated. The model draws on an atomic data base and gives insight into the temporal behavior of the material density and temperature of the fuse as well as the nonlinear electrical circuit interaction. The model includes an embedding insulating tamper and leads to a plausible explanation of fuse ''restrike.'' The model predicts time-scale compression of 500 for inductive store systems powered by explosive driven magnetic flux compression generators. A scenario for achieving multimegajoule foil implosions is predicted

  15. Fused upper central incisors: management of two clinical cases.

    Science.gov (United States)

    Sfasciotti, Gian Luca; Marini, Roberta; Bossù, Maurizio; Ierardo, Gaetano; Annibali, Susanna

    2011-03-01

    This paper reports the management of two clinical cases, in which the upper right central incisor was fused with a supernumerary tooth and the upper left central incisor was macrodontic. A radiographic examination revealed that the fused teeth had two separate roots. Hemisectioning of the fused teeth was performed, the supernumerary portion was extracted and the remaining part was reshaped to remove any sharp margins and to achieve a normal morphology. The macrodontic central incisors were not treated. At 12-months post-surgery there were no periodontal problems and no hypersensitivity. Orthodontic treatment was performed to appropriately align the maxillary teeth and to correct the malocclusion.

  16. Renal cell carcinoma in patient with crossed fused renal ectopia

    Directory of Open Access Journals (Sweden)

    Ozgur Cakmak

    2016-01-01

    Full Text Available Primary renal cell carcinomas have rarely been reported in patients with crossed fused renal ectopia. We presented a patient with right to left crossed fused kidney harbouring renal tumor. The most frequent tumor encountered in crossed fused renal ectopia is renal cell carcinoma. In this case, partial nephrectomy was performed which pave way to preservation of the uninvolved both renal units. Due to unpredictable anatomy, careful preoperative planning and meticulous delineation of renal vasculature is essential for preservation of the uninvolved renal units.

  17. Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter.

    Science.gov (United States)

    Clem, Brian F; Hudson, Elizabeth A; Clark, Barbara J

    2005-03-01

    Steroidogenic acute regulatory protein (StAR) transcription is regulated through cAMP-protein kinase A-dependent mechanisms that involve multiple transcription factors including the cAMP-responsive element binding protein (CREB) family members. Classically, binding of phosphorylated CREB to cis-acting cAMP-responsive elements (5'-TGACGTCA-3') within target gene promoters leads to recruitment of the coactivator CREB binding protein (CBP). Herein we examined the extent of CREB family member phosphorylation on protein-DNA interactions and CBP recruitment with the StAR promoter. Immunoblot analysis revealed that CREB, cAMP-responsive element modulator (CREM), and activating transcription factor (ATF)-1 are expressed in MA-10 mouse Leydig tumor cells, yet only CREB and ATF-1 are phosphorylated. (Bu)2cAMP treatment of MA-10 cells increased CREB phosphorylation approximately 2.3-fold within 30 min but did not change total nuclear CREB expression levels. Using DNA-affinity chromatography, we now show that CREB and ATF-1, but not CREM, interact with the StAR promoter, and this interaction is dependent on the activator protein-1 (AP-1) cis-acting element within the cAMP-responsive region. In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction. In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis. However, (Bu)2cAMP-treatment increased P-CREB and CBP interaction with the StAR promoter, demonstrating for the first time the physical role of P-CREB:DNA interactions in CBP recruitment to the StAR proximal promoter.

  18. Close linkage of the mouse and human CD3 γ- and δ-chain genes suggests that their transcription is controlled by common regulatory elements

    International Nuclear Information System (INIS)

    Saito, H.; Koyama, T.; Georgopoulos, K.; Clevers, H.; Haser, W.G.; LeBien, T.; Tonegawa, S.; Terhorst, C.

    1987-01-01

    Antigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-γ, -δ, -epsilon, and -zeta. The mouse CD3-γ gene, consisting of seven exons, was found to be highly homologous to the CD3-γ described earlier. Both the high level of sequence homology and the exon/intron organization indicate that the CD3-γ and -δ genes arose by gene duplication. Surprisingly, murine and human genomic DNA clones could be isolated that contained elements of both the CD3-γ and CD3-δ genes. In fact, the putative transcription start site of the mouse CD3-γ gene is less than 1.4 kilobases from the transcription initiation site of the mouse CD3-δ gene. Common elements that regulate the divergent transcription of the two genes are therefore proposed to be located in the intervening 1.4-kilobase DNA segment. This might contribute to the coordinate expression of the CD3-γ and -δ genes during intrathymic maturation of T lymphocytes

  19. Isolation of a solventogenic Clostridium sp. strain: fermentation of glycerol to n-butanol, analysis of the bcs operon region and its potential regulatory elements.

    Science.gov (United States)

    Panitz, J C; Zverlov, V V; Pham, V T T; Stürzl, S; Schieder, D; Schwarz, W H

    2014-02-01

    A new solventogenic bacterium, strain GT6, was isolated from standing water sediment. 16S-rRNA gene analysis revealed that GT6 belongs to the heterogeneous Clostridium tetanomorphum group of bacteria exhibiting 99% sequence identity with C. tetanomorphum 4474(T). GT6 can utilize a wide range of carbohydrate substrates including glucose, fructose, maltose, xylose and glycerol to produce mainly n-butanol without any acetone. Additional products of GT6 metabolism were ethanol, butyric acid, acetic acid, and trace amounts of 1,3-propanediol. Medium and substrate composition, and culture conditions such as pH and temperature influenced product formation. The major fermentation product from glycerol was n-butanol with a final concentration of up to 11.5 g/L. 3% (v/v) glycerol lead to a total solvent concentration of 14 g/L within 72 h. Growth was not inhibited by glycerol concentrations as high as 15% (v/v). The solventogenesis genes crt, bcd, etfA/B and hbd composing the bcs (butyryl-CoA synthesis) operon of C. tetanomorphum GT6 were sequenced. They occur in a genomic arrangement identical to those in other solventogenic clostridia. Furthermore, the sequence of a potential regulator gene highly similar to that of the NADH-sensing Rex family of regulatory genes was found upstream of the bcs operon. Potential binding sites for Rex have been identified in the promoter region of the bcs operon of solvent producing clostridia as well as upstream of other genes involved in NADH oxidation. This indicates a fundamental role of Rex in the regulation of fermentation products in anaerobic, and especially in solventogenic bacteria. Copyright © 2013 Elsevier GmbH. All rights reserved.

  20. Rapid kinetics of iron responsive element (IRE) RNA/iron regulatory protein 1 and IRE-RNA/eIF4F complexes respond differently to metal ions.

    Science.gov (United States)

    Khan, Mateen A; Ma, Jia; Walden, William E; Merrick, William C; Theil, Elizabeth C; Goss, Dixie J

    2014-06-01

    Metal ion binding was previously shown to destabilize IRE-RNA/IRP1 equilibria and enhanced IRE-RNA/eIF4F equilibria. In order to understand the relative importance of kinetics and stability, we now report rapid rates of protein/RNA complex assembly and dissociation for two IRE-RNAs with IRP1, and quantitatively different metal ion response kinetics that coincide with the different iron responses in vivo. kon, for FRT IRE-RNA binding to IRP1 was eight times faster than ACO2 IRE-RNA. Mn(2+) decreased kon and increased koff for IRP1 binding to both FRT and ACO2 IRE-RNA, with a larger effect for FRT IRE-RNA. In order to further understand IRE-mRNA regulation in terms of kinetics and stability, eIF4F kinetics with FRT IRE-RNA were determined. kon for eIF4F binding to FRT IRE-RNA in the absence of metal ions was 5-times slower than the IRP1 binding to FRT IRE-RNA. Mn(2+) increased the association rate for eIF4F binding to FRT IRE-RNA, so that at 50 µM Mn(2+) eIF4F bound more than 3-times faster than IRP1. IRP1/IRE-RNA complex has a much shorter life-time than the eIF4F/IRE-RNA complex, which suggests that both rate of assembly and stability of the complexes are important, and that allows this regulatory system to respond rapidly to change in cellular iron. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. An in silico approach reveals associations between genetic and epigenetic factors within regulatory elements in B cells from primary Sjögren’s syndrome patients

    Directory of Open Access Journals (Sweden)

    Orsia D. Konsta

    2015-08-01

    Full Text Available Recent advances in genetics have highlighted several regions and candidate genes associated with primary Sjögren's syndrome (SS, a systemic autoimmune epithelitis that combines exocrine gland dysfunctions, and focal lymphocytic infiltrations. In addition to genetic factors, it is now clear that epigenetic deregulations are present during SS and restricted to specific cell type subsets such as lymphocytes and salivary gland epithelial cells. In this study, 72 single nucleotide polymorphisms (SNPs associated with 43 SS gene risk factors were selected from publicly available and peer reviewed literature for further in silico analysis. SS risk variant location was tested revealing a broad distribution in coding sequences (5.6%, intronic sequences (55.6%, upstream/downstream genic regions (30.5%, and intergenic regions (8.3%. Moreover, a significant enrichment of regulatory motifs (promoter, enhancer, insulator, DNAse peak and eQTL characterizes SS risk variants (94.4%. Next, screening SNPs in high linkage disequilibrium (r2 ≥ 0.8 in Caucasians revealed 645 new variants including 5 SNPs with missense mutations, and indicated an enrichment of transcriptionally active motifs according to the cell type (B cells > monocytes > T cells >> A549. Finally, we looked at SS risk variants for histone markers in B cells (GM12878, monocytes (CD14+ and epithelial cells (A548. Active histone markers were associated with SS risk variants at both promoters and enhancers in B cells, and within enhancers in monocytes. In conclusion and based on the obtained in silico results, that need further confirmation, associations were observed between SS genetic risk factors and epigenetic factors and these associations predominate in B cells such as those observed at the FAM167A-BLK locus.

  2. Heat accumulation regime of femtosecond laser writing in fused silica and Nd:phosphate glass

    Energy Technology Data Exchange (ETDEWEB)

    Bukharin, M.A. [Moscow Institute of Physics and Technology, Moscow Region (Russian Federation); Optosystems Ltd., Troitsk, Moscow (Russian Federation); Khudyakov, D.V. [Optosystems Ltd., Troitsk, Moscow (Russian Federation); Physics Instrumentation Center of the General Physics Institute, Troitsk, Moscow (Russian Federation); Vartapetov, S.K. [Physics Instrumentation Center of the General Physics Institute, Troitsk, Moscow (Russian Federation)

    2015-04-01

    We investigated refractive index induced by direct femtosecond laser writing inside fused silica and Nd:phosphate glass in heat accumulation regime. Spatial profile and magnitude of induced refractive index were investigated at various pulse repetition rates and translation velocities. It was shown that the magnitude of induced refractive index significantly rises with decreasing in time interval between successive laser pulses below the time for thermal diffusion. Going from nonthermal regime to heat accumulation regime, we achieved induced refractive index growth from 4 x 10{sup -3} up to 6.5 x 10{sup -3} in fused silica and from -6 x 10{sup -3} to -9 x 10{sup -3} in Nd:phosphate glass. Aspect ratio of treated area decreased from 2.1 down to less than 1.5 without correcting optical elements. It was shown that in heat accumulation regime, the treated area was surrounded by region of alternatively changed refractive index with significant magnitude up to -2 x 10{sup -3}. Wide regions of decreased refractive index enable fabrication of depressed cladding waveguides. We demonstrated low-loss (0.3 dB/cm) tubular waveguide inside fused silica. For orthogonal polarizations of guiding light, we achieved a small difference between losses as 0.1 dB/cm using highly symmetric written tracks forming the cladding. The desired structure was simulated with the beam propagation method, and the results were in good agreement with experiment data. (orig.)

  3. Wideband two-port beam splitter of a binary fused-silica phase grating.

    Science.gov (United States)

    Wang, Bo; Zhou, Changhe; Feng, Jijun; Ru, Huayi; Zheng, Jiangjun

    2008-08-01

    The usual beam splitter of multilayer-coated film with a wideband spectrum is not easy to achieve. We describe the realization of a wideband transmission two-port beam splitter based on a binary fused-silica phase grating. To achieve high efficiency and equality in the diffracted 0th and -1st orders, the grating profile parameters are optimized using rigorous coupled-wave analysis at a wavelength of 1550 nm. Holographic recording and the inductively coupled plasma dry etching technique are used to fabricate the fused-silica beam splitter grating. The measured efficiency of (45% x 2) = 90% diffracted into the both orders can be obtained with the fabricated grating under Littrow mounting. The physical mechanism of such a wideband two-port beam splitter grating can be well explained by the modal method based on two-beam interference of the modes excited by the incident wave. With the high damage threshold, low coefficient of thermal expansion, and wideband high efficiency, the presented beam splitter etched in fused silica should be a useful optical element for a variety of practical applications.

  4. In-silico analysis of cis-acting regulatory elements of pathogenesis-related proteins of Arabidopsis thaliana and Oryza sativa.

    Science.gov (United States)

    Kaur, Amritpreet; Pati, Pratap Kumar; Pati, Aparna Maitra; Nagpal, Avinash Kaur

    2017-01-01

    Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation. CpG islands are observed only in rice PRs, which indicates that monocot genome contains more GC rich motifs than dicots. Tandem repeats were also observed in 5' UTR of PR genes. Thus, the present study provides an understanding of regulation of PR genes and their versatile roles in plants.

  5. The T box regulatory element controlling expression of the class I lysyl-tRNA synthetase of Bacillus cereus strain 14579 is functional and can be partially induced by reduced charging of asparaginyl-tRNAAsn

    LENUS (Irish Health Repository)

    Foy, Niall

    2010-07-22

    Abstract Background Lysyl-tRNA synthetase (LysRS) is unique within the aminoacyl-tRNA synthetase family in that both class I (LysRS1) and class II (LysRS2) enzymes exist. LysRS1 enzymes are found in Archaebacteria and some eubacteria while all other organisms have LysRS2 enzymes. All sequenced strains of Bacillus cereus (except AH820) and Bacillus thuringiensis however encode both a class I and a class II LysRS. The lysK gene (encoding LysRS1) of B. cereus strain 14579 has an associated T box element, the first reported instance of potential T box control of LysRS expression. Results A global study of 891 completely sequenced bacterial genomes identified T box elements associated with control of LysRS expression in only four bacterial species: B. cereus, B. thuringiensis, Symbiobacterium thermophilum and Clostridium beijerinckii. Here we investigate the T box element found in the regulatory region of the lysK gene in B. cereus strain 14579. We show that this T box element is functional, responding in a canonical manner to an increased level of uncharged tRNALys but, unusually, also responding to an increased level of uncharged tRNAAsn. We also show that B. subtilis strains with T box regulated expression of the endogenous lysS or the heterologous lysK genes are viable. Conclusions The T box element controlling lysK (encoding LysRS1) expression in B. cereus strain 14579 is functional, but unusually responds to depletion of charged tRNALys and tRNAAsn. This may have the advantage of making LysRS1 expression responsive to a wider range of nutritional stresses. The viability of B. subtilis strains with a single LysRS1 or LysRS2, whose expression is controlled by this T box element, makes the rarity of the occurrence of such control of LysRS expression puzzling.

  6. Fused Adaptive Lasso for Spatial and Temporal Quantile Function Estimation

    KAUST Repository

    Sun, Ying; Wang, Huixia J.; Fuentes, Montserrat

    2015-01-01

    and temporal data with a fused adaptive Lasso penalty to accommodate the dependence in space and time. This method penalizes the difference among neighboring quantiles, hence it is desirable for applications with features ordered in time or space without

  7. Fusing Intelligence With Law Enforcement Information: An Analytic Imperative

    National Research Council Canada - National Science Library

    Thornlow, Christopher C

    2005-01-01

    ... and Law Enforcement Communities to fuse and analyze foreign threat intelligence with domestic law enforcement information in a timely fashion to provide adequate indications and warning of such an...

  8. Quantification of residual stress from photonic signatures of fused silica

    International Nuclear Information System (INIS)

    Cramer, K. Elliott; Yost, William T.; Hayward, Maurice

    2014-01-01

    A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outer-most pane of Space Shuttle windows made from fused silica. A method and apparatus for calibration of the stress-optic coefficient using four-point bending is discussed. The results are validated on known material (acrylic) and are found to agree with literature values to within 6%. The calibration procedure is then applied to fused-silica specimens and the stress-optic coefficient is determined to be 2.43 ± 0.54 × 10 −12 Pa −1 . Fused silica specimens containing impacts artificially made at NASA’s Hypervelocity Impact Technology Facility (HIT-F), to simulate damage typical during space flight, are examined. The damage sites are cored from fused silica window carcasses and examined with the GFP. The calibrated GFP measurements of residual stress patterns surrounding the damage sites are presented

  9. Three-dimensional printing of transparent fused silica glass

    Science.gov (United States)

    Kotz, Frederik; Arnold, Karl; Bauer, Werner; Schild, Dieter; Keller, Nico; Sachsenheimer, Kai; Nargang, Tobias M.; Richter, Christiane; Helmer, Dorothea; Rapp, Bastian E.

    2017-04-01

    Glass is one of the most important high-performance materials used for scientific research, in industry and in society, mainly owing to its unmatched optical transparency, outstanding mechanical, chemical and thermal resistance as well as its thermal and electrical insulating properties. However, glasses and especially high-purity glasses such as fused silica glass are notoriously difficult to shape, requiring high-temperature melting and casting processes for macroscopic objects or hazardous chemicals for microscopic features. These drawbacks have made glasses inaccessible to modern manufacturing technologies such as three-dimensional printing (3D printing). Using a casting nanocomposite, here we create transparent fused silica glass components using stereolithography 3D printers at resolutions of a few tens of micrometres. The process uses a photocurable silica nanocomposite that is 3D printed and converted to high-quality fused silica glass via heat treatment. The printed fused silica glass is non-porous, with the optical transparency of commercial fused silica glass, and has a smooth surface with a roughness of a few nanometres. By doping with metal salts, coloured glasses can be created. This work widens the choice of materials for 3D printing, enabling the creation of arbitrary macro- and microstructures in fused silica glass for many applications in both industry and academia.

  10. Fused Microknot Optical Resonators in Folded Photonic Tapers for in-Liquid Durable Sensing

    Directory of Open Access Journals (Sweden)

    Alexandra Logvinova

    2018-04-01

    Full Text Available Optical microknot fibers (OMFs serve as localized devices, where photonic resonances (PRs enable self-interfering elements sensitive to their environment. However, typical fragility and drifting of the knot severely limit the performance and durability of microknots as sensors in aqueous settings. Herein we present the fabrication, electrical fusing, preparation, and persistent detection of volatile liquids in multiple wetting–dewetting cycles of volatile compounds and quantify the persistent phase shifts with a simple model relating to the ambient liquid, enabling durable in-liquid sensing employing OMF PRs.

  11. Hepatic nuclear sterol regulatory binding element protein 2 abundance is decreased and that of ABCG5 increased in male hamsters fed plant sterols.

    Science.gov (United States)

    Harding, Scott V; Rideout, Todd C; Jones, Peter J H

    2010-07-01

    The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P 6-fold (P = 0.029) and >2-fold (P sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis.

  12. Process for manufacturing hollow fused-silica insulator cylinder

    Science.gov (United States)

    Sampayan, Stephen E.; Krogh, Michael L.; Davis, Steven C.; Decker, Derek E.; Rosenblum, Ben Z.; Sanders, David M.; Elizondo-Decanini, Juan M.

    2001-01-01

    A method for building hollow insulator cylinders that can have each end closed off with a high voltage electrode to contain a vacuum. A series of fused-silica round flat plates are fabricated with a large central hole and equal inside and outside diameters. The thickness of each is related to the electron orbit diameter of electrons that escape the material surface, loop, and return back. Electrons in such electron orbits can support avalanche mechanisms that result in surface flashover. For example, the thickness of each of the fused-silica round flat plates is about 0.5 millimeter. In general, the thinner the better. Metal, such as gold, is deposited onto each top and bottom surface of the fused-silica round flat plates using chemical vapor deposition (CVD). Eutectic metals can also be used with one alloy constituent on the top and the other on the bottom. The CVD, or a separate diffusion step, can be used to defuse the deposited metal deep into each fused-silica round flat plate. The conductive layer may also be applied by ion implantation or gas diffusion into the surface. The resulting structure may then be fused together into an insulator stack. The coated plates are aligned and then stacked, head-to-toe. Such stack is heated and pressed together enough to cause the metal interfaces to fuse, e.g., by welding, brazing or eutectic bonding. Such fusing is preferably complete enough to maintain a vacuum within the inner core of the assembled structure. A hollow cylinder structure results that can be used as a core liner in a dielectric wall accelerator and as a vacuum envelope for a vacuum tube device where the voltage gradients exceed 150 kV/cm.

  13. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

    The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

  14. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    2005-01-01

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

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

    Science.gov (United States)

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

    2015-01-08

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

  16. The effect of high-pressure devitrification and densification on ballistic-penetration resistance of fused silica

    Science.gov (United States)

    Avuthu, Vasudeva Reddy

    perhaps alpha-quartz) within fused silica during ballistic impact. To rationalize the findings obtained, the all-atom molecular-level computational analysis is complemented by a series of quantum-mechanics density functional theory (DFT) computations. The latter computations enable determination of the relative potential energies of the fused silica, alpha-quartz and stishovite under ambient pressure (i.e. under their natural densities) as well as under imposed (as high as 50 GPa) pressures (i.e. under higher densities) and shear strains. In addition, the transition states associated with various fused-silica devitrification processes were identified. In the second part of the present work, the molecular-level computational results obtained in the first portion of the work are used to enrich a continuum-type constitutive model (that is, the so-called Johnson-Holmquist-2, JH2, model) for fused silica. Since the aforementioned devitrification and permanent-densification processes modify the response of fused silica to the pressure as well as to the deviatoric part of the stress, changes had to be made in both the JH2 equation of state and the strength model. To assess the potential improvements with respect to the ballistic-penetration resistance of this material brought about by the fused-silica devitrification and permanent-densification processes, a series of transient non-linear dynamics finite element analyses of the transverse impact of a fused-silica test plate with a solid right-circular cylindrical steel projectile was conducted. The results obtained revealed that, provided the projectile incident velocity and, hence, the attendant pressure, is sufficiently high, fused silica can undergo impact-induced energy-consuming devitrification, which improves its ballistic-penetration resistance.

  17. A prototype hybrid 7π quinone-fused 1,3,2-dithiazolyl radical.

    Science.gov (United States)

    Decken, A; Mailman, A; Passmore, J; Rautiainen, J M; Scherer, W; Scheidt, E-W

    2011-01-28

    Reaction of 1,4-naphthoquinone and SNSMF(6) (M = As, Sb) in SO(2) solution in a 1 : 2 molar ratio led to the naphthoquinone fused 1,3,2-dithiazolylium salts, 3MF(6) quantitatively by multinuclear NMR (87% isolated yield of 3SbF(6)) via the cycloaddition and oxidative dehydrogenation chemistry of SNS(+) with formation of NH(4)SbF(6) and S(8). The product 3SbF(6) was fully characterized by IR, Raman, multinuclear {(1)H, (13)C, (14)N} NMR, elemental analysis, cyclic voltammetry and single crystal X-ray crystallography. The reduction of 3SbF(6) with ferrocene (Cp(2)Fe) in refluxing acetonitrile (CH(3)CN) led to the first isolation of a fused quinone-thiazyl radical, 3˙ in 73% yield. The prototype hybrid quinone-thiazyl radical 3˙ was fully characterized by IR, Raman microscopy, EI-MS, elemental analysis, solution and solid state EPR, magnetic susceptibility (2-370 K) and was found to form π*-π* dimers in the solid state as determined by single crystal X-ray crystallography. Furthermore, the thermal decomposition of 3˙ led to a novel quinone-fused 1,2,3,4-tetrathiine, 10 (x = 2) and the known 1,2,5-thiadiazole, 11. The energetics of the cycloadditon and oxidative dehydrogenation chemistry of SNS(+) and 1,4-naphthoquinone leading to 3SbF(6) were estimated in the gas phase and SO(2) solution by DFT calculations (PBE0/6-311G(d)) and lattice enthalpies obtained by the volume based thermodynamic (VBT) approach in the solid state. The gas phase ion energetics (ionization potential (IP) and electron affinity (EA)) of 3˙ are compared to related 1,3,2- and 1,2,3-dithiazolyl radicals.

  18. Quantification of Residual Stress from Photonic Signatures of Fused Silica

    Science.gov (United States)

    Cramer, K. Elliott; Hayward, Maurice; Yost, William E.

    2013-01-01

    A commercially available grey-field polariscope (GFP) instrument for photoelastic examination is used to assess impact damage inflicted upon the outer-most pane of Space Shuttle windows made from fused silica. A method and apparatus for calibration of the stress-optic coefficient using four-point bending is discussed. The results are validated on known material (acrylic) and are found to agree with literature values to within 6%. The calibration procedure is then applied to fused-silica specimens and the stress-optic coefficient is determined to be 2.43 +/- 0.54 x 10(exp -12)/Pa. Fused silica specimens containing impacts artificially made at NASA's Hypervelocity Impact Technology Facility (HIT-F), to simulate damage typical during space flight, are examined. The damage sites are cored from fused silica window carcasses and examined with the GFP. The calibrated GFP measurements of residual stress patterns surrounding the damage sites are presented. Keywords: Glass, fused silica, photoelasticity, residual stress

  19. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  20. Ionization of Local Interstellar Gas Based on STIS and FUSE spectra of Nearby Stars

    Science.gov (United States)

    Redfield, Seth; Linsky, J. L.

    2009-01-01

    The ultraviolet contains many resonance line transitions that are sensitive to a range of ionization stages of ions present in the local interstellar medium (LISM). We couple observations of high resolution ultraviolet spectrographs, STIS and GHRS on the Hubble Space Telescope (HST) and the Far-Ultraviolet Spectroscopic Explorer (FUSE) in order to make a comprehensive survey of the ionization structure of the local interstellar medium. In particular, we focus on the sight line toward G191-B2B, a nearby (69 pc) white dwarf. We present interstellar detections of highly ionized elements (e.g., SiIII, CIII, CIV, etc) and compare them directly to neutral or singly ionized LISM detections (e.g., SiII, CII, etc). The extensive observations of G191-B2B provides an opportunity for a broad study of ionization stages of several elements, while a survey of several sight lines provides a comprehensive look at the ionization structure of the LISM. We acknowledge support for this project through NASA FUSE Grant NNX06AD33G.

  1. Dsc E3 ligase localization to the Golgi requires the ATPase Cdc48 and cofactor Ufd1 for activation of sterol regulatory element-binding protein in fission yeast.

    Science.gov (United States)

    Burr, Risa; Ribbens, Diedre; Raychaudhuri, Sumana; Stewart, Emerson V; Ho, Jason; Espenshade, Peter J

    2017-09-29

    Sterol regulatory element-binding proteins (SREBPs) in the fission yeast Schizosaccharomyces pombe regulate lipid homeostasis and the hypoxic response under conditions of low sterol or oxygen availability. SREBPs are cleaved in the Golgi through the combined action of the Dsc E3 ligase complex, the rhomboid protease Rbd2, and the essential ATPases associated with diverse cellular activities (AAA + ) ATPase Cdc48. The soluble SREBP N-terminal transcription factor domain is then released into the cytosol to enter the nucleus and regulate gene expression. Previously, we reported that Cdc48 binding to Rbd2 is required for Rbd2-mediated SREBP cleavage. Here, using affinity chromatography and mass spectrometry experiments, we identified Cdc48-binding proteins in S. pombe , generating a list of many previously unknown potential Cdc48-binding partners. We show that the established Cdc48 cofactor Ufd1 is required for SREBP cleavage but does not interact with the Cdc48-Rbd2 complex. Cdc48-Ufd1 is instead required at a step prior to Rbd2 function, during Golgi localization of the Dsc E3 ligase complex. Together, these findings demonstrate that two distinct Cdc48 complexes, Cdc48-Ufd1 and Cdc48-Rbd2, are required for SREBP activation and low-oxygen adaptation in S. pombe . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. miR-24 inhibits cell proliferation by suppressing expression of E2F2, MYC and other cell cycle regulatory genes by binding to “seedless” 3′UTR microRNA recognition elements

    Science.gov (United States)

    Lal, Ashish; Navarro, Francisco; Maher, Christopher; Maliszewski, Laura E.; Yan, Nan; O'Day, Elizabeth; Chowdhury, Dipanjan; Dykxhoorn, Derek M.; Tsai, Perry; Hofman, Oliver; Becker, Kevin G.; Gorospe, Myriam; Hide, Winston; Lieberman, Judy

    2009-01-01

    Summary miR-24, up-regulated during terminal differentiation of multiple lineages, inhibits cell cycle progression. Antagonizing miR-24 restores post-mitotic cell proliferation and enhances fibroblast proliferation, while over-expressing miR-24 increases the G1 compartment. The 248 mRNAs down-regulated upon miR-24 over-expression are highly enriched for DNA repair and cell cycle regulatory genes that form a direct interaction network with prominent nodes at genes that enhance (MYC, E2F2, CCNB1, CDC2) or inhibit (p27Kip1, VHL) cell cycle progression. miR-24 directly regulates MYC and E2F2 and some genes they transactivate. Enhanced proliferation from antagonizing miR-24 is abrogated by knocking down E2F2, but not MYC, and cell proliferation, inhibited by miR-24 over-expression, is rescued by miR-24-insensitive E2F2. Therefore, E2F2 is a critical miR-24 target. The E2F2 3′UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4 and FEN1 by recognizing seedless, but highly complementary, sequences. PMID:19748357

  3. HVI Ballistic Limit Characterization of Fused Silica Thermal Panes

    Science.gov (United States)

    Miller, J. E.; Bohl, W. D.; Christiansen, E. L.; Davis, B. A.; Deighton, K. D.

    2015-01-01

    Fused silica window systems are used heavily on crewed reentry vehicles, and they are currently being used on the next generation of US crewed spacecraft, Orion. These systems improve crew situational awareness and comfort, as well as, insulating the reentry critical components of a spacecraft against the intense thermal environments of atmospheric reentry. Additionally, these materials are highly exposed to space environment hazards like solid particle impacts. This paper discusses impact studies up to 10 km/s on a fused silica window system proposed for the Orion spacecraft. A ballistic limit equation that describes the threshold of perforation of a fuse silica pane over a broad range of impact velocities, obliquities and projectile materials is discussed here.

  4. Effects of 3D microlens transfer into fused silica substrate by CF{sub 4}/O{sub 2} dry etching

    Energy Technology Data Exchange (ETDEWEB)

    Grigaliūnas, Viktoras, E-mail: Viktoras.Grigaliunas@ktu.lt [Institute of Materials Science, Kaunas University of Technology, Barsausko 59, LT-51423 Kaunas (Lithuania); Jucius, Dalius; Lazauskas, Algirdas; Andrulevičius, Mindaugas; Sakaliūnienė, Jolita; Abakevičienė, Brigita; Kopustinskas, Vitoldas [Institute of Materials Science, Kaunas University of Technology, Barsausko 59, LT-51423 Kaunas (Lithuania); Smetona, Saulius [Qorvo, 7628 Thorndike Road Greensboro, NC 27409 United States (United States); Tamulevičius, Sigitas [Institute of Materials Science, Kaunas University of Technology, Barsausko 59, LT-51423 Kaunas (Lithuania)

    2017-01-30

    Highlights: • The etching rate of PMMA is dependent on the plasma etching time. • The etching rate ratio between PMMA and fused silica vary during plasma treatment. • The etching rate ratio variation must be assessed during the microlens design phase. - Abstract: Nowadays, 3D microoptical elements find a variety of applications from light emitting diodes and household appliances to precise medical endoscopes. Such elements, fabricated in a fused silica substrate by combining 3D e-beam patterning and dry etching, can be used as a mold for the high throughput replication in polymeric materials by UV nanoimprint technique. Flexible and precise control of 3D shape in the resist layer can be achieved by e-beam patterning, but it is also very important to know peculiarities of 3D pattern transfer from resist layer into the fused silica substrate. This paper reports on the effects of PMMA 3D microlens pattern transfer into fused silica substrate by CF{sub 4}/O{sub 2} dry etching. It is demonstrated that etching rate ratio between PMMA and fused silica changes during plasma treatment. Thus, the resulting shape of transferred 3D profile is different from the shape in PMMA and this variation must be assessed during the design phase.

  5. High-Speed Fuses in IGBT based Voltage Source Converters

    DEFF Research Database (Denmark)

    Iov, Florin; Blaabjerg, Frede; Rasmussen, Henrik

    2005-01-01

    The demand for protection of power electronic applications has during the last couple of years increased regarding the high-power IGBT modules. Even with an active protection, a high power IGBT still has a risk of exhibiting a violent rupture in the case of a fault if IGBT fuses do not protect it...... protection. First, the problem of adding inductance in the DC-link circuit is treated, second a short discussion of the protection of the IGBT module is done, and finally, the impact of the high frequency loading on the current carrying capability of the fuses is presented....

  6. Nondestructive detection system of faults in fuses using radioisotope

    International Nuclear Information System (INIS)

    Goncalves, D.

    1973-01-01

    A system is developed to show the viability of non-destructive detection of the faults of explosive safety fuses which are manufactured by Fabrica da Estrela do Ministerio do Exercito. The faults are detected by an ion-chamber based on the variation of the intensity of the beta particles that penetrate the fuse which passes through a collimator. The beta particles are emitted by Strontium-90 + Yttrium-90 encapsulated in either stainless steel or aluminum. The concept of 'bucking Voltage' is applied to differentiate electronically the signal generated by the ion-chamber. (author)

  7. Modelling and Analysis of Proximity Effect in IGBT Fuses

    DEFF Research Database (Denmark)

    Iov, Florin; Blaabjerg, Frede; Rasmussen, Henrik

    2005-01-01

    The demand for protection of power electronic applications has during the last couple of years increased regarding the high-power IGBT modules. The consequences of electrical faults can be severe in special cases; not only on the equipment but also to people, if safety principles are not applied....... Even with an active protection, a high power IGBT still has a risk of exhibiting a violent rupture in the case of a fault if e.g. IGBT fuses are not protecting it. By introducing fuses into voltage source converters a better protection of IGBT's can be achieved. However, skin and proximity effects...

  8. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

    Mapping out cellular networks in general and transcriptional networks in particular has proved to be a bottle-neck hampering our understanding of biological processes. Integrative approaches fusing computational and experimental technologies for decoding transcriptional networks at a high level of resolution is therefore of uttermost importance. Yet, this is challenging since the control of gene expression in eukaryotes is a complex multi-level process influenced by several epigenetic factors and the fine interplay between regulatory proteins and the promoter structure governing the combinatorial regulation of gene expression. In this chapter we review how the CAGE data can be integrated with other measurements such as expression, physical interactions and computational prediction of regulatory motifs, which together can provide a genome-wide picture of eukaryotic transcriptional regulatory networks at a new level of resolution. © 2010 by Pan Stanford Publishing Pte. Ltd. All rights reserved.

  9. Dedication for Safety-Related Fuses used in Class-1E Power System

    International Nuclear Information System (INIS)

    Hong, Younghee

    2014-01-01

    The safety-related fuses used in class-1E power system provide overcurrent protection for electrical system and isolate the class 1E circuit from a fault or overload condition. These days, the number of nuclear grade suppliers has been reduced. Accordingly, commercial grade, instead of safety-related, fuses are procured and used in the utilities through the dedication process. Therefore, this paper introduces the commercial grade fuse dedication process/engineering and how to assure the quality requirements with this process and engineering. The fuses used in class-1E power system are to protect overcurrent and to isolate fault. Therefore the fuse for acceptance in order to improve the quality and reliability for commercial grade fuses shall be dedicated. The fuse resistance value may be useful as an indicator of acceptance. The current carrying capacity test can change the fuse performance properties. Therefore these critical characteristics are needed for additional review and analysis with fuse manufactures

  10. Fuse and application of said fuse to the construction of an emergency shutdown system for a nuclear reactor

    International Nuclear Information System (INIS)

    Taulier, H.H.L.; Brugeille, G.

    1978-01-01

    A fuse device for an automatic emergency shutdown system in fast reactors provides a coupling between a casing tube placed within a fuel can and a series of neutron-absorbing masses held together above the reactor core under normal operating conditions but released in free fall to the lower portion of the casing tube at the level of the reactor core as a result of melting of the fuse when operating characteristics such as temperature or neutron flux attain a level which exceeds a predetermined threshold

  11. Fuse and application of said fuse to the construction of an emergency shutdown system for a nuclear reactor

    International Nuclear Information System (INIS)

    Taulier, H.H.L.; Brugeilles, G.

    1976-01-01

    A fuse device for an automatic emergency shutdown system in fast reactors provides a coupling between a casing tube placed within a fuel can and a series of neutron-absorbing masses held together above the reactor core under normal operating conditions. They are released in free fall to the lower portion of the casing tube at the level of the reactor core as a result of melting of the fuse when operating characteristics such as temperature or neutron flux attain a level which exceeds a predetermined threshold

  12. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  13. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  14. Vacuum fused deposition modelling system to improve tensile ...

    African Journals Online (AJOL)

    In the printing process, the interlayer bonding is made too quick thus the layers are not fully fused together causing the reduced tensile strength. This paper presents a possible solution to this problem by incorporating vacuum technology in FDM system to improve tensile strength of 3D printed specimens. In this study, a ...

  15. Fused silica thermal conductivity dispersion at high temperature

    International Nuclear Information System (INIS)

    Bouchut, P.; Decruppe, D.; Delrive, L.

    2004-01-01

    A continuous CO 2 laser is focused to locally anneal small fused silica spots. A noncontact radiometry diagnostic enables us to follow surface temperature variation that occurs from site to site. A 'steady state' dispersion of surface temperature is observed across our sample. We show that nonhomogeneous silica thermal conductivity, above 1000 K is responsible for this temperature dispersion

  16. New developments in fused deposition modeling of ceramics

    DEFF Research Database (Denmark)

    Bellini, Anna; Shor, L.; Guceri, S.I.

    2005-01-01

    Purpose - To shift from rapid prototyping (RP) to agile fabrication by broadening the material selection, e.g. using ceramics, hence improving the properties (e.g. mechanical properties) of fused deposition modeling (FDM) products. Design/methodology/approach - This paper presents the development...

  17. Evaluation of a color fused dual-band NVG

    NARCIS (Netherlands)

    Hogervorst, M.A.; Toet, A.

    2009-01-01

    We designed and evaluated a dual-band Night Vision Goggles sensor system. The sensor system consists of two optically aligned NVGs fitted with filters splitting the sensitive range into a visual and a near-infrared band. The Color-the-night technique (Hogervorst & Toet, FUSION2008) was used to fuse

  18. Evaluation of a color fused dual-band NVG

    NARCIS (Netherlands)

    Hogervorst, M.A.; Toet, A.

    2009-01-01

    We have tested a prototype dual-band NVG system consisting of two NVGs fitted with filters that split the NVG sensitive range into a short (visual) and a long wavelength (NIR) band. The Color-the-night technique (see Hogervorst & Toet, SPIE D&S ‘08) was used to fuse the images of the two sensors. We

  19. The burning fuse model of unbecoming in time

    Science.gov (United States)

    Norton, John D.

    2015-11-01

    In the burning fuse model of unbecoming in time, the future is real and the past is unreal. It is used to motivate the idea that there is something unbecoming in the present literature on the metaphysics of time: its focus is merely the assigning of a label "real."

  20. Crossed fused renal ectopia: Challenges in diagnosis and management

    Directory of Open Access Journals (Sweden)

    Shailesh Solanki

    2013-01-01

    Full Text Available Aim: Crossed fused renal ectopia is a rare congenital malformation, which is reported to be usually asymptomatic but may have varied presentations. This survey was conducted to study the clinical profile and the challenges posed in the management of this entity. Materials and Methods: Retrospective analysis of 6 patients diagnosed to have crossed fused renal ectopia during 1997-2010. The diagnosis was confirmed during surgical exploration in one patient. In one patient it was detected on antenatal ultrasonography and in the other 4 patients it was detected during investigations for abdominal pain, abdominal mass, anorectal malformation and urinary tract infection. Results: The left moiety was crossed and fused with the right moiety in 4 cases. Ultrasonography was found to be a good screening investigation with useful diagnostic contributions from CT scans, radionuclide scintigraphy and magnetic resonance urography. Micturating cystourethrography revealed presence of VUR in 4 cases, 3 of whom have undergone ureteric reimplantation. Two patients required pyeloplasty for pelviureteric junction obstruction; in one of these patients the upper ureter was entrapped in the isthmus. In one patient, a non-functioning moiety resulted in nephrectomy. All children were asymptomatic at last follow-up with stable renal functions. Conclusions: Crossed fused renal ectopia was detected in most patients during investigation for other problems. It was found more commonly in boys. The left moiety was crossed to the right in the majority of cases. Associated urological problems were found in most cases and required the appropriate surgical management.

  1. Surface roughening of ground fused silica processed by atmospheric inductively coupled plasma

    International Nuclear Information System (INIS)

    Xin, Qiang; Li, Na; Wang, Jun; Wang, Bo; Li, Guo; Ding, Fei; Jin, Huiliang

    2015-01-01

    Highlights: • The morphology evolution of ground fused silica, processed by atmospheric plasma, was investigated experimentally. • The roughness development results from opening and coalescing of the plasma-etched cracks. • The shapes of grain-like etched pits are the results of the adjacent cracks coalescing with one another. • The descent of the pits density is due to some smaller etched pits that are swallowed up by larger pits. • Leading role in surface smoothing is laterally etching away the side walls of the intersecting pits. - Abstract: Subsurface damage (SSD) is a defect that is inevitably induced during mechanical processes, such as grinding and polishing. This defect dramatically reduces the mechanical strength and the laser damage thresholds of optical elements. Compared with traditional mechanical machining, atmospheric pressure plasma processing (APPP) is a relatively novel technology that induces almost no SSD during the processing of silica-based optical materials. In this paper, a form of APPP, inductively coupled plasma (ICP), is used to process fused silica substrates with fluorocarbon precursor under atmospheric pressure. The surface morphology evolution of ICP-processed substrates was observed and characterized by confocal laser scanning microscope (CLSM), field emission scanning electron microscope (SEM), and atomic force microscopy (AFM). The results show that the roughness evolves with the etching depth, and the roughness evolution is a single-peaked curve. This curve results from the opening and the coalescing of surface cracks and fractures. The coalescence procedure of these microstructures was simulated with two common etched pits on a polished fused silica surface. Understanding the roughness evolution of plasma-processed surface might be helpful in optimizing the optical fabrication chain that contains APPP

  2. Surface roughening of ground fused silica processed by atmospheric inductively coupled plasma

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Qiang; Li, Na; Wang, Jun; Wang, Bo, E-mail: bradywang@hit.edu.cn; Li, Guo; Ding, Fei; Jin, Huiliang

    2015-06-30

    Highlights: • The morphology evolution of ground fused silica, processed by atmospheric plasma, was investigated experimentally. • The roughness development results from opening and coalescing of the plasma-etched cracks. • The shapes of grain-like etched pits are the results of the adjacent cracks coalescing with one another. • The descent of the pits density is due to some smaller etched pits that are swallowed up by larger pits. • Leading role in surface smoothing is laterally etching away the side walls of the intersecting pits. - Abstract: Subsurface damage (SSD) is a defect that is inevitably induced during mechanical processes, such as grinding and polishing. This defect dramatically reduces the mechanical strength and the laser damage thresholds of optical elements. Compared with traditional mechanical machining, atmospheric pressure plasma processing (APPP) is a relatively novel technology that induces almost no SSD during the processing of silica-based optical materials. In this paper, a form of APPP, inductively coupled plasma (ICP), is used to process fused silica substrates with fluorocarbon precursor under atmospheric pressure. The surface morphology evolution of ICP-processed substrates was observed and characterized by confocal laser scanning microscope (CLSM), field emission scanning electron microscope (SEM), and atomic force microscopy (AFM). The results show that the roughness evolves with the etching depth, and the roughness evolution is a single-peaked curve. This curve results from the opening and the coalescing of surface cracks and fractures. The coalescence procedure of these microstructures was simulated with two common etched pits on a polished fused silica surface. Understanding the roughness evolution of plasma-processed surface might be helpful in optimizing the optical fabrication chain that contains APPP.

  3. Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated receptor alpha (Pparα).

    Science.gov (United States)

    Shi, Li-juan; Shi, Lei; Song, Guang-yao; Zhang, He-fang; Hu, Zhi-juan; Wang, Chao; Zhang, Dong-hui

    2013-08-15

    The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously. © 2013 Elsevier B.V. All rights reserved.

  4. Identification of FUSE-binding proteins as interacting partners of TIA proteins

    International Nuclear Information System (INIS)

    Rothe, Francoise; Gueydan, Cyril; Bellefroid, Eric; Huez, Georges; Kruys, Veronique

    2006-01-01

    TIA-1 and TIAR are closely related RNA-binding proteins involved in several mechanisms of RNA metabolism, including alternative hnRNA splicing and mRNA translation regulation. In particular, TIA-1 represses tumor necrosis factor (TNF) mRNA translation by binding to the AU-rich element (ARE) present in the mRNA 3' untranslated region. Here, we demonstrate that TIA proteins interact with FUSE-binding proteins (FBPs) and that fbp genes are co-expressed with tia genes during Xenopus embryogenesis. FBPs participate in various steps of RNA processing and degradation. In Cos cells, FBPs co-localize with TIA proteins in the nucleus and migrate into TIA-enriched cytoplasmic granules upon oxidative stress. Overexpression of FBP2-KH3 RNA-binding domain fused to EGFP induces the specific sequestration of TIA proteins in cytoplasmic foci, thereby precluding their nuclear accumulation. In cytosolic RAW 264.7 macrophage extracts, FBPs are found associated in EMSA to the TIA-1/TNF-ARE complex. Together, our results indicate that TIA and FBP proteins may thus be relevant biological involved in common events of RNA metabolism occurring both in the nucleus and the cytoplasm

  5. Design and Analysis of Fused Deposition Modeling 3D Printer Nozzle for Color Mixing

    Directory of Open Access Journals (Sweden)

    Shanling Han

    2017-01-01

    Full Text Available Fused deposition modeling (FDM has been one of the most widely used rapid prototyping (RP technologies leading to the increase in market attention. Obviously it is desirable to print 3D objects; however, existing FDM printers are restricted to printing only monochrome objects because of the entry-level nozzle structure, and literature on the topic is also sparse. In this paper, the CAD model of the nozzle is established first by UG (Unigraphics NX software to show the structure of fused deposition modeling 3D printer nozzle for color mixing. Second, the flow channel model of the nozzle is extracted and simplified. Then, the CAD and finite element model are established by UG and ICEM CFD software, respectively, to prepare for the simulation. The flow field is simulated by Fluent software. The nozzle’s suitable temperature at different extrusion speeds is obtained, and the reason for the blockage at the intersection of the heating block is revealed. Finally, test verification of the nozzle is performed, which can produce mixed-color artifacts stably.

  6. Management of the Regulatory Authority Information

    International Nuclear Information System (INIS)

    Suman, H.

    2003-01-01

    Safe Management of the Regulatory Authority Information is one of the essential elements to ensure the effectiveness of the regulatory program as a whole. This paper briefly describes the information management basis in RNRO, which is in charge of the regulatory authority tasks in Syria. SINA-2, a computational tool prepared in RNRO for managing the information related to the inventory of radiation sources and users, is also introduced

  7. Regulatory control of fuel design and manufacturing

    International Nuclear Information System (INIS)

    1994-01-01

    The regulatory control of the design and manufacturing of the nuclear fuel and of the control rods aims to ensure conformance to set requirements during normal operating conditions, anticipated operational transients and postulated accident conditions. The regulatory control of design, manufacturing, receiving inspections and the start of operation of the nuclear fuel are specified in the guide. The regulatory control procedure also applies to the control rods and the shield elements

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

    Science.gov (United States)

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

    1995-01-01

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

  9. 30 CFR 75.601-2 - Short circuit protection; use of fuses; approval by the Secretary.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Short circuit protection; use of fuses... Trailing Cables § 75.601-2 Short circuit protection; use of fuses; approval by the Secretary. Fuses shall not be employed to provide short circuit protection for trailing cables unless specifically approved...

  10. Influence of System Parameters on Fuse Protection Use in Regenerative DC Drives

    Directory of Open Access Journals (Sweden)

    Isa Salman Qamber

    2009-06-01

    Full Text Available Current limiting fuses are widely used to protect the thyristors in DC drive systems. One very important problem is the choice of the correct voltage rating for fuses protecting regenerative DC drives, where many types of fault may occur, which makes fuse protection difficult. In the event of a commutation failure while regenerating, the fuses need to interrupt the loop supplied by the AC and DC voltages acting in series, which is the most difficult case for protection by fuses. In this paper a detailed study of the complete interruption process has been investigated by modeling of arcing process of the fuse protection against the regenerative circuit internal commutation fault. The effect of varying the motor time constant, supply impedance, number of fuses used to clear the fault and DC machine rating on the total transient response is studied. The model of a 200 A fuse is employed in this study. Fuses in series with both the semiconductor devices (F1 and fuses in AC lines (F2 are considered. Comparison was made between arc energy produced for fuses protecting the regenerative circuit if failure occurs, with the arc energy produced in a standard AC test in order to investigate the required voltage rating for the fuse.

  11. HVI Ballistic Limit Charaterization of Fused Silica Thermal Pane

    Science.gov (United States)

    Bohl, William E.; Miller, Joshua E.; Christiansen, Eric L.; Deighton, Kevin.; Davis, Bruce

    2015-01-01

    The Orion spacecraft's windows are exposed to the micrometeroid and orbital debris (MMOD) space environments while in space as well as the Earth entry environment at the mission's conclusion. The need for a low-mass spacecraft window design drives the need to reduce conservatism when assessing the design for loss of crew due to MMOD impact and subsequent Earth entry. Therefore, work is underway at NASA and Lockheed Martin to improve characterization of the complete penetration ballistic limit of an outer fused silica thermal pane. Hypervelocity impact tests of the window configuration at up to 10 km/s and hydrocode modeling have been performed with a variety of projectile materials to enable refinement of the fused silica ballistic limit equation.

  12. Crossed fused renal ectopia in a Persian cat

    Directory of Open Access Journals (Sweden)

    Sang-Hyuk Seo

    2017-03-01

    Full Text Available Case summary This report describes a rare case of crossed fused renal ectopia (CFRE in a cat. A mature intact male Persian cat presented with bloody nasal discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused with an orthotopic right kidney and a concurrent feline infectious peritonitis (FIP infection. The FIP was responsible for clinical signs in this cat, while clinical signs associated with CFRE were not obvious. Despite receiving intensive treatment, the cat died. A post-mortem examination was not performed because the owners declined approval. Relevance and novel information To the best of our knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this report describes the CT features of L-shaped CFRE in a cat.

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

    Science.gov (United States)

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

    2009-01-01

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

  14. Tetrakis(4-tert-butylphenyl) substituted and fused quinoidal porphyrins

    KAUST Repository

    Zeng, Wangdong

    2012-01-01

    4-tert-Butylphenyl-substituted and fused quinoidal porphyrins 1 and 2 are prepared for the first time. They show (1) intense one-photon absorption in the far-red/near-infrared region, (2) enhanced two-photon absorption compared with aromatic porphyrin monomers, and (3) amphoteric redox behavior. Their geometry and electronic structure are studied by DFT calculations. This journal is © 2012 The Royal Society of Chemistry.

  15. Bilateral maxillary fused second and third molars: a rare occurrence

    OpenAIRE

    Liang, Rui-Zhen; Wu, Jin-Tao; Wu, You-Nong; Smales, Roger J; Hu, Ming; Yu, Jin-Hua; Zhang, Guang-Dong

    2012-01-01

    This case report describes the diagnosis and endodontic therapy of maxillary fused second and third molars, using cone-beam computed tomography (CBCT). A 31-year-old Chinese male, with no contributory medical or family/social history, presented with throbbing pain in the maxillary right molar area following an unsuccessful attempted tooth extraction. Clinical examination revealed what appeared initially to be a damaged large extra cusp on the buccal aspect of the distobuccal cusp of the secon...

  16. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  17. Hybrid Z-Θ Pinches with fused capacitor banks

    International Nuclear Information System (INIS)

    Grandey, R.; Gersten, M.; Loter, N.; Rauch, J.; Rostoker, N.; Thompson, W.; Ware, K.

    1987-01-01

    The Hybrid Z-Θ Pinch circuit equations in the thin shell model were reexamined to see what advantages can be obtained by using a fused, high-energy (>--1MJ) bank driver. The DNA ACE facility at MLI utilizes a 36 μF capacitor band which can be charged to 120 kV to provide 250 kJ of stored energy. This configuration appears to be very appropriate to test the performance of a hybrid-stabilized fused-bank driven pinch. The circuit analyses suggest that the energy transfer efficiency from the bank to a pinched plasma can be increased from less than 1%, for a nonfused bank, to about 10% for a fused configuration. In the applicable region of parameter space, the Hybrid Pinch does not increase the efficiency of energy transfer into the plasma over that obtainable from a Z-pinch. The additional stability may allow larger initial radii to be used with concomitant improved coupling into radiation above 1 keV

  18. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  19. Expression of sterol regulatory element-binding transcription factor (SREBF 2 and SREBF cleavage-activating protein (SCAP in human atheroma and the association of their allelic variants with sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Kytömäki Leena

    2008-12-01

    Full Text Available Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2 and the SREBF cleavage-activating protein (SCAP. We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314 and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD. Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02 down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V, but not in the aorta or femoral arteries (p = NS for both, as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046. Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71, compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the

  20. The Role of Heterologous Chloroplast Sequence Elements in Transgene Integration and Expression1[W][OA

    Science.gov (United States)

    Ruhlman, Tracey; Verma, Dheeraj; Samson, Nalapalli; Daniell, Henry

    2010-01-01

    Heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. Nucleotide sequence identity in the photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. Secondary structure and predicted Gibbs free energy values of the psbA 5′ untranslated region (UTR) among different families reflected this variation. Therefore, chloroplast transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt) psbA promoter, 5′ UTR and 3′ UTR, regulating expression of the anthrax protective antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit (CTB). Unique lettuce flanking sequences were completely eliminated during homologous recombination in the transplastomic tobacco genomes but not unique tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA and 97% CTB-Pins expression when compared with endogenous psbA regulatory elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts containing endogenous 5′ UTR were stabilized in nonpolysomal fractions. Stromal RNA-binding proteins were preferentially associated with endogenous psbA 5′ UTR. A rapid and reproducible regeneration system was developed for lettuce commercial cultivars by optimizing plant growth regulators. These findings underscore the need for sequencing complete crop chloroplast genomes, utilization of endogenous regulatory elements and flanking sequences, as well as optimization of plant growth regulators for efficient chloroplast transformation. PMID:20130101

  1. The role of heterologous chloroplast sequence elements in transgene integration and expression.

    Science.gov (United States)

    Ruhlman, Tracey; Verma, Dheeraj; Samson, Nalapalli; Daniell, Henry

    2010-04-01

    Heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. Nucleotide sequence identity in the photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. Secondary structure and predicted Gibbs free energy values of the psbA 5' untranslated region (UTR) among different families reflected this variation. Therefore, chloroplast transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt) psbA promoter, 5' UTR and 3' UTR, regulating expression of the anthrax protective antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit (CTB). Unique lettuce flanking sequences were completely eliminated during homologous recombination in the transplastomic tobacco genomes but not unique tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA and 97% CTB-Pins expression when compared with endogenous psbA regulatory elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts containing endogenous 5' UTR were stabilized in nonpolysomal fractions. Stromal RNA-binding proteins were preferentially associated with endogenous psbA 5' UTR. A rapid and reproducible regeneration system was developed for lettuce commercial cultivars by optimizing plant growth regulators. These findings underscore the need for sequencing complete crop chloroplast genomes, utilization of endogenous regulatory elements and flanking sequences, as well as optimization of plant growth regulators for efficient chloroplast transformation.

  2. Fabrication of Through via Holes in Ultra-Thin Fused Silica Wafers for Microwave and Millimeter-Wave Applications

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2018-03-01

    Full Text Available Through via holes in fused silica are a key infrastructure element of microwave and millimeter-wave circuits and 3D integration. In this work, etching through via holes in ultra-thin fused silica wafers using deep reactive-ion etching (DRIE and laser ablation was developed and analyzed. The experimental setup and process parameters for both methods are presented and compared. For DRIE, three types of mask materials including KMPR 1035 (Nippon Kayaku, Tokyo, Japan photoresist, amorphous silicon and chromium—with their corresponding optimized processing recipes—were tested, aiming at etching through a 100 μm fused silica wafer. From the experiments, we concluded that using chromium as the masking material is the best choice when using DRIE. However, we found that the laser ablation method with a laser pulse fluence of 2.89 J/cm2 and a pulse overlap of 91% has advantages over DRIE. The laser ablation method has a simpler process complexity, while offering a fair etching result. In particular, the sidewall profile angle is measured to be 75° to the bottom surface of the wafer, which is ideal for the subsequent metallization process. As a demonstration, a two-inch wafer with 624 via holes was processed using both technologies, and the laser ablation method showed better efficiency compared to DRIE.

  3. Elements of a thermic method of preparing beta-sources with fused carriers, including strontium-90; Elements d'une methode thermique de preparation de sources beta avec des entraineurs fondus, y compris le strontium-90; Osnovy termicheskogo metoda prigotovleniya beta-istochnikov s plavlennymi nositelyami, vklyuchayushchimi strontsij-90; Bases de un metodo termico de preparacion de fuentes beta con portadores fundidos, incluido el estroncio-90

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanov, N I; Zakharova, K P; Zimakov, P V; Kulichenko, V V

    1962-01-15

    Sources of ionizing radiation based on the radioisotope Sr{sup 90} are widely used in apparatus and systems of automatic control and regulation of industrial processes. The technology of the preparation of sources is based on dehydration of a mixture of a radioactive solution of strontium nitrate with components such as boric anhydride, silica, and alumina. Thermic treatment of the dehydrated mixture at a high temperature produces a very mobile melt. This cools to a vitreous mass containing the required quantity of the radioisotope Sr{sup 90}. The paper gives data and discusses the results of dehydration of the system SrO - B{sub 2}O{sub 3} - SiO{sub 2} within a temperature range of 100 - 1000{sup o}C and justifies the choice of the main parameters of the technological process. It summarizes a method of mounting a vitreous preparation containing the required quantity of the radioisotope Sr{sup 90} on bases of various shapes and sizes made of steel, ceramic and other materials. The authors discuss the main parameters, ensuring that various types of sources shall be reliable and safe in operation, and give data of Sr{sup 90} sources prepared by the thermic method. (author) [French] Les sources de rayonnements ionisants a base de strontium-90 trouvent une large application dans les appareils et les systemes de controle et de reglage automatique des procedes de production. Le procede de preparation des sources se fonde sur la deshydratation d'un melange compose d'une solution radioactive de nitrate de strontium et d'elements comme l'anhydride borique, la silice, l'alumine, etc. Le traitement thermique du melange deshydrate a haute temperature donne lieu a la formation d'une masse fondue tres mobile, dont le refroidissement fournit une masse vitreuse contenant la quantite requise du radioisotope {sup 59}Sr. Les auteurs citent les donnees et examinent Jes resultats d'une etude sur la deshydratation du systeme SrO - B{sub 2}O{sub 3} - SiO{sub 2} a des temperatures

  4. Fiber fuse behavior in kW-level continuous-wave double-clad field laser

    International Nuclear Information System (INIS)

    Sun Jun-Yi; Xiao Qi-Rong; Li Dan; Wang Xue-Jiao; Zhang Hai-Tao; Gong Ma-Li; Yan Ping

    2016-01-01

    In this study, original experimental data for fiber fuse in kW-level continuous-wave (CW) high power double-clad fiber (DCF) laser are reported. The propagating velocity of the fuse is 9.68 m/s in a 3.1-kW Yb-doped DCF laser. Three other cases in Yb-doped DCF are also observed. We think that the ignition of fiber fuse is caused by thermal mechanism, and the formation of bullet-shaped tracks is attributed to the optical discharge and temperature gradient. The inducements of initial fuse and formation of bullet-shaped voids are analyzed. This investigation of fiber fuse helps better understand the fiber fuse behavior, in order to avoid the catastrophic destruction caused by fiber fuse in high power fiber laser. (paper)

  5. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  6. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  7. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  8. Tree Classification with Fused Mobile Laser Scanning and Hyperspectral Data

    Science.gov (United States)

    Puttonen, Eetu; Jaakkola, Anttoni; Litkey, Paula; Hyyppä, Juha

    2011-01-01

    Mobile Laser Scanning data were collected simultaneously with hyperspectral data using the Finnish Geodetic Institute Sensei system. The data were tested for tree species classification. The test area was an urban garden in the City of Espoo, Finland. Point clouds representing 168 individual tree specimens of 23 tree species were determined manually. The classification of the trees was done using first only the spatial data from point clouds, then with only the spectral data obtained with a spectrometer, and finally with the combined spatial and hyperspectral data from both sensors. Two classification tests were performed: the separation of coniferous and deciduous trees, and the identification of individual tree species. All determined tree specimens were used in distinguishing coniferous and deciduous trees. A subset of 133 trees and 10 tree species was used in the tree species classification. The best classification results for the fused data were 95.8% for the separation of the coniferous and deciduous classes. The best overall tree species classification succeeded with 83.5% accuracy for the best tested fused data feature combination. The respective results for paired structural features derived from the laser point cloud were 90.5% for the separation of the coniferous and deciduous classes and 65.4% for the species classification. Classification accuracies with paired hyperspectral reflectance value data were 90.5% for the separation of coniferous and deciduous classes and 62.4% for different species. The results are among the first of their kind and they show that mobile collected fused data outperformed single-sensor data in both classification tests and by a significant margin. PMID:22163894

  9. Endodontic treatment of a fused tooth. Report of a case.

    Science.gov (United States)

    Gallottini, L; Barbato Bellatini, R C; Migliau, G

    2007-01-01

    Dental fusion, a rare developmental anomaly present in 0.2% of the general population, consists of the union of two teeth originating from two different tooth germs. The irregular coronal morphology and the complex endodontic anatomy, characterized by the partial or total union of the pulp chambers, together with the peculiarity of the root canal systems, make diagnosis, therapy and rehabilitation difficult. The authors describe the endodontic treatment of a permanent lower second molar fused with a third molar and having four root canals.

  10. Textiles: Some technocal information and data VI: fusing

    CSIR Research Space (South Africa)

    Cawood, MP

    1980-09-01

    Full Text Available only one month is reauired to train an oDerator for fusing whereas 4 - 6 monthsare - - -- - necessary f i r sewing machine bperatod. 3. Higher production rates and a reduction in manufacturing costs'-7, 11. 14-11. It has been stated that although... less thanoncea day. Funhermore, confusionsG~ existed with respect to temperature (i e glue line or surface) and nressure laress or air line) s~ecifications and a wide ranee of temperatures &ere deingempibYedfor thesakeiype of adhesive. ~ ~ ~ a r e n...

  11. Stimulated resonant scattering at stressed fused silica surface

    International Nuclear Information System (INIS)

    Bouchut, Philippe; Reymermier, Maryse

    2015-01-01

    The radiative emission in CO 2 laser heated stressed fused silica is radically modified when gold microspheres are on the surface. At high heating rates, the emission dynamics changes from thermoluminescence to stimulated resonant scattering with an emission rate that is increased tenfold and the near infrared (NIR) spectrum is red-shifted. We show that the dynamic tensile stress that rises in heated silica is coupled with a fluctuating electromagnetic field that enables electromagnetic friction between moving OH emitters from silica bulk and NIR resonant scatterers at the silica surface. (paper)

  12. Cerium-doped scintillating fused-silica fibers

    Science.gov (United States)

    Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P.; Faulkner, J.; Kunori, S.

    2018-04-01

    We report on a set of measurements made on (scintillating) cerium-doped fused-silica fibers using high-energy particle beams. These fibers were uniformly embedded in a copper absorber in order to utilize electromagnetic showers as a source of charged particles for generating signals. This new type of cerium-doped fiber potentially offers myriad new applications in calorimeters in high-energy physics, tracking systems, and beam monitoring detectors for future applications. The light yield, pulse shape, attenuation length, and light propagation speeds are given and discussed. Possible future applications are also explored.

  13. Collaborative Filtering Fusing Label Features Based on SDAE

    DEFF Research Database (Denmark)

    Huo, Huan; Liu, Xiufeng; Zheng, Deyuan

    2017-01-01

    problem, auxiliary information such as labels are utilized. Another approach of recommendation system is content-based model which can’t be directly integrated with CF-based model due to its inherent characteristics. Considering that deep learning algorithms are capable of extracting deep latent features......, this paper applies Stack Denoising Auto Encoder (SDAE) to content-based model and proposes LCF(Deep Learning for Collaborative Filtering) algorithm by combing CF-based model which fuses label features. Experiments on real-world data sets show that DLCF can largely overcome the sparsity problem...... and significantly improves the state of art approaches....

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  15. Standard elements; Elements standards

    Energy Technology Data Exchange (ETDEWEB)

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

    1958-07-01

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

  16. Planning the FUSE Mission Using the SOVA Algorithm

    Science.gov (United States)

    Lanzi, James; Heatwole, Scott; Ward, Philip R.; Civeit, Thomas; Calvani, Humberto; Kruk, Jeffrey W.; Suchkov, Anatoly

    2011-01-01

    Three documents discuss the Sustainable Objective Valuation and Attainability (SOVA) algorithm and software as used to plan tasks (principally, scientific observations and associated maneuvers) for the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. SOVA is a means of managing risk in a complex system, based on a concept of computing the expected return value of a candidate ordered set of tasks as a product of pre-assigned task values and assessments of attainability made against qualitatively defined strategic objectives. For the FUSE mission, SOVA autonomously assembles a week-long schedule of target observations and associated maneuvers so as to maximize the expected scientific return value while keeping the satellite stable, managing the angular momentum of spacecraft attitude- control reaction wheels, and striving for other strategic objectives. A six-degree-of-freedom model of the spacecraft is used in simulating the tasks, and the attainability of a task is calculated at each step by use of strategic objectives as defined by use of fuzzy inference systems. SOVA utilizes a variant of a graph-search algorithm known as the A* search algorithm to assemble the tasks into a week-long target schedule, using the expected scientific return value to guide the search.

  17. Ball driven type MEMS SAD for artillery fuse

    International Nuclear Information System (INIS)

    Seok, Jin Oh; Jeong, Ji-hun; Eom, Junseong; Lee, Seung S; Lee, Chun Jae; Ryu, Sung Moon; Oh, Jong Soo

    2017-01-01

    The SAD (safety and arming device) is an indispensable fuse component that ensures safe and reliable performance during the use of ammunition. Because the application of electronic devices for smart munitions is increasing, miniaturization of the SAD has become one of the key issues for next-generation artillery fuses. Based on MEMS technology, various types of miniaturized SADs have been proposed and fabricated. However, none of them have been reported to have been used in actual munitions due to their lack of high impact endurance and complicated explosive train arrangements. In this research, a new MEMS SAD using a ball driven mechanism, is successfully demonstrated based on a UV LIGA (lithography, electroplating and molding) process. Unlike other MEMS SADs, both high impact endurance and simple structure were achieved by using a ball driven mechanism. The simple structural design also simplified the fabrication process and increased the processing yield. The ball driven type MEMS SAD performed successfully under the desired safe and arming conditions of a spin test and showed fine agreement with the FEM simulation result, conducted prior to its fabrication. A field test was also performed with a grenade launcher to evaluate the SAD performance in the firing environment. All 30 of the grenade samples equipped with the proposed MEMS SAD operated successfully under the high-G setback condition. (paper)

  18. Ball driven type MEMS SAD for artillery fuse

    Science.gov (United States)

    Seok, Jin Oh; Jeong, Ji-hun; Eom, Junseong; Lee, Seung S.; Lee, Chun Jae; Ryu, Sung Moon; Oh, Jong Soo

    2017-01-01

    The SAD (safety and arming device) is an indispensable fuse component that ensures safe and reliable performance during the use of ammunition. Because the application of electronic devices for smart munitions is increasing, miniaturization of the SAD has become one of the key issues for next-generation artillery fuses. Based on MEMS technology, various types of miniaturized SADs have been proposed and fabricated. However, none of them have been reported to have been used in actual munitions due to their lack of high impact endurance and complicated explosive train arrangements. In this research, a new MEMS SAD using a ball driven mechanism, is successfully demonstrated based on a UV LIGA (lithography, electroplating and molding) process. Unlike other MEMS SADs, both high impact endurance and simple structure were achieved by using a ball driven mechanism. The simple structural design also simplified the fabrication process and increased the processing yield. The ball driven type MEMS SAD performed successfully under the desired safe and arming conditions of a spin test and showed fine agreement with the FEM simulation result, conducted prior to its fabrication. A field test was also performed with a grenade launcher to evaluate the SAD performance in the firing environment. All 30 of the grenade samples equipped with the proposed MEMS SAD operated successfully under the high-G setback condition.

  19. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the \\'quinone-fusing\\' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.

  20. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

  1. Regulatory Expectations for Safety Culture

    International Nuclear Information System (INIS)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

    2014-01-01

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

  2. Regulatory interventions necessitated by non-conservative operator decisions

    International Nuclear Information System (INIS)

    Ojha, D.; Chande, S.K.; Sharma, S.K.

    2005-01-01

    Presently, India has 15 nuclear power units in operation and 8 units under construction. Though the safety performance of the Nuclear Power Plants (NPPs) in India has been excellent, a few recent events indicate that conservative decision making process can possibly get affected by perceived production goals. In one of the events, a need for some maintenance work arose while reactor start-up was in progress. After it was realized that the maintenance would require considerable time, the proper course of action would have been to shutdown the reactor and add neutron poison to moderator to ensure sufficient sub criticality. This was not done, as it would have delayed the start up of the reactor on completion of maintenance. In another incident, an unintended slow increase in reactor power occurred due to the adjuster rods becoming inoperable on account of blowing-off of fuses in their power supply. Under this condition, the reactor should have been tripped which was not done. Further, the automatic addition of boron poison to the reactor was inhibited. Regulatory review showed that both the incidents were indicative of degradation in safety culture and reflected operator's overriding concern for keeping the units in operation. Appropriate corrective actions were taken to prevent recurrence of such events in the respective units as also in all other operating units of similar type. In the wake of improved production performance operators may develop a tendency to create new operational records and compete with other units. This aspect points out to a need for careful study of events to check the presence of any element of non-conservative decision-making and to identify leading indicators of degradation in safety performance. (author)

  3. RR Tel: Getting Under the Flux Limit: An Observation with FUSE

    Science.gov (United States)

    Sonnenborn, George (Technical Monitor); Kenyon, Scott J.

    2004-01-01

    The goal of this program is to acquire a FUSE spectrum of the symbiotic binary RR Tel. With these data, we plan to derive improved constraints on the hot component, the nebula, and perhaps the red giant wind. Based on results from AG Dra, we should also be able to use some line detections to improve atomic parameters for high ionization emission lines. This results would benefit the general FUSE community. As of this writing, the FUSE observation of RR Tel has not been made. Because RR Tel is a very bright UV source, the FUSE team is assessing the likelihood that RR Tel will have an adverse affect on the instrument.

  4. Knowledge-fused differential dependency network models for detecting significant rewiring in biological networks.

    Science.gov (United States)

    Tian, Ye; Zhang, Bai; Hoffman, Eric P; Clarke, Robert; Zhang, Zhen; Shih, Ie-Ming; Xuan, Jianhua; Herrington, David M; Wang, Yue

    2014-07-24

    Modeling biological networks serves as both a major goal and an effective tool of systems biology in studying mechanisms that orchestrate the activities of gene products in cells. Biological networks are context-specific and dynamic in nature. To systematically characterize the selectively activated regulatory components and mechanisms, modeling tools must be able to effectively distinguish significant rewiring from random background fluctuations. While differential networks cannot be constructed by existing knowledge alone, novel incorporation of prior knowledge into data-driven approaches can improve the robustness and biological relevance of network inference. However, the major unresolved roadblocks include: big solution space but a small sample size; highly complex networks; imperfect prior knowledge; missing significance assessment; and heuristic structural parameter learning. To address these challenges, we formulated the inference of differential dependency networks that incorporate both conditional data and prior knowledge as a convex optimization problem, and developed an efficient learning algorithm to jointly infer the conserved biological network and the significant rewiring across different conditions. We used a novel sampling scheme to estimate the expected error rate due to "random" knowledge. Based on that scheme, we developed a strategy that fully exploits the benefit of this data-knowledge integrated approach. We demonstrated and validated the principle and performance of our method using synthetic datasets. We then applied our method to yeast cell line and breast cancer microarray data and obtained biologically plausible results. The open-source R software package and the experimental data are freely available at http://www.cbil.ece.vt.edu/software.htm. Experiments on both synthetic and real data demonstrate the effectiveness of the knowledge-fused differential dependency network in revealing the statistically significant rewiring in biological

  5. Neutronic study of a nuclear reactor of fused salts

    International Nuclear Information System (INIS)

    Garcia B, F. B.; Francois L, J. L.

    2012-10-01

    The reactors of fused salts called Molten Salt Reactor have presented a resurgence of interest in the last decade, due to they have a versatility in particular to operate, either with a thermal or fast neutrons spectrum. The most active development was by the middle of 1950 and principles of 1970 in the Oak Ridge National Laboratory. In this work some developed models are presented particularly and studied with the help of the MCNPX code, for the development of the neutronic study of this reactor, starting of proposed models and from a simple and homogeneous geometry until other more complex models and approximate to more real cases. In particular the geometry conditions and criticality of each model were analyzed, the isotopic balance, as well as the concentrations of the salts and different assigned fuel types. (Author)

  6. Fused Adaptive Lasso for Spatial and Temporal Quantile Function Estimation

    KAUST Repository

    Sun, Ying

    2015-09-01

    Quantile functions are important in characterizing the entire probability distribution of a random variable, especially when the tail of a skewed distribution is of interest. This article introduces new quantile function estimators for spatial and temporal data with a fused adaptive Lasso penalty to accommodate the dependence in space and time. This method penalizes the difference among neighboring quantiles, hence it is desirable for applications with features ordered in time or space without replicated observations. The theoretical properties are investigated and the performances of the proposed methods are evaluated by simulations. The proposed method is applied to particulate matter (PM) data from the Community Multiscale Air Quality (CMAQ) model to characterize the upper quantiles, which are crucial for studying spatial association between PM concentrations and adverse human health effects. © 2016 American Statistical Association and the American Society for Quality.

  7. Nanoimprint Lithography on curved surfaces prepared by fused deposition modelling

    International Nuclear Information System (INIS)

    Köpplmayr, Thomas; Häusler, Lukas; Bergmair, Iris; Mühlberger, Michael

    2015-01-01

    Fused deposition modelling (FDM) is an additive manufacturing technology commonly used for modelling, prototyping and production applications. The achievable surface roughness is one of its most limiting aspects. It is however of great interest to create well-defined (nanosized) patterns on the surface for functional applications such as optical effects, electronics or bio-medical devices. We used UV-curable polymers of different viscosities and flexible stamps made of poly(dimethylsiloxane) (PDMS) to perform Nanoimprint Lithography (NIL) on FDM-printed curved parts. Substrates with different roughness and curvature were prepared using a commercially available 3D printer. The nanoimprint results were characterized by optical light microscopy, profilometry and atomic force microscopy (AFM). Our experiments show promising results in creating well-defined microstructures on the 3D-printed parts. (paper)

  8. Unified design of sinusoidal-groove fused-silica grating.

    Science.gov (United States)

    Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lu, Peng

    2010-10-20

    A general design rule of deep-etched subwavelength sinusoidal-groove fused-silica grating as a highly efficient polarization-independent or polarization-selective device is studied based on the simplified modal method, which shows that the device structure depends little on the incident wavelength, but mainly on the ratio of groove depth to incident wavelength and the ratio of wavelength to grating period. These two ratios could be used as the design guidelines for wavelength-independent structure from deep ultraviolet to far infrared. The optimized grating profile with a different function as a polarizing beam splitter, a polarization-independent two-port beam splitter, or a polarization-independent grating with high efficiency of -1st order is obtained at a wavelength of 1064 nm, and verified by using the rigorous coupled-wave analysis. The performance of the sinusoidal grating is better than a conventional rectangular one, which could be useful for practical applications.

  9. Fused cerebral organoids model interactions between brain regions.

    Science.gov (United States)

    Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

    2017-07-01

    Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

  10. Fusing Quantitative Requirements Analysis with Model-based Systems Engineering

    Science.gov (United States)

    Cornford, Steven L.; Feather, Martin S.; Heron, Vance A.; Jenkins, J. Steven

    2006-01-01

    A vision is presented for fusing quantitative requirements analysis with model-based systems engineering. This vision draws upon and combines emergent themes in the engineering milieu. "Requirements engineering" provides means to explicitly represent requirements (both functional and non-functional) as constraints and preferences on acceptable solutions, and emphasizes early-lifecycle review, analysis and verification of design and development plans. "Design by shopping" emphasizes revealing the space of options available from which to choose (without presuming that all selection criteria have previously been elicited), and provides means to make understandable the range of choices and their ramifications. "Model-based engineering" emphasizes the goal of utilizing a formal representation of all aspects of system design, from development through operations, and provides powerful tool suites that support the practical application of these principles. A first step prototype towards this vision is described, embodying the key capabilities. Illustrations, implications, further challenges and opportunities are outlined.

  11. Visualization of conserved structures by fusing highly variable datasets.

    Science.gov (United States)

    Silverstein, Jonathan C; Chhadia, Ankur; Dech, Fred

    2002-01-01

    Skill, effort, and time are required to identify and visualize anatomic structures in three-dimensions from radiological data. Fundamentally, automating these processes requires a technique that uses symbolic information not in the dynamic range of the voxel data. We were developing such a technique based on mutual information for automatic multi-modality image fusion (MIAMI Fuse, University of Michigan). This system previously demonstrated facility at fusing one voxel dataset with integrated symbolic structure information to a CT dataset (different scale and resolution) from the same person. The next step of development of our technique was aimed at accommodating the variability of anatomy from patient to patient by using warping to fuse our standard dataset to arbitrary patient CT datasets. A standard symbolic information dataset was created from the full color Visible Human Female by segmenting the liver parenchyma, portal veins, and hepatic veins and overwriting each set of voxels with a fixed color. Two arbitrarily selected patient CT scans of the abdomen were used for reference datasets. We used the warping functions in MIAMI Fuse to align the standard structure data to each patient scan. The key to successful fusion was the focused use of multiple warping control points that place themselves around the structure of interest automatically. The user assigns only a few initial control points to align the scans. Fusion 1 and 2 transformed the atlas with 27 points around the liver to CT1 and CT2 respectively. Fusion 3 transformed the atlas with 45 control points around the liver to CT1 and Fusion 4 transformed the atlas with 5 control points around the portal vein. The CT dataset is augmented with the transformed standard structure dataset, such that the warped structure masks are visualized in combination with the original patient dataset. This combined volume visualization is then rendered interactively in stereo on the ImmersaDesk in an immersive Virtual

  12. Using conceptual spaces to fuse knowledge from heterogeneous robot platforms

    Science.gov (United States)

    Kira, Zsolt

    2010-04-01

    As robots become more common, it becomes increasingly useful for many applications to use them in teams that sense the world in a distributed manner. In such situations, the robots or a central control center must communicate and fuse information received from multiple sources. A key challenge for this problem is perceptual heterogeneity, where the sensors, perceptual representations, and training instances used by the robots differ dramatically. In this paper, we use Gärdenfors' conceptual spaces, a geometric representation with strong roots in cognitive science and psychology, in order to represent the appearance of objects and show how the problem of heterogeneity can be intuitively explored by looking at the situation where multiple robots differ in their conceptual spaces at different levels. To bridge low-level sensory differences, we abstract raw sensory data into properties (such as color or texture categories), represented as Gaussian Mixture Models, and demonstrate that this facilitates both individual learning and the fusion of concepts between robots. Concepts (e.g. objects) are represented as a fuzzy mixture of these properties. We then treat the problem where the conceptual spaces of two robots differ and they only share a subset of these properties. In this case, we use joint interaction and statistical metrics to determine which properties are shared. Finally, we show how conceptual spaces can handle the combination of such missing properties when fusing concepts received from different robots. We demonstrate the fusion of information in real-robot experiments with a Mobile Robots Amigobot and Pioneer 2DX with significantly different cameras and (on one robot) a SICK lidar.ÿÿÿÿ

  13. The anomalous yield behavior of fused silica glass

    Science.gov (United States)

    Schill, W.; Heyden, S.; Conti, S.; Ortiz, M.

    2018-04-01

    We develop a critical-state model of fused silica plasticity on the basis of data mined from molecular dynamics (MD) calculations. The MD data is suggestive of an irreversible densification transition in volumetric compression resulting in permanent, or plastic, densification upon unloading. The MD data also reveals an evolution towards a critical state of constant volume under pressure-shear deformation. The trend towards constant volume is from above, when the glass is overconsolidated, or from below, when it is underconsolidated. We show that these characteristic behaviors are well-captured by a critical state model of plasticity, where the densification law for glass takes the place of the classical consolidation law of granular media and the locus of constant-volume states defines the critical-state line. A salient feature of the critical-state line of fused silica, as identified from the MD data, that renders its yield behavior anomalous is that it is strongly non-convex, owing to the existence of two well-differentiated phases at low and high pressures. We argue that this strong non-convexity of yield explains the patterning that is observed in molecular dynamics calculations of amorphous solids deforming in shear. We employ an explicit and exact rank-2 envelope construction to upscale the microscopic critical-state model to the macroscale. Remarkably, owing to the equilibrium constraint the resulting effective macroscopic behavior is still characterized by a non-convex critical-state line. Despite this lack of convexity, the effective macroscopic model is stable against microstructure formation and defines well-posed boundary-value problems.

  14. Galvanic element. Galvanisches Element

    Energy Technology Data Exchange (ETDEWEB)

    Sprengel, D.; Haelbig, H.

    1980-01-03

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

  15. Safety culture as a matter of regulatory control and regulatory effectiveness

    International Nuclear Information System (INIS)

    Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

    2002-01-01

    More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

  16. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

    The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

  17. Application of resettable elements for electrical protection of solar batteries

    Directory of Open Access Journals (Sweden)

    Tonkoshkur A. S.

    2018-06-01

    Full Text Available The manifestation and formation of various defects in the process of exploitation in real photovoltaic cells and their compounds as well as their work in the regime of changing non-uniform illumination lead to the so-called series and parallel inconsistencies (differences of electrical characteristics between separate cells and their groups. This results in local overheating and intensifying of degradation processes. In some cases temporary disconnection (isolation of the corresponding elements of the solar batteries is more appropriate in order to increase their service life. In this work additional devices for insulation of overheating cells (and/or components of solar batteries such as «PolySwith» resettable fuses are proposed to be used as a perspective solution of such problems. These structures are polymer composites with nanosized carbon fillers. Electrical resistance of such a fuse increases abruptly by several orders of magnitude when certain threshold temperature is reached, and when the temperature decreases the fuse returns to its initial high-conductivity state. This study investigates the possibilities of using the specified type of fuses for electrical insulation of «overheated» photovoltaic cells. Particular attention is paid to the research of the effect of fuses on the working of the solar batteries in the operating temperature range and their functional applicability in emergency situations associated with overheating. The studies were carried out using a model structure of several series of parallel connected photovoltaic cells and specified fuses. Attention is paid to the influence of such factors as the ambient temperature and the drift of the fuses resistance in the conducting state in the process their multiple switching. It has been established that such protection elements do not influence the work of solar batteries in operating temperature range and are functionally applicable for the electrical isolation of local

  18. Characterization of noncoding regulatory DNA in the human genome.

    Science.gov (United States)

    Elkon, Ran; Agami, Reuven

    2017-08-08

    Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

  19. Croatian energy regulatory council - independent Croatian regulatory body

    International Nuclear Information System (INIS)

    Klepo, M.

    2002-01-01

    By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

  20. Morphological evaluation of maxillary second molars with fused roots: a micro-CT study.

    Science.gov (United States)

    Ordinola-Zapata, R; Martins, J N R; Bramante, C M; Villas-Boas, M H; Duarte, M H; Versiani, M A

    2017-12-01

    To evaluate the internal and external morphologies of fused-rooted maxillary second molars by means of micro-computed tomography (micro-CT) analysis. A total of 100 fused-rooted maxillary second molars from a Brazilian subpopulation were divided into six groups according to the root morphology. The samples were scanned at a resolution of 19.6 μm and evaluated with regard to the external morphology of the roots, the root canal configuration, the percentage frequency of C-shaped canals and isthmuses, as well as the morphology of the root canal system at 1, 2 and 3 mm from the anatomical apex of the fused roots. The most prevalent root canal fusions were type 1, mesiobuccal root fused with distobuccal root (32%), followed by type 3, DB root fused with P root (27%), and type 4, MB root fused with DB root, and P root fused with MB or DB roots (21%). The prevalence of C-shaped root canal systems were 22%. Depending on the type of root fusion, the percentage frequency of isthmuses in the apical level varied from 9.3% to 42.8%, whilst the presence of apical deltas ranged from 18.5% to 57.1% of teeth. The root canal system of maxillary second molars with fused roots may have a high incidence of merging canals, isthmuses, apical deltas and C-shaped configurations. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  1. High-voltage safety fuses for the transition-radiation tracking detector in the ATLAS experiment

    NARCIS (Netherlands)

    Voronov, SA; Voronov, YA; Onishchenko, EM; Simakov, AB; Sosnovtsev, VV; Suchkov, SI; Sugrobova, TA

    2004-01-01

    A safety fuse has been designed for the electrical protection of gas-filled detectors in the ATLAS experiment at CERN (Geneva, Switzerland). The fuse is a polished lithium niobate plate with a titanium strip of 91-kOmega resistance deposited by the photolithographic technique. The forced blow-out

  2. and 8-Membered Oxygen-containing Benzo-fused Rings using ...

    African Journals Online (AJOL)

    NJD

    A number of benzo-fused oxygen-containing heterocycles were synthesized from allyl-3-isopropoxy-4-methoxybenzaldehyde using metathesis or an alkene isomerization-metathesis sequence as key synthetic steps. Benzo-fused compounds thus formed included a 3,6-dihydro-1H-2-benzoxocine, ...

  3. Firefighters United for Safety, Ethics, and Ecology (FUSEE): Torchbearers for a new fire management paradigm

    Science.gov (United States)

    Timothy Ingalsbee; Joseph Fox; Patrick Withen

    2007-01-01

    Firefighters United for Safety, Ethics, and Ecology (FUSEE) is a nonprofit organization promoting safe, ethical, ecological wildland fire management. FUSEE believes firefighter and community safety are ultimately interdependent with ethical public service, wildlands protection, and ecological restoration of fire-adapted ecosystems. Our members include current, former,...

  4. Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines

    NARCIS (Netherlands)

    Rainoldi, Giulia; Begnini, Fabio; De Munnik, Mariska; Lo Presti, Leonardo; Vande Velde, Christophe M.L.; Orru, Romano; Lesma, Giordano; Ruijter, Eelco; Silvani, Alessandra

    2018-01-01

    We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures

  5. Comparing monolithic and fused core HPLC columns for fast chromatographic analysis of fat-soluble vitamins.

    Science.gov (United States)

    Kurdi, Said El; Muaileq, Dina Abu; Alhazmi, Hassan A; Bratty, Mohammed Al; Deeb, Sami El

    2017-06-27

    HPLC stationary phases of monolithic and fused core type can be used to achieve fast chromatographic separation as an alternative to UPLC. In this study, monolithic and fused core stationary phases are compared for fast separation of four fat-soluble vitamins. Three new methods on the first and second generation monolithic silica RP-18e columns and a fused core pentafluoro-phenyl propyl column were developed. Application of three fused core columns offered comparable separations of retinyl palmitate, DL-α-tocopheryl acetate, cholecalciferol and menadione in terms of elution speed and separation efficiency. Separation was achieved in approx. 5 min with good resolution (Rs > 5) and precision (RSD ≤ 0.6 %). Monolithic columns showed, however, a higher number of theoretical plates, better precision and lower column backpressure than the fused core column. The three developed methods were successfully applied to separate and quantitate fat-soluble vitamins in commercial products.

  6. Comparing monolithic and fused core HPLC columns for fast chromatographic analysis of fat-soluble vitamins

    Directory of Open Access Journals (Sweden)

    Kurdi Said El

    2017-06-01

    Full Text Available HPLC stationary phases of monolithic and fused core type can be used to achieve fast chromatographic separation as an alternative to UPLC. In this study, monolithic and fused core stationary phases are compared for fast separation of four fat-soluble vitamins. Three new methods on the first and second generation monolithic silica RP-18e columns and a fused core pentafluoro-phenyl propyl column were developed. Application of three fused core columns offered comparable separations of retinyl palmitate, DL-α-tocopheryl acetate, cholecalciferol and menadione in terms of elution speed and separation efficiency. Separation was achieved in approx. 5 min with good resolution (Rs > 5 and precision (RSD ≤ 0.6 %. Monolithic columns showed, however, a higher number of theoretical plates, better precision and lower column backpressure than the fused core column. The three developed methods were successfully applied to separate and quantitate fat-soluble vitamins in commercial products.

  7. Refractive index sensors based on the fused tapered special multi-mode fiber

    Science.gov (United States)

    Fu, Xing-hu; Xiu, Yan-li; Liu, Qin; Xie, Hai-yang; Yang, Chuan-qing; Zhang, Shun-yang; Fu, Guang-wei; Bi, Wei-hong

    2016-01-01

    In this paper, a novel refractive index (RI) sensor is proposed based on the fused tapered special multi-mode fiber (SMMF). Firstly, a section of SMMF is spliced between two single-mode fibers (SMFs). Then, the SMMF is processed by a fused tapering machine, and a tapered fiber structure is fabricated. Finally, a fused tapered SMMF sensor is obtained for measuring external RI. The RI sensing mechanism of tapered SMMF sensor is analyzed in detail. For different fused tapering lengths, the experimental results show that the RI sensitivity can be up to 444.517 81 nm/RIU in the RI range of 1.334 9—1.347 0. The RI sensitivity is increased with the increase of fused tapering length. Moreover, it has many advantages, including high sensitivity, compact structure, fast response and wide application range. So it can be used to measure the solution concentration in the fields of biochemistry, health care and food processing.

  8. CuFeO2 formation using fused deposition modeling 3D printing and sintering technique

    Science.gov (United States)

    Salea, A.; Dasaesamoh, A.; Prathumwan, R.; Kongkaew, T.; Subannajui, K.

    2017-09-01

    CuFeO2 is a metal oxide mineral material which is called delafossite. It can potentially be used as a chemical catalyst, and gas sensing material. There are methods to fabricate CuFeO2 such as chemical synthesis, sintering, sputtering, and chemical vapor deposition. In our work, CuFeO2 is prepared by Fused Deposition Modeling (FDM) 3D printing. The composite filament which composed of Cu and Fe elements is printed in three dimensions, and then sintered and annealed at high temperature to obtain CuFeO2. Suitable polymer blend and maximum percent volume of metal powder are studied. When percent volume of metal powder is increased, melt flow rate of polymer blend is also increased. The most suitable printing condition is reported and the properties of CuFeO2 are observed by Scanning Electron Microscopy, and Dynamic Scanning Calorimeter, X-ray diffraction. As a new method to produce semiconductor, this technique has a potential to allow any scientist or students to design and print a catalyst or sensing material by the most conventional 3D printing machine which is commonly used around the world.

  9. Increasing dimension of structures by 4D printing shape memory polymers via fused deposition modeling

    Science.gov (United States)

    Hu, G. F.; Damanpack, A. R.; Bodaghi, M.; Liao, W. H.

    2017-12-01

    The main objective of this paper is to introduce a 4D printing method to program shape memory polymers (SMPs) during fabrication process. Fused deposition modeling (FDM) as a filament-based printing method is employed to program SMPs during depositing the material. This method is implemented to fabricate complicated polymeric structures by self-bending features without need of any post-programming. Experiments are conducted to demonstrate feasibility of one-dimensional (1D)-to 2D and 2D-to-3D self-bending. It is shown that 3D printed plate structures can transform into masonry-inspired 3D curved shell structures by simply heating. Good reliability of SMP programming during printing process is also demonstrated. A 3D macroscopic constitutive model is established to simulate thermo-mechanical features of the printed SMPs. Governing equations are also derived to simulate programming mechanism during printing process and shape change of self-bending structures. In this respect, a finite element formulation is developed considering von-Kármán geometric nonlinearity and solved by implementing iterative Newton-Raphson scheme. The accuracy of the computational approach is checked with experimental results. It is demonstrated that the theoretical model is able to replicate the main characteristics observed in the experiments. This research is likely to advance the state of the art FDM 4D printing, and provide pertinent results and computational tool that are instrumental in design of smart materials and structures with self-bending features.

  10. Synthesis and biological activity of fused tetracyclic Pyrrolo[2,1-c][1,4]benzodiazepines

    Directory of Open Access Journals (Sweden)

    Joel K. Annor-Gyamfi

    2018-02-01

    Full Text Available Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines.

  11. Numerical evaluation of ABS parts fabricated by fused deposition modeling and vapor smoothing

    Directory of Open Access Journals (Sweden)

    Sung-Uk Zhang

    2017-12-01

    Full Text Available The automotive industry has focused to use polymer materials in order to increase energy efficiency. So, the industry pays attention to use 3D printing technologies using several polymers. Among several 3D printer technologies, fused deposition modeling (FDM is one of the popular 3D printing technologies due to an inexpensive extrusion machine and multi-material printing. FDM could use thermoplastics such as ABS, PLA, ULTEM so on. However, it has a problem related to the post-processing because FDM has relatively poor layer resolution. In this study, the mechanical properties of ABS parts fabricated by FDM were measured. The ABS parts were divided into one with vapor smoothing process and the other without the vapor smoothing process which is one of the post-processing methods. Using dynamic mechanical analysis (DMA and dilatometer, temperature-dependent storage modulus and CTE for ABS specimens were measured. Based on the measured thermo-mechanical properties of ABS parts, finite element analysis was performed for an automotive bumper made of ABS. Moreover, response surface methodology was applied to study relationships among design parameters of thickness of the bumper, ambient temperature, and application of the vapor smoothing process. In result, a design guideline for a ABS product could be provided without time-consuming experiments

  12. Femtosecond laser-induced structural difference in fused silica with a non-reciprocal writing process

    Science.gov (United States)

    Song, Hui; Dai, Ye; Song, Juan; Ma, Hongliang; Yan, Xiaona; Ma, Guohong

    2017-04-01

    In this paper, we report a non-reciprocal writing process for inducing asymmetric microstructure using a femtosecond laser with tilted pulse fronts in fused silica. The shape of the induced microstructure at the focus closely depends on the laser scan direction. An elongated end is observed as a kind of structural difference between the written lines with two reverse scans along + x and - x, which further leads to a birefringence intensity difference. We also find a bifurcation in the head region of the induced microstructure between the written lines along x and y. That process results from the focal intensity distortion caused by the pulse front tilt by comparing the simulated intensity distribution with the experimental results. The current results demonstrate that the pulse front tilt not only affects the free electron excitation at the focus but also further distorts the shape of the induced microstructure during a high-energy femtosecond laser irradiation. These results offer a route to fabricate optical elements by changing the spatiotemporal characteristics of ultrashort pulses.

  13. Interstellar Deuterium, Nitrogen and Oxygen Towards HZ43A: Results from the Far Ultraviolet Spectroscopic Explorer (FUSE) Mission

    Science.gov (United States)

    Kruk, J. W.; Howk, J. C.; Andre, M.; Moos, H. W.; Oegerle, William R.; Oliveira, C.; Sembach, K. R.; Chayer, P.; Linsky, J. L.; Wood, B. E.

    2002-01-01

    We present an analysis of interstellar absorption along the line of sight to the nearby white dwarf star HZ43A. The distance to this star is 68+/-13 pc, and the line of sight extends toward the north Galactic pole. Column densities of O(I), N(I), and N(II) were derived from spectra obtained by the Far Ultraviolet Spectroscopic Explorer (FUSE), the column density of D(I) was derived from a combination of our FUSE spectra and an archival HST GARDENS spectrum, and the column density of H(I) was derived from a combination of the GARDENS spectrum and values derived from EUVE data obtained from the literature. We find the following abundance ratios (with 2 sigma uncertainties): D(I)/H(I)=(1.66+/-0.28)x10(exp -5), O(I)/H(I)=(3.63+/-0.84)x10(exp -4), and N(I)/H(I)=(3.80+/-0.74)x10(exp -5). The N(II) column density was slightly greater than that of N(I), indicating that ionization corrections are important when deriving nitrogen abundances. Other interstellar species detected along the line of sight were C(II), C(III), O(VI), Si(II), Ar(I), Mg(II) and Fe(II); an upper limit was determined for N(III). No elements other than H(I) were detected in the stellar photosphere.

  14. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  15. Full spectrum endoscopy (FUSE) versus standard forward-viewing endoscope (SFV) in a high-risk population

    DEFF Research Database (Denmark)

    Roepstorff, Søren; Hadi, Sabah Anwar; Rasmussen, Morten

    2017-01-01

    OBJECTIVES: To investigate the diagnostic performance of Full Spectrum Endoscopy (FUSE) compared to a conventional standard forward-viewing endoscope (SFV). The primary outcome was adenoma detection rate (ADR) and mean adenoma detection. Secondary outcome was feasibility of FUSE opposed to SFV...... intubation time, fentanyl and midazolam sedation, CRC detection, ADR, diverticulosis, bowel preparation, patient discomfort and endoscopist difficulty rating. Participants underwent FUSE colonoscopy on days when the FUSE system was available, while the remaining participants had SFV. All colonoscopies were.......1 ± 6.2 min in the FUSE and SFV groups (p = .040). ADR was 67.0% and 59.6% (p = .097), while the mean adenoma detection was 1.79 and 1.38 (p = .022) in the FUSE and SFV groups. Endoscopists reported increased difficulty rating with FUSE compared to SFV (p > .001). CONCLUSION: FUSE colonoscopy provides...

  16. The compaction of fused silica resulting from ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, C.M.; Ridgway, M.C. [Australian National Univ., Canberra, ACT (Australia); Leech, P.L. [Telstra Research Laboratories, Clayton, Victoria (Australia)

    1996-12-31

    Ion implantation of fused silica results in compaction and consequently an increase in refractive index. This method of modifying the near-surface region has been shown as a potential means for fabricating single mode channel waveguides. This study has measured the compaction of the implanted regions for Si implantations as a function of dose (2x10{sup 12} - 6x10{sup l6} ions/cm{sup 2}), energy (1-9 MeV) and post-implantation annealing temperature (200-900 degree C). For a given energy, a dose-dependence of the step height (depth of compacted region) is observed for doses less than {approx}10{sup 15} ions/cm{sup 2}. At higher doses the step height saturates. For a given dose, a linear trend is evident for the step height as a function of energy suggesting that the major mechanism for this compaction is electronic stopping. As the annealing temperature increases, the step height gradually decreases from {approx}0.1-0.2 {mu} to -10-20% of the original value. From the annealing data, it is possible to extract an activation energy of 0.08 eV associated with the thermal removal of the compacted region. 4 refs., 4 figs.

  17. The compaction of fused silica resulting from ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, C M; Ridgway, M C [Australian National Univ., Canberra, ACT (Australia); Leech, P L [Telstra Research Laboratories, Clayton, Victoria (Australia)

    1997-12-31

    Ion implantation of fused silica results in compaction and consequently an increase in refractive index. This method of modifying the near-surface region has been shown as a potential means for fabricating single mode channel waveguides. This study has measured the compaction of the implanted regions for Si implantations as a function of dose (2x10{sup 12} - 6x10{sup l6} ions/cm{sup 2}), energy (1-9 MeV) and post-implantation annealing temperature (200-900 degree C). For a given energy, a dose-dependence of the step height (depth of compacted region) is observed for doses less than {approx}10{sup 15} ions/cm{sup 2}. At higher doses the step height saturates. For a given dose, a linear trend is evident for the step height as a function of energy suggesting that the major mechanism for this compaction is electronic stopping. As the annealing temperature increases, the step height gradually decreases from {approx}0.1-0.2 {mu} to -10-20% of the original value. From the annealing data, it is possible to extract an activation energy of 0.08 eV associated with the thermal removal of the compacted region. 4 refs., 4 figs.

  18. Cloud Detection by Fusing Multi-Scale Convolutional Features

    Science.gov (United States)

    Li, Zhiwei; Shen, Huanfeng; Wei, Yancong; Cheng, Qing; Yuan, Qiangqiang

    2018-04-01

    Clouds detection is an important pre-processing step for accurate application of optical satellite imagery. Recent studies indicate that deep learning achieves best performance in image segmentation tasks. Aiming at boosting the accuracy of cloud detection for multispectral imagery, especially for those that contain only visible and near infrared bands, in this paper, we proposed a deep learning based cloud detection method termed MSCN (multi-scale cloud net), which segments cloud by fusing multi-scale convolutional features. MSCN was trained on a global cloud cover validation collection, and was tested in more than ten types of optical images with different resolution. Experiment results show that MSCN has obvious advantages over the traditional multi-feature combined cloud detection method in accuracy, especially when in snow and other areas covered by bright non-cloud objects. Besides, MSCN produced more detailed cloud masks than the compared deep cloud detection convolution network. The effectiveness of MSCN make it promising for practical application in multiple kinds of optical imagery.

  19. Picosecond laser damage of fused silica at 355 nm

    International Nuclear Information System (INIS)

    Meng Xiangjie; Liu Hongjie; Wang Fang; Zhang Zhen; An Xinyou; Huang Jin; Jiang Xiaodong; Wu Weidong; Ren Weiyi

    2013-01-01

    This paper studies the initiated damage threshold, the damage morphology and the subsequent damage growth on fused silica's input-surface and exit-surface under picosecond laser irradiation at 355 nm. Defects induced fluorescence on surface of the optical component is observed. The results demonstrate a significant dependence of the initiated damage on pulse duration and surface defects, and that of the damage growth on self-focusing, sub-surface defects. The damage-threshold is 3.98 J/cm 2 of input surface and 2.91 J/cm 2 of exit surface. The damage morphologies are quite different between input surface and exit surface. Slow growth behavior appears for the diameter of exit-surface and linear growth one for the depth of exit-surface in the lateral side of damage site with the increase of shot number. Defects have changed obviously compared with nanosecond laser damage in the damage area. Several main reasons such as electric intensification and self-focusing for the observed initiated damage and damage growth behavior are discussed. (authors)

  20. STANDARDIZING QUALITY ASSESSMENT OF FUSED REMOTELY SENSED IMAGES

    Directory of Open Access Journals (Sweden)

    C. Pohl

    2017-09-01

    Full Text Available The multitude of available operational remote sensing satellites led to the development of many image fusion techniques to provide high spatial, spectral and temporal resolution images. The comparison of different techniques is necessary to obtain an optimized image for the different applications of remote sensing. There are two approaches in assessing image quality: 1. Quantitatively by visual interpretation and 2. Quantitatively using image quality indices. However an objective comparison is difficult due to the fact that a visual assessment is always subject and a quantitative assessment is done by different criteria. Depending on the criteria and indices the result varies. Therefore it is necessary to standardize both processes (qualitative and quantitative assessment in order to allow an objective image fusion quality evaluation. Various studies have been conducted at the University of Osnabrueck (UOS to establish a standardized process to objectively compare fused image quality. First established image fusion quality assessment protocols, i.e. Quality with No Reference (QNR and Khan's protocol, were compared on varies fusion experiments. Second the process of visual quality assessment was structured and standardized with the aim to provide an evaluation protocol. This manuscript reports on the results of the comparison and provides recommendations for future research.

  1. Standardizing Quality Assessment of Fused Remotely Sensed Images

    Science.gov (United States)

    Pohl, C.; Moellmann, J.; Fries, K.

    2017-09-01

    The multitude of available operational remote sensing satellites led to the development of many image fusion techniques to provide high spatial, spectral and temporal resolution images. The comparison of different techniques is necessary to obtain an optimized image for the different applications of remote sensing. There are two approaches in assessing image quality: 1. Quantitatively by visual interpretation and 2. Quantitatively using image quality indices. However an objective comparison is difficult due to the fact that a visual assessment is always subject and a quantitative assessment is done by different criteria. Depending on the criteria and indices the result varies. Therefore it is necessary to standardize both processes (qualitative and quantitative assessment) in order to allow an objective image fusion quality evaluation. Various studies have been conducted at the University of Osnabrueck (UOS) to establish a standardized process to objectively compare fused image quality. First established image fusion quality assessment protocols, i.e. Quality with No Reference (QNR) and Khan's protocol, were compared on varies fusion experiments. Second the process of visual quality assessment was structured and standardized with the aim to provide an evaluation protocol. This manuscript reports on the results of the comparison and provides recommendations for future research.

  2. Synthesis of a new class of fused cyclotetraphosphazene ring systems.

    Science.gov (United States)

    Beşli, Serap; Mutlu, Ceylan; İbişoğlu, Hanife; Yuksel, Fatma; Allen, Christopher W

    2015-01-05

    Octachlorocyclotetraphosphazene (1) was reacted with butylamines [n-butyl, i-butyl, sec-butyl, and t-butyl] in a 1:0.8 mol ratio in THF to obtain cyclotetraphosphazenes bearing a P-NH group, N4P4Cl7(NHR) [R = n-butyl (2a), i-butyl (2b), sec-butyl (2c), t-butyl (2d)](2a-d). The cyclotetraphosphazene derivatives 2a, 2b, and 2c were treated with sodium hydride giving rise to a new type of cyclophosphazene compounds (P8N8 ring) consisting of three fused tetramer rings (3a-c). Whereas reaction of sodium hydride with the t-butylaminocyclophosphazene derivative (2d) gave a P-O-P bridged compound (4) presumably as a result of hydrolysis reaction associated with moisture in the solvent. It is likely that the 16-membered cyclooctaphosphazene derivatives (3a-c) are formed by a proton abstraction/chloride ion elimination, intramolecular nucleophilic attack, ring opening and intermolecular condensation processes, respectively.

  3. Fusing metabolomics data sets with heterogeneous measurement errors

    Science.gov (United States)

    Waaijenborg, Sandra; Korobko, Oksana; Willems van Dijk, Ko; Lips, Mirjam; Hankemeier, Thomas; Wilderjans, Tom F.; Smilde, Age K.

    2018-01-01

    Combining different metabolomics platforms can contribute significantly to the discovery of complementary processes expressed under different conditions. However, analysing the fused data might be hampered by the difference in their quality. In metabolomics data, one often observes that measurement errors increase with increasing measurement level and that different platforms have different measurement error variance. In this paper we compare three different approaches to correct for the measurement error heterogeneity, by transformation of the raw data, by weighted filtering before modelling and by a modelling approach using a weighted sum of residuals. For an illustration of these different approaches we analyse data from healthy obese and diabetic obese individuals, obtained from two metabolomics platforms. Concluding, the filtering and modelling approaches that both estimate a model of the measurement error did not outperform the data transformation approaches for this application. This is probably due to the limited difference in measurement error and the fact that estimation of measurement error models is unstable due to the small number of repeats available. A transformation of the data improves the classification of the two groups. PMID:29698490

  4. Integrable Floquet dynamics, generalized exclusion processes and "fused" matrix ansatz

    Science.gov (United States)

    Vanicat, Matthieu

    2018-04-01

    We present a general method for constructing integrable stochastic processes, with two-step discrete time Floquet dynamics, from the transfer matrix formalism. The models can be interpreted as a discrete time parallel update. The method can be applied for both periodic and open boundary conditions. We also show how the stationary distribution can be built as a matrix product state. As an illustration we construct parallel discrete time dynamics associated with the R-matrix of the SSEP and of the ASEP, and provide the associated stationary distributions in a matrix product form. We use this general framework to introduce new integrable generalized exclusion processes, where a fixed number of particles is allowed on each lattice site in opposition to the (single particle) exclusion process models. They are constructed using the fusion procedure of R-matrices (and K-matrices for open boundary conditions) for the SSEP and ASEP. We develop a new method, that we named "fused" matrix ansatz, to build explicitly the stationary distribution in a matrix product form. We use this algebraic structure to compute physical observables such as the correlation functions and the mean particle current.

  5. Autophagy meets fused in sarcoma-positive stress granules.

    Science.gov (United States)

    Matus, Soledad; Bosco, Daryl A; Hetz, Claudio

    2014-12-01

    Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Interdiffusion of Polycarbonate in Fused Deposition Modeling Welds

    Science.gov (United States)

    Seppala, Jonathan; Forster, Aaron; Satija, Sushil; Jones, Ronald; Migler, Kalman

    2015-03-01

    Fused deposition modeling (FDM), a now common and inexpensive additive manufacturing method, produces 3D objects by extruding molten polymer layer-by-layer. Compared to traditional polymer processing methods (injection, vacuum, and blow molding), FDM parts have inferior mechanical properties, surface finish, and dimensional stability. From a polymer processing point of view the polymer-polymer weld between each layer limits the mechanical strength of the final part. Unlike traditional processing methods, where the polymer is uniformly melted and entangled, FDM welds are typically weaker due to the short time available for polymer interdiffusion and entanglement. To emulate the FDM process thin film bilayers of polycarbonate/d-polycarbonate were annealed using scaled times and temperatures accessible in FDM. Shift factors from Time-Temperature Superposition, measured by small amplitude oscillatory shear, were used to calculate reasonable annealing times (min) at temperatures below the actual extrusion temperature. The extent of interdiffusion was then measured using neutron reflectivity. Analogous specimens were prepared to characterize the mechanical properties. FDM build parameters were then related to interdiffusion between welded layers and mechanical properties. Understating the relationship between build parameters, interdiffusion, and mechanical strength will allow FDM users to print stronger parts in an intelligent manner rather than using trial-and-error and build parameter lock-in.

  7. Elements to evaluate the intention in the non-compliance s or violations to the regulatory framework in the national nuclear facilities; Elementos para evaluar la intencionalidad en los incumplimientos o violaciones al marco regulador en las instalaciones nucleares nacionales

    Energy Technology Data Exchange (ETDEWEB)

    Espinosa V, J. M.; Gonzalez V, J. A., E-mail: jmespinosa@cnsns.gob.mx [Comision Nacional de Seguridad Nuclear y Salvaguardias, Dr. Jose Ma. Barragan No. 779, Col. Narvarte, 03020 Mexico D. F. (Mexico)

    2013-10-15

    Inside the impact evaluation process to the safety of non-compliance s or violations, developed and implanted by the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS), the Guide for the Impact Evaluation to the Safety in the National Nuclear Facilities by Non-compliance s or Violations to the Regulatory Framework was developed, which indicates that in the determination of the severity (graveness level) of a non-compliance or violation, four factors are evaluated: real and potential consequences to the safety, the impact to the regulator process and the intention. The non-compliance s or intentional violations are of particular interest, since the development of the regulatory activities of the CNSNS considers that the personnel of the licensees, as well as their contractors, will act and will communicate with integrity and honesty. The CNSNS cannot tolerate intentional non-compliance s, for what this violations type can be considered of a level of more graveness that the subjacent non-compliance. To determine the severity of a violation that involves intention, the CNSNS also took in consideration factors as the position and the personnel's responsibilities involved in the violation, the graveness level of the non-compliance in itself, the offender's intention and the possible gain that would produce the non-compliance, if exists, either economic or of another nature. The CNSNS hopes the licensees take significant corrective actions in response to non-compliance s or intentional violations, these corrective actions should correspond to the violation graveness with the purpose of generating a dissuasive effect in the organizations of the licensees. The present article involves the legal framework that confers the CNSNS the attributions to impose administrative sanctions to its licensees, establishes the definition of the CNSNS about what constitutes a non-compliance or intentional violation and finally indicates the intention types (deliberate

  8. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  9. Performance evaluation of paper embossing tools produced by fused deposition modelling additive manufacturing technology

    Directory of Open Access Journals (Sweden)

    Gordana Delić

    2017-12-01

    Full Text Available From its beginnings, up to a few years ago, additive manufacturing technology was able to produce models or prototypes which have limited use, because of materials mechanical properties. With advancement and invention of new materials, this is changing. Now, it is possible to create 3D prints that can be used as final products or functional tools, using technology and materials with low environmental impact. The goal of this study was to examine opportunities for production of paper embossing tools by fused deposition modelling (FDM 3D printing. This study emphasises the use of environmentally friendly poly-lactic acid (PLA materials in FDM technology, contrary to the conventional method using metal alloys and acids. Embossing of line elements and letters using 3D printed embossing tools was done on six different types of paper. Embossing force was applied using SHIMADZU EZ-LX Compact Tabletop Testing Machine. Each type of paper was repeatedly embossed using different values of embossing force (in 250 N increments, starting at 1000 N to determine the optimal embossing force for each specific paper type. When determined, the optimal embossing force was used on ten samples for each paper type. Results of embossing were analysed and evaluated. The analysis consisted of investigating the effects of the applied embossing force and characteristics such as paper basis weight, paper structure, surface characteristic and fibre direction of the paper. Results show that paper characteristics determine the embossing force required for achieving a good embossing result. This means that with the right amount of embossing force, letters and borderlines can be equally well formed by the embossing process regardless of paper weight, surface characteristics, etc. Embossing tools produced in this manner can be used in case of the embossing elements that are not complex. The reason for this is the limitation of FDM technology and lack of precision needed for fine

  10. Overcurrent protection of transformers. Part 2: Traditional and new fusing philosophies for small and large transformers

    Energy Technology Data Exchange (ETDEWEB)

    Cook, C. J.; Niemira, J. K.

    2003-07-01

    New and traditional fusing philosophies for protecting transformers are discussed. This second in a two-part paper covers selection criteria for a transformer-primary fuse to protect the transformer consistent with industry-accepted through-fault protection curves. Also covered are the principles of coordination as they relate to the proper selection of the primary-side fuse and power fuses and the principles underlying the protection of load-side conductors and cables. The critical nature of secondary fault protection on small three-phase transformers used on industrial, commercial, and institutional power systems, as well as small-to-medium size three-phase power transformers used in utility substations is emphasized, in view of the long lead time and expense involved in replacing these transformers. In contrast, no special protection recommendations are made for small-kVA overhead distribution transformers, since they are not considered likely to experience secondary faults, and the rare faults that do occur will not likely be detected and cleared by the primary fuse. Also of importance is the fact that these transformers are inexpensive and readily available. Overall, large fuse rating, used in combination with a tank-mounted surge arrester is recommended, because it can provide better transformer protection than the smaller fuse ratings traditionally employed. 4 refs., 2 tabs., 4 figs.

  11. Non-destructive evaluation of UV pulse laser-induced damage performance of fused silica optics.

    Science.gov (United States)

    Huang, Jin; Wang, Fengrui; Liu, Hongjie; Geng, Feng; Jiang, Xiaodong; Sun, Laixi; Ye, Xin; Li, Qingzhi; Wu, Weidong; Zheng, Wanguo; Sun, Dunlu

    2017-11-24

    The surface laser damage performance of fused silica optics is related to the distribution of surface defects. In this study, we used chemical etching assisted by ultrasound and magnetorheological finishing to modify defect distribution in a fused silica surface, resulting in fused silica samples with different laser damage performance. Non-destructive test methods such as UV laser-induced fluorescence imaging and photo-thermal deflection were used to characterize the surface defects that contribute to the absorption of UV laser radiation. Our results indicate that the two methods can quantitatively distinguish differences in the distribution of absorptive defects in fused silica samples subjected to different post-processing steps. The percentage of fluorescence defects and the weak absorption coefficient were strongly related to the damage threshold and damage density of fused silica optics, as confirmed by the correlation curves built from statistical analysis of experimental data. The results show that non-destructive evaluation methods such as laser-induced fluorescence and photo-thermal absorption can be effectively applied to estimate the damage performance of fused silica optics at 351 nm pulse laser radiation. This indirect evaluation method is effective for laser damage performance assessment of fused silica optics prior to utilization.

  12. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

  13. Regulatory Hybridization in the Transnational Sphere

    DEFF Research Database (Denmark)

    Kjær, Poul Fritz; Jurcys, Paulius; Yrakami, Ren

    Hybridization has become a defining feature of regulatory frameworks. The combined forces of globalization and privatization together with increased reliance on self-regulation have resulted in the emergence of a multitude of regulatory arrangements which combine elements from several legal orders....... This book offers a conceptual framework as well as numerous empirical explorations capable of increasing our understanding of regulatory hybridization. A number of central dichotomies are deconstructed: national vs. transnational law; international vs. transnational law; convergence vs. divergence; … read...... moresoft law vs. hard law; territorial vs. non-territorial, ‘top-down’ vs. ‘bottom-up’ globalization and national vs. global just as the implications of regulatory hybridization for the question of choice of court and conflict of laws are analyzed....

  14. A system for the non-destructive detection of faults in safety fuses using radioisotopes

    International Nuclear Information System (INIS)

    Goncalves, D.

    1980-01-01

    Design of an equipment for on line detection of faults in the safety fuses for conventional explosives employing transmission of #betta#-radiation is reported. The faults are detected by an ion-chamber based on the variation of the intensity of the beta particles transmitted through the fuse during its passage across the collimated beam. Strontium-90 encapsulated in stainless steel or aluminum is used as the #betta#-source. An electrical signal corresponding the fault is obtained by subtraction of an external current, that is equivalent to the output of the ion-chamber in the presence of faultless fuse. (Author) [pt

  15. 77 FR 8072 - Semiannual Regulatory Flexibility Agenda

    Science.gov (United States)

    2012-02-13

    ... six months. ADDRESSES: Comments should be addressed to Jennifer J. Johnson, Secretary of the Board... Regulatory and Deregulatory Actions, which is coordinated by the Office of Management and Budget under... pledged; and certain other elements including a strategic analysis of the company's plans for maintaining...

  16. Microwave Assisted Synthesis of Some New Fused 1,2,4-Triazines Bearing Thiophene Moieties With Expected Pharmacological Activity

    Directory of Open Access Journals (Sweden)

    Mosselhi A. Mosselhi

    2011-06-01

    Full Text Available Rapid and efficient solvent-free synthesis of 4-amino-3-mercapto-6-[2-(2-thienylvinyl]-1,2,4-triazin-5(4H-one 1 under microwave irradiation is described. Some new fused heterobicyclic nitrogen systems such as 1,2,4-triazino[3,4-b][1,3,4]thiadiazinones, 1,3,4-thiadiazolo[2,3-c][1,2,4]triazinone and pyrazolo[5,1-c]-[1,2,4]triazine-7-carbonitrile, have been synthesized by treatment of 1 with bifunctional oxygen and halogen compounds, CS2/KOH and malononitrile via heterocyclization reactions, in addition to some uncondensed triazines. Structures of the products have been deduced from their elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR. Select new synthesized compounds were screened as anticancer agents, with some showing activity as cytotoxic agents against different cancer cell lines.

  17. Considerations on thermic and mechanic processes that appear when 3D printing using ABS fused deposition modelling technology

    Science.gov (United States)

    Amza, Catalin Gheorghe; Niţoi, Dan Florin

    2018-02-01

    3D printers are of recent history, but with an extremely rapid evolution both in technology and hardware involved. At present excellent performances are reached in applications such as 3D printing of various Acrylonitrile butadiene styrene (ABS) plastic parts for house building using Fused Deposition Modelling technology. Nevertheless, the thermic and mechanic processes that appear when manufacturing such plastic components are quite complex. This aspect is very important, especially when one wants to optimize the manufacturing of parts with certain geometrical complexity. The Finite Element Analysis/Modelling (FEA/FEM) is among the few methods that can study the thermic transfer processes and shape modifications that can appear due to non-seamar behavior that takes place when the ABS plastic material is cooling down. The current papers present such an analysis when simulating the deposition of several strings of materials. A thermic analysis is made followed by a study of deformations that appear when the structure cools down.

  18. Arsenic Sulfide Nanowire Formation on Fused Quartz Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Olmstead, J.; Riley, B.J.; Johnson, B.R.; Sundaram, S.K.

    2005-01-01

    Arsenic sulfide (AsxSy) nanowires were synthesized by an evaporation-condensation process in evacuated fused quartz ampoules. During the deposition process, a thin, colored film of AsxSy was deposited along the upper, cooler portion of the ampoule. The ampoule was sectioned and the deposited film analyzed using scanning electron microscopy (SEM) to characterize and semi-quantitatively evaluate the microstructural features of the deposited film. A variety of microstructures were observed that ranged from a continuous thin film (warmer portion of the ampoule), to isolated micron- and nano-scale droplets (in the intermediate portion), as well as nanowires (colder portion of the ampoule). Experiments were conducted to evaluate the effects of ampoule cleaning methods (e.g. modify surface chemistry) and quantity of source material on nanowire formation. The evolution of these microstructures in the thin film was determined to be a function of initial pressure, substrate temperature, substrate surface treatment, and initial volume of As2S3 glass. In a set of two experiments where the initial pressure, substrate thermal gradient, and surface treatment were the same, the initial quantity of As2S3 glass per internal ampoule volume was doubled from one test to the other. The results showed that AsxSy nanowires were only formed in the test with the greater initial quantity of As2S3 per internal ampoule volume. The growth data for variation in diameter (e.g. nanowire or droplet) as a function of substrate temperature was fit to an exponential trendline with the form y = Aekx, where y is the structure diameter, A = 1.25×10-3, k = 3.96×10-2, and x is the temperature with correlation coefficient, R2 = 0.979, indicating a thermally-activated process.

  19. Rheological characterization of plasticized corn proteins for fused deposition modeling

    Science.gov (United States)

    Chaunier, Laurent; Dalgalarrondo, Michèle; Della Valle, Guy; Lourdin, Denis; Marion, Didier; Leroy, Eric

    2017-10-01

    Additive Manufacturing (AM) of tailored natural biopolymer-based objects by Fused Deposition Modeling (FDM) opens new perspectives for applications such as biomedical temporary devices, or pharmaceutical tablets. This exploits the biocompatibility, resorbability and edibility properties of biopolymers. When adequately plasticized, zeins, storage proteins from endosperm of maize kernels, displayed thermomechanical properties possibly matching FDM processing requirements at a convenient temperature Tprinting=130°C. Indeed, with 20% glycerol added (Tg=42°C), plasticized zeins present a high modulus, E'>1GPa, at ambient conditions, which drops below 0.6 MPa at the processing temperature T=130°C, before flowing in the molten state. The rheological characterization shows that the processing window is limited by a progressive increase of viscosity linked to proteins aggregation and crosslinking by S-S bonding between cysteine amino acid residues, which can lead to gelation. However, for short residence time typical of FDM, the viscosity of plasticized zeins is comparable to the one of standard polymers, like ABS or PLA in their FDM processing conditions: indeed, in presence of glycerol, the molten zeins show a shear-thinning behavior with |η*|≈3kPa.s at 1s-1, decreasing to |η*|≈0.3kPa.s at 100s-1, at 130°C. Moreover, zeins presenting both hydrophilic and hydrophobic domains, amphiphilic plasticizers can be used supplementary to tune their rheological behavior. With 20% oleic acid added to the previous composition, the viscosity is divided down to a ratio about 1/2 at 100s-1 at 130°C, below the value of a standard polymer as PLA at its printing temperature. These results show the possible enhancement of the printability of zein-based materials in the molten state, by combining polar and amphiphilic plasticizers.

  20. Fused-data transrectal EIT for prostate cancer imaging.

    Science.gov (United States)

    Murphy, Ethan K; Wu, Xiaotian; Halter, Ryan J

    2018-05-25

    Prostate cancer is a significant problem affecting 1 in 7 men. Unfortunately, the diagnostic gold-standard of ultrasound-guided biopsy misses 10%-30% of all cancers. The objective of this study was to develop an electrical impedance tomography (EIT) approach that has the potential to image the entire prostate using multiple impedance measurements recorded between electrodes integrated onto an end-fired transrectal ultrasound (TRUS) device and a biopsy probe (BP). Simulations and sensitivity analyses were used to investigate the best combination of electrodes, and measured tank experiments were used to evaluate a fused-data transrectal EIT (fd-TREIT) and BP approach. Simulations and sensitivity analysis revealed that (1) TREIT measurements are not sufficiently sensitive to image the whole prostate, (2) the combination of TREIT  +  BP measurements increases the sensitive region of TREIT-only measurements by 12×, and (3) the fusion of multiple TREIT  +  BP measurements collected during a routine or customized 12-core biopsy procedure can cover up to 76.1% or 94.1% of a nominal 50 cm 3 prostate, respectively. Three measured tank experiments of the fd-TREIT  +  BP approach successfully and accurately recovered the positions of 2-3 metal or plastic inclusions. The measured tank experiments represent important steps in the development of an algorithm that can combine EIT from multiple locations and from multiple probes-data that could be collected during a routine TRUS-guided 12-core biopsy. Overall, this result is a step towards a clinically deployable impedance imaging approach to scanning the entire prostate, which could significantly help to improve prostate cancer diagnosis.

  1. Cervical facet dislocation adjacent to the fused motion segment

    Directory of Open Access Journals (Sweden)

    Kunio Yokoyama

    2016-01-01

    Full Text Available This study reports on a case that forces re-examination of merits and demerits of anterior cervical fusion. A 79-year-old male was brought to the emergency room (ER of our hospital after he fell and struck the occipital region of his head following excessive alcohol consumption. Four years prior, he had undergone anterior cervical discectomy and fusion of C5/6 and a magnetic resonance imaging (MRI performed 3 years after this surgery indicated that he was suffering from degeneration of C6/7 intervertebral discs. After arriving at the ER, he presented motor impairment at level C7 and lower of manual muscle testing grade 1 as well as moderate loss of physical sensation from the trunk and peripheries of both upper limbs to the peripheries of both lower limbs (Frankel B. Cervical computed tomography (CT indicated anterior dislocation of C6/7, and MRI indicated severe spinal cord edema. We performed manipulative reduction of C6/7 with the patient under general anesthesia. Next, we performed laminectomy on C5-T1 and posterior fusion on C6/7. Postoperative CT indicated that cervical alignment had improved, and MRI indicated that the spinal cord edema observed prior to surgery had been mitigated. Three months after surgery, motor function and sensory impairment of the lower limbs had improved, and the patient was ambulatory upon discharge from the hospital (Frankel D. In the present case, although C5 and 6 were rigidly fused, degeneration of the C6/7 intervertebral disc occurred and stability was compromised. As a result, even slight trauma placed a severe dynamic burden on the facet joint of C6/7, which led to dislocation.

  2. Development of a fused glass disc XRF facility and comparison with the pressed powder pellet technique at Instituto de Geociencias, Sao Paulo University, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Paulo Ernesto; Correia, Ciro Teixeira [Sao Paulo Univ., SP (Brazil). Dept. of Mineralogia e Geotectonia; Reeves, Shane [Melbourne Univ., Parkville, VIC (Australia). School of Earth Sciences; Haukka, Maunu [Melbourne Univ., Parkville, VIC (Australia). Dept. of Chemical Engineering

    1999-09-01

    An X-ray fluorescence spectrometry pressed powder pellet technique (PPP) currently in use at the X-ray facility of the Instituto de Geociencias, Sao Paulo University has been extended to include additional elements and complemented by a full major and trace element calibration by fused glass disc X-ray fluorescence. A total of 38 major and trace elements are available (F, Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Rb, Sr, Y, Zr, Nb, Mo, Sn, Sb, Ba, Pb, Bi, La, Ce, Nd, Th and U) with variable detection limits, but generally below 10 ppm for trace elements. Loss-on-ignitions determined by weight difference and totals provide extremely good control on data quality. A full analysis, including background, matrix correction and all relevant corrections can be achieved automatically in less than 60 minutes. Virtually any sample matrix can be accommodated. The data support the view that fused disc and power pellet techniques are complementary and together provide a definite, rigorous XRF analysis. However, both techniques require considerable attention to details, with the glass disc technique prone to losses of F and S and increase detection limits for certain elements. The powder pellet technique requires fine micronizing and caution when dealing with the light elements Si and Al. Additionally the paper presents a new, previously unpublished experimentally determined Alpha coefficients for all matrix-corrected elements, which are based on the lithium metaborate system and contrast with the Philips theoretical alpha coefficients. (author)

  3. Development of a fused glass disc XRF facility and comparison with the pressed powder pellet technique at Instituto de Geociencias, Sao Paulo University, Brazil

    International Nuclear Information System (INIS)

    Mori, Paulo Ernesto; Correia, Ciro Teixeira; Reeves, Shane; Haukka, Maunu

    1999-01-01

    An X-ray fluorescence spectrometry pressed powder pellet technique (PPP) currently in use at the X-ray facility of the Instituto de Geociencias, Sao Paulo University has been extended to include additional elements and complemented by a full major and trace element calibration by fused glass disc X-ray fluorescence. A total of 38 major and trace elements are available (F, Na, Mg, Al, Si, P, S, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Rb, Sr, Y, Zr, Nb, Mo, Sn, Sb, Ba, Pb, Bi, La, Ce, Nd, Th and U) with variable detection limits, but generally below 10 ppm for trace elements. Loss-on-ignitions determined by weight difference and totals provide extremely good control on data quality. A full analysis, including background, matrix correction and all relevant corrections can be achieved automatically in less than 60 minutes. Virtually any sample matrix can be accommodated. The data support the view that fused disc and power pellet techniques are complementary and together provide a definite, rigorous XRF analysis. However, both techniques require considerable attention to details, with the glass disc technique prone to losses of F and S and increase detection limits for certain elements. The powder pellet technique requires fine micronizing and caution when dealing with the light elements Si and Al. Additionally the paper presents a new, previously unpublished experimentally determined Alpha coefficients for all matrix-corrected elements, which are based on the lithium metaborate system and contrast with the Philips theoretical alpha coefficients. (author)

  4. Toxicology elements

    International Nuclear Information System (INIS)

    Viala, A.

    1998-01-01

    This work studies the different aspects of the modern toxicology: toxico-kinetic, biological, medico legal, food, professional, pharmaceuticals, environmental, social and regulatory. It is divided in three parts that consider the principle problems of general toxicology and analytical toxicology. (N.C.)

  5. Non-destructive testing of rocket fuse by thermal neutron radiography

    International Nuclear Information System (INIS)

    An Fulin; Li Furong

    1999-01-01

    A neutron radiography system in reactor horizontal hole of Tsinghua University was introduced, and its capability of neutron radiography was evaluated by theory and experiment, the non-destructive testing for rocket fuse is successful

  6. 2012 and 2013 Air Quality Fused Surface for the Conterminous U.S. Map Service

    Data.gov (United States)

    U.S. Environmental Protection Agency — This web service contains a polygon layer that depicts fused air quality predictions for 2012, 2013, and 2014 for census tracts in the conterminous United States....

  7. Endodontic management of a mandibular third molar fused with a fourth molar.

    Science.gov (United States)

    Turell, I L; Zmener, O

    1999-05-01

    Developmental anomalies in permanent molars frequently require surgical intervention. A case of a mandibular third molar fused with a fourth molar which was successfully treated with conservative endodontic therapy is reported.

  8. Technological aspects of using protective fuses in low-voltage mine networks

    Energy Technology Data Exchange (ETDEWEB)

    Kowalski, Z; Pudelko, H

    1986-04-01

    Protection systems are evaluated for mining equipment used in underground coal mining in Poland. Operation of contactor switches is analyzed. Systems for protection of vacuum contactor switches from overload are comparatively evaluated. Types of current reducers are reviewed. Design of the aM protection fuse which is activated only when overload current exceeds the limiting level is analyzed. Protection fuses with the aM characteristic meeting IEC and VDE requirements for fuses used in SV5, SV7 and SV8 vacuum contactors for power networks of up to 1000 V are evaluated. Characteristics of the vacuum contactors manufactured in Poland are given in 6 diagrams and 2 tables. Reliability of the vacuum contactors with aM protection fuses is analyzed. 8 references.

  9. Diagnosis and staging of breast cancer by SPECT images fused with CT images

    International Nuclear Information System (INIS)

    Li Yanjing; Zhu Qiaomei

    2007-01-01

    Objective: To evaluate the TNM staging value of 99mTc-MIBI scintimammotraphy with SPECT-CT images fusing for the diagnosis of breast cancer. Methods: 10 patients with breast cancer underwent scintimammography with 99mTc-MIBI, and SPECT images were fused with CT images. Images were compared with final diagnosis confirmed by histopathology. Results: Of the 19 breast cancer patients, one case of invasive ductal carcinoma showed false-negative. Among 18 cases of positive lesions, axillary metastases were involved in 10, supraclavicular nodes were also defined in 3, para-sternum nodes were involved in 2, 2 were missed and 1 cases without metastatic node. The axillary lymph nodes were divided into three levels with respect to their position relative to the pectoralis minor muscle by fused images. Conclusion: 99mTc-MIBI scintimammotraphy combined with SPECT-CT images fusing is of some clinical value in TNM staging of breast cancer. (authors)

  10. Synthesis and properties of nitrogenous heterocycles containing a spiro-fused cyclopropane fragment

    International Nuclear Information System (INIS)

    Tomilov, Yury V; Nefedov, Oleg M; Kostyuchenko, Irina V

    2000-01-01

    The published data on the methods of synthesis and chemical transformations of nitrogenous heterocyclic compounds spiro-fused with a cyclopropane fragment are described systematically and generalised. The bibliography includes 146 references.

  11. The chemistry of furazans fused to six- and seven-membered heterocycles with one heteroatom

    International Nuclear Information System (INIS)

    Sheremetev, Aleksei B

    1999-01-01

    The data on the synthesis and properties of furazan derivatives fused with pyridine, pyran, thiopyran, azepine and thiepine rings are surveyed and described systematically. The bibliography includes 85 references.

  12. Thermal conductivity contrast measurement of Fused Silica exposed to low-energy femtosecond laser pulses

    NARCIS (Netherlands)

    Bellouard, Y.J.; Dugan, M.; Said, A.A.; Bado, P.

    2006-01-01

    Femtosecond laser irradiation has various noticeable effects on fused silica. Of particular interest, pulses with energy levels below the ablation threshold can locally increase the refractive index and the material etching selectivity to hydrofluoric acid. The mechanism responsible for these

  13. Transplutonium elements

    Energy Technology Data Exchange (ETDEWEB)

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

    1973-07-01

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

  14. Search for stress dependence in the internal friction of fused silica

    International Nuclear Information System (INIS)

    Willems, Phil; Lamb, Corinne; Heptonstall, Alastair; Hough, Jim

    2003-01-01

    The quality factor (Q) of the vertical bounce mode of a fused silica fiber pendulum is measured at high and low stresses. The internal friction of fused silica fibers is found to be independent of stress from 12.8 to 213 MPa at a level of 1.6x10 -8 . Comparison with Q's of fiber bending modes is consistent with losses concentrated in the surface of the fiber

  15. Primary retroperitoneal teratoma and crossed fused renal ectopia with turner's syndrome -a case report-

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yun Jung; Hong, Ki Ung [St. Francisco General Hospital, New York (United States)

    1988-02-15

    In 1938, Turner described a clinical entity in phenotype females characterized by sexual infantilism, congenital webbed neck and cubitus valgus. After then, the occurrence of renal anomalies in patients with Turner's syndrome has been recognized. Associated crossed fused renal ectopia is very rare. Primary retroperitoneal teratoma is also rare and usually during childhood. The authors report a case of primary retroperitoneal teratoma and crossed fused renal ectopia with Turner's syndrome (mosaic type). The clinical, pathological and radiographical findings are reviewed.

  16. Primary retroperitoneal teratoma and crossed fused renal ectopia with turner's syndrome -a case report-

    International Nuclear Information System (INIS)

    Kim, Yun Jung; Hong, Ki Ung

    1988-01-01

    In 1938, Turner described a clinical entity in phenotype females characterized by sexual infantilism, congenital webbed neck and cubitus valgus. After then, the occurrence of renal anomalies in patients with Turner's syndrome has been recognized. Associated crossed fused renal ectopia is very rare. Primary retroperitoneal teratoma is also rare and usually during childhood. The authors report a case of primary retroperitoneal teratoma and crossed fused renal ectopia with Turner's syndrome (mosaic type). The clinical, pathological and radiographical findings are reviewed

  17. Cavity Formation Modeling of Fiber Fuse in Single-Mode Optical Fibers

    Directory of Open Access Journals (Sweden)

    Yoshito Shuto

    2017-01-01

    Full Text Available The evolution of a fiber-fuse phenomenon in a single-mode optical fiber was studied theoretically. To clarify both the silica-glass densification and cavity formation, which have been observed in fiber fuse propagation, we investigated a nonlinear oscillation model using the Van Der Pol equation. This model was able to phenomenologically explain both the densification of the core material and the formation of periodic cavities in the core layer as a result of a relaxation oscillation.

  18. Research on non-destructive testing (NDT) aerospace igniter fuse with neutron radiography (NR)

    International Nuclear Information System (INIS)

    Mo Dawei; Liu Yisi; Cai Qingsheng; Chen Boxian

    1995-01-01

    The research works, facilities and results of NDT aerospace igniter fuse with neutron radiography at Tsinghua University swimming-pool reactor are introduced. The image quality (NR) of ASTM E545-85 I level was approached. The NR experimental research of the typical and possible defects was performed. The theoretical analysis was performed too. The feasibility of NDT aerospace igniter fuse with NR was proved experimentally

  19. Anthracene-fused BODIPYs as near-infrared dyes with high photostability

    KAUST Repository

    Zeng, Lintao; Jiao, Chongjun; Huang, Xiaobo; Huang, Kuo-Wei; Chin, Weeshong; Wu, Jishan

    2011-01-01

    An anthracene unit was successfully fused to the zigzag edge of a boron dipyrromethene (BODIPY) core by an FeCl 3-mediated oxidative cyclodehydrogenation reaction. Meanwhile, a dimer was also formed by both intramolecular cyclization and intermolecular coupling. The anthracene-fused BODIPY monomer 7a and dimer 7b showed small energy gaps (∼1.4 eV) and near-infrared absorption/emission. Moreover, they exhibited high photostability. © 2011 American Chemical Society.

  20. Anthracene-fused BODIPYs as near-infrared dyes with high photostability

    KAUST Repository

    Zeng, Lintao

    2011-11-18

    An anthracene unit was successfully fused to the zigzag edge of a boron dipyrromethene (BODIPY) core by an FeCl 3-mediated oxidative cyclodehydrogenation reaction. Meanwhile, a dimer was also formed by both intramolecular cyclization and intermolecular coupling. The anthracene-fused BODIPY monomer 7a and dimer 7b showed small energy gaps (∼1.4 eV) and near-infrared absorption/emission. Moreover, they exhibited high photostability. © 2011 American Chemical Society.

  1. Enhancement of laser induced damage threshold of fused silica by acid etching combined with UV laser conditioning

    International Nuclear Information System (INIS)

    Chen Meng; Xiang Xia; Jiang Yong; Zu Xiaotao; Yuan Xiaodong; Zheng Wanguo; Wang Haijun; Li Xibin; Lu Haibing; Jiang Xiaodong; Wang Chengcheng

    2010-01-01

    Acid etching combined with UV laser conditioning is developed to enhance the laser induced damage threshold (LIDT) of fused silica. Firstly, the fused silica is etched for 1 ∼ 100 min with a buffered 1% HF solution. After acid etching, its transmittance, surface roughness and LIDT are measured. The results reveal that the fused silica has the highest LIDT and transmittance after etching for 10 min. Then UV laser (355 nm) conditioning is adopted to process the 10-min-etched fused silica. When the laser fluence is below 60% of fused silica's zero probability damage threshold, the LIDT increases gradually with the increase of laser conditioning fluence. However, the LIDT rapidly decreases to be lower than the threshold of the 10-min-etched fused silica when the conditioning fluence is up to 80% of the threshold. Proper acid etching and laser conditioning parameters will effectively enhance the laser damage resistance of fused silica. (authors)

  2. Hole-assisted fiber based fiber fuse terminator supporting 22 W input

    Science.gov (United States)

    Tsujikawa, Kyozo; Kurokawa, Kenji; Hanzawa, Nobutomo; Nozoe, Saki; Matsui, Takashi; Nakajima, Kazuhide

    2018-05-01

    We investigated the air hole structure in hole-assisted fiber (HAF) with the aim of terminating fiber fuse propagation. We focused on two structural parameters c/MFD and S1/S2, which are related respectively to the position and area of the air holes, and mapped their appropriate values for terminating fiber fuse propagation. Here, MFD is the mode field diameter, c is the diameter of an inscribed circle linking the air holes, S1 is the total area of the air holes, and S2 is the area of a circumscribed circle linking the air holes. On the basis of these results, we successfully realized a compact fiber fuse terminator consisting of a 1.35 mm-long HAF, which can terminate fiber fuse propagation even with a 22 W input. In addition, we observed fiber fuse termination using a high-speed camera. We additionally confirmed that the HAF-based fiber fuse terminator is effective under various input power conditions. The penetration length of the optical discharge in the HAF was only less than 300 μm when the input power was from 2 to 22 W.

  3. [Effects of laser welding on bond of porcelain fused cast pure titanium].

    Science.gov (United States)

    Zhu, Juan-fang; He, Hui-ming; Gao, Bo; Wang, Zhong-yi

    2006-04-01

    To investigate the influence of the laser welding on bond of porcelain fused to cast pure titanium. Twenty cast titanium plates were divided into two groups: laser welded group and control group. The low-fusing porcelain was fused to the laser welded cast pure titanium plates at fusion zone. The bond strength of the porcelain to laser welded cast pure titanium was measured by the three-point bending test. The interface of titanium and porcelain was investigated by scanning electron microscopy (SEM) and energy depressive X-ray detector (EDX). The non-welded titanium plates were used as comparison. No significant difference of the bond strength was found between laser-welded samples [(46.85 +/- 0.76) MPa] and the controls [(41.71 +/- 0.55) MPa] (P > 0.05). The SEM displayed the interface presented similar irregularities with a predominance. The titanium diffused to low-fusing porcelain, while silicon and aluminum diffused to titanium basement. Laser welding does not affect low-fusing porcelain fused to pure titanium.

  4. Toxic Elements

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

  6. Regulatory regime and its influence in the nuclear safety

    International Nuclear Information System (INIS)

    Laaksonen, J.

    1999-01-01

    Main elements of nuclear regulatory regime in general is presented. These elements are: national rules and safety regulations, system of nuclear facility licensing, activities of regulatory body. Regulatory body is needed to specify the national safety regulations, review and assess the safety documentation presented to support license application, make inspections to verify fulfilment of safety regulations and license conditions, monitor the quality of work processes of user organization, and to assess whether these processes provide a high safety level, promote high safety culture, promote maintenance and development of national infrastructure relevant to nuclear safety, etc

  7. Safeguards inventory and process monitoring regulatory comparison

    Energy Technology Data Exchange (ETDEWEB)

    Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2013-06-27

    Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

  8. Regulatory issues associated with the Multi-Purpose (MPC) system

    International Nuclear Information System (INIS)

    Roberts, J.P.; Desell, L.J.; Birch, M.L.; Morgan, R.G.

    1994-01-01

    The US Department of Energy Office of Civilian Radioactive Waste Management is developing a Multi-Purpose Canister system to promote compatibility between the waste program elements of storage, transportation, and disposal. The development of a Multi-Purpose Canister system requires meeting various regulatory requirements. These regulatory requirements are set forth in environmental and Nuclear Regulatory Commission (NRC) regulations. This paper discusses the more significant regulatory issues that must be addressed in the development of a Multi-Purpose Canister system by the Department of Energy

  9. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  10. PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE

    Directory of Open Access Journals (Sweden)

    Lahiri Debomoy K

    2013-01-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is intimately tied to amyloid-β (Aβ peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or “proximal regulatory element” (PRE, at −76/−47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2, nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF, and specificity protein 1 (SP1. These sites crossed a known single nucleotide polymorphism (SNP. EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also

  11. The Regulatory Framework for Privacy and Security

    Science.gov (United States)

    Hiller, Janine S.

    The internet enables the easy collection of massive amounts of personally identifiable information. Unregulated data collection causes distrust and conflicts with widely accepted principles of privacy. The regulatory framework in the United States for ensuring privacy and security in the online environment consists of federal, state, and self-regulatory elements. New laws have been passed to address technological and internet practices that conflict with privacy protecting policies. The United States and the European Union approaches to privacy differ significantly, and the global internet environment will likely cause regulators to face the challenge of balancing privacy interests with data collection for many years to come.

  12. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  13. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  14. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  15. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  16. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  17. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  18. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  19. Fuel element

    International Nuclear Information System (INIS)

    Armijo, J.S.

    1976-01-01

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

  20. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  1. Mechanical and chemical analyses across dental porcelain fused to CP titanium or Ti6Al4V

    International Nuclear Information System (INIS)

    Souza, Júlio C.M.; Henriques, Bruno; Ariza, Edith; Martinelli, Antonio E.; Nascimento, Rubens M.; Silva, Filipe S.; Rocha, Luís A.; Celis, Jean-Pierre

    2014-01-01

    The aim of this study was to evaluate the evolution of mechanical properties and chemical variation across veneering dental porcelain fused to different titanium-based substrates. Test samples were synthesized by fusing dental feldspar-based porcelain onto commercially pure titanium grade II or Ti6Al4V alloy. Samples were cross-sectioned at angles of 10 and 90° to the interface plane. Afterwards, nanoindentation tests and Scanning Electron Microscopy (SEM) imaging coupled to an Energy Dispersive Spectroscopy (EDS) system were carried out across interfaces extending from the metal towards the porcelain area. Elemental diffusion profiles across the porcelain-to-metal interfaces were also obtained by EDS analysis. The mismatch in mechanical properties found in porcelain-to-Ti6Al4V interfaces was lower than that of porcelain-to-CP titanium. Cracking was noticed at low-thickness veneering dental porcelain regions after the nanoindentation tests of samples cross-sectioned at low angles to the interface plane. A wide reaction zone between titanium and porcelain as well as higher incidence of defects was noticed at the porcelain-to-CP titanium interfaces. This study confirmed Ti6Al4V as an improved alternative to CP-titanium as it showed to establish a better interface with the veneering dental porcelain considering the slight chemical interaction and the lower mechanical properties mismatch. The elastic modulus of porcelain-to-Ti6Al4V samples showed to be less sensitive to porcelain thickness variations. - Highlights: • This study reveals mechanical and chemical behaviors across porcelain/titanium interfaces. • Cracks were noticed after nanoindentation on thin porcelain layers. • Ti6Al4V/porcelain showed a better mechanical behavior than that at CP-Ti/porcelain

  2. Recycling potential for low voltage and high voltage high rupturing capacity fuse links.

    Science.gov (United States)

    Psomopoulos, Constantinos S; Barkas, Dimitrios A; Kaminaris, Stavros D; Ioannidis, George C; Karagiannopoulos, Panagiotis

    2017-12-01

    Low voltage and high voltage high-rupturing-capacity fuse links are used in LV and HV installations respectively, protecting mainly the LV and HV electricity distribution and transportation networks. The Waste Electrical and Electronic Equipment Directive (2002/96/EC) for "Waste of electrical and electronic equipment" is the main related legislation and as it concerns electrical and electronic equipment, it includes electric fuses. Although, the fuse links consist of recyclable materials, only small scale actions have been implemented for their recycling around Europe. This work presents the possibilities for material recovery from this specialized industrial waste for which there are only limited volume data. Furthermore, in order to present the huge possibilities and environmental benefits, it presents the potential for recycling of HRC fuses used by the Public Power Corporation of Greece, which is the major consumer for the country, but one of the smallest ones in Europe and globally, emphasizing in this way in the issue. According to the obtained results, fuse recycling could contribute to the effort for minimize the impacts on the environment through materials recovery and reduction of the wastes' volume disposed of in landfills. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Electro-Deformation of Fused Cells in a Microfluidic Array Device

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2016-11-01

    Full Text Available We present a new method of analyzing the deformability of fused cells in a microfluidic array device. Electrical stresses—generated by applying voltages (4–20 V across discrete co-planar microelectrodes along the side walls of a microfluidic channel—have been used to electro-deform fused and unfused stem cells. Under an electro-deformation force induced by applying an alternating current (AC signal, we observed significant electro-deformation phenomena. The experimental results show that the fused stem cells were stiffer than the unfused stem cells at a relatively low voltage (<16 V. However, at a relatively high voltage, the fused stem cells were more easily deformed than were the unfused stem cells. In addition, the electro-deformation process is modeled based on the Maxwell stress tensor and structural mechanics of cells. The theoretical results show that a positive correlation is found between the deformation of the cell and the applied voltage, which is consistent with the experimental results. Combined with a numerical analysis and experimental study, the results showed that the significant difference of the deformation ratio of the fused and unfused cells is not due to their size difference. This demonstrates that some other properties of cell membranes (such as the membrane structure were also changed in the electrofusion process, in addition to the size modification of that process.

  4. FORECAST: Regulatory effects cost analysis software annual

    International Nuclear Information System (INIS)

    Lopez, B.; Sciacca, F.W.

    1991-11-01

    Over the past several years the NRC has developed a generic cost methodology for the quantification of cost/economic impacts associated with a wide range of new or revised regulatory requirements. This methodology has been developed to aid the NRC in preparing Regulatory Impact Analyses (RIAs). These generic costing methods can be useful in quantifying impacts both to industry and to the NRC. The FORECAST program was developed to facilitate the use of the generic costing methodology. This PC program integrates the major cost considerations that may be required because of a regulatory change. FORECAST automates much of the calculations typically needed in an RIA and thus reduces the time and labor required to perform these analysis. More importantly, its integrated and consistent treatment of the different cost elements should help assure comprehensiveness, uniformity, and accuracy in the preparation of needed cost estimates

  5. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

    In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

  6. 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.

  7. A comparative clinical, pathological, biochemical and genetic study of fused in sarcoma proteinopathies

    DEFF Research Database (Denmark)

    Lashley, Tammaryn; Rohrer, Jonathan D; Bandopadhyay, Rina

    2011-01-01

    Neuronal intermediate filament inclusion disease and atypical frontotemporal lobar degeneration are rare diseases characterized by ubiquitin-positive inclusions lacking transactive response DNA-binding protein-43 and tau. Recently, mutations in the fused in sarcoma gene have been shown to cause...... findings, as well as genetic and biochemical data in 14 fused in sarcoma proteinopathy cases. In this cohort, the age of onset was variable but included cases of young-onset disease. Patients with atypical frontotemporal lobar degeneration with ubiquitinated inclusions all presented with behavioural...... familial amyotrophic lateral sclerosis and fused in sarcoma-positive neuronal inclusions have subsequently been demonstrated in neuronal intermediate filament inclusion disease and atypical frontotemporal lobar degeneration with ubiquitinated inclusions. Here we provide clinical, imaging, morphological...

  8. Electromigration driven failures on miniature silver fuses at the Large Hadron Collider

    CERN Document Server

    Trikoupis, Nikolaos; Perez Fontenla, Ana Teresa

    2017-01-01

    Spurious faults were observed on the miniature silver fuses of electronic cards used for the cryogenics instrumentation in the LHC (Large Hadron Collider) accelerator at CERN. By applying analytical tools and techniques such as Scanning Electron Microscopy, spectrometry and Weibull reliability calculations and by the knowledge of operating temperatures and operational time of each unit, the origin of the problem has now been understood and can be attributed to electromigration. The selected fuse was operated at moderate temperature and load conditions and was considered as a “lifetime” component. However, it turned out to have a smaller than expected MTTF with failures following a Weibull distribution of $\\beta = 3.91$ and $\\eta = 2323$. The literature describes extensively the effects of electromigration, but there are only limited references referring to the impact of this phenomenon on miniature silver fuses for electronic circuits.

  9. Thermodynamic perturbation theory for fused hard-sphere and hard-disk chain fluids

    International Nuclear Information System (INIS)

    Zhou, Y.; Hall, C.K.; Stell, G.

    1995-01-01

    We find that first-order thermodynamic perturbation theory (TPT1) which incorporates the reference monomer fluid used in the generalized Flory--AB (GF--AB) theory yields an equation of state for fused hard-sphere (FHS) chain fluids that has accuracy comparable to the GF--AB and GF--dimer--AC theories. The new TPT1 equation of state is significantly more accurate than other extensions of the TPT1 theory to FHS chain fluids. The TPT1 is also extended to two-dimensional fused hard-disk chain fluids. For the fused hard-disk dimer fluid, the extended TPT1 equation of state is found to be more accurate than the Boublik hard-disk dimer equation of state. copyright 1995 American Institute of Physics

  10. Ultraviolet Laser Damage Dependence on Contamination Concentration in Fused Silica Optics during Reactive Ion Etching Process

    Directory of Open Access Journals (Sweden)

    Laixi Sun

    2018-04-01

    Full Text Available The reactive ion etching (RIE process of fused silica is often accompanied by surface contamination, which seriously degrades the ultraviolet laser damage performance of the optics. In this study, we find that the contamination behavior on the fused silica surface is very sensitive to the RIE process which can be significantly optimized by changing the plasma generating conditions such as discharge mode, etchant gas and electrode material. Additionally, an optimized RIE process is proposed to thoroughly remove polishing-introduced contamination and efficiently prevent the introduction of other contamination during the etching process. The research demonstrates the feasibility of improving the damage performance of fused silica optics by using the RIE technique.

  11. Environmental regulatory reform in Poland: lessons for industrializing economies

    Energy Technology Data Exchange (ETDEWEB)

    Brown, H.S.; Angel, D. [Clark University, Worcester, MA (USA). George Perkins Marsh Institute

    2000-09-01

    This paper examines the environmental regulatory reform in Poland during the 1990s and uses the findings to consider the extent to which elements of successful regulatory systems are transferable across national boundaries. Drawing on five case studies of privatized firms, a mailed questionnaire, and policy and institutional analysis, it investigates how Poland developed an effective system for managing industrial pollution while also achieving considerable socioeconomic progress. The fundamental legitimacy of the regulators and regulatory process, the availability of information about firms and regulatory intents, and the capacity for case-specific decision-making are among the key explanatory factors. The study also shows how in Poland a good 'fit' between regulatory institutions and policies on one hand and their social context on the other hand has evolved, and how it contributes to the effectiveness of the regulatory system. Industrializing economies can indeed simultaneously pursue environmental protection and socioeconomic welfare, but elements of a proven regulatory system cannot be automatically adopted among countries and cultures. Learning from each other's experience must be sensitive to the cultural and institutional context of each regulatory system. 42 refs., 3 figs., 1 tab.

  12. Sister kinetochores are mechanically fused during meiosis I in yeast.

    Science.gov (United States)

    Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L

    2014-10-10

    Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance. Copyright © 2014, American Association for the Advancement of Science.

  13. Alkaline phosphatase-fused repebody as a new format of immuno-reagent for an immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hyo-Deok; Lee, Joong-jae [Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of); Kim, Yu Jung [Industrial Biotechnology and Bioenergy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon (Korea, Republic of); Hantschel, Oliver [School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne (Switzerland); Lee, Seung-Goo [Industrial Biotechnology and Bioenergy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon (Korea, Republic of); Kim, Hak-Sung, E-mail: hskim76@kaist.ac.kr [Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of)

    2017-01-15

    Enzyme-linked immunoassays based on an antibody-antigen interaction are widely used in biological and medical sciences. However, the conjugation of an enzyme to antibodies needs an additional chemical process, usually resulting in randomly cross-linked molecules and a loss of the binding affinity and enzyme activity. Herein, we present the development of an alkaline phosphatase-fused repebody as a new format of immuno-reagent for immunoassays. A repebody specifically binding to human TNF-α (hTNF-α) was selected through a phage display, and its binding affinity was increased up to 49 nM using a modular engineering approach. A monomeric alkaline phosphatase (mAP), which was previously isolated from a metagenome library, was genetically fused to the repebody as a signal generator, and the resulting repebody-mAP fusion protein was used for direct and sandwich immunoassays of hTNF-α. We demonstrate the utility and potential of the repebody-mAP fusion protein as an immuno-reagent by showing the sensitivity of 216 pg mL{sup −1} for hTNF-α in a sandwich immunoassay. Furthermore, this repebody-mAP fusion protein enabled the detection of hTNF-α spiked in a serum-supplemented medium with high accuracy and reproducibility. It is thus expected that a mAP-fused repebody can be broadly used as an immuno-reagent in immunoassays. - Highlights: • A human TNF-α (hTNF-α)-specific repebody was selected using a phage display. • A monomeric alkaline phosphatase (mAP) was genetically fused to the repebody. • mAP-fused repebody enabled detection of hTNF-α with high sensitivity and accuracy. • mAP-fused repebody can be widely used as a new immuno-reagent in immunoassays.

  14. Measurements of fuse and resistor characteristics for multi-megajoule capacitor bank application

    International Nuclear Information System (INIS)

    McDonald, K.F.; Smith, T.; Golden, J.; Conley, B.

    1986-01-01

    Experimental tests have been conducted on commercially available fuses and resistors under fast high voltage pulsed (10 μsec) conditions to determine their ability to protect capacitor bank components during faults. NRL's Modified Betatron Accelerator uses two multi-megajoule capacitor banks to power the toroidal and betatron magnetic field coils. The expensive high energy density capacitors in these banks must be protected from excessive peak current, voltage reversal, or charging beyond their electrical ratings in the occurrence of a fault. Adequate protection can be obtained with fuses and resistors in series with each parallel connected capacitor. The fuses must open reliably and hold off high voltage D.C. (10 - 20 kV), and the resistors must conduct high current and di/dt without failing from energy deposition or magnetic forces. The performance of the commercial fuses is well documented at low AC frequencies and currents (60 Hz/100 A) but data was not previously available for the fast high current pulsed conditions that prevail under actual fault conditions. A 20 kV 200 kJ, low inductance capacitor bank and ignitron switch were used to conduct the experiments. Peak currents in the fuses were approximately 170 kA at t - 6.5 μs. The final fuse hold-off voltage exceeded 8 kV. Currents in the resistors ranged from - 20 - 40 kA per resistor. The experimental results have been compared to the manufacturers data from minimum melt and maximum let-through and to exploding bridge wire computer models

  15. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  16. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  17. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

    There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

  18. Fuel element

    International Nuclear Information System (INIS)

    Kennedy, S.T.

    1982-01-01

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

  19. Transactinide elements

    International Nuclear Information System (INIS)

    Hemingway, J.D.

    1975-01-01

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

  20. Evaluation of pulmonary emphysema by the fused image of CT image and ventilation SPECT image

    International Nuclear Information System (INIS)

    Okuda, Ituko; Maruno, Hiromasa; Mori, Kazuaki; Kohno, Tadashi; Kokubo, Takashi

    2007-01-01

    We evaluated pulmonary emphysema using a diagnostic device that could obtain a CT image, a ventilation single photon emission computed tomography (SPECT) image and a lung perfusion SPECT image in one examination. The fused image made from the CT image and SPECT image had very little position gap between images, and the precision was high. From the fused image, we were able to detect the areas in which emphysematous change was the most marked in the CT image, while the accumulation decrease was most remarkable in the ventilation SPECT image. Thus it was possible to obtain an accurate status of pulmonary emphysema, and our method was regarded as a useful technique. (author)

  1. Fusing Eye-gaze and Speech Recognition for Tracking in an Automatic Reading Tutor

    DEFF Research Database (Denmark)

    Rasmussen, Morten Højfeldt; Tan, Zheng-Hua

    2013-01-01

    In this paper we present a novel approach for automatically tracking the reading progress using a combination of eye-gaze tracking and speech recognition. The two are fused by first generating word probabilities based on eye-gaze information and then using these probabilities to augment the langu......In this paper we present a novel approach for automatically tracking the reading progress using a combination of eye-gaze tracking and speech recognition. The two are fused by first generating word probabilities based on eye-gaze information and then using these probabilities to augment...

  2. Ureteral Involvement Within an Incarcerated Inguinal Hernia in a Patient With Crossed-fused Renal Ectopia

    Directory of Open Access Journals (Sweden)

    Udit Singhal

    2016-07-01

    Full Text Available Crossed-fused renal ectopy is an uncommon abnormality of the genitourinary tract that results from errors during embryological development. Ureteral herniation represents another rare anatomic event and can often occur from spontaneous, postoperative, and congenital causes (Allam, Johnson, Grewal & Johnson 2015; Pollack, Popky & Blumberg 1975. Here, we discuss the complex clinical course of a patient with crossed-fused renal ectopia who presents with symptoms due to ureteroinguinal herniation and provide a brief overview of the literature. We highlight the clinical considerations in the management of this patient and provide a potential anatomical and embryological explanation for his presentation.

  3. Distribution and Orientation of Carbon Fibers in Polylactic Acid Parts Produced by Fused Deposition Modeling

    DEFF Research Database (Denmark)

    Hofstätter, Thomas; W. Gutmann, Ingomar; Koch, Thomas

    2016-01-01

    The aim of this paper is the understanding of the fiber orientation by investigations in respect to the inner configuration of a polylactic acid matrix reinforced with short carbon fibers after a fused deposition modeling extrusion process. The final parts were analyzed by X-ray, tomography......, and magnetic resonance imaging allowing a resolved orientation of the fibers and distribution within the part. The research contributes to the understanding of the fiber orientation and fiber reinforcement of fused deposition modeling parts in additive manufacturing....

  4. Surgical and orthodontic management of fused maxillary central and lateral incisors in early mixed dentition stage.

    Science.gov (United States)

    Ramamurthy, Suresh; Satish, Ramaswamy; Priya, Kalidass

    2014-01-01

    Fusion is one of the developmental dental anomalies in which two adjacent teeth are joined at the crown level forming a single tooth with an enlarged crown. Fusion causes some clinical problems such as unaesthetic appearance, pain, caries, and malocclusion. The management of fusion often needs multidisciplinary approach to give best possible esthetic and functional outcome. This paper reports a case of 9-year-old boy with fused maxillary left central and lateral incisors who was treated with 2 × 4 fixed orthodontic appliances after surgical separation of fused teeth.

  5. Surgical and Orthodontic Management of Fused Maxillary Central and Lateral Incisors in Early Mixed Dentition Stage

    Directory of Open Access Journals (Sweden)

    Suresh Ramamurthy

    2014-01-01

    Full Text Available Fusion is one of the developmental dental anomalies in which two adjacent teeth are joined at the crown level forming a single tooth with an enlarged crown. Fusion causes some clinical problems such as unaesthetic appearance, pain, caries, and malocclusion. The management of fusion often needs multidisciplinary approach to give best possible esthetic and functional outcome. This paper reports a case of 9-year-old boy with fused maxillary left central and lateral incisors who was treated with 2×4 fixed orthodontic appliances after surgical separation of fused teeth.

  6. Compositional characterization of sintered (U,Th)O2 pellets by EDXRF using fused bead specimens

    International Nuclear Information System (INIS)

    Sanjay Kumar, S.; Dhara, Sangita; Misra, N.L.; Aggarwal, S.K.

    2015-01-01

    Fused bead specimens were used for analyzing sintered (U,Th)O 2 pellets by Energy Dispersive X-Ray Fluorescence (EDXRF) spectrometry. The bead specimens of calibration mixtures U 3 O 8 and ThO 2 were made by fusing them in Lithium Tetraborate/Metaborate fusion mixtures using a fusion bead machine. The EDXRF spectra of these beads were used for making calibration plot for U% determination in (U+Th) amounts. Using these calibration plots and EDXRF spectra of bead of sintered (U,Th)O 2 pellets, U% in these pellets was successfully determined. (author)

  7. Synthesis of fused bicyclic piperidines: potential bioactive templates for medicinal chemistry.

    Science.gov (United States)

    Zhou, Jinglan; Campbell-Conroy, Erica L; Silina, Alina; Uy, Johnny; Pierre, Fabrice; Hurley, Dennis J; Hilgraf, Nicole; Frieman, Bryan A; DeNinno, Michael P

    2015-01-02

    An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.

  8. A Hybrid Color Mapping Approach to Fusing MODIS and Landsat Images for Forward Prediction

    OpenAIRE

    Chiman Kwan; Bence Budavari; Feng Gao; Xiaolin Zhu

    2018-01-01

    We present a new, simple, and efficient approach to fusing MODIS and Landsat images. It is well known that MODIS images have high temporal resolution and low spatial resolution, whereas Landsat images are just the opposite. Similar to earlier approaches, our goal is to fuse MODIS and Landsat images to yield high spatial and high temporal resolution images. Our approach consists of two steps. First, a mapping is established between two MODIS images, where one is at an earlier time, t1, and the...

  9. Laser-Induced Damage Growth on Larger-Aperture Fused Silica Optical Components at 351 nm

    International Nuclear Information System (INIS)

    Wan-Qing, Huang; Wei, Han; Fang, Wang; Yong, Xiang; Fu-Quan, Li; Bin, Feng; Feng, Jing; Xiao-Feng, Wei; Wan-Guo, Zheng; Xiao-Min, Zhang

    2009-01-01

    Laser-induced damage is a key lifetime limiter for optics in high-power laser facility. Damage initiation and growth under 351 nm high-fluence laser irradiation are observed on larger-aperture fused silica optics. The input surface of one fused silica component is damaged most severely and an explanation is presented. Obscurations and the area of a scratch on it are found to grow exponentially with the shot number. The area of damage site grows linearly. Micrographs of damage sites support the micro-explosion damage model which could be used to qualitatively explain the phenomena

  10. Three-port beam splitter of a binary fused-silica grating.

    Science.gov (United States)

    Feng, Jijun; Zhou, Changhe; Wang, Bo; Zheng, Jiangjun; Jia, Wei; Cao, Hongchao; Lv, Peng

    2008-12-10

    A deep-etched polarization-independent binary fused-silica phase grating as a three-port beam splitter is designed and manufactured. The grating profile is optimized by use of the rigorous coupled-wave analysis around the 785 nm wavelength. The physical explanation of the grating is illustrated by the modal method. Simple analytical expressions of the diffraction efficiencies and modal guidelines for the three-port beam splitter grating design are given. Holographic recording technology and inductively coupled plasma etching are used to manufacture the fused-silica grating. Experimental results are in good agreement with the theoretical values.

  11. Fiber fuse light-induced continuous breakdown of silica glass optical fiber

    CERN Document Server

    Todoroki, Shin-ichi

    2014-01-01

    This book describes the fiber fuse phenomenon that causes a serious problem for the present optical communication systems. High-power light often brings about catastrophic damage to optical devices. Silica glass optical fibers with ultralow transmission loss are not the exception. A fiber fuse appears in a heated region of the fiber cable delivering a few watts of light and runs toward the light source destroying its core region. Understanding this phenomenon is a necessary first step in the development of future optical communication systems. This book provides supplementary videos and photog

  12. Sequential Multicomponent Strategy for the Diastereoselective Synthesis of Densely Functionalized Spirooxindole-Fused Thiazolidines.

    Science.gov (United States)

    Rainoldi, Giulia; Begnini, Fabio; de Munnik, Mariska; Lo Presti, Leonardo; Vande Velde, Christophe M L; Orru, Romano; Lesma, Giordano; Ruijter, Eelco; Silvani, Alessandra

    2018-02-12

    We developed two Ugi-type three-component reactions of spirooxindole-fused 3-thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to give highly functionalized spirooxindole-fused thiazolidines. Two diverse libraries were generated using practical and robust procedures affording the products in typically good yields. The obtained thiazolidines proved to be suitable substrates for further transformations. Notably, both the Ugi-Joullié and the azido-Ugi reactions resulted highly diastereoselective, affording predominantly the trans-configured products, as confirmed by X-ray crystallographic analysis.

  13. Imaging subsurface damage of grinded fused silica optics by confocal fluorescence microscopy

    International Nuclear Information System (INIS)

    Neauport, J.; Cormont, P.; Destribats, J.; Legros, P.; Ambard, C.

    2009-01-01

    We report an experimental investigation of fluorescence confocal microscopy as a tool to measure subsurface damage on grinded fused silica optics. Confocal fluorescence microscopy was performed with an excitation at the wavelength of 405 nm on fixed abrasive diamond grinded fused silica samples. We detail the measured fluorescence spectrums and compare them to those of oil based coolants and grinding slurries. We evidence that oil based coolant used in diamond grinding induces a fluorescence that marks the subsurface damages and eases its observation. Such residual traces might also be involved in the laser damage process. (authors)

  14. Dictionary-Based Image Denoising by Fused-Lasso Atom Selection

    Directory of Open Access Journals (Sweden)

    Ao Li

    2014-01-01

    Full Text Available We proposed an efficient image denoising scheme by fused lasso with dictionary learning. The scheme has two important contributions. The first one is that we learned the patch-based adaptive dictionary by principal component analysis (PCA with clustering the image into many subsets, which can better preserve the local geometric structure. The second one is that we coded the patches in each subset by fused lasso with the clustering learned dictionary and proposed an iterative Split Bregman to solve it rapidly. We present the capabilities with several experiments. The results show that the proposed scheme is competitive to some excellent denoising algorithms.

  15. An unusual cause of chest pain: Fused cervical vertebra (C3-C4

    Directory of Open Access Journals (Sweden)

    Daipayan Chatterjee

    2014-01-01

    Full Text Available Cervicogenic angina is paroxysmal precordialgia usually due to lower cervical vertebral involvement. But upper cervical vertebral segmental anomaly causing cervicogenic angina is rare. Herein, we report a case of cervicogenic angina due to fused 3 rd and 4 th cervical vertebra in a 37-year female, which was initially misdiagnosed as angina and treated likewise. But, persistence of symptoms led to evaluation of her cervical spine and subsequent diagnosis. Cervical traction, physiotherapy and posture training relieved her of her symptoms with no recurrence till 6 months of follow-up. Fused C3-C4 can be a cause of precordialgia and physicians should be aware of it.

  16. Monascus-fermented red mold dioscorea protects mice against alcohol-induced liver injury, whereas its metabolites ankaflavin and monascin regulate ethanol-induced peroxisome proliferator-activated receptor-γ and sterol regulatory element-binding transcription factor-1 expression in HepG2 cells.

    Science.gov (United States)

    Cheng, Chih-Fu; Pan, Tzu-Ming

    2018-03-01

    Alcoholic hepatitis is a necroinflammatory process that is associated with fibrosis and leads to cirrhosis in 40% of cases. The hepatoprotective effects of red mold dioscorea (RMD) from Monascus purpureus NTU 568 were evaluated in vivo using a mouse model of chronic alcohol-induced liver disease (ALD). ALD mice were orally administered vehicle (ALD group) or vehicle plus 307.5, 615.0 or 1537.5 mg kg -1 (1 ×, 2 × and 5 ×) RMD for 5 weeks. RMD lowered serum leptin, hepatic total cholesterol, free fatty acid and hepatic triglyceride levels and increased serum adiponectin, hepatic alcohol dehydrogenase and antioxidant enzyme levels. Furthermore, ankaflavin (AK) and monascin (MS), metabolites of RMD fermented with M. purpureus 568, induced peroxisome proliferator-activated receptor-γ expression and the concomitant suppression of ethanol-induced elevation of sterol regulatory element-binding transcription factor-1 and TG in HepG2 cells. These results indicate the hepatoprotective effect of Monascus-fermented RMD. Moreover, AK and MS were identified as the active constituents of RMD for the first time and were shown to protect against ethanol-induced liver damage. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Characterization of chemical contaminants generated by a desktop fused deposition modeling 3-dimensional Printer.

    Science.gov (United States)

    Stefaniak, Aleksandr B; LeBouf, Ryan F; Yi, Jinghai; Ham, Jason; Nurkewicz, Timothy; Schwegler-Berry, Diane E; Chen, Bean T; Wells, J Raymond; Duling, Matthew G; Lawrence, Robert B; Martin, Stephen B; Johnson, Alyson R; Virji, M Abbas

    2017-07-01

    Printing devices are known to emit chemicals into the indoor atmosphere. Understanding factors that influence release of chemical contaminants from printers is necessary to develop effective exposure assessment and control strategies. In this study, a desktop fused deposition modeling (FDM) 3-dimensional (3-D) printer using acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA) filaments and two monochrome laser printers were evaluated in a 0.5 m 3 chamber. During printing, chamber air was monitored for vapors using a real-time photoionization detector (results expressed as isobutylene equivalents) to measure total volatile organic compound (TVOC) concentrations, evacuated canisters to identify specific VOCs by off-line gas chromatography-mass spectrometry (GC-MS) analysis, and liquid bubblers to identify carbonyl compounds by GC-MS. Airborne particles were collected on filters for off-line analysis using scanning electron microscopy with an energy dispersive x-ray detector to identify elemental constituents. For 3-D printing, TVOC emission rates were influenced by a printer malfunction, filament type, and to a lesser extent, by filament color; however, rates were not influenced by the number of printer nozzles used or the manufacturer's provided cover. TVOC emission rates were significantly lower for the 3-D printer (49-3552 µg h -1 ) compared to the laser printers (5782-7735 µg h -1 ). A total of 14 VOCs were identified during 3-D printing that were not present during laser printing. 3-D printed objects continued to off-gas styrene, indicating potential for continued exposure after the print job is completed. Carbonyl reaction products were likely formed from emissions of the 3-D printer, including 4-oxopentanal. Ultrafine particles generated by the 3-D printer using ABS and a laser printer contained chromium. Consideration of the factors that influenced the release of chemical contaminants (including known and suspected asthmagens such as styrene and

  18. Feature-fused SSD: fast detection for small objects

    Science.gov (United States)

    Cao, Guimei; Xie, Xuemei; Yang, Wenzhe; Liao, Quan; Shi, Guangming; Wu, Jinjian

    2018-04-01

    Small objects detection is a challenging task in computer vision due to its limited resolution and information. In order to solve this problem, the majority of existing methods sacrifice speed for improvement in accuracy. In this paper, we aim to detect small objects at a fast speed, using the best object detector Single Shot Multibox Detector (SSD) with respect to accuracy-vs-speed trade-off as base architecture. We propose a multi-level feature fusion method for introducing contextual information in SSD, in order to improve the accuracy for small objects. In detailed fusion operation, we design two feature fusion modules, concatenation module and element-sum module, different in the way of adding contextual information. Experimental results show that these two fusion modules obtain higher mAP on PASCAL VOC2007 than baseline SSD by 1.6 and 1.7 points respectively, especially with 2-3 points improvement on some small objects categories. The testing speed of them is 43 and 40 FPS respectively, superior to the state of the art Deconvolutional single shot detector (DSSD) by 29.4 and 26.4 FPS.

  19. Safety culture in regulatory expert organization : analysis result of survey for KINS employees

    International Nuclear Information System (INIS)

    Choi, G. S.; Choi, Y. S.

    2003-01-01

    Much has been discussed on safety culture of operating organizations, however, little has been done on that of regulatory organization. Current issues and activities related to nuclear safety culture at IAEA, OECD/NEA, etc. were investigated and relevant literatures were reviewed. Elements essential for safety culture of regulatory organization were proposed and survey questionnaire for employees of regulatory expert organization, KINS, was developed based on the elements proposed. The survey result was presented and its implications were discussed. Based on the result, elements of safety culture in regulatory organization were proposed. The result of this survey can be used in developing safety culture model of regulatory organization, measurement method and also promotion of safety culture in regulatory organization

  20. Communication planning by the nuclear regulatory body

    International Nuclear Information System (INIS)

    2002-01-01

    The national regulatory body, whose primary mission is to exercise regulatory control over nuclear facilities and the use of radiation sources, but not to promote their use, may be the most credible source of neutral, balanced and accurate information about issues relating to nuclear and radiation safety. It is therefore important for a regulatory body to establish and exercise an effective communication programme to acquaint the public with its oversight functions, capabilities and effectiveness. If the regulatory body is to maintain credibility and to deal promptly and effectively with nuclear or radiological accidents and any other events that may give rise to significant public concerns, and is to communicate clearly and effectively with the public, it must have adequate resources, including experts in nuclear safety. And if maintaining public confidence in the authorities and avoiding unnecessary concerns are among its principal objectives, it must be able to communicate understandably and truthfully about the known extent of any accident, the actions taken in response to it and its implications. In the past, psychological effects as a result of certain severe nuclear and radiological accidents have been compounded by a lack of candour with the public on the part of the authorities and an absence of an appropriate programme of public information. This publication describes good practices and gives practical examples of how the regulatory body can establish a systematic and structured programme for enhancing effective communication with various parties and under various circumstances. The report presupposes an adequate national infrastructure, including an independent regulatory body with sufficient authority and resources to discharge its responsibilities for the regulation of safety. This Safety Report covers the elements of a regulatory body's programme for communication with various audiences and under the different circumstances that may be encountered

  1. New elements

    International Nuclear Information System (INIS)

    Flerov, G.

    1976-01-01

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

  2. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

    Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

  3. Characterization of deep wet etching of fused silica glass for single cell and optical sensor deposition

    International Nuclear Information System (INIS)

    Zhu, Haixin; Holl, Mark; Ray, Tathagata; Bhushan, Shivani; Meldrum, Deirdre R

    2009-01-01

    The development of a high-throughput single-cell metabolic rate monitoring system relies on the use of transparent substrate material for a single cell-trapping platform. The high optical transparency, high chemical resistance, improved surface quality and compatibility with the silicon micromachining process of fused silica make it very attractive and desirable for this application. In this paper, we report the results from the development and characterization of a hydrofluoric acid (HF) based deep wet-etch process on fused silica. The pin holes and notching defects of various single-coated masking layers during the etching are characterized and the most suitable masking materials are identified for different etch depths. The dependence of the average etch rate and surface roughness on the etch depth, impurity concentration and HF composition are also examined. The resulting undercut from the deep HF etch using various masking materials is also investigated. The developed and characterized process techniques have been successfully implemented in the fabrication of micro-well arrays for single cell trapping and sensor deposition. Up to 60 µm deep micro-wells have been etched in a fused silica substrate with over 90% process yield and repeatability. To our knowledge, such etch depth has never been achieved in a fused silica substrate by using a non-diluted HF etchant and a single-coated masking layer at room temperature

  4. Solubility of fused silica in sub- and supercritical water: Estimation from a thermodynamic model

    Czech Academy of Sciences Publication Activity Database

    Karásek, Pavel; Šťavíková, Lenka; Planeta, Josef; Hohnová, Barbora; Roth, Michal

    2013-01-01

    Roč. 83, NOV (2013), s. 72-77 ISSN 0896-8446 R&D Projects: GA ČR(CZ) GAP106/12/0522 Institutional support: RVO:68081715 Keywords : amorphous silica * fused silica * supercritical water * aqueous solubility Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.571, year: 2013

  5. Dual function of the hemagglutinin H5 fused to chicken CD154 in a ...

    African Journals Online (AJOL)

    Dual function of the hemagglutinin H5 fused to chicken CD154 in a potential strategy of DIVA against avian influenza disease: preliminary study. AG Pose, ES Rodriguez, AC Mendez, JN Gomez, AV Redondo, ER Rodriguez, EMG Ramos, AA Gutierrez, MPR Molto, DG Roche, YS Ugalde, AM Lopez ...

  6. Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Evert Fuenmayor

    2018-04-01

    Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

  7. Synthesis of zeolite NaA membrane from fused fly ash extract

    CSIR Research Space (South Africa)

    Ameh, AE

    2016-01-01

    Full Text Available Zeolite-NaA membranes were synthesized from an extract of fused South African fly ash on a porous titanium support by a secondary growth method. The influence of the synthesis molar regime on the formation of zeolite NaA membrane layer...

  8. Synthetic Lipid (DOPG) Vesicles Accumulate in the Cell Plate Region But Do Not Fuse1

    NARCIS (Netherlands)

    Esseling-Ozdoba, A.; Vos, J.W.; Lammeren, van A.A.M.; Emons, A.M.C.

    2008-01-01

    Synthetic Lipid (DOPG) Vesicles Accumulate in the Cell Plate Region But Do Not Fuse1,[W],[OA] Agnieszka Esseling-Ozdoba2, Jan W. Vos, André A.M. van Lammeren and Anne Mie C. Emons* Laboratory of Plant Cell Biology, Department of Plant Sciences, Wageningen University, 6703¿BD Wageningen, The

  9. Synthesis, reactivity, and properties of N-fused porphyrin rhenium(I) tricarbonyl complexes.

    Science.gov (United States)

    Toganoh, Motoki; Ikeda, Shinya; Furuta, Hiroyuki

    2007-11-12

    The thermal reactions of N-fused tetraarylporphyrins or N-confused tetraarylporphyrins with Re2(CO)10 gave the rhenium(I) tricarbonyl complexes bearing N-fused porphyrinato ligands (4) in moderate to good yields. The rhenium complexes 4 are characterized by mass, IR, 1H, and 13C NMR spectroscopy, and the structures of tetraphenylporphynato complex 4a and its nitro derivative 15 are determined by X-ray single crystal analysis. The rhenium complexes 4 show excellent stability against heat, light, acids, bases, and oxidants. The aromatic substitution reactions of 4 proceed without a loss of the center metal to give the nitro (15), formyl (16), benzoyl (17), and cyano derivatives (19), regioselectively. In the electrochemical measurements for 4, one reversible oxidation wave and two reversible reduction waves are observed. Their redox potentials imply narrow HOMO-LUMO band gaps of 4 and are consistent with their electronic absorption spectra, in which the absorption edges exceed 1000 nm. Theoretical study reveals that the HOMO and LUMO of the rhenium complexes are exclusively composed of the N-fused porphyrin skeleton. Protonation of 4 takes place at the 21-position regioselectively, reflecting the high coefficient of the C21 atom in the HOMO orbital. The skeletal rearrangement reaction from N-confused porphyrin Re(I) complex (8) to N-fused porphyrin Re(I) complex (4) is suggested from the mechanistic study as well as DFT calculations.

  10. Simulation of microstructure evolution in fused-coating additive manufacturing based on phase field approach

    Directory of Open Access Journals (Sweden)

    Ru-wei Geng

    2017-11-01

    Full Text Available The mechanical properties of metal components are determined by the solidification behaviour and microstructure. A quantitative phase field model is used to investigate the microstructure evolution of fused-coating additive manufacturing, by which to improve the quality of deposition. During the fused-coating process, the molten metal in a crucible flows out of a nozzle and then reaches the substrate. The solidification happens at the moment when the molten metal comes into contact with substrate moving in three-dimensional space. The macroscopic heat transfer model of fused-coating is established to get the temperature field considered as the initial temperature boundary conditions in the phase field model. The numerical and experimental results show that the morphology of grains varies with different solidification environments. Columnar grains are observed during the early period at the bottom of fused-coating layer and the equiaxed grains appear subsequently ahead of the columnar grains. Columnar dendrites phase field simulations about the grains morphology and solute distribution are conducted considering the solidification environments. The simulation results are in good agreement with experimental results.

  11. SimFuse: A Novel Fusion Simulator for RNA Sequencing (RNA-Seq Data

    Directory of Open Access Journals (Sweden)

    Yuxiang Tan

    2015-01-01

    Full Text Available The performance evaluation of fusion detection algorithms from high-throughput sequencing data crucially relies on the availability of data with known positive and negative cases of gene rearrangements. The use of simulated data circumvents some shortcomings of real data by generation of an unlimited number of true and false positive events, and the consequent robust estimation of accuracy measures, such as precision and recall. Although a few simulated fusion datasets from RNA Sequencing (RNA-Seq are available, they are of limited sample size. This makes it difficult to systematically evaluate the performance of RNA-Seq based fusion-detection algorithms. Here, we present SimFuse to address this problem. SimFuse utilizes real sequencing data as the fusions’ background to closely approximate the distribution of reads from a real sequencing library and uses a reference genome as the template from which to simulate fusions’ supporting reads. To assess the supporting read-specific performance, SimFuse generates multiple datasets with various numbers of fusion supporting reads. Compared to an extant simulated dataset, SimFuse gives users control over the supporting read features and the sample size of the simulated library, based on which the performance metrics needed for the validation and comparison of alternative fusion-detection algorithms can be rigorously estimated.

  12. 3D printing of CNT- and graphene-based conductive polymer nanocomposites by fused deposition modeling

    NARCIS (Netherlands)

    Gnanasekaran, K.; Heijmans, T.; van Bennekom, S.; Woldhuis, H.; Wijnia, S.; de With, G.; Friedrich, H.

    2017-01-01

    Fused deposition modeling (FDM) is limited by the availability of application specific functional materials. Here we illustrate printing of non-conventional polymer nanocomposites (CNT- and graphene-based polybutylene terephthalate (PBT)) on a commercially available desktop 3D printer leading toward

  13. Hemi-fused structure mediates and controls fusion and fission in live cells.

    Science.gov (United States)

    Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J; Krystofiak, Evan S; Villarreal, Seth A; Chiang, Hsueh-Cheng; Kachar, Bechara; Wu, Ling-Gang

    2016-06-23

    Membrane fusion and fission are vital for eukaryotic life. For three decades, it has been proposed that fusion is mediated by fusion between the proximal leaflets of two bilayers (hemi-fusion) to produce a hemi-fused structure, followed by fusion between the distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission. This hypothesis remained unsupported owing to the lack of observation of hemi-fusion or hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed. Here we report the observation of a hemi-fused Ω-shaped structure in live neuroendocrine chromaffin cells and pancreatic β-cells, visualized using confocal and super-resolution stimulated emission depletion microscopy. This structure is generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, the transition to full fusion or fission is determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and is notably slow (seconds to tens of seconds) in a substantial fraction of the events. These results provide key missing evidence in support of the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion and fission, as fusion and fission mechanisms compete to determine the transition to fusion or fission.

  14. Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Tomonari Kasai

    2012-01-01

    Full Text Available Chlorotoxin is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion venom, which has been shown to inhibit low-conductance chloride channels in colonic epithelial cells. Chlorotoxin also binds to matrix metalloproteinase-2 and other proteins on glioma cell surfaces. Glioma cells are considered to require the activation of matrix metalloproteinase-2 during invasion and migration. In this study, for targeting glioma, we designed two types of recombinant chlorotoxin fused to human IgG-Fcs with/without a hinge region. Chlorotoxin fused to IgG-Fcs was designed as a dimer of 60 kDa with a hinge region and a monomer of 30 kDa without a hinge region. The monomeric and dimeric forms of chlorotoxin inhibited cell proliferation at 300 nM and induced internalization in human glioma A172 cells. The monomer had a greater inhibitory effect than the dimer; therefore, monomeric chlorotoxin fused to IgG-Fc was multivalently displayed on the surface of bionanocapsules to develop a drug delivery system that targeted matrix metalloproteinase-2. The target-dependent internalization of bionanocapsules in A172 cells was observed when chlorotoxin was displayed on the bionanocapsules. This study indicates that chlorotoxin fused to IgG-Fcs could be useful for the active targeting of glioblastoma cells.

  15. Mechanical and thermal cycling effects on the flexural strength of glass ceramics fused to titanium

    NARCIS (Netherlands)

    Vasquez, Vanessa; Ozcan, Mutlu; Nishioka, Renato; Souza, Rodrigo; Mesquita, Alfredo; Pavanelli, Carlos

    This study evaluated the effects of mechanical and thermal cycling on the flexural strength (ISO 9693) of three brands of ceramics fused to commercially pure titanium (cpTi). Metallic frameworks of 25 x 3 x 0.5 mm dimensions (N = 84) were cast in cpTi, followed by 150-mu m aluminum oxide airborne

  16. Near- and supercritical water as a diameter manipulation and surface roughening agent in fused silica capillaries

    Czech Academy of Sciences Publication Activity Database

    Karásek, Pavel; Planeta, Josef; Roth, Michal

    2013-01-01

    Roč. 85, č. 1 (2013), s. 327-333 ISSN 0003-2700 R&D Projects: GA ČR(CZ) GAP106/12/0522; GA ČR(CZ) GAP206/11/0138 Institutional support: RVO:68081715 Keywords : supercritical water * fused silica capillary * surface treatment Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 5.825, year: 2013

  17. Enzymatic Baeyer-Villiger Oxidation of Benzo-Fused Ketones : Formation of Regiocomplementary Lactones

    NARCIS (Netherlands)

    Rioz-Martinez, Ana; de Gonzalo, Gonzalo; Pazmino, Daniel E. Torres; Fraaije, Marco W.; Gotor, Vicente

    Baeyer-Villiger monooxygenases (BVMOs) are enzymes that are known to catalyse the Baeyer-Villiger oxidation of ketones in aqueous media using O(2) as oxidant. Herein, we describe the oxidation of a set of diverse benzo-fused ketones by three different BVMOs in both aqueous and non-conventional

  18. Development of electro fused aggregates for use in refractories for the burning zone of cement kilns

    International Nuclear Information System (INIS)

    Ferreira, Luis Leonardo Horne Curimbaba

    2006-01-01

    Electro fused aggregates are largely used in refractory production due to the better performance reached when they are employed. In this work electro fused aggregates were designed for application in refractories for the burning zone of cement kilns. Initially reaction evaluation was conducted aiming the identification of the most prone refractory systems when single refractory phases react with Portland cement phases at high temperatures. In the next step, raw materials of the best refractory systems were electro fused to generate different aggregate compositions. The electro fused aggregates properties were evaluated and the classified ones were used to produce refractory bricks for the burning zone of cement kilns. General characteristics of these bricks were measured and compared with a standard magnesia-spinel refractory. Aggregates of the system Mg O - TiO 2 - Ca O, more specifically aggregates belonged to the compatibility triangle Mg O - Mg 2 TiO 4 - CaTiO 3 , showed suitable characteristics for development of refractories for the burning zone cement kilns. (author)

  19. An Empirical Method to Fuse Partially Overlapping State Vectors for Distributed State Estimation

    NARCIS (Netherlands)

    Sijs, J.; Hanebeck, U.; Noack, B.

    2013-01-01

    State fusion is a method for merging multiple estimates of the same state into a single fused estimate. Dealing with multiple estimates is one of the main concerns in distributed state estimation, where an estimated value of the desired state vector is computed in each node of a networked system.

  20. Dual function of the hemagglutinin H5 fused to chicken CD154 in a ...

    African Journals Online (AJOL)

    Dual function of the hemagglutinin H5 fused to chicken CD154 in a potential strategy of DIVA against avian influenza disease: preliminary study. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like ...